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The clinical and economic impact of deep chest surgical site infections following coronary artery bypass graft surgery. To examine how deep chest surgical site infections following coronary artery bypass graft (CABG) surgery impact hospital inpatient length of stay (LOS), costs, and mortality. A large, Midwestern community medical center. All CABG patients who developed deep chest infection (n = 41) were compared to a set of control subjects (n = 160) systematically selected as every tenth uninfected CABG patient. Clinical data were abstracted from patient records, and cost information was obtained from the cost accounting database of the hospital. Variables that significantly increased the risk of deep chest surgical site infection included obesity (odds ratio [OR], 11; p = 0. 0001), renal insufficiency (OR, 8.9; p = 0.0001), connective tissue disease (OR, 25.4; p = 0.0003), reexploration for bleeding (OR, 8.2; p = 0.0015), and the timing of antibiotic prophylaxis (> 60 min before incision; OR, 5.3; p = 0.0128). Within 1 year postoperatively, patients with deep chest surgical site infection had a mortality rate of 22%, vs 0.6% for uninfected patients (p = 0.0001). Infected patients also incurred an average of 20 additional hospital days (p = 0.0001). Univariate analysis indicated that patients who developed deep chest surgical site infection incurred $20,012 in additional costs in the first year (p = 0.0001). Infected patients who died incurred on average $60,547 more than infected patients who survived (p = 0.034). Multivariate analysis confirmed the magnitude of the estimate of the cost for deep chest surgical site infection ($18, 938; p = 0.0001). Deep chest surgical site infections following CABG surgery are associated with significant increases in LOS, hospitalization costs, and mortality. These results suggest the need for improved infection control measures to reduce deep chest surgical site infection rates.
Identification of N-homocysteinylated apolipoprotein AI in normal human serum. In human serum, a portion of homocysteine (Hcy) exists as an N-linked form to the epsilon-amino group of protein lysine residues. N-homocysteinylated proteins differ structurally and functionally from native proteins. The present study strives to develop detection and potential semi-quantification methods for N-homocysteinylated apolipoprotein AI (N-Hcy-apoAI) in human serum. Serum treated with or without cysteamine was supplied to isoelectric focusing (IEF) followed by an immunoblot using an anti-apoAI antibody. Cysteamine treatment increased the isoelectric point for N-Hcy-apoAI, but not for unmodified apoAI, due to the presence of -SH group(s) derived from Hcy and the absence of a cysteine residue in the apoAI molecule. N-Hcy-apoAI was semi-quantified from the scanned immunoblot pattern via a computer. After cysteamine treatment, N-Hcy-apoAI in the serum was identified by IEF at the position with a higher pI value compared with intact apoAI. The reproducibility (between assays) of the semi-quantification method was 19.1% CV (coefficient of variation) for an average ratio 5.9% of N-Hcy-apoAI to the whole apoAI in the serum. Approximately 1.0-7.4% of apoAI was N-homocysteinylated in the serum obtained from 27 healthy subjects. Neither the ratio of N-Hcy-apoAI nor its concentration, calculated by total apoAI concentration, indicated correlation with the so-called total (free and S-linked) Hcy concentration. We directly found that a portion of apoAI in the serum undergoes homocysteinylation in an N-linkage manner, and used this to develop a potential semi-quantification method for N-Hcy-apoAI.
The effect of rest interval length on bench press performance with heavy vs. light loads. The purpose of the current study was to compare the effect of 3 different rest intervals on multiple sets of the bench press exercise performed with heavy vs. light loads. Sixteen resistance-trained men performed 2 testing sessions each week for 3 weeks. During the first testing session each week, 5 consecutive sets of the bench press were performed with 80% of 1 repetition maximum (1RM) and with a 1-, 2-, or 3-minute rest interval between sets. During the second testing session each week the same procedures were repeated with 50% of 1RM. The total repetitions completed and the sustainability of repetitions were compared between rest conditions and between loads. For each load, resting 3 minutes between sets resulted in significantly greater total repetitions vs. resting 2 minutes (p = 0.000) or 1 minute (p = 0.000) between sets. However, the sustainability of repetitions was not significantly different between loads (p = 0.849). These results can be applied to weekly bench press workouts that undulate between heavy (i.e., 80% 1RM) and light (i.e., 50% 1RM) intensities. When the training goal is maximal strength development, 3 minutes of rest should be taken between sets to avoid significant declines in repetitions. The ability to sustain repetitions while keeping the intensity constant may result in a higher training volume and consequently greater gains in muscular strength.
Insecticide interaction with carrier and neuroproteins. Binding of alpha-, beta-, gamma-hexachlorocyclohexane, p,p'-DDT and p,p'-DDE with bovine serum albumin (BSA) and locust brain homogenate was studied. Binding affinities of pesticides were higher for the locust brain homogenates than for BSA. Results of uptake by isolated locust brain revealed higher uptake of gamma-HCH than alpha-HCH. gamma-HCH uptake was also higher from locust haemolymph than either from BSA or from buffer.
Cyclic stretch upregulates SDF-1alpha/CXCR4 axis in human saphenous vein smooth muscle cells. Cyclic stretch (CS) mediates different cellular functions in vascular smooth muscle cells and involves in neointimal hyperplasia and subsequent atherosclerosis of vein grafts. Here, we investigated whether CS can modulate stromal cell-derived factor-1alpha (SDF-1alpha)/CXCR4 axis in human saphenous vein smooth muscle cells. We found CS induced the upregulation of SDF-1alpha and CXCR4 in human saphenous vein smooth muscle cells in vitro, which was dependent on PI3K/Akt/mTOR pathway. Furthermore, CS augmented human saphenous vein smooth muscle migration and focal adhesion kinase (FAK) activation by PI3K/Akt/mTOR pathway. Interestingly, the upregulation of SDF-1alpha/CXCR4 axis was instrumental in CS-induced saphenous vein smooth muscle cell migration and FAK activation, as showed by AMD3100, an inhibitor of SDF-1alpha/CXCR4 axis, partially but significantly blocked the CS-induced cellular effects. Thus, those data suggested SDF-1alpha/CXCR4 axis involves in CS-mediated cellular functions in human saphenous vein smooth muscle cells.
A phase II trial of induction epirubicin, oxaliplatin, and fluorouracil, followed by surgery and postoperative concurrent cisplatin and fluorouracil chemoradiotherapy in patients with locoregionally advanced adenocarcinoma of the esophagus and gastroesophageal junction. Preoperative chemoradiotherapy improves local control in patients with locoregionally advanced adenocarcinoma of the esophagus and gastroesophageal junction (GEJ). Distant failure remains common, however, suggesting potential benefit from additional chemotherapy. This phase II study investigated the addition of induction chemotherapy to surgery and adjuvant chemoradiotherapy. Patients with cT3-4 or N1 or M1a (American Joint Committee on Cancer 6th edition) adenocarcinoma of the esophagus and GEJ were eligible. Induction chemotherapy, with epirubicin 50 mg/m/d, oxaliplatin 130 mg/m/d, and fluorouracil 200 mg/m/d continuous infusion for 3 weeks, was given every 21 days for three courses, followed by surgery. Adjuvant chemoradiotherapy consisted of 50 to 55 Gy at 1.8 to 2.0 Gy/d and two courses of cisplatin (20 mg/m/d) and fluorouracil (1000 mg/m/d) during weeks 1 and 4 of radiotherapy. Between February 2008 and January 2012, 60 evaluable patients enrolled. Resection was accomplished in 54 patients (90%) and adjuvant chemoradiotherapy in 48 (80%) patients. Toxicity included unplanned hospitalization in 18% of patients during induction chemotherapy and 19% of patients during adjuvant chemoradiotherapy. There was one chemotherapy-related and two postoperative deaths. With a median follow-up of 43 months, the projected 3-year locoregional control is 88%, distant metastatic control 46%, relapse-free survival 41%, and overall survival 47%. Symptomatic response to chemotherapy and the percentage of remaining viable tumor at surgery proved the strongest predictors of survival and distant control. Chemotherapy, surgery, and adjuvant chemoradiotherapy are feasible and produce outcomes similar to other multimodality treatment schedules in locoregionally advanced adenocarcinoma of the esophagus and GEJ. Symptomatic response and less residual tumor at surgery were associated with improved outcomes.
Pseudohypoparathyroidism type 1A and morbid obesity in infancy. To describe an infant with early excessive weight gain as the principle manifestation of pseudohypoparathyroidism (PHP) type 1a and Albright hereditary osteodystrophy (AHO). We describe the clinical and laboratory findings in an infant with early excessive weight gain without evidence of hyperphagia and review relevant literature. The proband's birth weight was 4047 g (1.4 SD). She was breastfed from birth. Excessive weight gain was noted by 1 month of age. At 3 months of age, hard subcutaneous nodules were observed, and histologic analysis of a biopsied lesion suggested a possible diagnosis of ossified pilomatricoma. At 6 months of age, she was documented to have mild hypothyroidism. Abnormal weight gain continued despite a caloric intake of about 65 kcal/kg per day. At 11 months of age, 2 new subcutaneous hard nodules were identified, which in the context of excessive weight gain and evolving mild primary hypothyroidism, suggested a unifying diagnosis of PHP type 1a and AHO. GNAS sequence analysis was performed, which revealed a 4-base deletion (Nt565delGACT) in exon 8. As more monogenic causes of severe early obesity are described, it is important to consider PHP type 1a in the differential diagnosis. Lack of short stature, skeletal abnormalities, or absence of PTH resistance should not exclude this diagnosis in a young child.
Predictors of lower extremity arterial injury after total knee or total hip arthroplasty. Lower extremity arterial injury is a rare complication following total knee (TKA) or total hip arthroplasty (THA). To date, no multi-institutional study has identified preoperative factors that may portend increased risk for these injuries. We queried a large clinical database for the incidence and predictors of arterial injury and/or compromise following lower extremity arthroplasty. Prospectively collected preoperative and postoperative data by the National Surgical Quality Improvement Program (NSQIP) of the Veterans Affairs Medical Centers were analyzed. All patients from 1996 to 2003 in the NSQIP database who underwent TKA or THA were identified via CPT codes. NSQIP defined, 30-day, postoperative outcomes were analyzed. Data were compared using bivariable analysis, as well as limited multivariable logistic regression. A total of 41,633 arthroplasties (24,029 TKA, 2077 redo-TKA, 13,494 THA, 2033 redo-THA) were identified in the NSQIP database. A total of 34 (0.08%) lower extremity arterial injuries were recognized (0.08% TKA, 0.19% redo-TKA, 0.04% THA, 0.20% redo-THA). Eighteen injuries were repaired on the same day of surgery (seven intraop, 11 postop), eight between postoperative days 1 and 5, and 8 between days 6 and 30. Only two patients underwent lower extremity amputation (overall limb loss rate of 5.9% of patients who had arterial injury). Statistically significant predictors of lower extremity arterial injury identified on logistic regression analysis included redo procedure (odds ratio [OR] 2.7, 95% confidence interval [CI] 1.2-6.0, P = .013) and African American race (OR 2.5, 95% CI 1.2-5.3, P = .02). Lower extremity arterial injury was exceedingly rare after total knee or total hip arthroplasty. There is an increased incidence in African American patients and those undergoing redo arthroplasty. Among patients who sustain vascular injury, excellent limb salvage rates can be achieved with close postoperative surveillance to achieve early detection and repair of injuries.
[Flavonols and flavones of vegetables. VIII. Flavones of carrot leaves (author's transl)]. The flavonoid constituents of carrot leaves (Daucus carota L. ssp. sativa) were separated by means of cellulose column chromatography, and the following compounds were obtained crystalline and identified by usual procedures: luteolin 7-beta-D-glucoside as the main flavon, luteolin 4'-beta-D-glucoside, luteolin 7-beta-D-glucuronide, apigenin 7-beta-D-glucoside, apigenin 7-rutinoside, chrysoeriol 7-beta-D-glucoside. Luteolin 7-rutinoside also was identified, but could not be obtained crystalline.
A model-fitting implementation of the DeFries-Fulker model for selected twin data. In this research note, DeFries-Fulker (DF) regression analysis is reframed in model-fitting terms, where an individual's expected score is modeled as a function of their co-twin's proband status. This more flexible implementation of the DF model allows DZ-O twins to be incorporated in a sex-limitation model. Brief simulation results are presented along with the Mx scripts used.
Non-cultivable microorganisms from symbiotic associations of insects and other hosts. Many symbiotic associations involve microorganisms which cannot be cultivated on laboratory media. These organisms remained little known until the recent advent of methods of recombinant DNA analysis and molecular phylogenetics. Applications of these methods to endosymbionts have resulted in substantial new insights concerning the genetics and evolution of these organisms. This communication provides a listing of recently studied associations involving non-cultivable symbionts. The associations involve a diverse set of host taxa and a wide range of effects, both favorable and deleterious, on host biology. Among beneficial endosymbionts, a variety of nutritional interactions have been documented. One type of association has been demonstrated for a number of animal hosts, namely endosymbioses that result from a single infection of an ancestral host by a prokaryote. In these associations, endosymbionts are transmitted maternally and are not exchanged between host lineages, resulting in a long-term pattern of codiversification of hosts and endosymbionts. The association between aphids and non-cultivable prokaryotic endosymbionts is a well studied example of such a symbiosis.
Emotional discomfort and impairments in verbal memory in schizophrenia. Research has demonstrated that impairments in verbal memory in schizophrenia are linked with psychosocial deficits. Less is known, however, about their relationship to clinical features of illness. This study explores the hypothesis that impairments in verbal memory, particularly forms of memory requiring deeper levels of encoding, are uniquely linked to symptoms of dysphoria or emotional discomfort. Accordingly, we examined the association between concurrent measures of symptoms and verbal memory for 84 subjects with schizophrenia. Measures of positive, negative, cognitive, excitement and emotional discomfort symptoms were derived from factor scores of the Positive and Negative Syndrome Scale. Verbal memory was assessed using two tests requiring relatively superficial levels of encoding: The Hopkins Verbal Memory Test and the Digit Span subtest; and one test requiring deeper levels of encoding: the Logical Memory subtests I and II. As predicted, multiple regressions controlling for age, education and attention revealed that poorer performance on Logical Memory was strongly associated with greater levels of emotional discomfort (R(2)=0.22 and 0.25, respectively) while performance on the Hopkins test was related to cognitive symptoms scores (R(2)=0.08 and 0.09, respectively). Implications for the conceptualization of verbal memory deficits in schizophrenia are discussed.
