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Biomedical subjects

M Wolff

Publications and source records attributed to M Wolff.

At least 73 records · Page 4Linked to original sources
PubMed2001

Contractile hyporesponsiveness of hepatic arteries in humans with cirrhosis: evidence for a receptor-specific mechanism.

Splanchnic vasodilatation and vascular hyporesponsiveness to vasopressors are characteristic features of patients with cirrhosis. Although the vascular response to different vasopressors has been shown to be attenuated in cirrhosis, alterations on the receptor level are discussed controversially. Thus, impaired postreceptor signaling has been postulated. However, so far this has not been studied in human splanchnic vessels. Therefore, we assessed the vascular response of human hepatic arteries after activating the G-protein-dependent signal transduction pathway by stimulation with angiotensin II, the thromboxane A(2) analog U46619, or by G-protein activation with NaF/AlCl(3). After endothelium denudation, cumulative isometric concentration contraction curves were obtained for hepatic arteries from 32 cirrhotic patients undergoing liver transplantation and from 40 organ donors after stimulation with either angiotensin II (10(-11)-10(-5) mol/L), U46619 (10(-10)-10(-6) mol/L) or AlCl(3) (30 micromol/L)/NaF (10(-4)-3 x 10(-2) mol/L). Hepatic arteries from cirrhotic patients were markedly less responsive to angiotensin II (P <.0001) than those from organ donors. Both stimulation of the G-protein phospholipase C pathway via the thromboxane A(2) receptor and receptor-independent G-protein stimulation with AlCl(3)/NaF, induced an intact contractile response. In conclusion, the G-protein-dependent signal transduction system itself is unaltered in cirrhosis. Hence, the cause of the hyporesponsiveness to some vasoconstrictors in cirrhosis appears to be a receptor-specific phenomenon localized upstream from the G-protein level.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2001

Surveillance of antibiotic resistance in European ICUs.

Antibiotic resistance among bacteria causing hospital-acquired infections poses a threat, particularly to patients in intensive care units (ICUs). In order to control the spread of resistant bacteria, local, regional and national resistance surveillance data must be used to develop efficient intervention strategies. In an attempt to identify national differences and the dynamics of antibiotic resistance in European ICUs, data have been merged from several networks of resistance surveillance performed during the 1990s. It should be stressed, however, that comparisons of results from different studies using different methods and different population samples must be made with caution. Antibiotic resistance across all species and drugs was, with some exceptions, highest in southern European countries and Russia, and lowest in Scandinavia. More effective strategies are needed to control the selection and spread of resistant organisms. Antibiotic intervention policies, efficient infection control measures and an overall awareness of the serious implications at public health level will contribute to the management of antibiotic resistance.

Acinetobacter↗
PubMed2001

[Obstruction of surgical portosystemic shunts in the early postoperative phase: interventional treatment by angioplasty with stent implantation].

PURPOSE: Recurrent variceal bleeding in patients treated with surgical porto-systemic shunting is most often due to shunt stenoses or occlusion. Radiological interventional procedures are a possible method of therapy and our experience herein is described in this report. PATIENTS AND METHODS: From 1997 to 1999 54 patients with recurrent variceal bleeding were treated with a surgical porto-systemic shunt procedure. Of these early shunt occlusion occurred in 5 patients, which was treated with percutaneous transcatheter techniques. RESULTS: In only one patient was PTA alone sufficient to reestablish shunt patency, in four patient stent placement was necessary in addition. In the follow-up period 1 patient died 26 month after intervention with (autopsy-proven) patent shunt, in one patient shunt reocclusion occurred after 11 months and in 3 patients the shunt is still patent. CONCLUSIONS: PTA, if necessary in combination with stent placement, is an attractive alternative method of therapy in case of an early surgical porto-systemic shunt occlusion.

Adult↗
PubMed2001

Late detection of neuroblastoma in a patient with prolonged cerebellar ataxia without opsoclonus.

A 19-month-old boy presented with acute-onset cerebellar ataxia following immunisation. Ataxia was prolonged with a fluctuating course over a period of two years. Opsoclonus was never observed. Extensive diagnostic studies were negative during this time. Finally, a neuroblastoma was discovered. Ataxia disappeared completely during polychemotherapy. This report suggests that occult neuroblastoma must be considered in any child with unexplained prolonged cerebellar ataxia. Specific investigations are recommended for such cases.

