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8041930
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[The superior and inferior venae cavae: angiography by TOF 2D magnetic resonance versus spin-echo sequences].
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This work was aimed at assessing the usefulness of magnetic resonance angiography (MRA) in the investigation and diagnosis of vena cava conditions. Forty-five subjects that is 20 volunteers and 25 patients, were examined with MRA using a 1.5 T superconductive system (SE and angiography pulse sequences). In the 25 patients, 8 cases of thrombosis were diagnosed, together with 4 cases of suspected tumor spread into either the superior or the inferior vena cava, 2 cases of inferior vena cava agenesis, 5 cases of retroaortic left renal vein and 5 cases of abdominal aortic aneurysm. MRA was performed with the 2D time-of-flight (TOF) technique (FA 18 degrees, TR 30-40 ms, TE 10 ms); the images were acquired on the coronal, sagittal and axial planes with and without presaturation pulse and rotated in the post-processing according to the maximum intensity projection. In all volunteers MRA identified jugular veins, subclavian veins, anonymous veins, superior vena cava, inferior vena cava and common iliac veins. The main limitation of MRA was its spatial resolution. MRA proved to be less accurate than SE sequences in the assessment of tumor spread. As for thrombotic conditions, MRA provided useful additional information and is therefore considered a complementary technique to SE MRI. As for venous anomalies (double inferior vena cava, vena cava agenesis and retroaortic left renal vein) and in the study of the relationships with abdominal aortic aneurysms, MRA proved to be the more accurate of the two techniques.
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8041929
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[Atypical radiological images in Pneumocystis carinii infection in HIV-positive patients].
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To assess the prevalence of atypical PCP patterns in AIDS patients, the chest films of 300 patients with clinical and laboratory diagnosis of PCP were reviewed. We considered as atypical patterns the finding of an asymmetric lesion, the involvement of apical regions, pleural effusion, hilar and/or mediastinal lymphadenopathy, parenchymal nodules and pneumatoceles. In some patients more than one of these patterns was found. Atypical patterns were observed in 32% of cases and consisted of: unilateral involvement in 11% of cases, apical involvement in 6%, pleural effusion in 9%, hilar and/or mediastinal lymph nodes in 4%, parenchymal nodules in 6% and finally pneumatocele in 12% of cases.
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8041928
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[The role of stereotactic radiography in nonpalpable breast lesions. The authors' own experience].
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Stereotaxis is a well-known technique allowing fine-needle aspiration cytology and preoperative localization of the nonpalpable breast lesions seen on mammograms, permitting early diagnosis and easy surgical ablation. The authors report on their experience (126 cases) with stereotactic aspiration (85 cases) and preoperative localization (41 cases) of nonpalpable lesions. The technique allowed to hit the lesion in 115/126 cases (91.3%). Cytology showed 24 cases of cancer and 38 benign lesions (3 of them were false negatives); in 8 cases cytology was suspect (7 cancers and 1 sclerosing adenosis) and in 15 inadequate (17.7%). Sensitivity and specificity were confirmed by histology or follow-up (6 months + 6 months); sensitivity was 91.2% and specificity 97.2% (excluding inadequate cases). The 41 needle localizers were useful to detect 37 malignancies. Fifty-one lesions were biopsied: 37 of them were malignant and 14 benign (benign/malignant ratio = 0.38/1).
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8041927
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[The mammographic aspect and the prognosis of breast carcinoma].
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The authors report on 354 consecutive cases of invasive breast carcinoma followed up 3 to 13 years. The prognostic value of the mammographic appearance of cancer, determined according to Broberg, was studied, as well as that of other indicators, such as pT, pN and estrogen receptor content. An association was found between the mammographic appearance and the other prognostic indicators, but such an association was at the limits of statistical significance (pT p = 0.033, pN p = 0.039, ER p = 0.033) and the mammographic patterns associated with more favorable indicators were not consistent across the three variables. Ten-year actuarial overall survival was significantly associated with pT (p < 0.0001), pN (p < 0.0001) or estrogen receptor content (p < 0.001), but not with mammographic appearance. Multivariate analysis confirmed such results. We found no evidence, as suggested in some literature reports, of any association of the mammographic appearance of breast cancer with survival, and we believe that this indicator has no practical use in predicting prognosis in breast cancer patients.
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8041926
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[Skeletal changes in the kidney transplant patient].
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The skeletal status was investigated with noninvasive diagnostic procedures in 44 renal transplant patients (mean time since intervention: 5 to 195 months) treated with steroid and azathioprine (21 cases) or with steroid, azathioprine and cyclosporine (23 cases). 38.6% of the patients had reduced renal function (creatininemia: 1.6-3.0 mg/dl). Our patients underwent biochemical and hormonal tests of bone metabolism, digital radiographs of the skeleton and bone mineral density measurement with dual-energy X-ray absorptiometry (DXA, Hologic QDR 1000). All the patients exhibited moderate to severe osteopenia at both radiographic and densitometric investigations; the risk of fracture was high in 47% of cases. Radiographic signs of vertebral fractures were observed in 4.5% of cases. Other major radiographic patterns were the aseptic necrosis of femoral head (9%), of carpal bone (4.5%) and of humeral head (2.2%). Fibrous osteitis was demonstrated in three patients. Geodes in the wrist were also observed. The correlation of bone densitometry values and time since renal transplantation was statistically significant (r = 0.381; p < 0.01). Moreover, the grade of osteopenia correlated with serum levels of calcitonin and calcitriol--the latter especially in the patients with severe osteopenia.
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8041925
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[The radiodiagnosis of bone metastases from melanoma].
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The records of 3,795 cases of malignant melanoma treated at the INT (Milan) from 1975 to 1992 were reviewed. Histologic confirmation was obtained in all cases. Thirty-one patients (0.82%) with solitary or multiple skeletal metastases were identified. The review of conventional films, tomograms, CT, MR and bone scintigraphy images enabled us to detect 120 single bone lesions. The X-ray features were divided into two groups according to typical and atypical skeletal lesions. Typical bone metastases are osteolytic (87.5%), with medullary origin (91.6%), and they cannot be distinguished from other osteolytic metastases on the basis of imaging criteria alone. Lesion growth causes cortical erosion and destruction (46.6%), pathologic fractures (22.5%) and soft tissue involvement (12.5%). Lytic areas usually have ill-defined margins. Clear-cut outline is an uncommon finding. Atypical skeletal metastases exhibit a mixed osteolytic-osteoblastic pattern (10%), which is hardly ever completely osteoblastic (2.5%). Other unusual metastatic patterns include intense trabecular rarefaction with no detectable single lesion (3.3%), the presence of a well-defined sclerotic rim and periosteal reaction (12.5%). Atypical growth may cause extensive cortical destruction and periosteal production resembling osteogenic osteosarcoma. The various imaging methods show that conventional radiology has relatively poor sensitivity because of anatomical reasons, while MRI is the most sensitive method to detect skeletal localizations. Treatment changes the radiologic patterns of the lesions: recalcification, sclerotic rim, periosteal reaction are common response patterns. Finally, in spite of the above limitations, conventional radiology remains the method of choice to assess lesion evolution during the follow-up.
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8041924
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[An analysis of a case series of 342 short-stature patients examined by the Tanner-Whitehouse 2 (TW2) method].
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342 short-stature patients were examined to assess the agreement between anagraphic and bone ages. 190 men and 152 women (age range: 0 to 17.5 years) underwent conventional radiographs of the left wrist. The radiographs were studied with the TW2 method which provides an index of the skeletal maturity of short and long bones and a global index of the hand. The bone ages thus obtained were compared with anagraphic ages. Patients' statures were compared with their parents' ones. Finally, radiation exposures were evaluated. Anagraphic and bone ages were in agreement in 199 patients and in disagreement in 220. Three patients were adult. The short stature in 78 patients was in agreement with their parents' one, while 253 patients had at least one parent with normal stature. No comparison could be made in 11 patients. In conclusion, TW2 is a simple method to calculate bone age (in months and years) and to select the patients to submit to further examinations and to hormone therapy.
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8041917
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The cohort mortality perspective: the emperor's new clothes of epidemiology, an illustration using cancer mortality.
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Cohort analysis of cancer mortality in industrialized countries has led to the generally accepted conclusion that these populations have been exposed to increasing levels of carcinogenic influences. Age-specific cancer mortality rates in the United States from 1962 to 1988 were portrayed in both cross-sectional and cohort manners. Both representations are consistent with the Strehler-Mildvan modification of the Gompertz relationship between aging and mortality. These observations suggest that environmental cohort effects are not responsible for rising cancer mortality. The cohort mortality perspective in epidemiology is inherently biased due to the effects of competing mortality. Competing mortality, like environmental exposures, is applied in a cross-sectional manner across multiple birth cohorts. Competing mortality produces selective mortality, or differential survival, within a birth cohort. Differential survival, an underappreciated form of selection bias, alters the gene pool of surviving birth cohort members. Since cross-sectional competing mortality risks vary with age, the gene pool of different birth cohorts is not uniformly altered. Consequently, differences between birth cohorts in age-specific mortality rates with respect to a particular disorder, for example, cancer, do not specifically imply differences in environmental exposures.
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8041916
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Evaluation of reduced protocols for carcinogenicity testing of chemicals: report of a joint EPA/NIEHS workshop.
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The current U.S. Environmental Protection Agency (EPA) and other national/international guidelines specify the use of two species and two sexes rodents (usually the rat and the mouse) for carcinogenicity testing of chemicals. In view of the enormous number of chemicals to be tested, the high cost of testing, and the large number of animals used in the present protocol, many academic, industrial, and government authorities are examining the possibility of using a reduced protocol (less than two species and two sexes of rodents) for carcinogenicity testing of chemicals. The use of a reduced protocol offers many advantages as well as some disadvantages. To pursue further the potential implications and impacts of using a reduced protocol for carcinogenicity testing on the processes of hazard identification and risk assessment, a workshop entitled "Evaluation of Reduced Protocols for Carcinogenicity Testing of Chemicals" was held at the Embassy Suites Hotel in Alexandria, Virginia on September 22 and 23, 1992. It was cosponsored by EPA's Office of Prevention, Pesticides and Toxic Substances (OPPTS) and the National Toxicology Program of the National Institutes of Environmental Health Sciences (NTP/NIEHS) and attended by more than 60 participants from government, industry, academia, and the general public. The Expert Consensus Panel and most of the participants supported the use of reduced protocols in carcinogenicity testing. However, it was recognized that reduced protocols may not be appropriate for the testing of all chemicals and that additional analyses/data may be needed for selection of the most appropriate reduced protocol for certain chemicals/chemical classes.
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8041915
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Evidence that cell toxicity may contribute to the genotoxic response.
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Comparisons of the structural determinants associated with genotoxic effects with those associated with cell or systemic toxicity indicate extensive overlaps. These findings can be taken to indicate that toxicity may contribute to genotoxicity.
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8041914
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FDA recommendations for preclinical testing of gonadotropin releasing hormone (GnRH) analogues.
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Gonadotropin-releasing hormone (GnRH) agonists and antagonists are synthetic analogues synthesized by modifications of the naturally occurring hypothalamic decapeptide GnRH. These modifications significantly increase the biological potency and duration of action of GnRH agonists as well as the solubility, potency, and duration of action of GnRH antagonists while decreasing GnRH antagonists toxicity. The field of GnRH analogues has expanded significantly during the past few years in terms of the number of analogues, therapeutic indications, formulations, and mode of administration. This paper provides recommendations for nonclinical testing of GnRH analogues and reflects the type and degree of toxicity testing expected by the Division. However, these recommendations are not formal guidelines in that alternative testing methods will be considered. Furthermore, these recommendations should not be used as guidance for testing of other new drugs.
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8041912
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Tumor incidence in a chemical carcinogenesis study of nonhuman primates.
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This report covers a 32-year period of an ongoing chemical carcinogenesis study in nonhuman primates, which was initiated by the National Cancer Institute in 1961. Autopsy records of 373 breeders and normal controls showed very low incidence of spontaneous malignant tumors in cynomolgus (1.5%) and rhesus (2.8%) monkeys, but considerably higher incidence in African green monkeys (8%). A large number of substances including a variety of food additives, food components, environmental contaminants, N-nitroso compounds, "classical" rodent carcinogens, antineoplastic agents, and immunosuppressive agents have been evaluated for long-term carcinogenic activity. Food components tested which are probably most relevant to human exposure are the artificial sweeteners, cyclamate and saccharin. After 22 years of continuous dosing, neither cyclamate nor saccharin have shown any evidence of carcinogenic effects. Similarly, the tumorigenic potential of arsenic and DDT was negligible after dosing for 15-22 years. In contrast, the fungal food contaminants, aflatoxin B1 (AFB1) and sterigmatocystin (SMT), were found to be potent hepatocarcinogens. AFB1 also induced adenocarcinomas of the pancreas, osteosarcomas, and other tumors. Also, the aglycone of cycasin, MAM acetate, induced a variety of tumors, but primarily hepatocellular and renal cell carcinomas. The compounds most recently introduced into the colony include three heterocyclic amines present in cooked meat. One of these compounds, 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) has proven to be one of the most potent hepatocarcinogens in the history of the monkey project, inducing malignant liver tumors in 65% of animals over a 7-year period of exposure. Of the classical rodent carcinogens studied, urethane was the only one which produced malignant tumors in the monkeys. Conversely, all except two of the N-nitroso compounds were carcinogenic. Diethylnitrosamine (DENA) was the most potent and predictable hepatocarcinogen in cynomolgus, rhesus, and African green monkeys. However, when administered intraperitoneally to galagos (a prosimian), DENA induced primarily mucoepidermoid carcinoma of the nasal cavity. N-Methyl-N-nitrosourea (MNU) was the only carcinogen persistently producing tumors in the digestive tract, mostly squamous cell carcinomas of the esophagus. Among the antineoplastic and immunosuppressive agents, procarbazine (MIH) was the only unequivocal carcinogen, with a 33% tumor incidence, causing acute nonlymphocytic leukemia in most of the cases.
