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Biomedical subjects

M Wolff

Publications and source records attributed to M Wolff.

At least 55 records · Page 3Linked to original sources
PubMed2002

[Acinetobacter, a nosocomial pathogen. Contribution of experimental models].

EPIDEMIOLOGY: The increasing importance of Acinetobacter as a nosocomial pathogen responsible for outbreaks in intensive care units has been pointed out for twenty years. Today Acinetobacter infections are essentially pneumonia in patients under mechanical ventilation. EXPERIMENTAL MODELS: Most clinical isolates are resistant to b-lactam antibiotics as well as to other drugs. Animal models represent an essential step between in vivo testing an<d clinical studies, necessary to understand physiopathology, pharmacology and efficacy of therapy. The virulence of clinical isolates of Acinetobacter spp has been studied in a mouse model of systemic infection. Pharmacological studies and efficacy of antibiotics have been studied in a mouse model of Acinetobacter pneumonia. HUMAN THERAPEUTICS: The majority of strains are multi-resistant to antibiotics and the infections they cause are difficult to treat. Isolated or combined Sulbactam has often been used with success.

Acinetobacter↗
PubMed2002

[The management of treatment failures for staphylococcal infections].

Therapeutic failure is a situation to be feared in severe infections due to staphylococci. In this article, we consider the difficulties faced is achieving a positive diagnosis in the context of such failures, and an approach to analysing their causes. The possible reasons for therapeutic failure must be considered systematically. The two principle causes are unquestionably the persistence in the patient of an infected, foreign body (intravenous catheter or prosthesis) and endovascular infections (thrombophlebitis or endocarditis). The rules for the prescription of antibiotics are followed, target concentrations are achieved and drug failures are a rarity today. This observation may be called into question by the emergence of strains with diminished sensitivity to glycopeptides. These therapeutic failures remain exceptional cases today.

Anti-Bacterial Agents↗
PubMed2002

The changing clinical aspects of infective endocarditis: descriptive review of 90 episodes in a French teaching hospital and risk factors for death.

OBJECTIVE: We wanted to describe the epidemiological aspects of infective endocarditis (IE) in a French hospital and identify the prognostic factors. METHODS: We reviewed the clinical, echocardiographic and microbiological features, and the outcome of 89 patients (90 episodes, median age 60 years) with IE over 18 months. Logistic regression analysis was used to identify prognostic factors for death. RESULTS: A native valve was involved in 68 cases (75.5%); in 7 of these the patient was an intravenous drug user. A prosthetic valve was involved in 22 cases (24.5%); 5 of these were of early onset. Diagnosis was definite in 87% of cases. Median time to diagnosis was 3 days. Twenty-five patients (28%) were immunocompromised. A portal of entry, usually cutaneous, was identified in 65% of cases. Sixty-two percent of patients had an underlying heart disorder, usually degenerative. The infection involved the left heart in more than 75% of cases. One or more vegetations were detected in 75% of cases. The median size of vegetation was 15 mm. Isolated agents were mainly staphylococci (n=40 (44%), including 12 coagulase-negative isolates), and streptococci (n=23 (25%), including 7 enterococci). In 11 cases (12%), cultures remained negative. Nineteen episodes were nosocomial and Staphylococcus aureus was implicated in 11 of them. Fifty percent of patients had at least one complication: heart failure (n=42), kidney failure (n=44), embolism (n=35), septic shock (n=19). Surgery was performed in 49 cases (54%) due to heart failure (n=19), cerebral embolism (n=12), and/or severe valve lesions (n=27). Eighteen patients died, 10 of whom were infected with S. aureus. Nosocomial IE (P=0.0008), heart failure (P=0.004) and prosthetic valve (P=0.01), but not S. aureus were independently associated with death. CONCLUSIONS: S. aureus was the main microorganism isolated in our patients. However, it was not independently predictive of fatal outcome.

Adult↗
PubMed2002

[MRI in cavernous transformation of the portal vein: secondary biliary abnormalities and portoportal collaterals].

