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Biomedical subjects

S Shapiro

Publications and source records attributed to S Shapiro.

At least 127 records · Page 7Linked to original sources
PubMed1997

Low drug attributability of aplastic anemia in Thailand. The Aplastic Anemia Study Group.

From 1989 to 1994, a population-based, case-control study of aplastic anemia was conducted in Thailand, including the regions of Bangkok, Khonkaen in the northeast, and Songkla in the south. An annual incidence in Bangkok of 3.7 cases per million population, about twice as high as in Western countries, has been reported. To evaluate the etiologic role of drugs, 253 subjects were compared with 1,174 hospital controls. With multivariate adjustment for confounding, a significant association was identified for exposure 2 to 6 months before admission to thiazide diuretics (relative risk estimate 7.7; 1.5 to 40). There were crude associations with sulfonamides (relative risk estimate, 7.9; P = 0.004) and mebendazole (6.3; P = 0.03) (there were insufficient data for multivariate adjustment). Excess risks for the three drugs were in the range of 9 to 12 cases per million users. There was no significant association with chloramphenicol, although the multivariate relative-risk estimate was elevated (2.7; 0.7 to 10). Other drugs that have been reported to increase the risk of aplastic anemia, such as nonsteroidal anti-inflammatory drugs and anticonvulsants, were not commonly used. There were no associations with commonly used drugs, including benzodiazepines, antihistamines, oral contraceptives, and herbal preparations. For all associated drugs, the overall etiologic fraction (the proportion of cases attributable to an exposure) was 5%, compared with 25% in Europe and Israel. Drugs are uncommon causes of aplastic anemia in Thailand, and their use does not explain the relatively high incidence of the disease in that country.

Adolescent↗
PubMed1997

Three different GB virus C/hepatitis G virus genotypes. Phylogenetic analysis and a genotyping assay based on restriction fragment length polymorphism.

The 5'-untranslated region (5'-UTR) sequences of 33 GB virus C/hepatitis G virus (GBV-C/HGV) obtained from different geographic areas were determined through reverse-transcription polymerase chain reaction and dideoxy chain termination sequencing, the alignment of sequences, the estimation of the number of nucleotide substitution per site, and construction of phylogenetic trees. The 5'-UTR of GBV-HGV was found to be heterogeneous, with 70.9-99.5% homology. Three distinct phylogenetic branches were observed consistently in all phylogenetic trees. GBV-C is the prototype for one, HGV for another, and there is a new branch which consisted of GBV-C/HGV isolates from Asia. Genotype-specific restriction sites for the restriction enzymes, ScrFI and BsmFI, were identified, and a simple restriction fragment polymorphism analysis was developed for genotyping. These data provide evidence that GBV-C/HGV consists of three different genotypes. Our simple genotyping assay will also provide a tool for epidemiological studies of GBV-C/HGV infection.

Base Sequence↗
PubMed1997

Interferon-beta and -gamma, but not tumor necrosis factor-alpha, demonstrate immunoregulatory effects on carcinoma cell lines infected with human papillomavirus.

BACKGROUND: Mechanisms whereby cells infected with human papillomavirus (HPV) escape immune surveillance, ultimately leading to invasive cervical carcinoma, may involve changes in local cytokine production, loss of responsiveness to cytokines, and alterations in the expression of immune-regulatory molecules such as histocompatibility-related leukocyte antigen (HLA) Class 1 and 2 and ICAM-I. This study examined the separate and combined effects of immune-activating cytokines, interferon (IFN)-gamma, IFN-beta, and tumor necrosis factor (TNF)-alpha, on the expression of these molecules. METHODS: Membrane protein expression and cellular mRNA levels were analyzed in cervical carcinoma-derived cell lines, SiHa and CaSki (with low and high HPV16 copy number, respectively), after exposure to cytokines. RESULTS: Both cell lines demonstrated constitutive expression of HLA Class 1 but not HLA Class 2 membrane antigens. IFN-gamma and -beta induced changes in Class 1 mRNA levels but not in membrane molecule expression. IFN-gamma induced dose-dependent expression of Class 2 membrane and mRNA molecules in both cell lines (more pronounced in SiHa than in CaSki cells), which was antagonized by IFN-beta. Constitutive ICAM-I membrane expression was observed only on CaSki cells, although ICAM-I mRNA was expressed in both cell lines. IFN-gamma up-regulated the membrane expression of this molecule, whereas IFN-beta led to its suppression. Differential modulation of ICAM-I mRNA was observed in both cell lines. A lack of response to TNF-alpha was observed throughout the experiments. CONCLUSIONS: The findings of this study point to possible mechanisms leading to suppression of local immune response in the pathogenesis of HPV-associated neoplasia. They also emphasize the complexity of developing an efficient cytokine therapy for patients with premalignant cervical disease.