Adrenal Gland Neoplasms↗
PubMed2001

Varicella-zoster virus limbic encephalitis in an immunocompromised patient.

A case of limbic encephalitis in a patient who had undergone prolonged immunosuppressive treatment with i.v. cyclophosphamide and oral prednisolone for a microscopic polyangeitis is reported. A brain MRI scan revealed symmetric mesial temporal lobe lesions. Studies of cerebrospinal fluid (CSF) revealed a positive PCR for varicella-zoster virus (VZV) DNA in 2 separate samples. Owing to a delay in diagnosis, intravenous acyclovir was initiated only after 11 d of symptoms. PCR of CSF for VZV DNA became negative on day 14 of treatment while brain lesions had resolved on subsequent MRI scans. Limbic encephalitis is a novel form of VZV infection. When brain imaging is suggestive of limbic encephalitis in an immunocompromised patient, PCR of CSF for VZV DNA should be performed, as early antiviral treatment may improve the outcome.

Acyclovir↗
PubMed2001

Working with our communities: moving from service to scholarship in the health professions.

CONTEXT: As faculty at health professionals schools have become increasingly engaged with their communities in partnerships to improve health, new questions have arisen about faculty rewards for such activities. To sustain the community work of their faculty, institutions need to reconceptualize faculty rewards, promotion, and tenure that are relevant to community activities. HISTORICAL PERSPECTIVE: Scholarship has evolved since the 17th century from a focus on character-building to the practical needs of the nation to an emphasis on research. In 1990, Boyer proposed four interrelated dimensions of scholarship: (1) discovery; (2) integration;(3) application; and (4) teaching. The challenge became the development of criteria and innovative and creative ways to assess community scholarship. CURRENT MODELS FOR COMMUNITY SCHOLARSHIP: This paper reviews four evidence-based models to document and evaluate scholarly activities that are applicable to community scholarship. PROPOSED MODEL FOR COMMUNITY SCHOLARSHIP: We propose a new model for community scholarship that focuses on both processes and outcomes, crosses the boundaries of teaching, research, and service, and reshapes and integrates them through community partnership. We hope this model will generate national discussion about community scholarship and provide thought-provoking information that will move the idea of community scholarship to its next stage of development.

Journal Article↗
PubMed2001

Building effective community-academic partnerships to improve health: a qualitative study of perspectives from communities.

PURPOSE: To identify, through a qualitative study, community perspectives on the critical factors that facilitate the development, effectiveness, and sustainability of community-academic partnerships. METHOD: Between June 1998 and April 1999, 25 semistructured interviews were conducted with community members who represented eight partnerships at five academic health centers. Content analysis and open coding were performed on the data, and patterns of ideas and concepts were categorized. RESULTS: After review of the data, responses from three partnerships were excluded. Nine major themes that community respondents thought strongly influenced the effectiveness of community-academic partnerships emerged from respondents from the remaining five partnerships: (1) creation and nurturing of trust; (2) respect for a community's knowledge; (3) community-defined and prioritized needs and goals; (4) mutual division of roles and responsibilities; (5) continuous flexibility, compromise, and feedback; (6) strengthening of community capacity; (7) joint and equitable allocation of resources; (8) sustainability and community ownership; and (9) insufficient funding periods. CONCLUSION: The themes that emerged from this study of the perceptions and experiences of the community partners in community-academic partnerships can be critical to further developing and evolving these partnerships.

Academic Medical Centers↗
PubMed2001

Safety, vaccine virus shedding and immunogenicity of trivalent, cold-adapted, live attenuated influenza vaccine administered to human immunodeficiency virus-infected and noninfected children.