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8041913
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Calculation of benchmark doses from teratology data.
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The benchmark dose approach has several potential advantages over the no observed adverse effect level (NOAEL) as a basis for risk assessment of toxic chemicals, based upon animal toxicity data. The practical use of the benchmark dose has been evaluated by applying dose-response models to an extensive historical database of teratology bioassays. Doses corresponding to 1 and 5% increases in incidence of lesions are calculated and compared to NOAELs. The statistical accuracy of these estimates was determined by calculating confidence intervals. The lower confidence limit on the 5% benchmark dose (LED05) is found to be comparable to the NOAEL for most datasets, and slightly higher on average. Benchmark doses at the 1% level could not be estimated accurately (i.e., they had wide confidence intervals) for a significant fraction of the datasets. LED01 values were lower on average than the NOAEL. Based on these results, it is concluded that benchmark doses for a 5% increases in incidence can be calculated for most datasets, and could be used as a satisfactory basis for risk assessment, e.g., to set reference doses or acceptable daily intakes. An exception occurs when the benchmark dose exceeds the highest dose of the study. This is only likely to occur when the chemical causes a small, but significant, increase in a finding that is uncommon in untreated animals.
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8041900
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Replacement corrections of a Farmer-type ionization chamber for the calibration of Cs-137 and Ir-192 sources in a solid phantom.
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Calibrating Cs-137 and Ir-192 brachytherapy sources in a solid phantom has the advantage over calibration in air that the positioning of the sources is very accurate and straightforward. In order to determine the air kerma rate at the point of measurement it is, however, necessary to take the replacement of the phantom material by the ionization chamber into account. The replacement correction factor pr of a Farmer-type ionization chamber has been determined for a few types of 137Cs and 192Ir sources at a source to chamber distance of 5 cm. For spherical 137Cs sources the replacement correction was determined by means of measurements with chambers with decreasing diameter and length. Additional measurements were performed for some other source configurations in order to determine pr for 137Cs micro-seed trains. For an 192Ir-HDR source pr was determined for a source chamber configuration equal to that for spherical 137Cs sources by comparing measurements in-phantom with measurements free in-air. Finally, measurements were performed with source configurations that yielded pr values for 192Ir seed trains and 192Ir wires. The resulting replacement correction factors are all within +/- 2% of unity. It can be concluded that, although the dose nonuniformity over the chamber volume caused by each source is rather substantial, the replacement correction that has to be applied is rather small.
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8041899
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Radiation dose heterogeneity in receptor and antigen mediated boron neutron capture therapy.
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Boron neutron capture therapy, BNCT, might be a valuable tumour therapeutical modality for the treatment of cells that are difficult to handle with conventional methods such as surgery or external radiotherapy. The principle is that tumour associated 10B atoms capture thermal neutrons and thereby forms high-LET helium and lithium ions as reaction products. An interesting development is to conjugate 10B atoms to macromolecules that bind to tumour cells with over-expressed receptors or specific antigens. The targeting macromolecules might be receptor-ligands, antibodies or antibody-fragments containing 10B. The present study deals with the limitations of such an approach. One problem is the background dose from capture of neutrons in physiologically occurring elements, especially nitrogen. We showed, with computer simulations, that the background specific energy (the stochastic analogy of dose) in the cell nuclei, due to captures in nitrogen, had a wide spread and could be rather high, up to 3 Gy in some cells, when relevant neutron fluencies were applied. The maximal amount of 10B that can be delivered to single tumour cells due to receptor-ligand, receptor-antibody or antigen-antibody mediated binding is probably in the range 10(8)-10(10) atoms/cell. Our calculations showed that the tumour cells had to contain about 10(9) 10B/cell to give a therapeutically interesting dose to the nuclei of the targeted cells. The doses were highest when the boron was in the cell nucleus. There was also a wide spread of specific energy absorbed by the nuclei after neutron capture in 10B. When, for example, 10(8) 10(10)B/nucleus were applied the specific energy to the analysed nuclei varied from 0 Gy up to about 7 Gy. These variations were due to the stochastic nature of the capture processes. Some helium or lithium ion tracks passed through the centre of the cell nuclei delivering a lot of energy, some passed through only a smaller part delivering small amounts of energy and sometimes the nuclei escaped without any hits at all. The results were obtained when relevant neutron fluencies (2-5 x 10(12) n/cm2) were applied. Increased neutron fluencies gave higher doses both due to capture in boron and in nitrogen but in order to improve the ratio between the dose to targeted tumour cells and the dose to normal cells, the number of 10B atoms in the targeted cells had to be increased and/or the boron placed in the cell nuclei.
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8041898
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Disruption of the blood-brain barrier as the primary effect of CNS irradiation.
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The blood-brain barrier (BBB) is believed to be unique in organ microcirculation due to the 'tight junctions' which exist between endothelial cells and, some argue, the additional functional components represented by the perivascular boundary of neuroglial cells; these selectively exclude proteins and drugs from the brain parenchyma. This study was designed to examine the effects of irradiation on the BBB and determine the impact of the altered pathophysiology on the production of central nervous system (CNS) late effects such as demyelination, gliosis and necrosis. Rats, irradiated at 60 Gy, were serially sacrificed at 2, 6, 12 and 24 weeks. Magnetic resonance image analysis (MRI) was obtained prior to sacrifice with selected animals from each group. The remaining animals underwent horse-radish peroxidase (HRP) perfusion at the time of sacrifice. The serial studies showed a detectable disruption of the BBB at 2 weeks post-irradiation and this was manifested as discrete leakage; late injury seen at 24 weeks indicated diffuse vasculature leakage, severe loss of the capillary network, cortical atrophy and white matter necrosis. Reversal or repair of radiation injury was seen between 6 and 12 weeks, indicating a bimodal peak in events. Blood-brain barrier disruption is an early, readily recognizable pathophysiological event occurring after radiation injury, is detectable in vivo/in vitro by MRI and HRP studies, and appears to precede white matter necrosis. Dose response studies over a wide range of doses, utilizing both external and interstitial irradiation, are in progress along with correlative histopathologic and ultrastructural studies.
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8041897
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The influence of transurethral resection of prostate on prognosis of patients with adenocarcinoma of the prostate treated by radical radiotherapy.
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Results of 999 patients with carcinoma of the prostate treated with radical radiotherapy were evaluated to assess the impact of pre-treatment transurethral resection of the prostate. (TURP). A total of 427 patients had a needle biopsy and 541 patients had a TURP. In 31 patients the diagnostic procedure could not be ascertained. In patients with stage T1/T2 disease (411) no adverse effect on prognosis was observed following TURP compared with needle biopsy. In patients with stage T3/T4 disease (534) a significantly higher distant relapse rate and cause-specific mortality were observed after TURP but overall survival was similar after TURP and needle biopsy. A significant correlation was observed between the probability of TURP and poorly differentiated cancers. Multivariate analysis which evaluated the influence of age, T stage, histologic differentiation and TURP did not demonstrate diagnostic TURP to be a significant independent prognostic variate for patients with prostate cancer managed by radical radiotherapy.
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8041896
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Controversies in the management of laryngeal cancer: results of an international survey of patterns of care.
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Cancer of the larynx is the most prevalent non-cutaneous malignancy of the head neck region and its treatment presents a threat to both natural speech and survival. This study examines the manner in which two separate specialties in the same and different geographic regions vary in their opinions about the treatment of glottic laryngeal cancer. The goal was to define options available to patients and to classify controversies about optimal treatment which might be resolved in clinical trials. Questionnaires depicting different presentations of glottic larynx cancer were mailed to 1649 otolaryngologists and radiation oncologists in North America, Europe and Australasia. Half the doctors were asked to describe their preferred treatment for a patient while the others were asked to imagine that they themselves were the patient. In all the disease situations opinions varied significantly with respect to the treatment modality advised (whether to employ surgical or radiotherapy approaches) and in more extensive disease situations the intention of treatment also varied depending on whether a curative approach should involve conservation or loss of the larynx. Doctors also recommended similar treatment for their patients as they would for themselves. Apart from disease extent the most significant variables influencing recommendations were the physicians' specialty (P = 0.0001) and where they practice (P = 0.0001). These findings demonstrate diversity of opinion which is influenced more profoundly by the traditions of the specialties and geographic location of practice than by the reported results of treatments for laryngeal cancer. Convictions about optimal management have become barriers to the assessment of the relative value of different treatments and to ensuring that patients are fully informed about management options. The profession should regard as a high priority efforts to resolve these therapeutic conflicts which are associated with major differences in quality of life.
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8041895
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Influence of radiotherapy treatment time on control of laryngeal cancer: comparisons between centres in Manchester, UK and Toronto, Canada.
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A comparison has been made of the influence of treatment time on tumour control rates for 496 (T2 and T3) larynx cancer cases in Manchester, UK and 1001 (T1-T4) cases in Toronto, Canada. Both series of patients were treated in fairly short overall times, commonly 3 weeks in Manchester and 4-5 weeks in Toronto. All the tumour control data were analysed using the same method to obtain values of fitted dose, fractionation and time parameters. The analysis showed the following. (a) Differences between the total combined (T2 + T3) data sets from the two centres, fitted using direct analysis and the LQ model incorporating a parameter for overall treatment time, were not significant (p = 0.17) and close similarity in control rates was observed using treatment regimens common to both series. (b) The Manchester series over 9-41 days and the Toronto series over 14-84 days are both consistent in showing for (T2 + T3) tumours the presence of a mean time factor of 0.6-0.8 Gy/day required to abrogate the decrease in tumour control concomitant with an increase in overall treatment time from the minimum the maximum employed in each series. (c) When a parameter was included in the model to test for the possible presence of a lag period before the time factor became operative, the lag was not significant for the Toronto data, in contrast to a significant lag for the Manchester data alone (T2 + T3 data).(ABSTRACT TRUNCATED AT 250 WORDS)
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8041894
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The molecular basis for cell cycle delays following ionizing radiation: a review.
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Exposure of a wide variety of cells to ionizing (X- or gamma-) irradiation results in a division delay which may have several components including a G1 block, a G2 arrest or an S phase delay. The G1 arrest is absent in many cell lines, and the S phase delay is typically seen following relatively high doses (> 5 Gy). In contrast, the G2 arrest is seen in virtually all eukaryotic cells and occurs following high and low doses, even under 1 Gy. The mechanism underlying the G2 arrest may involve suppression of cyclin B1 mRNA and/or protein in some cell lines and tyrosine phosphorylation of p34cdc2 in others. Similar mechanisms are likely to be operative in the G2 arrest induced by various chemotherapeutic agents including nitrogen mustard and etoposide. The upstream signal transduction pathways involved in the G2 arrest following ionizing radiation remain obscure in mammalian cells; however, in the budding yeast the rad9 gene and in the fission yeast the chk1/rad27 gene are involved. There is evidence indicating that shortening of the G2 arrest results in decreased survival which has led to the hypothesis that during this block, cells repair damaged DNA following exposure to genotoxic agents. In cell lines examined to date, wildtype p53 is required for the G1 arrest following ionizing radiation. The gadd45 gene may also have a role in this arrest. Elimination of the G1 arrest leads to no change in survival following radiation in some cell lines and increased radioresistance in others. It has been suggested that this induction of radioresistance in certain cell lines is due to loss of the ability to undergo apoptosis. Relatively little is known about the mechanism underlying the S phase delay. This delay is due to a depression in the rate of DNA synthesis and has both a slow and a fast component. In some cells the S phase delay can be abolished by staurosporine, suggesting involvement of a protein kinase. Understanding the molecular mechanisms behind these delays may lead to improvement in the efficacy of radiotherapy and/or chemotherapy if they can be exploited to decrease repair or increase apoptosis following exposure to those agents.
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8041893
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Israel in the elimination phase of poliomyelitis--achievements and remaining problems.
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Following the introduction of a combined EIPV and OPV schedule in 1990, no more cases of paralytic poliomyelitis were diagnosed and no wild poliovirus strain was isolated in the sewage. 100% seropositivity and high geometric mean titers (GMTs) to the three types of poliovirus vaccine strains and to the type 1 poliovirus 1988 epidemic strain were observed at the completion of the immunization schedule and one year later. The study of the immune profile of various age groups vaccinated with either EIPV or OPV had shown that the immunity to the epidemic poliovirus strain was less satisfactory, in terms of percent of seropositivity and GMTs, than to the poliovirus vaccine strains. In individuals previously immunized with either EIPV or OPV a high and quick immune response to both the 1988 epidemic and vaccine strains was observed after a booster dose of OPV. Follow-up to four years after the booster pointed to some decrease in the extent and intensity of the seropositivity to the 1988 epidemic strain as compared to the immune profile to the poliovirus vaccine strains. Maintaining Israel in the phase of polio elimination requires: > 95% national coverage, homogenously distributed; maintaining high immune profile to the three poliovirus types, including a satisfactory immune level to the 1988 epidemic strain in all the age groups at risk of polio; early detection of the introduction of wild poliovirus into the environment and of the occurrence of foci of indigenous activity; reducing the risk of exposure to massive infectious doses.(ABSTRACT TRUNCATED AT 250 WORDS)
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8041892
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Poliomyelitis in selected African and Asian countries.
