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9451680 | Distinct clinicopathologic characteristics of diffuse- and intestinal-type gastric cancer in Taiwan. | The clinicopathologic features of 221 patients with intestinal-type (IT) gastric cancer pared retrospectively with those of 290 diffuse type (DT). Intestinal type was characterized by an older mean age (65.0 +/- 10.8 years vs. 56.2 +/- 13 years), a higher male-female ratio (2.56 vs. 1.06), predominance of blood group O (46.2% vs. 31.1%), and frequent habitual smoking (50.7% vs. 31.4%) and drinking (28.5% vs. 17.6%) than did DT. In contrast, DT had a higher frequency of positive history of parent or sibling with gastric cancer (9.3% vs. 4.1%) and blood group A (40.3% vs. 27.6%) than did IT. The distinguishing histologic features of DT included more Borrmann type IV (13.1% vs. 1.3%) but less Borrmann type I (1% vs. 7.2%), more frequent involvement of middle third (26.9% vs. 15.9%) and whole stomach (4.1% vs. 0%), and more peritoneal seeding (15.5% vs. 9%), lymph node metastasis (67.2% vs. 51%), and nerve permeation (34.1% vs. 24.4%), but less Helicobacter pylori infection (55.9% vs. 69.2%) pared with those of IT. There was no difference in depth of tumor invasion, venous permeation, duodenal involvement, and postoperative survival between IT and DT. These distinct clinicopathologic features between IT and DT in Taiwan suggest the presence of a different pathogenic process for these two histologic subtypes of gastric cancer. |
9451681 | Prevalence of hepatitis B, C, and D markers in sub-Saharan African immigrants. | We determined the prevalence of hepatitis B, C, and D virus markers in a cohort of 229 (adult group, n = 187; pediatric group, n = 42) asymptomatic sub-Saharan African immigrants recently arrived to Madrid, Spain. Evidence of a recent or past hepatitis B virus infection marker was seen in 68 of 187 (36.4%) adults and in 14 of 42 (33.3%) children. The rate of chronic carriers of hepatitis B surface antigen in the entire population was 10.9% (25 of 229). Anti-hepatitis C virus antibodies were seen in 16 of 187 (8.6%) of the adults and in 1 of 42 (2.4%) of the children. Two of the 20 adults (10%) who were positive for hepatitis B surface antigen and none of the children had anti-hepatitis D virus antibodies. We found no significant differences in the prevalence of any viral infection marker between the two groups. Ten of the 125 (8%) patients in the adult group and none of the pediatric group had serologic evidence (recent or past) of hepatitis B and C coinfection. The hepatitis markers of this group should be studied and these persons should be considered a risk group in the hepatitis B virus vaccination campaigns. |
9451682 | Crohn's disease and Escherichia coli. A new approach in therapy to maintain remission of colonic Crohn's disease? | Involvement of pathogenic or potentially pathogenic bacteria in the pathogenesis of inflammatory bowel disease has long been suggested because, among other reasons, the inflammatory response resembles that in infectious bowel diseases. Elevated antibody levels to pathogen antigens and a changed metabolic activity of the intestinal microflora have been detected in patients with Crohn's disease. Several studies have revealed a possible etiologic link between intestinal microorganisms and inflammatory bowel disease. Therefore, several therapeutic strategies, including reduction or dilution of ponents in the intestine by antibiotics or intestinal lavage, respectively, inactivation of inflammatory bacterial products, and reconstitution of intestinal microflora have been employed, substantiating the idea that dysfunction of the intestinal mucosal barrier and an alteration of position contribute to the inflammatory disease. However, the beneficial effect of restoration of the physiologic intestinal microflora in colonic inflammation by exogenous administration of a viable nonpathogenic bacterium has not been investigated before in a placebo-controlled study. Promising results came from the present pilot study in which the nonpathogenic Escherichia coli strain Nissle 1917 was tested for efficacy and tolerance in maintaining remission in patients with colonic Crohn's disease. Application of the physiologic bacteria reduced the risk for relapse and minimized the need for glucocorticoids. Therefore we are convinced that in Crohn's disease parts of the intestinal microflora, including the host's immune response toward indigenous flora or an impairment of the gut flora's metabolic activity are involved in the development or at least in the onset of relapse from remissive of colonic Crohn's disease. However, more data are necessary to prove the benefit of E. coli strain Nissle 1917 as a new therapy to maintain remission of colonic Crohn's disease. |
9451683 | A decade's experience with a preceptorship. A model for gastroenterologic education. | I have conducted an experiment in medical subspecialty education during the last 10 years in the division of gastroenterology of the Mount Sinai School of Medicine in the form of 3-month preceptorships during the second year of the fellowship. I recognized that our training program, along with other subspecialty training programs, was no longer a purely hospital affair, but its future lay as well in the outpatient setting. I wanted to have the fellows participate in the daily care of patients in the realistic setting of practice. I hoped to offer them the excitement, as well as the problems, of daily gastroenterology practice. By seeing new and established patients with gastrointestinal problems in four daily sessions, and caring for hospitalized patients, including those being operated on, the fellows were to participate in every aspect of a busy office. The flavor of reality was to be heightened by their exposure to the preceptor's uncensored discussions with the patient, the family, the radiologists, endoscopists, and referring physicians. Here I report what the fellows and I have learned from experience, and I address the problems we all must face in the era of managed care, with the ongoing reduction in the number of specialists. I also consider who will do the teaching and who will pay them to protect the time they need. |
9451684 | Teaching gastroenterology in a private outpatient clinic. | In this essay I review how I have taught clinical gastroenterology to residents and fellows and medical students for the past 40 years in an academic private outpatient clinic. Private patients can serve as "teaching patients," even in an ambulatory setting, and even in a managed care environment that encourages productivity. |
9451685 | The origin of gastroenterology societies during the twentieth century. | In this article, I describe briefly how a group of major gastroenterologic organizations, which have contributed to the steady advance of gastroenterology during this century, developed. My purpose in this presentation is not only to provide a memoir of what, to me, were very exciting times but also to help today's younger e to appreciate those past events that make today's opportunities possible. |
9451686 | Gastric inlet patch containing submucosally infiltrating adenocarcinoma. | We describe a patient with an unusual segment of ectopic gastric mucosa in the proximal esophagus. The gastric heterotopia was circumferential and unusually long at 7 cm. It contained benign rugal-type folds, a stricture at the mid-portion of the gastric inlet patch was lined by normal antral-type gastric mucosa but harbored submucosally infiltrating adenocarcinoma. There was no evidence of Helicobacter pylori infection by biopsy or serologic screening. Malignancy, including submucosally infiltrating adenocarcinoma, should be considered in patients with strictures involving ectopic gastric mucosa in the proximal esophagus. |
9451687 | Hyperammonemic encephalopathy after chemotherapy. Survival after treatment with sodium benzoate and sodium phenylacetate. | A 16-year-old boy had hyperammonemia and encephalopathy develop after high-dose chemotherapy for acute lymphoblastic leukemia. He was treated successfully with the ammonia-trapping agents sodium benzoate and sodium phenylacetate. |
9451688 | Retroperitoneal abscess presenting as emphysema of the thigh. | Leg pain may be a presenting symptom of intra-abdominal disease. I report a case of subcutaneous emphysema of the thigh that was plication of diverticular perforation and abscess formation. Healthy leg muscle was found at operation, showing that myonecrosis need not necessarily be present even with finding of extensive gas accumulation. |
9451689 | Pneumoperitoneum and ascites secondary to bacterial overgrowth. | Abdominal bloating, weight loss, pneumoperitoneum, and ascites developed in a 73-year-old woman. She had scleroderma, megajejunum, small bowel dysmotility, and bacterial overgrowth. After treatment with a course of antibiotics, the pneumoperitoneum and ascites resolved, but her symptoms and the pneumoperitoneum recurred after the antibiotics were stopped. She was placed on cyclical antibiotics, and during a 2-year follow-up period she has remained well. The pneumoperitoneum and ascites may have been secondary to small bowel bacterial overgrowth. Ours is the first case that demonstrates this association. |
9451690 | Visceral leishmaniasis diagnosed by colonoscopy. | Zoonotic visceral leishmaniasis mon in western Mediterranean countries. A strong link between visceral leishmaniasis and human immunodeficiency virus (coinfection) has been proved, especially in Spain, which is an endemic area. This suggests that Leishmania may behave opportunistically. We report a case of colonic leishmaniasis in a 23-year-old Spanish woman infected with the human immunodeficiency virus. |
9451712 | Chronic electroconvulsive shock and 5-HT autoreceptor activity in rat brain: an in vivo microdialysis study. | In vivo microdialysis was used to determine the effects of chronic electroconvulsive shock (ECS), given daily for 10 days, on basal 5-HT levels in rat frontal cortex and hippocampus and on the effect of systemic administration of the 5-HT-la receptor agonist, 8-OH-DPAT (0.2 mg/kg), to reduce 5-HT levels in these areas by activation of somatodendritic autoreceptors. Neither basal 5-HT levels nor the effects of 8-OH-DPAT on 5-HT levels were altered after chronic ECS. The effect of systemic administration of the 5-HT1A and 5-HT1B antagonist, (+/-)-pindolol (10 mg/kg), to increase 5-HT levels in hippocampus, was also not affected by chronic ECS. |
9451713 | Electroconvulsive shock blocks the opioid-mediated inhibition of dopamine release in rat striatal slices. | The fractional release technique was applied to investigate the effects of single electroshock (ECS) on the opioid-mediated inhibition of dopamine release in rat striatal slices. Animals were submitted to ECS 24h before the experiments. The results demonstrate that pre-treatment with ECS suppresses the inhibition of dopamine release mediated by kappa opioid receptors. These data suggest that single ECS treatment modifies the sensitivity of the kappa opioid receptors located on the presynatic dopamine terminals in the rat striatum. |
9451714 | Effect of dantrolene on KCl- or NMDA-induced intracellular Ca2+ changes and spontaneous Ca2+ oscillation in cultured rat frontal cortical neurons. | Dantrolene has been known to affect intracellular Ca2+ concentration ([Ca2+]i) by inhibiting Ca2+ release from intracellular stores in cultured neurons. We were interested in examining this property of dantrolene in influencing the [Ca2+]i affected by the NMDA receptor ligands, KCl, L-type Ca2+ channel blocker nifedipine, and two other intracellular Ca2(+)-mobilizing agents caffeine and bradykinin. Effect of dantrolene on the spontaneous oscillation of [Ca2+]i was also examined. Dantrolene in microM concentrations dose-dependently inhibited the increase in [Ca2+]i elicited by NMDA and KCl. AP-5, MK-801 (NMDA antagonists), and nifedipine respectively reduced the NMDA and KCl-induced increase in [Ca2+]i. Dantrolene, added to the buffer solution together with the antagonists or nifedipine, caused a further reduction in [Ca2+]i to a degree similar to that seen with dantrolene alone inhibiting the increase in [Ca2+]i caused by NMDA or KCl. At 30 microM, dantrolene partially inhibited caffeine-induced increase in [Ca2+]i whereas it has no effect on the bradykinin-induced change in [Ca2+]i. The spontaneous oscillation of [Ca2+]i in frontal cortical neurons was reduced both in amplitude and in base line concentration in the presence of 10 microM dantrolene. Our results indicate that dantrolene's mobilizing effects on intracellular Ca2+ stores operate independently from the influxed Ca2+ and that ponent of the apparent increase in [Ca2+]i elicited by NMDA or KCl represents a dantrolene-sensitive Ca2+ release from intracellular stores. Results also suggest that dantrolene does not affect the IP3-gated release of intracellular Ca2+ and that the spontaneous Ca2+ oscillation is, at least partially, under the control of Ca2+ mobilization from internal stores. |
9451715 | No changes in cerebrospinal fluid levels of nitrite, nitrate and cyclic GMP with aging. Short communication. | Nitric oxide (NO) is a free radical gas that plays a role in various signal transduction processes. NO has been proposed to have a function in the mechanism of synaptic plasticity, including long-term potentiation and memory formation in vivo. Because a failure in synaptic plasticity is considered to be involved in aging-associated brain dysfunction, NO production in the brain may be altered by aging. In the present study, we measured the levels of NO metabolites, nitrite and nitrate, and cyclic GMP in the cerebrospinal fluid (CSF) of human subjects without neurological or psychiatric disorders. There were no age-related changes in the CSF levels of either nitrite, nitrate or cyclic GMP. These results suggest that NO production in the brain may be maintained during the aging process. |
