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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

Septic shock in patients with the acquired immunodeficiency syndrome.

OBJECTIVE: To evaluate the prognosis of patients with septic shock admitted to an intensive care unit (ICU), according to their HIV serostatus. DESIGN: Retrospective study. SETTING: Medical ICU of a university hospital. PATIENTS: 76 patients with septic shock admitted to the same ICU, of whom 28 were HIV positive and 48 were HIV negative. MEASUREMENTS AND RESULTS: Severity scores, number and type of organ failures, and survival rates were assessed in the two groups of patients. Glasgow Coma Scale and general severity scores [Acute Physiology and Chronic Health Evaluation II and Simplified Acute Physiology Score (SAPS)] were significantly worse in HIV-infected patients. The total number of organ failures was also higher in the HIV-positive group: 3.7 +/- 0.2 vs 3.1 +/- 0.2 in the HIV-negative group (p < 0.001). On day 28, 21 (46%) HIV-negative patients were dead compared to 26 (93%) patients in the HIV-positive group (p < 0.001). In the multivariate analysis, HIV infection was an independent risk factor for mortality, as were the SAPS score, use of mechanical ventilation, and the McCabe score. CONCLUSIONS: This study reports a considerable excess mortality in HIV-infected patients with septic shock. Although severity of illness was clearly much more pronounced in HIV-positive patients, retroviral infection was independently associated with death. Improving survival in HIV-positive patients with septic shock may require earlier diagnosis and treatment of the causative infection.

AIDS-Related Opportunistic Infections

Perioperative use of recombinant human erythropoietin in patients refusing blood transfusions. Pathophysiological considerations based on 5 cases.

The efficacy of the administration of recombinant human erythropoietin (rHuEPO) in the treatment of anaemia in critically ill surgical patients refusing red cell transfusions requires further documentation. Herein, we report the outcome of 5 consecutive severely anaemic Jehovah's Witness patients (lowest haemoglobin concentration 27 g/1), who were discharged from the hospital in good condition after treatment. RHuEPO (50-280 U/kg body weight) was daily administered to 4 of the patients, who either exhibited preoperative anaemia or developed postoperative anaemia refractory to endogenous EPO probably due to inflammation. RHuEPO treatment was followed by a steep rise in reticulocytes and haemoglobin concentration. The fifth patient, who exhibited no signs of systemic inflammation following emergency hemicolectomy, was also treated with intravenous iron, but not with rHuEPO. His blood haemoglobin concentration rose from 27 g/l to 92 g/l in 3 wk. These observations indicate that the administration of rHuEPO is justified in the management of life-threatening anaemia, although only on a humanitarian basis, because there is no predictor for the possible spontaneous recovery.

Adult

alpha 1-Proteinase inhibitor in gingival crevicular fluid of humans with adult periodontitis: serpinolytic inhibition by doxycycline.

The serum protein, alpha 1-proteinase inhibitor (alpha 1-PI), defends the host against serine proteinases, e.g. PMN elastase. Using a rabbit anti-serum against human alpha 1-PI, this protein in GCF was quantified from a standard curve constructed from dot-blot analysis and characterized by Western blot. GCF was collected on filter paper strips from healthy (H), gingivitis (G) and adult periodontitis (AP) patients, then extracted with Tris/NaCl/CaCl2 buffer, pH 7.6. alpha 1-PI concentration increased with G and was highest in AP subjects. H sites only showed intact alpha 1-PI (52 kDa); no degradation fragments (48 kDa) were detected. In G and AP subjects, alpha 1-PI degradation fragments were seen in 17% and 71% of GCF samples, respectively. Both collagenase and alpha 1-PI-degrading activities in GCF increased with severity of inflammation (GCF flow). Moreover, the alpha 1-PI degrading (or serpinolytic) activity was characterized as a matrix metalloproteinase, probably collagenase, based on its in vitro response to a panel of different proteinase inhibitors including doxycycline. We propose: (1) that collagenase promotes periodontal breakdown not only by degrading collagen, but also by depleting alpha 1-PI regulation of elastase and other serine-proteinases, thereby favoring a broader attack on extracellular matrix (ECM) constituents, and (2) based on a recent longitudinal double-blind study using the techniques described above for alpha 1-PI analysis, that low-dose doxycycline administration to humans with adult periodontitis can inhibit this broad cascade of ECM degradation.