Interpreting in vitro micronucleus positive results: simple biomarker matrix discriminates clastogens, aneugens, and misleading positive agents. The specificity of in vitro mammalian cell genotoxicity assays is low, as they yield a high incidence of positive results that are not observed in animal genotoxicity and carcinogenicity tests, that is, "misleading" or "irrelevant" positives. We set out to develop a rapid and effective follow-up testing strategy that would predict whether apparent in vitro micronucleus-inducing effects are due to a clastogenic, aneugenic, or secondary irrelevant mode(s) of action. Priority was given to biomarkers that could be multiplexed onto flow cytometric acquisition of micronucleus frequencies, or that could be accomplished in parallel using a homogeneous-type assay. A training set of 30 chemicals comprised of clastogens, aneugens, and misleading positive chemicals was studied. These experiments were conducted with human TK6 cells over a range of closely spaced concentrations in a continuous exposure design. In addition to micronucleus frequency, the following endpoints were investigated, most often at time of harvest: cleaved Parp-positive chromatin, cleaved caspase 3-positive chromatin, ethidium monoazide bromide-positive chromatin, polyploid nuclei, phospho-histone H3-positive (metaphase) cells, tetramethylrhodamine ethyl ester-negative cells, cellular ATP levels, cell cycle perturbation, and shift in γ-H2AX fluorescence relative to solvent control. Logistic regression was used to identify endpoints that effectively predict chemicals' a priori classification. Cross validation using a leave-one-out approach indicated that a promising base model includes γ-H2AX shift and change in phospho-histone H3-positive events (25/30 correct calls). Improvements were realized when one or two additional endpoints were included (26-30/30 correct calls). These models were further evaluated with a test set of 10 chemicals, and also by evaluating 3 chemicals at a collaborating laboratory. The resulting data support the hypothesis that a matrix of high throughput-compatible biomarkers can effectively delineate two important modes of genotoxic action as well as identify cytotoxicity that can lead to irrelevant positive results.
Forced expiratory manoeuvres in children: do they meet ATS and ERS criteria for spirometry? The aim of this study was to evaluate the applicability of American Thoracic Society and European Respiratory Society criteria for spirometry in children. Maximal expiratory flow/volume (MEFV) measurements from 446 school-age children, experienced in performing MEFV manoeuvres, were studied and acceptability (start-of-test (backward extrapolated volume as a percentage of forced vital capacity (FVC) ([Vbc%FVC) or as an absolute value (Vbe), end-of-test (forced expiratory time (FET)) and reproducibility criteria (absolute and percentage difference between best and second-best FVC and forced expiratory volume in one second (FEV1) (deltaFVC, deltaFVC %, deltaFEV1 and deltaFEV1 %)) were applied to these manoeuvres. The Vbe%FVC criterion was met by 91.5%, the Vbe <0.15 L criterion by 94.8% and the Vbe <0.10 L by 60.1% of children. Vbe <0.15 L appeared to be a more useful parameter than Vbe%FVC. The FET criterion was met by only 15.3% of children. deltaFVC <0.2 L and deltaFEV1 <0.2 L were met by 97.1% and 98.4%, and deltaFVC <0.1 L and deltaFEV1 <0.1 L by 79.8% and 84.3% of the children, respectively. These criteria appeared to be less useful compared to percentage criteria (deltaFVC % and deltaFEV1 %). Even experienced children did not meet all international criteria for spirometry. However, most of their MEFV curves are useful for interpretation. Based on the performance of these children, a re-evaluation of criteria for maximal expiratory flow/volume measurements in children is proposed.
Allergy in long-term hemodialysis. II. Allergic and atopic patterns of a population of patients undergoing long-term hemodialysis. Maintenance hemodialysis is widely used throughout the world, and anaphylactic reactions appear to be increasing in number and severity. However, the exact incidence of sensitization and the role of atopy in these reactions are not yet fully understood. All of the 111 patients routinely dialyzed in a center were tested. All patients had a complete investigation of atopy, RAST to chemicals released during the procedure of dialysis (ethylene oxide (Eto), formaldehyde, phthalic anhydride, and toluene diisocyanate), skin tests with the effluent, and the titration of blood eosinophils. The incidence of atopy was found to be lower (13.5%) than in the normal population of the area. Skin tests with either histamine or allergens are significantly (p less than 0.001) smaller than those of nondialyzed subjects, and this method does not appear to be ideal in this population of patients. Eto sensitivity ranked first (5.5%), followed by phthalic anhydride sensitivity (3.6%); 5/6 patients who had a sensitivity to Eto and/or phthalic anhydride presented symptoms during dialysis, but they never were life threatening. Formaldehyde RAST was only found in one patient who had a life-threatening reaction. Finally, three patients presenting pruritus had positive skin prick tests with the effluent of the dialyzer. All patients having a first use syndrome and 80/81 symptom-free patients did not have serum-specific IgE against the released chemicals, 5/17 patients who had a pruritus during dialysis had either positive RAST to released chemicals or skin tests to the effluent, 5/8 patients who suffered from anaphylaxis had positive RAST to released chemicals, but only those who had a positive RAST presented a severe reaction.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of local inhibition of gamma-aminobutyric acid uptake in the dorsomedial hypothalamus on extracellular levels of gamma-aminobutyric acid and on stress-induced tachycardia: a study using microdialysis. Previous studies involving local microinjection of drugs that interfere with gamma-aminobutyric acid (GABA)A receptor-mediated synaptic inhibition have led to the suggestion that endogenous GABA suppresses the activity of a sympatho-excitatory mechanism in the dorsomedial hypothalamus in rats. In this study, microdialysis was used to assess and to alter pharmacologically extracellular-levels of GABA within this region while simultaneously monitoring heart rate and blood pressure. In anesthetized rats, local microdialysis for 15 min with 2.5, 10 and 40 mM nipecotic acid, an inhibitor of GABA uptake, caused concentration-related increases in GABA and taurine in the extracellular space, but no significant change in heart rate or arterial pressure. Similar perfusion with 37.5, 75 and 150 mM KCl caused concentration-related increases in GABA as well as aspartate, glutamate, taurine, glycine and alanine. Only modest, variable increases in heart rate and no effect on arterial pressure were observed during the perfusions with high potassium. In conscious rats, unilateral microdialysis of the dorsomedial hypothalamus with 0.5 mM nipecotic acid for 2 to 2.5 hr before stress coupled with contralateral microinjection of muscimol (88 pmol/250 nl) 5 min before stress significantly reduced air stress-induced tachycardia; this reduction in tachycardia was associated with markedly elevated levels of GABA in dialysates collected from the dorsomedial hypothalamus. Neither treatment alone significantly influenced stress-induced increases in heart rate, although perfusion with nipecotic acid alone evoked similar elevations in extracellular GABA. These results suggest that extracellular levels of endogenous GABA in the dorsomedial hypothalamus may regulate the cardiovascular response to stress.
Impact of pyrethroids and organochlorine pesticides residue on IGF-1 and CYP1A genes expression and muscle protein patterns of cultured Mugil capito. This study aimed to assess the levels of pyrethroids and organochlorine residues in the tissues of cultured Mugil capito and in water samples obtained from three different sites (Al-Hamol, Al-Riad and Sidi Salem; referred to as Area 1, Area 2, and Area 3, respectively) in the Delta region, Egypt. The study also assessed the biochemical markers in exposed mullet and evaluated the impact of these residues on the expression of insulin-like growth factor 1 (IGF-1) in muscle and cytochrome P4501A (CYP1A) in liver tissues using qRT-PCR and SDS-PAGE methods. The results revealed that pesticide residue levels in the water were variable, but were lower than detected levels in fish. Significant (P < 0.05) differences were found across the three study areas in terms of serum ALT, but the serum AST level was not significantly (P > 0.05) elevated in all study regions. Serum creatinine and urea levels were significantly (P < 0.05) elevated in area 3. Furthermore, glutathione and malondialdehyde concentrations significantly increased (P < 0.05) in liver tissues in area 3. Using the qRT-PCR technique, the results revealed that the expression level of IGF-1 was most significant in area 3, while the expression level of CYP1A was most significant in area 1. The protein profile showed some differences in band numbers and molecular weights of protein bands across different regions. Overall, the alteration in biochemical parameters revealed pesticide interference with the metabolic processes of fish. Furthermore, the pesticide pollution had an effect on the expression of IGF-1 and CYP1A genes and led to changes in the protein profile. Therefore, these markers can be used to monitor fish distress following exposure to the pollutant.
[Biliary ileus: personal cases]. After a short review of world literature on the subject, four cases of biliary ileus, all with favourable outcome, are reported. Some considerations on the pathogenesis of occlusion of biliary origin and on its treatment are then set out: such treatment must always be surgical and of emergency type, providing not only for removal of the obstructing calculus, but also for exploration of the whole ileus. Where possible, cholecystectomy and closure of the bilio-digestive fistula should also be performed.
Laparoscopic fenestration of a simple hepatic cyst. Hepatic cysts are usually asymptomatic, most being detected incidentally during imaging. Distinction has to be made between a simple hepatic cyst from more sinister types such as a parasitic cyst and a cyst occurring as part of a neoplastic process. Intervention in a simple hepatic cyst is only indicated when they become symptomatic or when they grow at a rapid rate. Surgery is the mainstay of treatment, with laparoscopic intervention becoming more and more widely accepted. We present here the first case of laparoscopic fenestration of liver cyst performed in our hospital and also review the literature on this modality of treatment.
Meeting the psychosocial needs of pacemaker patients. A review of the literature concerning patients who have received permanently implanted cardiac pacemakers indicates that a substantial number of these patients experience difficulties in adjusting to their medical condition. Common feelings among these patients are anxiety and depression. It is suggested that difficulties often arise from the patient's misconceptions about the pacemaker and inadequate psychosocial support. To assist such patients in their adjustment, the Pacemaker Support Program was developed to provide psychosocial counseling and pacemaker education from the preoperative phase through to the outpatient pacemaker follow-up clinic phase. In the year of the program's operation a marked decline in adjustment problems has been observed, the program has been readily integrated into the hospital routine, and it has been enthusiastically accepted by both the hospital staff and the patients.
The effects of transcranial direct current stimulation on short-interval intracortical inhibition and intracortical facilitation: a systematic review and meta-analysis. Transcranial direct current stimulation (tDCS) is increasingly being used to affect the neurological conditions with deficient intracortical synaptic activities (i.e. Parkinson's disease and epilepsy). In addition, it is suggested that the lasting effects of tDCS on corticospinal excitability (CSE) have intracortical origin. This systematic review and meta-analysis aimed to examine whether tDCS has any effect on intracortical circuits. Eleven electronic databases were searched for the studies investigating intracortical changes induced by anodal (a) and cathodal (c) tDCS, in healthy individuals, using two paired-pulse transcranial magnetic stimulation (TMS) paradigms: short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF). Additionally, motor-evoked potential (MEP) size alterations, assessed by single-pulse TMS, were extracted from these studies to investigate the probable intracortical origin of tDCS effects on CSE. The methodological quality of included studies was examined using Physiotherapy Evidence Database (PEDro) and Downs and Black's (D&B) assessment tools. Thirteen research papers, including 24 experiments, were included in this study scoring good and medium quality in PEDro and D&B scales, respectively. Immediately following anodal tDCS (a-tDCS) applications, we found significant decreases in SICI, but increases in ICF and MEP size. However, ICF and MEP size significantly decreased, and SICI increased immediately following cathodal tDCS (c-tDCS). The results of this systematic review and meta-analysis reveal that a-tDCS changes intracortical activities (SICI and ICF) toward facilitation, whereas c-tDCS alters them toward inhibition. It can also be concluded that increases and decreases in CSE after tDCS application are associated with corresponding changes in intracortical activities. The results suggest that tDCS can be clinically useful to modulate intracortical circuits.
Skipping of Duplicated Dystrophin Exons: In Vitro Induction and Assessment. Duplications of one or more dystrophin exons that disrupt the reading frame account for about 15% of all Duchenne cases, and like the more common genomic deletions, most pathogenic duplications of single or multiple dystrophin exons are also amenable to targeted exon skipping. However, additional considerations must be taken into account: (1) skipping of all duplicated exons, and, flanking exons as necessary, will frequently be required to restore the reading frame and generate an in-frame Becker muscular dystrophy-like mRNA, (2) the phosphorodiamidate morpholino oligomer chemistry is more effective than the 2'-O-methyl modified oligonucleotides at inducing multiple exon skipping, and (2) the apparent efficiency of exon skipping can be confounded by the choice of RT-PCR system. Standard RT-PCR systems can preferentially amplify the shorter amplicons, implying more efficient exon skipping than may actually be induced. Unless high fidelity RT-PCR systems are used, strand slippage during annealing/elongation steps will generate normal length transcripts that are artifacts of the amplification.
Stability of theophylline elimination rate. The elimination rate for theophylline varies greatly among patients, but recommendations for maintenance dosing schedules have assumed relatively little intrapatient variability even over extended time periods. Reports of large intrapatient variability of theophylline elimination rate and consequent clearance raise concerns regarding this assumption and also challenge the practice of assuming relative constancy of elimination rate in the performance of bioavailability studies of slow-release formulations. We therefore systematically studied under controlled conditions the elimination rate of theophylline in 10 patients over an extended time interval. The initial elimination rate constants ranged from 0.062 to 0.136 hours-1. The changes ranged from -5.9% to 9.4% of the initial value during intervals of 2 to 11 months. Correlation of the first and second values was 0.96. Thus the elimination rate of theophylline generally appears to vary little within individuals over time when studied under controlled conditions.
[Presinusoidal portal hypertension due to portal thrombosis in a patient with Alagille's syndrome]. We present the case of a 16-year old woman with Alagille's syndrome, who had upper gastrointestinal bleeding due to rupture of esophageal varices secondary to presinusoidal portal hypertension without liver fibrosis. Portal thrombosis is a manifestation previously unreported in association to this syndrome.
A phosphatidylinositol 3-kinase of Candida albicans influences adhesion, filamentous growth and virulence. To determine if cellular functions of the phosphatidylinositol 3-kinase CaVps34p are related to processes governing Candida albicans pathogenicity, both copies of the gene were sequentially disrupted. Homozygous deletion of C. albicans VPS34 resulted in a mutant strain which exhibited defects not only in intracellular vesicle transport processes but also in morphogenesis. The CaVPS34 null mutant was unable to form hyphae on different solid media whilst showing a significantly delayed yeast-to-hyphae transition in liquid media. In addition, the mutant was rendered hypersensitive to temperature and osmotic stresses and had a strongly decreased ability to adhere to mouse fibroblast cells compared to the wild-type strain SC5314. Finally, evidence was obtained that CaVPS34 is essential for pathogenicity of C. albicans as the CaVPS34 null mutant was shown to be avirulent in a mouse model of systemic infection. C. albicans pathogenicity was restored to a near wild-type degree upon reintroduction of CaVPS34 into the chromosome of the null mutant, demonstrating that the observed avirulence corresponded to the loss of CaVPS34. Thus, the results suggest that CaVPS34 may serve as a potential target for antifungal drugs.
