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Biomedical subjects

J B McCormick

Publications and source records attributed to J B McCormick.

At least 37 records · Page 2Linked to original sources

Longitudinal cohort study of the epidemiology of malaria infections in an area of intense malaria transmission II. Descriptive epidemiology of malaria infection and disease among children.

A large-scale longitudinal cohort project was initiated in western Kenya in June 1992. Between June 1992 and July 1994, 1,848 children less than 15 years of age were monitored prospectively for a mean of 236 days. During this period, 12,035 blood smears were examined for malaria and only 34% were found to be negative. Parasite prevalence (all species) decreased with age (from a high of 83% among children 1-4 years old to 60% among children 10-14 years old). Even more dramatic decreases were noted in the prevalence of high density falciparum infection (from 37% among children 12-23 months old to < 1% among 10-14-year-old children) and in clinical malaria (20% to 0.3% in the same age groups). Children < 1 year of age accounted for 55% of all cases of anemia detected. Anemia was consistently associated with high density infection in children < 10 years of age (20% to 210% increased risk relative to aparasitemic children). These results demonstrate the relationship between high-density malaria infection and two clinical manifestations of malarial illness.

Adolescent↗

HIV antibody seroprevalence and associated risk factors in sex workers, drug users, and prisoners in Sindh, Pakistan.

OBJECTIVE: To determine prevalence of HIV infection and risk behaviors in commercial sex workers (CSWs), drug users, and prisoners in Sindh, Pakistan. METHODS: A medical clinic was established in a "red-light" district of Karachi. Eighty-one CSWs who registered at the clinic between November 1993 and June 1994 were provided HIV counseling and testing and administered a risk factor questionnaire. Next, 316 male drug users were tested for HIV-1 antibody from April to July 1994. Finally, a voluntary serosurvey of HIV-1 and HIV-2 and risk behaviors of 3525 prisoners in Sindh was conducted between July 1994 and December 1994. Abbott Recombinant HIV third-generation enzyme-linked immunosorbent assay (ELISA) and confirmatory testing with Western blot analysis were used in all three groups. RESULTS: None of 81 CSWs tested for HIV-1 antibody were positive. None of 316 drug users tested positive for HIV-1 antibody. Of 3441 male prisoners, 1 was HIV-1 infected, and of 84 female prisoners, 1 was HIV-1 infected. No prisoner was positive for HIV-2 antibody. DISCUSSION: The prevalence of HIV in CSWs, drug users, and prisoners in Sindh is low at present. Intervention programs implemented at this stage can make an impact in HIV prevention.

Adolescent↗

Epidemiology of emerging/re-emerging antimicrobial-resistant bacterial pathogens.

The rapid global expansion of bacteria resistant to antimicrobials is the most important development over the past year in emerging bacterial diseases. The critical events are the emergence of Staphylococcus aureus with decreased sensitivity to vancomycin, worldwide resistance to penicillin in Streptococcus pneumoniae, and the remorseless progression of multiply-resistant Mycobacterium tuberculosis. Most startling was the isolation from a human in Madagascar of a plague bacillus possessing a plasmid readily transferable to Escherichia coli, which confers multiple antibiotic resistance. The hospital environment continues to see the transmission of resistant organisms, notably vancomycin-resistant enterococci. Finally, as food markets become more open around the world, food-borne outbreaks of E. coli O157 and cholera demonstrate how difficult it can be to establish effective health and safety barriers.

Bacteria↗

Risk factors for typhoid fever in an endemic setting, Karachi, Pakistan.

We conducted a study to evaluate risk factors for developing typhoid fever in a setting where the disease is endemic in Karachi, Pakistan. We enrolled 100 cases with blood culture-confirmed Salmonella typhi between July and October 1994 and 200 age-matched neighbourhood controls. Cases had a median age of 5.8 years. In a conditional logistic regression model, eating ice cream (Odds ratio [OR] = 2.3; 95% confidence interval [CI] 1.2-4.2, attributable risk [AR] = 36%), eating food from a roadside cabin during the summer months (OR = 4.6, 95% CI 1.6-13.0; AR = 18%), taking antimicrobials in the 2 weeks preceding the onset of symptoms (OR = 5.7, 95% CI 2.3-13.9, AR = 21%), and drinking water at the work-site (OR = 44.0, 95% CI 2.8-680, AR = 8%) were all independently associated with typhoid fever. There was no difference in the microbiological water quality of home drinking water between cases and controls. Typhoid fever in Karachi resulted from high-dose exposures from multiple sources with individual susceptibility increased by young age and prior antimicrobial use. Improving commercial food hygiene and decreasing unnecessary antimicrobial use would be expected to decrease the burden of typhoid fever.

