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Biomedical subjects

J B McCormick

Publications and source records attributed to J B McCormick.

At least 73 records · Page 4Linked to original sources

Electrocardiographic abnormalities in patients with Lassa fever.

Electrocardiograms from 32 patients with acute Lassa fever were abnormal in over 70% of cases. The changes noted included non-specific ST-segment and T-wave abnormalities, ST-segment elevation, generalized low-voltage complexes, and changes reflecting electrolyte disturbance. None of the abnormalities correlated with clinical severity of infection, serum transaminase levels, or eventual outcome. ECG changes are common in Lassa fever, but usually unassociated with clinical manifestations of myocarditis.

Adolescent↗

A prospective study of maternal and fetal outcome in acute Lassa fever infection during pregnancy.

Several viral infections have been reported to result in more severe disease in pregnant than non-pregnant women, but the relative risks have not been well characterised. This has now been done for Lassa fever in a prospective study of 68 pregnant and 79 non-pregnant women who were admitted to hospital in Sierra Leone with confirmed Lassa fever. Lassa fever was the main cause of maternal mortality in the hospital, accounting for 25% of maternal deaths. Twelve of 40 patients in the third trimester died, compared with two of 28 in the first two trimesters and 10 of 79 non-pregnant women. The odds ratio for death in the third trimester compared with the first two trimesters was 5.57 (95% confidence intervals 1.02 to 30.26). The condition of the mother improved rapidly after evacuation of the uterus, whether by spontaneous abortion, evacuation of retained products of conception, or normal delivery; 10 of 26 women without uterine evacuation died, but only four of 39 women with evacuation died (p = 0.0016). The odds ratio for death with pregnancy intact was 5.47 (95% confidence interval 1.35 to 22.16). Fetal and neonatal loss was 87%. The risk of death from Lassa fever in the third trimester is significantly higher than that in the first two trimesters and higher than that for non-pregnant women, but evacuation of the uterus can significantly improve the mother's chance of survival.

Acute Disease↗

The prevalence of infection with human immunodeficiency virus over a 10-year period in rural Zaire.

In 1985 we tested 659 human serum samples, collected in the remote Equateur province of Zaire in 1976, for antibody to human immunodeficiency virus (HIV). Five (0.8 percent) were positive, and HIV was isolated from one of these. Follow-up investigations in 1985 revealed that three of the five seropositive persons had died of illnesses suggestive of acquired immunodeficiency syndrome (AIDS), and two remained healthy but seropositive. In 1986, a serosurvey we conducted using a cluster-sampling technique in the same region showed a seroprevalence of 0.8 percent in 389 randomly selected residents. The seroprevalence in 283 prostitutes was 11 percent. Patients with AIDS were identified in various hospitals in the province. Risk factors for AIDS included a greater than average number of sexual partners and residence outside the area. We believe that the long-term stability of HIV infection in residents of rural Zaire suggests that social change may have promoted the spread of AIDS in Africa.

Acquired Immunodeficiency Syndrome↗

Hematologic dysfunction in Lassa fever.

Lassa fever is widespread in West Africa, where the case fatality is about 16% in hospitalized adult patients. The clinical course is highly variable, with a few patients developing severe disease with bleeding, adult respiratory distress syndrome, encephalopathy and hypovolemic shock. We studied 70 patients admitted with suspected Lassa fever to a hospital in Sierra Leone, West Africa. Fourteen patients classified as having severe Lassa fever on the basis of serum aspartate amino transferase (AST) greater than 150 IU/L or viremia of greater than 10(3.6) tissue culture infective dose (TCID) 50/ml were found to have statistically significantly depressed lymphocyte counts when compared with patients with mild Lassa fever (AST less than 150 IU/L or viremia, less than 10(3.6)TCID50/ml), (P less than 0.0001) and with febrile control patients, in whom Lassa infection had been excluded by laboratory criteria (P less than 0.0008). Maximum depression occurred a mean of 10.9 days post onset. Patients with severe Lassa fever also had moderate thrombocytopenia, which was statistically significant when compared with febrile control patients (P less than 0.0003) and this occurred a mean of 10.8 days postonset. The most significant changes were in platelet function, which was markedly depressed in patients with severe Lassa fever (P less than 0.0035 in response to ADP and P = 0.0081 for collagen) when compared with patients with mild Lassa fever, and when compared with febrile controls, (P = 0.0013 for ADP and P less than 0.00001 for collagen). This abnormality was usually maximal on admission to hospital, and probably is an early event, preceding hospitalization in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

Construction of a recombinant vaccinia virus expressing the Lassa virus glycoprotein gene and protection of guinea pigs from a lethal Lassa virus infection.

