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Biomedical subjects

M Wolff

Publications and source records attributed to M Wolff.

At least 37 records · Page 2Linked to original sources

The efficacy in Navajo infants of a conjugate vaccine consisting of Haemophilus influenzae type b polysaccharide and Neisseria meningitidis outer-membrane protein complex.

BACKGROUND AND METHODS: Several conjugate vaccines against Haemophilus influenzae type b have been developed in the search for one that induces protection even in young infants. We evaluated the safety and efficacy of a conjugate vaccine that links the H. influenzae type b capsular polysaccharide to the outer-membrane protein complex (OMPC) of Neisseria meningitidis serogroup B. We conducted a double-blind, placebo, controlled trial in Navajo infants, who are at high risk for systemic infections caused by H. influenzae type b. The infants were randomly assigned to receive the first dose of vaccine or placebo at 42 to 90 days of age and the second at 70 to 146 days of age. RESULTS: Of the infants in the trial, 2588 were assigned to receive the vaccine and 2602 to receive placebo. The mean follow-up was 269 days in the vaccine group and 267 days in the placebo group. Before the age of 18 months, there was 1 systemic H. influenzae type b infection in the vaccine group, as compared with 22 in the placebo group (P less than 0.001; point estimate of efficacy, 95 percent; 95 percent confidence interval, 72 to 99 percent). Of the 22 H. influenzae type b infections in the placebo group, 13 were meningitis. Among the children who received both doses, there was 1 H. influenzae type b infection in the vaccine group (n = 2056) and 14 in the placebo group (n = 2105) (P less than 0.001; point estimate of efficacy, 93 percent; 95 percent confidence interval, 53 to 98 percent). The single infection in the vaccine group occurred at 15 1/2 months of age in an infant with osteomyelitis. Between the first and second doses there were no H. influenzae type b infections in the vaccine group and eight in the placebo group (P less than 0.005; point estimate of efficacy, 100 percent; 95 percent confidence interval, 41 to 100 percent). CONCLUSIONS: The H. influenzae type b OMPC vaccine, administered at 2 and 4 months of age, is safe and induces a high rate of protection against invasive disease caused by H. influenzae type b in infants under the age of 18 months. Protection begins after the first dose.

Antibody Formation

Erythropoiesis and erythropoietin levels in renal transplant recipients.

Moderately increased blood levels of endogenous erythropoietin (Epo) usually induce complete restoration of renal anemia after successful kidney transplantation. With good graft function erythropoiesis is maintained by normal Epo serum levels. Persistent anemia can be related to iron deficiency, low excretory graft function, and high dosage of immunosuppressive agents leading to marrow suppression or nephrotoxicity. Acute early rejection is associated with a fall in serum Epo and abrogation of reticulocytosis. About 15% of recipients fail to exhibit the normal feedback regulation and develop a mostly transient posttransplant erythrocytosis. Both an increased sensitivity of erythrocytic progenitors to Epo and inappropriate Epo secretion by the native kidneys may account for this overshooting reaction.

Anemia

Antibiotic levels in bronchial tree and in serum during selective digestive decontamination.

Selective digestive decontamination has been found to prevent pulmonary infections in mechanically ventilated patients. The aims of this study were: 1) to determine whether detectable levels of antibiotics could be found in bronchial tree secretions of patients receiving SDD, and 2) to evaluate antibiotic serum levels. In 15 patients receiving mechanical ventilation and SDD for 10 days or more, tobramycin and amphotericin B levels were determined every 3 days in the following specimens: tracheal aspirates, distal bronchial secretions and blood samples. 82% of tracheal aspirates contained detectable (greater than 0.18 mg/l), tobramycin concentrations; the levels varied widely between patients and large day-to-day variations were observed. Every patient had at least 1 tracheal aspirate with tobramycin level higher than 0.5 mg/l during his course. 40% of distal specimens contained detectable tobramycin levels (10 patients). Serum determinations showed detectable concentration of tobramycin in 50% of the specimens (9 patients). Two patients with renal failure had serum tobramycin levels higher than 2 mg/l. In 13 tracheal aspirates cultures were positive and 15 species were isolated; 13 had a MIC higher than the corresponding tobramycin level in tracheal secretions. We conclude that substantial levels of antibiotics can be found frequently in respiratory tract specimens of patients receiving SDD. Therefore, the usual microbiological criteria used to assess respiratory tract infection may be unreliable in this setting and other criteria may be required. Follow-up of antibiotic serum levels is required, especially in patients with renal failure.