Adult

Use of a new mouse model of Acinetobacter baumannii pneumonia to evaluate the postantibiotic effect of imipenem.

Acinetobacter baumannii is responsible for severe nosocomial pneumonia. To evaluate new therapeutic regimens for infections due to multiresistant strains and to study the pharmacodynamic properties of various antibiotics, we developed an experimental mouse model of acute A. baumannii pneumonia. C3H/HeN mice rendered transiently neutropenic were infected intratracheally with 5 x 10(6) CFU of A. baumannii. The mean log10 CFU/g of lung homogenate (+/- the standard deviation) were 9 +/- 0.9, 9.4 +/- 0.8, 8.6 +/- 1.2, and 7.7 +/- 1.4 on days 1, 2, 3, and 4 postinoculation. The lung pathology was characterized by pneumonitis with edema and a patchy distribution of hemorrhages in the peribronchovascular spaces of both lungs. Abscesses formed on days 3 and 4. Four days after inoculation, subacute pneumonitis characterized by alveolar macrophage proliferation and areas of fibrosis was observed. The cumulative mortality on day 4 was 85%. This new model was used to study the effects of 1, 2, or 3 50-mg/kg doses of imipenem. Imipenem concentrations in lungs were above the MIC for 2 h after the last dose. The in vivo postantibiotic effect (PAE) was determined during the 9-h period following the last dose; it decreased in duration with the number of doses: 9.6, 6.4, and 4 h after 1, 2, and 3 50-mg/kg doses, respectively. In contrast, no in vitro PAE was observed. This model offers a reproducible acute course of A. baumannii pneumonia. The presence of a prolonged in vivo PAE supports the currently recommended dosing intervals of imipenem for the treatment of human infections due to A. baumannii, i.e., 15 mg/kg three times a day.

Acinetobacter

Antibody to human immunodeficiency virus type 1 (HIV-1) gp160 in mucosal specimens of asymptomatic HIV-1-infected volunteers parenterally immunized with an experimental recombinant HIV-1 IIIB gp160 vaccine. The National Institute of Allergy and Infectious Diseases-sponsored AIDS Vaccine Evaluation Group.

Twenty-two human immunodeficiency virus type 1 (HIV-1)-infected, asymptomatic volunteers with CD4 cell counts of >600 cells/mm3 who were enrolled in a phase I immunotherapy trial comparing two schedules of immunization of an HIV-1 IIIB-based recombinant gp160 (rgp160) experimental vaccine were evaluated for rgp160-specific antibodies in parotid saliva, genital secretions, and serum. When the study was unblinded, it was determined that five volunteers had received rgp160 on a month 0, 1, 2, 3, 4, and 5 immunization schedule, seven volunteers had received rgp160 on a month 0, 1, 2, and 5 schedule, five had received alum/deoxycholate placebo, and seven had received a licensed hepatitis B virus vaccine. Five volunteers consented to the donation of parotid saliva but not genital secretions. Prior to immunization, parotid saliva specimens were available for 11 of 22 volunteers, seminal plasma (SP) specimens were available for 7 of 22 volunteers, cervicovaginal lavage (CVL) specimens were available for 5 of 22 volunteers, and serum was available for 22 of 22 volunteers. These baseline specimens and specimens collected at 1 and 7 months after the final immunizations were assessed by enzyme-linked immunosorbent assay for immunoglobulin G (IgG) and IgA antibodies specific for HIV-1 LAI rgp160 or HIV-1 MN rgp160. No augmentation in HIV rgp160-specific IgG or IgA antibody production in either parotid saliva or serum specimens of vaccinees compared to that in controls was observed after immunization. There were insufficient numbers of SP or CVL specimens available for statistical comparisons between vaccinees and controls. Overall, anti-LAI rgp160 IgG antibodies were detected in the parotid saliva specimens of 20 of 22 volunteers, the seminal plasma specimens of 11 of 11 volunteers, and the CVL specimens of 6 of 6 volunteers and in 21 of 22 serum specimens. Fewer volunteers expressed anti-LAI rgp160 IgA antibodies in mucosal or serum specimens: 11 of 22 parotid saliva specimens, 3 of 11 SP specimens, 3 of 5 CVL samples, and 12 of 22 sera.