9451711 | Causes and consequences of the loss of serotonergic presynapses elicited by the consumption of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") and its congeners. | The massive and prolonged stimulation of serotonin (5-HT)-release and the increased dopaminergic activity are responsible for the acute psychomimetic and psychostimulatory effects of 3,4-methylenedioxy-methamphetamine (MDMA, "ecstasy") and its congeners. In vulnerable subjects, at high doses or repeated use, and under certain unfavorable conditions (crowding, high ambient temperature), severe, in some cases fatal, averse systemic reactions (hyperthermia, serotonin-syndrome) may occur during the first few hours. Animal experiments revealed the existence of similar differences in vulnerability and similar dose- and context-related influences on a similar sequence of acute responses. The severity of these acute systemic responses is closely related to the severity of the long-term damage to 5-HT axon terminals caused by the administration of substituted amphetamines. Attempts to identify the mechanisms involved in this selective degeneration of 5-HT presynapses brought to light a multitude of different factors and conditions which either attenuate or potentiate the loss of 5-HT terminals caused by MDMA and related amphetamine derivatives. These puzzling observations suggest that the degeneration of 5-HT presynapses represents only the final step in a sequence of events promise the ability of 5-HT terminals to maintain their functional and structural integrity. Substituted amphetamines selectively tax energy metabolism in 5-HT presynapses through their ability to exchange with 5-HT and to dissipate transmembrane ion gradients. The active carrier systems in the vesicular and presynaptic membrane operate at a permanently activated state. The resulting energy deficit can no longer adequately restored by the 5-HT presynapses when their availability of substrates for ATP production is additionally reduced by the hyperthermic and other energy consuming reactions which are elicited by the systemic administration of substituted amphetamines. The exhaustion of energy in 5-HT nerve promised all energy-requiring endogenous mechanisms involved in the regulation of transmembrane-ion exchange, internal Ca(++)-homeostasis, prevention of oxidative stress, detoxification, and repair. Above a critical threshold the failure of these self-protective mechanisms will lead to the degeneration of the 5-HT axon terminals. Based on the role of 5-HT as a global modulatory transmitter-system involved in the stabilization and integration of impulse flow between distributed multifocal neuronal networks, the partial loss of 5-HT presynapses must be expected to impair the ability of these networks to maintain the integrity of signal flow pattern, and increase the likelihood of switching to unstable information processing. Behavioral responding may therefore e more dominated by activities generated in individual networks, and hitherto "buffered" personality traits and predisposition may e manifested as defined psychiatric syndromes in certain predisposed subjects. |
9451716 | Multi-modality mapping of motor cortex: comparing echoplanar BOLD fMRI and transcranial magnetic stimulation. Short communication. | Multiple non-invasive methods of imaging brain function are now available for presurgical planning and neurobiological research. As these new methods e available, it is important to understand their relative advantages and liabilities, as well as how the information pares across different methods. A current and future trend in neurobiological studies as well as presurgical planning is bine information from different imaging techniques. Multi-modal integration may perhaps give more powerful information than each modality alone, especially when one of the methods is transcranial magnetic stimulation (TMS), with its ability to non-invasively activate the brain. As an initial venture in paring new imaging methods, we performed the following 2 studies, locating motor cortex with echoplanar BOLD fMRI and TMS. The two methods can be readily integrated, with concurring results, although each have important limitations. |
9451717 | Supranuclear gaze palsy and eyelid apraxia in postencephalitic parkinsonism. | We describe six patients with clinicopathologically confirmed post-encephalitic parkinsonism (PEP) in whom oculomotor abnormalities developed several years after suffering the initial episode of encephalitis lethargica. Four of the cases had vertical supranuclear gaze palsy and two eyelid apraxia, features typically associated with progressive supranuclear palsy (PSP). Our findings indicate that the presence of gaze palsy alone may not be a reliable clinical discriminator between PEP and PSP. Involvement of the dorsal central gray nucleus, nucleus centralis pontis oralis, nucleus dorsal raphe interpositus, rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF), nucleus interstitialis of Cajal, nucleus of the missure, pedunculopontine nuclei and frontal cortex was observed in several of our PEP cases and may contribute to the oculomotor abnormalities in this disorder. Whether the dorsal tegmental nucleus, caudal to the supratrochlear nucleus, severely affected in all our PEP cases, has a role in vertical gaze needs to be further studied. |
9451718 | Pergolide binds tightly to dopamine D2 short receptors and induces receptor sequestration. | Pergolide is an ergotamine derivative with potent D1 and D2 receptor activity. In this study we showed that pergolide binds tightly to dopamine D2 short receptors, as indicated by the long period of occupancy of the receptors after washing. Furthermore, pergolide induces receptor internalization to a larger extent than dopamine, seeing that no recycling of the receptors to the plasma membrane was observed for either agonist. The dissociation of pergolide from dopamine receptors occurs during the endocytotic process, leaving the receptors accessible to [3H]methylspiperone. Pergolide is a pound that can reach pete with [3H]methylspiperone for binding to sequestered receptors. If internalized receptors are still a target for drug action, pergolide could be a pound of therapeutic interest in cases where receptor sequestration could prevent dopamine efficacy, as in levodopa therapy. |
9451719 | Attenuation of 1-methyl-4-phenylpyridinium (MPP+) neurotoxicity by deprenyl in organotypic canine substantia nigra cultures. | Systemic administration of MPTP to experimental animals induces neurodegeneration of dopaminergic neurons in the central nervous system. MPTP crosses the blood-brain barrier where it is taken up by astrocytes and converted to MPP+ by monamine oxidase-B (MAO-B). Subsequently, MPP+ is selectively taken up by dopaminergic neurons upon which it exerts intracellular neurotoxic effects. Systemic administration of the selective MAO-B inhibitor deprenyl prevents the conversion of MPTP to MPP+ and by this mechanism is able to protect against MPTP neurotoxicity. Deprenyl has also been reported to exert neuroprotective effects that are independent of its MAO-B inhibitory properties, but since MPP+ itself does not cross the blood-brain barrier it is difficult to directly study the MAO-B independent in vivo effects of MPP+ itself. One approach is to use organotypic tissue cultures of the canine substantia nigra (CSN) which permit administration of precise concentrations of pharmacological agents directly to mature, well-developed and metabolically active dopaminergic neurons. These neurons as well as ponents of the cultures exhibit morphological and biochemical characteristics identical to their in vivo counterparts. This study was undertaken to evaluate the neuroprotective effects of deprenyl in MPP(+)-treated cultures by measuring changes in the levels of HVA as an indicator of dopamine release and metabolism by dopaminergic neurons and to correlate this indication of dopaminergic function with morphological evidence of survival or loss of dopaminergic neurons in mature CSN cultures. Mature CSN cultures, at 44 days in vitro (DIV), were exposed to either MPP+ alone, deprenyl alone or simultaneously to both deprenyl and MPP+ or to MPP+ following 4 day pretreatment with deprenyl. Exposure to MPP+ alone caused significant reduction in HVA levels, evidence of widespread injury and ultimate disappearance of large neurons in the cultures. These effects were attenuated by simultaneous exposure to MPP+ and deprenyl and the destructive effects of MPP+ appeared to be prevented by pretreatment with deprenyl. Thus the neuroprotective effects of deprenyl on MPP(+)-induced reduction of HVA levels in living cultures appears similar to the effects of deprenyl on dopamine levels and tyrosine hydroxylase activity reported by others in cultures previously exposed to deprenyl and MPP+. These studies also confirm that the neuroprotective effects of deprenyl against MPP+ in dopaminergic neurons are, at least in part, independent of deprenyl's inhibition of MAO-B. |
9451720 | Cognitive improvement during Tolcapone treatment in Parkinson's disease. | The aim of this study was to evaluate the effects of Tolcapone, a reversible, selective inhibitor of catechol-O-methyltransferase, on the cognitive function of eight patients with advanced Parkinson's disease. They underwent neuropsychological and motor assessment at baseline and were re-evaluated after 6 months. During this period, they received Tolcapone three times daily, while the L-dopa dosage was progressively reduced. Significant improvements were observed in the attentional task, auditory verbal short-term memory, visuo-spatial recall, constructional praxia and motor symptoms. These data suggest that treatment with Tolcapone, bination with L-dopa therapy, may determine a significant improvement in cognitive resources of patients with advanced Parkinson's disease. |
9451721 | Effects of increasing doses of apomorphine during stereotaxic neurosurgery in Parkinson's disease: clinical score and internal globus pallidus activity. Short communication. | We analysed the firing activity of internal globus pallidus cells in two Parkinson's disease patients undergoing stereotaxic surgery. Both patients showed an advanced rigid-akinetic syndrome with disabling levodopa induced dyskinesias. Apomorphine, intraoperatively administered at doses (1-2 mg) inducing a short but clear clinical improvement without involuntary movements, reduced the pallidal discharge rate by > 50% in both patients. An higher apomorphine dose (2.5 mg), tested in one hemisphere, blocked the firing activity with a time course independent from the occurrence of dyskinesias. These finding suggest that the reduction of internal pallidus excitability is one of the mechanisms underlying the efficacy of dopaminergic therapy, but also that changes in other basal ganglia stations are likely to be involved in dyskinesias. |
9451722 | Relationship between EEG reactivity and neuropsychological tests in vascular dementia. | 17 patients with vascular dementia (VaD) representing moderate to severe stage of the disease and 11 age-matched control subjects were examined with spectral analysis of EEG and a neuropsychological test prising visual, praxic, verbal and memory functions as well as Mini-Mental Status test. VaD patients did not have less activity in the alpha band than control subjects, but the alpha amplitude ratio between eyes closed (EC) and eyes open (EO) situations (EC/EO ratio) was decreased in VaD pared to controls. In VaD the variables of the awake background EEG with eyes closed (amplitude of alpha, beta, theta and delta activity; mean frequency) had only a few correlations to neuropsychological test scores. However, the (EC)/(EO) alpha ratio showed significant correlations with several neuropsychological variables in the temporo-occipital and centro-parietal derivations and some of these correlations were lateralized to the left or right hemisphere. Frontal EEG derivations with less alpha activity did not reveal any correlations to neuropsychological variables. We conclude that the dynamic EC/EO alpha ratio variable may be even more sensitive in the assessment of brain dysfunction in VaD than the background EEG variables. |
9451723 | Apolipoprotein E epsilon 4 allele distribution in Wernicke-Korsakoff syndrome with or without global intellectual deficits. | Recent genetic studies show that the apolipoprotein E (ApoE) epsilon 4 allele is a risk factor for Alzheimer's disease (AD). Whether this allele is associated with other dementing diseases is the next important question. The information could provide a clue to the pathogenetic role of ApoE. In the present study, patients with Wernicke-Korsakoff syndrome (WKS) of alcoholic etiology were divided into two groups according to the severity of intellectual deficits, i.e., those of "classical" Korsakoff patients with preserved intellectual function other than amnesia and those with global intellectual deficits. Genotyping showed that the frequency of ApoE epsilon 4 allele was significantly higher in the patients with global deficits, suggesting the involvement of this allele in the intellectual decline of WKS. In contrast, distributions of other two markers, alpha 1-antichymotrypsin and presenilin-1, did not differ between the two groups. These results added further support to the notion that the consequence of acute insult to the brain is influenced by the ApoE genotype, and suggested ApoE's role in the development of a certain group of "alcoholic dementia." |
9451724 | High affinity [3H]imipramine and [3H]paroxetine binding sites in suicide brains. | Specific binding of [3H]imipramine and [3H]paroxetine was simultaneously examined in human brains (frontal cortex, temporal cortex, cingulate cortex, hypothalamus, hippocampus and amygdala) from 11 controls and 11 depressed suicide victims. A single saturable high affinity site was obtained for both radioligands. Age was not related to significant changes in [3H]imipramine and [3H]paroxetine binding parameters, which indicates the stability of the brain serotonergic system with increasing age. A major finding of the present study concerns the existence of a significant decrease in the maximum number (Bmax) of [3H]imipramine binding sites in hippocampus from depressed suicides pared with the control group, without changes in the binding affinity (Kd). In contrast, when [3H]paroxetine was used as radioligand, no changes in either Bmax or Kd were detected in any of the brain regions studied. These findings suggest that [3H]imipramine may be a better marker than [3H]paroxetine when alterations in the presynaptic serotonergic uptake site are to be detected. |