Adjuvants, Immunologic↗
PubMed1997

Association of seropositivity for hepatitis viruses and aplastic anemia in Thailand.

Aplastic anemia is more common in the Orient than in western countries, with an incidence in Thailand that is 2- to 3-fold higher than in Europe. Aplastic anemia after hepatitis is a well characterized clinical entity, and clinical hepatitis is also prevalent in the Far East. We performed a prospective case-control study to determine risk factors for aplastic anemia in Bangkok and two rural regions during 1989 to 1994. A total of 375 cases were identified, along with 1,174 hospital controls matched for age and sex. Historical data were collected by trained interviewers. Sera from a subset of cases (N = 177) and controls (N = 183) were tested for antibodies to hepatitis viruses A, B, and C and hepatitis B surface antigen. There was no evidence of association of aplastic anemia with hepatitis B or hepatitis C. Previous exposure to hepatitis A, as determined by immunoglobulin G (IgG) seropositivity, was significantly associated with aplastic anemia: the relative risk adjusted for confounding was 2.9 (95% confidence interval 1.2-6.7). The same association also existed for persons under age 25 years, in whom the prevalence of hepatitis A IgG was lower than in the total population. However, no patients showed evidence of recent infection with hepatitis A (immunoglobulin M [IgM] seropositivity). These results indicate that exposure to a hepatitis virus is a risk indicator for aplastic anemia in Thailand, and while itself unlikely to be etiologic, hepatitis A may be a surrogate marker for another enteric microbial agent.

Adult↗
PubMed1997

Induced and spontaneous abortion in relation to risk of breast cancer (United States).

The relation of induced and spontaneous abortion to the risk of breast cancer is evaluated in a hospital-based case-control interview study conducted in three cities in the United States from 1985 through 1995. Cases were 1,803 women aged 25 to 64 years with newly diagnosed invasive breast cancer; controls were 4,182 women of the same ages admitted for conditions unrelated to reproductive factors. Other breast cancer risk-factors were controlled through multiple logistic regression. The reference for all analyses was women who had never had an abortion, either induced or spontaneous. Among parous women, the relative risk (RR) estimate was 1.1 (95 percent confidence interval [CI] = 0.9-1.5) for induced abortion overall, 1.0 (CI = 0.7-1.4) for abortion before the first birth, and 1.3 (CI = 1.0-1.8) for abortion after at least one birth. Among nulliparous women, the relative risk estimate for induced abortion was 1.3 (CI = 0.9-1.9). There was no trend of increased risk with number of abortions, nor was there consistent evidence of an increased risk in any particular subgroup. Spontaneous abortion was not associated with increased risk of breast cancer, either among nulliparous women or among parous women. These findings provide little support for the hypothesis that induced abortion increases breast cancer risk overall or in particular subgroups.

Abortion, Induced↗
PubMed1997

Urokinase-generated plasmin activates matrix metalloproteinases during aneurysm formation.

