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Biomedical subjects

R N Miller

Publications and source records attributed to R N Miller.

At least 19 recordsLinked to original sources

45-year follow-up of hepatitis C virus infection in healthy young adults.

BACKGROUND: The sequelae during the first two decades after acute hepatitis C virus (HCV) infection have been well studied, but the outcome thereafter is unknown. OBJECTIVE: To conduct an extended study of the natural history of HCV infection by using archived serum specimens originally collected between 1948 and 1954. DESIGN: Retrospective cohort study. SETTING: A university, a Veterans Affairs medical center, and a medical follow-up agency that had access to the serum specimens and accompanying demographic and medical records. PARTICIPANTS: 8568 military recruits who were evaluated for group A streptococcal infection and acute rheumatic fever between 1948 and 1954. Blood samples were taken from the recruits and, after testing, were stored frozen for almost 45 years. MEASUREMENTS: The presence of antibodies to HCV was determined by enzyme-linked immunoassay, supplementary recombinant immunoblot assay, and polymerase chain reaction for HCV RNA. Morbidity and mortality were also assessed. RESULTS: Of 8568 persons, 17 (0.2%) had positive results on enzyme-linked immunosorbent assay and recombinant immunoblot assay. The rate was 1.8% among the African-American persons and 0.1% among the white persons in the total sample (relative risk, 25.9 [95% CI, 8.4 to 80.0]). During the 45-year follow-up, liver disease occurred in 2 of the 17 HCV-positive persons (11.8%) and 205 of the 8551 HCV-negative persons (2.4%) (ethnicity-adjusted relative risk, 3.56 [CI, 0.94 to 13.52]). Seven of the 17 HCV-positive persons (41 %) and 2226 of the 8551 HCV-negative persons (26%) had died by December 1996 (ethnicity-adjusted relative risk, 1.48 [CI, 0.8 to 2.6]). Of persons who were HCV-positive, 1 (5.9%) died of liver disease 42 years after the original phlebotomy, 5 (29%) died of non-liver-related disease a median of 37 years after the original phlebotomy, and 1 (5.9%) died of unknown causes. One hundred nineteen HCV-negative persons (1.4%) died of liver disease. CONCLUSIONS: The rate of HCV infection from 1948 to 1954 among a sample of military recruits parallels that among present-day military recruits and volunteer blood donors. During 45 years of follow-up, HCV-positive persons had low liver-related morbidity and mortality rates. This suggests that healthy HCV-positive persons may be at less risk for progressive liver disease than is currently thought.

Aged↗

Cirrhosis mortality among former American prisoners of war of World War II and the Korean conflict: results of a 50-year follow-up.

In our earlier, 30-year follow-up of American prisoners of war (POWs) of World War II and the Korean conflict, we found evidence of increased cirrhosis mortality. Using federal records, we have now extended our follow-up to 50 years (42 years for Korean conflict veterans) and have used proportional hazards analysis to compare the mortality experience of POWs with that of controls. Compared with their controls, World War II POWs had a 32% higher risk of cirrhosis mortality (statistically significant), and mortality risk was higher in the first 30 years of follow-up and also among those aged 51 years and older. Korean POWs had roughly the same risk of cirrhosis mortality as their controls. Neither self-reported data on alcohol consumption nor supplemental morbidity data satisfactorily explained the differences in risk between POWs and controls, although there was evidence that POWs tended to have higher rates of hepatitis, helminthiasis, and nutritional deprivation.

Case-Control Studies↗

Laboratory evaluation of a dot-blot enzyme immunoassay for serologic confirmation of illness due to Rickettsia conorii.

Of the 169 United States Army soldiers who deployed on a field training exercise to a remote area of Botswana for two weeks in January 1992, more than 30% developed a febrile illness within five days of their return. A diagnosis of South African tick typhus was suggested by soldiers' exposure to ticks, as well as the presence of eschars and vesicles at the site of tick bites, and tender regional lymphadenopathies. This high attack rate, experienced during such a short exposure period, emphasizes the hazard of illness due to Rickettsia conorii to persons visiting endemic areas. A rapid, diagnostic, semiquantitative enzyme immunoassay (DS) for detection of IgG and IgM antibodies to R. conorii was performed on 209 acute and convalescent sera from soldiers in the outbreak and on 75 control sera. For the acute sera from soldiers meeting the probable case definition of having both regional lymphadenopathy and tick bite eschar, as judged by an IgG indirect fluorescent antibody (IFA) test, the resulting sensitivity and specificity of the DS test were 100% and 48%, respectively. In the analysis of the acute sera, the DS test identified as reactive more of the probable cases (62%) than either the IgG (16%) or IgM (55%) IFAs. This simple and rapid diagnostic test could be useful in establishing a preliminary diagnosis of R. conorii rickettsiosis in remote settings when immediate confirmation by IFA is impossible.