PURPOSE: Evaluation of portoportal collateral vessels and associated biliary abnormalities in patients with cavernous transformation of the portal vein by MRI. MATERIAL AND METHODS: Review of 34 MRI examinations performed on patients with angiographically or MR-angiographically proven cavernous transformation. The analysis included the pattern of the portoportal collateral circulation and the abnormalities of the biliary system, such as wall thickening, stenosis, dilations and irregularities of the extra-and intrahepatic bile ducts. RESULTS: 23 (67.6%) of 34 patients with cavernous transformation had paracholedochal portoportal collateral vessels, with 22 (64.7%) showing visible luminal channels. Epicholedochal venous collaterals could be observed in 8 (23.5%) patients. 24 (70.5%) of 34 patients demonstrated biliary abnormalities due to portoportal collaterals, leading to stenosis with dilatation of the proximal bile ducts in 8 (23.5%) patients. The ductal walls were irregular in 7 (20.5%) patients, and thickened in 11 (32.3%). The gallbladder wall was thickened in 4 (12.9%) patients. CONCLUSION: Portoportal collaterals in patients with cavernous transformation of the portal vein can be identified by MRI. These collaterals frequently alter the biliary system, which must be considered in differential diagnosis of biliary abnormalities observed in the presence of portoportal collaterals.

Adult↗
PubMed2001

[Septic shock with liver abscess in an immunocompetence patient. Presentation of an unusual Fusobacterium nucleatum infection].

BACKGROUND: Fusobacterium septicemia with septic metastasis is a very rare and potentially serous condition when complicated by septic shock. Most cases have been described in patients with humoral immunity disorders and/or severe underlying chronic disease. CASE REPORT: A 24-year-old immunocompetent woman with a tonsil infection developed F. nucleatum septic shock with liver abscess formation. Outcome was rapidly favorable with antibiotic treatment and adapted intensive care, probably favored by the absence of an associated immune deficit. DISCUSSION: Despite its low incidence, F. nucleatum should be entertained as a possible cause of septicemia originating from a pelviperitoneal, pulmonary with abscess formation, or upper airway infection. Proper diagnosis is essential due to the risk of poor prognosis. Fusobacterium nucleatum is a commensal strictly anaerobic bacteria of the buccal cavity. It can cause dental and upper airway infections. Septicemia with secondary localization of F. nucleatum is very rare and the severity depends on the presence of associate septic shock. The immunopathological implications of these infections remain to be elucidated.

Adult↗
PubMed2001

UBA domains mediate protein-protein interactions between two DNA damage-inducible proteins.

The Saccharomyces cerevisiae genes RAD23 and DDI1 were identified in a screen for multicopy suppressors of the temperature-sensitivity of a mutant allele of S. cerevisiae PDS1. Pds1 is a regulator of anaphase that needs to accumulate and then be degraded by the ubiquitin-proteasome pathway at the metaphase-anaphase transition for cells to progress normally through mitosis. Both the Rad23 and Ddi1 pds1 suppression phenotypes depend on a shared motif known as a UBA domain found in a variety of proteins associated with ubiquitin metabolism. UBA domains were found to be essential for homodimerization of Rad23 and heterodimerization between Rad23 and Ddi1, but not for homodimerization of Ddi1. This observation, coupled with the findings that Rad23 and Ddi1 UBA domains bind ubiquitin and that dimerization of Rad23 blocks ubiquitin binding, suggests a possible mechanism for regulating Rad23 and Ddi1 function.

Amino Acid Sequence↗
PubMed2001

A preliminary study of forensic entomology in Medellín, Colombia.