The molecular mechanisms predisposing to atherosclerotic aneurysm formation remain undefined. Nevertheless, rupture of aortic aneurysms is a major cause of death in Western societies, with few available treatments and poor long-term prognosis. Indirect evidence suggests that matrix metalloproteinases (MMPs) and plasminogen activators (PAs) are involved in its pathogenesis. MMPs are secreted as inactive zymogens (pro-MMPs), requiring activation in the extracellular compartment. Plasmin, generated from the zymogen plasminogen by tissue-type plasminogen activator (t-PA) or urokinase-type plasminogen activator (u-PA; refs 14,15), has been proposed as a possible activator in vitro, but evidence for such a role in vivo is lacking. Analysis of atherosclerotic aorta in mice with a deficiency of apoliprotein E (Apoe-/-; ref. 18), singly or combined with a deficiency of t-PA (Apoe-/-:Plat-/-) or of u-PA (Apoe-/-:Plau-/-; ref. 19), indicated that deficiency of u-PA protected against media destruction and aneurysm formation, probably by means of reduced plasmin-dependent activation of pro-MMPs. This genetic evidence suggests that plasmin is a pathophysiologically significant activator of pro-MMPs in vivo and may have implications for the design of therapeutic strategies to prevent aortic-wall destruction by controlling Plau gene function.

Animals↗
PubMed1997

Do trans fatty acids increase the risk of coronary artery disease? A critique of the epidemiologic evidence.

On the basis of metabolic and epidemiologic data it has been claimed that trans fatty acid intake causes coronary artery disease (CAD), with > or = 30,000 deaths/y in the United States and a considerably greater number of nonfatal cases. The metabolic evidence is still controversial; the epidemiologic evidence is reviewed here. In most studies the likelihood that CAD "caused" margarine use, rather than the reverse, was not excluded. Uncontrolled confounding (particularly confounding by indication) was ubiquitous. Selection bias conditional on margarine use was common. The projection of 30,000 deaths/y is not justified. If the metabolic evidence, when fully evaluated, is deemed to be suggestive, then the question of whether trans fatty acids are indeed harmful to human populations will be resolved only by means of a randomized controlled trial.

Coronary Disease↗
PubMed1997

Use of household pesticides and the risk of aplastic anaemia in Thailand. The Aplastic Anemia Study Group.

BACKGROUND: Aplastic anaemia is a severe blood dyscrasia that is more common in Thailand than in Western countries. Its a etiology remains poorly understood. METHODS: A case-control study was conducted in Bangkok and two rural regions of Thailand. The effect of household pesticides was evaluated among 253 incident cases of aplastic anaemia and 1174 hospital controls. RESULTS: A total of 54% of the cases and 61% of the controls were exposed 1-6 months previously. For most individual household pesticides and for groups classified according to chemical type (organophosphates, pyrethrins, and organochlorines), the relative risk (RR) estimates approximated 1.0; upper 95% confidence limits were below 2.0 for many comparisons. A significant association was observed for exposure to combination products containing dichlorvos and propoxur, with an overall RR estimate of 1.7 (95% confidence interval [CI]: 1.1-2.6); the estimate for regular use was 1.6 (95% CI: 0.9-2.9). CONCLUSIONS: The absence of a higher risk for the regular use of dichlorvos/propoxur reduces the credibility of the apparent association, which could well have been an artefact of multiple comparisons. We conclude that most household pesticides used in Thailand do not appear to increase the risk of aplastic anaemia.

Adult↗
PubMed1997

Periodic screening for breast cancer: the HIP Randomized Controlled Trial. Health Insurance Plan.

This paper summarizes the findings of the first breast cancer screening trial, which was initiated in December 1963 to explore the efficacy of screening. Women aged 40-64 years were selected from enrollees in the Health Insurance Plan (HIP) of Greater New York and were randomly assigned to study and control groups. Study group women were invited for screening, an initial examination, and three annual reexaminations. Screening consisted of film mammography (cephalocaudal and lateral views of each breast) and clinical examination of breasts. Breast cancer and mortality from breast cancer were examined by treatment group (study vs. control) and by entry-age subgroup. By the end of 18 years from entry, the study group had about a 25% lower breast cancer mortality among women aged 40-49 and 50-59 at time of entry than did the control group. However, to a large extent the difference among the 40-49-year-olds occurred in the subgroup with breast cancer diagnosed after these women had passed their 50th birthday, and utility of screening women in their forties is questionable.