Histologic studies of the effects of circulating hot saline on the uterus before hysterectomy. To evaluate a new device for endometrial ablation. (Canadian Task Force classification II-1). University-affiliated hospital. Thirty-two women scheduled for hysterectomy. Endometrial ablation and hysterectomy. The new device for endometrial ablation was evaluated by studying depth of necrosis after staining for the oxidative enzyme NADH. Uniform endomyometrial necrosis was achieved at a depth of 2 to 4 mm with 90 degrees C saline circulated for 10 minutes. The procedure was successful in all patients, and there were no adverse clinical sequelae. (J Am Assoc Gynecol Laparosc 6(3):269-273, 1999)
Magnesium Modulates Doxorubicin Activity through Drug Lysosomal Sequestration and Trafficking. Magnesium is directly involved in the control of cell growth and survival, but its role in cancer biology and therapy is multifaceted; in particular, it is highly controversial whether magnesium levels can affect therapy outcomes. Here we investigated whether magnesium availability can modulate cellular responses to the widely used chemotherapeutic doxorubicin. We used an in vitro model consisting of mammary epithelial HC11 cells and found that high magnesium availability was correlated with diminished sensitivity both in cells chronically adapted to high magnesium concentrations and in acutely magnesium-supplemented cells. This decrease in sensitivity resulted from reduced intracellular doxorubicin accumulation in the face of a similar drug uptake rate. We observed that high-magnesium conditions caused a decrease in intracellular drug retention by altering drug lysosomal sequestration and trafficking. In our model, magnesium supplementation correspondingly modulated expression of the TRPM7 channel, which is known to control cytoskeletal organization and dynamics and may be involved in the proposed mechanism. Our findings suggest that magnesium supplementation in hypomagnesemic cancer patients may hinder response to therapy.
Mutant isoforms of the anti-Müllerian hormone type II receptor are not expressed at the cell membrane. Anti-Müllerian hormone, a member of the transforming growth factor beta superfamily, produces early regression of Müllerian ducts in the male fetus through binding to a serine/threonine kinase receptor, homologous to type II receptors of the transforming growth factor beta (TGF-beta) family. A splice mutation of this receptor, described in a patient with abnormal retention of Müllerian derivatives, generates two mutant isoforms, one lacking the second exon and the other bearing an insertion of 12 bases between exons 2 and 3. Using hemagglutinin-tagged recombinant receptors, we have visualized wild type and mutant receptors in COS cells by Western blotting and immunoprecipitation. The 82-kDa, endoglycosidase H-insensitive, mature form of the wild type receptor is reduced to 68 kDa by N-glycosidase F treatment. Mutant receptor isoforms, 73 and 63 kDa for the long and short form, respectively, are sensitive to endoglycosidase H, suggesting that they are retained in the endoplasmic reticulum. Indeed, only the wild type receptor was expressed on the cell surface and bound iodinated anti-Müllerian hormone. These results provide a biological explanation for the failure of the mutant receptor to induce Müllerian regression.
A rice quantitative trait locus for salt tolerance encodes a sodium transporter. Many important agronomic traits in crop plants, including stress tolerance, are complex traits controlled by quantitative trait loci (QTLs). Isolation of these QTLs holds great promise to improve world agriculture but is a challenging task. We previously mapped a rice QTL, SKC1, that maintained K(+) homeostasis in the salt-tolerant variety under salt stress, consistent with the earlier finding that K(+) homeostasis is important in salt tolerance. To understand the molecular basis of this QTL, we isolated the SKC1 gene by map-based cloning and found that it encoded a member of HKT-type transporters. SKC1 is preferentially expressed in the parenchyma cells surrounding the xylem vessels. Voltage-clamp analysis showed that SKC1 protein functions as a Na(+)-selective transporter. Physiological analysis suggested that SKC1 is involved in regulating K(+)/Na(+) homeostasis under salt stress, providing a potential tool for improving salt tolerance in crops.
The use of neuropsychological data to detect altered neurological functioning in a child with myelomeningocele. Although children with myelomeningocele often display atypical patterns on psychometric testing, this case study demonstrates the sensitivity of neuropsychological instruments to detect altered neurological functioning in a patient with spina bifida. The subject had a history of myelomeningocele at the lumbosacral level and placement of a ventriculoperitoneal shunt. During a routine neuropsychological evaluation, a 44-point discrepancy between his verbal (verbal IQ = 98) and nonverbal abilities (performance IQ = 54) on the Wechsler Intelligence for Children-Revised was found. In comparison to high average academic achievement, test findings suggested depressed memory skills and extreme slowing in psychomotor speed. A pattern of acute decline in overall cognitive functioning was suggested. Magnetic resonance imaging revealed a left frontoparietal brain mass, which was surgically removed. Follow-up neuropsychological testing 9 months postsurgery indicated an increase in nonverbal intelligence with improved psychomotor speed and information processing. This case study illustrates the importance of obtaining baseline evaluations in this neurologically high-risk population as well as the clinical usefulness of psychometric data in diagnostic workups.
Induction of micronuclei in haemocytes and gill cells of zebra mussels, Dreissena polymorpha, exposed to clastogens. Zebra mussels, Dreissena polymorpha, were exposed to four directly acting reference clastogens (mitomycin C, bleomycin, dimethylarsinic acid and potassium chromate) under laboratory conditions. The aim was to examine the inducibility of micronuclei (MN) in haemocytes and gill cells. Positive responses were observed in both tissues for all four substances used under the given test conditions. The mean MN frequencies in treated mussels ranged between 3.2 and 6.9/1000 in haemocytes and between 5.4 and 6.7/1000 in gill cells. The spontaneous MN levels averaged 1.2 and 2.8/1000 in haemocytes and gill cells, respectively. The MN induction capacity of the different chemicals was equivalent in both tissues, except for the treatment with dimethylarsinic acid which generated a significantly higher MN rate in gill cells than in haemocytes. Several characteristics suggest that haemolymph is the more appropriate test tissue for environmental genotoxicity assessment: (1) a shorter preparation time of slides, (2) a more accurate identification of unambiguous MN, (3) a lower baseline MN frequency and a higher induction factor.
Impaired antigen-specific suppressor cell activity in psoriasis and psoriatic arthritis. Antigen specific suppressor cell activity of peripheral blood mononuclear cells was investigated in 20 patients with psoriatic arthritis and 18 patients with uncomplicated psoriasis and compared to that of 27 age- and sex-matched healthy controls and 18 patients with osteoarthritis. Topical skin therapy and nonsteroidal anti-inflammatory medications were allowed but patients who had taken disease suppressive, immunosuppressive, cytotoxic, and systemic steroid therapy were excluded. The results demonstrate reduced suppressor cell activity (SCA) in patients with psoriatic arthritis compared to normal controls (54.8% +/- 4.9 vs 68.4 +/- 2.8, p less than 0.005). Similarly, the response of patients with uncomplicated psoriasis was significantly lower than normal (50.1 +/- 4.9 vs 67.3 +/- 3.0% p less than 0.005). Five of the 20 patients with psoriatic arthritis and 7 of the 18 patients with uncomplicated psoriasis demonstrated SCA of more than 2 SD below the normal mean. The SCA of patients with osteoarthritis was normal. The plaque forming cell (PFC) response of patients with psoriatic arthritis and uncomplicated psoriasis was not different from those of the normal controls or of patients with osteoarthritis. There was no correlation between impaired suppression and disease activity or therapy.
[Aetiology of depressive disorders--the biopsychosocial model]. The biopsychosocial model has been developed from general system theory and describes the interaction of body and mind. Unipolar depression has a complex pathogenesis which on an individual level presents in very diverse ways. The article focuses on biological factors such as heritability, changes in neurotransmitters, endocrinological factors and chronobiological patterns. The psychosocial factors include critical life events, social pressure, cognitive and learning theory-based factors as well as personality factors.It was found that the biological, psychological and (eco-) social factors that contribute to etiopathogenesis frequently interact. The biopsychosocial model lends itself to collecting all the factors that are linked to a depression etiopathogenetically and to using them for the purpose of diagnostics.It thus provides a suitable basis for individually tailored therapy and also has valuable applications in the field of psychoeducation.
[Clinical analysis of conjunctival papilloma]. Objective: To summarize and analyze the clinical manifestation of conjunctival papilloma, its relationship with human papillomavirus (HPV) infection and the recurrence after the combination of operation and pharmacotherapy. Methods: A retrospective case series study. Analysis of 40 patients (41 eyes) with conjunctival papilloma treated at Peking Union Medical College Hospital from January 2008 to June 2018 was performed. All patients were given routine blood and urine, hepatitis B virus surface antigen, antibodies to hepatitis C virus, antibodies to human immunodeficiency virus and antibodies to Treponema pallidum testing, and HPV testing for the urethra epithelial tissue. Direct contact of the tumor with instruments was avoided during surgery, and freezing treatment was combined. HPV testing was performed for the resected conjunctival papilloma. Multiple medications were used after surgery. Results: In 40 cases with 41 eyes, there were 22 males (23 eyes) and 18 females (18 eyes). A single tumor was seen in 27 eyes, and multiple tumors were seen in 14 eyes. Thirteen patients (13 eyes) older than 50 years old had pedicel-free papillpma, and 27 patients (28 eyes) aged from 12 to 40 years had pedicel-type papillpma. All cases were confirmed by pathology as conjunctival papilloma, of which 9 cases showed moderate to severe atypical hyperplasia on squamous cells. The HPV test was positive in 17 out of the 40 cases (42.5%) of conjunctival papilloma. Urine test results of 16 patients (40.0%) were positive for occult blood and showed that urinary white blood cell was elevated. Of the 40 patients, 33 were newly diagnosed and 7 had a relapse. The average follow-up time was (37.4±11.9) months after combined therapy and no recurrence was found in any patients. Conclusions: Conjunctival papilloma is usually observed in people aged from 20 to 40 years and older than 50 years, and it often occurs in one eye. Its main pathological feature is benign tumors of the papillary hyperplasia on the conjunctival epithelial tissue. Some patients have atypical hyperplasia of squamous cells. The cause of the disease may be related to the infection of HPV and the urinary tract. Combined treatment can reduce the recurrence rate of conjunctival papilloma. (Chin J Ophthalmol, 2019, 55: 369-373).
The K+-and HCO3-stimulated phosphatase activities in renal microsomes of rats. The K+-stimulated phosphatase activity of microsomes from rat kidney was not inhibited by L-phenylalanine, but the HCO3-stimulated phosphatase activity was markedly inhibited by L-phenylalanine. Valinomycin enhanced the HCO3-stimulated phosphatase activity, but did not enhance the K+-stimulated phosphatase activity. Ouabain did not inhibit the HCO3-stimulated phosphatase activity, but inhibited the K+-stimulated phosphatase activity. The renal K+-stimulated phosphatase activity was suppressed to 40% of the control values by adrenalectomy, but the renal HCO3-stimulated phosphatase activity was little suppressed by adrenalectomy. The renal K+-stimulated phosphatase activity in intact and adrenalectomized rats was found to be significantly elevated, in a manner similar to the elevation of the renal (Na+ + K+)-ATPase activity by aldosterone treatment (P less than 0.02).
Benzo(a)pyrene suppresses tracheal antimicrobial peptide gene expression in bovine tracheal epithelial cells. Respiratory disease is an important cause of morbidity and mortality in cetaceans, which are also threatened by environmental degradation caused by crude oil spills. Following oil spills, cetaceans at the water surface may inhale droplets of oil containing toxic polycyclic aromatic hydrocarbons (PAHs), which could potentially alter respiratory immunity via activation of the aryl hydrocarbon receptor (AHR) and its subsequent interaction with nuclear factor kappa B (NF-κB). β-defensins are antimicrobial peptides secreted by airway epithelial cells and their expression is known to be dependent on NF-κB. We hypothesized that PAHs may suppress the expression of β-defensins, and thereby contribute to the pathogenesis of pneumonia. This hypothesis was modeled by measuring the in vitro effects of benzo(a)pyrene (BAP), phenanthrene, and naphthalene on tracheal antimicrobial peptide (TAP) gene expression in bovine tracheal epithelial cells. Stimulation with lipopolysaccharide (LPS) induced 20 ± 17-fold (mean ± SD) increased TAP gene expression. Exposure of tracheal epithelial cells to 5 μM BAP for 4 or 8 h, followed by incubation with a combination of LPS and 5 μM BAP for another 16 h, significantly (P = 0.002) suppressed LPS-induced TAP gene expression by 40.6 ± 21.8% (mean ± SD) in tracheal epithelial cells from 9 calves tested. BAP-induced suppression of TAP gene expression coincided with induction of cytochrome P450 1A1 gene expression. In contrast, phenanthrene and naphthalene had no consistent effect, and exposure to PAHs did not significantly affect constitutive TAP gene expression (i.e. without LPS). These findings characterize the suppressive effects of BAP-a toxic pollutant found in crude oil-on this respiratory innate immune response.
Seventy-Two-Hour Returns Are Not Useful in Identifying Emergency Department Patients With a Concerning Intra-Abdominal Process. Seventy-two-hour returns to the emergency department (ED) have been used to identify patients who are believed to have been more likely to have suffered medical errors, missed diagnoses, or failure or inadequacy of previous treatment or discharge planning. This approach has been criticized as arbitrary, however, citing the lack of evidence to support its homogenous application to all organ system-based complaints and the unclear implication of returns. Given the significant burden of gastrointestinal (GI)-related illness, our objective was to determine if an audit of 72-hour returns of GI-related diagnoses appropriately captures patients who return with a concerning diagnosis (CD) on their second visit. Ten emergency physicians were surveyed and a list of concerning, "not to be missed" diagnoses were generated. The demographic and clinical variables were collected and analyzed on all patients with a GI International Classification of Diseases, 9th revision code presenting to an urban, university-affiliated ED between July 2013 and March 2014. There were 10,012 patient visits during the study period, including 1006 patients (10%) with ≥ 1 return visits. One hundred forty-seven patients (15%) returned within 72 hours, and 859 patients (85%) returned in > 72 hours. Patients that returned within 72 hours were no more likely to have a CD than those that returned at a later time (13.6% vs. 14.4%; p = 0.79). An audit of 72-hour returns only captures a small percentage of patients that return with a CD, and these patients are at no greater risk of harboring a CD than those that return at a later date.
Accumulation of apolipoprotein E and beta-amyloid-like protein in a trace of the hippocampal CA1 pyramidal cell layer after ischaemic delayed neuronal death. We found that apolipoprotein E (apo E) accumulates in a trace of the hippocampal CA1 pyramidal cell layer within 6 months after 5 min ischaemia. Intense methenamine-silver (M-S) stainings were seen in the entire CA1 subfield 3 months after ischaemia. The M-S staining pattern may imply the appearance of soluble A beta-like proteins. The apo E-positive trace was also positively stained with anti-beta-amyloid (A beta) protein antibodies, but not with anti-beta-amyloid protein precursor (APP) antibodies. These results suggest that A beta-like protein accumulates in ischaemic brain after neuronal cell death. Adjacent reactive astrocytes showed both apo E- and A beta-immunoreactivities. These astrocytes may be involved in the clearance of apo E- and A beta-positive material. We presume that the coincident distribution pattern for apo E- and A beta-immunoreactivity implies formation of the insoluble and stable A beta-apo E complex which is known to exist in the brain of individuals with Alzheimer's disease. The ischaemic model may be useful in studying apo E and A beta deposition in the brain.
