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Biomedical subjects

S E Zimmerman

Publications and source records attributed to S E Zimmerman.

At least 19 recordsLinked to original sources

Semiquantitative Epstein-Barr virus (EBV) polymerase chain reaction for the determination of patients at risk for EBV-induced lymphoproliferative disease after stem cell transplantation.

Epstein-Barr virus-induced lymphoproliferative disease (EBV-LPD) is a serious and potentially fatal complication after allogeneic stem cell transplantation (SCT). To evaluate levels of EBV DNA in SCT patients, a semiquantitative polymerase chain reaction (PCR) assay was developed. DNA was extracted from peripheral blood leukocytes and diluted, and PCR was performed by using a primer set specific for a well-conserved sequence of the internal repeat 1 region of the EBV genome. Forty-one SCT patients were screened with this method. Thirty-seven patients received allogeneic transplants, of which 18 were T-cell-depleted marrow. Four additional patients received autologous SCT, one of which was T-cell depleted. The mean time of follow-up by EBV PCR was 147 days (range, 47 to 328 days) posttransplant. The range of EBV copies/microg DNA from normal EBV sero-positive donors was 40 to 4,000. Seven patients had >/=40,000 copies of EBV DNA/microg DNA, all of whom were recipients of T-cell-depleted SCT. Five of the seven patients with elevated levels of EBV DNA developed EBV-LPD. Four of these five patients with EBV-LPD had elevated levels of EBV DNA from 1 to 8 weeks before diagnosis. Two patients with EBV-LPD had normal levels of EBV DNA, and two patients with >/=40,000 copies EBV/microg DNA did not develop EBV-LPD. In one patient, clinical resolution of disease correlated with a decrease in EBV DNA and an increase in the level of EBV-specific cytotoxic T-cell precursors. These data indicate that the measurement of EBV viral load with semiquantitative PCR is useful in detecting EBV-LPD in high-risk patients before the onset of clinical symptoms. Because not all patients with elevated levels of EBV DNA develop EBV-LPD, semiquantitative PCR results cannot substitute for clinical, radiographic, and pathological confirmation of this diagnosis.

Adolescent↗

The use of genetic tests and genetic information by life insurance companies: does this differ from the use of routine medical information?

Questions regarding insurance companies' access to and use of genetic test results and genetic information have been raised since the advent of the Human Genome Project. The ability to place applicants of similar risks in groups, a process known as underwriting, is critical to the availability and affordability of individually underwritten life, disability income, and long-term care insurance. This paper focuses on how life insurance companies use medical information and particularly genetic test results and other genetic information in the risk assessment process. Issues and concerns raised about differences between routine medical information and genetic information are addressed and policies with regard to privacy and confidentiality are presented.

Confidentiality↗

Genetic testing legislation: a review of the past two years.

The American Council of Life Insurance is a national trade association that represents the interests of legal reserve life insurance companies in legislative, regulatory and judicial matters at the federal, state and municipal levels of government and at the National Association of Insurance Commissioners. Its member companies hold more than 90 percent of the life insurance in force in the United States.

Confidentiality↗

Nephrotoxicity of notexin in experimental mice.

Notexin, a well known neurotoxin, derived from tiger snake venom, was shown to have direct nephrotoxic properties in experimental mice. A single subcutaneous dose of 1.38 micrograms/kg body weight of notexin produced renal tubular and glomerular damage within 24 hours. Renal damage increased in severity proportional to the dose of notexin injected. At a high dose of notexin, thrombotic "spherules" were found in glomeruli. These thrombotic spherules have not been previously reported to be associated with notexin or snake venoms.

Animals↗

Helicobacter pylori infection in recurrent abdominal pain in childhood: comparison of diagnostic tests and therapy.