Adult↗
PubMed1997

Radiation therapy for intrathoracic recurrence of non-small cell lung cancer.

Fifty-two of 2,315 patients (2.4%) with non-small cell lung cancer (NSLC) treated with radiation therapy at the Mallinckrodt Institute of Radiology and St. Luke's Hospital between 1975 and 1988 presented with local recurrence after definitive surgery. No patient received radiation therapy after surgery as part of initial treatment and none had evidence of distant metastases at the time of local recurrence. The median time to first recurrence was 14 months. At recurrence, patients presented with disease in the bronchial stump (eight patients), ipsilateral lung parenchyma (10), chest wall (six), regional lymph nodes (five), or some combination thereof (23). Sixty-five percent of patients had histologic evidence of recurrence. Radiation therapy consisted of > 5,000 cGy in conventional fractionation to areas of gross disease in 35 of 52 patients. Of 15 patients receiving > 6,000 cGy, 13 had a favorable--complete (CR) or partial (PR) response--tumor response to radiation therapy. Among these patients, local control was achieved in 70% of patients with marginal recurrences (i.e., stump, parenchyma, or chest wall) and in 50% with nodal recurrences. The median survival after radiation therapy for all patients was 8.5 months. The best indicators for long-term survival were the interval from initial surgery to first recurrence and tumor response to radiation therapy.

Carcinoma, Non-Small-Cell Lung↗
PubMed1997

Postoperative radiation therapy in non-small cell lung cancer.

One hundred seventy-three patients with the diagnosis of non-small cell lung cancer (NSCLC) were treated with surgery and postoperative radiation therapy (RT) at the Radiation Oncology Center, Washington University, St. Louis. All patients had been retrospectively reviewed and restaged according to the new American Joint Committee (AJC) staging classification. Seventeen patients were stage I, 69 were stage II, 74 were stage IIIA, and 2 patients were stage IIIB. In 11 patients, accurate staging could not be determined. Indications for postoperative RT were positive surgical margins (32 patients), metastatic hilar nodes (78 patients), and metastatic mediastinal nodes (62 patients). Locoregional control for stages I, II, and IIIA was 85, 75, and 85%, respectively. Five-year actuarial survival was 35% for stage I and 20% for stages II and IIIA. Patients with N0 disease (positive margins) had 5-year survival of 25%, whereas patients with N1 and N2 disease had a 5-year survival of 20%.

Adenocarcinoma↗
PubMed1997

Composite pleomorphic xanthoastrocytoma and ganglioglioma: report of four cases and review of the literature.

Composite pleomorphic xanthoastrocytoma (PXA)-ganglioglioma (GG) is a rare recently described entity. Only three examples have been documented, one of which showed evidence of malignant transformation. We report an additional four cases and update the literature. With the exception of an 82-year-old man, all patients have been under 30 years of age. The temporal lobe was involved in three cases and cerebellum in another three. Radiologic features were those common to PXA and GG. Histologically, all were "collision tumors" composed of abutting, although spatially distinct, PXA and GG components. In two cases, the second element was only recognized at reexcision or recurrence. Histologic anaplasia, always in the PXA component, was evident as brisk mitotic activity and/or necrosis in five cases. Of the seven patients, one died of disease 17 years after the onset of seizures and after multiple recurrences, the last of which largely resembled glioblastoma. We conclude that the composite PXA-GG is a rare neoplasm that shares many features of its individual components. In addition to its temporal lobe predilection, the cerebellum is frequently affected. As when it occurs in isolation, the PXA component of composite PXA-GG possesses the potential for malignant transformation.

Adolescent↗
PubMed1997

Neurotransmission by neurons that use serotonin, noradrenaline, glutamate, glycine, and gamma-aminobutyric acid in the normal and injured spinal cord.