Adolescent↗

The relationship between therapeutic injections and high prevalence of hepatitis C infection in Hafizabad, Pakistan.

To determine the prevalence and routes of transmission of hepatitis C virus (HCV) infection in Hafizabad, Pakistan, we collected sera in 1993 from a geographically based random sample of residents, and in 1994 identified 15 HCV-infected individuals (cases) and 67 age and sex matched uninfected individuals (controls). Initially we approached 504 households, and collected serum from a randomly selected household member in 309 (64%). Twenty persons (6.5%) had anti-HCV antibody; 31% percent had hepatitis B core antibodies, and 4.3% had hepatitis B surface antigen. In the case-control study, persons who received more therapeutic injections (categorized as averaging 1, 2-4, 5-9 or > 10 injections per year in the previous 10 years) were more likely to be infected with HCV (odds ratio 0, 1.5, 2.5 and 6.9 respectively, P = 0.008) compared to persons averaging 0 injections per year. Efforts to limit therapeutic injections to only those that are medically indicated and that use sterile equipment are essential in order to prevent transmission of HCV.

Adolescent↗

Circadian relationships between circulating atrial natriuretic peptides and serum calcium and phosphate in healthy humans.

Long-acting natriuretic peptide (LANP), vessel dilator (VSDL), and atrial natriuretic factor (ANF) consisting of amino acids (aa) 1 to 30, 31 to 67, and 99 to 126, respectively, of the 126-aa ANF prohormone circulate in humans. Among the biologic properties of these peptides is the ability of ANF to decrease intracellular calcium concentrations. To determine if atrial natriuretic peptides are directly related to serum calcium and/or phosphate in healthy normocalcemic humans, we examined 21 24-hour profiles of VSDL, LANP, ANF, and serum calcium and phosphate in 14 healthy humans. VSDL, LANP, and ANF each had significant (P < .001) circadian rhythms, with peak concentrations late during sleep (at 4:00 AM) being nearly twice the concentrations in the afternoon and evening. Serum calcium and phosphate also had significant circadian rhythms (P < .001) with troughs nearly opposite to those of the atrial natriuretic peptides, suggesting that atrial peptides may be important in the modulation of the circadian rhythms of calcium and phosphate. The nearly identical circadian rhythms of the atrial natriuretic peptides and of parathyroid hormone (PTH) reported by others, along with evidence that PTH may increase atrial peptide release, suggest that some of the effects attributed to PTH may be mediated by atrial natriuretic peptides.

Adult↗

Circadian relationships between circulating atrial natriuretic peptides and serum sodium and chloride in healthy humans.

Long-acting natriuretic peptide (LANP), vessel dilator (VSDL), and atrial natriuretic factor (ANF) consisting of amino acids 1-30, 31-67, and 99-126 of the 126 amino acid ANF prohormone, respectively, circulate in humans and have potent natriuretic properties. To determine whether these peptides have a direct relationship to serum Na and/or Cl, we examined 21 24-hour profiles of these peptides and Na and Cl in 14 healthy humans. LANP, VSDL, ANF, and Cl had significant (p < 0.001) circadian rhythms with peak concentrations at 04.00 h. The circadian rhythm of serum Na was exactly opposite. Sodium correlated negatively with LANP (p = 0.021) and ANF (p = 0.007), while Cl correlated positively with LANP (p = 0.003) and VSDL (p = 0.001). These data suggest that the atrial peptides may be important for the maintenance of serum Na and Cl within their normal ranges and in the modulation of their daily circadian rhythms.

Adult↗

Demographic and socio-economic determinants of contraceptive use in a low income community of Karachi.

