A critical issue. Intensive insulin treatment and macrovascular disease.
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Cardiovascular Diseases↗
Biomedical subjects
S Levin
Publications and source records attributed to S Levin.
Predictive value of response to treatment of T-lymphocyte subpopulations in idiopathic pulmonary fibrosis.
T-cell types are important in maintaining immune homeostasis in the lung and their imbalance may be associated with several diseases. We examined the relationship between bronchoalveolar lavage (BAL) T-cell subset profiles and the clinical course of 46 patients with idiopathic pulmonary fibrosis (IPF). A flow cytometry cell sorter (FACS) was used to analyse the T-cell subsets. Pulmonary function tests (PFT) were performed at baseline and 6-12 months later. Patients were divided into two groups according to their CD4/CD8 ratio: CD4/CD8 >1 (group 1, n=21); and CD4/CD8 <1 (group 2, n=25). A lower percentage of lymphocytes, a higher percentage of CD8/S6F1 cells (cytotoxic T-lymphocytes) and a higher percentage of neutrophils were found in the BAL in group 2 compared to group 1 (11+/-7.5% versus 19+/-13.2%; p=0.024 and 29.8+/-17.6% versus 13.3+/-6.9%; p=0.068, respectively for lymphocytes and cytotoxic T-lymphocytes; and 8+/-11% versus 29+/-27%; p=0.003 for neutrophils). Inversely, in the peripheral blood, the distribution of CD8/S6F1 cells was lower in group 1 than in group 2 (8.3+/-6.9% versus 33.4+/-16.5%; p=0.0048). The patients were followed over a period of 1 yr in order to test whether those findings could determine efficacy of therapy. The baseline transfer factor of the lung for carbon monoxide (TL,CO) capacity in group 1 and group 2 was 59+/-22% and 51+/-21%, respectively (p=0.29), but only in group 1 was the TL,CO capacity improved significantly in response to steroids treatment after 6-12 months. IPF patients with a higher percentage of lymphocytes, a lower percentage of neutrophils, CD4/CD8 >1 and a low percentage of CD8/S6F1 may have a more benign course of disease. These parameters may identify an early stage of reversible disease responsive to therapy. We conclude that these measurements may be a useful tool in monitoring response to treatment in patients with idiopathic pulmonary fibrosis.
Bronchoalveolar Lavage Fluid↗
Cell membrane fluctuations are regulated by medium macroviscosity: evidence for a metabolic driving force.
Extracellular fluid macroviscosity (EFM), modified by macromolecular cosolvents as occurs in body fluids, has been shown to affect cell membrane protein activities but not isolated proteins. In search for the mechanism of this phenomenon, we examined the effect of EFM on mechanical fluctuations of the cell membrane of human erythrocytes. The macroviscosity of the external medium was varied by adding to it various macromolecules [dextrans (70, 500, and 2,000 kDa), polyethylene glycol (20 kDa), and carboxymethyl-cellulose (100 kDa)], which differ in size, chemical nature, and in their capacity to increase fluid viscosity. The parameters of cell membrane fluctuations (maximal amplitude and half-width of amplitude distribution) were diminished with the elevation of solvent macroviscosity, regardless of the cosolvent used to increase EFM. Because thermally driven membrane fluctuations cannot be damped by elevation of EFM, the existence of a metabolic driving force is suggested. This is supported by the finding that in ATP-depleted red blood cells elevation of EMF did not affect cell membrane fluctuations. This study demonstrates that (i) EFM is a regulator of membrane dynamics, providing a possible mechanism by which EFM affects cell membrane activities; and (ii) cell membrane fluctuations are driven by a metabolic driving force in addition to the thermal one.