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The most common cause for the persistence of poliomyelitis in developing countries has been the failure of routine immunization programs to provide > or = three doses of poliovirus vaccine to a high proportion of infants. However, a more worrisome pattern of disease can be attributed more to vaccine failure than failure to vaccinate, as illustrated by epidemics in selected African and Asian countries during the 1980s. The efficacy of oral poliovirus vaccine (OPV) has been shown in these and other instances to be considerably lower in developing countries than in industrialized countries, indicating that reliance on routine administration of OPV alone will not be sufficient to achieve global eradication of wild poliovirus transmission. Because more aggressive approaches will likely be needed to achieve global eradication of poliomyelitis, various tactics have evolved over the past decade. The most promising approach has been the use of biannual national vaccination days, which have been used with great success in Latin America. However, these campaigns have certain drawbacks, including enormous OPV requirements and difficult logistics. A second approach, which has been used primarily in the West Bank and Gaza, involves the use of combined schedules of OPV and enhanced-potency inactivated vaccine (IPV). This approach requires far fewer contacts and doses of OPV; allows for more reliable and consistent serum neutralizing antibody responses in both the short- and long-term; and for boosting of secretory antibody responses in both the nasopharynx and gastrointestinal tract.(ABSTRACT TRUNCATED AT 250 WORDS)
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8041891
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Experience with poliovaccines in the control of poliomyelitis in India.
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OPV was introduced in the National Immunisation Programme (NIP) in 1979. The reported number of cases of poliomyelitis was about 20,000 in 1979, 38,000 in 1981; it gradually declined to the pre-immunisation level of 20,000 in 1986, but increased to 28,000 in 1987. In 1989, 10 years after NIP, the reported number of cases fell below the pre-immunisation level, and has further declined to 5669 in 1991. The 3-dose OPV coverage during infancy was estimated to be about 80% in 1991. If reporting efficiency is 10%, then about 60,000 cases would have occurred in 1991, for an incidence of disease of about 7/100,000 in the total population of 840 million. Three questions arise: (1) Why did it take over 10 years of NIP to reduce the disease burden? (2) Why is the disease occurring at a high incidence level in spite of 80% immunisation coverage? (3) Will we be able to eliminate poliomyelitis and eradicate polioviruses by the year 2000 by sustaining the high immunisation coverage using 3 doses of OPV? In most countries, the incidence of disease has declined immediately after instituting NIP including OPV. The vaccine efficacy (VE) of 3 doses of OPV in India is 70-93%. Hence the lack of decline of incidence during 10 years of NIP was most probably because sufficient proportions of infants were not being immunised. The incidence remains high because the VE and herd effect of 3 doses of OPV are insufficient. Vaccine failure cases will account for 2-9 cases per 100,000 per year since pre-immunisation incidence was 30 and VE is 70-93%.(ABSTRACT TRUNCATED AT 250 WORDS)
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8041890
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Poliomyelitis in the eastern European countries--achievements and remaining problems.
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All European countries adopted in 1984 the Regional Target 5 of Health for All 2000 aimed at the elimination of poliomyelitis. From 1991 to 1992 the number of independent states in Eastern Europe has doubled (from 9 to 20). Physical and social environment, life-styles of the population, as well as public health and medical services in the majority of these states began to deteriorate due to political and economic crises. This led to increases in incidence of some infectious diseases, notably diphtheria and poliomyelitis. The incidence of poliomyelitis has risen in the Caucasus, Middle Asia, and Balkans, thus indicating new or ongoing epidemics in these areas. The highest incidence of the disease in the Balkan states was observed in 1991 (74 cases), in the Caucasian states in 1990 (251 cases), and in Middle Asia in 1991 (140 cases). There were two main reasons for the epidemics: (1) decreasing immunization coverage and (2) poor surveillance of poliomyelitis (late reporting, low sensitivity, etc.). Effective surveillance for cases of acute flaccid paralysis as the key strategy for guiding immunization policies is not yet organized in the overwhelming majority of states. Affected countries do not have national immunization programmes formulated according to the WHO/EPI standard. Difficulties in production or purchasing of vaccines, lack of competence and managerial skills, and inadequate political and financial support may play a negative role in eliminating poliomyelitis. However, even under these unfavorable conditions, supplementary immunization activities, such as appropriate outbreak response and mass immunization campaigns, helped to reduce the incidence of the disease in 1991 four- to eight-fold compared to the previous period.
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8041889
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Elimination of poliomyelitis in France: epidemiology and vaccine status.
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In France, both inactivated poliovirus vaccine (IPV) and oral poliovirus vaccine (OPV) were used until 1983. By that time a new enhanced-potency IPV (eIPV) was licensed and recommended by the French Ministry of Health as the vaccine of choice. Ninety-five per cent of infants have received four doses of eIPV by 24 months of age. No cases of vaccine-associated paralysis among either recipients or those in contact with recipients have been reported since 1983. Only four wild indigenous cases of paralytic poliomyelitis have been reported among unvaccinated children in the past five years and none since 1990. Although paralytic poliomyelitis has been virtually eliminated in France, vaccination programs as well as active surveillance of the community and environment for poliovirus circulation should be reinforced to reach the goal of wild poliovirus eradication.
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8041888
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Surveillance of poliomyelitis in the United Kingdom.
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Routine surveillance of poliomyelitis is undertaken through statutory notification, laboratory reporting, and examination of death certificates where poliomyelitis is mentioned. All health districts report weekly and include zero reporting of poliomyelitis in their returns. UK weekly reports on poliomyelitis are forwarded to WHO Europe. There have been no wild virus cases for over a decade. Since August 1991, there has been active surveillance of acute flaccid paralysis (AFP) in children under 16 years. All Consultant Paediatricians are contacted monthly through the British Paediatric Surveillance Unit and asked for reports of any cases of AFP. These are then investigated further. The study protocol specifies the investigations that are required for AFP cases, including stool samples for virology. AFP rates from this surveillance, approximately one per hundred thousand children under 16 years, provide a valuable guide for industrialised countries; consideration is being given to extending this scheme into the adult population. In 1992, a 44-year-old man died after sudden onset of AFP. Histology suggested poliomyelitis, and intensive investigations were undertaken to establish a diagnosis. The role of AFP surveillance and investigation of suspected cases are discussed in the light of the need to establish that poliomyelitis has been eliminated.
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8041886
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The elimination of polio in the Scandinavian countries.
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The Nordic countries, i.e., Denmark, Finland, Iceland, Norway, and Sweden, together with Holland, have all continued to use the killed poliovaccine introduced in the middle of the 1950s and they still use it today. In Denmark, combined vaccination has been practised since 1966, starting with three doses of the killed vaccine and continuing with the oral vaccine. Norway used oral vaccine alone during the 14-year period from 1965 to 1979. In all these countries, the immunizations with the killed vaccine were immediately successful. Poliomyelitis was practically eliminated already by the beginning of the 1960s. After this initial successful period, the different countries experienced different events, from which valuable conclusions can be drawn: 1. Nationwide vaccination with killed vaccine was highly effective. 2. It is of the utmost importance that the potency of the killed vaccine is high. 3. Oral vaccine may cause higher rates of vaccine-associated secondary cases than have been reported in general. 4. In the Nordic countries, the general circulation of wild virus appeared to cease simultaneously with the disease. 5. When virus is reintroduced into the country, unvaccinated groups are vulnerable. Outbreaks in unvaccinated "pockets" have occurred. This phenomenon, however, has also been experienced in countries using oral vaccine. 6. In Stockholm, both wild poliovirus and vaccine-like polio strains were isolated from the sewage water, indicating a constant import of both types of viruses. Virus isolation from thousands of patients with meningitis or diarrhoea have been negative throughout the years.
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8041884
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Basic conditions for the eradication of poliomyelitis--indications for a common prescription.
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The efforts of the last decade to achieve the world eradication of poliomyelitis have resulted in several problems of methodology and field implementation of the polio control program: (1) The concept of eradication. Its present definition refers to the complete absence of activity of the wild poliovirus. It is the result of the decision to recommend the use of OPV for the world control of polio and leaves unanswered the problem of the paralytic disease associated with OPV. (2) Besides a successful vaccination policy the control of polio implies a satisfactory environment. Risk factors in the environment mean persistence of endemicity and reoccurrence of disease, even after several years of absence of polio activity. (3) Concerning the limitations of the two available vaccines, problems of immunogenicity, safety, and thermostability are associated with OPV. Use of EIPV requires a high coverage of all the ages at risk of infection, and gut immunity is lower than that induced by OPV. On the other hand, several observations point to the limitation of OPV to prevent the spread of the wild virus into the vaccinated community, as claimed for EIPV. Limitations of OPV are mainly vaccine associated paralytic disease in the developed countries, and wild virus associated disease in "vaccinated" individuals in the developing countries. Disease associated with EIPV programs is observed practically only in nonvaccinated individuals. EIPV, particularly if associated with OPV, offers a clear advantage over OPV alone, in terms of immunogenicity, safety, and protective efficacy. (4) Total elimination of paralytic poliomyelitis can hardly be conceived of without the use of the EIPV.
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8041883
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Combined OPV and IPV program in control of poliomyelitis in two endemic areas--a potential tool in the struggle to eradicate poliomyelitis.
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Success in control of poliomyelitis since 1978 and eradication of cases since 1988 in Gaza and the West Bank was achieved by use of a combination of oral polio vaccine and inactivated polio vaccine despite presence of the wild virus in the environment and among visitors from endemic areas. This approach may be a useful strategy in the international struggle to control or eradicate poliomyelitis.
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8041881
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Global eradication of poliomyelitis: reinvent the wheel or use existing options effectively?
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The development of serum and nasopharyngeal antibody response, and the magnitude and temporal pattern of fecal shedding of vaccine and revertant polioviruses was examined in infants previously immunized with one or more doses of oral poliovirus vaccine (OPV), enhanced-potency inactivated poliovirus vaccine (EIPV), or both. The fecal samples were collected at different intervals after the last OPV dose. The nucleic acid sequences of the purified RNA obtained from all virus isolates were examined in the 5' noncoding region by dideoxysequencing to determine whether the viruses shed represent revertants (vaccine), nonrevertants, or both. The frequency and duration of vaccine virus-shedding appeared to be similar in both immunization schedules. Revertant virus shedding was not demonstrated 30 days after immunization with OPV alone. However, shedding of revertants was detected for as long as 60 days in some subjects previously immunized with EIPV. The duration of shedding of revertant virus differed with different serotypes and different immunization regimens. Prior immunization with one or more doses of OPV reduced the length of shedding of revertant virus. Significantly, however, prior immunization with one or more doses of EIPV was not associated with reduced shedding of revertant virus types. The nature of serum immune response as determined by ELISA or neutralizing antibody appeared to be similar after either immunization schedule, although the antibody titers were quantitatively higher after two doses of IPV than observed after a similar schedule with OPV. Highest antibody activity was detected in subjects immunized with a combination of IPV followed by OPV. ELISA antibody activity in the nasopharynx was regularly detected after either form of immunization.(ABSTRACT TRUNCATED AT 250 WORDS)
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8041880
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Can we agree on a prescription? A view from the perspective of the developing countries.
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There are serious obstacles, particularly on the African Continent, to the application of the official strategy for eradication of poliomyelitis. Outbreaks in countries where a potent OPV was used keep raising the question of its efficacy in routine programs. Based on the South American strategy, 200 million doses of OPV are needed for the 11 million children born each year. Such quantities of vaccine can hardly be procured for the rest of the world. Organization of vaccination campaigns will be competing with other public health programs. Studies in Africa and in the Middle East have shown the good performance of one or two doses of eIPV combined with DTP. At the current price of the quadruple vaccine DTP-eIPV, its cost effectiveness not only in money, but in practical terms, especially for the inventory, the cold chain, and the delivery, would be extremely attractive.
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8041879
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An end to Manicheism.
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Although each vaccine has limitations, both OPV and E-IPV have made a considerable contribution to the effective control of polyomyelitis. In view of the complementary advantages of the two vaccines, more use of their association in a common schedule is quite justified. An association of OPV and E-IPV, in which the latter is combined with DTP, seems particularly advantageous immunologically, logistically, and economically. There are several alternative ways in which the two vaccines could be associated sequentially or simultaneously. In addition, each vaccine could be used as a booster for routine programs with the other vaccine.
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8041878
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Methods for poliomyelitis eradication: is there a consensus?
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I have been a strong advocate, for many years, for the merits of IPV for the control of poliomyelitis, and the ultimate eradication of the disease and of poliovirus from the environment (Beale AJ. Poliovaccines: time for a change in immunization policy? Lancet 1990; 335:839-842). I have also recognized how fortunate we are in the Public Health field to have such an excellent vaccine as Sabin's OPV. Dr. Foege has argued aloquently and cogently for an approach that uses both vaccines: OPV and IPV. The EPI programme has used 3 or 4 doses of OPV, but in a number of developing countries this has proved inadequate to provide satisfactory control. In South America the use of 10 or more doses has been required to bring the disease under control. A combined approach of using killed poliovaccine combined in DTP and three doses of OPV seems to be the preferred consensus solution. It would cause the minimum and, hopefully, no disruption of the existing programmes of the EPI. It would almost certainly bring forward the day when poliomyelitis will be controlled and the disease at least will be eradicated. It is clear that the sooner this is done the better. It is cheaper to do it now, although it requires more funds in the short term; and it is better for the children of the world--present and future. The extra cost of putting IPV into DTP is probably about one US$ per course, which is probably no more expensive than giving six more doses of OPV, when the total costs of administration are considered.(ABSTRACT TRUNCATED AT 250 WORDS)
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8041877
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Poliomyelitis eradication in Europe: programme and activities.