OBJECTIVE: To assess the safety of live, attenuated influenza vaccine (LAIV) administered to relatively asymptomatic or mildly symptomatic HIV-infected children and non-HIV-infected children. METHODS: Twenty-five non-HIV and 24 HIV-infected children (CDC Class N or A1,2) were enrolled into this double blind, placebo-controlled study. Children were randomized within each HIV status group to one of two dosing regimens: Regimen 1, Dose 1 = LAIV, Dose 2 = placebo, Dose 3 = LAIV; or Regimen 2, Dose 1 = placebo, Dose 2 = LAIV, Dose 3 = LAIV. Study doses were separated by 28 to 35 days. Reactogenicity events within 10 days and adverse events within 28 to 35 days after each study dose were recorded. Blood HIV RNA concentrations, CD4 counts and CD4% were measured throughout the study on HIV-infected children. Quantitative influenza cultures were performed on nasal aspirates collected periodically from all children up to 28 to 35 days after each study dose. Influenza isolates were assessed for retention of the temperature-sensitive phenotype. Serum influenza HAI antibodies were measured before and after each LAIV vaccination. RESULTS: No significant differences were found in rates of reactogenicity events and vaccine-related adverse events after placebo or the first dose of LAIV within each HIV status group, nor were differences found between HIV-infected and HIV-uninfected children after each dose of LAIV. Overall none of the HIV-infected children experienced a significant LAIV-related serious adverse event or influenza-like illness, making the one sided 95% CI of such a serious event occurring after LAIV 0 to 12%. No significant changes in geometric mean HIV RNA concentrations, CD4 counts or CD4% or prolonged or increased quantity of LAIV virus shedding occurred in HIV-infected children after receiving either dose of LAIV. All recovered influenza isolates retained the temperature-sensitive phenotype. After two doses of LAIV, 83% of the non-HIV-infected and 77% of the HIV-infected children had a > or = 4-fold rise in influenza antibody to at least one of the three LAIV strains. CONCLUSION: If relatively healthy HIV-infected children become exposed to LAIV inadvertently, then serious adverse outcomes would not be expected to occur frequently.

Child↗
PubMed2001

Dosage suppressors of pds1 implicate ubiquitin-associated domains in checkpoint control.

In budding yeast, anaphase initiation is controlled by ubiquitin-dependent degradation of Pds1p. Analysis of pds1 mutants implicated Pds1p in the DNA damage, spindle assembly, and S-phase checkpoints. Though some components of these pathways are known, others remain to be identified. Moreover, the essential function of Pds1p, independent of its role in checkpoint control, has not been elucidated. To identify loci that genetically interact with PDS1, we screened for dosage suppressors of a temperature-sensitive pds1 allele, pds1-128, defective for checkpoint control at the permissive temperature and essential for viability at 37 degrees C. Genetic and functional interactions of two suppressors are described. RAD23 and DDI1 suppress the temperature and hydroxyurea, but not radiation or nocodazole, sensitivity of pds1-128. rad23 and ddi1 mutants are partially defective in S-phase checkpoint control but are proficient in DNA damage and spindle assembly checkpoints. Therefore, Rad23p and Ddi1p participate in a subset of Pds1p-dependent cell cycle controls. Both Rad23p and Ddi1p contain ubiquitin-associated (UBA) domains which are required for dosage suppression of pds1-128. UBA domains are found in several proteins involved in ubiquitin-dependent proteolysis, though no function has been assigned to them. Deletion of the UBA domains of Rad23p and Ddi1p renders cells defective in S-phase checkpoint control, implicating UBA domains in checkpoint signaling. Since Pds1p destruction, and thus checkpoint regulation of mitosis, depends on ubiquitin-dependent proteolysis, we propose that the UBA domains functionally interact with the ubiquitin system to control Pds1p degradation in response to checkpoint activation.

Amino Acid Sequence↗
PubMed2001

[Prospective follow-up of a HIV infected population with and without access to antiretroviral therapy: impact of survival and complications].

