Biomedical subjects
D M Morens
Publications and source records attributed to D M Morens.
Should the Declaration of Helsinki be revised?
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Summary of antibody workshop: The Role of Humoral Immunity in the Treatment and Prevention of Emerging and Extant Infectious Diseases.
In the era before antibiotics, human diseases were commonly treated with immune animal and human sera, often with life-saving results. With the advent of emerging infectious diseases, many of which cannot be adequately treated or prevented, attempts to develop antibody treatments have taken on new importance. The role of humoral immunity in treatment and prevention was the focus of discussion at a 1996 workshop. The cellular and molecular mechanisms of neutralization were examined in detail. It was noted that success in passive immunity has frequently been the key element in devising a successful strategy to develop a vaccine for active immunization. The workshop concluded on a cautious note of optimism that antibody-based treatment and prevention for diseases such as human immunodeficiency virus infection, Ebola fever, and others of clinical and public health importance deserve further development and clinical trial.
Serological screening tests for antibody to human immunodeficiency virus--the search for perfection in an imperfect world.
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Sequence and phylogenetic analyses of HIV-1 infection in Vietnam: subtype E in commercial sex workers (CSW) and injection drug users (IDU).
More than 4,000 persons with human immunodeficiency virus type 1 (HIV-1) infection have been identified in Vietnam through sentinel surveillance since 1990, when the first case of HIV-1 infection was diagnosed in a young woman in Ho Chi Minh City. Currently, the estimated HIV-1 seroprevalences of 10% for injection drug users (IDU) and 3% for female commercial sex workers (CSW) in Vietnam are comparable to those observed in the same risk groups in Thailand five years ago. To clarify if concurrent epidemics with different HIV-1 subtypes (or clades) are occurring among different high-risk behavior groups in Vietnam, we conducted a genotypic analysis of HIV-1 by amplifying and sequencing a 325-nucleotide region spanning the principal neutralizing domain, or V3 loop, of the gp120-encoding env gene from genomic DNA extracted from dried, filter paper-blotted blood samples, collected in April/May and August/September 1995 from 8 HIV-1-seropositive CSW in Ho Chi Minh City, Can Tho and An Giang provinces and from 16 IDU in Ho Chi Minh City, Hanoi, Nha Trang and An Giang province. Sequence alignment and comparison with other HIV-1 subtypes indicated that the HIV-1 strains from CSW and IDU in Vietnam were genetically most similar to subtype E strains from Cambodia. The interstrain genetic variation among the Vietnam HIV-1 env sequences ranged from 0.3% to 9.0% (mean, 4.6%). Phylogenetic analysis verified that some of the Vietnam HIV-1 strains formed discrete clusters and were indistinguishable from other Southeast Asian strains. The demonstration of subtype E in both CSW and IDU in Vietnam contrasts sharply with the previously observed HIV-1 clade restriction in these high-risk behavior groups in nearby Thailand.
Observations on serum uric acid levels and the risk of idiopathic Parkinson's disease.
Uric acid, an antioxidant found in high concentrations in serum and in the brain, has been hypothesized to protect against oxidative damage and cell death in Parkinson's disease. The authors tested this hypothesis among men participating in a 30-year prospective study known as the Honolulu Heart Program. Serum uric acid was measured in 7,968 men at the baseline examination held from 1965 to 1968. Of these men, 92 subsequently developed idiopathic Parkinson's disease (IPD). In analyses adjusted for age and smoking, men with uric acid concentrations above the median at enrollment had a 40% reduction in IPD incidence (rate ratio (RR) = 0.6; 95% confidence interval (CI) 0.4-1.0). Reduced IPD incidence rates persisted in analyses restricted to nonsmokers (RR = 0.5; 95% CI 0.3-1.0) and cases younger than age 75 years (RR = 0.5; 95% CI 0.3-0.9). Incidence rates were not notably affected when analyses were restricted to cases that occurred more than 5 years after uric acid measurement (RR = 0.6; 95% CI 0.4-1.0). Inclusion of known or computed correlates of uric acid in regression models did not substantially change risk of IPD. This study provides prospective evidence of an association between uric acid and reduced occurrence of IPD and indicates that further investigations of this association are warranted.