9451726 | The effect of acute and chronic lithium on forskolin-induced reduction of rat activity. | Forskolin is a diterpene derivative that activates adenylate cyclase and raises cAMP levels in the cell. Both i.p. and i.c.v. forskolin cause behavioral hypoactivity. Lithium has been reported for many years to block cAMP accumulation, but the behavioral relevance of this biochemical effect is not clear. We studied the effect of acute and chronic lithium on icv forskolin-induced hypoactivity. Acute lithium had no effect, but chronic lithium significantly blocked forskolin-induced hypoactivity. The effect of chronic lithium occurred with both forskolin in DMSO and with a water-soluble forskolin derivative. These results suggest that this behavioral model can be used to investigate whether new inhibitors of adenylate cyclase possess lithium-like effects. |
9451725 | Homozygous thermolabile methylenetetrahydrofolate reductase in schizophrenia-like psychosis. | The gene for methylenetetrahydrofolate reductase (MTHFR) has shown polymorphism in the general human population. In its homozygous form, a C677T mutation occurs in more than 5% of the grown-up population and produces a thermolabile variant which reduces the overall enzyme activity to less than 30% of normal. We investigated patients with schizophrenia-like psychosis. If hyperhomocysteinemic, their DNA-genotype for thermolabile C677T mutation was determined. Seven of 11 patients, six males and one female, were homozygous for thermolabile MTHFR. One male patient was heterozygous and all three normal homozygotes were females. In the patients who were homozygous for the C677T mutation, the homocysteine concentrations did not respond to vitamin B12 but were normalized by folate supplementation. In the normal homozygotes, however, the homocysteine concentrations were reduced by vitamin B12 alone. Our results suggest that homozygosity for thermolabile MTHFR is a risk factor for schizophrenia-like psychosis. Possibly, this risk may be reduced by folate supplementation. |
9451727 | Fluoxetine increases norepinephrine release in rat hypothalamus as measured by tissue levels of MHPG-SO4 and microdialysis in conscious rats. | The selective serotonin uptake inhibitor fluoxetine (10 mg/kg i.p.) increased tissue levels of the norepinephrine metabolite 3-methoxy-4-hydroxyphenylethylene glycol sulfate (MHPG-SO4) in rat hypothalamus, indicating an increased release of norepinephrine. Microdialysis studies in conscious rats showed that fluoxetine (10 mg/kg i.p.) increased extracellular concentrations of norepinephrine as well as serotonin in the hypothalamus. In contrast, desipramine (10 mg/kg i.p.) increased extracellular concentration of norepinephrine but not serotonin in the hypothalamus. Consistent with its mechanism of being a selective serotonin uptake inhibitor, local perfusion of fluoxetine (10 microM) caused a 7-fold increase in hypothalamic extracellular serotonin and a small non-significant increase in extracellular norepinephrine. The subsequent systemic injection of fluoxetine (10 mg/kg s.c.) after local perfusion caused a 3-fold increase in extracellular norepinephrine, indicating that fluoxetine's action leading to an increase in extracellular norepinephrine was not occurring in the terminal areas of the hypothalamus but elsewhere in the brain, possibly cell bodies in the locus coeruleus. |
9451728 | A simplified routine assay for urinary 3-methoxy-4-hydroxyphenylglycol. | Urinary 3-methoxy-4-hydroxyphenylglycol (MHPG) level may provide us with a biochemical index for central noradrenergic activity. Previous methods for assaying MHPG in urine often lacked specificity, sensitivity, cost-effectiveness or convenience. We now describe a simplified routine assay for urinary MHPG by high-pressure liquid chromatography using electrochemical detection. For convenience and cost-effectiveness within a typical batch assay of total MHPG, 0.5 mL of urine sample, 50 microL of glusulase and 4 micrograms iso-vanillyl alcohol (internal standard) were used to hydrolyze conjugated MHPG at 37 degrees C overnight. Alternatively, for a same-day operation, it is efficient to hydrolyze the sample at 50 degrees C for 3 hours. Each sample was separated isocratically on a reversed-phase column (Ultracarb 5 ODS) at 25 degrees C with the flow rate at 1 mL/min. Intra- and inter-assay coefficients of variation were found to be 4.0% (n = 10) and 5.0% (n = 27), respectively, for MHPG at a mean concentration of 1.9 mg/L. Sulfatase or glucuronidase can be substituted for glusulase to obtain either sulfate- or glucuronide-conjugated MHPG. This procedure requires smaller sample amounts and less preparation time promising sensitivity and reproducibility. |
9451729 | [Combined neuronal and endocrine tumors of the sellar region]. | Gangliocytomas or gangliogliomas of the sellar region are very rare tumors. In a great proportion of those cases an adenoma of the anterior pituitary develops from the cell type that is hyperstimulated by the releasing hormone produced from the gangliocytoma. Five GHRH secreting gangliocytomas are reported. Four of these were localized adjacent to a GH secreting adenoma. In one case, no adenoma tissue was found beside the ganglicytoma. As only the adenomas can secrete GH, the adenomas and not the gangliocytomas are directly responsible for acromegaly so that such an adenoma has to be present in cases of acromegaly. A CRH secreting gangliocytoma bined with an ACTH cell adenoma that had induced Cushing's disease. A ganglioglioma of the posterior pituitary had led to an inappropriate secretion of Vasopressin. The morphology of the different tumors is presented. |
9451730 | [Telomeres and telomerase]. | Complex mechanisms have evolved in mammalian cells for regulating cellular lifespan. Normal cells demonstrate a strictly limited growth potential and senescence after a defined number of cell divisions. In contrast, tumor cells often exhibit an apparently unlimited proliferation potential and are termed immortalized. It has been proposed that the progressive shortening of the tips of the eukaryotic chromosomes--the telomeres--is an ponent of senescence and is involved in the control of cell cycle. The enzyme telomerase adds TTAGGG repeats onto mammalian telomeres, preventing their shortening. Telomerase is normally inactive in most somatic cells, but detectable in tumor cells. The activation of telomerase in malignant cancers seems to be an important step in tumorigenesis in order to gain the ability of indefinite proliferation and to e immortal. This review describes the present knowledge of telomeres and telomerase and their role in cellular senescence and human aging. It summarizes aspects of telomerase in cancer and its function as a diagnostic and prognostic tumor marker. |
9451731 | [Heterotopic (extraosseous) calcification (calcinosis). Etiology, pathogenesis and clinical importance]. | Heterotopic tissue calcification represents a pathological event which goes along with active extra- and intracellular metabolic processes. The heterotopic calcification is not the manifestation of tissue ageing. Aetiologically, metastatic calcification, dystrophic calcification and genetic-hereditary calcification are distinguished. Two pathogenetic mechanisms play a role during the heterotopic calcification. The intracellular calcification is based upon the function of mitochondria as regulator of the calcium concentration and as "lime-catcher". The extracellular calcification is initiated by membraneous organelles--so-called matrix vesicles. The further steps are the production of hydroxylapatite crystals which are eliminated from the matrix vesicles in the extracellular spaces. Special types of heterotopic calcification are hypercalcaemias (tumour-associated hypercalcaemias, primary and tertiary hyperparathyroidism, drug-induced hypercalcaemias), tumoral calcinosis, intratumoral calcifications, calcifications of different organs (lung, heart, vessels, joints, ligaments, skin or kidney). Some calcifications of organs show partly overlapping aetiological factors and pathogenetic mechanisms. |
9451732 | [Methodologic aspects of a standardized evaluation of mitotic activity in tumor tissues]. | Although estimation of mitotic activity is generally a recognized clinical practice in the diagnosis and grading of tumors, there are several methodologic aspects that merit special consideration. Our results, in relation to those of others, lead to the following conclusions: 1. The values attained by calculating the mitotic activity of tumor cells in paraffin-embedded tumor tissue are lower than those obtained in vivo. The results cannot always be interpreted clinically due to plexity of some of the factors associated with it which require special attention. That the method still has clinical relevance and value in spite of the associated problems may be due to the fact that tumor tissues generally undergo long periods of hypoxia before being fixed for histomorphological analyses--a condition which by itself is a decisive factor in the reduction of mitotic activity--so that additional changes in some individual factors from case to case do not make much difference to the estimated or calculated value. 2. Mitotic activity should be calculated in areas of tumor sections where there are numerous mitotic tumor cells. Additionally, only cells with nuclei showing lysed nuclear membranes and identifiable single chromosomes at higher magnification ought to be considered in the calculation. Apoptotic and pyknotic elements should not be calculated. 3. The specification of the final magnification (e.g., x 400) is not a sufficient basis parison of optical conditions for the mitotic estimation, since the visual fields of standard light microscopes may differ up to 2.6-fold. A temporary streamlining of the standard may be the application of a 0.159 mm2 visual field (x 40 objective, x 10 ocular by visual field value 18). As an intermediate goal, mitosis should be calculated in percentages of the tumor cells or areas of the total tumor tissue. 4. The interspecific reproducibility of the quantified mitosis makes it reliable for clinical application. pares well with cytometric and morphometric methods in assessment of tumor cells and is of higher clinical relevance than the conventional histomorphological tumor grading systems. |
9451733 | [Modern fetal autopsy oriented to clinical demands using technical information methods]. | Modern ultrasonic diagnostic instruments with high resolution and color Doppler sonography allow the obstetrician to describe pathological findings very precisely and at an early stage of pregnancy. The use of high-resolution ultrasound makes it possible to detect heart malformations already between the 8th and 10th week of gestation. This development has essentially changed the clinical requirements on fetal autopsy which in its traditional way no longer meets the increased demands. Unless the pathologists faces this challenge the importance of fetal autopsy will diminish. Modern image databases munication techniques allow the pathologist to have direct access to text and images of pre-findings by other clinics. Great importance, however, must be attached to the interdisciplinary cooperation with obstetricians and geneticists. We report on routine fetal autopsy by using an interdisciplinary database an the Charité. |
9451734 | [Systematic calciphylaxis in chronic renal failure: fulminant course after kidney transplantation]. | Description of a 27 years old patient with chronic renal failure due to diabetes, which requires dialysis, and tertiary hyperparathyroidism, who developed fulminant systemic calciphylaxis after successful renal transplantation. Characteristic of this syndrome, there occurred soft tissue calcification, mediacalcinosis of the small and medium-sized arteries and ischemic skin necrosis. The pathogenesis is pletely clear, but challenging agents like corticosteroids or immunosuppressants, in a sensitized organism (at hypercalcemia or elevated parathormon) could lead to calcium deposits. These are showing a particular affinity for elastic tissue. Lungs, stomach, kidneys, cutis, heart and vascular system are most frequently involved. Treatment is primarily supportive; an early parathyroidectomy seems to have the best prognosis. |
9451736 | [Serous psammocarcinoma of the ovary. Case report and literature review]. | We report a rare case of psammocarcinoma which presented as a mass in the lower abdomen of an otherwise asymptomatic woman. Ultrasonographically, the tumor showed extensive calcification and was suspected to be a myoma. DNA image cytometry and assessment of proliferative activity were performed and showed an euploid, low proliferating tumor cell population. This underlines the low malignancy of this type of carcinoma, which parable to that of serous borderline lesions of the ovary and explains the benign clinical course. |
9451735 | [Calcifying granulomatous peritendinitis after local dexamethasone treatment]. | In this article we report on a 43-year-old man, who had been treated with two cortisone injections containing soja bean oil for epicondylitis humeri radialis. Four weeks after the second injection necrotized fat which had been extracted surgically was sent to us for histological examination. We could show a calcifying collagen fibre necrosis being cleared by a granulomatous reaction and resorbed by granulation tissue. The calcifying necrosis of collagen fibres might have been induced by soja bean oil which were used as carrier of the drug. |
9451737 | [Cystic adventitial degeneration of the popliteal artery. Rare cause of intermittent claudication in middle-aged adults]. | We report on a 36-year old male patient with clinically prolonged intermittent claudication of the right leg. An operative specimen measuring 8.0 cm of the A. poplitea was sent for examination, which was sheathed by an aneurysmal cyst having a maximal diameter of 1.5 cm. Examination under the light microscope showed an plete septated ganglion-like cystic formation with flat connective tissue-like cells or even larger histiocytoid cell elements as inner lining. Immunohistochemically, the cells on the inner lining of the cyst showed to be strongly positive to macrophage marker PG-M1, KP1 and Ki-Mp1. The endothelium of the vessels of the wall of the cyst showed a marked expression of cytokeratin 18. Immunohistochemically as well as in conventional histology, there are general parallels between cysts in cystic adventitial degeneration, ganglia and normal synovia as the two last mentioned tissues also show an expression of cytokeratin 18 at the endothelia of smaller vessels as well as an expression of macrophage-associated antigens on cells of the inner lining. Aetiopathologically, the cysts developing in the course of the disease are rather adventitial ganglia. |