Antibodies, Bacterial↗

Evidence that adenosine contributes to maintenance of hepatosplanchnic blood flow during peritoneal sepsis in rats.

Sepsis induced derangements in hepatosplanchnic perfusion can contribute to organ damage and death. Adenosine, a common and potent metabolic vasodilator, has not been evaluated as a mechanism for maintenance of blood flow during sepsis. We tested the hypothesis that adenosine receptor blockade would cause a decrease in hepatosplanchnic blood flow during intraperitoneal (i.p.) sepsis in the rat. Rats (250-350 g) were catheterized for hemodynamic and blood flow measurements with tracer microspheres. Sepsis was induced with an i.p. injection of cecal material (150 mg/kg in D5W; 5 mL/kg), and baseline measurements were taken 24 h later. Animals then received either the adenosine receptor antagonist 8-PTH (10 mM, 1.5 mL/kg), its vehicle (1.5 mL/kg) or normal saline (1.5 mL/kg), intravenously, and measurements were repeated 1 and 10 min later. There was a significant increase in hepatosplanchnic portal resistance in septic animals given 8-PTH, with no change in mean arterial blood pressure (MAP) or heart rate. Regionally, there was a significant decrease in gastric, small intestinal, cecal, and pancreatic blood flow when compared with vehicle. Adenosine receptor blockade caused a significant reduction in hepatosplanchnic blood flow during sepsis, suggesting that maintenance of splanchnic blood flow during sepsis involves receptor mediated adenosine actions.

Adenosine↗

Expression of S9 and actin CyIIa mRNAs reveals dorso-ventral polarity and mesodermal sublineages in the vegetal plate of the sea urchin embryo.

We have used whole amount in situ hybridization to analyze the patterns of expression of two genes, S9 and actin CyIIa, during the development of the sea urchin, Strongylocentrotus purpuratus. We demonstrate that at the late blastula stage, these two mRNAs are expressed specifically by cells of the vegetal plate. Their domains of expression, however, are different. S9 mRNA is broadly distributed within most of the vegetal plate except for the central region, while CyIIa expression is restricted to a population of 10-15 cells in the ventral region of the plate. S9-expressing secondary mesenchyme cells (SMCs) migrate from the vegetal plate into the blastocoel early in gastrulation and later populate the dorsal ectoderm. The numbers, morphology, and migratory behavior of these cells strongly suggest that they are pigment cells. Throughout gastrulation, CyIIa mRNA is expressed by a population of presumptive SMCs at the ventral aspect of the archenteron tip. The pattern of expression of this mRNA is dynamic, however, and by the early pluteus stage, CyIIa mRNA accumulates in primary mesenchyme cells (PMCs), SMCs, and endodermal cells of the gut. When embryos are treated with NiCl2, a compound that has been shown to ventralize other embryonic tissues, CyIIa mRNA is expressed by an increased number of cells in the vegetal plate in a radially symmetrical pattern. The spatial pattern of CyIIa expression provides the first direct molecular evidence that the vegetal plate is polarized along the dorso-ventral (D-V) axis of the embryo. This gene product should be a valuable marker in future studies of D-V axis specification, as it can be detected at earlier developmental stages than existing molecular markers of this axis. Our observations show that the vegetal plate consists of subterritories of gene expression, and provide further support for the view that diversification of the presumptive, non-skeletogenic mesoderm begins prior to the onset of invagination.

Actins↗

Epidemic streptococcal disease among Army trainees, July 1989 through June 1991.