IBS subjects with methane on lactulose breath test have lower postprandial serotonin levels than subjects with hydrogen. We have previously shown that methane on lactulose breath test (LBT) is highly associated with constipation in IBS and that methane gas itself slows small bowel transit in dogs. Previous studies suggest that serotonin may have a role in the control of transit in IBS. In this study, we aim to evaluate the role of serotonin in methane producing IBS subjects. Rome I-positive IBS subjects were recruited into the study after exclusion criteria were met. A fasting LBT was performed after subjects filled out a questionnaire rating the degree of constipation and diarrhea. Within 7 days of this test, subjects returned fasting for determination of serotonin before and after a 75-g oral glucose meal. The serotonin response was compared between hydrogen and methane producing IBS subjects. After 2 subjects were excluded for inadequate blood samples, 18 subjects completed the study. Four of 18 subjects produced methane. The postprandial serotonin level in methane producing IBS subjects was lower than in hydrogen producers (P < 0.05). Methane producers had a reduction in serotonin after glucose. Methane producing IBS subjects have reduced postprandial serotonin. Whether methane is a surrogate marker of constipation or contributing to the reduced serotonin remains to be determined.
Inherited thrombotic disorders: an update. Significant advances in identification of etiologies of inherited thrombosis have been recently reported. A point mutation in coagulation factor V (factor V Leiden) results in resistance to activated protein C and probably represents the most common genetic risk factor for venous thrombosis. A metabolic disorder, homocysteinemia, is now known to be an important risk factor for both arterial and venous thrombosis. Many patients with recurrent thrombosis will have more than one genetic risk factor identified. Recognition of these new disorders should permit a diagnosis to be achieved in at least half of patients evaluated for inherited thrombosis.
Dynamic and volumetric variables of fluid responsiveness fail during immediate postresuscitation period. Fluid therapy after resuscitation from cardiac arrest is challenging since both hypovolemia and fluid overload may cause circulatory failure. Therefore, prediction of fluid responsiveness is a major issue in optimizing hemodynamic therapy. The aim of the present study was to evaluate the performance of stroke volume variation, pulse pressure variation, variation of Doppler-derived velocity time integral, and global end-diastolic volume index to predict fluid responsiveness in the postcardiac arrest period. Prospective animal study. University-affiliated research laboratory. Twenty anesthetized and ventilated Goettinger minipigs. Animals were equipped with a central venous catheter, a thermistor-tipped arterial catheter, and a transesophageal echo probe. Electrically induced cardiac arrest of 8 mins was followed by cardiopulmonary resuscitation. Hemodynamic measurements were performed before and after a two-step fluid bolus at baseline and both 1 and 4 hrs after return of spontaneous circulation. Fluid responsiveness was defined by an increase in stroke volume of at least 15%. Performance of variables was analyzed using receiver operator characteristics analysis. Variables reliably indicated fluid responsiveness at baseline. Fifteen animals were successfully resuscitated. Left ventricular ejection fraction was significantly reduced 1 hr after return of spontaneous circulation (52.6% ± 6.4%; p < .01) compared with baseline (69.9% ± 5.3%). One hour after return of spontaneous circulation, fluid responsiveness could not be predicted by any variable. In contrast, pulse pressure variation, variation of the velocity time integral, and global end-diastolic volume index, but not stroke volume variation, were able to predict fluid responsiveness 4 hrs after return of spontaneous circulation, since area under the curve was 0.85 (p < .01), 0.94 (p < .01), 0.77 (p = .02), and 0.68 (p = .12), respectively. Prediction of fluid responsiveness failed 1 hr after successful cardiopulmonary resuscitation from cardiac arrest. Four hours after return of spontaneous circulation, however, the variables pulse pressure variation, variation of the velocity time integral, and global end-diastolic volume index, but not stroke volume variation, enabled prediction of fluid responsiveness and may, therefore, be considered for subsequent hemodynamic optimization after successful cardiopulmonary resuscitation.
VEGF polymorphisms are associated with severity of diabetic retinopathy. To determine whether single nucleotide polymorphisms (SNPs) in the vascular endothelial growth factor (VEGF) gene are associated with severity of diabetic retinopathy. A case-control study was conducted in which 45 individuals with type 1 or 2 diabetes with proliferative diabetic retinopathy (PDR) and 61 individuals with type 1 or 2 diabetes without retinopathy (DWR) were genotyped for 14 SNPs in the VEGF promoter and gene. Three of the promoter SNP genotypes, -160C, -152A (rs13207351), and -116A (rs1570360), showed significant independent associations with PDR, as well as the minihaplotype CAA (P = 0.00017). Two promoter haplotypes were associated with severity of retinopathy: -460C, -417T, -172C, -165C, -160C, -152A, -141A, -116A, +405C was associated with PDR (OR [95% CI] = 29.92 [3.91, 228.78], P = 1.62 x 10(-5)) and -460C, -2417T, -172C, -165C, -160C, -152A, -141A, -116G, +405G was associated with DWR (OR = 0.05 [0.01, 0.35], P = 0.000373). Furthermore, two haplotype-tagged (ht) SNPs, +4618 (rs735286) and +5092 (rs2146323), and five htSNP haplotypes were associated with severity of retinopathy. When the nine promoter/5' untranslated region [UTR] and five htSNP genotypes were combined into a 14-SNP haplotype, a single haplotype, -460C, -417T, -172C, -165C, -160C, -152A, -141A, -116A, +405C, +674T, +4618C, +5092A, +9162C, +9512C was found to be significantly associated with the PDR group (OR = 18.45 [2.35, 144.67], P = 0.00622). A clear association was demonstrated between VEGF SNPs and severity of diabetic retinopathy. Furthermore, two of the htSNP haplotypes appear to be more generalized markers for angiogenesis, in that these have been found in prior work to be associated with neovascular age-related macular degeneration.
Long-term prognosis of human herpesvirus 6 reactivation following allogeneic hematopoietic stem cell transplantation. Patients undergoing hematopoietic stem cell transplantation (HSCT) frequently have HHV-6 reactivation typically during the early phase following HSCT. The long-term clinical complications and prognosis, however, remain unclear. Between September 2010 and October 2012, whole blood samples from 105 patients collected weekly from prior to 6 weeks after HSCT underwent multiplex polymerase chain reaction (PCR) to screen for viral DNA, followed by real-time PCR for quantitative estimation. In 48 patients, only HHV-6 was detected in at least one sample. In 30 patients, no viral DNA was detected. Long-term clinical records were reviewed in March 2016. All 48 HHV-6-positive patients, and 24 patients in whom no viral DNA detected, were followed up. Median maximum HHV-6 DNA load in the blood of the HHV-6 reactivation group (n = 48) was 11 800 copies/μg peripheral blood leukocyte DNA (range, 52-310 000 000). Hemophagocytic syndrome (HPS) was diagnosed in two subjects with HHV-6 reactivation. Acute graft-versus-host disease (GVHD) developed more frequently in patients with HHV-6 reactivation than in patients without viral reactivation (P = 0.002), but there was no difference in incidence of chronic GVHD. There was no difference in engraftment of neutrophils and platelets between groups. There was also no difference in overall survival between groups. Onset of HPS, however, was associated with lower overall survival (P = 0.009). Human herpesvirus 6 reactivation was associated with acute GVHD, but not with chronic GVHD, engraftment or overall survival. Onset of HPS, however, predicts lower overall survival.
Laparoscopic partial nephrectomy for centrally located renal tumors. LPN is frequently reserved for small, peripherally located tumors. Centrally located tumors typically require complex intracorporeal suturing and reconstruction with hilar clamping, which is a laparoscopically advanced maneuver given the constraints of renal ischemia. We retrospectively compared our experience with central vs peripheral tumors treated with LPN. Between January 2001 and March 2004, 363 patients underwent LPN for tumor. The tumor was located centrally in 154 patients and peripherally in 209. Central tumors were defined as tumors centrally extending into the kidney in direct contact with or invading into the pelvicaliceal system and/or renal sinus on preoperative 3-dimensional computerized tomography. Lesions with no contact with the pelvicaliceal system were classified as peripheral. Preoperative, intraoperative, postoperative and pathological data were compared. Central tumors were larger (median 3 vs 2.4 cm, p < 0.001) and had larger specimens at surgery (median 43 vs 22 gm, p < 0.001) than peripheral tumors. Although blood loss was similar (median 150 cc), central tumors required longer warm ischemia time (median 33.5 vs 30 minutes, p < 0.001), operative time (median 3.5 vs 3 hours, p = 0.008) and hospital stay (median 67 vs 60 hours, p < 0.001). A positive cancer margin occurred in 1 patient per group. Median postoperative serum creatinine was similar (1.2 vs 1.1 mg/dl). Intraoperative and late postoperative complications were comparable. However, more early postoperative complications occurred in the central group (6% vs 2%, p = 0.05). LPN for central tumors can be performed safely by an experienced laparoscopic surgeon with perioperative outcomes comparable to those of peripheral tumors. Given the requisite laparoscopic expertise, indications for LPN should be expanded to include centrally located tumors.
Efficient adsorption of diclofenac sodium from aqueous solutions using magnetic amine-functionalized chitosan. In this study, we prepared a magnetic composite based on amine-functionalized chitosan (aminochitosan; AmCS) and Fe3O4 to remove diclofenac sodium (DS) from water. The fabricated AmCS@Fe3O4 composite was characterized using Fourier-transform infrared spectroscopy, transmission electron microscopy, scanning electron microscopy, vibrating sample magnetometry, X-ray diffraction, and thermogravimetric analysis. Furthermore, we investigated the influence of pH, initial DS concentration, and adsorbent dosage on the adsorption of DS. Through thermodynamic analysis, we found that the data corresponded with the Langmuir adsorption isotherm model. The maximum adsorption capacity reached 469.48 mg g-1, and the adsorption process followed the pseudo-second-order kinetic model. Finally, the AmCS@Fe3O4 composite retained good adsorption characteristics after four consecutive cycles, with removal efficiency exceeding 70%. Therefore, the developed adsorbent could be used for efficient adsorptive removal of trace drugs and personal care products from water bodies.
Insulin sensitivity and periodontal infection in a non-diabetic, non-smoking adult population. The aim of this study was to examine whether there is an association of insulin sensitivity with periodontal infection in a non-diabetic, non-smoking adult population. A subpopulation of the Health 2000 Survey (effective n=2050) consisted of dentate subjects without any indication of diabetes, aged between 30 and 64, and who had never smoked. The outcome variable was periodontal infection measured by means of the number of teeth with deepened periodontal pockets. Insulin sensitivity was measured using the homeostasis model assessment index for insulin resistance. Poisson regression models were used to estimate the relative risks and 95% confidence intervals. We found that insulin sensitivity was associated with periodontal infection in the age group 30-49, but not in persons aged 50-64. Controlling for body weight made the association between insulin sensitivity and periodontal infection disappear. The lack of knowledge of the underlying causal model prevents making definite conclusions about the role of reduced insulin sensitivity in the pathogenesis of periodontal infection.
Suspected foodborne carbamate pesticide intoxications associated with ingestion of hydroponic cucumbers. In the period April 1--15, 1977, nine residents of one Nebraska town experienced violent illnesses with short duration following ingestion of locally grown hydroponic cucumbers. Despite a thorough investigation, the etiologic agent of illness was not determined. From July 16--25, 1978, a second similar outbreak occurred in an adjacent city. Five individuals experienced illness similar to that which occurred in 1977, also following ingestion of hydroponic cucumbers grown at the same greenhouse involved in the 1977 outbreak. The carbamate insecticide, aldicarb, was detected in some cucumbers grown at the hydroponic greenhouse. The source of this chemical in the greenhouse could not be determined.
Mental health service provision in juvenile justice facilities: pre- and postrelease psychiatric care. High prevalence rates of mental illness among adolescents in juvenile justice facilities require multifaceted interventions. Children entering justice systems are frequently underserved and having their first contact with psychiatric services. Programming must be multidisciplinary and multifaceted, combining treatment within the facility with postrelease planning. It examines the role of the psychiatrist and the structure of mental health services within juvenile justice facilities.
The activity of guanine exchange factor NET1 is essential for transforming growth factor-beta-mediated stress fiber formation. To examine signaling pathways underlying transforming growth factor-beta (TGF-beta)-mediated changes in cell morphology, we used a microarray system to identify downstream target genes that may play a role in this process. Through this approach, we found that the NET1 gene was induced upon TGF-beta treatment in several cell types. NET1 is a guanine nucleotide exchange factor for RhoA whose activity has been implicated in stress fiber formation. In the Swiss 3T3 cell line, TGF-beta induces NET1 expression, and this correlated with an increase in stress fiber formation. Overexpression of the wild type NET1 gene increases stress fiber formation, and overexpression of a dominant negative NET1 mutant (L392E) prevented TGF-beta dependent increase in stress fiber formation. Furthermore, treatment of the cells with a RhoA kinase inhibitor Y-27632 blocks TGF-beta-induced stress fiber formation. By using a stable cell line expressing dominant negative Smad3, we found that the Smad signaling pathway is essential for the induction of NET1, which in turn leads to the increase of Rho activity. Taken together, those data suggest that induction of NET1 is important for the increase of Rho activity upon TGF-beta treatment, which may represent the critical trigger for a variety of downstream events in different cells. Our results support the presence of a novel signaling pathway by which TGF-beta may regulate the formation of stress fibers and reorganization of cytoskeletal structures.
A comparison of the grip force distribution in natural hands and in prosthetic hands. The aim of this study is to analyse the grip force distribution for different prosthetic hand designs and the human hand fulfilling a functional task. A cylindrical object is held with a power grasp and the contact forces are measured at 20 defined positions. The distributions of contact forces in standard electric prostheses, in a experimental prosthesis with an adaptive grasp, and in human hands as a reference are analysed and compared. Additionally, the joint torques are calculated and compared. Contact forces of up to 24.7 N are applied by the middle and distal phalanges of the index finger, middle finger, and thumb of standard prosthetic hands, whereas forces of up to 3.8 N are measured for human hands. The maximum contact forces measured in a prosthetic hand with an adaptive grasp are 4.7 N. The joint torques of human hands and the adaptive prosthesis are comparable. The analysis of grip force distribution is proposed as an additional parameter to rate the performance of different prosthetic hand designs.