The study objectives were to assess multiple factors associated with the use of contraceptives among married women living in a low income community in Karachi. The study was a cross sectional survey of 608 women between the ages of 15 and 49 years. The mean number of living children per woman was 3.7 (confidence intervals 3.49-3.9). The literacy rate was 53%. The current use of contraceptives was 29%. Among many variables examined and in consistence with studies in other countries, women were 4 to 5 times more likely to use contraceptives if they had 3 or more living children than if they had two or fewer living children (p = .000). These results strongly suggest that the number of surviving children and women's education are key determinants in decision-making about contraceptive use and as such are intervention points to increase contraceptive use. Stronger policies focused on improving child survival, reducing the perceived ideal family size through increased female education will be more likely to reduce fertility.

Adolescent↗

Review of cases of nosocomial Lassa fever in Nigeria: the high price of poor medical practice.

OBJECTIVE: To investigate two hospital outbreaks of Lassa fever in southern central Nigeria. SETTING: Hospitals and clinics in urban and rural areas of Imo State, Nigeria. DESIGN: Medical records were reviewed in hospitals and clinics in both areas. Patients with presumed and laboratory confirmed Lassa fever were identified and contracts traced. Hospital staff, patients, and local residents were questioned, records were carefully reviewed, and serum samples were taken. Serum samples were assayed for antibody specific to Lassa virus, and isolates of Lassa virus were obtained. RESULTS: Among 34 patients with Lassa fever, including 20 patients, six nurses, two surgeons, one physician, and the son of a patient, there were 22 deaths (65% fatality rate). Eleven cases were laboratory confirmed, five by isolation of virus. Most patients had been exposed in hospitals (attack rate in patients in one hospital 55%). Both outbreak hospitals were inadequately equipped and staffed, with poor medical practice. Compelling, indirect evidence revealed that parenteral drug rounds with sharing of syringes, conducted by minimally educated and supervised staff, fuelled the epidemic among patients. Staff were subsequently infected during emergency surgery and while caring for nosocomially infected patients. CONCLUSION: This outbreak illustrates the high price exacted by the practice of modern medicine, particularly use of parenteral injections and surgery, without due attention to good medical practice. High priority must be given to education of medical staff in developing countries and to guidelines for safe operation of clinics and hospitals. Failure to do so will have far reaching, costly, and ultimately devastating consequences.

Clinical Competence↗

Crimean Congo-haemorrhagic fever treated with oral ribavirin.

Crimean-Congo Haemorrhagic Fever (CCHF) is an often-lethal haemorrhagic fever caused by a tick-borne virus. There are no published data on ribavirin treatment of CCHF-infected patients, despite established in-vitro and in-vivo sensitivity. We report three health workers--two surgeons and a hospital worker--infected with CCHF virus in Pakistan who were treated with oral ribavirin 4 g/day for four days, then 2.4 g/day for six days. Intravenous ribavirin was unavailable. All three patients were severely ill with low platelet and white-cell counts, raised aspartate transaminase and evidence of impaired haemostasis. Based on published reports, all had an estimated probability of death of 90% or more. The patients became afebrile, and their haematological and biochemical abnormalities returned to normal within 48 h of ribavirin treatment; all made a complete recovery, and developed IgG and IgM antibody to CCHF virus. Our experience with ribavirin treatment is encouraging, but does not constitute evidence of efficacy. Given the difficulties in gathering adequate treatment data, we propose a consensus protocol for both intravenous and oral treatment of CCHF. This protocol could be distributed to key medical personnel in areas endemic for CCHF and used to provide a firm basis for effective treatment recommendations.

Acute Disease↗

Spatial and temporal analysis of the Drosophila FMRFamide neuropeptide gene product SDNFMRFamide: evidence for a restricted expression pattern.