9451738 | [Primary leiomyosarcoma in the left atrium--a rarity. Case report and literature review]. | The case presents a 61 year old woman which came into the hospital with left heart failure. After an unsuccessful trial to treat the heart failure in an habitual method the echocardiographic showed a mass lesion which had filled out mostly of the left atrium. Histological features demonstrated a a with an origin from the wall of the left atrium. Immunohistochemical preparations revealed a positivity for actin, desmin and vimentin. Despite an operative resection and an attach of polychemotherapy it developed a local relapse and multiple lymph node metastases. Within the scope of this case report apart from an detailed bibliography it ought to be discussed the origin of the tumor into the atrium and the differential diagnosis from other a. |
9451739 | [Neurofibromatosis type 1 associated arteriopathy. Case report and literature review]. | Reported is the case of a 36-year-old man with neurofibromatosis type 1 with lethal haemorrhage from rupture of the mon iliac artery. Histologically and immunohistochemically, no hints on angiodysplasia as a possible cause of bleeding were detected. Considering the literature and the histological findings in the area of rupture, a local weakness of the vascular wall caused by the neighbouring neurofibromatous proliferates was most probably the reason for bleeding. |
9451740 | [Paraganglioma of the cauda equina]. | We report on a case of paraganglioma of the cauda equina in a 48-year-old man. These slow-growing, mostly benign and encapsulated intradural-extramedullar tumours are clinically characterized by lumbago, paraesthesia and motor deficits as well as occasionally by incontinence. Paragangliomas of the cauda equina show monomorphous (main) cells arranged in a typical cell cluster pattern, demonstrating a lobular architecture and a fine net of connective tissue formed by so-called sustentacular cells; some tumours show focal ganglionic differentiation. Because of their morphological similarity to the mon ependymomas, paragangliomas of the cauda equina are sometimes misdiagnosed so that their incidence is likely to be higher than previously estimated. Immunohistochemistry findings are positive for neuron-specific enolase, chromogranin and other neuronal markers as well as neuropeptides (main cells) and S-100 protein (sustentacular cells) while widely lacking reactivity for GFAP. Paragangliomas of the cauda equina represent a rare entity, of which only 80 cases have been described in the literature. Because they only occur sporadically, they are often not included in the differential diagnosis of mass lesions of the region of the cauda equina. |
9451741 | [Regeneration of bronchial mucosa after short-term repetition of biopsy versus bronchial carcinoma]. | We report on two patients, 74 and 73 years old, each of whom had had biopsy of the bronchial mucosa elsewhere. Histologically, normal mucosa and mild bronchitis was seen, respectively. In both patients a second biopsy specimen from the same site was taken, 4 and 7 days after the first biopsy. Now the diagnosis was carcinoma in situ (not excluding early squamous carcinoma) and squamous carcinoma, respectively. One of the patients came to our lung clinic for operation on the basis of the mentioned diagnosis. A third biopsy was performed for control purposes. It revealed just a perforation of a lymph node in the bronchial wall and some epithelioid granulomas without evidence of acid-fast bacilli. There was no evidence of malignancy in this specimen. Because of the discrepancy, the pathologist at the first institution was asked to send us the previous slides. On review of these slides, the described findings were seen, but they were interpreted as regenerative-atypical. In this way, an unnecessary surgical intervention was avoided. After a follow-up of 3 1/2 years the patient is healthy. In the other patient, because of the diagnosis of squamous carcinoma a lobectomy was undertaken by a surgeon elsewhere. The pathologist could not find any carcinoma in the surgical specimen. The biopsy material was reviewed in our department, the findings being interpreted as atypical, originating in reparative changes. Like the postoperative pathologist, we did not find any carcinoma in the surgical specimen. In both cases, therefore, regenerative-atypical changes after re-biopsy were first misinterpreted as a malignant process. |
9451743 | The Leeuwenhoek Lecture, 1997. Marek's disease herpesvirus: oncogenesis and prevention. | There are a number of neoplasias for which a herpesvirus is an essential part of the aetiology. Of these, Marek's disease is the mon and provides excellent opportunities for the study of a herpesvirus-induced tumour both experimentally and under natural conditions in the field. Marek's disease is caused by an alpha herpesvirus; it differs from the other oncogenic herpesviruses which are gamma herpesviruses. It is a ubiquitous virus in poultry populations of the world and is highly cell-associated and contagious, yet only a proportion of infected fowl develop tumours. Evidence is presented to suggest that at least one of the reasons for a wide variation in the incidence of the disease is a temporal interplay between virulent viruses and viruses of low or no virulence. The viral genes associated with the oncogenicity of Marek's disease virus (MDV) are discussed and it is concluded that it is likely that several genes are involved. Finally, a brief history of vaccination to control Marek's disease is given and mode of action discussed. It is concluded that the mechanism of protection is mainly through an antiviral cell mediated immune response, resulting in a lowered challenge virus burden. Marek's disease viruses over the past 40 years have been evolving greater oncogenicity, some of which are not adequately controlled by the vaccines that are currently available. It is suggested that for MDV to produce tumours, there is a need for the cytolytic infection phase and that infection must be with an MDV which possesses a functional gC, ICP4 for maintaining latency which allows the expression of at least the 1.8 kb family, pp38, meq, and possibly pp14 genes, for maintaining the tumour state and possibly initiating this state. Intervention in this process reduces the chance of tumour formation and incidence in a population which can occur through natural or man-mediated infection with non-pathogenic MDVs. |
9451745 | Alcohol and cancer: a review for psycho-oncologists. | Researchers have documented a link between alcohol consumption and the development of certain types of cancers. In addition, the prevalence of alcoholism orbid psychiatric disorders has been well-documented both the general population and medical settings. The role of the psycho-oncologist in the assessment and management of alcoholism orbid psychiatric disorders is crucial to improving both treatment adherence and the quality of life of the patient. This paper will provide psycho-oncologists with a review of: (1) the relationship of alcoholism to cancer; (2) orbidity frequently encountered in alcoholics, as a key to assessment and management; and (3) the goals and strategies of management of alcoholic cancer patient. |
9451746 | Stress, social support and negative affectivity in children with newly diagnosed cancer: a prospective transactional analysis. | Conceptually-driven investigations on the potentially modifiable predictors of individual differences among children with newly-diagnosed cancer may facilitate the identification of pediatric cancer patients at risk for maladjustment during the profound adversity associated with this life-threatening disease and aversive biomedical treatment. Within a risk and resistance theoretical framework, perceived stress and social support were investigated concurrently and prospectively within an exploratory design as predictors of negative affectivity (anxiety and depressive posite construct) in newly-diagnosed pediatric cancer patients at Time 1 (within one month after diagnosis), Time 2 (6 months postdiagnosis), and Time 3 (9 months postdiagnosis). Hierarchical multiple regression analysis findings indicate that perceived stress and social support have direct and independent effects on negative affectivity principally at the 9-month time interval. These findings are discussed in terms of the cognitive-behavioral treatment implications for enhancing child adjustment during the transition from the initial cancer diagnosis and aversive biomedical treatment to subsequent school and social reintegration. |
9451744 | Axonal processes and neural plasticity. III. Competition for dendrites. | In previous work we have developed putational framework for topographic map formation and plasticity based on axonal process sprouting and retraction, in which sprouting and retraction are governed petition for neurotrophic support. Here we show that such an approach can account for certain aspects of the dendritic morphology of cortical maps. In particular, we model the development of ocular dominance columns in the primary visual cortex and show that cortical cells near to column boundaries prefer to elaborate dendritic fields which avoid crossing the boundaries. This emerges as different functional inputs are spatially separated. We predict that afferent segregation occurs before or simultaneously with, but not after, the emergence of dendritic bias. We predict that animals reared plete but asynchronous stimulation of the optic nerves do not develop a dendritic bias. We suggest that the emergence of a dendritic bias might provide a partial account for the critical period for a response to monocular deprivation. In particular, we predict that animals reared with asynchronous optic nerve stimulation might exhibit an extended critical period. Our results also indicate that the number of synapses supported by cortical cells depends on the intra-ocular image correlations used in our simulations. This suggests that inter-ocular image correlations, and thus strabismic rearing of kittens, may also affect the innervation density. |
9451747 | A qualitative study of breast cancer self-help groups. | This study reports on the experience of women in munity breast cancer self-help groups in Ontario, Canada. Semi-structured interviews were conducted with 24 women, asking them about benefits and limitations of their group involvement, and about their perspectives on group processes and structures. Overall, participants reported their group involvement to be extremely helpful for navigating the short and long-term impact of breast cancer. Emotional support benefits included connecting with other breast cancer survivors, feeling understood and sharing experiences, providing hope, and sharing healing laughter. Informational and practical support benefits included sharing of important information and learning how to get what you want. Even where there were concerns about limitations or tensions of group experience, these occurred against a backdrop of appreciation mitment. From the discussion of group processes and structures, a number of issues were identified as problematic. Most notable were how to deal with deaths of group members and how to balance the group's primary purpose of providing mutual support with secondary goals of dealing with group business and engaging in meaningful advocacy. |
9451748 | The psychological and psychiatric effects of rIL-2 therapy: a controlled clinical trial. | It has been suggested that binant interleukin-2 (rIL-2) may cause pyschological and psychiatric problems, although the effects of rIL-2 on its own have not been well documented. To evaluate these effects, 17 patients with advanced colorectal cancer took part in a randomised, parallel group study of rIL-2 with chemotherapy (5-fluorouracil and leucovorin) versus chemotherapy alone. Patients were assessed regularly by means of various psychometric tests including the Hospital Anxiety and Depression Scale, the Mood Rating Scale, the Mini-Mental State Examination, the Digit Symbol Substitution Test, the Trail-Making Test and the Benton Revised Visual Retention Test. Rigorous discontinuation criteria were applied to ensure that the effect of time-related variables did not influence the results. Compared with patients who were given chemotherapy alone, patients receiving immunochemotherapy reported reduced energy, impaired confidence, higher depressed mood and more confusion. Immunochemotherapy was rated as more distressing than chemotherapy alone and patients reported a greater incidence of appetite impairment, weight loss, poor concentration and fever. Cognitive assessments indicated that brain dysfunction can be caused by rIL-2. Compared with the control group, patients receiving immunochemotherapy showed significant impairment on Trail Making Test B and the Digit Symbol Substitution Test. One patient developed repeated transient psychotic episodes associated with rIL-2 infusions and another regularly became confused. These effects were not due to sleep deprivation or pyrexia. Treatment with rIL-2 should not be discarded on psychosocial grounds, although in each case the psychological morbidity and adverse effects on quality of life need to be balanced carefully against potential therapeutic benefits. |
9451749 | Effects of a nursing pain programme on patient outcomes. | The effectiveness of a continuing pain education program, directed to surgical cancer nurses, was investigated in a pretest posttest controlled intervention study. ANCOVA for repeated measures revealed that the programme resulted in a lower pain intensity of surgical colon and breast cancer patients (p = 0.02). However, no effects were found on pain duration, sleepless hours as a result of pain, state anxiety, mood disturbances, and duration of hospitalization. It is assumed that because the pain CE programme had a moderate impact on pain intensity, this had no consequences for the other e variables mentioned. |
9451750 | Pre-operative [correction of Properative] psychological variables predict immunological status in patients with operable breast cancer. | In a prospective study of psychobiological responses in patients with operable breast cancer, psychological data were collected one day before surgery and immunological data one day before and seven days after surgery. |
