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Biomedical subjects

J I Smith

Publications and source records attributed to J I Smith.

17 recordsLinked to original sources
PubMed1999

Rhesus differential susceptibility to endotoxin is not associated with activation of plasma prekallikrein.

This study is part of a project aimed at understanding individual responses to acute endotoxemia in a catheter-free rhesus (Macaca mulatta) model of inflammation. In the previous study [J. Endotoxin Res. 2 (1995) 411-420.], we showed that of 14 endotoxin 0111:B4 (ETX)-infused monkeys, only three died at < 13.5 h and one at 6 days postinfusion. Doses of ETX correlated neither with the magnitude of hypotension nor with rhesus outcome. Survival (and death at 6 days) or death at < 13.5 h was rather associated with controllable or uncontrollable rise of plasma levels of proinflammatory cytokines and reversible or irreversible shock. In the current study, we used plasmas of 5 survivors and of one of the monkeys that died at < 13.5 h (each infused with 3 X 10(6) EU ETX/kg), and of two saline control monkeys of the previous study. We analyzed changes in parameters of coagulation and contact systems. After ETX infusion, activated partial thromboplastin time (APTT) and prothrombin time (PT) values increased modestly in survivors but markedly in the nonsurvivor; responses of platelet counts and levels of fibrinogen, antithrombin, alpha2-macroglobulin (alpha2M), Cl-inhibitor (C1INH) and alpha1 -antitrypsin were similar in survivors and the nonsurvivor; the rate of plasma prekallikrein (PK) activation measured by hydrolysis of the kallikrein (KAL) substrate D-Pro-Phe-Arg-p-nitroanilide was not altered by ETX infusion; and the distribution of PK activation products, analyzed by MAb 13G11/immunoblotting in plasmas with or without artificial activation, was similar in survivors and the nonsurvivor. Responses in controls were relatively stable. Since we used defined experimental conditions, this primate model has the potential to be useful to study further correlation of inflammatory parameters with differential outcome.

Animals↗
PubMed1994

Failure of doxycycline as a causal prophylactic agent against Plasmodium falciparum malaria in healthy nonimmune volunteers.

OBJECTIVE: To determine whether doxycycline, 100 mg administered as a single daily oral dose, is effective as a causal prophylactic agent, an agent active against the pre-erythrocytic liver stage of Plasmodium falciparum malaria parasites, in healthy nonimmune persons. If effective, the recommendation by the Centers for Disease Control and Prevention (CDC) that doxycycline be continued for 4 weeks after returning from malaria-endemic areas could be shortened to 1 week. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Medical ward at the U.S. Army Research Institute of Infectious Diseases, Fort Detrick, Maryland. PARTICIPANTS: 18 nonimmune, healthy, adult male volunteers, age 21.7 +/- 2.9 (SD) years, were enrolled in two groups, one of 8 persons and one of 10 persons. Six participants in the first group and 7 in the second group received doxycycline. The remaining participants received placebo. Two volunteers were dropped from the study, leaving 16 participants for analysis. INTERVENTION: Each participant received doxycycline, 100 mg, or placebo in a single daily oral dose starting 3 days before exposure to P. falciparum-infected mosquitoes and ending 6 days after exposure. MEASUREMENTS: Monitoring for parasitemia, plasma doxycycline concentrations, and mosquitoes' salivary-gland sporozoite grade. RESULTS: 6 of 6 (100% [95% Cl, 54% to 100%]) participants on doxycycline in the first group and 2 of 6 (33% [Cl, 4% to 78%]) in the second group were protected from malaria. No differences were found between protected and nonprotected participants in the doxycycline elimination half-life (T1/2) (20.8 +/- 5.0 h compared with 21.9 +/- 5.2 h), the steady-state average plasma concentration (1626 +/- 469 ng/mL compared with 1698 +/- 651 ng/mL), or other pharmacokinetic parameter estimates. The mean mosquito salivary-gland sporozoite grade was significantly higher (P = 0.02) in protected (3.5 +/- 0.3) than in nonprotected persons (3.1 +/- 0.1). Overall, 8 of 12 persons on doxycycline were protected from malaria, yielding a causal prophylactic efficacy rate of 67% (Cl, 35% to 90%). CONCLUSIONS: A dosing regimen of doxycycline, 100 mg once daily, administered as a causal prophylactic agent against P. falciparum malaria in healthy, nonimmune volunteers, had an unacceptably high failure rate. Therefore, the CDC recommendation that doxycycline should be taken daily starting 1 to 2 days before travel, during travel, and for 4 weeks after travel should still be followed.

Administration, Oral↗
PubMed1993

Early analysis of viremia and clinical tests in patients with epidemic hemorrhagic fever.