Adenosine Triphosphate↗
Allelopathy in Spatially Distributed Populations
In a homogeneously mixing population of E. coli, colicin-producing and colicin-sensitive strategies both may be evolutionarily stable for certain parameter ranges, with the outcome of competition determined by initial conditions. In contrast, in a spatially-structured population, there is a unique ESS for any given set of parameters; the outcome is determined by how effective allelopathy is in relation to its costs. Furthermore, in a spatially-structured environment, a dynamic equilibrium may be sustained among a colicin-sensitive type, a high colicin-producing type, and a "cheater" that expends less on colicin production but is resistant. Copyright 1997 Academic Press Limited
Journal Article↗
The glutathione S-transferase theta and mu deletion polymorphisms in asbestosis.
The glutathione S-transferases (GSTs) catalyze the conjugation of a wide variety of reactive, electrophilic substrates with glutathione, facilitating their excretion. There is also evidence that GSTs can catalyze glutathione conjugation of lipid radicals as well as act in the generation of leukotriene inflammatory mediators. Studying construction carpenters screened for the presence of asbestos-related diseases, we have previously reported that the constitutional deletion of GSTM1 (the gene coding for glutathione S-transferase class mu) is associated with an increased risk of asbestos-related interstitial lung disease, measured radiographically. In the current work, we have further studied this group of workers, investigating the distribution of a novel deletion polymorphism in the newly described GSTT1 gene, that codes for the GST class theta enzyme. A total of 666 carpenters were studied, and 124 (19%) had the deleted genotype. There was no association between the GSTT1 deletion and the radiographic diagnosis of either asbestos-related pleural or parenchymal disease. The GSTM1 deletion remained associated with the presence of x-ray evidence of asbestosis after adjustment for GSTT1 genotype. The GSTM1 null genotype was also associated with a family history of any malignancy. These data suggest that the association of polymorphic GSTs with asbestos-induced radiographic changes is specific for substrates of the GST class mu.
Adult↗
Late recurrences and the necessity for long-term follow-up in corneal and conjunctival intraepithelial neoplasia.
PURPOSE: The purpose of the study was to elucidate the natural history of corneal-conjunctival intraepithelial neoplasia (CIN) and suggest treatment and follow-up guidelines. METHODS: The records of all histologically proven cases of CIN at the Royal Victorian Eye and Ear Hospital between 1979 and 1994 were reviewed. RESULTS: Seventy-nine eyes of 76 patients had a pathologic diagnosis of CIN and were observed for up to 15 years. The lesion recurred in 31 eyes (39%) overall. There was no statistical difference shown in the likelihood of recurrence based on histologic classification. Complete excision was attempted in each case. In 18 eyes, dysplastic cells were evident at the excision margin. Ten (56%) of these tumors recurred, compared to a 33% recurrence rate in completely excised lesions. The time to the first recurrence ranged from 33.0 days to 11.5 years between the first and second surgeries, with 11 lesions recurring after more than 4 years. Incompletely excised lesions reappeared more rapidly (average, 2.5 years) than did those with clear surgical margins (average, 3.8 years). Seven cases progressed to invasive squamous cell carcinoma and four cases led to blindness or removal of the eye. CONCLUSIONS: This study suggests that excision margin at the time of surgery is the most important factor in predicting recurrence. The slow growth of the recurrent lesions combined with the ever-present malignant potential leads the authors to suggest that all patients with a history of CIN warrant annual follow-up for the remainder of their lives.
Adult↗
Clinical predictors of mortality from asbestosis in the North American Insulator Cohort, 1981 to 1991.