9451751 | Doctors in limbo: the United States 'DNR' debate. | Cardiopulmonary resuscitation is unlike any other medical intervention in its emotional impact. Its original use in reversible conditions has been replaced by its expected use in irreversible ones. The history of this transformation and its psychological mitants are reviewed. New York State is unusual in having a 'DNR' law where resuscitation is the default position unless actively refused by patient or surrogate. The paradoxical genesis of this law, and plex effect on a tertiary care hospital are described. Attention is focused on the emotional stresses on medical staff, and the extensive teaching program mounted by the institution's mittee to enable a positive adaptation. The difficulties inherent in surrogate decision-making are also reviewed. |
9451752 | Is dietary intake of methionine associated with a reduction in risk for neural tube defect-affected pregnancies? | Results from experimental animals and other laboratory data have suggested a role for methionine, an essential amino acid, in normal closure of the neural tube. We hypothesized that women who had higher dietary intakes of methionine would be at lower risk for neural tube defect (NTD)-affected pregnancies. Data were derived from a population-based case-control study of fetuses and liveborn infants with NTDs among a 1989-1991 California birth cohort. Interviews, which included a 100-item food frequency questionnaire, were conducted with mothers of 424 NTD cases and 440 nonmalformed controls. Risk for having an NTD-affected pregnancy was estimated according to quartiles (established from intakes among control mothers) of average daily maternal dietary intake of methionine in the 3 months before conception. We observed an approximately 30-40% reduction in NTD-affected pregnancies among women whose average daily dietary intake of methionine was above the lowest quartile of intake (> 1,341.86 mg/ day). These reductions in NTD risk were observed for both anencephaly and spina bifida; remained after adjustment for maternal race/ethnicity and education; and were observed irrespective of maternal level of folate intake. Although we were unable to establish whether the observed reductions in NTD risk were attributable to maternal periconceptional methionine intake or to another highly correlated nutrient, these data add to the growing body of evidence that maternal diet plays a role in neural tube closure. |
9451753 | Transient cranial hemorrhage does not cause depressed contractility in cardiac neural crest-ablated chick embryos. | Ablation of cardiac neural crest results in cardiovascular malformations. Depressed ventricular contractility has been noted in cardiac neural crest-ablated embryos several hours before the time when neural crest cells would have arrived in the cardiac outflow tract and several days before the appearance of any malformations. The reason for this depressed heart function is not known. Recently, transient cranial hemorrhages were found in chick embryos during the third day of incubation, several hours before depressed ventricular contractility can be measured. We sought to determine whether depressed ventricular contractility could be associated with these transient hemorrhages. We were also interested in defining some of the factors that influence the incidence and severity of hemorrhaging. Three groups of embryos were used: cardiac neural crest-ablated, sham-operated, and unopened controls. All groups were found to experience transient hemorrhage from mon origin in the forebrain. However, the incidence and degree of hemorrhage were higher and more severe in embryos with cardiac neural crest ablation than in the other two groups. The cardiac ejection and shortening fractions were measured at stage 18 in embryos with and without hemorrhaging, and it was found that a decrease in these parameters was associated solely with ablation of cardiac neural crest and not with hemorrhage. By altering the incubation conditions, we determined that conditions that increase the oxygen in the air space are associated with increased severity and occurrence of hemorrhage and decreased viability in the first 3 days of incubation. Our results indicate that transient cranial hemorrhages does not cause depressed contractility in cardiac neural crest-ablated embryos, and increased severity of hemorrhaging is most likely due to an increase in oxygen availability. |
9451754 | Protective effect of liposome encapsulation on paclitaxel developmental toxicity in the rat. | Paclitaxel is an anticancer drug that has demonstrated severe embryotoxicity in chicks. This embryotoxicity is reduced by liposome encapsulation of the drug. The current study was designed to evaluate the potential of liposome encapsulation for reducing paclitaxel embryotoxicity in rats. Wistar rats were treated with paclitaxel on day 8 of pregnancy (plug = day 0) at doses of 0.67, 2.0, or 10.0 mg/kg intravenously. The same doses of paclitaxel encapsulated in liposomes were administered intravenously to other groups of animals. Control animals were given blank liposomes. Free paclitaxel produced maternal and embryotoxicity at 10.0 mg/kg with three of seven dams dying and resorption of all embryos in surviving dams. Liposome encapsulation at 10.0 mg/kg was not associated with maternal death and there were live fetuses on evaluation at term, although litter size was reduced and malformations occurred in surviving fetuses. At 2.0 mg/kg free paclitaxel, fetal weight was decreased and resorptions increased. Liposome encapsulation at 2.0 mg/kg produced litter results similar to those obtained in control animals given empty liposomes. Malformations were prominent at 2.0 mg/kg free paclitaxel and at 10.0 mg/kg paclitaxel in liposomes and included exencephaly/anencephaly, ventral wall defects, facial clefts, anophthalmia, diaphragmatic hernia, and defects of the kidney, cardiovascular system, and tail. Liposome encapsulation appeared to shift the developmental response to paclitaxel such that 10 mg/kg encapsulated drug produced effects similar to 2.0 mg/kg free drug. These results may have implications for drug delivery of therapeutic agents used during human pregnancy. |
9451756 | Incidence of fetal alcohol syndrome and prevalence of alcohol-related neurodevelopmental disorder. | We critique published incidences for fetal alcohol syndrome (FAS) and present new estimates of the incidence of FAS and the prevalence of alcohol-related neurodevelopmental disorder (ARND). We first review criteria necessary for valid estimation of FAS incidence. Estimates for three population-based studies that best meet these criteria are reported with adjustment for underascertainment of highly exposed cases. As a result, in 1975 in Seattle, the incidence of FAS can be estimated as at least 2.8/1000 live births, and for 1979-81 in Cleveland, approximately 4.6/1,000. In Roubaix, France (for data covering periods from 1977-1990), the rate is between 1.3 and 4.8/1,000, depending on the severity of effects used as diagnostic criteria. Utilizing the longitudinal neurobehavioral database of the Seattle study, we propose an operationalization of the Institute of Medicine's recent definition of ARND and estimate its prevalence in Seattle for the period 1975-1981. bined rate of FAS and ARND is thus estimated to be at least 9.1/1,000. This conservative rate--nearly one in every 100 live births--confirms the perception of many health professionals that fetal alcohol exposure is a serious problem. |
9451755 | Di(2-ethylhexyl) phthalate induces a functional zinc deficiency during pregnancy and teratogenesis that is independent of peroxisome proliferator-activated receptor-alpha. | Di(2-ethylhexyl) phthalate (DEHP) is a peroxisome proliferator whose administration to rodents induces a pleiotropic response mediated by the peroxisome proliferator-activated receptor-alpha (PPAR alpha). The mechanisms underlying DEHP-induced reproductive toxicity and teratogenicity are not well understood but could be the result of an alteration in gene expression by PPAR alpha. Additionally, phthalate exposure is known to impair fetal zinc (Zn) levels during pregnancy. In this work, we investigated whether the reproductive toxicity and teratogenicity of DEHP are mediated by PPAR alpha and whether the receptor influences maternal and/or embryonic Zn metabolism. Pregnant female mice, homozygous wild-type (+/+) or PPAR alpha -null (-/-), were intubated with either vehicle alone or 1,000 mg DEHP/kg body weight on gestation day (GD) 8 and 9. Pregnancy e was evaluated on GD10 and GD18 in two cohorts of animals. Compared to controls, DEHP administration resulted in maternal toxicity, embryo/ fetal toxicity, and teratogenicity in both (+/+) and (-/-) mice. Maternal liver mRNA for cytochrome P-450 4A1 (CYP4A1) was higher in DEHP-treated (+/+) mice but not in DEHP-treated (-/-) mice on GD10, consistent with their respective phenotype. Maternal liver MT and Zn levels were significantly higher than in controls on GD10. In addition, embryonic Zn content was significantly lower in both genotypes treated with pared to controls. Results from this work show that DEHP-induced reproductive toxicity, teratogenicity, and altered Zn metabolism are not mediated through PPAR alpha-dependent mechanisms. In addition, this work suggests that DEHP-induced alterations in Zn metabolism contribute to the mechanisms underlying DEHP-induced reproductive toxicity and teratogenicity. |
9451757 | Repeated administration of alpha-hederin results in alterations in maternal zinc status and adverse developmental outcome in the rat. | The administration of alpha-hederin, an inducer of metallothionein, results in a secondary zinc deficiency that may be an important maternally mediated mechanism of developmental toxicity. Previous studies have shown adverse developmental e with a single administration of alpha-hederin to rats on gestation day (GD) 8 or 11. The objective of this study was to determine whether dosing of alpha-hederin throughout organogenesis would result in a sustained elevation of maternal hepatic metallothionein and subsequent developmental abnormalities. Rats were administered dosage levels of 0 (vehicle only), 20, or 30 mumol/kg from GD 6-15. Maternal hepatic metallothionein levels were 10-fold higher on GD 16 in the treatment groups than the controls. Consequently, liver zinc concentrations increased 60% and 54%, whereas plasma levels decreased 23% and 33% in the 20 and 30 mumol/kg treatment groups, respectively. At GD 20, mean fetal weights of the treatment litters were 11% less than control litters. The administration of alpha-hederin resulted in a threefold increase in the number of offspring that exhibited developmental abnormalities, including visceral and skeletal malformations. Following an oral pulse of 65Zn subsequent to treatment with 0 or 20 mumol/kg of alpha-hederin, the distribution of 65Zn to the liver of treated dams was twice that of controls, whereas the radiolabeled zinc apportioned to the decidua and uterus decreased by 44%. Furthermore, the 65Zn detected in the embryos from treated dams was 70% lower than in embryos from control dams. In conclusion, low doses of a metallothionein inducer administered to the dam from GD 6-15 resulted in a sustained elevation of hepatic metallothionein and a subsequent redistribution of zinc leading to a decrease in the zinc available to the embryo and ultimately to adverse development of the offspring. Repeated dosing throughout organogenesis, as required in regulated safety assessment testing, increased the severity of the effects previously observed with single large dosages of the toxicant administered during midgestation. |
9451758 | Population-based case-control study of teratogenic potential of corticosteroids. | The teratogenic potential of oral and topical corticosteroid treatment during pregnancy was evaluated in the population-based large dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1994. Corticosteroid tablet pregnancy exposure was 1.55% among 20,830 malformed cases and 1.41% among 35,727 healthy control births (P = 0.2). Corticosteroid ointment pregnancy exposure was 0.35% among malformed and 0.33% among control births (P = 0.7). The absolute risk of oral and ointment corticosteroid treatment was low in pregnancy and particularly in the second and third months of gestation, i.e., in the critical period for major congenital abnormalities. The adjusted odds ratio and the analysis of case-control pairs did not show any association between the rate of different congenital abnormalities and the corticosteroid treatment in the second and third months of gestation. Thus, treatments with corticosteroids in pregnancy do not appear to noticeably increase the risk of congenital abnormalities in humans. |
9451759 | [The dromedary: ancestry, history of domestication and medical treatment in early historic times]. | Research on camel bones from archaeological excavations in North Africa and the Near East contradict the current opinion in textbooks that the dromedary and the Bactrian camel are domesticated forms derived from a single species, the two-humped wild camel (C. ferus). The probable ancestor of the domestic one-humped camel is Thomas' camel (C. thomasi). The wild dromedary was probably domesticated on the Arabian peninsula, perhaps as early as the 4th millennium BC. From the 2nd millennium BC onward there is evidence for the use of the one-humped camel for riding and transport purposes. Camel-keeping also implied the therapy of diseased animals, the main source of information about their treatment being medieval arabic texts dealing with veterinary medicine. An expert of such an early 13th century text is presented and discussed. From this it can be seen that the medieval camel treatment fits the principles of the so-called humoral theory, a medical concept which at that time already existed for more than 1500 years. |
9451761 | [Importance of differential diagnosis of ringing and splashing sounds in the abdomen of adult cattle]. | In cattle liquid and gas in the abdominal cavity can be detected from the outside by use of simultaneous auscultation and percussion or by auscultation with simultaneous shaking of the abdominal wall. Size, area and the quality of the "ping" and splashing sounds are helpful to determine which organs are involved in the disease. Nine possible reasons for intraabdominal gas- and liquid accumulation are discussed. In 12 schematic figures the areas of externally detectable "ping" and splashing sounds pared with the topographic anatomical situation inside the abdomen. |