Outbreaks of group A streptococcal infection occurred at four of seven US Army basic training installations between 1 July 1989 and 30 June 1991. Study data were collected through a respiratory disease surveillance program and on-site epidemiologic investigations. Although hospitalizations were frequent (range, 191-334) during each outbreak, average rates of hospitalization were low (2.4-4.8 hospitalizations/1000 trainees/week). Outbreak-associated morbidity included streptococcal toxic shock syndrome (2 cases, 1 fatal), acute rheumatic fever (6), acute glomerulonephritis (1), scarlet fever (1), and numerous other invasive sequelae. Four serotypes of Streptococcus pyogenes (M-1, -3, -5, and -18) were identified; M-18 caused significant disease at 2 installations. Disease control was rapidly achieved through prophylaxis programs using benzathine penicillin G in nonallergic trainees. These outbreaks extend other reports that document an evolution of the nature and severity of circulating S. pyogenes in the United States.

Disease Outbreaks↗

Concordance rates for benign prostatic disease among twins suggest hereditary influence.

OBJECTIVES: The etiology of benign prostatic hyperplasia (BPH) is unknown. Evidence for a hereditary trait would provide new avenues for investigation. METHODS: We compared the concordance for benign prostate disease in monozygotic (MZ) and dizygotic (DZ) twins who served in the United States military in World War II and have been followed by the Medical Follow-up Agency, Institute of Medicine of the National Academy of Sciences. Questionnaires completed in 1985 by 10,000 twins were reviewed for evidence of prostatic disease. Key words indicating benign prostatic disease (prostate, prostatectomy, BPH, TURP, and prostatism) were identified in 533 (5.3%) of the questionnaires. RESULTS: The average age was 64 +/- 3 years (range 56 to 68 in 1985). After eliminating men with known prostate cancer, there were 256 twin pairs that were informative for benign prostatic disease: both twins were concordant in 25 instances and discordant in 231, with only one twin mentioning benign prostatic disease. The pairwise concordance for MZ twins was 14.7% (19 of 129) and for DZ pairs it was 4.5% (5 of 112). The relative risk for benign prostatic disease for MZ twins was thus 3.3 (p = 0.008). The probandwise concordance rates, which express the probability of BPH in a cotwin of an affected twin, were 25.7% for MZ twins and only 8.5% for DZ twins. A covariance analysis estimated that 49% of the observed variance between twins could be attributed to genetic effects. CONCLUSIONS: These data provide preliminary evidence for the heritability of benign prostatic disease.

Aged↗

The status of home care training for physician assistants.

Homebound individuals represent a medically underserved and rapidly growing population. Nonphysician practitioners--physician assistants and nurse practitioners--in the home care setting afford increased availability of and access to medical services by homebound patients.

Data Collection↗

Turnover of inositol polyphosphate pyrophosphates in pancreatoma cells.

There is little information concerning the intracellular function of inositol 1,3,4,5,6-pentakis- and hexakisphosphate, despite their being the most abundant inositol polyphosphates. Current opinions that they play passive roles as antioxidants (Graf, E., Mahoney, J. R., Bryant, R. G., and Eaton, J. W. (1987) J. Biol. Chem. 259, 3620-3624) or "housekeeping" molecules (Berridge, M. J., and Irvine, R. F. (1989) Nature 341, 197-205) arises from belief in their metabolic lethargy. However, we have discovered that cell homogenates, incubated with 5 mM fluoride and 5 mM ATP, converted both inositol hexakisphosphate (Km = 2 +/- 0.5 microM, Vmax = 9 +/- 2 pmol/mg of protein/min) and inositol 1,3,4,5,6-pentakisphosphate (Km = 13 +/- 4 microM, Vmax = 11 +/- 5 pmol/mg of protein/min) to more polar products. These reactions were also observed in intact cells treated with 0.5-20 mM fluoride, and the precursor/product relationships were confirmed by comparing the effects of fluoride on cells differentially labeled with [3H]inositol in either short-term or pulse-chase protocols. The novel products were determined to be inositol pyrophosphates because of their relatively specific hydrolysis by tobacco pyrophosphatase and alkaline phosphatase. The pyrophosphates were metabolized rapidly by cell homogenates back to their pentakisphosphate and hexakisphosphate precursors. This endogenous pyrophosphatase activity was inhibited by up to 99% by 5 mM fluoride in vitro. In intact cells incubated with 10 mM fluoride, about 20% of the inositol 1,3,4,5,6-pentakisphosphate pool, and 50% of the inositol hexakisphosphate pool were each converted to pyrophosphate derivatives within 1 h.

Animals↗

Broad and persistent effects of benzathine penicillin G in the prevention of febrile, acute respiratory disease.