Recorded mortality from asbestosis has increased markedly in the United States in recent decades, from 0.49 to 3.06 per million persons between 1970 and 1990. Although asbestosis is generally considered to be a slowly progressive disorder, little is known about how clinical and exposure parameters among individuals with asbestosis quantitatively predict subsequent risk of death from asbestosis. We followed 2,609 insulators from the North American insulator cohort 10 yr to determine cause of death and to relate clinical findings to risk of death. This group had undergone clinical and radiologic examination between 1981 and 1983 in 19 cities in the United States. Seventy-four (11.0%) of 674 deaths during the subsequent 10 yr were due to asbestosis, according to the best clinical and radiologic evidence available at the time of death. The 10 yr risk of death (expressed as a percentage) due to asbestosis rose sharply with increasing interstitial fibrosis as identified on the baseline chest X-ray, from 0.9% to 2.4%, 10.8%, and 35.4% for International Labor Office (ILO) profusion categories 0, 1, 2, and 3, respectively. Dyspnea, a low FVC, and/or physical examination findings typical of interstitial fibrosis (rales, clubbing, or cyanosis) raised the risk of subsequent death from asbestosis by 2- to 6-fold. The effect of cigarette smoking on risk of death from asbestosis was small and disappeared after adjustment for ILO profusion score.
Analysis of Variance↗
Resolution of enantiomers of uridine analogs, potential antiviral agents.
Racemic mixtures of 5-substituted carbocyclic analogs of uracil nucleosides, 2"- and 3"-furyl, 2"- and 3"-thienyl and 2"-selenienyl, potentially anti-viral agents, were resolved using amylose tris(3,5-dimethylphenyl)carbamate as the stationary phase. The mobile phase was n-hexane with ethanol or 2-propanol. Effects of some structural features on the extent of discrimination between the enantiomers were examined through the selectivity and resolution factors as well as the elution order. The structural features were as follows; the type and position of the hetero-atom O, S or Se, in the cyclopentadienyl substituent 5 of the uracil and hydroxymethyl vs. acetoxymethyl groups on the cyclopentene moiety of the uridine analogs. It appeared that effects of the structural features on the separation were solvent dependent, with some very unusual solvent effects. For example, average retention, which did not follow the polarity of the mobile phase modifiers, was much higher when ethanol was used compared to 2-propanol. Also, the elution order of the two enantiomers of several pairs was reversed when ethanol was changed to 2-propanol. In general, ethanol affected higher selectivity and resolution of all the enantiomeric pairs.
Antiviral Agents↗
Bacteriologic and clinical applications of a new extended-spectrum parenteral cephalosporin.
Although third-generation cephalosporins have been considered the backbone of antibiotic therapy for the treatment of many kinds of serious infections, including those in hospitalized patients, lack of activity against some important pathogens still exists among currently available drugs. In addition, increasing accounts of antibiotic resistance, particularly in the hospital environment, are of deep concern and have thus led to the need for the development of newer antimicrobial agents. Cefepime is a now parenteral cephalosporin with an extended spectrum of antibacterial activity that includes both aerobic gram-negative and gram-positive bacteria. It is also active against many gram-negative organisms resistant to ceftriaxone and cefotaxime, as well as many strains of Enterobacter and Citrobacter resistant to ceftazidime. Cefepime appears to be less likely to select out resistant organisms, and it may be less likely to change hospital flora than currently available antimicrobials. Cefepime has been shown to be very well tolerated and effective in the treatment of a variety of infections including moderate-to-severe pneumonia (including cases associated with concurrent bacteremia), complicated and uncomplicated urinary tract infections (also including cases associated with concurrent bacteremia), and skin and skin-structure infections. Clinical response rates are > or = 75% for most infections and have been comparable to ceftazidime in comparative trials. In addition, pretreatment susceptibility testing indicates that >94% of organisms isolated in patients enrolled in clinical trials were susceptible to cefepime.
Bacteria↗
Cardiac tamponade without pericardial effusion after blunt chest trauma.
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Cardiac Tamponade↗
Retreatment after excimer laser photorefractive keratectomy. The Melbourne Excimer Laser Group.