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The WHO Regional Office for Europe is committed to the eradication of poliomyelitis in Europe, as a part of the WHO effort to achieve the world eradication of polio by the year 2000. The European Advisory Group on EPI has adapted in 1993 the operational targets for the regional eradication of polio, which focus on surveillance, outbreak response, and immunization coverage. Policies recommended by WHO have been translated into plans for action by 9 European countries among those which still reported cases of polio. The Regional Office for Europe of WHO has concentrated its efforts in the following areas: 1. Implementation of essential strategies on immunization (mopping-up or national immunization days) in countries having high-risk areas with endemic transmission of wild poliovirus. 2. Improvement of surveillance, which is a major strategic component. Its key element is the surveillance of acute flaccid paralysis. Its implementation started in Europe in 1991. 3. Development of a regional laboratory network involved in the routine diagnosis of poliomyelitis. The network began to be operational in 1991. In 1992 polio morbidity, reported by 17 countries, has shown a downward trend as compared to 1991. Anyhow, some foci of wild poliovirus activity still persist in the Balkan countries, the Trans-Caucasian region, and several Central Asia republics of the former Soviet Union. The main limitations to progress in polio eradication in Europe are: absence of strong political support at the national level; lack of financial support, which may delay the translation of WHO recommendations into proper action at the national level; availability of polio vaccine, which may become a problem in the absence of adequate support; and the unsatisfactory pace of improvement of the polio surveillance.
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8041876
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Elimination of poliomyelitis in Europe: remaining problems to solve.
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Global eradication of paralytic poliomyelitis is feasible since the causative agents, three serotypes of poliovirus, have no other natural host species and since the vaccines developed against poliomyelitis are highly effective. The WHO program for 'Global Eradication of Paralytic Poliomyelitis by the Year 2000' has made great progress during the last few years. Yet, more than 100,000 new cases of the disease still occur annually in the world. In Europe, paralytic poliomyelitis is a rare disease but appears to persist in restricted areas and occurs at a very low incidence in several European countries, mostly as an imported entity. Importation of wild polioviruses to Europe will continue as long as endemic circulation of the viruses is taking place somewhere in the world. Attention has to be paid to improve the surveillance of both suspected clinical cases and of putative wild poliovirus circulation in the population. In several Eastern European countries political and economic turbulence may endanger the maintenance of immunization programs. International collaboration is needed to prevent reestablishment of indigenous poliovirus circulation in these regions.
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8041875
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The polio epidemic in The Netherlands, 1992/1993.
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Starting September 1992, an outbreak of poliomyelitis occurred in the Netherlands. Until now a total of 67 cases have been notified. These were the first indigenous cases since 1978. None of the patients had been vaccinated before, and all but one belong to small Protestant groups that refuse vaccination for religious reasons. The age of the patients varies from several days to 61 years (mean age 19) and the male to female ratio is 1.6:1.0. The epidemic is caused by wild poliovirus type 3. Partial genomic sequencing showed closest resemblance to a virus isolated in India in 1991. The epidemiological characteristics of the present outbreak are similar to those of previous outbreaks in the seventies. Although vaccination coverage in the Netherlands is excellent (97% coverage for the first series of three doses with IPV vaccine), outbreaks can be expected because some socially closely interrelated small groups refuse vaccination (totalling about 200,000 persons) for religious reasons. Experience from this epidemic, from previous epidemics, and preliminary results of random stool and sewage sampling indicate very little circulating virus among the general population. Changes in (implementation of) the vaccination policy, including a mixed strategy with OPV and IPV, are being considered to reduce the risk of similar outbreaks in the future.
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8041874
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Studies on the etiology of acute acalculous cholecystitis: the effect of lipopolysaccharide on human gallbladder mucosal cells.
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Previous studies in animals have shown that lipopolysaccharide produces experimental cholecystitis possibly through a platelet-activating factor-prostanoid mediated process. In this study it was intended to evaluate the effect of LPS on primary cultures of human gallbladder mucosal cells. Gallbladder mucosal cells were isolated from gallbladders removed during routine cholecystectomies or other operations. The cells were cultured for 24 h before treatment. Unstimulated cells produced low levels of prostanoids and significant basal levels of PAF. LPS produced stimulation of eicosanoid and PAF secretion. The increased prostanoid formation was not enhanced when LPS and PAF were administered together. Prostanoid synthesis was inhibited by the administration of a cyclooxygenase inhibitor while administration of a PAF receptor antagonist significantly increased prostanoid formation, suggesting that increased PAF levels function as a negative control mechanism to decrease prostanoid synthesis. The results suggest that endotoxemia may produce a cascade of inflammatory processes in human gallbladder mucosal cells resulting in the development of acute acalculous cholecystitis.
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8041873
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Fish oil supplementation attenuates free radical generation in short-term coronary occlusion-reperfusion in cholesterol-fed rabbits.
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We studied the changes in lipid peroxidation and prostanoid metabolism in short-term coronary occlusion-reperfusion in controls and those rabbits (11 in each group) fed a 1% high cholesterol diet with or without 10% fish oil supplementation for one week. Acute coronary occlusion for 10 minutes was induced by ligating the marginal branch of the left circumflex coronary artery. The vessels were then reperfused for 1 hour. The cholesterol and fish oil treated rabbits had the lowest malondialdehyde levels both in the ischemic and non-ischemic (normal) areas, the least increase of malondialdehyde level in the ischemic area, and the highest 6-keto-PGF1 alpha/thromboxane B2 ratio in the non-ischemic area after reperfusion among the 3 groups. These rabbits had the highest myocardial superoxide dismutase levels both in the ischemic and normal areas, and the least decrease of superoxide dismutase level in the ischemic area. These data suggest that rabbits fed a high cholesterol diet with fish oil supplementation had an attenuated lipid peroxidation, which reflected a reduced free radical generation during a short-term coronary occlusion followed by reperfusion.
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8041872
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Measurement of canine urinary thromboxanes by GC-MS and HPLC-RIA.
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Immunoaffinity extraction/gas chromatography-mass spectrometry (IA/GC-MS) and high-performance liquid chromatography-radioimmunoassay (HPLC-RIA) methods were developed to analyse a major human urinary thromboxane metabolite, 2,3-dinor thromboxane B2, in the urine of dogs, a species commonly used for functional studies of thromboxane pharmacology. The beta-metabolite 2,3-dinor TXB2 was unequivocally identified in pooled normal canine urine by IA/GC-MS, and its excretion measured in 6 anesthetized dogs over a 7h period as 2001 +/- 132 pg 2,3-dinor TXB2/mg creatinine (range 624-4493 pg/mg). Thromboxane immunoreactivity co-eluting with synthetic 2,3-dinor TXB2 was also identified by HPLC-RIA and similarly determined (2585 +/- 276 pg/mg creatinine). Exogenous 2,3-dinor TXB2 could be quantitatively recovered by both methodologies over a wide range of concentrations (50-5000 pg/mL), although with better precision by IA/GC-MS (added vs recovered; m = 1.05, r = 0.99) compared with HPLC-RIA (added vs recovered; m = 0.89, r = 0.89). The cyclooxygenase inhibitor indomethacin given by infusion in anaesthetized dogs (2.5, 8 and 25 micrograms/kg/min) dose-dependently inhibited 2,3-dinor TXB2 excretion measured by IA/GC-MS, with maximal inhibition (83.0 +/- 4.2%) being achieved after 6h (25 micrograms/kg/min). Similar results were obtained by HPLC-RIA, with a correlation of 0.88 (slope = 0.9) between the methodologies in samples after drug treatment. These data suggest that the profile of metabolism and excretion of thromboxanes in dogs resembles that of man, and provide a useful animal model for the non-invasive in vivo assessment of inhibitors of thromboxane biosynthesis.
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8041871
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An improved assay for urinary LTE4.
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An improved method for the measurement of urinary LTE4 is described, based on the combined use of solid phase extraction (SPE)-HPLC-enzyme-immunoassay (EIA). This allows the use of homologous radioactive tracer in easily measurable amount for HPLC retention time evaluation and recovery estimation. Recovery linearly correlated with the total amount of LTE4 present in the extracted sample, indicating the existence of a carrier effect. Identification of immunoreactivity in HPLC fractions as LTE4 was based on parallel dilution assay and confirmed by the observable isotopic separation between tritium labeled LTE4 and immunoreactive LTE4. Critical selection of urine sample size, on the basis of creatinine content, together with efficient purification by SPE, resulted in total absence of aspecific immunoreactivity in fractions surrounding those associated with LTE4. Urinary LTE4 was measured in normal subjects and in cirrhotic patients, where an increased LTE4 excretion has been reported. The method described fulfils the criteria of specificity, sensitivity and accuracy necessary for a potential successful use in the study of sulfidopeptide leukotrienes formation in normal and pathological conditions.
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8041869
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Humidity regulation in the management of asthma patients sensitized to house dust mites.
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Substances in the faeces of house dust mites are well-recognized as common allergens in the pathogenesis of asthma. There have been many trials of interventions aimed at reducing mite populations in the home, but most have been uncontrolled, too small, or too short to determine with confidence any beneficial effects. Of those which succeeded, very few used methods which reduced mite populations on a permanent basis. House dust mites are sensitive to humidity. Their geographical distribution is closely correlated to the availability of moisture. Very little work has been done on the effects of reducing humidity in the home environment in the long term, with a view to controlling dust mite populations. Two different methods which might reduce humidities to levels which could successfully reduce dust mite numbers are dehumidifiers, and mechanical ventilation with heat recovery (MVHR). To date there has been no work assessing the effectiveness of dehumidifiers and very little (although promising) work on MVHR. We discuss the potential of humidity control as an adjunct to the clinical treatment of asthma.
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8041868
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Hyperparathyroidism, glucose tolerance and platelet intracellular free calcium in chronic renal failure.
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Disturbance in the vitamin D/parathyroid hormone (PTH) axis may be important in the pathogenesis of glucose intolerance and insulin resistance in uraemia. To investigate possible relationships between hyperparathyroidism, intracellular free calcium ([Ca2+]i), and glucose tolerance in chronic renal failure, we measured serum intact PTH (I-PTH) by two-site immunometric assay, platelet [Ca2+]i using the fluorescent indicator fura-2, and plasma glucose and insulin after 14 h overnight fast and at 30, 60 and 120 min following a 75 g oral glucose load, in 18 chronic haemodialysis patients with elevated serum I-PTH. Calcitriol (1 microgram) was administered parenterally at the end of each dialysis session for four weeks. This significantly decreased serum I-PTH (p < 0.001) and platelet [Ca2+]i (p < 0.01). Uraemic patients initially showed marked glucose intolerance, with increased area below the glucose curve compared to healthy controls, but after 4 weeks of calcitriol treatment, this effect was significantly decreased, and there was a significant rise in the area under the insulin curve after glucose load. The insulinogenic index also increased significantly after calcitriol treatment. These data suggest that calcitriol treatment of haemodialysis patient with secondary hyperparathyroidism is associated with increased insulin secretion in response to glucose challenge, and that this change is linked to the decrease in intracellular free calcium.
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8041867
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Primary angiitis of the CNS diagnosed by angiography.
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Sixteen patients (8 female, 8 male) with primary angiitis of the CNS (PACNS), were followed prospectively in a vasculitis clinic. Diagnosis was by angiography in patients without underlying disease. Median age at diagnosis was 36.5 years, and median duration of follow-up was 28 months. Onset was acute in 14 patients (88%), with 3.5 weeks (median) from onset symptoms to diagnosis. Three women developed symptoms within 3 weeks postpartum. The most frequent symptoms were severe headaches (12, 75%), stroke (6, 30%), transient ischaemic attack (TIA) (4, 28%), seizures (7, 44%), visual aberration (3, 19%), and cognitive impairment (5, 31%). Laboratory data included high ESR (2, 13%), leucocytosis (8, 80%), thrombocytosis (1, 6%), positive antinuclear antibody titre (3, 15%), and high levels of complement (5, 31%). Lumbar puncture was performed in 12 patients (75%). CSF analysis was abnormal in five patients (42%). EEG was abnormal in 5/9 patients. The major CT/MRI scan findings were cerebral haemorrhage (4, 25%), brain infarcts (5, 31%), brain atrophy (2, 13%) and non-specific lesions (2, 13%). Four patients had normal studies. All patients received corticosteroids (CS), and five were treated with oral cyclophosphamide. Two patients relapsed despite CS and cyclophosphamide therapy. All patients are alive, and at the last assessment, eight had a permanent neurological deficit, which included paresis (3, 19%), neurocognitive abnormalities (2, 13%), visual loss (2, 13%) and seizure activity (5, 31%). Our data suggest a non-progressive, non-fatal course in those PACNS patients diagnosed angiographically and treated with CS with or without cyclophosphamide.
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8041866
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Cryptococcal meningitis (C. neoformans var. gattii) leading to blindness in previously healthy Melanesian adults in Papua New Guinea.
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Cryptococcal meningitis is a common cause of chronic meningitis in Papua New Guinea, affecting apparently immunocompetent people. The majority of infections are believed to be due to Cryptococcus neoformans var. gattii. We have reviewed the records of 49 Melanesian adults who presented with proven cryptococcal meningitis to the University teaching hospital in Port Moresby, and compare our findings with other published studies of cryptococcal meningitis in the tropics and sub-tropics. None of the patients had an obvious cause of immunosuppression. Visual disturbances and fundoscopic changes of papilloedema or papillitis were particularly common. The in-hospital case fatality rate for patients treated with amphotericin B and flucytosine was 22.4%. Of the fully treated patients, 31% became completely blind before being discharged from hospital. Therapy directly aimed at reducing intracranial pressure may improve outcome.
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8041865
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Glomerular disease as a cause of isolated microscopic haematuria.