Endoluminal reconstruction of the canine common biliary duct. Extrahepatic biliary duct injuries such as transections, stenoses, and biliary leaks are well-known complications of upper abdominal surgeries. The popularization of laparoscopic cholecystectomies in the early 1990's resulted in an increase in the numbers of these reported injuries. The surgical repair of these injuries may be challenging. In this feasibility study, we were presented with the opportunity to evaluate a novel polytetrafluoroethylene (PTFE) covered stent graft that could be useful in common bile duct reconstructions. The long-term goal of this research is to offer the surgeon a new technique for reconstructing the biliary duct or repairing biliary strictures.John G. Zografakis MD, was the first place winner in the Basic Sciences Resident Competition at the Ohio American College of Surgeons meeting. Seven dogs were originally enrolled in the study. After general endotracheal anesthesia and open cholecystectomy, the common bile duct was identified in each dog. A guide wire was then passed through the neck of the cystic duct, anterograde into the common bile duct, through the Ampulla of Vater and into the duodenum. A stent graft delivery system was placed over the wire, and the covered stent graft was deployed within the lumen of the common bile duct. Study outcomes included graft patency and assessment of the bio-incorporation of the graft and the effectiveness of the graft to drain the biliary system as determined by liver enzyme tests. Three implants were harvested at 1 month, and 2 grafts were harvested each at 3 months and 6 months postoperatively. All of the stent grafts were patent. Liver enzyme tests revealed that all dogs had increased serum levels of alkaline phosphatase, alanine aminotransferase (ALT) serum glutamate pyruvate transaminase (SGPT) and aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase (SGOT). Four dogs had increased total bilirubin. These increases were all measured in the immediate postoperative period. Peak levels for each measure were reached between 4 and 10 days and then gradually trended toward baselines by 1 month postoperatively. We did not observe meaningful changes in serum albumin or total protein. One dog suffered a tear in the common bile duct due to balloon overinflation. This tear was suture repaired when the graft was implanted. However, bile leakage was found when the graft was harvested at 1 month postoperatively. There appeared to be minimal bio-incorporation of the stent-grafts into the biliary duct wall, and there was no pronounced inflammatory response found in the duct wall or surrounding tissues. We are encouraged by these early results. Additional studies are planned to evaluate a self-expanding PTFE covered stent graft and a percutaneous delivery system.
Photoinduced reductive cleavage of some chlorobenzylic compounds. New insights from comparison with electrochemically induced reactions. The photoinduced reductive cleavage of the carbon-chlorine bond in some chlorobenzylic nitro- and cyano-substituted compounds has been studied by transient absorption spectroscopy. The influence of the nature of the electroattractive group as well as its relative position and of the mixture composition of the solvent were investigated to give new clues into the mechanisms and into the factors that control the concerted or stepwise character of the process. Experimental results have been compared with previous results obtained by electrochemical techniques on the same molecules. Analysis leads to the conclusion that, beside the molecular structure, the solvation conditions and the driving force offered to the reaction, the formation of an excited state may control the reactivity.
Basiliximab reduces the incidence of acute cellular rejection in live-related-donor kidney transplantation: a three-year prospective randomized trial. The aim of this work was to investigate the benefit of basiliximab induction therapy in living-related-donor kidney transplantation. One hundred adult recipients of a first kidney allograft were randomized into two treatment groups, one to receive basiliximab and the second as a control. All patients received maintenance triple immunosuppressive therapy (steroids, cyclosporine microemulsion and azathioprine). The patients were followed up for a minimum of three years. The end points for evaluation included the incidence of acute rejection episodes, severity of rejection, cumulative steroid dose, patients' and graft survival. Basiliximab significantly reduced the proportion of patients who experienced an acute rejection in the first year (18/50) compared to the control group (31/50). At three years there were 26 acute rejections in the basiliximab group and 36 in control group. The cumulative steroid dose at three and 12 months was significantly lower in the basiliximab group. The overall incidence of post-transplant complications was comparable in the two groups. Prophylactic basiliximab is well tolerated and significantly reduces the incidence of acute rejection episodes in living-related-donor kidney transplantation.
Magnesium and calciprotein particles in vascular calcification: the good cop and the bad cop. Vascular calcification is a major contributor to increased cardiovascular mortality in chronic kidney disease (CKD). Recently, calciprotein particles (CPP) were identified to drive the calcification process. CPP may explain the effects of high phosphate on vascular calcification. Magnesium is a promising novel therapeutic approach to halt vascular calcification, because it inhibits CPP maturation and is associated with reduced cardiovascular mortality in CKD. We aim to examine the current evidence for the role of CPP in the calcification process and to explain how magnesium prevents calcification. A recent meta-analysis concluded that reducing high phosphate levels in CKD patients does not associate with lowering cardiovascular mortality. Inhibition of CPP formation prevents phosphate-induced calcification in vitro. Consequently, delaying CPP formation and maturation may be a clinical approach to reduce calcification. Magnesium inhibits CPP maturation and vascular calcification. Clinical pilot studies suggest that magnesium is a promising intervention strategy against calcification in CKD patients. CPP induce vascular calcification and are modulated by serum phosphate and magnesium concentrations. Magnesium is a strong inhibitor of CPP maturation and therefore, a promising therapeutic approach to reduce vascular calcification in CKD. Currently, several studies are being performed to determine the clinical outcomes of magnesium supplementation in CKD.
[Monitoring routines at Danish anesthesia departments]. By means of a questionnaire investigation, 84 Danish anaesthetic departments were questioned in January 1987 about their monitoring routines during anaesthesia and recovery. 100% replied. The investigation revealed that measurement of the blood pressure in adults was the routine in all of the departments. Patients were monitored routinely with EGG in 62 departments where minor surgical interventions were concerned while, in major surgical intervention, ECG monitoring was the routine in 91% of the departments. Patients were observed postoperatively in the recovery room or intensive care unit in 51% of the departments. The questionnaire investigation revealed great variation in the monitoring and supervision routines in the anaesthetic departments in Denmark. Hitherto, it has not been possible to demonstrate that monitoring of the functions of vital organs in operation patients can reduce the morbidity and mortality connected with the anaesthesia. It is concluded that it would be desirable to carry out clinically controlled investigations to illustrate whether monitoring equipment can reduce the morbidity connected with anaesthesia and to develop a Danish recommendation concerning peroperative monitoring and postoperative observation.
Urodynamic findings in patients with urogenital fistulae. To assess the feasibility of carrying out a urodynamic investigation in patients with a urogenital fistula and to establish the incidence of abnormal lower urinary tract function in such patients. Of 38 patients referred within the last 3 years with a diagnosis of lower urinary tract genital fistula, 30 were investigated by dual-channel subtracted cystometry before surgical treatment of their fistula; in addition, urethral pressure profilometry was carried out in 19 patients. Fourteen of the patients had fistulae into the vaginal vault; the urodynamic findings in this subgroup were compared with those of 12 patients with bladder neck and urethrovaginal fistulae. Twenty-six of the 30 patients underwent surgical treatment and 24 (92%) were cured anatomically by their first procedure. Ten patients complained of residual lower urinary tract symptoms and were re-investigated. Of the 38 patients, 47% had genuine stress incontinence, 40% showed systolic detrusor instability and 17% impaired bladder compliance. Half had evidence of voiding dysfunction; most appeared to be of a hypotonic detrusor type, although four cases showed an obstructive pattern. Fifteen patients had more than one abnormality and only five (17%) had entirely normal urodynamic findings. The overall incidence of functional abnormality was highest in the patients with urethral or bladder neck fistulae, with only one showing entirely normal urodynamic findings. Genuine stress incontinence was found more than twice as often associated with urethral or bladder neck fistulae and detrusor instability was also more common in this group. Voiding dysfunction of both hypotonic and obstructive types was found equally in the two groups. After surgical treatment, most patients became continent and free from lower urinary tract symptoms, although one complained of residual stress incontinence and nine of urgency or urge incontinence. Of the latter, six were found to have detrusor instability, one after repair of vault fistula, three after urethral or bladder neck fistulae and the other two after mid-vaginal fistulae. There is a high incidence of abnormal lower urinary tract function in patients with urogenital fistulae. Patients with urethral or bladder neck fistulae had a higher incidence of both detrusor instability and genuine stress incontinence than those with fistulae into the vaginal vault. Many of these abnormalities appear to resolve after successful repair of the fistula, although detrusor instability may persist and require further treatment in some women. These findings are relevant to the counselling of patients before repair and may be of medico-legal significance.
Fusarium oxysporum is an onychomycosis etiopathogenic agent. To evaluate and characterize the etiopathogenesis of the fusarial onychomycosis in an ex vivo study through fragments of sterile human nail, without the addition of any nutritional source. The infection and invasion of Fusarium oxysporum in the nail were evaluated by scanning electron microscopy (SEM), CFU, matrix, histopathology and Fourier Transform Infrared Spectrometer coupled to an equipment with diamond accessory (FTIR-ATR). F. oxysporum infected and invaded across the nail, regardless of application face. However, the dorsal nail surface was the strongest barrier, while the ventral was more vulnerable to infection and invasion process. The fungal-nail interaction resulted in the formation of a dense biofilm. F. oxysporum infect and invade the healthy human nail, resulting in biofilm formation. Therefore, F. oxysporum is likely a primary onychomycosis agent.
Effect of increases in myocardial epinephrine content on epinephrine release from the dog heart. The effect of short-term (10 min) and prolonged (180 min) epinephrine (E) infusion (92.5 ng.kg-1.min-1) on E content of the myocardium and on the subsequent release of E from the heart during stimulation of the left stellate ganglion (4 and 10 Hz, 4 V, 2 ms, 1 min) was studied in anesthetized dogs. The E content in the free wall of the left ventricle significantly increased 1.7- and 4.2-fold following short-term and prolonged E infusion, respectively, compared with a control group infused with saline. Tissue norepinephrine (NE) content was not modified by E infusion. The plasma E concentration gradient across the heart indicated a significant release of E during electrical stimulation of the left stellate ganglion, which was related to the amount of E stored in the tissue (e.g., control, 126 +/- 60; 10-min infusion, 279 +/- 105; 180-min infusion, 1487 +/- 287 pg.mL-1; at 10 Hz). NE release from the heart also tended to increase with the amount of E stored in the myocardium and released upon electrical stimulation of the left stellate ganglion, although the difference did not reach statistical significance. These results provide further direct evidence that blood-borne E can be taken up and stored in sympathetic nerve endings and can be released as a cotransmitter with NE. Locally released E could favor NE release.
[The use of PCR technique in the evaluation of the frequency of HPV infection in vulvar and cervical carcinoma]. In this study we estimated the frequency of human papillomavirus (HPV) infection in patients with vulvar and cervical carcinoma by polymerase chain reaction (PCR). We took into consideration the age of patients, the HPV infection status and frequency of HPV types. Vulvar and cervical smears obtained from 88 patients with vulvar and cervical carcinoma, treated in 1997 in II Department of Obstetrics and Gynecology, Medical University in Gdańsk were investigated for HPV DNA. We used the multiplex polymerase chain reaction (M-PCR) with four primer pairs: two primer pairs located in the E6, E7 open reading frame (ORF) for HPV6, 11, 16, 18, 31, 33, 35, 39, 45, 52b i 58 and primer par located in L1 ORF and type-specific primer for HPV16 (E6 ORF). We used restriction fragments length polimorphism PCR (RFLP-PCR) method for HPV typing. HPV DNA was detected in 3 (19%) of the 18 patients with vulvar carcinoma, of whom 3 (100%) had HPV16. In cervical carcinoma, DNA HPV identified in 50 (71%) of the 70, of whom 43 (86%) had HPV16, 3 had HPV31, 3 HPV33 and one was positive for HPV52-b. We did not find significant differences between the frequency of the HPV infection in different age groups of patients with cervical carcinoma. In vulvar cancer, we found the HPV infections significantly more often in group of patients in the age below 55.
Meningioma: an update. Recent clinical and molecular research has shed new light on the biology of meningiomas--a common but understudied CNS neoplasm. This review will focus on recent advances and their significance for future research and treatment. Meningiomas represent the second most common brain tumor in adults, and while improved diagnostic modalities are available, these tumors remain underreported. Radiosurgery is an effective adjuvant therapy against meningioma; however, no effective chemotherapy exists. In addition to histologic grading and estimates of the extent of resection, biomarkers, such as progesterone receptor, cyclooxygenase 2, S100A5 and ornithine decarboxylase may be useful in predicting tumor recurrence and/or progression potential in patients with meningioma. On the genetic level, cytogenetic losses on chromosomes 1, 7, 10 and 14 and telomerase activation are observed in clinically aggressive meningioma, whereas monosomy 22 is a common early molecular event in tumor formation. Several candidate growth regulatory genes have been identified, including the Neurofibromatosis 2 (NF2), Tumor Suppressor in Lung Cancer-1 (TSLC1), Protein 4.1B, p53/MDM2 and S6-Kinase genes. The roles of these genes in meningioma formation and progression, as well as the clinical implications of these genetic changes, are discussed. The recent insights into the molecular biology and genetics of meningioma provide new avenues for basic science research aimed at understanding the mechanisms underlying meningioma formation and malignant progression. These advances may be useful in improving our ability to predict clinical outcome and developing targeted therapies to improve outcomes in patients with clinically aggressive meningiomas.
Thermal oxidative degradation studies of phosphate esters. Five phosphate esters - tri-p-tolyl phosphate, tributyl phosphate, tris(1,3-dichloro-2-propyl)phosphate, tris(2,3-dibromopropyl)phosphate, and tris(2-chloroethyl)phosphate- were subjected to thermal oxidative degradation in air at 370 degrees C. Degradation mechanisms were postulated and the toxic hazards assessed based on the volatiles produced. Tri-p-tolyl phosphate was found to undergo only minimal degradation; the other compounds were decomposed extensively. Butene was the main product formed on tributyl phosphate decomposition; hydrogen halides and halogenated C2- and C3- species were the main products formed by the halogenated phosphate ester. In the case of tris(1,3-dichloro-2-propyl)phosphate acrolein, not hydrogen chloride, presented the major toxic hazard.
A large mediastinal tumor with spontaneous regression 30 years after esophageal bypass surgery. We describe the case of an 80-year-old man admitted to the hospital for the first time with chest pain and progressive respiratory difficulty. Radiographic findings of the chest showed a large, cystic mediastinal mass from the jugulum to the diaphragm. The patient's history revealed bypass operation for a benign esophageal stricture 30 years ago. During the hospital stay, clinical symptoms resolved within 48 hours without specific treatment. Seven days after admission a chest roentgenogram showed almost complete regression of the tumor, which was supposed to be a mucocele of the colon bypassing the esophagus.