After an outbreak of acute rheumatic fever at a US Army training installation, a benzathine penicillin G prophylaxis program was instituted. Surveillance data were analyzed to measure rates of febrile, acute respiratory disease (ARD) among trainees before and after prophylaxis was begun. Annual admissions for ARD decreased from 1927 to 690 (-64.2%) after benzathine penicillin G prophylaxis was begun. Admissions with throat cultures positive for Streptococcus pyogenes fell from 595 to 63 (-89.4%), a reduction that accounted only for a minority (43%) of the total 1237 "prevented" admissions. Temporal changes in disease rates at other installations where drug was not administered were also analyzed. Only a small decrease in the number of annual ARD admissions (-6.3%) was observed at other training installations. These findings support a hypothesis that benzathine penicillin G has a broad effect in the prevention of ARD that extends beyond the simple elimination of group A streptococcal infection.

Acute Disease↗

Epidemiologic investigation of an outbreak of cutaneous leishmaniasis in a defined geographic focus of transmission.

An outbreak of cutaneous leishmaniasis occurred in a unit of 608 Puerto Rican national guardsmen conducting jungle warfare training in the Panama Canal Area in July 1984. An epidemiologic investigation of reported nonhealing, ulcerating skin lesions was conducted among 540 (89%) unit members in November and December 1984. Fifteen (88%) of 17 individuals with chronic, ulcerating skin lesions were confirmed as cases of cutaneous leishmaniasis by culture or histopathology. Twelve cases yielded positive Leishmania cultures, identified as L. braziliensis panamensis by cellulose acetate electrophoresis. Evaluation of different diagnostic techniques revealed that direct examination of tissues by Giemsa-stained histological examination was the most sensitive test (87% sensitivity), with an indirect immunofluorescent antibody test being rather insensitive (67%). All but one of the confirmed cases operated in small units that trained and slept overnight at a mortar firing site for a period of three days, yielding a site-specific attack rate of 22% (14 of 64). This contrasted with a much lower attack rate of 0.2% (1 of 476), experienced by unit members who trained at other locations during the same time frame (P less than 0.001). The median incubation period calculated from day of arrival at the mortar firing site was 17 days (range 2-78) for the 15 confirmed cases. Available personal protection methods, such as the use of insect repellents, were not appropriately implemented by unit personnel and thus, were not found to effectively protect against Leishmania infection. This is the largest reported outbreak of cutaneous leishmaniasis in military personnel associated with a single geographic focus of infection and contrasts with the usual sporadic disease experience in Panama.

Adult↗

HIV infection among members of the US Army Reserve Components with medical and health occupations.

Over 58,000 members of the US Army Reserve Components tested for human immunodeficiency virus (HIV) antibody had military or civilian medical occupations. The availability of HIV status and occupational information permits the assessment of prevalence and incidence of infection in this population. Levels of infection were not higher among women or among currently married men with medical occupations compared with those with nonmedical occupations. Prevalence and incidence were elevated among never-married men with either military or civilian medical occupations compared with never-married men with nonmedical occupations. Based on reported civilian occupation, male registered nurses and men with other medical occupations, excluding physicians and dentists, had a significantly higher prevalence of infection than men with nonmedical occupations. The patterns of infection suggest that the higher levels of infection found among never-married men with medical occupations may not be entirely due to occupational exposure. These findings may have applications in the design and interpretation of results of health care worker HIV surveillance programs.

Dentists↗

Trends of HIV seroconversion among young adults in the US Army, 1985 to 1989. US Army Retrovirus Research Group.

Because soldiers in the US Army are recurrently tested for the presence of antibody to the human immunodeficiency virus (HIV), HIV seroconversion rates can be directly measured. From November 1985 through October 1989, 429 HIV seroconversions were detected among 718,780 soldiers who contributed 1,088,447 person-years of follow-up time (HIV seroconversion rate, 0.39 per 1000 person-years). Period-specific seroconversion rates declined significantly from 0.49 per 1000 person-years (November 1985 through October 1987) to 0.33 per 1000 person-years (November 1987 through October 1988) to 0.29 per 1000 person-years (November 1988 through October 1989). The HIV seroconversion risk among active-duty soldiers was significantly associated with race/ethnic group, age, gender, and marital status. Based on these trends, we estimate that approximately 220 soldiers (95% confidence interval, 160 to 297 soldiers) were infected with HIV during 1989 and 1990, with potentially fewer in future years.