PURPOSE: To determine the risk factors for undercorrection of myopia after photorefractive keratectomy and to evaluate the efficacy and safety of retreatment. METHODS: A VISX Twenty/Twenty excimer laser was used to treat myopia and myopic astigmatism of up to -15.00 diopters (spherical equivalent) at the corneal plane. Retreatments were performed primarily for undercorrection with or without coexistent corneal haze or abnormalities on videokeratoscopy. Not every patient who was undercorrected requested retreatment. RESULTS: Of 645 eyes (440 patients) followed up for more than 12 months, 58 eyes (9%) required retreatment. The retreatment rate increased with increasing myopia: 17 (5%) eyes with myopia of less than -5.00 diopters, 30 (13%) eyes with myopia of -5.01 to -10.00 diopters, and 11 (19%) eyes with myopia of greater than -10.00 diopters required a second procedure. A higher retreatment rate was observed after astigmatic corrections than after spherical corrections. Corneal haze after retreatment was no greater than that observed after initial procedures. Twelve months after primary procedures, 378 (75%) of 504 eyes were within 1.00 diopter of emmetropia, whereas 27 (69%) of 39 eyes attained this result after retreatment. A total of 383 (76%) of 504 eyes attained uncorrected visual acuity of 20/40 or better after primary procedures, compared with 25 (64%) of 39 eyes after retreatment. CONCLUSIONS: The risk of undercorrection requiring retreatment after photorefractive keratectomy increases with the magnitude of the primary treatment. Although less successful than initial procedures, retreatment appears to enhance the results of photorefractive keratectomy.
Adult↗
Safeguards in embryo donation.
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Embryo, Mammalian↗
Fever in the solid organ transplant patient.
Fever is common in the solid organ transplant patient and may be produced by a variety of processes. The approach to the febrile transplant patient must include an extensive search for infection, which may be aided by considering the organ transplanted, time after transplantation, and the patient's immunosuppressed state. In addition, a number of noninfectious causes of fever exist in this population, including allograft rejection, drug fever, and thromboembolic disease. A review of the pathogens commonly noted in posttransplant patients is presented, emphasizing risk factors for disease, typical time of presentation, and particular organ groups affected. In addition, the authors review the noninfectious causes of fever in the solid organ transplant patient.
Bacterial Infections↗
F-actin sequesters elongation factor 1alpha from interaction with aminoacyl-tRNA in a pH-dependent reaction.
The machinery of eukaryotic protein synthesis is found in association with the actin cytoskeleton. A major component of this translational apparatus, which is involved in the shuttling of aa-tRNA, is the actin-binding protein elongation factor 1alpha (EF-1alpha). To investigate the consequences for translation of the interaction of EF-1alpha with F-actin, we have studied the effect of F-actin on the ability of EF-1alpha to bind to aa-tRNA. We demonstrate that binding of EF-1alpha:GTP to aa-tRNA is not pH sensitive with a constant binding affinity of approximately 0.2 microM over the physiological range of pH. However, the sharp pH dependence of binding of EF-1alpha to F-actin is sufficient to shift the binding of EF-1alpha from F-actin to aa-tRNA as pH increases. The ability of EF-1alpha to bind either F-actin or aa-tRNA in competition binding experiments is also consistent with the observation that EF-1alpha's binding to F-actin and aa-tRNA is mutually exclusive. Two pH-sensitive actin-binding sequences in EF-1alpha are identified and are predicted to overlap with the aa-tRNA-binding sites. Our results suggest that pH-regulated recruitment and release of EF-1alpha from actin filaments in vivo will supply a high local concentration of EF-1alpha to facilitate polypeptide elongation by the F-actin-associated translational apparatus.
Actins↗
Modified thioglycolate medium: a simple and reliable means for detection of Trichomonas vaginalis.