Lamellar macular hole formation in patients with diabetic cystoid macular edema. To report lamellar macular hole formation in four patients with diabetic cystoid macular edema (CME). A review of the medical records of four patients with diabetic CME in whom lamellar macular hole formation was observed. The morphologic changes of CME, seen using optical coherence tomography (OCT), and best-corrected visual acuity were evaluated. Lamellar macular hole formation had occurred, as determined by slit-lamp biomicroscopy and OCT. Although the inner retinal layer had disappeared, the outer retinal layer was preserved. On OCT, the reflective line of an epiretinal membrane or a posterior hyaloid membrane was seen on the surface of juxtafoveal retina, and visual acuity remained unchanged in all four patients. In diabetic patients with CME, the CME occasionally changes spontaneously to a lamellar macular hole. Although the central cystoid space disappears and foveal thickness decreases after this transformation, visual acuity may be little affected as long as the structure of the outer retina remains intact.
Effects of aminoglutethimide, alone and in combination with surgical castration, on pancreatic carcinogenesis in rats and hamsters. The present 12-month study was carried out to investigate the effects of the aromatase inhibitor aminoglutethimide, alone and in combination with orchiectomy, on pancreatic carcinogenesis in azaserine-treated rats and N-nitrosobis(2-oxopropyl)-amine-treated hamsters. Treatment of the animals started 4 months after the last injection with the carcinogen. They were surgically castrated and/or treated with aminoglutethimide. Aminoglutethimide-treated rats developed less pancreatic tumours than did untreated controls. Multiplicity of (pre-)-neoplastic acinar lesions was lower in orchiectomized rats than in intact rats. Inhibition of pancreatic carcinogenesis was most pronounced in rats that were both orchiectomized and treated with aminoglutethimide. These effects were statistically significant after 8 months, but not after 4 months, of treatment. In hamsters, aminoglutethimide showed an enhancing rather than an inhibitory effect on the formation of ductular pancreatic tumours. Castration appeared to have no effect on the development of N-nitrosobis(2-oxopropyl)amine-induced ductular lesions in the pancreas, either alone, or in combination with aminoglutethimide. The present findings indicate that aminoglutethimide, alone and in combination with surgical castration, might be of value for the treatment of pancreatic acinar tumours, whereas the usefulness of aminoglutethimide for treatment of ductular adenocarcinomas of the pancreas is somewhat doubtful.
Solubilization of polyaromatic hydrocarbons by recombinant bioemulsifier AlnA. AlnA is the protein responsible for the emulsifying and solubilizing activity of the Acinetobacter radioresistens KA53 bioemulsifier alasan. AlnA was produced in Escherichia coli, purified to homogeneity and then used to measure the enhanced solubility of 12 polyaromatic hydrocarbons (PAHs). The amount of PAH solubilized was directly proportional to AlnA concentration. The ratio of PAH solubilized by 40 micro g/ml AlnA compared to that soluble in the aqueous buffer varied greatly, from 4 (fluorene) to 81 (hexylbenzylcyclosilane). Calculations of moles PAH solubilized per mole AlnA yielded values from 4.3 (hexylphenylbenzene) to 55.8 (1,10-phenanthrolene). There was no obvious relationship between the amount of PAH solubilized and its molecular weight or intrinsic solubility. Native gel electrophoresis indicated that AlnA formed hexamers in the presence of PAHs. With molar ratios of fluorene to AlnA of 0.75 or less, only the monomer was observed, whereas at ratios of 7.5 or higher, only the hexamer was detected. At an intermediate molar ratio of 2.6, both monomer and hexamer appeared. The data indicate that PAHs are initially solubilized by binding to the monomeric form of AlnA, and as the amount bound increases above one molecule PAH per AlnA, the protein aggregates to form a specific oligomer of 5-8 monomers which allows for the binding and solubilization of more PAH.
Transcriptomic and hormone analyses reveal mechanisms underlying petal elongation in Chrysanthemum morifolium 'Jinba'. Auxin regulates chrysanthemum petal elongation by promoting cell elongation. Transcriptomic analysis shows that auxin signal transduction may connect with other transcription factors by TCPs to regulate chrysanthemum petal elongation. As an ornamental species, Chrysanthemum morifolium has high ornamental and economic value. Petal size is the primary factor that influences the ornamental value of chrysanthemum, but the mechanism underlying the development of C. morifolium petals remains unclear. In our study, we tracked the growth of petals and found that the basal region of 'Jinba' petals showed a higher elongation rate, exhibiting rapid cell elongation during petal growth. During petal elongation growth, auxin was demonstrated to promote cell elongation and an increase in cell numbers in the petal basal region. To further study the molecular mechanisms underlying petal growth, the RNA-seq (high-throughput cDNA sequencing) technique was employed. Four cDNA libraries were assembled from petals in the budding, bud breaking, early blooming and full blooming stages of 'Jinba' flower development. Analysis of differentially expressed genes (DEGs) showed that auxin was the most important regulator in controlling petal growth. The TEOSINTEBRANCHED 1, CYCLOIDEA and PCF transcription factor genes (TCPs), basic helix-loop-helix-encoding gene (bHLH), glutaredoxin-C (GRXC) and other zinc finger protein genes exhibited obvious up-regulation and might have significant effects on the growth of 'Jinba' petals. Given the interaction between these genes in Arabidopsis thaliana, we speculated that auxin signal transduction might exhibit a close relationship with transcription factors through TCPs. In summary, we present the first comprehensive transcriptomic and hormone analyses of C. morifolium petals. The results offer direction in identifying the mechanism underlying the development of chrysanthemum petals in the elongated phase and have great significance in improving the ornamental characteristics of C. morifolium via molecular breeding.
Color Doppler ultrasonography and multislice computer tomography angiography in carotid plaque detection and characterization. Cerebrovascular diseases are the third leading cause of mortality in the world, following malignant and cardiovascular diseases. Therefore, their timely and precise diagnostics is of great importance. The aim of this study was to compare duplex scan Color Doppler ultrasonography (CDU) with multislice computed tomography angiography (MSCTA) in detection of morphological and functional disorders at extracranial level of carotid arteries. The study included 75 patients with 150 carotid arteries examined in the period from January 2008 to April 2009. The patients were firstly examined by CDU, then MSCTA, followed by the surgery of extracranial segment of carotid arteries. In 10 patients, the obtained material was referred for histopathological (HP) examination. We used both CDU and MSCT in the analysis of: plaque surface, plaque structure, degree of stenosis, and the presence of in-traplaque hemorrhage. The results obtained by CDU and MSCTA were first compared between themselves, and then to intraoperative findings. Retrospective analysis showed that MSCTA is more sensitive than CDU in assessment of plaque surface (for smooth plaques CDU 89%: MSCTA 97%; for plaques with irregular surface CDU 75% : MSCTA 87%; for ulcerations CDU 54%: MSCTA 87%). Regarding determination of plaque structure (mixed plaque CDU 66% : MSCTA 70%; correlation with HP findings CDU 94% : MSCTA 96%) and localization (CDU 63%: MSCTA 65%), and in terms of sensitivity and specificity, both methods showed almost the same results. Also, there is no statistical difference between these two methods for the degree of stenosis (CDU 96%: MSCTA 98%). Atherosclerotic disease of extracranial part of carotid arteries primarily affects population of middle-aged and elderly, showing more associated risk factors. Sensitivity and specificity of CDU and MSCTA regarding plaque composition, the degree of stenosis and plaque localization are almost the same. These results and the fact that there are no adverse effects (high radiation dose) compared to MSCTA indicate that CDU should be the initial method in diagnostic algorythm for carotid arteries.
Reversal of experimental posthepatectomy liver failure in pigs: a new application of hepatocyte bioreactors. Postoperative liver failure remains a major cause of morbidity and mortality after extensive hepatectomies. This study aims to evaluate the effectiveness of a hepatocyte bioreactor in the treatment of experimental post-hepatectomy liver failure. Our experimental model included a combination of a side-to-side portacaval shunt, occlusion of the hepatoduodenal ligament for 150 min, 70% hepatectomy, and reperfusion. Following the development of liver failure, 12 pigs were randomized into a control group (n = 6) and a treatment group (n = 6). Both groups underwent extracorporeal perfusion through a plasma separation device, a membrane oxygenator, and two parallel bioreactors. In the latter group, the bioreactors were loaded with 10 billion fresh hepatocytes, isolated from a donor pig. Following hepatocyte treatment, all animals were maintained for 24 h under mechanical ventilation, with intravenous fluid and glucose supplementation. Hemodynamic parameters, intracranial pressure, and biochemical parameters were measured. Liver biopsies were obtained during the 24-h autopsy. The extracorporeal circuit was well-tolerated hemodynamically. Treated animals had lower intracranial pressure compared with controls (at 24 h, 15 ± 3.1 vs. 22 ± 3.5 mm Hg, P = 0.006). Plasma ammonia in treated animals was lower compared with controls at 12 h (100 ± 29 vs. 244 ± 131 µmol, P = 0.026). Liver histological study showed decreased necrosis and increased regeneration activity in treated animals compared with controls. Treatment through an extracorporeal hepatocyte bioreactor attenuates brain edema and improves histological and functional parameters of the liver remnant of pigs with posthepatectomy liver failure.
Impaired myogenic tone in isolated cerebral and coronary resistance arteries from the goto-kakizaki rat model of type 2 diabetes. Type 2 diabetes is associated with stroke and cardiac dysfunction. We therefore investigated isolated middle cerebral arteries and coronary septal arteries from the diabetic Goto-Kakizaki (GK) rat model of nonobese type 2 diabetes. Myogenic tone and agonist-induced responses were investigated under isobaric conditions with simultaneous recording of [Ca2+]i. Rho-kinase and NO pathways were investigated using specific pharmacological tools. Arteries from GK rats developed less tone at pressures from 20 to 100 mm Hg than arteries from control Wistar (CW) rats while [Ca2+]i was similar. Blocking the Rho-kinase pathway decreased the pressure-induced development of tone and after blockade no difference in myogenic tone between arteries from GK and CW rats was seen. Cerebral arteries had similar tone to a maximal concentration of U46619 (GK: 35.5±2% vs. CW: 31.6±5%), while coronary arteries from GK rats developed less tone than arteries from CW rats (12±3 vs. 26.1±3%). Endothelium-dependent vasodilation to A23187 (cerebral) and to acetylcholine (coronary) was not different between arteries from GK and CW rats. Our data suggest that in resistance arteries from the brain and the heart of GK rats the myogenic tone is decreased due to impaired calcium sensitivity likely due to a defective Rho-kinase pathway.
The effects of acute carbon monoxide intoxication on the cerebral energy metabolism of the rat. The cerebal metabolic effects of 60 min exposure to 0.5, 1.0, 1.5, and 2.0% carbon monoxide (CO) and 60 min exposure to 1.0% CO were studied in lightly anesthetized rats by measurement of brain tissue contents of glycolytic and citric acid cycle intermediates, as well as tissue energy phosphates. The results indicate that cerebral energy homeostasis is maintained until advanced levels of CO intoxication (2.0%) are reached. Animals exposed to 2.0% CO developed significant decreases in systemic blood pressure, with attendent decreases in cerebral ATP, increases in ADP and AMP, plus early depletions of tissue citrate and alpha-oxyglutarate. The similarity of this pattern to that previously documented for various cerebral oligemic states suggests a possible modifying role for altered cerebral production in its production. A correlation between conscious behavior and cerebral energy state was suggested by the observation that unanesthetized animals exposed to 1.0% CO for 30 and 60 min retained consciousness, whereas animals exposed to 2.0% CO for 30 min became unresponsive late on in the exposure. A comparison of CO induced changes in intermediary metabolites, energy phosphates, intracellular pH, and cytoplasmic redox state with those seen in hypoxemia indicate no basic qualitative or quantiative differences in the metabolic response of brain tissue to the two conditions.
Medicine in the 21st century: the situation in a rural Iraqi community. To describe the health beliefs and practice in a rural Iraqi community. Personal observations and practice; narratives of colleagues. Rural Iraqi society has remained unchanged in beliefs and practices in many ways since the Babylonian and Sumerian eras over four millennia ago. Like other rural societies, it has a culture that includes values, beliefs, customs, communication style, and behaviors. Those beliefs often invoke supernatural agents such as evil, jinni, witchcraft and the results of sin, bad luck and envy. Primitive and current religious beliefs join with the effects of poverty and illiteracy. These rural people view health and disease quite differently from the views of their physicians and these cultural beliefs and practices confound current patient-clinician communication. Although physicians view the medical encounter as the main tool of diagnosis and therapy, especially when biomedical technology is lacking, ignorance of the characteristics of the rural society and people may make physicians' work all the more difficult. As with all cross-cultural interactions, better understanding of the patient or family's beliefs allow the clinician to find compromises and reach agreements that ignorance of their beliefs would deny. Simply asking the patient and the family how they view the illness, what they consider to be the cause, what treatments they have already tried and what treatments they hope you will use, may go a long way toward building a therapeutic relationship.
Breast-fed infants have higher leptin values than formula-fed infants in the first four months of life. Leptin is a hormone present in breast milk, which regulates food intake and energy metabolism. To investigate whether leptin levels are different in breast-fed (BF) or formula-fed (FF) infants in the first months of life. We evaluated serum leptin by radio-immunoassay and anthropometric parameters in 51 infants at the average age of 62.8+/-30 days, 25 exclusively BF and 26 exclusively FF. Leptin serum values were higher in BF (7.1+/-10.4 ng/ml) than in FF (3.7+/-3.87 ng/ml) infants (p <0.05). Leptin values were higher in females (6.9+/-9.87 ng/ml) than in males (3.5+/-3.88 ng/ml) (p <0.05). No differences were found in anthropometric measurements and body mass index. The kind of feeding might be a factor affecting serum leptin concentration in term infants. The long-term consequences of this difference between BF and FF infants and leptin's role in promoting obesity later in life are unknown.
A longitudinal study of cerebral glucose metabolism, MRI, and disability in patients with MS. To study the time-related changes in cerebral metabolic rate of glucose (CMRglc) in MS patients and to correlate these with changes in MRI lesion load and disability. Measurements of MRI lesion load and neurologic disability are used widely to monitor disease progression in longitudinal studies of MS patients, but little is known about the associated changes in cerebral neural function. The authors studied 10 patients with clinically definite MS who underwent serial measurements of CMRglc, MRI T2-weighted total lesion area (TLA), and clinical evaluation of disability (Expanded Disability Status Scale [EDSS]) over a period of approximately 2 years (three examinations). CMRglc was calculated using PET and 18-fluorodeoxyglucose (FDG). The global cortical CMRglc decreased with time (p<0.001) and the most pronounced reductions of CMRglc were detected in frontal and parietal cortical areas. There was a statistically significant increase of disability (p<0.01) and TLA (p<0.05) measurements during the study, but changes in CMRglc were not correlated to changes in TLA and EDSS. Global cortical cerebral metabolism in MS is decreased significantly during a 2-year observation period, suggesting a deterioration of cortical activity with disease progression. The time-related changes of cortical CMRglc are statistically stronger than changes in TLA measurements and neurologic disability, and might be a useful secondary measure of treatment efficacy.