This is the first report of an ongoing study of insect succession on carrion carried out in Medellín, Colombia, using pigs (Sus scrofa) as a model to determine the insect sequence over 207 days. During this period, 2314 insects belonging to the following orders and families were collected: Diptera: Calliphoridae, Muscidae, Piophilidae, Sarcophagidae, Syrphidae, Otitidae; Hymenoptera: Apidae, Formicidae, Halictidae, Mutilidae, Vespidae; Coleoptera: Staphylinidae, Histeridae, Carabidae, Scarabaeidae, Silphidae, Dermestidae, Cleridae, Nitidulidae; Dermaptera: Forficulidae; Hemyptera: Gelastocoridae, Coreidae; Lepidoptera: Hesperiidae. Five decomposition stages were observed (fresh, bloated, active decay, advanced decay, and dry remains) and four insect ecological categories (necrophagous, predators, omnivorous, and incidental). During the fresh stage, the first insects that appeared were flies of the families Sarcophagidae and Muscidae and specimens of Formicidae (Hymenoptera). During the bloated period, species of Calliphoridae (Diptera) were predominant and the first to oviposit. During the third and fourth stages (active decay and advanced decay), the most abundant families were Calliphoridae and Muscidae, although Staphilinidae (Coleoptera) also stood out. During the last stage (dry remains), the dominant family was Formicidae (Hymenoptera) followed by Dermestidae (Coleoptera) with a large number of immature insects.

Animals↗
PubMed2001

Resurgence of blackwater fever in long-term European expatriates in Africa: report of 21 cases and review.

Blackwater fever (BWF) is a severe clinical syndrome, characterized by intravascular hemolysis, hemoglobinuria, and acute renal failure that is classically seen in European expatriates chronically exposed to Plasmodium falciparum and irregularly taking quinine. BWF virtually disappeared after 1950, when chloroquine superseded quinine. We report 21 cases of BWF seen in France from 1990 through 1999 in European expatriates who lived in sub-Saharan Africa. All patients had macroscopic hemoglobinuria, jaundice, and anemia. Acute renal failure occurred in 15 patients (71%), 7 of whom required dialysis. The presumed triggers of BWF were halofantrine (38%), quinine (24%), mefloquine (24%), and halofantrine or quinine (14%). Glucose-6-phosphate dehydrogenase (G6PD) activity was normal in the 14 patients who underwent this test. Low-level P. falciparum parasitemia was found in 8 patients. All 21 patients survived. Our data and 13 cases reported in the literature suggest a resurgence of classic BWF among Europeans living in Africa and a need to discuss attendant therapeutic implications.

Adolescent↗
PubMed2001

QS-21 promotes an adjuvant effect allowing for reduced antigen dose during HIV-1 envelope subunit immunization in humans.

Three separate studies were undertaken in HIV-1 uninfected persons to determine if the adjuvant QS-21 improves the magnitude or kinetics of immune responses induced by recombinant soluble gp120 HIV-1(MN) protein (rsgp120) immunization. The QS-21 was administered at two doses (50 and 100 microg), either alone or in combination with aluminum hydroxide (600 microg). At the highest doses of rsgp120 (100, 300, and 600 microg), QS-21 exerted no significant effect on either binding or neutralizing antibody titers. Antibody binding and neutralizing responses fell dramatically when rsgp120, formulated with alum alone, was given at low doses (3 and 30 microg). In contrast, antibody responses similar in titer to those in the high dose antigen groups were induced with the low dose rsgp120 formulated with QS-21. In addition, the lymphocyte proliferation and delayed type hypersensitivity skin testing were superior in the QS-21 recipients compared with the alum recipients at the low antigen doses. Moderate to severe pain was observed in majority of the volunteers receiving QS-21 formulations, and vasovagal episodes and hypertension were not infrequent. Thus, the use of QS-21 may provide a means to reduce the dose of a soluble protein immunogen.

AIDS Vaccines↗
PubMed2001

Safety and immunogenicity of a recombinant hemagglutinin vaccine for H5 influenza in humans.