Adolescent↗

Acute and subacute effects of naturally occurring estrogens on luteinizing hormone secretion in the ovariectomized rat: Part 2.

Acute intravenous administration of the phytoestrogen genistein (G) blocks the gonadotropin-releasing hormone-(GnRH)-induced rise of luteinizing hormone (LH) in ovariectomized rats. The present experiments were performed to determine whether subacute administration of G or the mycoestrogens zearalenone and zearalenol would affect GnRH-induced or progesterone-induced LH secretion in ovariectomized rats. Charles River CD rats were ovariectomized and used 2 to 5 weeks later. Blood samples were obtained either via decapitation or via intraatrial cannulae three days after compounds were injected subcutaneously in sesame oil or corn oil vehicle. LH was measured by RIA. Pretreatment with estradiol benzoate suppressed LH levels at 1200 h, while G had no effect. Challenge with progesterone (8 mg/kg BW, sc) evoked LH release at 1600 h in rats pretreated with estradiol benzoate, but LH levels did not change in rats pretreated with G, zearalenone, or zearalenol. While GnRH-induced LH secretion was preserved in rats pretreated with estradiol, no LH response was detected in rats pretreated with the higher dose of G (8 mg/kg BW) or either dose of zearalenol (0.8 mg/kg BW or 8 mg/kg BW). We conclude that in the ovariectomized rat 1) subacute administration of G, zearalenone, or zearalenol do not inhibit tonic LH secretion, 2) G, zearalenone, and zearalenol do not provide "estrogenic priming" for progesterone-induced LH secretion; however, 3) G and zearalenol do block GnRH-induced LH secretion. The seemingly selective neuroendocrine effects of these naturally-occurring dietary estrogens emphasize that actions of each putative estrogen must be characterized for each "estrogenic" endpoint.

Animals↗

HIV infection among members of the Army Reserve components residing in New York City.

A total of 10,722 members of the US Army Reserve and Army National Guard residing within the five boroughs of New York City (NYC) were tested for antibody to human immunodeficiency virus (HIV). The crude prevalence in NYC was found to be 10.6 per 1,000, compared with a national prevalence of 1.6 per 1,000. The highest prevalences were found among Blacks and Hispanics, males, and among those aged 30-39 years. Patterns of infection were found to be similar to those found among heterosexual and drug abusing populations. Prevalence was highest in the Bronx and varied by less than twofold over all boroughs. Comparisons with reported cases of acquired immunodeficiency syndrome (AIDS) in New York City indicated differences in the demographic and geographic characteristics of the current epidemic of AIDS and HIV infection among members of the Army Reserve components.

Adult↗

Continuous postoperative epidural analgesia for gynecologic oncology patients.

The efficacy of continuous postoperative epidural analgesia (CPEA) was assessed in 193 patients who collectively underwent 254 gynecologic oncology procedures. Seventy-five patients elected to receive CPEA; 118 did not. The CPEA patients received an epidural catheter the morning of surgery. Postoperatively, a bolus of meperidine was placed in each catheter. An IVAC pump continued to deliver meperidine at the rate of 14 to 20 mg per hour. The 193 patients also received a total of 655 postoperative intramuscular narcotic injections. CPEA patients were three times less likely to request injections, and those who did required an average of 6.58 compared with 12.42 for non-CPEA patients. The presence or absence of CPEA was the only significant variable. The use of CPEA led to no secondary complications, and it greatly enhanced mood and ability to participate in postoperative care. We conclude that CPEA provides excellent postoperative analgesia for such high-risk patients.

Adult↗

Human immunodeficiency virus infection among members of the reserve components of the US Army: prevalence, incidence, and demographic characteristics. The Walter Reed Retrovirus Research Group.

Since routine testing began, 677,463 members of the Reserve Components of the US Army have been tested for antibody to human immunodeficiency virus (HIV). Of these, 1063 were positive, for a crude prevalence of 1.57/1000 tested. Prevalence varied greatly among different groups as defined by sex, ethnicity, marital status, age, and geographic location. Multivariate analysis indicated that prevalence was higher among men, blacks, and unmarried men and peaked at ages 30-34. The crude incidence density was 0.20/1000 person-years, and multivariate analysis of incidence revealed patterns similar to those for prevalence. Comparison of prevalence and incidence data provides evidence that an increasing proportion of infection is occurring among women and in nonmetropolitan and small urban areas.

Acquired Immunodeficiency Syndrome↗