OBJECTIVE: To determine the role of Helicobacter pylori infection in children with recurrent abdominal pain and the usefulness of serologic tests in screening H pylori infection and monitoring treatment of H pylori-associated gastritis. METHODS: During a 3 year period, we investigated the presence of serum immunoglobulin G (IgG) antibody to H pylori in 456 children using the high-molecular-weight cell-associated protein H pylori enzyme immunoassay kit. Among the 456 children studied, 218 (age range, 3 to 18 years; mean age, 9.5 years) had symptoms of recurrent abdominal pain (RAP syndrome) with or without vomiting, and the remaining 238 (age range, 3 to 18 years; mean age, 9.8 years) had no RAP (non-RAP syndrome). We performed upper gastrointestinal endoscopy on 111 consecutive children of the 218 with RAP syndrome and obtained mucosal biopsies for culture, histologic analysis, CLO test (Delta West, Perth, Australia), and H pylori detection by polymerase chain reaction. RESULTS: Thirty-eight (17.4%) of 218 children in the RAP group and 25 (10.5%) of 238 children in the non-RAP group were seropositive for H pylori. Of the 111 children endoscoped, 95 were found to be negative, and 12 were positive by all five assays. Specimens from 2 children were negative by culture and the CLO test but positive by the other three assays. Specimens from 1 child were negative by histologic analysis but positive by all other tests. The remaining child was positive for anti-H pylori IgG but negative by all of the other four assays. Upper gastrointestinal endoscopy detected 14 children with peptic ulcer disease (9 duodenal ulcer and 5 gastric ulcer) and 12 with antral nodular gastritis. Only 4 of the 14 diagnosed with peptic ulcer were H pylori positive by all five assays, whereas all 12 children with antral nodular gastritis were H pylori positive. Nine of the 12 H pylori-positive children were treated with a combination of bismuth subsalicylate, amoxicillin, and metronidazole for 2 weeks. Sera obtained at 2, 4, and 6 months after treatment from all 9 children showed a decrease in anti-H pylori IgG titer. Three H pylori-infected children who did not receive any treatment served as control children, and their IgG levels remained elevated or increased over time. CONCLUSION: The results from our study indicate that screening for the serum IgG antibody to H pylori is a practical method for diagnosing H pylori infection in children, and that serial measurements of the H pylori IgG antibody are useful for monitoring treatment of H pylori because of its high sensitivity and ease of performance. Only 4 of the 14 children diagnosed with peptic ulcer disease were confirmed to be infected with H pylori, whereas all 12 children with antral nodular gastritis were found to be infected by H pylori. These observations suggest that H pylori infection is more frequently associated with gastritis than with peptic ulcer disease in children, and that H pylori gastritis is a cause of RAP syndrome in children.

Abdominal Pain↗

Proliferative glomerulonephritis in mice induced by sea snake (Aipysurus laevis) venom.

Aipysurus laevis venom has been shown to have a direct nephrotoxic effect in mice. A single subcutaneous injection (0.075 mg/kg body wt.) of the whole venom caused acute renal tubular degeneration and proliferative glomerulonephritis. The tubular changes appeared within 1 hour and remained for at least 14 days. Mesangial proliferative glomerulonephritis developed within 3-10 days, and is characterised by mild mesangial proliferation, mesangial and glomerular basement membrane deposits. This is followed by a partial resolution and subsequent mesangial sclerosis. The exact pathogenesis of venom-induced glomerulonephritis is not clear although it may have an immunological basis similar to that seen in human poststreptococcal glomerulonephritis. It was not possible to clarify the nature of the deposits by conventional immunohistochemical stains.

Animals↗

Variability in commercial histoplasma complement fixation antigens.

Using Immuno-Mycologics (IMMY; Norman, Okla.) histoplasmal yeast (HY) and mycelial (HM) antibody complement fixation test antigens, we retested 1,386 samples that were initially tested with Meridian Diagnostics, Inc. (Cincinnati, Ohio), antigens. Histoplasma antibody was identified (greater than or equal to 1:16) in 20% of HY and 5% of HM samples reported to have titers of less than 1:8 with Meridian reagents. IMMY titers were at least fourfold higher than Meridian titers in 39% of HY and 54% of HM samples that initially had titers of greater than or equal to 1:8 with Meridian antigens. Because 30 of 58 (52%) samples from confirmed cases of histoplasmosis yielded negative results with Meridian antigens and positive results upon retesting with IMMY antigens, we concluded that the Meridian antigens had less reactivity with human histoplasmal antibody.

Antigens, Fungal↗

Evaluation of an enzyme-linked immunosorbent assay that uses ferrous metal beads for determination of antihistoplasmal immunoglobulins G and M.

A rapid enzyme-linked immunosorbent assay (ELISA) for the detection of human class-specific antibodies to Histoplasma capsulatum (histoplasmal immunoglobulin M [HIgM] and histoplasmal IgG [HIgG]) was developed by using antigen adsorbed onto polycarbonate-coated ferrous beads. In the ELISA method all the reagents used were commercially available. In 135 specimens from patients with confirmed histoplasmosis, sensitivities were 76% for complement fixation (CF), 53% for immunodiffusion (ID), and 64% for the ELISA for HIgM and HIgG combined. The ELISA detected histoplasmal antibody in 36% of the specimens with negative antibody titers by CF and 46% of the specimens with negative antibody titers by ID. The ELISA detected histoplasmal antibody in 27% of specimens that were negative by both CF and ID. When limited to specimens collected within 4 months of the onset of histoplasmosis symptoms, sensitivities were 82% for CF, 63% for ID, and 86% for ELISA for HIgG and HIgM combined. Within this group, ELISA detected histoplasmal antibody in 90% of the specimens that were negative by CF, 76% that were negative by ID, and 100% that were negative by both CF and ID. The specificity of the ELISA could not be fully addressed since sera from patients with other fungal infections were not available.