Recent outbreaks of avian influenza in humans have demonstrated the need for vaccines for influenza viruses with pandemic potential. Recombinant hemagglutinins are an attractive option for such vaccines because they do not require handling potentially highly pathogenic influenza viruses for vaccine production. In order to evaluate the immunogenicity, optimum dosing and timing of administration of a recombinant baculovirus-expressed H5 HA (rH5) in humans, 147 healthy adults were assigned randomly to receive intramuscular rH5 as two doses of 25, 45 or 90 microg each, one dose of 90 microg followed by a dose of 10 microg, or two doses of placebo, at intervals between doses of 21, 28 or 42 days. All doses of rH5 were well tolerated. The rH5 vaccine was modestly immunogenic at high dose. Neutralizing antibody responses to a titer of 1:80 or greater were seen in 23% (14/60) of individuals after a single dose of 90 microg, and in 52% (15/29) after two doses of 90 microg. Varying intervals between doses from 21 to 42 days had no significant effect on antibody responses to vaccination. These results suggest that baculovirus-expressed H5 HA can induce functional antibody in individuals who have not had prior exposure to H5 viruses, but that further studies to improve the immunogenicity of the vaccine are needed.

Adult↗
PubMed2001

Fludrocortisone acetate to treat neurally mediated hypotension in chronic fatigue syndrome: a randomized controlled trial.

CONTEXT: Patients with chronic fatigue syndrome (CFS) are more likely than healthy persons to develop neurally mediated hypotension (NMH) in response to prolonged orthostatic stress. OBJECTIVE: To examine the efficacy of fludrocortisone acetate as monotherapy for adults with both CFS and NMH. DESIGN: Randomized, double-blind, placebo-controlled trial conducted between March 1996 and February 1999. SETTING: Two tertiary referral centers in the United States. PATIENTS: One hundred individuals aged 18 to 50 years who satisfied Centers for Disease Control and Prevention criteria for CFS and had NMH provoked during a 2-stage tilt-table test. Eighty-three subjects had adequate outcome data to assess efficacy. INTERVENTION: Subjects were randomly assigned to receive fludrocortisone acetate, titrated to 0.1 mg/d (n = 50) or matching placebo (n = 50) for 9 weeks, followed by 2 weeks of observation after discontinuation of therapy. MAIN OUTCOME MEASURE: Proportion of subjects in each group with at least a 15-point improvement on a 100-point global wellness scale. RESULTS: Baseline demographic and illness characteristics between the groups were similar; CFS had been present for at least 3 years in 71%. Using an intention-to-treat analysis, 7 subjects (14%) treated with fludrocortisone experienced at least a 15-point improvement in their wellness scores compared with 5 (10%) among placebo recipients (P =.76). No differences were observed in several other symptom scores or in the proportion with normal follow-up tilt test results at the end of the treatment period. CONCLUSIONS: In our study of adults with CFS, fludrocortisone as monotherapy for NMH was no more efficacious than placebo for amelioration of symptoms. Failure to identify symptomatic improvement with fludrocortisone does not disprove the hypothesis that NMH could be contributing to some of the symptoms of CFS. Further studies are needed to determine whether other medications or combination therapy are more effective in treating orthostatic intolerance in patients with CFS.

Adult↗
PubMed2001

Usefulness of a strategy based on bronchoscopy with direct examination of bronchoalveolar lavage fluid in the initial antibiotic therapy of suspected ventilator-associated pneumonia.