9451762 | [Incidence, diagnosis, therapy and subsequent fertility in goats with hydrometra]. | The hydrometra is mon disease in dairy goats. The etiology and pathophysiology of this pathological uterine condition has not pletely clarified yet. In the present study 143 cases of hydrometra were found in 2434 goats which had been subjected to pregnancy diagnosis with transrectal ultrasonography for three years. The mean incidence was 5.78%. The uterus of the goats was filled with a clear or slightly turbid fluid which contained small blobs to a certain extent. The amount of the aseptic fluid in the uterus varied from 0.25 to 8.3 l. Hydrometra occurred in goats which had been mated as well as in those which had not been mated. Hydrometra may also be panied by embryonic/fetal mortality. The incidence of hydrometra was significantly increased in older does and in does which had been mated after estrus synchronisation with gestagens and PMSG. Out of the breeding season the incidence was higher than during the breeding season. The breed of the does and the milk yield did not influence the incidence of hydrometra. The application of prostaglandin analoques performed a luteolysis and the cloudburst in the goats with high efficiency. After therapy the performance in breeding was significantly decreased. The performances improved when does were mated in a longer distance to the disease. The goats showed a high risk of developing hydrometra again. |
9451763 | [Stress free anesthesia induction ZESTRANI (ZEro STRess ANesthesia Induction) in Göttingen minipigs. An experimental method]. | The Göttingen Mini-pig is a popular laboratory animal, that is used i.a. in experimental surgery and anaesthesia. For ethical and scientific reasons it is mandatory to minimize the stress the laboratory animals are exposed to. The presented stress-free experimental anaesthesia induction (ZESTRANI) is based on innovative means to achieve adequate analgesia using different substances appropriate for the animal's state of consciousness. Markedly lower heart rates and mean arterial pressures are seen when the ZESTRANI-method is used pared retrospectively to the previously used "conventional" anaesthesia induction. With the ZESTRANI method no "fight or flight"-reactions are seen. |
9451764 | [Program for early detection of illness level in foals during the first 24 hours of life]. | Basing on exact investigations of normal behaviour and abnormalities in newborn and up to 24 hours old foals a program for prehending exogeniously judgable criteria, was developed. It aims at a quick recognition of aberrations in behaviour. The program includes a score, which allows early diagnosis of even subtile abnormalities. As a result, a veterinary surgeon should be consulted if the score exposes a critical situation, so that therapy can be started in time. Furthermore informations about investigations on blood-glucose- and immunoglobulin-G-concentration in relation to neonatal foal diseases are given. |
9451765 | [Enzootic spinal ataxia in fallow and wild red deer in Upper Bavaria]. | Since 1993 several cases of spinal ataxia occurred in adult red and/or fallow deer in four farms in Southern Bavaria. The disease based on a secondary copper deficiency due to a high level of molybden and a low level of copper content in the feed. Some of the animals suffer from a severe disturbance of motion. In most cases the animals are shot at the beginning of illness. Histologically the most important lesions are in the spinal cord consisting mainly in a bilateral symmetric degeneration of dorsolateral and ventral areas of the white matter. Degeneration is caused by lamellar disintegration of the myelin connected with deposition of fine-granulated substances detectable by electronmicroscopical investigation. In the liver and other organs we always found a hemosiderosis which is also believed to be caused by copper deficiency. |
9451766 | [Infectious laryngotracheitis in chickens, peacocks and pheasants and means and limitations for its control with attenuated live vaccines]. | All hitherto examined gallinaceous birds (Phasianiformes) are susceptible for the virus of infectious laryngotracheits, an avian alpha-herpesvirus. Degree and duration of the disease are highly variable. Chickens of all breeds, peacocks and some of the numerous species of pheasants (diamont, blue and white ear, impeyanus, Reeve's, Elliott and argus pheasant) suffer from severe haemorrhagic or fibrinous laryngotracheitis. The ring-necked pheasant displays a distinct conjunctivitis and sinusitis following natural exposure. An attenuated live virus vaccine is sofar developed, tested and registered only for the chicken. The vaccine is usually administered in the conjunctival sac (eye drop method). All vaccinated chickens are to be kept separately from unvaccinated chickens for four weeks post vaccinationem. Separation is also necessary for peacocks and pheasants because these birds may suffer from infection of vaccinal virus. The attenuated live virus vaccine should only be administered to chickens in areas in which ILT is endemic. Chickens less than four weeks of age as well as any of the peacock and pheasant species must not be vaccinated. Turkeys do normally not contract the disease and therefore need no protection by vaccination. |
9451767 | [Pathogenesis and diagnosis of systemic acidosis in animals with conclusions for effective forms of therapy]. | Intermediary metabolism produces daily approximately 285 mmol hydrogen ions per kilogramm metabolic body weight (BWkg 0.75). If the lung fails to eliminate the volatile acid H2CO3 sufficiently and/or if the kidneys do not eliminate the also produced nonvolatile acids a retention of acids in the organism results. This way, as well as increased acid production through metabolic processes, leads to a systemic acidosis. Systemic acidosis develops after a primary dysfunction of an organ. If there is only one cause of an acid-base-disturbance, e.g. metabolic acidosis, the organism will respond pensation by the correspondent organ, e.g. the lung, which reduces the drop in the pH. If metabolic and respiratory acidosis occur simultaneously pensation is impaired and the fall in the pH is greater by additive effects. This can lead to a severe, life-threatening decline in the blood-pH (< 7.00). If the pH falls from normal value of 7.40 below 7.20, buffer therapy is necessary. Most alkalinizing agents in veterinary medicine, such as bicarbonate, lactate or acetate are only effective after increased pulmonary elimination of CO2 produced in buffer reactions. These substances are not suitable and are even contraindicated in therapy of primary respiratory or mixed respiratory-metabolic acidosis. New buffer agents, e.g. an equimolar mixture of NaHCO3 and Na2CO3 (= Carbicarb) open new promising possibilities in the treatment of acidotic disorders in animals. However clinical trials to determine the efficacy of Carbicarb in animals are still to be conducted. |
9451768 | Electrosyntheses from aromatic aldehydes in a flow cell. Part I. The reduction of benzaldehyde. | The reduction of benzaldehyde in acidic water-methanol mixtures has been re-investigated in a membrane flow cell with a lead cathode with the objective of defining conditions where le- reduction occurs and the C6H5CH.OH radical intermediate is formed in high selectivity. It is shown that it is the cathode potential which controls the ratio of le-/2e- product (i.e. hydrobenzoin to benzyl alcohol) and a high rate generation of the radicals is also favoured by an efficient mass transport regime. |
9451769 | Electrosyntheses from aromatic aldehydes in a flow cell. Part II. The cross-coupling of benzaldehydes to unsymmetrical diols. | It is demonstrated that the reduction of mixtures of two benzaldehydes in acidic water-methanol in a membrane flow cell with a lead cathode can lead to a mixture of diols including the unsymmetrical diol, e.g. 4-F-C6H4-CH(OH)-CH(OH)-C6H5. In the conditions employed, the ratio of the three diol products follows the statistical distribution expected for the coupling of two different radical intermediates produced in the same ratio as the concentrations of their precursors. The yield and current efficiency for the diols are excellent when the pH and potential are selected so that a le- reduction of both benzaldehydes occurs. The yield of unsymmetrical dimer based on one reactant can be increased substantially by using the other pound as a sacrificial reagent. |
9451771 | The state-of-the-art on worldwide studies in some environments with elevated naturally occurring radioactive materials (NORM). | Direct observations and studies of the radiobiological and epidemiological effects of ionizing radiation from naturally occurring radioactive materials (NORM) on man, in particular in areas with elevated NORM, are ing of prime concern in radiation protection. This is due to existing discrepancies in the application of the linear no-threshold theory in obtaining radiation risks at low doses by extrapolation from high dose to low dose using dose and dose-rate effective factors. Many areas in the world have elevated NORM caused either by the geological and geochemical structure of the soil, or by the radioactive content of the water flowing from hot springs and/or due to technologically enhanced radioactivity as well as due to cosmic rays. Such areas, with relatively large cohort sizes, have been the subject of intensive dosimetry, radiobiological and epidemiological studies. It is the purpose of this article to review: sources of NORM and human exposure, needs and problems in study of areas with elevated NORM; the criteria for their classification; some areas with elevated NORM and the results of related studies, and some conclusions and mendations for unification of an approach in future studies aimed at obtaining better estimates of human radiation risk factors from the effects of ionizing radiation. |
9451772 | Potential environmental and regulatory implications of naturally occurring radioactive materials (NORM). | The immense volume of naturally occurring radioactive materials (NORM) wastes produced annually by extracting industries throughout the world deserves e to the attention of international and national environmental protection agencies and regulatory bodies. Although a great deal of work has been done in the fields of radiation protection and remedial actions concerning uranium and other mines, the need to dispose of diffuse NORM wastes will have environmental and regulatory implications that thus far are not fully appreciated. NORM wastes constitute, by and large, unwanted byproducts of industrial activities as diverse as thorium and uranium milling, niobium, tin and gold mining extraction, water treatment, and the production of oil, gas, phosphate fertilizer, coal fire and aluminum. The volumes of NORM wastes produced annually could reach levels so high that the existing low level radioactive waste (LLRW) facilities would be readily occupied by NORM if controlled disposal procedures were not adopted. On the other hand, NORM cannot just be ignored as being below radiological concern (BRC) or lower than exempt concentration levels (ECLs), because sometimes NORM concentrations reach levels as high as 1 x 10(3) kBq/kg for 226Ra, and not much less for 228Ra. Unfortunately, thus far there is not enough information available concerning NORM wastes in key industries, though the international munity has been concerned, for a long time now, with technologically enhanced natural radiation exposures (TENRE). This article is written with the intention of examining, to the extent possible, the potential environmental and regulatory implications of NORM wastes being produced in selected industries. |
9451773 | Field survey instrumentation and radioanalytical procedures for NORM. | prehensive monitoring and analysis of NORM is extremely difficult and involves a wide range of equipment and techniques. The instruments to be used can depend on both the national legislation of the country in which the measurements are being undertaken and the operational conditions under which they are carried out. These can dictate whether dose rate, alpha/beta contamination or gamma contamination measurements are taken. In some circumstances the total activity of the samples can be estimated using the gamma activities of the radionuclides present, while in others only full gamma and alpha spectral analysis will suffice. |
9451774 | Exposures at work to ionising radiation due to the use of naturally occurring radioactive materials in industrial processes. | In its role as specialist radiation protection adviser to industries in the United Kingdom, the National Radiological Protection Board has had extensive involvement with industrial users of raw materials with low activity concentrations of naturally occurring radionuclides. The magnitude of the exposure to ionising radiation in these establishments has been investigated. This paper reviews the pathways of exposure and gives estimates of worker dose in the light of revised dose coefficients. It concludes that doses are lower than previously reported and are generally in the order of a few millisieverts per year or less. |
9451775 | Regulatory control and NORM--the U.K. position. | The historical background to the development of regulatory control of NORM in the workplace is described. The current U.K. approach is illustrated in terms of the basis of the legislation and the arrangements required for the employer to satisfy the legislation. The importance of ALARA is emphasised. Future changes to U.K. legislation, under a new European Directive, are outlined. The awareness of employers about the potential risk of chronic exposure of employees to NORM is judged to be generally low. |
9451776 | Issues in the disposal of waste containing naturally occurring radioactive material. | This article considers a number of key issues in the disposal of waste containing enhanced levels of naturally occurring radioactive material (NORM), including gaseous, liquid and solid media. A brief review is made of sources of natural radioactivity in the biosphere and of anthropogenic enhancement of the concentration of NORM in the various media. The factors controlling the mobility of radionuclide activity in the environment are examined and disposal options are parison also being made with disposal of nuclear fuel cycle materials, in particular the tailings of uranium mining. Current and proposed disposal practices and policies for NORM are cited, reference being made to experiences in a number of countries. |