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Microscopic haematuria is a common clinical finding, with reported prevalences of up to 22%. The role of renal biopsy in the investigation of this condition is still debated. Currently urological investigation including cystourethroscopy is often regarded as adequate. We investigated 165 patients (94 male, 71 female; mean age 37.5 years, range 10-71) referred with isolated microscopic haematuria, using renal biopsy and cystourethroscopy. All patients were normotensive with normal serum creatinine, no proteinuria, sterile urine and a normal IVU. Renal biopsy abnormalities were found in 77/165 (46.6%): IgA nephropathy (49), global or segmental mesangial proliferative glomerulonephritis without IgA deposits (16), thin membrane nephropathy (7), vascular changes suggestive of hypertension (3), interstitial nephritis (1), and membranous nephropathy (1). Only five abnormalities were found on cystourethroscopy (cystitis 3, urethral stricture 1, bladder stone 1). Two patients with cystitis also had IgA nephropathy. Biopsy abnormalities were commonest under the age of 20 (69.2%), but 40% of biopsies were abnormal even in the seventh decade of life. Because renal biopsy abnormalities are very frequent in patients with isolated haematuria, renal biopsy is indicated in patients over 45 years of age if renal imaging and cystoscopy are normal. In those under 45 years, renal biopsy should replace cystoscopy as the investigation to follow normal renal imaging.
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8041861
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Change in the number of informal helpers of frail older persons.
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Little is known of the extent to which helper networks of frail older persons change over time and what factors are associated with change. Few national estimates of the scope of change exist to aid policy planners. This study provides national estimates of changes in the size of the informal helping network of frail elderly by sociodemographic and functional status subgroups of this segment of the population. The data are drawn from the 1982-84 National Long Term Care Survey, which included longitudinal followup of 4,530 respondents living in the community at both times. Bivariate patterns of change over 2 years in the number of informal helpers were analyzed. Sociodemographic factors (sex, age group, and race) of the frail elderly may be more important influences on change in the number of helpers than functional status expressed in terms of their limitations in activities of daily living.
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8041860
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Evaluation of the Consensus Health Status Indicator for assessing adolescent pregnancies and births.
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The authors used vital statistics and population data for DeKalb County, GA, in an evaluation of the accuracy of the Consensus Health Status Indicator for assessing adolescent pregnancies and births. The indicator used was the number of births to females 10-17 years of age, expressed as a percentage of all births in the population. The investigators found no significant changes in the proportions of births to adolescents for the period 1982-90. Births to adolescents were 5.3 percent of all births during 1982-84 and 5.2 percent during 1988-90. However, the pregnancy rate for adolescents in those years increased significantly, from 27.9 per 1,000 births for 1982-84 to 33.1 per 1,000 for 1988-90. The results indicate that, in localities with substantial changes in the age distribution of the population, the health status indicator does not adequately reflect trends in pregnancies among those 10-17 years of age.
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8041859
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Evaluation of Group Health Cooperative of Puget Sound's Senior Influenza Immunization Program.
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The goal of this study was to identify areas in which an influenza immunization campaign for seniors, sponsored by a health maintenance organization (HMO), could be improved. This study was conducted at Group Health Cooperative of Puget Sound (GHC), serving approximately 470,000 enrollees in Washington State. A survey was administered to two groups of seniors drawn at random--those who received influenza vaccine and those who did not, during the fall and winter of 1991. Immunization rates were almost 75 percent for "well" seniors and 85 percent for "chronically ill" seniors. Bivariant analysis showed that two activities of the influenza campaign were associated with vaccine compliance: a provider-generated recruitment letter and exposure to an immunization article in the enrollee newsletter. Using a broader framework for predicting vaccine compliance, logistic regression showed that vaccine compliance was associated positively with previous immunizations and belief that "my doctor wants me to get a shot," and negatively with fear of adverse reaction and belief that the vaccine is ineffective. There were few suggestions for improving the immunization program, among both vaccinated and unvaccinated enrollees. Approximately two-thirds of unvaccinated enrollees said there was nothing GHC could do to convince them to be vaccinated. These findings suggest high vaccine compliance and satisfaction with an HMO-sponsored influenza campaign. Strategies and potential to further increase vaccination rates are discussed.
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8041858
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Is the high ischemic heart disease mortality rate in New York State just an urban effect?
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To determine whether New York State's high ischemic heart disease mortality rate was due primarily to an urban effect, rates for regions in the State were compared with each other and with national data. New York State mortality rates for the period 1980-87 were highest for New York City (344.5 per 100,000 residents), followed by upstate urban and rural areas (267.1-285.1), and New York City suburbs (272.5). However, the overall 1986 age-adjusted rate for the New York State region with the lowest mortality rate (265.7) exceeded that of 42 States. New York State's number one ischemic heart disease mortality ranking reflects the need for statewide intervention programs, because even regions with relatively low mortality rates are high when they are compared with national rates.
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8041857
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Risk behavior for HIV transmission among gay men surveyed in Seattle bars.
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Men attending four Seattle gay bars were asked to complete a self-administered questionnaire including measures of sexual behavior, perceptions of peer norms in the area of sexual safety, personal human immunodeficiency virus (HIV) risk estimate, and knowledge and use of a variety of acquired immunodeficiency syndrome (AIDS) prevention services. Twenty-nine percent of the sample reported engaging in unprotected anal intercourse at least once during the 2 months before the survey. Differences in peer norm perceptions, age, HIV risk estimate, and intent to be sexually safe in the future were found between those engaging in unprotected anal intercourse and those not reporting unprotected anal intercourse. No significant differences were found in level of education, use of AIDS prevention services, and whether or not a person had been tested for HIV. Implications for prevention programs are discussed.
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8041856
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Building a community-based consortium for AIDS patient services.
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The authors describe a 3-year effort by a public health care system in a large metropolitan area to obtain Federal funds for treating patients with acquired immunodeficiency syndrome (AIDS). During that process, program planners moved incrementally from proposing an exclusively medical model to one emphasizing the activities of a coalition of community based organizations (CBO). Successive proposals for Federal funding reflected increasing understanding of the nature and functioning of CBOs in providing case management and other support services. The third application proposed devoting 34.5 percent of the budget to CBO activities. That application, which was successfully funded, provided leverage and momentum for the concept of the interdisciplinary, broadly based services consortium which has evolved in Denver since 1989. The consortium has been instrumental in the 55.9 percent reduction in the cost of medical care for AIDS patients that has occurred.
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8041855
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The impact of providing incentives for attendance at AIDS prevention sessions.
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The research literature on AIDS prevention efforts contains many reports on the impact of intervention sessions. Little information is available, however, on the success of various strategies to recruit clients to attend these sessions. An assessment of the comparative impact of money and other types of incentives on group attendance in two AIDS risk reduction projects, in the Harlem area of New York City and in Cleveland, OH, was undertaken. In both projects, injecting drug users and the sex partners of injecting drug users were recruited to participate in group sessions that focused on the reduction of AIDS risk behaviors. Data on group attendance were analyzed for 838 people in the New York project and 1,168 in the Ohio project. After the projects were underway, attendance incentives at both were changed from money to food coupons or gift certificates. Results indicated that a nonmonetary incentive was associated with a significant decline in group attendance. Concerns regarding paying monetary incentives to injecting drug users are discussed.
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8041854
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Sexual risk behavior of incarcerated, drug-using women, 1992.
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In this study, sexual risk behavior of 104 incarcerated female drug users is examined. Findings demonstrate that incarcerated women who use drugs are at high risk for human immunodeficiency virus (HIV) infection because of their behavior prior to arrest. During the month prior to arrest, the majority of respondents were sexually active. Half reported past sexual contacts with injecting drug users, and more than one-third had traded sex for money or drugs. Consistent with other studies, condom use was more frequent with casual or commercial partners. Those who traded sex for money were less likely to be white Anglo or regular heroin users, and more likely to be regular crack users and alcoholic, have fathers who were drug or alcohol users, and perceive themselves as at-risk for contracting HIV and other sexually transmitted diseases.
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8041853
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Prevalence of illicit drugs detected in the urine of women of childbearing age in Alabama public health clinics.
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Each year, it is estimated that from 350,000 to 739,000 U.S. infants are exposed in utero to one or more illicit drugs. To estimate the prevalence of and risk factors for illicit drug use by women of childbearing age in Alabama, during 2 months in 1991 the authors collected patient-reported histories, clinical histories, and urine specimens from 6,195 women statewide attending public health maternity clinics, family planning clinics, and a high-risk referral obstetrical clinic. Blind drug screening of urine specimens for marijuana, cocaine, opiates, barbiturates, and amphetamines was performed with the use of a fluorescent polarization immunoassay. The overall prevalence of positive results for drugs tested was 10.1 percent, including 8.4 percent of the 3,554 pregnant and 12.3 percent of the 2,571 nonpregnant women screened. The drugs most frequently detected were marijuana and cocaine. Characteristics of the subjects associated with a higher prevalence of positive results for any drug tested or for marijuana included white race, older age, being divorced, non student occupation, having 12 or less years of education, attending a clinic located in a suburban county, self-reported substance use, increased risk for human immunodeficiency virus infection, and reproductive history. Characteristics of women with positive screening for cocaine results were similar to those who tested positive for any drug, except that the prevalence of cocaine was higher among black women and those attending urban county clinics and did not vary by years of education. Patient-reported histories of drug use were insensitive in identifying women who had positive drug screening results (sensitivity, 6.3 percent; specificity, 98.2 percent). Thus, in this study,the use of illicit drugs among women of childbearing age attending public clinics in Alabama was common and emphasizes the need for targeted drug education and interventions to reduce the impact of drug use on this high-risk population.
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8041852
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A state program for postpartum HIV counseling and testing.
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The New York State Department of Health began its Obstetrical HIV Counseling/Testing/Care Initiative in 1989. The objective of the initiative was to expand the availability of and access to human immunodeficiency virus (HIV) infection counseling and voluntary testing in the postpartum setting. Programs have been initiated in 24 hospitals statewide. The initiative emphasizes cooperative arrangements within participating hospitals for referring patients to medical and social services. Participation by hospitals in the initiative is voluntary. Initial grants to hospitals for the initiative ranged from $50,000 to $80,000. The main obstacle in implementing the initiative has been a lack of such resources as administrative or clinical support, phlebotomy services, and office or clinical space. During the period from August 1, 1990, through March 31, 1992, 16,436 women at risk for HIV infection were counseled in the postpartum setting at 24 hospitals participating in the initiative. Of them, 6,754 (41.1 percent) consented to HIV testing. Of the 6,754 tested, 3,000 women (44.5 percent) returned to receive test results and posttest counseling. Counseling and testing activities supported through the initiative identified 196 of 1,227 (16 percent) of the HIV-positive women who gave birth at participating hospitals and 196 of 892 (22 percent) seropositive women not previously identified. Combining testing data from the initiative with other data on seropositivity, the authors estimated that 43.3 percent of HIV-positive women delivering infants at participating hospitals were identified by voluntary testing. Hospital performance in the program varied markedly. Further study is needed to determine how to improve the effectiveness of the effort to identify HIV-positive childbearing women at the less successful hospitals and to enhance the rates of patients returning for posttest counseling and community followup.
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8041851
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Peer discussions of cancer among Hispanic migrant farm workers.
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Hispanic migrant agricultural workers' exposure to pesticides and other agrichemicals places them at increased risk for a variety of acute and chronic conditions, including cancer. As a socioeconomically disadvantaged group, migrant workers also face many barriers to effective cancer control. In 1992, a series of focus groups was held with 55 Hispanic migrant agricultural workers (22 women, 33 men) in central Wisconsin to gather information on their knowledge and attitudes regarding cancer etiology and treatment, their practices regarding cancer screening and early detection, and their concerns regarding occupational exposure to pesticides. Beliefs that pesticides are toxic and can cause health problems were common among participants. In addition, however, participants reported that they are reluctant to demand occupational protections to which they are entitled because they are afraid of losing their jobs. Study results also suggest that barriers to effective primary and secondary prevention of cancer in this Hispanic migrant agricultural worker population include knowledge and information barriers, cultural barriers, and socioeconomic barriers. A lack of knowledge and information regarding the causes of cancer, its prevention, and its early detection and treatment was evident among participants, which in turn was reflected in strong fatalistic attitudes toward the disease. Cultural barriers included attitudes of embarrassment and shame associated with physical examinations and women's strong discomfort with male clinicians. Socioeconomic barriers to secondary prevention included the cost of obtaining health services, time constraints associated with the need to work and long working days, and a lack of transportation. Efforts to improve cancer screening as well as other preventive health services in the Hispanic migrant agricultural worker population must acknowledge these barriers and address as many of them as possible to be successful.
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8041850
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Factors influencing the return rate in a direct mail campaign to inform minority women about prevention of cervical cancer.
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The Forsyth County Cervical Cancer Prevention Project was a 5-year community-based health education program funded by the National Cancer Institute. The program was developed to reduce cervical cancer mortality among black women in Forsyth County, and it was targeted to those ages 18 and older. The program tried to educate the target population through a combination of mass media and direct education. This paper reports on an experiment conducted to investigate sources of influence on the effectiveness of direct mail, a technique used to augment mass media health education. Direct mail has shown promise as a method for reaching target populations that are difficult to reach with other mass media approaches. Using commercially prepared mailing lists sorted by zip code and other characteristics of the resident, health-related materials can be targeted to persons at their homes. A randomized experiment involving 1,000 households was carried out to estimate the influence of type of postage and address (name versus "resident or occupant") on the response rate to direct mail. Results indicated that there was no significant advantage from use of first class over bulk rate postage, but the return was significantly greater when the envelope bore a name rather than "resident or occupant."
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8041849
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The urban church and cancer control: a source of social influence in minority communities.