The expression of SDNFMRFamide, one of five different FMRFamide-containing peptides encoded by the Drosophila melanogaster FMRFamide gene, has been determined. To study expression, we generated antisera to the N-terminus of SDNFMRFamide to avoid crossreactivity with FMRFamide-containing peptides. The antisera were purified and the specificity characterized. SDNFMRFamide immunoreactive material is present in the central nervous system throughout development. Immunoreactivity is first observed in embryonic neural tissue in a cluster of cells in the subesophageal ganglion and immunoreactive fibers projecting from these cells to the brain and ventral ganglion. This pattern of expression is also observed in neural tissue dissected from larva, pupa, and adult. Double-labelling experiments indicate that cells recognized by SDNFM-antisera are also stained with FMRFamide antisera. Based on position, SDNFMRFamide immunoreactive material is expressed in a limited number of cells that contain the FMRFamide polypeptide precursor. This finding suggests that the Drosophila FMRFamide precursor undergoes differential post-translational processing.

Amino Acid Sequence↗

A serotypic study of hemorrhagic fever with renal syndrome in rural China.

Apodemus agrarius was trapped in the fields and Rattus norvegicus was trapped within the houses in the villages of Jiande County, a region in the Zhejiang Province of China endemic for hemorrhagic fever with renal syndrome (HFRS). Antibodies to hantaviruses were detected in three (16.7%) of 18 A. agrarius and 12 (13.5%) of 89 R. norvegicus, whereas hantavirus antigens were detected in the lung tissues of four (22.2%) of 18 and nine (10.1%) of 89 of these rodents, respectively. Three hantaviruses, one from A. agrarius and two from R. norvegicus, were isolated and found to be antigenically similar to Hantaan and Seoul serotype viruses, respectively. A serologic study of 437 clinically defined HFRS patients conducted in Jiande County in 1988 revealed that the ratio of Hantaan (72.5%) to Seoul (26.8%) serotype virus infections was 2.7:1. Two epidemic seasons were found, with a major peak in November and a minor peak in June, and both were associated with Hantaan serotype virus infections that coincided with two seasonal peaks of the A. agrarius population and local agricultural activities in the fields. Seoul serotype virus infections occurred with a small peak during the months of December through May, in which in-house activities were dominant. All data suggested that Jiande County was an area endemic for HFRS, predominantly of the Hantaan virus serotype, combined with Seoul serotype virus infections.

Animals↗

Retrospective and prospective studies of hemorrhagic fever with renal syndrome in rural China.

Residents of two villages in Zhejiang Province, China, were interviewed and serum samples were collected to assess prevalence of hantavirus infection. Antibody prevalence was 12% (219/1811), with a ratio of illness to infection of 1.0:5.4. Seroprevalence increased with age, but no association was found with sex. There was also no evidence of vertical transmission. One year later, 2.3% (30/1325) of seronegative subjects had seroconverted including 2 who had hemorrhagic fever with renal syndrome. Peak incidence of infection occurred in those 15-39 years old. Hantaan was the dominant serotype; Seoul serotype was less common (5:1). Host reservoirs were Apodemus agrarius in agricultural fields and Rattus norvegicus in houses. Risk factors for infection were traces of rat-contaminated food, travel to other areas for farm work, direct rodent contact, camping in grain fields, living in a house on the periphery of a village, stacking straw stacks outside houses, and keeping cats. All may provide exposure to infectious rodent reservoirs.

Adolescent↗

Ebola protein analyses for the determination of genetic organization.

Amino-acid sequencing of the purified major nucleoprotein (NP), VP35 and VP40 from purified Ebola virus proved that they are the protein products of the first three genes, and that the open reading frame (ORF) of the NP begins at nucleotide 470. Because of the many unusual features of the ORFs of Ebola virus, we thought that our conclusions should be substantiated. Comparisons of in vitro-translation products to purified viral proteins were used to demonstrate conclusively that the NP, VP35 and VP40 were the protein products of genes one, two, and three, respectively. Studies using antibodies to synthetic peptides matching the N- and C-termini of the deduced sequences from these genes confirmed these conclusions and that the ORF for the NP begins at nucleotide 470. Subsequent studies confirmed that VP30 is encoded by the fifth gene.

Amino Acid Sequence↗

Evaluation of the polymerase chain reaction for diagnosis of Lassa virus infection.