AIDS Vaccines

Ets-1 and Ets-2 proto-oncogenes exhibit differential and restricted expression patterns during Xenopus laevis oogenesis and embryogenesis.

Xenopus XI-ets-1 and XI-ets-2 are maternally expressed. From late oogenesis to early embryogenesis their transcripts are localized to the animal pole and the intermediate zone, suggesting a function in the differentiation of animal blastomeres and future mesoderm. Their presence at the level of germ plasm suggests also a role in the differentiation of the germinal lineage. Both zygotic genes are expressed ubiquitously beginning at MBT, and then restricted to a circumblastoporal collar. In neurula and tailbud stages, ets-1 and ets-2 transcripts are detected in neural crest cells and their derivatives. Specific transcription can also be observed for ets-1 in the hemangioblastic precursors, in endothelial cells of the forming heart and blood vessels. Ets-2 is itself specifically expressed in the putative pronephros and in the forming pronephric tubules and extending pronephric duct. Like another member of the ets-gene family (XI-fli), both genes are transcribed in regions of the embryo undergoing important morphogenetic modifications, especially in migrating cells and/or along their migration pathways. We postulate that these genes orchestrate modifications of cellular adhesion. Changes in the expression of cadherins and integrins repertories would be consistent with such a role and could account for the phenotypes we reported earlier for XI-fli overexpression. Such a role would be critical for tumor cell dissemination, in addition to the one already ascribed to ets-1 in the expression of proteases specific for the extracellular matrix.

Animals

[Pulmonary cryptococcosis during HIV infection. 15 cases].

We reviewed the records of 15 Human Immunodeficiency Virus (HIV) infected patients with pulmonary cryptococcosis (PC). PC was the first AIDS-defining manifestation in nine patients. HIV infection was identified simultaneously with the onset of PC in 4 patients. The CD4+ lymphocyte count was low in all cases (median, 24/m3). Chest radiography showed interstitial infiltrates in 13 instances, associated with pleural effusion in 5 cases and hilar adenopathy in 2 cases. In one case, chest-X-ray showed isolated pleural effusion and was normal in one patient. For 11 of 12 patients, bronchoalveolar lavage fluid culture was positive for Cryptococcus neoformans. Seven of 15 patients had evidence of extrapulmonary cryptococcal disease with positive cerebrospinal fluid culture. Serum cryptococcal antigen was detected in all 15 patients. Concomitant lung infection with Pneumocystis carinii was diagnosed in 4 patients. First-line regimen was fluconazole in 10 patients and amphotericin B in 4 patients. Fluconazole has been prescribed in 7 patients as a permanent suppressive therapy and should be continued indefinitely.

AIDS-Related Opportunistic Infections

[Occupational accidents with exposure to biological fluids. Recommendations for the management of exposed workers].