We analysed the early viremia and clinical tests in 82 patients with epidemic hemorrhagic fever (EHF). The results showed that the changes in viremia and clinical tests are related to the severity of the disease and prognosis. Higher concentrations of the virus in infected patients might cause a more unfavourable prognosis and more abnormalities in clinical tests. CK-MB, SGOT, SGPT, serum creatinine and urea nitrogen contents increased markedly, while serum total protein, albumin and calcium contents decreased markedly, indicating that the heart, liver and kidney in EHF patients were severely damaged. Markedly increased WBC and monocytes showed that the patients were seriously infected. Platelet count, antithrombin-III and plasminogen decreased markedly, demonstrating that there were marked changes in the coagulation-anticoagulation and fibrinolytic system of the EHF patients. Changes in RBC, Hb and HCT contents indicated that the blood in the EHF patients had a higher concentration. This study gives further evidence that EHFV plays an important role in the pathogenesis of EHF.

Adolescent↗
PubMed1993

The changing pattern of early breast cancer and its primary management at CAMC.

To gauge the impact of screening mammography and the results of clinical trials on the pattern of primary surgical care of early breast cancer, tumor registry data from the Charleston Area Medical Center for 1980-81 was compared to tumor registry data at the hospital for 1990-91. Over the course of 10 years, there was a significant increase in the proportion of patients with T1 tumors (52% vs. 66%, p = .004), a significant increase of cases diagnosed by mammography alone (6% vs. 34%, p < .001), a significant decrease in the proportion of patients with positive axillary nodes (41% vs. 28%, p = .016), and a significant increase in the proportion of patients undergoing breast-sparing procedures (4% vs. 16%, p = .003). However, the percentage of breast-sparing operations at CAMC from 1990-91 was lower than the number reported in the National Cancer Data Base of 1988 (16% vs. 29%). A future study to assess reasons for patient selection of mastectomy or local excision is being planned.

Adult↗
PubMed1992

Structure, kinetics, and function of human and rhesus plasma prekallikreins are similar.

To determine if rhesus monkeys (Macaca mulatta) could serve as a model for studying the role of the contact system in the pathophysiology of human infections, we compared structural, kinetic, and functional characteristics of plasma prekallikrein and its activation products in rhesus and humans. Three prekallikrein variants (85-, 89- and 93-kDa) were revealed in rhesus plasma as compared with the two variants (85- and 88-kDa) in human plasma by immunoblotting with the monoclonal antibody MAb 13G11. The prekallikrein concentration in rhesus plasma was 1.5-fold that in human plasma as determined by computerized immunoblot analyses (CIBA) and amidolytic activity. The electrophoretic mobility of prekallikrein from plasma of both species increased after deglycosylation. Inhibition of prekallikrein activation by MAb 13G11 was 55% (rhesus plasma) and 76% (human plasma), with similar inhibition curves. Immunoblots of activated rhesus plasma showed prekallikrein, complexes of kallikrein with C1 inhibitor, alpha 2-macroglobulin and approximately 60-kDa inhibitor(s) (viz. antithrombin III), and 45-kDa fragments, like those in activated human plasma. Concentrations and molecular masses of factor XII and high molecular weight kininogen were similar in rhesus and human plasma. The activated partial thromboplastin time (APTT) and prothrombin time were 20.1 +/- 1.6 and 9.7 +/- 0.3 s for rhesus and 32.0 +/- 5.6 and 12 +/- 0.5 s for human plasma. Human and rhesus APTTs were similar when prekallikrein concentrations in human and rhesus plasma became alike by adding human purified prekallikrein.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Prospective, double-blind, concurrent, placebo-controlled clinical trial of intravenous ribavirin therapy of hemorrhagic fever with renal syndrome.

A prospective, randomized, double-blind, concurrent, placebo-controlled clinical trial of intravenous ribavirin (loading dose of 33 mg/kg, 16 mg/kg every 6 h for 4 days, and 8 mg/kg every 8 h for 3 days) was conducted in 242 patients with serologically confirmed hemorrhagic fever with renal syndrome (HFRS) in the People's Republic of China. Mortality was significantly reduced (sevenfold decrease in risk) among ribavirin-treated patients, when comparisons were adjusted for baseline risk estimators of mortality (P = .01; two-tailed). HFRS typically consists of five consecutive but frequently overlapping clinical phases. Only occurrence of oliguric phase and hemorrhage was associated with severity of clinical disease in the placebo group. Ribavirin therapy also resulted in a significant reduction in the risk of entering the oliguric phase and experiencing hemorrhage. The only ribavirin-related side effect was a well-recognized, fully reversible anemia after completion of therapy.

Anemia, Hemolytic↗
PubMed1991

Interruption study of viremia of patients with hemorrhagic fever with renal syndrome in the febrile phase.