Acute Kidney Injury

A field study of the safety and efficacy of two candidate rotavirus vaccines in a Native American population.

A double-blind, randomized, placebo-controlled trial was conducted to evaluate the safety and efficacy of a rhesus rotavirus vaccine and RIT 4237, a bovine rotavirus vaccine, in a Navajo population. Infants aged 2-5 months were randomized to receive one dose of either 10(4) pfu of the rhesus rotavirus vaccine or 10(8) pfu of the RIT 4237 vaccine or placebo. Eleven (10.2%) of 108 infants in the rhesus vaccine group, 11 (10.4%) of 106 in the RIT 4237 group, and 9 (8.4%) of 107 in the placebo group experienced rotavirus diarrhea during the follow-up period of 17 months. Thus, in this population, neither vaccine was efficacious in preventing rotavirus diarrhea.

Diarrhea, Infantile

Safety and immunogenicity of a Haemophilus influenzae type b conjugate vaccine in a high risk American Indian population.

The safety and immunogenicity of a Haemophilus influenzae type b polysaccharide conjugate vaccine linked to the outer membrane protein complex of Neisseria meningitidis (Hib-OMP) were evaluated among Apache and Navajo infants and children. One dose of the Hib-OMP was given to 42 children who were from 12 and 60 months of age. Ninety-two infants 6 to 8 weeks old were given one dose of Hib-OMP at the time of enrollment. A subsequent dose of the vaccine was given 2 months later and a third dose was offered between 12 and 15 months of age. All of the 12- to 60-month-old children achieved a protective antibody concentration (greater than 1 microgram/ml) 1 month postvaccination. Among the 6- to 8-week-old infants only 11% of the Apaches and 8% of Navajos had a protective anti-PRP antibody concentration prevaccination. One month post vaccination 68% of the Apaches and 69% of the Navajos had protective anti-PRP antibody concentrations. One month after the second immunization 67% of the Apaches and 75% of Navajos had protective anti-PRP concentrations. Among the infants that received the third (booster) immunization (N = 28) 74% had protective anti-PRP antibody titers just before the booster immunization. One month after the booster immunization all of the infants had protective concentrations of anti-PRP antibody. We conclude that the Hib-OMP is safe and highly immunogenic among Apache and Navajo infants and children.

Antibodies, Bacterial

Clinical and bacterial features of infections caused by Streptococcus milleri.

The clinical and bacteriological features of 51 infections due to Streptococcus milleri observed in 43 patients over a 2-year period were reviewed. Clinical syndromes included bacteremia in 6 cases, endocarditis in 4 cases, cellulitis and subcutaneous abscesses in 8 cases, pleural empyema in 8 cases, brain abscesses in 5 cases, abdominal infections in 5 cases, and other miscellaneous infections in 15 cases. An underlying condition was associated with infection in 33/43 patients (77%). S. milleri was the only pathogen isolated in 19 patients (44%). All strains of S. milleri were susceptible to penicillin. Surgery was combined with antimicrobial therapy in 27 (63%) patients. Nine patients died during hospitalization, and death was directly related to S. milleri infection in 4 patients (9%). These results confirm that S. milleri frequently causes serious suppurative infections and that species identification is a clinically useful procedure.

Abscess

[HIV infection and "malignant" strongyloidiasis].