OBJECTIVE: The science of neurotransmission in the normal and injured spinal cord has grown. This is a review of neurotransmission using serotonin, noradrenaline, glutamate, glycine, and gamma-aminobutyric acid. METHODS: The literature on spinal cord neurotransmission and changes that occur with trauma are reviewed. CONCLUSION: Serotonergic and noradrenergic bulbospinal tracts influence interneurons and motor neurons via postsynaptic inhibition. Colocalization of serotonin and thyrotropin-releasing hormone occur in bulbospinal tracts, and reduction in uptake and thyrotropin-releasing hormone immunoreactivity quantitates the degree of injury in chronic spinal cord injury (SCI). Glutamate functions as an excitatory transmitter of some dorsal root afferent neurons and interneurons modulating nociceptive and motor neurons via at least five different receptors. Reactive synaptogenesis occurs after SCI, leading to an increase in the number of excitatory glutamatergic synapses below the level of SCI. gamma-Aminobutyric acid is an inhibitory transmitter of spinal interneurons that functions both pre- and postsynaptically. After SCI, a reduction occurs in the number of inhibitory synapses related to gamma-aminobutyric acid. Glycine is an inhibitory neurotransmitter that functions postsynaptically and also modulates the N-methyl-D-aspartate receptor. After SCI, a reduction in glycine adds to the loss of local inhibition below the SCI.

Animals↗
PubMed1997

Methods for precise sizing, automated binning of alleles, and reduction of error rates in large-scale genotyping using fluorescently labeled dinucleotide markers. FUSION (Finland-U.S. Investigation of NIDDM Genetics) Study Group.

Large-scale genotyping is required to generate dense identity-by-descent maps to map genes for human complex disease. In some studies the number of genotypes needed can approach or even exceed 1 million. Generally, linkage and linkage disequilibrium analyses depend on clear allele identification and subsequent allele frequency estimation. Accurate grouping or categorization of each allele in the sample (allele calling or binning) is therefore an absolute requirement. Hence, a genotyping system that can reliably achieve this is necessary. In the case of affected sib-pair analysis without parents, the need for accurate allele calling is even more critical. We describe methods that permit precise sizing of alleles across multiple gels using the fluorescence-based, Applied Biosystems (ABI) genotyping technology and discuss ways to reduce genotyping error rates. Using database utilities, we show how to minimize intergel allele size variation, to combine data effectively from different models of ABI sequencing machines, and automatically bin alleles. The final data can then be converted into a format ready for analysis by statistical genetic packages such as MENDEL.

Alleles↗
PubMed1997

Evaluation of case reports of aplastic anemia among patients treated with felbamate.

PURPOSE: Felbamate (FBM) is a new antiepileptic drug (AED) that is often effective in seizure disorders refractory to other treatments; its use has been greatly restricted after cases of aplastic anemia were reported. To elucidate the putative association between FBM and aplastic anemia, we made a detailed evaluation of the first 31 reports. METHODS: Hematologic review according to the criteria of the International Agranulocytosis and Aplastic Anemia Study (IAAAS) confirmed 23 cases (74%) as aplastic anemia; FBM was judged to be the only plausible cause for three; confounding (mostly by other drugs) was considered possible, but FBM remained the most likely cause for 11; and there was at least one other plausible cause for 9. RESULTS: Using a denominator from sales data of 110,000 persons exposed and a numerator of the cases for which FBM was considered the only plausible cause, we established a lower limit of incidence of 27 cases of aplastic anemia per million users as compared with the general population rate of 2.0 per million per year. With all confirmed cases used as the numerator, the upper limit of incidence was 209 per million. The 'most probable" incidence was estimated to be 127 per million. CONCLUSIONS: Intensive, systematic investigation can maximize the utility of case reports for assessing risks of newly released drugs. The present evaluation confirmed an association between FBM and aplastic anemia; however, confounding was significant for most cases and there was a tenfold range in the "best case" and "worst case" incidence estimates among users.

Adult↗