Kinetic changes of viremia were observed in 287 cases of hemorrhagic fever with renal syndrome (HFRS) in whom ribavirin was administered with double blind random control studied by means of virus isolation, indirect immunofluorescence assay and enzyme-linked immunosorbent assay. The positive rate of viremia was 79.7% (Sp = 3%) and positive rate of HERS IgM was 85% (Sp = 3.1%) before treatment. Viremia could be interrupted by ribavirin as in the ribavirin treated group, the viremia positive rate decreased, duration of viremia was shortened, viral antigen products, virus titer and HFRS IgG antibody level were reduced as compared with the control group. This showed that viremia was very frequent in patients in the febrile phase and ribavirin is an effective antiviral drug in HFRS during the febrile phase. Dosage and course of treatment of this drug are discussed.

Double-Blind Method↗
PubMed1990

In vitro surface properties of the newly recognized gastric pathogen Helicobacter pylori.

There appears to be a particular association between Helicobacter pylori and the gastric antrum, but the mechanisms by which the organism adheres to and colonizes the gastric mucosa are unclear. Surface hydrophobicity and surface charge mediate the adherence of other bacterial pathogens to mucosal epithelial cell surfaces. Therefore, in this study we characterized both the surface hydrophobicity and the surface charge of 10 H. pylori strains grown in broth culture. Four complementary methods were used to determine hydrophobicity: hydrophobic interaction chromatography, the salt aggregation test, comparison of bacterial adherence to polystyrene with adherence to sulfonated polystyrene, and measurement of contact angle with droplets of water. Three of the methods (salt aggregation test, adherence to polystyrene, and contact angles) indicated that each of the 10 strains expressed a relatively hydrophilic cell surface. In contrast, hydrophobic interaction chromatography determinations with both phenyl- and octyl-Sepharose suggested that the H. pylori strains were relatively hydrophobic. However, tetramethyl urea (0.4 M) did not reduce the binding of H. pylori to phenyl-Sepharose columns. DEAE-cellulose ion-exchange chromatography showed that each of the 10 strains of H. pylori had a surface which, overall, was highly negatively charged. We conclude that H. pylori expresses an overall relatively hydrophilic and negatively charged surface in vitro.

Bacterial Adhesion↗
PubMed1989

Rapid diagnosis of malaria by acridine orange staining of centrifuged parasites.

A rapid diagnostic test for malaria based on acridine orange staining of centrifuged parasites in a microhaematocrit tube ('QBC' tube) was compared with the thick blood smear in 12 volunteers experimentally infected with Plasmodium falciparum, 408 residents of a malaria endemic area, and 180 hospital patients with suspected malaria. In the experimentally infected volunteers, the QBC tube test and the thick blood smear were comparable and the QBC tube could detect as few as 4 parasites/microliter blood. When used for mass screening in the field study, the test had a sensitivity of 70% for the diagnosis of malaria compared with 92% for a single thick blood smear. However, when used to diagnose malaria in hospital patients, the test detected as few as 3 parasites/microliter in 91 of 92 patients with asexual parasitaemia. For the three studies, the QBC tube was highly specific (98.4%), indicating malaria in only 8 of 487 subjects with negative blood films. The species of parasite was correctly identified in 77% of species. Processing the QBC tube was easier and much more rapid than was processing a thick blood smear, taking only 5 min for centrifugation and 5 min for examination. The QBC tube is not a substitute for the blood smear, but its speed and ease of use make it an important new tool for the diagnosis of malaria.

Acridine Orange↗
PubMed1987

Longitudinal study of rotavirus infection and gastroenteritis in families served by a pediatric medical practice: clinical and epidemiologic observations.

During 29 months of prospective longitudinal study of diarrhea in the home, human rotaviruses (HRVs) infected one or more members in 51% of 65 families, 35 of 126 children (28%) and 16 of 124 adults (13%). Within the 33 affected families, 57% of 62 children and 25% of 65 adults were infected. HRV gastroenteritis peaked at 40/100 person years at ages 12 to 23 months and decreased to 5 episodes/100 person years in adults. Among 25 children 0 through 36 months of age who had HRV infection, 88% were symptomatic. Of the 22 children with symptomatic HRV infection, 1 required hospitalization and 8 were seen by their physician for supportive care. HRVs were found in 12% of 216 stools obtained during gastrointestinal illness, but in only 0.2% of 1238 non-illness stools tested. HRV infections were noted as early as October and as late as April. Of 33 families who were studied for 2 seasons, at least 1 individual in each of 3 families experienced HRV infections in both years, but only one, an adult, shed virus and had symptoms in both seasons.

Adolescent↗
PubMed1987

Studies of the coagulation system in arenaviral hemorrhagic fever: experimental infection of strain 13 guinea pigs with Pichinde virus.