9451777 | Technologically enhanced naturally occurring radioactive material (NORM): pathway analysis and radiological impact. | The main pathways by which technologically enhanced radioactive materials can impact on human health have been examined. Analytical methods are presented for calculation of the radiation doses for the dominant pathways for external and internal exposure. The application puter modelling to the assessment of the radiological impact of NORM is also discussed. |
9451778 | Disposal options and case-study pathway analyses. | This paper presents an overview of alternatives that currently are employed for the disposal of wastes containing enhanced concentrations of naturally occurring radioactive materials (NORM). The application of pathway assessment methodology to the derivation of acceptable cleanup criteria for residual NORM is described. A specific example is provided drawing on experience with a site containing above-background levels of natural uranium-series and thorium-series nuclides. The options for safe, permanent disposal of U and Th bearing NORM waste are discussed and the application of pathway analysis to performance assessment of a typical engineered disposal cell is illustrated. Typical methods for disposal of other NORM waste forms also are described. This includes radium-contaminated wastes from petroleum sludges, uranium milling, and geothermal power plant operation as well as thorium wastes from production of thorium-magnesium alloys. |
9451779 | The establishment of a radioactive waste disposal facility in Western Australia for low level waste. | The Radiation Health Section of the Health Department of Western Australia has been a repository for unwanted radioactive sources for many years. They had been placed in the radioactive store located on the Queen Elizabeth II Medical Centre Campus. After a collection period of more than 20 years the storage facilities of the Radiation Health Section were nearing capacity. A decision was made to relocate these sources into a permanent near surface burial facility. Following munity consultation and site investigations, waste originating in Western Australia was disposed of at Mt Walton (East), 80 km North East of Koolyanobbing, Western Australia in November 1992. |
9451780 | Near-surface disposal of concentrated NORM wastes. | Naturally occurring radioactive material (NORM) in concentrated forms arises in nature and in industry where natural radioisotopes e mobile and then accumulate at particular sites. In industry this often occurs in an acidic environment, where precipitates containing radionuclides plate out onto pipe walls, filters, tank linings, etc. As the radionuclides are selectively deposited, they build up and there is a multiplying effect in terms of the radioactivity concentration. Conditions often tend to favour the build-up of radium, particularly when barium is present and can cause the co-precipitation of pounds. As radium is highly radiotoxic, the handling and disposal of such material requires careful management. The state of Western Australia currently has the only low level waste repository in Australia, located at Mt Walton East. To date this repository has been used predominantly to dispose of packaged radioactive waste containing artificial radioisotopes, but there is an increasing demand for the repository to accept bulk concentrated NORM wastes from mining and related industries. Already steelwork from a dismantled phosphoric acid plant and other items contaminated with NORM have been disposed of. The Mt Walton East repository is now proposed as the disposal site for 6000 tonnes per annum of gangue residue from the processing of monazite. The residue contains thorium and a small amount of radium. This paper looks at the technical and related considerations of these disposal operations. |
9451781 | Characterization and optimization of microelectrode arrays for in vivo nerve signal recording and stimulation. | Revealing plex signal-processing mechanisms and interconnection patterns of the nervous system has long been an intriguing puzzle. As a contribution to its understanding the optimization of the impedance behavior of implantable electrode arrays with via holes is discussed here. Peripheral axons will regenerate through these holes allowing for simultaneous nerve stimulation and signal recording. This approach is part of the ESPRIT project INTER and may eventually lead to devices driving sensory motor prosthesis with closed loop control. In the first set of experiments, micromachined platinum electrode arrays were prepared, characterized and optimized for nerve signal recording. The results of these studies are based on impedance spectroscopy and microscopic techniques. Equivalent circuits were modeled describing formally the electrical response behavior with ohmic resistances between 500 omega and 10 k omega. To attain low impedances for all electrodes on the INTER device, platinum from H2PtCl6 was electrodeposited, and sputter technology as well as electrochemical deposition from H2IrCl6 solution were used to produce thin iridium films. For the former, a lift-off process was established at one of the institutes to generate electrode structures with a line width of 5 microns. As a result in all three cases the electrodes showed almost constant impedances over the entire frequency range (10 Hz-1 kHz), which is relevant for nerve signal recording. In the second set of experiments, electrodes were optimized to allow for nerve stimulation. For this purpose, the charge delivery capacity (CDC) had to be increased and the impedance had to be decreased. Iridium oxide is the material of choice, because its CDC is much higher than the CDC of platinum at 75 microC/cm2 (Ziaie et al., 1991, IEEE Sensors & Actuators Transducers, 6, 124-127). A significant increase of the electrochemically active surface of the electrode structures could be observed by measuring the surface roughness. In first experiments, an activated iridium oxide film was formed with cyclic voltammetry and was evaluated using scanning force microscopy and impedance spectroscopy. The evaluation of the cyclic voltammograms showed a CDC up to 400 mC/cm2 for sputter deposited and oxidatively treated iridium films. Further investigations are directed towards increasing the stability of the iridium oxide electrodes with regard to long-term implants. Parallel experiments aim at the controlled axon adhesion without changing the impedance behavior of the described electrodes. |
9451782 | A microflow amperometric glucose biosensor. | We investigate a small glucose sensor that uses a flow-through enzyme bed and reaction endpoint approach that seems particularly suited to microdialysis-type subcutaneous or intravascular glucose sensors. The particular configuration has the advantage of relative insensitivity to blood oxygen changes and also to factors which affect enzyme pared to conventional polarographic type glucose sensors. We evaluate the placement of a microdialysis fiber into a near-surface blood vessel in the dog model as a means of blood glucose sampling and to determine the effects of protein deposition. We observe a progressive decline in intravascular membrane fiber transport that must be considered in sensor design. |
9451783 | Application of fuzzy logic in multicomponent analysis by optodes. | Fuzzy logic can be a useful tool for the determination of substrate concentrations applying optode arrays bination with flow injection analysis, UV-VIS spectroscopy and kinetics. The transient diffuse reflectance spectra in the visible wavelength region from four optodes were evaluated to carry out the simultaneous determination of artificial mixtures of ampicillin and penicillin. The discrimination of the samples was achieved by changing position of the receptor gel and working pH. Different algorithms of pre-processing were applied on the data to reduce the spectral information to a few analytic-specific variables. These variables were used to develop the fuzzy model. After calibration the model was validated by an independent test data set. |
9451784 | Fiber optic-based biosensor for ricin. | We report on an evanescent wave fiber-optic biosensor for detecting a potently toxic protein, ricin, in the picograms per milliliter range. A sandwich immunoassay scheme was used to detect ricin. First, an anti-ricin IgG was immobilized onto the surface of an optical fiber in two different ways. In the first method, the antibody was directly coated to the silanized fiber using a crosslinker. Second, avidin-coated fibers were incubated with biotinylated anti-ricin IgG to immobilize the antibody using an avidin-biotin bridge. The assay using the avidin-biotin linked antibody demonstrated higher sensitivity and wider linear dynamic range than the assay using antibody directly conjugated to the surface. The linear dynamic range of detection for ricin in buffer using the avidin-biotin chemistry is 100 pg/ml-250 ng/ml. The limits of detection for ricin in buffer solution and river water are 100 pg/ml and 1 ng/ml, respectively. At higher concentrations of ricin (> 50 ng/ml), we observe a strong interaction of ricin with the avidin coated on the surface of the fibers. We have demonstrated that this interaction is primarily due to the lectin activity of ricin and is significantly reduced using fibers coated with neutravidin or by adding galactose to the ricin samples. |
9451785 | Ultrasensitive bienzyme sensor for adrenaline. | A biosensor consisting of an analyte-recycling two-enzyme system using laccase (Coriolus hirsutus) and PQQ-dependent glucose dehydrogenase bination with the electrochemical detection of oxygen depletion at a platinum electrode was used for adrenaline determination in the nano- and subnanomolar concentration range. Measurements were performed in a flow cell providing excellent baseline stability and fast recovery of the sensor. Improved design of the polymer matrix resulted in a lower detection limit of 200 pmol/l for adrenaline. The sensor has successfully been applied to the analysis of adrenaline in effluate of isolated rabbit hearts. |
9451786 | Dielectric measurements of lysozyme and tri-N-acetyl-D-glucosamine association at radio and microwave frequencies. | Time domain dielectric measurements were applied to the monitoring of molecular recognition by proteins. Lysozyme and tri-N-acetyl-D-glucosamine((NAG)3) were selected as a typical lock and key type recognition system. After association of (NAG)3, relaxation related to lysozyme itself was increased and depended on the pH of the solution. No change was detected in hydration of the enzyme before and after association. |
9451787 | A chemiluminescent FIA biosensor for phosphate ion monitoring using pyruvate oxidase. | We have constructed an automatic phosphate ion sensing system for the quality control of drinking water. The analyte was detected using the phosphate ion-dependent pyruvate oxidase reaction and the hydrogen peroxide produced was detected by luminol chemiluminescence catalyzed by Arthromyces ramosus peroxidase. We obtained a detection limit of 0.16 microM phosphate ion (5 ppb phosphorus) and it was possible to detect 0.32 microM phosphate ion for 48 days using pyruvate oxidase immobilized on Chitopearl BCW-2601 beads. An excellent correlation (r2 = 1.00) was obtained between the results obtained using our phosphate ion sensor and those using a modified Molybdenum Blue method. |
9451788 | Methodological aspects of glucose monitoring with a slow continuous subcutaneous and intravenous ultrafiltration system in rats. | A method for the continuous ultrafiltration of venous blood or subcutaneous fluid is demonstrated with glucose monitoring in the living rat. Ultrafiltrate was withdrawn at a constant flow rate of approximately 100 nl/min. Glucose content of the ultrafiltrates was electrochemically determined with a flow injection analysis method and a bi-enzyme reactor. After glucose loading, the time course of glucose in the ultrafiltrate from the jugular vein was virtually identical, whereas that from the partment was attenuated and the peaks blunted pared to glucose levels in itantly assayed arterial blood. Our study demonstrates the potential of low rate ultrafiltration for monitoring metabolism with biosensor technology in vivo. |
9451789 | Capacitive monitoring of protein immobilization and antigen-antibody reactions on monomolecular alkylthiol films on gold electrodes. | Self-assembled monolayers of omega-mercaptohexadecanoic acid and omega-mercaptohexadecylamine on gold electrodes are stable at neutral pH and display pure capacitive behavior at frequencies around 20 Hz. Different methods of covalent immobilization of proteins on these monolayers pared. Various reagents including succinimides, thionylchloride, p-nitrophenol and carbodiimides were used to activate the carboxy groups of the adsorbed monolayer of omega-mercaptohexadecanoic acid. Glutaraldehyde, cyanuric chloride and phenylene diisocyanate were used to activate the amino groups of the monolayer of omega-mercaptohexadecylamine. The immobilization of albumin on the activated surface was studied by capacitive measurements. The N-hydroxysuccinimide and carbodiimide methods were identified as most suitable for protein immobilization in that they did promise the insulating properties of the alkylthiol layer and led to maximal increase of its dielectric thickness. These approaches were used for a layer-by-layer preparation of a capacitive immunosensor. Specifically, antibodies to human serum albumin were immobilized on the alkylthiol mono-layer. Binding of the antigen led to a decrease of the electrode capacitance. The detection limit of the immunosensor is as low as 15 nM (1 mg/l). |
9451790 | Ion exchanger modified PVC membranes--selectivity studies and response amplification of oxalate and lactate enzyme electrodes. | We report on a novel method of oxidase enzyme electrode response amplification, using unplasticized PVC and plasticized PVC, respectively. The anion exchanger tricaprylylmethylammonium chloride (Aliquat 336s) and hydrophobic isopropylmyristate (IPM) plasticizer have been used together to modify PVC. Resulting structures are anionic substrate selective and hydrogen peroxide impermeable and can be used as outer membranes of a classical dual membrane amperometric enzyme electrode where an oxidase is used to generate H2O2 for electrochemical detection. Their effect on sensor sensitivity and linearity is considered. |
9451791 | A novel method for diabetes diagnosis based on electronic nose. | A novel non-invasive method for diabetes diagnosis based on an electronic nose is proposed in this paper. The principles of the method and results of clinical experiments are presented. These results show the convenience, painlessness and non-invasiveness of the method. |