Hidden high rate of pre-eclampsia in twin compared with singleton pregnancy. To examine the gestational age at delivery in dichorionic (DC) and monochorionic (MC) twin pregnancies, with and without pre-eclampsia (PE), and to determine the relative risk of total and preterm PE compared with that in singleton pregnancies. This was a screening study for PE in twin pregnancies undergoing first-trimester combined screening for aneuploidy and subsequently delivering two phenotypically normal live or stillborn babies at ≥ 24 weeks' gestation. The distribution of gestational age at delivery in DC and MC twins was determined and compared with that in singleton pregnancies from the same population. The relative risk for total and preterm PE in twins compared with singleton pregnancies was determined. Kaplan-Meier estimates of the cumulative incidence of PE in twin and singleton pregnancies, assuming no other cause for delivery, were determined and hazard ratios for twins relative to singletons were obtained from a Cox proportional hazards regression model. The incidence of PE in singletons was 2.3% (2162/93 297), in DC twin pregnancies was 8.1% (145/1789) and in MC twin pregnancies was 6.0% (26/430). Compared with singletons, the relative risk of total PE was 3.5 for DC twins and 2.6 for MC twins. Delivery < 37 weeks' gestation occurred in 5.5% of singletons, 46.5% of DC twins and 91.4% of MC twins. The incidence of preterm PE was 0.6%, 5.5% and 5.8% for singletons, DC twins and MC twins, respectively. Compared with singletons, the relative risk of preterm PE was 8.7 for DC twins and 9.1 for MC twins. In the Cox proportional hazards regression model, the hazard ratios for DC and MC twin pregnancies relative to singleton pregnancies were 14 and 23, respectively. The relative risk of preterm PE in DC and MC twins is similar and substantially higher than in singleton pregnancies. In ongoing twin pregnancies, the high relative risk of PE may merit a higher intensity of monitoring than is routine for singleton pregnancies. © 2017 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.
Allogeneic stem cell transplantation for adult Philadelphia chromosome-negative acute lymphocytic leukemia: comparable survival rates but different risk factors between related and unrelated transplantation in first complete remission. To identify factors to improve the outcomes of related and unrelated allogeneic stem cell transplantations (allo-SCT) for Philadelphia chromosome-negative acute lymphocytic leukemia (Ph(-) ALL) in the first complete remission (CR1), we retrospectively analyzed 1139 Ph(-) ALL patients using the registry data, particularly the details of 641 patients transplanted in CR1. Overall survival was significantly superior among patients transplanted in CR1, but no significant difference was observed between related and unrelated allo-SCTs (related vs unrelated: 65% vs 62% at 4 years, respectively; P = .19). Among patients transplanted in CR1, relapse rates were significantly higher in related allo-SCT compared with unrelated allo-SCT, and multivariate analysis demonstrated that less than 6 months from diagnosis to allo-SCT alone was associated with relapse. On the other hand, nonrelapse mortality (NRM) was significantly higher in unrelated allo-SCT compared with related allo-SCT, and multivariate analysis demonstrated that 10 months or longer from diagnosis to allo-SCT, human leukocyte antigen mismatch, and abnormal karyotype were associated with NRM. In conclusion, our study showed comparable survival rates but different relapse rates, NRM rates, and risk factors between related and unrelated allo-SCTs. After a close consideration of these factors, the outcome of allo-SCT for adult Ph(-) ALL in CR1 could be improved.
Assessment of sleep impairment in persistent allergic rhinitis patients using polysomnography. Although questionnaires have demonstrated an association between impairment of quality of sleep and symptoms in allergic rhinitis (AR) patients, to date there is no report of an objective assessment of sleep in patients with persistent allergic rhinitis (PER) as defined by ARIA guidelines. The aim of the present study was therefore to assess sleep disturbance in PER patients by polysomnography (PSG). Ninety-eight PER patients with moderate-to-severe nasal obstruction and 30 healthy volunteers were included in the study. All patients underwent PSG during nocturnal sleep to assess the presence and severity of sleep disorders. Peak nasal inspiratory flow (PNIF) was also measured to assess nasal resistance. There were statistically significant, though clinically modest, differences between PER patients and healthy controls in most PSG parameters including sleep efficiency, arousal index, average SaO(2), lowest SaO(2), time spent with a saturation below 90%, and snoring time. Although the apnea-hypopnea index (AHI) was not significantly different between the 2 groups, 17 subjects (17.3%) in the PER group but none of the control subjects had an AHI >5. Patients with higher T5SS scores (12 ≤ T5SS ≤ 15) had a greater tendency to snore than did patients with lower scores (8 ≤ T5SS ≤ 11). Finally, PNIF in the PER group was significantly lower than in the control group. Weak correlations between the arousal index and PNIF, average SaO(2), and PNIF were found. PSG showed modest changes in PER patients versus control subjects.
"Your ears become your eyes": managing the absence of visibility in NHS Direct. To identify and describe nurses' perceptions of interactional practices they use to manage the absence of visual cues in telephone consultations with callers at an NHS Direct site. A routine activity in telephone consultations is visualizing the patient and the situation from which the call is made, that is, "building a picture of the patient". Little is known about interactional practices between nurse and caller that contribute to shaping a conception of the caller, or other activities that nurses do to manage the absence of visibility in the consultation. Qualitative analysis of semi-structured interviews conducted with nurses new to NHS Direct telephone consultations, the first immediately prior to the NHS Direct site's opening, and the second 6 months later. The activity of visualizing patients and their environment is closely linked to interactional practices carried out between nurse and caller. Nurses described a range of interactional activities that they perceive help callers to describe with more precision what the nurse cannot see. Nurses also tailor interaction to a nonvisual environment in order to manage the more emotional aspects of telephone consultations, such as delivering information, advice, reassurance, and building trust and rapport. Nurses developed skills to manage interaction with callers in order to compensate for the absence of visibility. Skills were based on their professional backgrounds and experience and developed in an ad hoc way. Further research could examine the efficacy of these strategies, and be a prerequisite to adding them to training programmes.
Immunohistochemical expression of cytokeratins and epithelial membrane protein 2 in nasopharyngeal carcinoma and its potential implications. Nasopharyngeal carcinoma (NPC) is an aggressive disease and tends to involve surrounding tissues, and biomarkers for better management are yet to be identified. One hundred and fifty tissue samples with NPC diagnosis were were investigated using pan cytokeratin (CK) and epithelial membrane protein 2 (EMP2) antibodies. Immunohistochemical expression of CK was identified in 144/150 (96%) and of EMP2 in 120/150 (80%). There is a high loss of EMP2 in NPC, especially high grade examples. Loss of CK expression is also linked to high grade NPC types.
Is cosmetic surgery an effective psychotherapeutic intervention? A systematic review of the evidence. Elective cosmetic surgery (ECS) in the absence of physical indications is often performed to improve psychosocial function. Third-party funders need evidence of its effectiveness if they are to respond in an evidence-based way to increasing demand in the context of constrained resources. Our first aim was to review recent evidence of psychosocial outcome in a way that was systematic with respect to study inclusion and methodological evaluation. Our second aim was to review evidence for the validity of currently used selection criteria. Electronic and manual literature and database search identified prospective cohort or controlled studies of psychosocial outcomes of surgery performed for appearance reasons reported in English from 1992 to 2004. Data were extracted to describe outcomes and evaluate methodological quality. Twenty-three reports of 22 separate studies were reviewed. All were prospective observational studies and most provided low standards of evidence because of the absence of comparison groups, short follow-up periods and loss to follow-up. The evidence suggests that breast reduction improves health-related quality of life, but does not indicate enduring improvement in quality of life after other procedures, or enduring improvement in mental health, self-esteem or body image after any procedure. Similarly, there was insufficient evidence for the validity of criteria for patient selection. The negative conclusions reflect, not the existence of negative evidence, but methodological limitations of published research. The problem for third-party funders is that, although evidence does not justify the continued general provision of ECS in the absence of physical need, it is not strong enough to justify withholding such treatment. Even though randomised controlled trials are probably impractical, we identify several improvements in design whereby future prospective cohort studies could provide higher standards of evidence.
An emerging 1q21.1 deletion-associated neurodevelopmental phenotype. In this study, we describe the neurodevelopmental and epileptic phenotypes in a family with an inherited 1q21.1 deletion. During the pregnancy with the proband, increased nuchal translucency and oligohydramnion were detected. The proband showed mild global developmental delay and ataxic gait. Seizures started in the proband at the age of 2 years and manifested as generalized tonic-clonic seizures, atypical absence seizures, head drops, and drop attacks with no abnormal findings on interictal electroencephalogram. We performed an Agilent Human Genome CGH (comparative genomic hybridization) Microarray 105A, and a microdeletion on chromosome 1q21.1 was identified in both the patient and his asymptomatic father. This deletion encompasses 1.65 Mb and is larger than the reported recurrent class I deletions in this region. Cryptic cytogenetic abnormalities should be considered in patients with neurodevelopmental problems and atypical presentation of epilepsy with a normal electroencephalography (EEG).
Coicenals A-D, four new diterpenoids with new chemical skeletons from the plant pathogenic fungus Bipolaris coicis. Coicenals A-C (1-3) possessing a previously undescribed 10-(sec-butyl)-6-hydroxy-1,7,9-trimethyl-1,6,7,8,9,9a-hexahydro-1,4-methanobenzo[d]oxepin-2(4H)-ylidene)acetaldehyde skeleton and coicenal D (4) with a new 2-(sec-butyl)-5-hydroxy-1,6,8-trimethyl-2,5,6,7,8,8a-hexahydro-1H-4a,1-(epoxymethano)naphthalen-10-ylidene)acetaldehyde skeleton were isolated from the solid culture of the plant pathogenic fungus Bipolaris coicis. The absolute configurations in 1 and 4 were assigned by electronic circular dichroism (ECD) calculations. Compounds 1 and 2 were transformed into 4 and 5 by treatment with acetyl chloride, respectively. Compounds 1-4 showed moderate inhibitory activity against NO release with IC50 values of 16.34 ± 1.12, 23.55 ± 1.37, 10.82 ± 0.83, and 54.20 ± 2.82 μM, respectively.
Primary structure of the plant serpin BSZ7 having the capacity of chymotrypsin inhibition. The primary structure of barley grain serpin BSZ7 was deduced from a cDNA encoding 397 amino-acid residues. More than 70% of the residues were confirmed by sequencing peptide fragments. The N-terminus was identified as an acetylated Ala by using mass spectrometry coupled with amino-acid analysis. None of the four putative N-glycosylation sites were found to be glycosylated. The positional identity of BSZ7 with plant and mammalian serpins is 69-72% and 25-32%, respectively.
[Clinical aspects and prognostic factors of intracerebral hemorrhage]. Intracerebral hemorrhage represents approximately 20% of all strokes. In spontaneous intracerebral hemorrhage the essential etiological factor is arterial hypertension, and the most frequent site the putamen and lobes of the cerebrum (lobar hematoma). The mortality is higher than in cerebral infarct, although the long-term prognosis is similar. We review the most relevant forms of presentation and clinical findings of intracerebral hemorrhage in adults, which show a combination of symptoms common to all types of hematoma and those symptoms which depend on their site. We also analyse the factors and studies which have sought to recognize variables predicting morbimortality.
Elevated nocturnal desaturation index predicts mortality in interstitial lung disease. Nocturnal desaturation may contribute to long-term pulmonary vascular stress in interstitial lung disease (ILD). We study the prevalence, severity and prognostic utility of nocturnal desaturation across ILD. ILD patients with overnight oximetry (June 2006-August 2008) were reviewed (n = 134). Significant nocturnal desaturation was considered as > 10% of sleep with SpO2 < 90%. Desaturation index (DI) was defined as the number of desaturation events > 4%/hr. Covariates, including indices of nocturnal desaturation, were evaluated against mortality. Nocturnal desaturation was present in 49 (37%) patients. 31% of patients had pulmonary hypertension (PH) on echocardiography. Increased DI was associated with higher mortality independent of age, gender and BMI (HR 1.04; 95% CI 1.00, 1.06; p = 0.009). In separate models, DI and a) elevated brain natriuretic peptide (BNP; HR 1.04; 95% CI 1.00, 1.08; p = 0.04); b) moderate-severe PH on echocardiography (HR 3.15; 95% CI 1.24, 8.00; p = 0.02); and c) daytime resting SpO2 (HR 0.92; 95% CI 0.85, 0.99; p = 0.04) independently predicted mortality following adjustment for age, gender and BMI. Nocturnal desaturation is common and may be severe in ILD. Elevated nocturnal DI predicts higher mortality across ILD, independent of other vascular parameters. This finding may have important implications for the pathogenesis of PH in IPF.
Glomerulonephritis causing acute renal failure during the course of bacterial infections. Histological varieties, potential pathogenetic pathways and treatment. To illustrate diagnostic approaches, potential pathogenetic differences, epidemiological implications and therapeutic dilemmas posed by glomerulonephritis (GN) with acute renal failure (ARF) complicating bacterial infections, we analyzed the course of four male patients, aged 53-71 years, who developed GN and ARF following bacterial infections. The first two patients developed GN with immunoglobulin A (IgA) deposits after infections with hospital-acquired methicillin resistant Staphylococcus aureus (MRSA). Clinical, serologic and histological features, classification of GN and treatment differed between the two patients. In the first patient, serological features (transient hypocomplementemia, normal serum protein electrophoresis) and histological findings were consistent with typical post-infectious GN. Treatment with antibiotics alone resulted in normalization of the renal function despite the severity of ARF, which required temporary hemodialysis. In the second patient, serological features (normal serum complement, polyclonal elevation of gamma globulins) and histological picture of the kidneys were characteristic of IgA nephropathy with fibrocellular crescents, and skin histology was consistent with vasculitis. Cyclophosphamide and corticosteroids were added to the antibiotics, with partial improvement of the renal failure. The third patient developed simultaneous acute rheumatic fever and post-streptococcal GN causing severe ARF requiring hemodialysis. Complete recovery of ARF and migratory polyarthritis followed initiation of corticosteroids. The fourth patient developed ARF and cerebral vasculitis following a prolonged course of Streptococcus mutans endocarditis with delayed diagnosis. He also developed multiple serological abnormalities including elevated titers of antineutrophil cytoplasmic antibodies (ANCA), antinuclear antibodies (ANA), anti-phospholipid antibodies, rheumatoid factor, and modest hypocomplementemia. Kidney biopsy revealed ANCA-mediated focal GN with 10% crescents and acute interstitial nephritis. Treatment with cyclophosphamide plus corticosteroids, but not with antibiotics alone, resulted in resolution of both the ARF and the features of cerebral vasculitis. GN following bacterial infections may have various pathogenetic mechanisms, presents complex diagnostic challenges, may be preventable in the case of hospital-acquired MRSA, and, in addition to antibiotics, may require immunosuppressive therapy in carefully selected and monitored cases.