Health Care Workers (HCW) are continually exposed to body fluids from patients. Some of these fluids may carry pathogens potentially transmissible to HCWs if the exposure is considered to be of "high risk" (mainly percutaneous exposure). The main agents that have been transmitted by occupational exposure are hepatitis B and C viruses and human immunodeficiency virus (HIV). The risk of transmission after risky occupational exposure to these agents is about 2-40%, 3-10% and 0.2-0.3% respectively. This review presents an operational recommendation for the management of HCWs occupationally exposed to patients' body fluids. The recommendations, through a system of algorithms focus in assessing the actual risk of the accident and the body fluid involved, the possibility of the fluid harboring a transmissible pathogen, the susceptibility of the HCW to that pathogen and the post exposure measure to be taken. For hepatitis B, pre exposure immunization is highly recommended and that vaccine in addition to hyperimmune globulin for post exposure prophylaxis is advisable. For risky occupational exposures to HIV counselling is mandatory; the role of post exposure drug prophylaxis is discussed. Hepatitis C can be occupationally transmitted; no known post exposure prophylactic measures are available. Due to the low incidence of these and other transmissible pathogens in the general population the author's recommendation is that occupational exposure to body fluids from unidentifiable or unknown sources or from patients without clinical evidence of these infections be considered as low risk, and no baseline or follow up serologic studies or measures besides counselling be taken. For other causes, the serologic follow up for exposed HCWs for each of these infections is presented.

Accidents, Occupational

The prevalence and aetiology of persistent diarrhoea in adults in urban Zambia.

As the AIDS pandemic has spread, diarrhoea in adults has become a major burden on health care institutions in central Africa and on the families of sufferers. In order to assess the magnitude of the problem, we carried out a survey of households in a high population density township of Lusaka to determine the prevalence of persistent diarrhoea in adults. We also carried out a study of the causes of persistent diarrhoea in patients attending the University Teaching Hospital, Lusaka. The community survey assessed 460 households, representing a sample of 1440 adults. 94 adults were reported as having had diarrhoea in the 2 weeks prior to the survey, implying an attack rate of 1.74 per adult per year. Of these 94 cases, six had diarrhoea of between 2 and 4 weeks duration, and ten had diarrhoea of over 4 weeks duration. In the hospital study, 75 (97%) out of 77 patients with diarrhoea of over 1 months' duration were HIV seropositive; potentially pathogenic parasites were found in 61/75 (81%) of seropositives. This information indicates that persistent diarrhoea in adults, mostly related to HIV infection, is likely to be an important and growing reservoir of enteric pathogens and represents a significant burden on hospitals and relatives. This emerging problem in sub-Saharan Africa may foreshadow developments in other continents.

Adult

Outbreak of multiply resistant enterobacteriaceae in an intensive care unit: epidemiology and risk factors for acquisition.

A prospective study was initiated in an intensive care unit (ICU) where extended-spectrum beta-lactamase-producing enterobacteriaceae (ESBLPE) were endemic. From July 1990 to July 1991, patients hospitalized for > or = 5 days were screened for ESBLPE acquisition by means of weekly rectal sampling and clinical cultures. Baseline characteristics and various ICU procedures in 62 cases of ESBLPE were compared with those for 205 patients without ESBLPE, with use of Cox's model. Risk for acquiring ESBLPE (Klebsiella pneumoniae in most cases) increased during the ICU stay, from 4.2% in the first week to 24% in the fourth week. Baseline characteristics were not different between the two groups. Urinary catheterization (P = .04) and arterial catheterization (P = .03) were independent risk factors for acquiring ESBLPE and probably reflected frequency of health care manipulations. The first site of ESBLPE acquisition was the digestive tract in 58 of the 62 patients; 28 infections developed in 22 patients, and these followed or occurred simultaneously with rectal colonization in 18 of those 22. DNA macrorestriction analysis suggested that the same strain was responsible for most cases. In conclusion, ESBLPE acquisition depends on length of stay in the ICU and the use of invasive procedures. Colonization is a prerequisite for infection.

Adult

Tuberculous meningitis in adults: review of 48 cases.