BACKGROUND: Three-drug antiretroviral therapy (ART-3) has reduced complications and improved survival in HIV+ patients. The Chilean Public Health System began dual therapy (ART-2) in 1997, covering approximately 40% of patients in need. AIM: To report the results of a follow-up of patients with and without access to ART in a Chilean public hospital. PATIENT AND METHODS: Prospective follow-up of patients with ART-2 and 3 (cases) and patients with no access to ART (controls). All patients needed ART but it was available to a minority of them. Selection for ART was at random. Follow-up was between 6-24 months (11/96 to 3/99). Basal and periodic clinical and laboratory parameters were determined. Mortality and occurrence of new AIDS-defining events (ADE) were compared statistically using chi square. RESULTS: One hundred and fifty cases (106 ART2, 28 ART3 and 16 ART2 expanded to ART3) and 166 controls were studied. Basal parameters were similar except prior ART (32.7 and 18.7% in cases and controls respectively). Close to 1/3 patients had AIDS. Cases had a mean follow up of 527 days; controls, 478. Six cases (4%) (5 in ART-2) and 17 controls (10%) died. Mortality x 100/pts/yr was 2.7 in cases and 7.7 in controls, p < 0.05. ADE per 100/pts/yr was 21 in cases (24.4 in ART2, 15.1 in TAR3) and 54.5 in controls, p < 0.05. Cases had a reduction of: esophageal candidiasis (84%), tuberculosis (75%), cryptococcosis and toxoplasmosis (66%), P carinii pneumonia (55%) and bacterial pneumonia (46%) and they had fewer hospitalizations (73%). Late assessment: 70 of 101 ART-2 patients had changed to ART-3 (1 death); 22 of 101 kept original ART-2 (12 dead, 10 alive), 39 of 43 ART-3 patients were alive and 1 died. CONCLUSIONS: Short-term ART-2 and 3 significantly reduced mortality (60% and 73%) ADE (65% and 76% respectively) and hospitalizations. Benefits of ART-2 were short lived. Resource-constrained countries cannot depend on weaker than standard ART for proper care of people with HIV disease.

Adult↗
PubMed2000

A phase II study of two HIV type 1 envelope vaccines, comparing their immunogenicity in populations at risk for acquiring HIV type 1 infection. AIDS Vaccine Evaluation Group.

Several immunogens induce HIV-specific neutralization and in vitro lymphoproliferation in adults at low HIV-1 risk, but responses in persons at high HIV-1 risk are not known. We performed a multicenter, double-blinded, adjuvant-controlled trial with two gp120 vaccines in 296 HIV-1-uninfected volunteers, including 176 reporting higher HIV-1 risk activities. The immunogens were remarkably well tolerated. After three immunizations, 210 of 241 vaccinees (87%) developed neutralizing antibodies, which persisted in 59% after 2 years. The injection drug users receiving SF-2/gp120 had decreased antibody responses relative to the lower risk groups. Envelope-specific lymphoproliferation peaked after two immunizations, and 54% of vaccinees mounted a DTH reaction to gp120 after 4 years. In summary, these immunogens have low adverse reactogenicity and induce durable antibody and T cell responses to the prototype strains. Unexpected differences in antibody responses among diverse HIV-1 risk strata lend support to the conduct of expanded phase II trials in populations other than low-risk volunteers.

AIDS Vaccines↗
PubMed2000

Inhibition of neuraminidase with neuraminic acid C-glycosides.

Neuraminic (sialic) acid based alpha-C-glycosides have been synthesized and their inhibitory activity towards bacterial neuraminidase (sialidase) was examined. While some C-glycosides were found to be potent inhibitors (Ki 15-30 microM) of this neuraminidase, others afforded no measurable activity. The structure-activity relationship of these C-glycosides is discussed in the context of other previously reported sialidase inhibitors.

Buffers↗
PubMed2000

[Orthotopic liver transplantation in a 33-year-old patient with fulminant hepatitis B and HIV infection].

HISTORY AND CLINICAL FINDINGS: A 33-year-old man with fulminant hepatitis B infection was to have an orthotopic liver transplantation (OLTX) because of the otherwise poor prognosis. During preparations for it he was found also to have an HIV-infection. INVESTIGATIONS: Preoperatively the Quick value was 9%, and he had a grade 2 encephalopathy. His immune status was impaired: 477 CD4-T-helper cells/microliter. Virus load, measured with a quantitative HIV-RNA test, was < 80 copies/ml (i.e. below demonstrable level). DIAGNOSIS, TREATMENT AND COURSE: After the first transplantation had ended in organ failure, a second one two days later was successful. But there were several complications postoperatively: ischaemic-toxic tubular renal failure requiring haemodialysis, underperfusion of the right lobe of the liver due to arterial stenosis, pleural effusion, cytomegalovirus infection and cyclosporin-induced hypertension. But all these were successfully managed. At the time of this report, 27 months later, the patient felt well and his immune state was stable. During these 2 years he had a practically normal T-helper count and HIV-RNA measured below 80 copies/ml with good liver function. There has been no indication for antiviral treatment and there have been no complications relating to immunosuppression. CONCLUSION: The low life expectancy before effective antiviral drugs are available explains the reluctance to perform OLTX in HIV-infected patients. The favourable course in this case, using highly efficacious combined antiretroviral treatment now being available, indicates that after careful consideration, OLTX can be performed in selected patients with HIV.