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A study was conducted to examine the efficacy of a church-based model of social influence in improving access to and participation of underserved minority women in a cervical cancer control program. The model expanded on strategies used in previous hypertension control and health promotion research. A total of 24 churches, stratified by faith tradition, were randomly selected to participate in the cancer control program from a pool of 63 churches in a defined geographic area of Los Angeles County, CA. Female parishioners ages 21 years and older were eligible to participate in cervical cancer education sessions, and screening was offered to adult women who had not had Papanicolaou tests within the last 2 years. Church participation rate was 96 percent. Thirty lay health leaders were selected by the clergy to serve as messengers, recruiters, and organizers for their respective congregations. Ninety-seven percent of these lay health leaders participated in two training sessions designed to prepare them for their leadership role. Social support structures such as child care, meals, or transportation for targeted women were organized by lay health leaders in 78 percent of the churches. A total of 1,012 women between the ages of 21 and 89 years attended educational sessions. Forty-four percent of the eligible women were targeted for screening because they had not had a Papanicolaou test within the last 2 years or had never been screened. Black women were 6.6 times more likely than Hispanics to have been screened in the past 2 years. Hispanic women were 4.2 times more likely than African Americans never to have had a Papanicolaou test or been tested in 3 or more years.Overall, 90 percent of the women targeted for screening recruitment presented for tests.Fifty-two percent of the churches initiated cancer control activities by the end of the 2-year period following the culmination of the intervention program.The findings suggest that a church-based model of social influence can leverage the participation of minority women in cervical cancer control, provide access to underserved Hispanic women in particular,and sustain cancer control activities beyond the life of an intervention program.The findings further suggest that a more discrete assessment of screening history may improve the participation levels of African American women, and that the gratis offering of screening services may adversely affect their participation rates.
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8041848
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Medical community involvement in a breast cancer screening promotional project.
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The analysis, mobilization, and involvement of medical communities in two counties targeted for intervention by the Washington State Community Breast Cancer Screening Project is described. Principles of community organization were applied to the health care sectors in the counties, and the PRECEDE-PROCEED model was used as a conceptual framework for considering individual physician behavior. Quantitative and qualitative medical community assessment methods included a demographic study, a survey of primary care physicians, personal interviews with physicians, and medical office staff focus groups. In both intervention areas, physician planning groups selected, developed, and helped implement intervention activities targeting the health care sectors. These activities included informational mailings to physicians, training of medical office staff members and clinical mammographers, and support for a reminder system. The experience demonstrated that physicians practicing in medium-sized cities are willing to be active in community disease prevention programs.
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8041847
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Analyzing organizational practices in local health departments.
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Few researchers have examined the problem of comparing the performances of local health departments. A contributing factor is the lack of a uniform method for describing the range of public health activities. The Centers for Disease Control and Prevention's Public Health Practice Program Office has identified 10 organizational practices that may be used to assure that the core functions of public health are being carried out at a local health department. The researchers determined the percentage of time devoted to each of the 10 practices by individual employees at a local public health unit in Tampa, FL. They identified the manpower expenditures and hours allocated to each of the 10 practices within the major program divisions of the unit. They found that the largest portion of manpower resources was allocated to implementing programs. A much smaller fraction of agency resources was devoted to analysis of the health needs of the community and to the development of plans and policies. Together, primary care and communicable disease programs accounted for fully three-quarters of the resources, environmental health for 11 percent, and administrative support services for 13 percent. With continuing refinement and modification, the methodology could provide a highly effective basis for describing and analyzing the activities and performances of local health departments.
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8041846
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Implementing and assessing organizational practices in local health departments.
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One of the most difficult forms of public health practice to characterize involves governmental public health agencies, especially at the local level. A lack of consensus within the public health community as to the purpose and content of organizational public health practice inhibits efforts to increase the capability of public health to address effectively its core functions of assessment, policy development, and assurance. Meaningful capacity building efforts must establish both benchmarks and expectations for the organizational practice of public health. Those markers must be established so that the impact of practice on outcomes and health status can be examined. A model identifying 10 organizational practices was established through the work of the Centers for Disease Control and Prevention (CDC) in collaboration with national practice organizations. Early applications of the model to public health capacity building activities have been effective. Among the applications have been approaches to surveillance of health department practice, certification of local health departments using practice guidelines, and development of leadership within the public health enterprise. Although results are promising, use of the model requires additional external examination and validation, as well as acceptance and consensus within the public health community. The development of organizational practice guidelines for public health agencies may be useful in further efforts to characterize and measure public health practice and its impact on the public's health.
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8041845
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Money for guns: evaluation of the Seattle Gun Buy-Back Program.
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Community involvement in local firearms policy is advocated to be an important component of efforts to curtail violence. This report describes the first evaluation of one such effort, a gun buy-back program conducted in Seattle, WA, during the fall of 1992. The evaluation included (a) surveys of 500 participants and a description of the firearms exchanged; (b) monitoring police reports, trauma center admissions, and medical examiners' data to assess short-term effects on the frequency of firearm-related events; and (c) an assessment of community beliefs by random-digit dialing telephone interviews of 1,000 residents. Of the 1,172 firearms relinquished, 95 percent were handguns, 83 percent were operational, and 67 percent were owned for more than 5 years. Twenty-five percent were exchanged by women. The mean age of participants in the exchange program was 51 years. Females and persons in older age groups were more likely than males (83 percent versus 70 percent, P < 0.01) and minors (88 percent versus 55 percent, P < 0.05) to select safe disposal as motivation to participate. Comparing firearm-related events per month before and after the program, crimes and deaths increased, and injuries decreased, but the changes were not statistically significant. Telephone interviews revealed broad support for publicly funded gun buy-back programs even among households (61 percent) with firearms. Gun buy-back programs are a broadly supported means to decrease voluntarily the prevalence of handguns within a community, but their effect on decreasing violent crime and reducing firearm mortality is unknown.
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8041836
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Recycling unused medical supplies: a surgeon's response.
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In Third World countries, there is a desperate need for basic medical supplies. Surgeons are responsible for a significant amount of medical waste in operating rooms, and much of that waste comes from partially used prepackaged sterile operative sets. In October 1992, InterVol established a regional pilot program in Rochester, N.Y., to test the feasibility of collecting unused medical supplies from area health-care facilities and shipping them to countries that need them. This project was designed to help hospitals dispose of reusable medical supplies while providing direct support to Third World hospitals and to medical teams that volunteer in Third World countries. In the process, a data base was created, which could be analyzed to find new ways of limiting unused materials that needed to be discarded. This project operated in four phases: (1) setup and education, (2) collection, (3) sorting and inventory, and (4) distribution. The program was proved to be effective and may serve as a model to help other communities establish similar programs.
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8041835
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Refinement of McIndoe's vaginal reconstruction with ORFIT "S" vaginal stent.
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Using McIndoe's vaginal reconstruction with the ORFIT "S" vaginal stent, we achieved good results in 5 patients with congenital vaginal absence over the past 3 years. The ORFIT "S" vaginal stent is a semirigid, porous, and inexpensive stent. The application is easy intraoperatively, and minimal daily care is required for long-term postoperative dilatation. The stent keeps the neovagina in full acceptance of the speculum after long-term follow-up.
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8041834
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Surgery of the aging chin.
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A technique is described for surgery of the aging chin that I use in every rhytidectomy patient. A mentalis-periosteal flap is developed, advanced downward, and sutured in a "vest over pants" manner over the platysma muscle under the submental crease. The submental crease is obliterated by the double layer of muscle created by the muscle closure. The same technique is used in chin reductions and chin augmentations, as well as normal aging ptosis of the chin. Since muscle and fat are never excised, one can use this simple procedure on every face lift without fear of creating a contour deformity. This technique gives consistently good results but should only be used when combined with face lift surgery which includes a wide cervical dissection.
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8041833
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An unusual periosteal osteochondromatous proliferation in the hand.
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A very rare case of an unusual periosteal osteochondromatous proliferation is reported. For this tumor, there exists a discrepancy between the malignant histopathologic characteristics and the good prognosis. Therefore, it is very important to consider this pathologic entity in the preoperative differential diagnosis of hand and foot tumors so that no serious functional or cosmetic damage is caused by an inappropriate radical operation.
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8041832
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Abdominal-wall reconstruction with expanded musculofascial tissue in a posttraumatic defect.
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An anatomic basis for expansion of the abdominal wall is presented and clinically demonstrated in an adult man with a posttraumatic defect. The patient demonstrates an intact, functional abdominal wall 4 years after the procedure. The procedure provides autogenous, innervated, well-vascularized, contractile tissue for repair of abdominal-wall hernias. Large tissue expanders are placed between the external oblique and internal oblique muscles. A small incision in the posterior rectus sheath is made in order to gain access to the potential space between these muscles. The incision in the posterior rectus sheath is kept small to minimize risk of denervation of the rectus abdominis muscle. Tissue expansion is carried out over several weeks. After removal of the expanders, abundant musculofascial tissue is available for reconstruction of the abdominal wall. The abdominal wall is then reconstructed with innervated, functioning tissue.
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8041831
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Free composite latissimus dorsi muscle-rib flap not containing the intercostal artery and vein for reconstruction of bone and soft-tissue defects.
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Reconstruction of bone and soft-tissue defects of the forehead and leg was done with use of a free latissimus dorsi muscle-rib flap. By utilizing the curve characteristic of the rib and by filling the cavity with latissimus dorsi muscle, the forehead could be restored in a good shape. In our application of this flap to the leg, it is considered in retrospect that reconstruction with the use of two ribs should have been done. Furthermore, it was concluded that in comparison with the heretofore employed vascularized rib graft, the scope of operative invasion is small in the use of this flap with hardly any risk of thoracostomy.
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8041830
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Gigantic lipomas.
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Two cases of unusually giant lipomas--weighting 5070 and 4000 gm--are described. Tumors were present for 5 years on the back in a 55-year-old man and for 20 years at the anterior compartment of the thigh in an 80-year-old woman. Difficulty in fitting clothes was the first patient's sole complaint, and social pressure was actually the reason that brought him to his doctor. The second patient suffered from pain during the last 2 years. The weight of the bigger tumor was calculated preoperatively from the uptake of technetium-99m DTPA during scanning. Dissection of the tumors from the surrounding tissues was extremely easy in both cases. At 5 years and 1 year following surgery, there is no evidence of recurrence.
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8041829
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Earlobe reconstruction with a reversed-flow chondrocutaneous postauricular flap and a local flap.
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An earlobe reconstructive method using a reserved-flow chondrocutaneous flap and a local flap is described. Two patients are reported whose earlobes were reconstructed by this method. By this method, earlobes of bilateral symmetry can be produced without fail. The blood circulation of both flaps is satisfactory. Since conchal cartilage is used, an earlobe of satisfactory shape can be maintained for a long period, but the reconstructed earlobe is slightly firm when palpated.
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8041826
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The effects of lip repair with and without soft-tissue undermining and delayed palate repair on maxillary growth: an experimental study in beagles.
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Undermining of the soft tissue on the surface of the maxilla at the time of cleft lip repair remains a controversial issue in cleft management. Using 64 eight-week-old beagles, we tested the hypothesis that lip repair with soft-tissue undermining contributes more to maxillofacial growth aberrations than lip repair without these additional procedures. Animals were assigned to four groups: unoperated controls, unrepaired controls, and two experimental groups (with and without undermining). Defects simulating cleft of the lip, alveolus, and palate were surgically created in the unrepaired and experimental animals. At 36 weeks of age, 11 measurements were made directly on the cleaned maxillae. Analysis revealed that all groups with surgically created defects were significantly different from normal; however, animals with undermining exhibited the greatest group deviation from normal. These findings reaffirm our earlier conclusions that undermining of the soft tissue on the surface of the maxilla is detrimental to maxillofacial growth.
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8041825
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Multiple CT imaging in pressure sores.
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In patients affected by pressure sores, bones can be reached easily by the infection. This suggested a new way for a more precise diagnostic evaluation, looking at the most recent technological knowledge, which can offer a better evaluation of single lesions for a better planning of surgical operations. The possibility of performing multiple imaging under a CT guide, as well as a simple technique for contrast permanence within the sore, led the authors to demonstrate the validity of modern CT scanning as a main diagnostic method.
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8041824
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Autotransfusion and reduction mammaplasty: a reappraisal in the 1990s.
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Since the first report of autotransfusion and blood loss in major anesthetic procedures by Noone et al. in 1972, much has changed. The single most significant event is the development of the AIDS epidemic. With today's stringent and precisely defined transfusion criteria, the current practice of routinely using autologous units for reduction mammaplasties has caused considerable controversy. This study reviews the mean estimated blood loss during reduction mammaplasty and the use of autologous transfusion during a 46-month period at the Hospital of the University of Pennsylvania ending in November of 1991. The need for red blood cell transfusion is retrospectively analyzed. One-hundred female patients were entered into the study. The results demonstrate a decrease in blood loss from an average of 865 ml in the 1970s to 385 ml in the 1990s and suggest that routine employment of autologous transfusion is no longer necessary.
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8041823
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What influences public perceptions of silicone breast implants?
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In an effort to determine public attitude regarding breast implants in the wake of what many might consider biased media publicity, surveys of women and men in Milwaukee were made. Questionnaires appropriate to each of four groups [patients with reconstructions (n = 54), mastectomy without reconstruction (n = 14), those with augmentation mammaplasty (n = 26), and the general public (n = 60)] were administered. Some of the findings included the following: Over 98 percent had heard of the controversy; most had received their information from the media, with less than 10 percent referring to a medical journal; only 6 percent felt that the media coverage was objective, while 88 percent felt that the media were biased; almost two-thirds of those in the general population were not aware of any other method of reconstruction; and almost half that same group would have significant hesitancy in having the procedure on themselves or a family member were it indicated. In summary, our findings would substantiate the fact that the media do exert a very significant influence on the public's perception of silicone breast implants. Though most people surveyed generally consider the media biased, they still use them as the primary source for their negative conclusions on the matter. Though the media cannot be viewed as our ally in this matter, we, as a group, might be better served by minimizing conflict, which makes the whole issue less newsworthy.