Evidence against the operation of selective mortality in explaining the association between cigarette smoking and reduced occurrence of idiopathic Parkinson disease.
To investigate the association between idiopathic Parkinson disease (IPD) and reduced frequency of prior cigarette smoking, the authors compared the 29-year follow-up mortality rates and IPD incidence rates of men who were either cigarette smokers or nonsmokers at the time of enrollment in the Honolulu Heart Study (1965-1968). Based on IPD cases detected up to June 30, 1994, the age-adjusted incidence rate in smokers was less than half that in nonsmokers: 34.4 versus 94.2 cases per 100,000 person-years of pre-illness follow-up, respectively. When data were stratified by 5-year age group, lower IPD incidence in smokers was observed at all ages between 50 and 90 years. Age-specific mortality trends for smokers and nonsmokers with and without IPD suggested that increased mortality in IPD patients was mostly associated with IPD itself and not with smoking. The slight excess mortality in smokers without IPD, versus nonsmokers without IPD, appeared insufficient to account for the "missing" incident IPD cases in smokers. These IPD incidence and mortality data are not highly consistent with the "selective mortality" hypothesis, which attributes reduced prior smoking frequency, typically reported by persons with IPD, to accelerated mortality in undiagnosed IPD-affected persons who smoke. The "protective" association of cigarette smoking with IPD occurrence may thus be real, suggesting the need for further study of biologic mechanisms of protection.
Re: "The frequency of idiopathic Parkinson's disease by age, ethnic group, and sex in northern Manhattan, 1988-1993".
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HIV type 1 subtype E in commercial sex workers and injection drug users in southern Vietnam.
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Dengue 1 virus binding to human hepatoma HepG2 and simian Vero cell surfaces differs.
We analysed the binding and infectivity of dengue virus serotype 1 (DEN-1) for the human hepatoma cell line HepG2 in comparison with the simian kidney cell line Vero. The higher susceptibility of Vero cells to DEN-1 correlated with greater binding affinity of DEN-1 to these cells. In contrast, the capacity of virus attachment was higher for HepG2 than for Vero cells. Profiles of DEN-1 binding at different pH were markedly different between the two cell types. A type-specific neutralizing monoclonal antibody reduced initial virus binding to both cell types similarly but complex- and group-specific neutralizing antibodies affected virus adhesion differently. Altogether, these results suggest the involvement of different receptors or receptors presented in a different environment on the cell surface in the two cell lines. The sensitivity to proteolytic enzymes and to ionic detergent of the binding sites on the two cell types was tested and results indicated that they may be multimeric proteins or protein complexes.
Epidemiologic observations on Parkinson's disease: incidence and mortality in a prospective study of middle-aged men.
We determined age-specific and age-adjusted incidence rates and mortality rates of idiopathic Parkinson's disease (PD) in a cohort of men followed for 29 years. Since enrollment in 1965, the Honolulu Heart Study has followed 8,006 American men of Japanese or Okinawan ancestry. Rescreening of the entire cohort, completed in 1994, included attempts to detect all prevalent and incident cases of PD, parkinsonism, and related conditions. PD incidence rates and age-incidence patterns were similar to rates previously published for Caucasian men in Europe and the United States, and were higher than incidence rates published for Asian men living in Asian nations. Prevalence patterns appeared to correspond more closely to patterns observed in developed nations than in Asian nations. PD was associated with markedly increased mortality that appeared to result from effects of both absolute age and disease duration. There was no firm evidence for differences in birth cohort risks of PD. These data may have implications for maturational and environmental theories of PD etiology.
Case-control study of idiopathic Parkinson's disease and dietary vitamin E intake.