A cloned cDNA (1.65 kb) containing the complete glycoprotein gene of the Josiah strain of Lassa virus was inserted into the thymidine kinase (TK) gene of the New York Board of Health (WYETH) strain of vaccinia virus. The Lassa virus glycoprotein precursor, GPC, and the posttranslational cleavage products, G1 and G2, were shown by Western blot analysis to be properly expressed in cells infected with the recombinant virus. Northern blot hybridization of total cytoplasmic RNA extracted from recombinant virus infected cells demonstrated the presence of RNA transcripts of appropriate size considering the site of transcription initiation from the vaccinia P7.5 promoter, the size of the Lassa glycoprotein gene, and the presumed location of the transcription terminator in the vaccinia thymidine kinase gene. All guinea pigs vaccinated with the recombinant virus survived a lethal challenge infection with Lassa virus, whereas 80% of control animals died. The vaccinated guinea pigs did, however, develop transient, low-grade, fevers and detectable viremias following infection with Lassa virus, indicating that protection was not complete.

Animals↗

Seroprevalence of HIV-1 and HIV-2 in Guinea Bissau in 1980.

To determine the past prevalence of HIV-1 and HIV-2 in West Africa, we tested 440 serum samples collected in 1980 from people living in rural areas of Guinea Bissau. The sera were screened for antibodies by enzyme immunoassay (EIA) using purified simian immunodeficiency virus (SIV) isolated from rhesus macaque monkeys (SIVmac) and then confirmed by immunoblot and immunofluorescence assays for antibodies to SIV, HIV-2, and HIV-1. Five of the serum samples were repeatedly reactive by all assays to both SIV and HIV-2. None were positive for antibodies to HIV-1 by immunofluorescence, immunoblot or radio-immunoprecipitation (RIP) assays, with the exception of one HIV-2-seropositive samples which reacted with HIV-1 glycoproteins by RIPA. Thus, in 1980, at least 1.4% (six out of 440) of a random sample of people in rural Guinea Bissau had been exposed to a virus highly related to HIV-2 and SIV. One of these subjects may have been dually infected with HIV-1 and HIV-2.

Animals↗

Physicochemical properties of Marburg virus: evidence for three distinct virus strains and their relationship to Ebola virus.

The physicochemical and antigenic properties of three groups of Marburg (MBG) virus isolates, separated temporally and geographically, were compared to each other and to another member of the same family, Ebola (EBO) virus. Each MBG isolate contained seven virion proteins, one of which was a glycosylated surface protein. Peptide mapping of glycoproteins, nucleoproteins (NP) and viral structural protein (VP40) demonstrated extensive sequence conservation in the proteins of viruses isolated over a 13-year period, but homology was not evident in VP24. Some homology between the NPs of MBG and EBO was observed. A close antigenic relationship between MBG strains was found by radioimmunoassay but no evidence was found of antigenic cross-reactivity with EBO viruses. MBG virion proteins are produced from virus-specific monocistronic mRNA species. Five of the seven viral proteins were produced by in vitro translation of these RNAs. MBG virions contained one RNA species with an Mr of 4.2 x 10(6) and virions had a density of 1.14 g/ml in potassium tartrate. Virus isolates from different outbreaks had distinct T1 oligonucleotide maps, but had approximately 95% homology in base sequence. No two geographically distinct virus pairs were more closely related to each other than to a third virus isolate. MBG viruses are thus similar to EBO viruses in morphology and other physicochemical properties and are very similar to each other in RNA and protein composition. Each of the three geographically and temporally distinct MBG virus outbreaks appears to have been due to a genetically distinguishable, but antigenically closely related virus strain. In addition, these studies confirm the belief that MBG and EBO viruses are members of the new virus family, the Filoviridae.

Animals↗

Ten-year-replicated circadian profiles for 36 physiological, serological and urinary variables in healthy men.

At 3-hr intervals over a 24-hr span, 36 systemic, serologic and urinary variables were examined in 7 men in their mid 20's in the Spring of 1969, and again in the same 7 men in the Spring of 1979 under a similar chronobiologic protocol, using the same chemical and numerical analytical procedures. The variables examined for rhythms by cosinor were: vital signs--blood pressure (systolic, diastolic, pulse pressure and mean arterial pressure), heart rate, intraocular pressure (left and right), oral temperature; serum components--albumin, albumin/globulin ratio, total bilirubin, calcium, carbon dioxide, chlorides, bilirubin, cholesterol, globulin, glucose, potassium, sodium, sodium/potassium ratio, transaminase, triglycerides, total protein, urea nitrogen; and urine components--calcium, calcium/magnesium ratio, creatinine, magnesium, pH, potassium, sodium, sodium/potassium ratio, urea clearance, urea nitrogen, volume and zinc. Although all subjects appeared clinically healthy in 1969 and in 1979, certain inter-study differences were observed in a number of rhythm parameters of different variables. Statistically significant increases in mesor for the group as a whole were observed for serum Ca, cholesterol, Cl, CO2, K, Na, and while statistically significant mesor decreases for a group as a whole were noted in serum glucose and transaminase. Statistically significant increases in amplitude for the group as a whole were observed in serum chloride and urinary Na/K ratio, while statistically significant decreases were observed in amplitude for blood pressure, heart rate, serum albumin, A/G ratio, globulin, glucose, protein, sodium and transaminase.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Viral hemorrhagic fever antibodies in Nigerian populations.