Antibodies, Fungal↗

Comparison of sandwich solid-phase radioimmunoassay and two enzyme-linked immunosorbent assays for detection of Histoplasma capsulatum polysaccharide antigen.

Detection of a Histoplasma capsulatum polysaccharide antigen (HPA) has proved a useful approach to diagnosis of histoplasmosis. Two sandwich enzyme-linked immunosorbent assays (ELISAs) using alkaline phosphatase (AP)-or horseradish peroxidase (HRP)-conjugated antibodies were compared with solid-phase radioimmunoassay (RIA) for detection of HPA. The AP-ELISA and HRP-ELISA were each positive in 17 (89.5%) of 19 urine specimens from patients with disseminated histoplasmosis, while the RIA was positive in 18 (94.7%) of 19. Specimens from patients with nondisseminated histoplasmosis were positive by AP-ELISA in 8 of 32, by HRP-ELISA in 4 of 25, and by RIA in 12 of 25. Of control specimens from patients with other fungal infections, the AP-ELISA was negative in 22 (91.7%) of 24, the HRP-ELISA in 23 (95.8%) of 24, and the RIA in 23 (95.8%) of 24. Reproducibilities AP-ELISA and HRP-ELISA were 95.1% and 95.1%, respectively. Thus, AP-ELISA and HRP-ELISA appear less sensitive than RIA and may be falsely negative in specimens containing low levels of HPA.

Antigens, Fungal↗

Adaptation of a commercially available indirect fluorescent antibody slide test for measuring measles-specific immunoglobulins.

A commercially available indirect fluorescent antibody (IFA) test was evaluated for the determination of measles-specific immunoglobulins G and M (MIgG, MIgM). The IFA test detected fourfold rises of MIgG in 34 of 35 (97%) cases of measles confirmed by complement fixation or hemagglutination inhibition. In determining immune status, MIgG-IFA correlated with hemagglutination inhibition in 22 of 23 (96%) cases. The IFA test detected MIgM in only 11 of 34 acute-phase sera collected within 5 days of the reported onset of rash and in the convalescent specimens of another 13 of the 35 specimens. The IFA test is an effective method for the conventional diagnosis of measles and for determining immune status. This IFA test has a limited role as a rapid diagnostic test for measles when used to detect measles-specific MIgM in acute-phase sera obtained from patients with suspected measles.

Agglutination Tests↗

Rapid diagnosis of measles using enzyme-linked immunosorbent assay for measles immunoglobulin M.

An enzyme-linked immunosorbent assay (ELISA) for measles-specific immunoglobulin M (MIgM) was developed for use as a rapid diagnostic test for acute measles. A titer greater than or equal to 1:20 in both the acute and convalescent sera was present in 100% of patients with measles and was diagnostic of acute measles infection in children. Interference by rheumatoid factor (RF) was avoided by pretesting sera for RF and absorption with aggregated gamma globulin. Ion exchange separation of IgM and IgG should eliminate RF interference. The ELISA MIgM assay can easily be used in any laboratory for the serologic confirmation of measles infection.

Adult↗

Immunoglobulin M and G histoplasmal antibody response in histoplasmosis.

Radioimmunoassays for IgM and IgG histoplasmal antibodies were developed and proved to be specific for their respective immunoglobulin classes, sensitive, and reproducible. Elevated IgM antibodies were detected in 59.8% of patients with histoplasmosis and 7.9% of control subjects. Elevated IgG antibodies occurred in 80.4% of patients with histoplasmosis but in only 12.9% of control subjects. Radioimmunoassay was nearly twice as sensitive as complement fixation for identifying patients with mild, presumably asymptomatic, infection. Of 13 patients with serologic follow-up at least 1 yr later, elevated IgM antibodies cleared, whereas IgG antibodies persisted in 7. In an epidemiologic investigation of a recurrent histoplasmosis outbreak, only the radioimmunoassay was able to prove the hypothesis that construction for a swimming complex was the source of exposure. These assays promise to be useful for clinical and epidemiologic investigations.

Antibodies, Fungal↗

Gastric carcinoma and thrombotic thrombocytopenic purpura: association with plasma immune complex concentrations.