9451792 | Hydrogen peroxide augmentation in a rat striatum after methamphetamine injection as monitored in vivo by a Pt-disk microelectrode. | We fabricated a Pt-disk microelectrode (diameter 30 microns) to conduct differential double-pulse amperometry (first step: 750 mV, 1 s; second step: 1,100 mV, 1 s) to detect hydrogen peroxide in the brain of a freely moving animal. This measurement determined hydrogen peroxide (detection limit, 0.03 microM) without any observable influence from other oxidizable species, such as dopamine (DA), ascorbic acid, or uric acid. The electrode was implanted into the right striatum of a rat. After intraperitoneal injection of methamphetamine (MAP), hydrogen peroxide concentrations were directly detected while the behavioral changes were monitored. MAP injection led to significant augmentation of hydrogen peroxide, the elevation of which depended on the dose of MAP. This is consistent with a previous report on the increase of DA-release caused by amphetamines and indirect evidence of the production of hydrogen peroxide via DA-metabolism. |
9451793 | Assembling and evaluation of new dehydrogenase enzyme electrode probes obtained by electropolymerization of aminobenzine isomers and PQQ on gold, platinum and carbon electrodes. | Pt, Au and graphite electrodes have been coated by electropolymerization of 1,2-, 1,3-, 1,4-diaminobenzene (DAB) and 4-aminobiphenyl in the presence of PQQ using cyclic voltammetry. The activity of the modified electrodes for the oxidation of paracetamol, ascorbic and uric acid was reduced by approximately 90% pared to the bare electrodes. Polymerization in the presence 4,5-dihydro-4,5-dioxo-1H-pyrrolo(2,3-f)quinoline-2,7,9-tricarboxilic+ ++ acid, pyrroloquinolinequinone (PQQ) led, after optimization, to electrodes capable of catalysing the electrooxidation of beta-nicotinamide adenine dinucleotide, reduced form (NADH), in the range 10(-4)-10(-2) mol/l with a detection limit of 5 x 10(-5) mol/l. Amperometric measurements of NADH have been carried out at +0.2 V and the efficiency of different electrodes based on different materials has been studied. By co-entrapment of dehydrogenase highly selective enzymes, electrodes for glucose, L-lactate and L-glutamate were obtained. Dehydrogenase substrates such as glucose, lactate and glutamate were measured in the range 5 x 10(-5)-1 x 10(-2) mol/l, with detection limits of 10(-5) and 5 x 10(-6) mol/l, respectively. Probe stability under non-dynamic conditions was evaluated over 2 months. All the probes showed a decrease of 10% over 1 month and a residual activity of 50% over 2 months. |
9451795 | A user-friendly method for calibrating a subcutaneous glucose sensor-based hypoglycaemic alarm. | A crucial step in developing a glucose monitoring system using a subcutaneous implanted glucose sensor is the transformation of the sensor signal (a current) into an estimation of a blood glucose concentration. We have developed an Electronic Control Unit (ECU) able to recognize, before and after a glucose load, that the sensor current presents a plateau, thus triggering an alarm asking for blood glucose determination. The system, fed with these results, subsequently transforms the current into an estimation of glucose concentration by linear extrapolation based on the sensor sensitivity and the background puted from the two sets of current and glycaemia values (two-point calibration). In addition, the system is able to trigger an alarm when this estimation decreases below a threshold that can be set by the user. This system was evaluated in experiments performed in 12 normal rats. The quality of the calibration was assessed paring, by error grid analysis, the data displayed on the liquid-crystal display of the ECU to itant plasma glucose concentration determined at frequent intervals, 65 +/- 6 and 26 +/- 5% of the values were in zones A (good) and B (acceptable estimation) of the grid, respectively. The system was set to trigger an alarm when the estimation of glucose concentration decreased below 70 mg/dl. Following an insulin administration, the alarm was triggered when the system displayed a 64 +/- 2 mg/dl glucose concentration. The itant plasma glucose concentration was 59 +/- 5 mg/dl (NS). In conclusion, this work validates experimentally the new, user-friendly method for calibrating the glucose sensor integrated into the ECU, based on an automatic detection of plateaus. The quality of the sensor calibration performed with this procedure patible with the appropriate functioning of this continuous glucose monitoring system, which was demonstrated by its ability to detect mild hypoglycaemia following insulin injection. |
9451796 | Minimal-Fouling enzyme electrode for continuous flow measurement of whole blood lactate. | A new membrane system evaluated in an enzyme electrode for monitoring of whole blood lactate under continuous flow conditions has been developed. The membrane confers functional patibility and has been coupled to an electrode based on amperometric detection of hydrogen peroxide with lactate oxidase interposed between the patible membrane acting as diffusion barrier and an inner membrane excluding interfering electroactive species. Here, the enzyme electrode bined with a flow-through measuring chamber and a double lumen catheter permitting continuous sampling and heparinization of blood. The blood contacting membranes have unique patibility properties and were produced through modification of poly(vinyl chloride), with the nonionic surfactant Pluronic F-68. On-line monitoring of whole blood samples with different amounts of added lactate was carried out to simulate fluctuations in blood lactate levels during extracorporeal monitoring and results pared with a standard lactate analyser. |
9451797 | The lipoxygenase sensor, a new approach in essential fatty acid determination in foods. | Both an enzyme electrode and enzyme column with immobilized lipoxygenase, respectively, were used for the determination of essential fatty acids. The former was applied in a batch system, the latter was part of a fully automated flow injection analysis (FIA)-system. The oxygen consumption due to the lipoxygenase catalysed oxygenation of essential fatty acids was monitored amperometrically. Both systems pared with regard to linear ranges of the calibration plots, sensitivities, detection limits, apparent Michaelis-Menten constants and lifetimes. The enzyme electrode showed different sensitivities for linoleic and alpha-linolenic acids, the mon essential fatty acids. The reason for this was not a second oxygenation step by lipoxygenase in case of alpha-linolenic acid, but a different dialytic behaviour of the two substrates. Hence, only the FIA-system was used for the determination of these fatty acids in real matrices such as vegetable oils and margarines. In the presence of detergent the triglycerides of the hydrophobic food samples were converted into water soluble glycerol and free fatty acids by a 15 min incubation with a ready to use lipase/esterase-mix, thus avoiding the use of organic solvents for analysis. Results obtained by the enzymatic FIA-system were in excellent agreement with those obtained by standard gas chromatography. |
9451798 | Antibody immobilization using heterobifunctional crosslinkers. | Covalent attachment of functional proteins to a solid support is important for biosensors. One method employs thiol-terminal silanes and heterobifunctional crosslinkers such as N-succinimidyl 4-maleimidobutyrate (GMBS) to immobilize proteins through amino groups onto glass, silica, silicon or platinum surfaces. In this report, several heterobifunctional crosslinkers pared to GMBS for their ability to immobilize active antibodies onto glass cover slips at a high density. Antibodies were immobilized at densities of 74-220 ng/cm2 with high levels of specific antigen binding. Carbohydrate-reactive crosslinkers were pared to GMBS using a fiber optic biosensor to detect fluorescently-labeled antigen. At the concentrations tested, the antibodies immobilized with carbohydrate-reactive crosslinkers bound more antigen than GMBS immobilized antibodies as indicated by the fluorescence signal. |
9451799 | Studies towards a disposable screen-printed amperometric biosensor for progesterone. | A screen-printed carbon electrode (SPCE) has been investigated as the base transducer for a disposable amperometric progesterone biosensor. The biorecognition element was a monoclonal sheep anti-progesterone antibody (mAb). This was immobilized onto the transducer by interaction with a layer of rabbit IgG which had been previously coated onto the SPCE; optimum conditions for these loadings were deduced experimentally. The device was employed in petitive assay using alkaline phosphatase-labelled progester-one. Three possible substrates for the enzyme were considered, namely, phenyl phosphate, phenolphthalein phosphate and 4-aminophenol phosphate. Cyclic voltammetry and amperometry were carried out on the corresponding aromatic phenols and phenol itself was found to give the best electrochemical characteristics; consequently, phenyl phosphate was employed as the substrate. Chronoamperometry was used to measure the phenol produced by the reaction of bound enzyme-labelled progesterone and substrate. The chronoamperometric response was dependent on unlabelled progesterone over at least three orders of magnitude with a detection limit of about 1 x 10(-9) mol/dm3. This suggests that the device may have applications for the analysis of biological fluids. |
9451800 | An immunosensor based on disposable electrodes for rapid estimation of fatty acid-binding protein, an early marker of myocardial infarction. | An immunosensor was developed that allows the rapid estimation of fatty acid-binding protein (FABP) in neat plasma samples. FABP is released into the blood following myocardial infarction and elevated levels are found already 3 h after onset of symptoms. The sensor is based on screen-printed graphite working and Ag/AgCl reference electrodes and an immunosandwich procedure for the quantification of FABP. The capture antibodies are bound to the electrode surface by adsorption and will trap FABP from the plasma sample. The sandwich is pleted by a second monoclonal antibody conjugated with alkaline phosphatase. The enzyme converts p-aminophenylphosphate to p-aminophenol, which is detected amperometrically at +350 mV. The high binding capacity and very short response time of the working electrode allow within 20 min the quantification of FABP in the measuring range 10-350 ng/ml, covering the pathological range of FABP release into the circulation. Measurements of plasma samples from a patient with acute myocardial infarction show an excellent correlation of the results obtained with the biosensor and those obtained with the respective reference ELISA. Owing to the long stability of the electrodes with immobilized capture antibody (> 3 months) a quick application without the need of labour-intensive electrode preparation is possible. |
9451803 | Localization of SH-PTP1 to synaptic vesicles: a possible role in neurotransmission. | The tyrosine kinase pp60src is known to phosphorylate synaptophysin and in doing so may regulate neurotransmitter release. The tyrosyl phosphorylated state of synaptophysin is dependent on pp60src kinase and the unknown protein tyrosine phosphate phosphohydrolase (PTPase, EC 3.1.3.48). Here we report the protein tyrosine phosphate phosphohydrolase SH-PTP1, to associate with synaptic vesicles and interact with synaptophysin. These studies identify SH-PTP1 as a new member of the secretory machinery at the nerve terminal and suggest its involvement in neurotransmission. |
9451804 | Induction of keratinocyte proliferation by a short treatment with keratinocyte-conditioned medium. | The effect of a short treatment with keratinocyte-conditioned medium (KCM) on the growth of normal human epidermal keratinocytes was investigated. Serum-free MCDB153 medium was conditioned by keratinocytes for 24 h after plating. Following attachment to uncoated plastic surfaces (4 h after plating), cells were exposed for 20 h to KCM. After 10 days of culture in MCDB153 medium, an increase of about six-fold in cell number was observed in KCM-treated plates over controls, indicating that a short treatment with KCM is sufficient to induce cell proliferation. The effect of addition of KCM at different times after plating was also evaluated: KCM treatment resulted to exert its maximum effect on cell proliferation, when performed immediately after pletion of attachment of cells to the surface of the dish. Mitogenic activity present in KCM is not inhibited by heparin sulphate. The kinetics of accumulation of this early secreted growth-stimulating activity showed that a plateau is reached within 24 h of conditioning. These data suggest that this mitogenic activity should not be amphiregulin. The observation that, following KCM treatment, the majority of cells is able to incorporate [3H]-thymidine pared to controls suggests that the observed final increase in cell number is due to an increase in the number of cycling cells rather than to a shortening of the cell cycle. |
9451805 | Confocal analysis of primary cilia structure and colocalization with the Golgi apparatus in chondrocytes and aortic smooth muscle cells. | Detyrosinated and acetylated alpha-tubulins represent a stable pool of tubulin typically associated with microtubules of the centrosome and primary cilium of eukaryotic cells. Although primary cilium-centrosome and centrosome-Golgi relationships have been identified independently, the precise structural relationship between the primary cilium and Golgi has yet to be specifically defined. Confocal immunohistochemistry was used to localize detyrosinated (ID5) and acetylated (6-11B-1) tubulin antibodies in primary cilia of chondrocytes and smooth muscle cells, and to demonstrate their relationship to the plex identified plementary lectin staining with wheat germ agglutinin. The results demonstrate the distribution and inherent structural variation of primary cilia tubulins, and the anatomical interrelationship between the primary cilium, the Golgi apparatus and the nucleus. We suggest that these interrelationships may form part of a functional feedback mechanism which could facilitate the directed secretion of newly synthesized connective tissue macromolecules. |