Disseminated Strongyloides stercoralis infection occurs in immunocompromised patients. Despite the epidemiological overlap of HIV infection and strongyloidiasis observed in certain parts of the world, only six cases of dissemination have been reported in AIDS patients. The clinical presentation has no special features, except for the frequency of other opportunistic infections. The prognosis is poor. This lack of association between disseminated strongyloidiasis and HIV infection had led to the exclusion of extra-intestinal forms of this paraistosis from the revised classification of AIDS.

HIV Infections

Severe tuberculosis in patients with human immunodeficiency virus infection.

Tuberculosis has now been well documented as a complication of infection with human immunodeficiency virus (HIV), but no studies concern patients requiring admission to the ICU. We report 12 cases of severe disseminated tuberculosis in patients who were seropositive for HIV. Eight patients had diffuse pulmonary involvement responsible for acute respiratory failure, 7 of whom required mechanical ventilation. Four developed septic shock, and in 3 blood cultures were positive for M. tuberculosis. Four patients had central nervous system involvement, with coma requiring mechanical ventilation 3 times. Rapid diagnosis was permitted in 10 patients by acid-fast smears of pulmonary specimens (8 patients) and/or tissue biopsies (4 patients). Seven patients died despite intensive therapy; autopsy was performed in 4 patients, showing disseminated tuberculosis. On the basis of this report, tuberculosis in HIV infection may present as an overwhelming systemic disease and thus requires an aggressive diagnostic and therapeutic approach.

Acquired Immunodeficiency Syndrome

Comparison of the activity of three antibiotic regimens in severe Legionnaires' disease.

Comparison of the activity of different antibiotic regimens in Legionnaire's disease has never been made because of the rarity of well documented cases of that disease. We have retrospectively compared severe cases of Legionnaires' disease treated with pefloxacin alone or in combination with erythromycin and/or rifampicin using computer-matched cases treated either with erythromycin or with erythromycin in combination with rifampicin. This study suggests that: (1) combined therapy including erythromycin, rifampicin and/or pefloxacin is superior to therapy with erythromycin alone; (2) combinations including pefloxacin may be the most active ones; and (3) pefloxacin alone may be as active as combination therapy. Although these results are in agreement with data obtained in cell and in animal models of legionella infection they need to be further confirmed by the study of larger number of patients.

Cause of Death

Modulation of the production of erythropoietin by cytokines: in vitro studies and their clinical implications.

The etiology of the anemia of chronic disorders is complex. Factors which clearly contribute to the suppression of erythropoiesis are (a) reduced iron availability and (b) stimulation of the synthesis of immunomodulatory peptides such as IL-1, TNF-alpha and IFN-gamma, which inhibit the proliferation of erythrocytic progenitors in the bone marrow. The question as to whether lack of EPO is of general importance in the pathogenesis of the anemia of chronic inflammatory and malignant diseases is still a subject of controversy. The present in vitro studies show that IL-1 and TNF-alpha, but not IFN-gamma significantly lower the pO2-dependent formation of EPO in HepG2 cultures. In addition, clinical examples are given of anomalously low or high EPO levels in association with diseases involving the immune system. It is proposed that monokines and related immunomodulatory peptides could play a role in the control of the production of EPO.

Erythropoietin

[The use of the ion exchange polymer Wofatit CP for sample preparation of drugs from urine for high pressure liquid chromatographic and spectrophotometric determinations].

The sample preparation of the alkaline drugs dioxopromethazinehydrochloride and trapidil from urine was studied systematically. The weak acid cation exchanger Wofatit CP was used as stationary phase. Batch mode and column chromatographic sample preparation were compared. The usable capacity of the ion exchanger for the analyte is an important characteristic for the sample preparation. The great influence of pH and ionic strength of the sample on the usable capacity was proved.

Acrylic Resins

[Retinitis disclosing subacute sclerosing panencephalitis].

SSPE is a panencephalitis who involves children and who leads to death. It is due to a defective measles virus. Ophthalmologic features are frequent and may be the first manifestation of the disease. The most typical ocular involvement is retinitis which can be misdiagnosed as a toxoplasmosis.

Adult