A nested case-control study of 84 incident cases of patients with idiopathic Parkinson's disease (PD) detected by June 30, 1994 and 336 age-matched control subjects, compared previously-documented intake of total dietary vitamin E and of selected vitamin E-containing foods. All study subjects had been followed for 27 to 30 years after diet recording in the 8,006-man Honolulu Heart Study cohort. We determined PD outcomes by periodic cohort re-examination and neurologic testing, private physician reports, examination of O'ahu neurologists' office records, and continual death certificate and hospital discharge diagnosis surveillance. Data on vitamin E intake, obtained from three dietary data sets at the time of cohort enrollment (1965 to 1968), included a food-frequency questionnaire and a 24-hour photograph-assisted dietary recall administered by trained dietitians. Although absence of PD was significantly associated with prior consumption of legumes (adjusted OR = 0.27, 95% CI 0.09 to 0.78), a dietary variable preselected for high vitamin E content, neither food categories nor quartiles nor continuous variables of vitamin E consumption were significantly associated with PD occurrence. Though consistent with prior reports of PD protection afforded by legumes, and with speculation on the possible benefits of dietary or supplemental vitamin E in preventing PD, these preliminary data do not conclusively document a beneficial effect of dietary vitamin E on PD occurrence.
Mass fainting at medieval rock concerts.
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Lessons from a nursing home outbreak of influenza A.
OBJECTIVE: To characterize risk factors for outbreak-associated influenza illness and death in a nursing home. DESIGN: Outbreak investigation with predetermined and concurrently determined risk information. SETTING: A nursing home service in a multiward chronic care hospital, Honolulu, Oahu, 1989 to 1990. PATIENTS: Elderly nursing home patients receiving long-term care. INTERVENTIONS: Influenza vaccination, amantadine administration, and infection control measures. RESULTS: Neither routine infection control measures nor vaccination prevented illness, complications, or death in a nursing home outbreak of influenza A. The 55% case-fatality rate resulted from severe pneumonia. Influenza transmission may have been mediated by staff via either contaminated hands or fomites. CONCLUSIONS: Data from this and other outbreaks suggest that recommendations for preventing nosocomial influenza in the nation's 1.5 million nursing home residents should be reconsidered.
Cigarette smoking and protection from Parkinson's disease: false association or etiologic clue?
We reviewed 46 published reports associating cigarette smoking and Parkinson's disease. Although the majority indicated an approximate halving of smoking frequency in persons with Parkinson's disease, many observers have suggested that the effect could be a spurious result. That the association may be real is suggested by at least six observations: (1) the consistency of findings between independent studies of different design, conducted by different investigators, in different nations, over 35 years; (2) the association's predominance and strength in prospective studies; (3) the apparent detection of a dose-response relation; (4) the inability to explain the association by confounding variables; (5) the flaws in certain arguments against the association's validity; and (6) the identification of a similar association, of similar magnitude, between smoking and reduced occurrence of Alzheimer's disease. A protective association of cigarette smoking for Parkinson's disease may constitute an important etiologic clue.
Thoughts on the relevance of medical history.
Clinicians are, by their very nature, historians--a question remains as to whether and how the history of medicine should be studied as a subject. In recent years medical educators have increasingly answered this question by deleting medical history from the curriculum. But this may be a mistake: among other things of value, medical history provides a much-needed perspective of medical knowledge, and a pigeon holer into which essential new facts--basic, clinical, whatever--can be filed without getting lost. But linear learning, the piling-on of facts, is more likely to bring exhaustion than comprehension.
"Thucydides syndrome" reconsidered: new thoughts on the "Plague of Athens".
A recently published theory (N Engl J Med 1985;313:1027-30) argues that the famous Athenian epidemic of 430 B.C. was caused by a combination of influenza and toxin-producing staphylococci (the "Thucydides syndrome"). Although it is accepted by some medical authorities, and ostensibly supported by identification of modern cases, the theory's plausibility has not been carefully examined. The authors used an epidemiologic approach supplemented by historical and clinical observations to examine the likelihood that a "Thucydides syndrome" could have caused the Athenian epidemic. Arguing against the influenza theory are epidemiologic and clinical features of the disease, mathematical models of the spread of influenza, and empirical observations of epidemic influenza in premodern populations of known size and crowding. The authors conclude that neither influenza nor a "Thucydides syndrome" could have produced the Athenian epidemic. Epidemiologic features suggest either a zoonotic or vectorborne disease, a disease associated with an environmental source, or a respiratory infection with unusual alternative mechanisms of spread.