Significant coagulation abnormalities were associated with experimental infection of strain 13 guinea pigs with Pichinde virus, an arenavirus related to the virulent human pathogens Junin, Machupo, and Lassa viruses. Infected animals developed decreased activity of multiple coagulation factors, decreased antithrombin III levels, high levels of fibrin-fibrinogen degradation products, impaired platelet function, and thrombocytopenia. Testing for the presence of a coagulation inhibitor revealed a pattern consistent with factor deficiency. Fibrin thrombi were not found at necropsy. The findings of high fibrin-fibrinogen degradation product levels and decreased antithrombin III levels, in association with decreased activity of multiple coagulation factors and thrombocytopenia, suggest that intravascular coagulation is a feature of this experimental infection. The demonstration of abnormal platelet function is also significant, as this could contribute to defective hemostasis despite the moderate thrombocytopenia which usually occurs in arenaviral disease.

Animals↗
PubMed1985

Fecal adenoviruses from a longitudinal study of families in metropolitan Washington, D.C.: laboratory, clinical, and epidemiologic observations.

During a 29-month period, we studied enteric infection in 70 families from a pediatric practice in suburban Washington, D.C. Fecal adenoviruses were detected in stools of 18 patients by tissue culture and electron microscopic procedures. From 6 through 11 months of age, the incidence of fecal adenoviruses associated with enteritis was seven per 100, and of confirmed enteric adenoviruses (EAds), three per 100 individuals per year. All EAds belonged to subgenus G (type 41). All three patients with EAds had diarrhea; two had vomiting and one had fever, but none required hospitalization. Ten of the 15 patients with non-EAds were younger than 2 years, and 60% had diarrhea, 40% had vomiting, and 20% had fever. Combined gastrointestinal and respiratory symptoms occurred more often in those who shed non-EAds (three of 11) than in matched controls (two of 48, P = 0.04). An adenovirus was detected in approximately 6% of gastroenteritis episodes, and confirmed EAds were present in approximately 2% of episodes of gastroenteritis in children younger than 2 years of age. None of the contacts of patients with non-EAds shed such virus in their stools. None of nine family contacts of those with EAd appeared to shed adenovirus in stool. In contrast, rotavirus spread readily to exposed adults (25% of 65) and children (56% of 62) when a child in similar families had rotavirus infection.

Adenoviridae↗
PubMed1976

Circuit librarian serves five hospitals in shared program.

There is increasing emphasis on continuing education of hospital personnel, who need and want access to information in order to be aware of advances in health care. Small hospitals cannot afford to duplicate extensive collections. Personnel of hospitals that are remote from urban centers often do not have opportunities to visit a resource library on a regular basis and do not have experience in searching the medical literature through the use of reference tools. It is increasingly evident that the circuit librarian program has served as a catalyst in establishing relationships between the hospitals and the university health sciences center. The director of the CHSL has consulted with the deans of the nursing and the medical schools and with various professors. They have promised that the schools will try to address identifiable continuing education needs or requests from the hospitals. Moreover, the circuit librarian meets with individual hospital personnel and then obtains information for them from the CHSL and its staff. The circuit librarian program is one way to meet community hospitals' needs for access to health sciences literature and to initiate peer interaction for information exchange.

Education, Continuing↗
PubMedDate not supplied

Summary of clinical trials of inactivated influenza vaccine - 1978.

This report summarizes the clinical trials of the A/USSR/77 (H1N1) influenza vaccines performed in 1978. A total of 2,091 subjects participated in these trials. The results of these clinical trials indicated that two doses of H1N1 viral antigen were necessary to produce serum titers of hemagglutinin-inhibiting (HAI) antibody of greater than 1:40 in 80% or more of the test subjects younger than 25 years of age, who were unlikely to have experienced natural infection during the earlier period of prevalence of H1N1 virus (1947-1957). Only one dose of the A/Texas/77 (H3N2) or B/Hong Kong/72 antigen was necessary to stimulate equivalent titers of HAI antibody in serum. Thus, previous natural exposure to H1N1 viruses primed individuals 26 years of age or older to respond to H1N1 antigens. No major differences in antigenicity were noted between whole-virus and split-virus vaccines. No differences in reaction indexes measuring systemic reactions were noted when vaccine types were compared. Only one vaccine was associated with a reaction index appreciably higher than that of placebo. The relatively uniform antibody responses observed were attributed to the newer methods of vaccine standardization introduced after the clinical trials in 1976. No cases of vaccine-related neurological problems, including Guillain-Barré syndrome, were found during these trials. Vaccines containing 7-21 micrograms of each viral antigen were antigenic and were well tolerated.

Adolescent↗