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Biomedical subjects

M Wolff

Publications and source records attributed to M Wolff.

At least 91 records · Page 5Linked to original sources

Excitability of the soma in central nervous system neurons.

The ability of the soma of a spinal dorsal horn neuron, a spinal ventral horn neuron (presumably a motoneuron), and a hippocampal pyramidal neuron to generate action potentials was studied using patch-clamp recordings from rat spinal cord slices, the "entire soma isolation" method, and computer simulations. By comparing original recordings from an isolated soma of a dorsal horn neuron with simulated responses, it was shown that computer models can be adequate for the study of somatic excitability. The modeled somata of both spinal neurons were unable to generate action potentials, showing only passive and local responses to current injections. A four- to eightfold increase in the original density of Na(+) channels was necessary to make the modeled somata of both spinal neurons excitable. In contrast to spinal neurons, the modeled soma of the hippocampal pyramidal neuron generated spikes with an overshoot of +9 mV. It is concluded that the somata of spinal neurons cannot generate action potentials and seem to resist their propagation from the axon to dendrites. In contrast, the soma of the hippocampal pyramidal neuron is able to generate spikes. It cannot initiate action potentials in the intact neurons, but it can support their back-propagation from the axon initial segment to dendrites.

Action Potentials↗

Efficacy of vaccination with live attenuated, cold-adapted, trivalent, intranasal influenza virus vaccine against a variant (A/Sydney) not contained in the vaccine.

OBJECTIVE: To determine the safety, immunogenicity, and efficacy of revaccination of children with live attenuated influenza vaccine. STUDY DESIGN: A 2-year multicenter, double-blind, placebo-controlled, efficacy field trial of live attenuated, cold-adapted trivalent influenza vaccine administered by nasal spray to children. This report summarizes year 2 results, a year in which the epidemic strain of influenza A/Sydney was not well matched to the vaccine strains. Each year, vaccine strains were antigenically equivalent to the contemporary inactivated influenza vaccine. In year 2, a single intranasal revaccination was administered. Active surveillance for influenza was conducted during the influenza season by means of viral cultures. Influenza cases were defined as illnesses with wild-type influenza virus isolated from respiratory secretions. RESULTS: In year 2, 1358 (85%) children, 26 to 85 months of age, returned for revaccination. The intranasal vaccine was easily accepted, well tolerated, and immunogenic. Revaccination resulted in 82% to 100% of the vaccinated children in a subset studied for immunogenicity being seropositive as compared with 26% to 65% of placebo recipients, depending on the influenza strain tested. No serious adverse events were associated with the vaccine. In addition to the strains in the vaccine, antibody was induced to the variant strain A/Sydney/H3N2. In year 2, influenza A/Sydney/H3N2, a variant not contained in the vaccine, caused 66 of 70 cases of influenza A; nonetheless, intranasal vaccine was 86% efficacious in preventing A/Sydney influenza. Eight cases of lower respiratory tract disease were associated with A/Sydney influenza; all cases were in the placebo group. CONCLUSIONS: This live attenuated, cold-adapted influenza vaccine was safe, immunogenic, and efficacious against influenza A/H3N2 (including a variant, A/Sydney, not contained in the vaccine) and influenza B. The characteristics of this vaccine make it suitable for routine use in children to prevent influenza.

Administration, Intranasal↗

Genetic aspects of obsessive-compulsive disorder.

Developments in molecular genetic methods have proved to be powerful tools in the search for genes involved in complex diseases, and they hold the promise of understanding the genetic basis of OCD. The next step in understanding the genetics of OCD is the localization and characterization of the genes that confer susceptibility. A more complete understanding of the genetic basis of OCD and of the interactions between relevant genotypes and relevant environmental factors is important for clarification of the cause, pathogenesis, and treatment of this complex disorder. These genetic methods must be combined with careful clinical and epidemiologic work to correctly elucidate the cause of OCD. Future research also should define subsets of endophenotypes of the disorder. Factors such as neuropsychological functioning, personality testing, comorbidity, and age of onset are extremely useful in the continued study of genetic mechanisms involved in the cause of OCD.

Alleles↗

Brain mechanisms of selective learning: event-related potentials provide evidence for error-driven learning in humans.

Selective learning has been observed in Pavlovian conditioning in animals and in judgements of event contingencies in humans. This analogy led to the suggestion that the formation of associations underlies both types of learning. An alternative theory proposes that both tasks involve the computation of event contingencies as prescribed by probability theory. Error-driven models of learning incorporate trial-by-trial error-correction mechanisms during training whereas probabilistic models view learning merely as the storage of frequency information for later use during judgement of event contingencies. Competitive interaction between cues was observed in a contingency judgement task. Event-related brain potentials (ERPs) provided evidence for brain events related to the discrepancy between actual and expected outcomes during training thus supporting error-driven accounts of selective learning.

Adult↗

Visualization of percutaneous 3H-estradiol and 3H-norethindrone acetate transport across human epidermis as a function of time.