Despite the declining rate of sexually transmitted diseases in developed countries, trichomoniasis is still one of the most common venereal infections. While diagnosis of this condition is commonly based on the microscopic wet-mount method, culture remains the most accurate single procedure for detecting the presence of Trichomonas vaginalis in clinical samples. In the present study, the efficacy of a modified formula of the commonly available thioglycolate medium was compared with that of the standard Diamond's medium for detection of T. vaginalis in samples from 176 women with vaginal symptoms. Thioglycolate medium supplemented with yeast extract, horse serum, and antimicrobial agents was as reliable as Diamond's medium for detection of T. vaginalis in vaginal fluid samples. Modified thioglycolate medium may be used as a readily available, low-cost substitute for the standard medium for culturing T. vaginalis.
Animals↗
Treatment of Rasmussen's syndrome with ganciclovir.
Since cytomegalovirus (CMV) has been implicated in the pathogenesis of Rasmussen's syndrome, we treated four patients with ganciclovir, a potent anti-CMV drug. A 7-year-old girl with seizures escalating to 60/day over 3 months despite triple antiepileptic drug therapy became seizure-free 5 days after initiation of treatment with no recurrence at 1.5 years follow-up. Focal neurologic signs, cognitive function, and the EEG returned to normal. Two patients treated 34 and 72 months after disease onset in association with epilepsy surgery had a reduction in seizures and one had no response. CMV genome was detected in the brains of two of the three patients in whom it was assessed. The response to antiviral therapy supports a viral etiology for chronic encephalitis of Rasmussen. If the disease is suspected, treatment with ganciclovir should be considered as early as possible.
Adult↗
Evaluations of retinopathy in the VA Cooperative Study on Glycemic Control and Complications in Type II Diabetes (VA CSDM). A feasibility study.
OBJECTIVE: The main goal of the study of 153 male veterans was to determine whether a statistically and clinically significant difference in HbA1c could be achieved between a standard therapy and an intensively treated group of patients with type II diabetes. A second major goal was to assess the feasibility of collecting reliable high-quality endpoint data, including microvascular and macrovascular events. Retinopathy was defined as a key microvascular endpoint. RESEARCH DESIGN AND METHODS: This was a randomized prospective trial of 153 men between the ages of 40 and 69 years, with type II diabetes for 15 years or less. Of the patients, 78 were assigned to the standard therapy arm and 75 to the intensive therapy arm. The goal of standard therapy was good general medical care and well-being and avoiding excessive hyperglycemia, glycosuria, ketonuria, or hypoglycemia. This was generally accomplished with one shot of insulin per day. The goal of intensive therapy was to obtain an HbA1c within two standard deviations of the mean of nondiabetic subjects (4.0-6.1%). This was obtained by a four-step management technique, with patients moving to the next step only if operational goals were not met. The steps were as follows: step 1: evening intermediate or long-acting insulin only; step 2: evening insulin with daytime glipizide; step 3: insulin, twice a day, no glipizide; and step 4: more than two injections of insulin, no glipizide. Retinopathy was assessed at baseline, 12, and 24 months by seven-field stereo fundus photography done at each of the five participating VA medical centers and read at the Central Reading Center at the Department of Ophthalmology, University of Wisconsin Medical School, Madison. Visual acuity was determined by ophthalmologists at each of the participating hospitals. RESULTS: After the 6th month of the 24-month study, an average HbA1c of approximately 7.1% in the intensively treated group was sustained for the full study and was significantly lower than that seen in the standard group (9.2%, P < 0.001). Compliance in obtaining fundus photographs was excellent. Near normalization of glycemia did not cause transient worsening of retinal morphology nor did it prevent the onset or delay the progression of retinopathy. There was no effect on visual acuity. CONCLUSIONS: 1) A glycemic control intervention study in people with type II diabetes is feasible and safe; 2) intensive control did not cause transient deterioration of retinopathy; and 3) although no improvement was seen in retinopathy, the follow-up was 24 months, an interval shorter than the 3 years or more of intensive therapy before improvement is seen in type 1 diabetic studies. This does not rule out the possibility that longer periods of intensive therapy would have improved retinopathy. A full-scale intervention trial in type II diabetes is needed to resolve this issue.
Adult↗