Using the immunofluorescence test, a serosurvey for antibodies to five viral agents associated with hemorrhagic febrile infections was conducted with 1,677 human sera from different parts of Nigeria. Three hundred fifty-seven (21.3%) were positive for Lassa virus antibody, while antibodies to Rift Valley fever virus were detected in 42 (2.5%) of the sera. Testing for Rift Valley fever virus antibody was confirmed by plaque reduction neutralization test. Antibodies to Ebola and Marburg viruses were detected in 30 and 29 sera, respectively. Of the 357 Lassa virus antibody-positive sera, 297 (83.2%) were positive for Lassa only. In contrast, sera positive for Marburg were positive in combination with Lassa, Ebola, or Rift Valley fever viruses. Antibodies to Lassa and Rift Valley fever viruses were found in all locations in Nigeria, whereas Ebola and Marburg antibodies were found mainly in the northern savanna zones of Benue and Gongola, but not in the rain forest area of Ondo.

Adolescent↗

Evaluation of the WHO clinical case definition for AIDS in rural Zaire.

The clinical case definition for AIDS proposed by WHO for use in Africa was evaluated against HIV antibody status in 72 patients in rural Zaire. Twenty-one (29%) of the patients were antibody-positive. For diagnosing anti-HIV seropositivity, the case definition had a sensitivity of 52%, a specificity of 78%, a positive predictive value of 50% and a negative predictive value of 80%. Calculation of the positive predictive value at different levels of prevalence of HIV infection suggests that the case definition operates at maximum reliability in selected high-risk groups. Modifications to the case definition should be evaluated to try and improve its sensitivity and positive predictive value.

Acquired Immunodeficiency Syndrome↗

Synthetic peptide immunoassay distinguishes HIV type 1 and HIV type 2 infections.

Efforts to solve the epidemiologic puzzle of AIDS in Africa are complicated by the presence of multiple human retroviruses. Simple serologic tests that unambiguously distinguish among infections by these retroviruses are essential. To that end, a partially conserved immunoreactive epitope was identified in the transmembrane glycoproteins of human immunodeficiency viruses (HIV) types 1 and 2. Synthetic peptides derived from these conserved domains were used in sensitive and specific immunoassays that detect antibodies in sera from patients infected with HIV-1 or HIV-2. By making single amino acid substitutions in the HIV-1 peptide, it was possible to demonstrate HIV-1 strain-specific antibody responses to this epitope. Such custom-designed peptides synthesized from this domain are likely to detect newly discovered HIV types, define infection with specific HIV strains, and allow detection of group-common antibodies.

Amino Acid Sequence↗

Serologic and immunologic studies in patients with AIDS in North America and Africa. The potential role of infectious agents as cofactors in human immunodeficiency virus infection.

Serologic and immunologic studies were performed in 38 African and 60 US patients with acquired immunodeficiency syndrome (AIDS), 100 African and 100 US heterosexual men and women, and 100 US homosexual men to examine the potential role of infectious agents in human immunodeficiency virus (HIV) infection. There were no significant differences in the prevalence of antibodies to cytomegalovirus, Epstein-Barr virus, hepatitis A and B viruses, herpes simplex virus, syphilis, and toxoplasmosis among the African and US patients with AIDS, African heterosexual controls, and US homosexual men. However, these four groups all demonstrated a significantly greater prevalence of antibodies to each of these infectious agents compared with US heterosexual men. Immunologic studies demonstrated a significant elevation of activated lymphocytes (HLA-DR and T3 positive) and immune complexes in both AIDS populations and African heterosexual and US homosexual populations, compared with the US heterosexual population. These data demonstrate that the immune systems of African heterosexuals, similar to those of US homosexual men, are in a chronically activated state associated with chronic viral and parasitic antigenic exposure, which may cause them to be particularly susceptible to HIV infection or disease progression.

Acquired Immunodeficiency Syndrome↗