A patient with metastatic adenocarcinoma of the stomach developed microangiopathic haemolytic anaemia, thrombocytopenia, renal insufficiency, and fluctuating neurological abnormalities in association with appreciably raised plasma concentrations of immune complexes. This syndrome, similar to thrombotic thrombocytopenic purpura, occurred while the tumour was in sustained objective remission after successful treatment with fluorouracil, doxorubicin, and mitomycin. Reversal of the syndrome was achieved with plasmapheresis, azathioprine, corticosteroids, and antiplatelet treatment; this response was paralleled by a reduction in immune complex concentration, suggesting an immune aetiology for the syndrome. Antibodies eluted from the immune complexes reacted with 50% of cells from the gastric cancer but less than 10% of cells from normal gastric mucosa. There was no reactivity with either carcinoembryonic antigen or mitomycin. A 17S immune complex reacted with a glycoprotein from the patient's autologous platelets and produced platelet aggregation. It is postulated that reducing the tumour and the pre-existing state of antigen excess by chemotherapy allowed soluble antigen-antibody complexes to form and the syndrome to develop.

Adenocarcinoma↗

Immunoglobulin M antibody titers in the diagnosis of Legionnaires disease.

The purpose of this study was to determine whether measurement of immunoglobulin M (IgM) antibodies against Legionella pneumophila serogroup 1 can aid in the diagnosis of Legionnaires disease. On the basis of measurements of antibody levels in 1,942 control sera, we used an IgM titer of 1:256, observed in 2.3% of the controls, as presumptive evidence of Legionnaires disease. Measurement of IgM titers permitted us to presumptively or definitively diagnose Legionnaires disease in 13 of 34 patients earlier than we would have if only IgG titers had been measured. Of the 13 patients, 5 were diagnosed serologically only by IgM antibody determination. IgM titers were presumptively diagnostic in week 1 of clinical symptoms in 4 of the 13 patients. We conclude that conjugates used for antilegionella indirect fluorescent-antibody tests should be capable of detecting IgM antibodies so that the value of serological results in diagnosing and managing Legionnaires disease will be maximized.

Fluorescent Antibody Technique↗

The diagnostic laboratory tests for histoplasmosis: analysis of experience in a large urban outbreak.

Of 495 patients reported in a large urban histoplasmosis outbreak, we studied 276 whose serologic tests were done in a single laboratory. Serologic test results were positive in 96% of these patients (compared with less than 5% of controls from an endemic area), cultures were positive in 22%, and special stains in 19%. The immunodiffusion test results were negative in 13% of patients who had positive findings by complement fixation, and 1% had positive results only by immunodiffusion. The complement fixation test was almost twice as sensitive as the immunodiffusion test in patients with subclinical infection. The serologic response differed significantly among the clinical syndromes with higher titers in cavitary and lower titers in disseminated disease. Factors associated with titers of 1:64 or greater to both antigens were black race and immunocompetence. High mycelial titers were also associated with more intense exposure, and high yeast titers were associated with age less than 36 years. No prognostic significance could be proved for fourfold titer rises or falls or persistence of precipitins.

Adolescent↗

Chemotherapy of pancreatic carcinoma.

Cancer of the pancreas is the fourth leading cause of cancer death in the United States. Until recently, this tumor has not been the subject of a systematic evaluation of nonsurgical therapies. In particular, there have been remarkably few anticancer agents specifically studied for activity in pancreatic cancer, but at the present time 5-fluorouracil, mitomycin-C, streptozotocin, and Adriamycin have demonstrated single-agent effectiveness. Despite the limited number of agents available for the development of combination chemotherapy, several programs have demonstrated an apparent improvement in response relative to single-agent treatment. These include 5-FU and mitomycin-C, SMF, and FAM; response rates of 30-43% have been reported for patients with advanced measurable pancreatic cancer. For the locally advanced stage of this disease, the combined modality approach of 5-fluorouracil plus external irradiation has produced superior survivals when compared with radiation therapy used alone. Although chemotherapy of pancreatic cancer is a developing field, clinically meaningful responses correlated with improved patient survival can be obtained with existing regimens. Phase II trials of new anticancer agents remain a high priority research effort with the intent of identifying useful drugs for future regimens of combination chemotherapy.

Adenocarcinoma↗

Comparison of enzyme-linked immunosorbent assay for acute measles with hemagglutination inhibition complement fixation, and fluorescent-antibody methods.

An enzyme-linked immunosorbent assay (ELISA) using commercially available reagents was compared with standard serological tests for determination of antibody titers in patients with acute measles. The measles-specific ELISA was as sensitive as complement fixation, hemagglutination inhibition, and indirect fluorescent-antibody methods. The ELISA method used was simple, sensitive, inexpensive, and reproducible and may conveniently be used in a small clinical laboratory.

Antibodies, Viral↗