Adult↗
PubMed2000

Invasive and noninvasive strategies for management of suspected ventilator-associated pneumonia. A randomized trial.

BACKGROUND: Optimal management of patients who are clinically suspected of having ventilator-associated pneumonia remains open to debate. OBJECTIVE: To evaluate the effect on clinical outcome and antibiotic use of two strategies to diagnose ventilator-associated pneumonia and select initial treatment for this condition. DESIGN: Multicenter, randomized, uncontrolled trial. SETTING: 31 intensive care units in France. PATIENTS: 413 patients suspected of having ventilator-associated pneumonia. INTERVENTION: The invasive management strategy was based on direct examination of bronchoscopic protected specimen brush samples or bronchoalveolar lavage samples and their quantitative cultures. The noninvasive ("clinical") management strategy was based on clinical criteria, isolation of microorganisms by nonquantitative analysis of endotracheal aspirates, and clinical practice guidelines. MEASUREMENTS: Death from any cause, quantification of organ failure, and antibiotic use at 14 and 28 days. RESULTS: Compared with patients who received clinical management, patients who received invasive management had reduced mortality at day 14 (16.2% and 25.8%; difference, -9.6 percentage points [95% CI, -17.4 to -1.8 percentage points]; P = 0.022), decreased mean Sepsis-related Organ Failure Assessment scores at day 3 (6.1+/-4.0 and 7.0+/-4.3; P = 0.033) and day 7 (4.9+/-4.0 and 5.8+/-4.4; P = 0.043), and decreased antibiotic use (mean number of antibiotic-free days, 5.0+/-5.1 and 2.2+/-3.5; P < 0.001). At 28 days, the invasive management group had significantly more antibiotic-free days (11.5+/-9.0 compared with 7.5+/-7.6; P < 0.001), and only multivariate analysis showed a significant difference in mortality (hazard ratio, 1.54 [CI, 1.10 to 2.16]; P = 0.01). CONCLUSIONS: Compared with a noninvasive management strategy, an invasive management strategy was significantly associated with fewer deaths at 14 days, earlier attenuation of organ dysfunction, and less antibiotic use in patients suspected of having ventilator-associated pneumonia.

Anti-Bacterial Agents↗
PubMed2000

Estimation of the efficacy of live, attenuated influenza vaccine from a two-year, multi-center vaccine trial: implications for influenza epidemic control.

The authors provide an analysis of data from a two-year (1996-1998), multicenter (ten US cities), double-blinded, placebo-controlled influenza vaccine trial in children. The vaccine was the trivalent cold-adapted influenza vaccine. Estimates are made of the vaccine efficacy for susceptibility to culture-confirmed influenza (VE(S)) while taking inter-center variability in the risk of infection into account. Our overall estimate of VE(S) against influenza is 0.92 (95% confidence interval (CI) 0.89-0.94). In addition, for the second year, although the vaccine contained antigen for A/Wuhan-like (H3N2), the estimated VE(S) for epidemic variant A/Sydney-like (H3N2) was 0.89 (95% CI 0.81-0.94). Thus, the vaccine showed a high degree of protection against a variant not closely matched to the vaccine antigen. With regard to natural immunity, an influenza A infection in the first year reduces the estimated risk of an influenza A infection in the second year by a factor of 0.88 (95% CI 0.21-0.98). When comparing year 1 to year 2, there is a negative correlation of -0.50 in the center-specific attack rates in the placebo groups. This is consistent with the theory that natural immunity provides overall community protection to children. The authors argue that mass vaccination of 70% of the children with the cold-adapted influenza vaccine could provide substantial protection to the community at large.

Child, Preschool↗