The cases of 48 adult patients with tuberculous meningitis who were admitted to intensive care unit (ICU) between 1982 and 1993 were reviewed. An underlying disease was present in 24 patients (50%), including 10 with human immunodeficiency virus infection. Forty-seven patients were referred to the ICU because of neurological deterioration; 22 were comatose at admission. Forty-six patients received antituberculous treatment; 36 required mechanical ventilatory support, and 16 underwent neurosurgery. Thirty-one patients died within 4 months after admission, and the remaining 17 were alive at a 1-year follow-up. Univariate prognostic analysis selected three variables, all assessed at admission, associated with outcome: time to onset of treatment of > or = 3 days (P = .003), coma (P = .006), and simplified acute physiology score of > 11 (P = .03). Thus, the outcome of tuberculous meningitis is mainly determined by the clinical stage at admission and the delay in starting treatment. These findings underscore the need to initiate early therapy as soon as the diagnosis of tuberculous meningitis is suspected.

Adolescent

Cryptococcus neoformans infection in France: epidemiologic features of and early prognostic parameters for 76 patients who were infected with human immunodeficiency virus.

We retrospectively carried out a descriptive and prognostic study of 76 human immunodeficiency virus-infected patients with cryptococcosis diagnosed by a positive culture of cerebrospinal fluid (CSF), blood, urine, or other body fluid or tissue. We focused on the 65 patients with cryptococcal meningitis. At diagnosis, the mean CD4 lymphocyte count was 46/mm3; 86% of patients had fever; 67%, headache; 37%, stiff neck; 29%, altered mentation or confusion; 20% cranial nerve deficiency; and 48%, other focal deficiencies. Analysis of CSF specimens revealed the following results: normal (25% of the specimens), leukocyte count of < 20/mm3 (62%), positive India ink smear (87%), and positive cryptococcal antigen (92%). Twenty patients died within the first 3 months (3-month survival rate, 70%). A Cox regression model selected the following as prognostic parameters: age older than 30 years (relative risk [RR] = 2.1), CSF glucose level of < 2 mmol/L (RR = 3.7), previous admission to an intensive care unit (RR = 4.7), and mechanical ventilation (RR = 4.6). The outcome of cryptococcal meningitis in patients with AIDS remains difficult to predict at admission, and every case should be considered as potentially severe.

AIDS-Related Opportunistic Infections

How valid are clinical signs of dehydration in infants?

Our objective was to determine the ability of several clinical signs of dehydration to distinguish among degrees of dehydration in infants with acute diarrhea. The design was a prospective cohort study in a pediatric referral hospital in Cairo, Egypt. Infant boys, 3-18 months old, with a history of acute diarrhea (5 or more watery stools per day for no more than 7 days) were eligible, except those with frank protein-energy malnutrition, serious nongastrointestinal illness, or being exclusively breast-fed. Several clinical signs of dehydration were assessed upon study entry. Subjects were then rehydrated with an oral rehydration solution and fed a standardized diet until diarrhea ceased (no watery or loose stools for 16 h). The main outcome measure was percent body weight gain at rehydration and at resolution of illness. Data from 135 subjects were available for analysis. Average (SD) rehydration phase duration was 5.2 (2.1) h, and average (SD) duration of illness was 54.5 (38) h. Multiple regression analysis selected prolonged skinfold, altered neurologic status, sunken eyes, and dry oral mucosa as the clinical signs that correlated best with percent dehydration (R2 for model 0.244, p < 0.001). Mean weight gain for the two assessment systems was 3.6-3.9% for mild, 4.9-5.3% for moderate, and 9.5-9.8% for severe dehydration. The most valid clinical signs of dehydration include prolonged skinfold, altered neurologic status, sunken eyes, and dry oral mucosa. Children with clinical signs of mild or moderate dehydration have fluid deficits on the order of 3 or 5% body weight, respectively.

Acute Disease

Nosocomial cerebral aspergillosis: a report of 3 cases.

Cerebral aspergillosis carries a mortality rate close to 100%, especially in immunocompromised patients. We describe 3 patients who contracted cerebral aspergillosis after neurosurgery, 2 of whom survived after exhaustive surgical treatment and medical treatment with high doses of amphotericin B (once liposomal), 5-fluorocytosine and itraconazole. We review the few non-fatal cases of cerebral aspergillosis reported. We consider that surgical excision must be complete and repeated if necessary, always in combination with medical treatment.

Adolescent