Levamisole pharmacokinetics and bioavailability in dogs. Levamisole was given intravenously and orally (with and without food) to six dogs. All dogs reacted adversely to intravenous dosage and one died. For the remaining five, intravenous data fitted a one compartment model with first order elimination and a mean half-time of elimination of 1.8 hours. In fasting dogs drug absorption from the gut was rapid and the mean fraction absorbed (F) was 0.64. When levamisole was given with food, drug bioavailability was impaired, as absorption was slowed and possibly reduced (F = 0.49). The effect of ingesta on bioavailability of levamisole could affect treatment efficacy and side effects.
MicroRNA-202 induces cell cycle arrest and apoptosis in lung cancer cells through targeting cyclin D1. MicroRNAs are critical regulators in tumorigenesis. This study is aimed at investigating the function of miR-202 in the proliferation of human lung cancer cells. Lung cancer tissues and paired adjacent normal tissues were collected from 20 patients; the expression of miR-202 was tested by Realtime PCR; cell proliferation and cell cycle distribution were determined by CCK-8 assay and flow cytometry, respectively; apoptosis was determined by TUNEL assay and Western blot analysis of cleaved-PARP; the relationship between miR-202 and cyclin D1 mRNA 3'UTR was determined by luciferase activity assay. MiR-202 was significantly reduced in lung cancer tissues compared with the adjacent normal tissues. Overexpression of miR-202 inhibited cell proliferation and induced a G0/G1 cell cycle arrest and apoptosis. Luciferase activity assay and Western blot analysis together showed that miR-202 can bind to the 3'UTR of cyclin D1 mRNA directly and inhibits cyclin D1 expression at the protein level. In addition, restoration of cyclin D1 expression partially abolished cell cycle arrest and apoptosis induced by miR-202. MiR-202 is constantly downregulated in lung cancer and functions as a tumor suppressive gene via targeting cyclin D1. Modulating the level of miR-202 may be a novel therapeutic method for lung cancer.
Construction of human antibody gene libraries and selection of antibodies by phage display. Antibody phage display is the most commonly used in vitro selection technology and has yielded thousands of useful antibodies for research, diagnostics, and therapy.The prerequisite for successful generation and development of human recombinant antibodies using phage display is the construction of a high-quality antibody gene library. Here, we describe the methods for the construction of human immune and naive scFv gene libraries.The success also depends on the panning strategy for the selection of binders from these libraries. In this article, we describe a panning strategy that is high-throughput compatible and allows parallel selection in microtiter plates.
[Preliminary studies on the retention of hydroxylated PCDF metabolites in rat blood]. We recently reported that certain hydroxylated PCB (OH-CB) metabolites were selectively retained in blood of rats experimentally dosed with PCB (Aroclor 1254), and also in blood of seals and humans environmentally exposed to PCBs. We also showed that metabolism in vivo of polychlorinated dibenzofurans (PCDFs) gave rise to a large number of hydroxylated PCDF (OH-CDF) metabolites, excreted in faeces, after oral administration to rats of PCDFs mixture (1, 2, 7, 8-tetraCDF 14%, 2, 3, 7, 8-tetraCDF 35%, 1, 2, 3, 7, 8-pentaCDF 48%). These results suggest that OH-CDFs could be present in blood. In the present study, potential retention of OH-CDF metabolites in blood (serum) was investigated in a female Wistar rat exposed to the PCDFs mixture. Serum was analyzed for the methylated OH-CDFs by gas chromatography (GC) and GC-mass spectrometry. Two major metabolites were determined in serum 1 day after oral administration. These were identified to be 3-OH-2, 4, 7, 8-tetraCDF (A) and 3-OH-2, 4, 7, 8, 9-pentaCDF (B) by comparison with synthesized reference compounds. 3-OH-2, 4, 7, 8-tetraCDF and 1, 2, 3, 7, 8-pentaCDF, respectively, via 3, 4(6, 7)-epoxide intermediate and subsequent NIH-shift of the 3(7)-chlorine to the 4(6)-position. The amounts of 3-OH-2, 4, 7, 8-tetraCDF and 3-OH-2, 4, 7, 8, 9-pentaCDF in the serum (5.72 g) analyzed accounted for 0.018% of 2, 3, 7, 8-tetraCDF and 0.003% of 1, 2, 3, 7, 8-pentaCDF dosed, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Unwitting self-disclosures in psychodynamic psychotherapy: deciphering their meaning and accessing the pain within. Unwitting self-disclosures (USDs), unconscious yet observable parts of personality, are often behavioral relics of past suffering and, as such, constitute valuable though frequently underutilized clinical information. While ego-syntonic aspects of personality can be commented on with impunity, dealing therapeutically with patients' USDs--manifestations of their blind spots--requires sensitivity, empathy, and timing. Providing many clinical examples of patient and therapist USDs from individual and group psychotherapy, this report discusses the origins, possible meanings, and the countertransference and empathic challenges encountered in the handling of these blind spots. The importance of establishing a narcissistic alliance and of employing the methods of the existential school of psychotherapy in processing USDs is described. Self-aware therapists can minimize the clinical impasse that may result when therapist-patient blind spots overlap.
[Radionuclide cisternography: SPECT- and 3D-technique]. Radionuclide cisternography is indicated in the clinical work-up for hydrocephalus, when searching for CSF leaks, and when testing whether or not intracranial cystic lesions are communicating with the adjacent subarachnoid space. This paper demonstrates the feasibility and diagnostic value of SPECT and subsequent 3D surface rendering in addition to conventional rectilinear CSF imaging in eight patients. Planar images allowed the evaluation of CSF circulation and the detection of CSF fistula. They were advantageous in examinations 48 h after application of 111In-DTPA. SPECT scans, generated 4-24 h after tracer application, were superior in the delineation of basal cisterns, especially in early scans; this was helpful in patients with pooling due to CSF fistula and in cystic lesions near the skull base. A major drawback was the limited image quality of delayed scans, when the SPECT data were degraded by a low count rate. 3D surface rendering was easily feasible from SPECT data and yielded high quality images. The presentation of the spatial distribution of nuclide-contaminated CSF proved especially helpful in the area of the basal cisterns.
Asymmetric synthesis of tetrahydroquinolines through supramolecular organocatalysis. Functionalized chiral tetrahydroquinolines were synthesized through supramolecular organocatalysis using quinidine-NH-thiourea 3c/L-phenylalanine 4i followed by reductive amination from the simple substrates.
Combinatorial expression of different β-carotene hydroxylases and ketolases in Escherichia coli for increased astaxanthin production. In natural produced bacteria, β-carotene hydroxylase (CrtZ) and β-carotene ketolase (CrtW) convert β-carotene into astaxanthin. To increase astaxanthin production in heterologous strain, simple and effective strategies based on the co-expression of CrtZ and CrtW were applied in E. coli. First, nine artificial operons containing crtZ and crtW genes from different sources were constructed and, respectively, introduced into E. coli ZF237T, a β-carotene producing host. Among the nine resulting strains, five accumulated detectable amounts of astaxanthin ranging from 0.49 to 8.07 mg/L. Subsequently, the protein fusion CrtZ to CrtW using optimized peptide linkers further increased the astaxanthin production. Strains expressing fusion proteins with CrtZ rather than CrtW attached to the N-terminus accumulated much more astaxanthin. The astaxanthin production of the best strain ZF237T/CrtZAs-(GS)1-WBs was 127.6% and 40.2% higher than that of strains ZF237T/crtZAsWBs and ZF237T/crtZBsWPs, respectively. The strategies depicted here also will be useful for the heterologous production of other natural products.
Prenatal echographic diagnosis of laryngeal atresia as part of a multiple congenital anomalies (MCA) syndrome. Prenatal echographic diagnosis of laryngeal atresia as part of a multiple congenital anomalies (MCA) syndrome: In this report we present the prenatal second trimester echographic diagnosis of laryngeal atresia in a male fetus with multiple associated congenital anomalies: oesophageal atresia, crossed fused ectopy of the right kidney, mild cutaneous syndactyly of fingers III-V and toes II-III, distinct facial appearance and single umbilical artery. Bilateral voluminous echogenic lungs were the major echographic diagnostic sign. The associated multiple congenital anomalies were not diagnostic for a distinct, recognizable multiple malformation syndrome.
The crystal structure of staphylococcal superantigen-like protein 11 in complex with sialyl Lewis X reveals the mechanism for cell binding and immune inhibition. Staphylococcus aureus is a major pathogen that produces a family of 14 staphylococcal superantigen-like (SSL) proteins, which are structurally similar to superantigens but do not stimulate T cells. SSL11 is one member of the family that is found in all staphylococcal strains. Recombinant SSL11 bound to granulocytes and monocytes through a sialic acid-dependent mechanism and was rapidly internalized. SSL11 also bound to sialic acid-containing glycoproteins, such as the Fc receptor for IgA (FcalphaRI) and P-selectin glycoprotein ligand-1 (PSGL-1), and inhibited neutrophil attachment to a P-selectin-coated surface. Biosensor analysis of two SSL11 alleles binding to sialyl Lewis X [sLe(x)- Neu5Acalpha2-3Galbeta1-4(Fuc1-3)GlcNAc] coupled to bovine serum albumin gave dissociation constants of 0.7 and 7 mum respectively. Binding of SSL11 to a glycan array revealed specificity for glycans containing the trisaccharide sialyllactosamine (sLacNac - Neu5Acalpha2-3Galbeta1-4GlcNAc). A 1.6 A resolution crystal structure of SSL11 complexed with sLe(x) revealed a discrete binding site in the C-terminal beta-grasp domain, with predominant interactions with the sialic acid and galactose residues. A single amino acid mutation in the carbohydrate binding site abolished all SSL11 binding. Thus, SSL11 is a staphylococcal protein that targets myeloid cells by binding sialyllactosamine-containing glycoproteins.
Perceived support among Iranian mothers of children with learning disability. This qualitative phenomenological study explores the lived experiences of perceived support by Iranian mothers who have children with learning disability. Twelve open interviews with six mothers of learning-disabled children (7-12 years of age) were audiotape-recorded with participants' consent. The interviews were transcribed and data were analyzed using Van Manen methodology. Two major themes emerged from 138 thematic sentences. The mothers'experiences could be interpreted as a sense of being in the light or being in the shade of support, with variations for different participants. The results indicate a need for more specialized and individually adjusted support for mothers in Iran.
Ictal autoscopic phenomena and near death experiences: a study of five patients with ictal autoscopies. Autoscopic phenomena in general may-among other conditions-occur during epileptic seizures and near death experiences. We set the hypothesis that ictal autoscopic phenomena and near death experiences have a similar semiology as measured by the Near Death Experience Questionnaire. We also investigated whether patients with aura before temporal lobe seizures with or without autoscopic phenomena could be distinguished by this questionnaire. For these purposes, we examined five patients with ictal autoscopy and 12 patients with aura before temporal lobe seizures without ictal autoscopy as controls. We used a cut-off of 7 points or higher on the Near Death Experience Questionnaire for indicating the semiology of a near death experience and for distinguishing patients with ictal autoscopy from controls. This cut-off separated patients with ictal autoscopic phenomena from aura before temporal lobe seizures without autoscopy (p = 0.0002, two-sided, exact Fisher's Test; specificity: 100 % [CI95 % 77.9 and 100 %], sensitivity: 100 % [CI95 % 54.9 and 100 %]). Furthermore, all autoscopic patients (range 7-10) and none of the controls (range 0-5) had scores of 7 points or higher. Thus, the individual experiences during simple partial autoscopic seizures and near death experiences are similar, at least in some prominent aspects. These findings might be of particular interest for the pathophysiology of near death experiences, as all patients with ictal autoscopic phenomena had an epileptic dysfunction at the temporo-parietal junction or its neighboring regions. Therefore, a malfunction of this brain region might also be involved in near death experiences of other origins especially during states which could cause a near death experience and a cerebral excitability.
Strategies to control alkoxy radical-initiated relay cyclizations for the synthesis of oxygenated tetrahydrofuran motifs. Radical relay cyclizations initiated by alkoxy radicals are a powerful tool for the rapid construction of substituted tetrahydrofurans. The scope of these relay cyclizations has been dramatically increased with the development of two strategies that utilize an oxygen atom in the substrate to accelerate the desired hydrogen atom transfer (HAT) over competing pathways. This has enabled a chemoselective 1,6-HAT over a competing 1,5-HAT. Furthermore, this allows for a chemoselective 1,5-HAT over competing direct cyclizations and β-fragmentations. Oxygen atom incorporation leads to a general increase in cyclization diastereoselectivity over carbon analogues. This chemoselective relay cyclization strategy was utilized in the improved synthesis of the tetrahydrofuran fragment in (−)-amphidinolide K.
Damage to Reissner's membrane in the guinea-pig cochlea following acute atoxyl intoxication. The ototoxic effects of the arsenic compound atoxyl has been earlier demonstrated by Anniko & Wersäll (1975) in the stria vascularis of the guinea pig cochlea. The aim of the present investigation was to study the morphological degeneration at the ultrastructural level after damaging the Reissner's membrane experimentally. In acute atoxyl intoxication the first signs of degeneration appear after approximately 12 hours. After 24 hours, the membrane may be markedly degenerated. Both the epithelial and mesothelial cells become vacuolized, the mitochondria lose their internal structure and become swollen, and lipid granules are found in the cytoplasm. Mesothelial cells are damaged to a lesser extent than the epithelial cells in the same specimen.
Perovskite-Ion Beam Interactions: Toward Controllable Light Emission and Lasing. Achieving controllable coherent and incoherent light sources is crucial to meet the requests of the constantly developing integrated optics, which, however, remains challenging for the existing semiconductor materials and techniques. All-inorganic lead halide perovskites (ILHPs) are emerging as the promising semiconductors, featuring the defect-tolerant nature and tunable band gap. Herein, an experimental design, based on the interaction between ILHPs and energetic ions, for achieving controllable light emitters and microlasers is reported. We reveal that the photoluminescence intensity from ILHPs can be modulated by more than 1 order of magnitude upon low-dose gallium ion (∼1015 ions/cm2) irradiation, which can be attributed to the generation of vacancy/interstitial defects, metallic lead, and crystal-to-amorphization transition. Such ion-dependent light emission can be exploited to make the colorful photopatterns and in situ tailor the lasing behavior from CsPbBr3 microplates. Further, a strong sputtering effect is observed with the increase of the ion dose (∼1017 ions/cm2), which enables the top-down fabrication of microlasers based on ILHPs. These findings represent a significant step toward controllable light sources leveraging on perovskite-ion interactions.

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