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8041822
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Hyaluronic acid-filled mammary implants: an experimental study.
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Issues of radiolucency and biocompatibility of currently available mammary implants have prompted the search for alternatives. Several new filler materials have been suggested recently but have involved the use of materials foreign to the body. We have studied the use of a naturally found polysaccharide molecule, hyaluronic acid, as an alternative filler material to silicone gel. We tested hyaluronic acid-filled implants using standard mammographic techniques, applanation tonometry, and in an in vivo animal model (n = 24) up to 1 year after implantation. The present study demonstrates that hyaluronic acid-filled implants have softness comparable with that of silicone gel and saline implants and are more radiolucent, allowing better visualization of breast structures around the implant. Furthermore, in vivo studies fail to demonstrate any adverse reactions to the material over a period of 1 year. Hyaluronic acid has unique properties in modulating the process of wound healing, and these properties may be applied to the tissues surrounding the implants as a result of leaching of hyaluronic acid through the covering shell. Although further studies using larger volumes of filler, characterization of the hyaluronic acid within the implant, quantification of the exact amounts of hyaluronic acid leached into surrounding tissues, and a more appropriate primate model need to be undertaken, this pilot study points out that there may be more biologically compatible materials for the use in breast implants that warrant further investigation.
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8041821
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Periprosthetic bacteria and the breast implant patient with systemic symptoms.
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This report presents seven women with breast implants who experienced systemic symptoms which resolved rapidly after implant removal. A hypothesis is that these symptoms (which have been labeled "silicone poisoning" or "silicone adjuvant disease") may actually be caused by periprosthetic bacteria which have generally been considered innocuous, e.g., Staphylococcus epidermidis. In these cases, systemic symptoms such as malaise, fatigue, diarrhea, muscle aches, and arthralgia rapidly resolved after an antibacterial regimen plus implant removal without capsulectomy. Of cultures taken by swab in four patients, all were positive; of those taken by irrigation in three patients, one was positive. I believe that these patients' symptoms were real and offer the hypothesis that treatment of periprosthetic bacteria might explain rapid clinical improvement following explantation.
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8041820
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Health risks of failed silicone gel breast implants: a 30-year clinical experience.
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The purpose of this paper is an assessment of clinically evident systemic health problems associated with failed silicone gel breast implants. A computer search of the medical records of 2033 patients receiving implants in the years 1962-1992 revealed that between 1970 and 1992, 200 women 14 to 75 years of age underwent secondary silicone gel breast implant procedures by a single surgeon. This allowed determination of the exact integrity status of 681 implants collectively placed in these 200 patients between 1962 and 1992 and followed clinically for a median of 49 months. The common indications for surgical reexploration in these 200 patients were capsulectomy, open capsulotomy, or implant exchange/removal. All patients had a minimum clinical follow-up of 6 months. Surgical findings revealed that 577 (85 percent) implants were intact in 135 (67.5 percent) patients and that in 65 (32.5 percent) patients, 104 (15 percent) implant failures were found. The patients' medical records were reviewed with specific attention to diagnoses suggesting immune-related disorders, siliconoma, acquired non-breast malignancies, metachronous breast cancer, and recurrent breast carcinomas. In this very select subgroup of 65 patients with silicone gel breast implants which had failed or were deteriorating, no excess of expected immune-related disorders or malignancies was identified. Our 30-year clinical experience with silicone gel breast implants for augmentation mammaplasty or breast reconstruction failed to demonstrate that clinically evident adverse health problems are incurred by those women who subsequently experience a silicone gel breast implant failure.
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8041819
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Surgical treatment of axillary osmidrosis: an analysis of 343 cases.
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From July of 1986 to July of 1992, 343 patients have received surgery for axillary osmidrosis by partially removing skin and cellular tissue en bloc and removing the subcutaneous cellular tissue of the adjacent area. A total of 102 patients were followed for 4 months to 6 years, with an average of 32 months. The total satisfaction rate was 91 percent (93 of 102). The wound complication rate was 6.715 percent (46 of 685). There were no scar contractures or limitations of arm abduction. In this paper we emphasize three merits of our procedure. One is that partially removing the skin promises definite excision of more than half the eccrine glands which were located in the dermis of the operative field. The second merit is good exploration for undermining and defatting of the under-surface of the adjacent area. The third merit is a low wound complication rate because the width of the skin excision is less than 3 cm. Therefore, partial removal of skin and cellular tissue en bloc and the subcutaneous cellular tissue of the adjacent area is the choice for surgical treatment for axillary osmidrosis.
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8041818
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A retrospective study of 66 esophageal reconstructions using microvascular anastomoses: problems and our methods for atypical cases.
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We have studied 66 patients who underwent esophageal reconstruction using microvascular anastomoses. This series comprises 28 patients with reconstruction using a free jejunal interposition between the pharynx and the cervical esophagus following pharyngolaryngoesophagectomy for hypopharyngeal carcinoma and 38 atypical patients in whom other methods of reconstruction were used. Successful transfer was achieved in 98.5 percent (65 of 66). Issues concerning atypical reconstruction and our procedures in these cases are discussed. In order to obtain adequate tension in the jejunum on the anal side, in particular, since the anastomosis is located in a deep or narrow space, autosuture instruments were used. The anastomotic leakage rate was 2.8 percent (1 of 36); the stenosis rate was 2.8 percent (1 of 36). To prevent necrosis in the trachea, a greater omentum flap was used in three patients, a mesenterium flap in two, and a pectoralis major musculocutaneous flap in one. There were no significant complications. In patients with a short gastric pedicle or in those in whom a double cancer occurred in the hypopharynx and thoracic esophagus, a gastric pedicle and a free jejunum flap were used together. As a result of this method, the incidence of any reflux of digestive juice was reduced to 0 percent (0 of 6). To reduce the possibility of an ischemic complication at the oral end of the colonic pedicle, we added a microvascular anastomosis of the colonic pedicle, thereby reducing both leakage [0 percent (0 of 9)] and necrosis [0 percent (0 of 9)]. These procedures involving microvascular anastomoses have reduced the incidence of complications in esophageal reconstructions.
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8041817
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New perioral arterial flaps: anatomic study and clinical application.
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We studied the vascular anatomy of the perioral region by dissecting fresh cadavers. The anatomy of perioral branches of the facial artery consistently confirmed the existence of a septal branch and an alar branch to the upper lip and a vertical labiomental branch to the lower lip. New regional flaps supplied by these perioral arterial branches are proposed in this paper. The mucosal flap from the upper lip supplied by the deep septal branch or the alar branch of facial artery can be used to restore lower lip defects. A composite flap from the lower lip supplied by the vertical labiomental branch of the facial artery can be used safely to restore combined defects of the upper lip and nose or partial defects of the lower lip.
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8041816
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Secondary reconstruction for unfavorable microtia results utilizing temporoparietal and innominate fascia flaps.
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Unfavorable results in reconstruction of the auricle for microtia can be encountered from time to time, in which secondary reconstruction of the auricle is usually performed. One must note that secondary reconstruction is much more difficult than primary reconstruction for the following reasons: (1) all necrotic skin and scar tissue from the primary reconstruction must be removed, thus limiting the surface area of the skin for the secondary reconstruction; (2) the presence of scar tissue and loss of tensility in the subdermal layer makes it difficult to construct a subcutaneous pocket for grafting of the three-dimensional costal cartilage framework; and (3) in patients with full-thickness skin grafts in the conchal and postauricular regions, contraction of the grafted skin was noted. In order to resolve these problems, the temporoparietal fascia flap was used in the first-stage three-dimensional frame grafting operation, and the innominate fascia flap, obtained from the same site as the temporoparietal fascia in the first-stage operation, was used for the second-stage operation. The retroauricular full-thickness skin graft was utilized for color match on the anterior surface of the auricle where it is visible, and substitute skin from the groin was used to cover the donor site. The procedures and results for secondary reconstruction for unfavorable microtia are presented in this article.
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8041815
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Oculonasal synkinesis.
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A phenomenon the authors have termed oculonasal synkinesis has been observed in 13 individuals in two independent practices. This complex presents as simultaneous contraction of the orbicularis oculi and the compressor narium minor muscles. When the patient blinks, the compressor narium minor muscle contracts, causing depression of the ala. Its etiology is postulated as the formation of anomalous connections between the temporal and zygomatic branches of the facial nerve, innervating the orbicularis oculi muscle, and the buccal branches of the facial nerve, innervating the compressor narium minor muscle. All 13 individuals who exhibited this phenomenon are female. This anomaly was displayed bilaterally in 7 patients, on the right side in 2 patients, and on the left side in 4 patients. A 2-month-old daughter of one of the patients who had bilateral presentation, also displayed the phenomenon. In 6 patients who underwent rhinoplasty, resection of the compressor narium minor muscle resulted in complete elimination of the abnormal muscle movement. The plastic surgeon who performs rhinoplasty should be cognizant of the synkinesis and discuss its presence with the patient, since a patient may consider this a surgical sequela upon discovering the condition postoperatively. Furthermore, this unintentional muscle function is aesthetically displeasing.
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8041814
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The use of Gore-Tex for nasal augmentation: a retrospective analysis of 106 patients.
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Numerous implant materials have been used in nasal surgery, including autogenous, homogeneous, and alloplastic grafts. Autogenous cartilage remains the ideal graft material; however, situations exist where an alternative or an additional grafting material is needed. Homogeneous materials have demonstrated significant resorption. Alloplastic grafts have offered varying degrees of success but have resulted in significant complications as well. Gore-Tex has undergone extensive research and clinical application in various surgical fields with reported success. This analysis examines 106 patients over a 5-year time period in which the Gore-Tex soft-tissue patch was used in a wide variety of situations from extensive nasal dorsal reconstruction to small localized nasal defects or irregularities. Postoperative follow-up has revealed a stable implant material with no complications relating to the graft material.
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8041813
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Cartilage engineered in predetermined shapes employing cell transplantation on synthetic biodegradable polymers.
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Cartilage is often used as structural support tissue for cosmetic repair in plastic and reconstructive surgery. We describe the efficacy of a new approach for the generation of cartilage in predetermined shapes using specially configured biodegradable synthetic polymer devices as delivery vehicles for transplanted cells. Synthetic biodegradable polymer scaffolds were configured in one of four specific shapes, i.e., a triangle, a rectangle, a cross, and a cylinder. The polymer matrices were seeded with freshly isolated bovine articular chondrocytes and then implanted subcutaneously into nude mice. Gross examination of excised specimens 12 weeks after implantation revealed the presence of new hyaline cartilage of approximately the same dimensions as the original construct. This cartilage showed no signs of resorption or overgrowth over the 12-week time course of the experiment. Histologic evaluation using hematoxylin and eosin stains confirmed the presence of normal mature hyaline cartilage in 46 of 48 specimens. These results suggest that cartilage can be created in predetermined shapes and dimensions using cell transplantation on appropriate polymer templates. This technology would be useful in cosmetic and reconstructive surgery.
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8041812
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In situ fluorescence spectroscopic studies on bovine cornea.
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The cornea is a transparent ocular tissue and its transparency is thought to be a result of intramolecular interactions and the supramolecular organization of its protein constituents. We have studied the intrinsic fluorescence properties of intact bovine corneas and compared these with that of the opaque sclera. It was observed that with increasing excitation wavelengths the emission maxima shifted toward the red edge exhibiting the phenomenon of red edge excitation shift, which is indicative of immobilization of the constituent fluorophores. The magnitude of the shift increased after photodamage by irradiation at 295 nm. Many of the spectral characteristics of the cornea are shown to be due to its proteoglycans, which show surprisingly significant red edge excitation shift in solution.
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8041811
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UVA-induced autocrine stimulation of fibroblast-derived collagenase/MMP-1 by interrelated loops of interleukin-1 and interleukin-6.
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Previous work has shown that fibroblast-derived collagenase/matrix-metalloproteinase-1 (MMP-1), responsible for the breakdown of dermal interstitial collagen, was dose-dependently induced in vitro and in vivo by UVA irradiation and this induction was at least partly mediated by interleukin-6 (IL-6). We here provide evidence that UVA-induced IL-1 alpha and IL-1 beta play a central role in the induction of the synthesis both of IL-6 and collagenase/MMP-1. In contrast to the late increase of IL-1 alpha and IL-1 beta mRNA levels at 6 h postirradiation, bioactivity of IL-1 is already detectable at 1 h postirradiation. This early peak of IL-1 bioactivity appears to be responsible for the induction of IL-6 synthesis and together with IL-6 lead to an increase of the steady-state mRNA level of collagenase/MMP-1 as deduced from studies using IL-1 alpha and IL-1 beta antisense oligonucleotides or neutralizing antibodies against IL-1 alpha and IL-1 beta. Besides the early posttranslationally controlled release of intracellular IL-1, a latter pretranslationally controlled synthesis and release of IL-1 perpetuates the UV response. From these data we suggest a UV-induced cytokine network consisting of IL-1 alpha, IL-1 beta and IL-6, which via interrelated autocrine loops induce collagenase/MMP-1 and thus may contribute to the loss of interstitial collagen in cutaneous photoaging.
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8041810
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Photosensitization with a chlorin-thiobarbiturate conjugate.
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The photobiologic properties of a chlorin-thiobarbiturate conjugate were examined. In addition to the characteristic 670 nm chlorin absorbance, the conjugate exhibited new absorbance bands at 517 and 743 nm, but these were not a part of the fluorescence emission spectra, nor was fluorescence observed at wavelengths > 670 nm. The action spectrum indicated that the long-wavelength absorbance of the conjugate was not involved in phototoxicity in cell culture, and that only irradiation at wavelengths associated with the chlorin moiety yielded a cytotoxic effect. In vivo cytotoxicity elicited by 745 nm irradiation is attributed to thermal effects.