OBJECTIVES: To evaluate (a) the routine accuracy of bronchoalveolar lavage by direct examination (BAL-D) in diagnosing ventilator-associated pneumonia (VAP), and (b) the impact of a diagnostic strategy including clinical judgment, bronchoscopy, and BAL-D on the initial diagnosis and appropriateness of treatment when VAP is suspected. DESIGN AND SETTING: Prospective cohort study in two academic ICUs in Paris, France. PATIENTS AND PARTICIPANTS: Mechanically ventilated patients with suspected VAP underwent bronchoscopy with BAL and protected specimen brush (PSB). BAL-D results were available within 2 h, BAL on culture and PSB results after 24 h, and antibiotic susceptibility after 48 h. At each step in the strategy the senior and the resident in charge of the patient were asked their diagnosis and their therapeutic plan on the basis of presently available data. Definite diagnosis of suspected VAP was based on histology, appearance of cavitation, positive pleural fluid culture, results of PSB and BAL culture, and follow-up. MEASUREMENT AND RESULTS: A total of 110 episodes of suspected VAP were studied; 94 definite diagnoses were made (47 VAP, 47 no VAP). Using a threshold 1% of infected cells, BAL-D discriminated well between patients with and those without VAP (sensitivity 93.6%, specificity 91.5%, area under the receiver-operating characteristic curve 0.953). The senior clinical judgment was correct in 71% cases. It was correct in 78% and 94% of cases after airway visualization and BAL-D findings, respectively. After BAL-D the positive and negative predictive values in diagnosing VAP were 90% and 98%, respectively. However, the therapeutic plan was correct in only 65% using clinical judgment (15 untreated patients, 3 ineffective treatment, 15 useless treatment), 66% using airway visualization (14 untreated VAP, 4 ineffective treatment, 14 useless treatment), and 88% using BAL-D results (1 untreated patients, 6 ineffective, 4 useless), according to definite diagnosis and final antibiotic susceptibility testings. CONCLUSIONS: A strategy based on bronchoscopy and BAL-D generally leads to a rapid and appropriate treatment of nosocomial pneumonia in ventilated patients.

Anti-Bacterial Agents↗
PubMed2001

Dual microsporidial infection with Encephalitozoon cuniculi and Enterocytozoon bieneusi in an HIV-positive patient.

This report describes the first dual microsporidial infection with Encephalitozoon cuniculi and Enterocytozoon bieneusi in an HIV-positive patient. In view of clinical and epidemiological findings, our E. cuniculi isolate was deduced to be of the dog strain. The patient's occupational involvement with dogs indicates that canines should be considered as a reservoir of human infections for both microsporidial species. Furthermore, our report provides detailed clinical and radiological information on a rare case of a symptomatic pulmonary infection by E. cuniculi and its improvement after treatment with albendazole.

AIDS-Related Opportunistic Infections↗
PubMed2001

A violence-prevention and evaluation project with ethnically diverse populations.

The purpose of this paper is to describe some of the challenges encountered and lessons learned while providing and evaluating a violence-prevention program for and with ethnically diverse populations in child care settings. The paper discusses Safe Start, a violence prevention education program for child care staff and parents, and the evaluation of the program. Safe Start was designed to include culturally relevant content to increase cultural awareness for child care staff and parents from diverse ethnic backgrounds. The evaluation project enrolled child care centers with families representing the ethnically diverse communities in which they were located. Violence prevention research involving children from diverse ethnic backgrounds presents new methodologic challenges, but also provides new opportunities for creative, novel methods. This paper describes some of the challenges encountered with curriculum development, staff recruitment, instrument selection, and data collection procedures.

Child↗
PubMed2001

UBA domains of DNA damage-inducible proteins interact with ubiquitin.

Rad23 is a highly conserved protein involved in nucleotide excision repair (NER) that associates with the proteasome via its N-terminus. Its C-terminal ubiquitin-associated (UBA) domain is evolutionarily conserved from yeast to humans. However, the cellular function of UBA domains is not completely understood. Recently, RAD23 and DDI1, both DNA damage-inducible genes encoding proteins with UBA domains, were implicated genetically in Pds1-dependent mitotic control in yeast. The UBA domains of RAD23 and DDI1 are required for these interactions. Timely degradation of Pds1 via the ubiquitin/proteasome pathway allows anaphase onset and is crucial for chromosome maintenance. Here, we show that Rad23 and Ddi1 interact directly with ubiquitin and that this interaction is dependent on their UBA domains, providing a possible mechanism for UBA-dependent cell cycle control. Moreover, we show that a hydrophobic surface on the UBA domain, which from structural work had been predicted to be a protein-protein interaction interface, is indeed required for ubiquitin binding. By demonstrating that UBA domains interact with ubiquitin, we have provided the first indication of a cellular function for the UBA domain.

Amino Acid Sequence↗