We evaluated the polymerase chain reaction (PCR) and hybridization procedures for diagnosis of Lassa fever. Primers were derived from a region of the small RNA segment of Lassa virus coding for the glycoprotein. Serum samples stored for a 14-year period from patients in Sierra Leone, West Africa were examined retrospectively. Blinded samples were then tested prospectively. Eighty-eight virus isolation-negative control sera were negative by PCR and hybridization. In the retrospective study, virus was isolated from 51 of 98 specimens from patients with Lassa fever, and 33 of these were positive for Lassa virus RNA by PCR, and 42 by PCR and hybridization. Fifteen were positive by PCR and hybridization but isolation-negative, and nine were positive by isolation but PCR/hybridization-negative. Thirty-two were negative by all methods (sensitivity by PCR/hybridization compared with virus isolation 0.82, specificity 0.68). In a prospective blinded study of 195 patient sera, 51 were positive by PCR and virus isolation, and 24 were PCR positive but virus isolation-negative (sensitivity 0.66, specificity 0.71). After hybridization, 66 virus isolation-positive sera were positive. The sensitivity was 0.86 and the specificity was 0.59, and the probability of false-positive results compared with virus isolation was 32%, (chi 2 = 21.9, by McNemar's test). Since some specimens may not have contained viable virus, we re-analyzed the data of individual patients using laboratory-confirmed case definitions for Lassa fever. All specimens from patients in whom Lassa fever was excluded by serologic tests were negative by PCR/hybridization.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Lymphocytic choriomeningitis outbreak associated with nude mice in a research institute.

OBJECTIVE: After an employee at a cancer research institute was diagnosed with lymphocytic choriomeningitis, an investigation was performed to determine the extent of lymphocytic choriomeningitis virus (LCMV) infections among the institute's employees and to identify risk factors for infection. DESIGN: Retrospective cohort study. SETTING: A US cancer research institute. PARTICIPANTS: Eighty-two of 90 institute employees. MAIN OUTCOME MEASURES: Serum LCMV antibodies. RESULTS: Seven workers (9%) with definite LCMV infection (LCMV IgG antibody titer greater than or equal to 16) and one worker (1%) with probable infection (IgG titer = 8) were identified (10% overall seroprevalence). All infected employees handled animals or animal tissues and were more likely than other animal handlers to have worked with nude mice (Mus musculus) (P less than .02). Among the 31 employees who worked with nude mice at the institute, infected workers were more likely to clean the cages of nude mice (P much less than .001), change their bedding (P less than .01), and change their water (P less than .001). The institute had been injecting nude mice with LCMV-infected tumor cell lines and had recently increased the nude mouse population and the duration of experiments. These changes would have increased the LCMV burden at the facility and were temporally associated with the cluster of LCMV infections in employees. CONCLUSIONS: This LCMV outbreak, the first reported since 1974, is the first associated with nude mice. It illustrates the ongoing hazard LCMV poses in research laboratories. Since the symptoms of LCMV infection can be nonspecific, clinicians should consider this diagnosis in ill patients who report laboratory rodent exposure.

Adult↗

Inactivated Lassa virus elicits a non protective immune response in rhesus monkeys.

We attempted to protect three rhesus monkeys from Lassa fever by vaccination with a preparation of purified whole Lassa virus which had been inactivated by gamma irradiation. The vaccinated monkeys developed antibodies against the three major viral proteins of Lassa virus demonstrated by radioimmunoprecipitation. When the three vaccinated monkeys and two unvaccinated control monkeys were challenged all five became severely ill and died. Prior to death a secondary, high-titer antibody response to Lassa virus was observed in the three vaccinated monkeys, whereas the two unvaccinated monkeys developed a primary, low-titer antibody response. Though titers of Lassa virus in serum reached peak levels earlier following challenge in the non vaccinated, at the time of death serum and organ virus titers did not differ significantly. Changes in platelet aggregation, leukocyte counts, and liver enzymes, abnormalities of which have been associated with severity of Lassa fever, were found to be comparable in the two groups. The humoral antibody response measured in these animals following vaccination, although of the same magnitude as found in humans recovered from Lassa fever, was insufficient to protect the animals from this fatal disease. Evidence is now accumulating that the cell-mediated immune response must be activated in order to protect against challenge with arenaviruses.

Animals↗