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8041809
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Stratospheric ozone depletion between 1979 and 1992: implications for biologically active ultraviolet-B radiation and non-melanoma skin cancer incidence.
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The depletion of stratospheric ozone (O3) has predictable implications for increases in biologically damaging solar ultraviolet-B radiation (UVB, 280-320 nm) reaching the earth's surface. A radiative transfer analysis of satellite-based O3 measurements between January 1979 and December 1992 shows that surface UVB levels increased substantially at all latitudes except the tropics, if other factors such as cloud cover and local pollutant levels have remained constant over this period. Exposure to UVB radiation is known to induce basal cell and squamous cell skin cancers, and dose-response relationships derived from epidemiological data can be combined with the UVB enhancements to estimate the seasonal and latitudinal distribution of future expected increases in the incidence of these cancers.
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8041808
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UV induction of cyclobutane thymine dimers in the DNA of cultured melanocytes from foreskin, common melanocytic nevi and dysplastic nevi.
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We compared the induction of cyclobutane thymine dimers after exposure to 302 nm UV in foreskin-derived melanocytes and melanocytes from nevocellular nevi, as well as in melanocytes cultured from dysplastic nevi, precursor lesions of melanoma, derived from four, three and four individuals, respectively. Cyclobutane thymine dimers were quantified in situ by means of an immunofluorescence assay with a specific monoclonal antibody. A method was developed to compare separately performed experiments in a standardized manner. For melanocytes from each source, we demonstrated a linear relationship between UV dose and immunofluorescence. In nevocellular and dysplastic nevi, two subpopulations could be detected, distinguished by their nuclear size. Large nucleated nevocellular nevus cells were most susceptible to the induction of thymine dimers (49% higher induction compared to induction in foreskin melanocytes), while in normal-sized nuclei of these nevus cells the same induction of thymine dimers was found as in nuclei from foreskin melanocytes. In contrast, large nucleated dysplastic nevus melanocytes did not differ from the foreskin melanocytes, while normal-sized nuclei of dysplastic nevus cells showed a lower induction (32% lower induction than in foreskin melanocytes).
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8041807
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Laser photosensitization of cells by hypericin.
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Administering a light dose of 90 J/cm2 at 599 nm during incubation with hypericin to a highly differentiated normal epithelial cell line (FRTL-5), derived from Fisher rat thyroid, and to a neoplastic cell line (MPTK-6), derived from the lung metastases of a thyroid carcinoma induced in Fisher rats, produces cell kill at drug doses 1000 times lower than those necessary to cause the same mortality in the dark. The photocytocidal activity of this polycyclic quinone drug on neoplastic cells is superior to that of antitumor anthraquinone drugs, such as daunomycin and mitoxanthrone, and to the photosensitized antiviral activity previously reported for hypericin.
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8041806
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Structure-specific binding and photosensitized cleavage of branched DNA three-way junction complexes by cationic porphyrins.
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The interactions of cationic porphyrins with DNA oligonucleotides that form branched, three-way junction complexes (TWJ) were investigated using native gel electrophoresis, absorption spectroscopy and photochemical probing using DNA sequencing techniques. Meso-tetra(para-N- trimethylaniliniumyl)porphine (TMAP), meso-tetra(4-N-methylpyridiniumyl)porphine (T4MPyP) and meso-tetra(3-N-methylpyridiniumyl)porphine(T3MPyP) were found to bind more tightly to DNA TWJ than to DNA duplexes. The binding to the junction DNA persists at high ionic strength, conditions that greatly decrease porphyrin binding affinity to duplex DNA. THe TWJ DNA binding sites of TMAP and T4MPyP were localized to the junction region based on the observation of site- and structure-specific, porphyrin-sensitized photodamage to guanosine residues flanking the junction region.
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8041805
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The role of DNA damage in PM2 viral inactivation by methylene blue photosensitization.
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This study investigates the importance of DNA damage in viral inactivation by phenothiazines and light. Phenothiazines, including methylene blue (MB), toluidine blue and azure B are of particular interest because of their ability to bind to nucleic acids in vitro. Initial studies employing phages T7, MS2 and PM2 indicated that both DNA and RNA phages as well as enveloped and nonenveloped phages can be inactivated by phenothiazine photosensitization. PM2, which contains a lipid-protein bilayer and supercoiled DNA, was used for the mechanistic studies to model blood-borne viruses. Viral DNA damage was assessed following treatment of phage to known levels of viral inactivation by extracting the DNA and analyzing for both direct and piperidine-catalyzed strand cleavage by gel electrophoresis. DNA strand cleavage was found to be both sensitizer concentration and light dose dependent. Both viral inactivation and DNA damage were found to be oxygen-dependent events. In parallel experiments, strand cleavage of isolated PM2 DNA treated with MB and light was also found to be oxygen dependent, in contrast to some previous reports. Transfection studies, which measure the infectivity of the extracted viral DNA, indicated that DNA from MB-treated phage was just as capable of generating progeny virus as the untreated controls. It was therefore concluded that the observed DNA damage is not correlated with loss of phage infectivity.
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8041804
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Photodegradation of sulfamethoxazole: a chemical system capable of monitoring seasonal changes in UVB intensity.
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Sulfamethoxazole (SMX) in its nonionized form in aqueous solution has ultraviolet (UV) absorption that is maximal at 268 nm but extends through the ultraviolet-B (UVB) region. It was found to be extremely susceptible to photodegradation when exposed to artificial UV radiation through a Pyrex filter or to unfiltered natural sunlight. The SMX anion was more stable. The quantum yields of the photodegradation of both forms were determined by use of monochromatic light and ferrioxalate chemical actinometry, the values of 0.47 (pH 3.0) and 0.084 (pH 9.0) at the maximum absorption wavelengths (268 and 257 nm, respectively) being obtained. Using literature data on sunlight intensity, the photochemical shelf-life of SMX solutions exposed to direct sunlight was calculated for Sydney (latitude 33.5 degrees S) as a function of season of the year and verified experimentally. A fixed correlation was established between the rate constant for SMX degradation and UVB intensity measured by a radiometer, suggesting the capacity of this chemical system to monitor changes in the UVB region of sunlight.
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8041803
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Genetic analysis of Creutzfeldt-Jakob disease and related disorders.
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Genetic studies of over 200 cases of Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker syndrome (GSS), fatal familial insomnia (FFI) and kuru have brought a reliable body of evidence that the familial forms of CJD and all known cases of GSS and FFI are linked to germline mutations in the coding region of the PRNP gene on chromosome 20, either point substitutions or expansion of the number of 24-nucleotide repeat units. Phenotypic expression of FFI and familial CJD, clinically and pathologically distinct syndromes linked to the 178Asp-->Asn substitution, is dependent on a polymorphism at codon 129. Synthetic peptides homologous to several regions of PrP spontaneously form insoluble amyloid fibrils with unique morphological characteristics and polymerization tendencies. Peptides homologous to mutated regions of PrP exhibit enhanced fibrillogenic properties and, if mixed with the wild-type peptide, produce even more abundant and larger fibrous aggregates. A similar process in vivo may be the primary event leading to amyloid accumulation and disease.
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8041802
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An epidemiologist's view of bovine spongiform encephalopathy.
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Bovine spongiform encephalopathy was first recognized in Great Britain in 1986 and was the result of infection with a scrapie-like agent surviving in meat and bone meal used in feedstuffs. This effective exposure commenced in 1981-82 and was associated with a reduction in the use of hydrocarbon solvents in the manufacture of meat and bone meal. The epidemiological features are consistent with sheep scrapie as the original source, but the epidemic was amplified by the recycling of infected cattle tissue resulting in a marked increase in incidence from 1989. The food borne source was eliminated by legislation introduced in July 1988. The first effects of this became apparent during 1991 and these have become more obvious during 1993 with a reduction in the national incidence. Specific studies are still in progress to determine whether other means of transmission can occur, but none capable of maintaining the epidemic have been detected.
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8041798
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Cloning of four cyclins from maize indicates that higher plants have three structurally distinct groups of mitotic cyclins.
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While a large number of cyclins have been described in animals and yeasts, very limited information is available regarding cyclins in plants. We describe here the isolation of cDNA clones encoding four putative mitotic cyclins from maize. All four cyclins were able to induce maturation of Xenopus oocytes, demonstrating that they can act as mitotic cyclins in this system. Northern analysis showed that all four cyclins were expressed only in actively dividing tissues and organs, with a stronger correlation between expression and mitotic activity than is observed with cdc2. The deduced protein sequences suggest that the four maize cyclins belong to the cyclin A and B families identified from animal and yeast studies but that they cannot be described easily as either A-type or B-type cyclins. However, comparison with previously cloned plant cyclins shows that cyclins in higher plants form three distinct structural groups that have been conserved in both monocotyledonous and dicotyledonous species and that cyclins from all three groups are present within a single plant species.
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8041797
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Isolation and characterization of the gene encoding 2,3-oxidosqualene-lanosterol cyclase from Saccharomyces cerevisiae.
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The ERG7 gene encoding oxidosqualene-lanosterol cyclase [(S)-2,3-epoxysqualene mutase (cyclizing, lanosterol forming), EC 5.4.99.7] from Saccharomyces cerevisiae has been cloned by genetic complementation of a cyclase-deficient erg7 strain. The DNA sequence of this gene has been determined and found to contain an open reading frame of 2196 nt (including stop codon) that encodes a predicted protein of 731 amino acids. The predicted molecular mass of the S. cerevisiae cyclase, 83.4 kDa, is similar to the predicted molecular masses of the oxidosqualene-lanosterol cyclase from Candida albicans and the oxidosqualene-cycloartenol cyclase from Arabidopsis thaliana, as well as to the molecular masses assigned to vertebrate oxidosqualene-lanosterol cyclases; however, it is substantially larger than the molecular mass assigned to purified S. cerevisiae cyclase. At the level of DNA and predicted amino acid sequences, the S. cerevisiae and C. albicans cyclases share 56% and 63% identity, respectively. Tryptophan and tyrosine residues are unusually abundant in the predicted amino acid sequences of (oxido)-squalene cyclases, leading to a hypothesis that electron-rich aromatic side chains from these residues are essential features of cyclase active sites.
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8041796
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Targeted insertions of two exogenous collagen genes into both alleles of their endogenous loci in cultured human cells: the insertions are directed by relatively short fragments containing the promoters and the 5' ends of the genes.
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Previous studies demonstrated that type II procollagen is synthesized by HT-1080 cells that are stably transfected with constructs of the human COL2A1 gene that contain the promoter and 5' end of either the COL2A1 gene or the human COL1A1 gene. Since the host HT-1080 cells were from a human tumor line that synthesizes type IV collagen but not type II or type I procollagen, the results suggested that the constructs were integrated near active enhancers or promoters. Here, however, we demonstrate that a 33-kb construct of the COL2A1 gene containing a 5' fragment from the same gene was inserted into both alleles of the endogenous COL2A1 gene on chromosome 12, apparently by homologous recombination by a nonconservative pathway. In contrast, a similar construct of the COL2A1 gene in which the 5' end was replaced with a 1.9-kb fragment from the 5' end of the COL1A1 gene was inserted into both alleles of the locus for the COL1A1 gene on chromosome 17. Therefore, targeted insertion of the gene construct was not directed by the degree of sequence homology. Instead, it was directed by the relatively short 5' fragment from the COL1A1 gene that contained the promoter and the initially transcribed sequences of the gene. After insertion, both gene constructs were expressed from previously inactive loci.
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8041795
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Energy transfer analysis of Fos-Jun dimerization and DNA binding.
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The protooncogenes fos and jun encode proteins that bind to DNA as dimeric complexes and regulate gene expression. Protein dimerization is mediated by a leucine zipper and results in juxtaposition of regions of each protein rich in basic amino acids that comprise a bimolecular DNA binding domain. We have developed an approach based on resonance energy transfer for the quantitative analysis of dimerization and DNA binding by Fos and Jun in solution. Fos-(118-211) and Jun-(225-334) polypeptides were labeled with either 5-iodoacetamidofluorescein or rhodamine X iodoacetamide on unique cysteine residues located in their DNA binding domains. Formation of heterodimeric complexes between the labeled proteins allowed resonance energy transfer between the donor fluorescein and the acceptor rhodamine fluorophores. DNA binding induced a conformational transition that increased the efficiency of resonance energy transfer. This increase was consistent with a 3-A reduction in the distance between the fluorophores. Using this assay, we determined the affinity of the Fos-Jun interaction and examined the kinetics of dimerization and DNA binding as well as the rate of subunit exchange. Dimerization and DNA binding by Fos and Jun were rapid, with half-times of < 10 s. In the absence of DNA, Fos and Jun subunits exchanged rapidly, with a half-time of < 10 s. In contrast, in the presence of DNA, the complex was extremely stable. Thus, leucine zipper-containing transcription factors may exchange subunits readily when free in solution, but not when bound to DNA.
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8041794
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Differential expression and activation of a family of murine peroxisome proliferator-activated receptors.
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To gain insight into the function of peroxisome proliferator-activated receptor (PPAR) isoforms in mammals, we have cloned and characterized two PPAR alpha-related cDNAs (designated PPAR gamma and -delta, respectively) from mouse. The three PPAR isoforms display widely divergent patterns of expression during embryogenesis and in the adult. Surprisingly, PPAR gamma and -delta are not activated by pirinixic acid (Wy 14,643), a potent peroxisome proliferator and activator of PPAR alpha. However, PPAR gamma and -delta are activated by the structurally distinct peroxisome proliferator LY-171883 and linoleic acid, respectively, indicating that each of the isoforms can act as a regulated activator of transcription. These data suggest that tissue-specific responsiveness to peroxisome proliferators, including certain fatty acids, is in part a consequence of differential expression of multiple, pharmacologically distinct PPAR isoforms.
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