Developing transdermal therapeutic systems for estradiol and norethindrone acetate raised questions about the steroids penetration pathway across and retention in the skin. This paper describes the distribution of 3H-estradiol and 3H-norethindrone acetate in human stratum corneum after topical application to dermatomed skin in vitro. The study involved (a) permeation experiments to determine the steroid flux, (b) autoradiographical visualization of the steroid distribution in the same skin samples, and (c) a correlation between flux and skin distribution in time. On correlating the steroid flux with intraepidermal steroid distribution, it was concluded that both permeants were bound in the skin tissue. The steroids were preferentially located in or close to the intercellular lipids of the stratum corneum, indicating that both transport and binding occurred via this domain of the stratum corneum. This study demonstrated the importance of correlating drug flux with intraepidermal drug distribution as a function of time.

Administration, Cutaneous↗

Comparison of the safety, vaccine virus shedding, and immunogenicity of influenza virus vaccine, trivalent, types A and B, live cold-adapted, administered to human immunodeficiency virus (HIV)-infected and non-HIV-infected adults.

Fifty-seven human immunodeficiency virus (HIV)-infected (CDC class A1-2) and 54 non-HIV-infected adults, not prescreened for influenza susceptibility, were randomized to receive trivalent live attenuated influenza vaccine (LAIV) or placebo intranasally. LAIV was safe and well tolerated with no serious adverse events attributable to vaccine. Reactogenicity rates were similar in LAIV and placebo recipients except that runny nose/nasal congestion was significantly more common in LAIV recipients regardless of HIV status. No prolonged shedding of LAIV was observed in HIV-infected participants. HIV RNA levels were not increased and CD4 counts were not decreased in HIV-infected LAIV recipients compared with placebo recipients after immunization. Shedding of LAIV and increases in antibody titers were infrequent, consistent with prior experience in unscreened adults. The data suggest that inadvertent vaccination with LAIV in relatively asymptomatic HIV-infected adults would not be associated with frequent significant adverse events.

Adult↗

Correlates of immune protection induced by live, attenuated, cold-adapted, trivalent, intranasal influenza virus vaccine.

The authors conducted a 2-year, multicenter, double-blind, placebo-controlled efficacy field trial of live, attenuated, cold-adapted, trivalent influenza vaccine administered by nasal spray to children 15-71 months old. Overall, vaccine was 92% efficacious at preventing culture-confirmed infection by influenza A/H3N2 and influenza B. Because influenza A/H1N1 did not cause disease during the years in which this study was conducted, the authors sought to determine vaccine efficacy and correlates of immune protection against experimental challenge with 107 TCID50 of attenuated H1N1 (vaccine strain) by intranasal spray. Prechallenge assessments included serum hemaglutination-inhibiting (HAI) antibody and nasal wash IgA antibody to H1N1. Vaccine was 83% efficacious (95% confidence interval, 60%-93%) at preventing shedding of H1N1 virus after challenge. Any serum HAI antibody or any nasal wash IgA antibody was correlated with significant protection from H1N1 infection as indicated by vaccine-virus shedding, and high efficacy against H1N1 challenge was demonstrated.

Administration, Intranasal↗

In vivo activity of levofloxacin alone or in combination with imipenem or amikacin in a mouse model of Acinetobacter baumannii pneumonia.

We evaluated the in vivo activity of levofloxacin alone or in combination with imipenem or amikacin in a mouse model of Acinetobacter baumannii pneumonia using a susceptible strain and one with low-level resistance (MIC/MBC of levofloxacin: 0.06/0.06 and 4/4 mg/L, respectively). As demonstrated previously with other pathogens, the AUC/MIC ratio predicted the efficacy of fluoroquinolones against A. baumannii. This parameter correlated with bactericidal effect and survival. Combination therapy did not enhance the efficacy of levofloxacin.

Acinetobacter Infections↗

Comparison of direct examination of three types of bronchoscopy specimens used to diagnose nosocomial pneumonia.

OBJECTIVE: To compare direct examination of bronchial aspirate and plugged telescopic catheter specimens (PTC) with infected cell counts in bronchoalveolar lavage (BAL) specimens for the diagnosis of nosocomial pneumonia. DESIGN: Prospective study of critically ill patients. SETTING: Intensive care unit in a university hospital. PATIENTS: A total of 64 patients hospitalized for >48 hrs with suspected nosocomial pneumonia. INTERVENTIONS: Fiberoptic bronchoscopy with bronchial aspirate and quantitative protected specimen brush, PTC, and BAL cultures. PTC and bronchial aspirate specimens were Gram-stained. BAL specimens for infected cell counts were examined as described previously in the literature. MEASUREMENTS AND MAIN RESULTS: Nosocomial pneumonia was diagnosed by the medical staff based on all available clinical, radiologic, laboratory test, and microbiological data and on the course before and after appropriate therapy. A total of 71% of patients were ventilated, and 70.1% were receiving antibiotics. Nosocomial pneumonia was diagnosed in 54% of the cases. On direct examination, sensitivity (Se) and specificity (Sp) of bronchial aspirate specimens were Se, 82% and Sp, 60%; of BAL with 5% infected cells, Se, 56% and Sp, 100%; of BAL with 3% infected cells, Se, 74% and Sp, 96%; of PTC specimens, Se, 65% and Sp, 76%; and of PTC specimens plus BAL with 3% infected cells, Se, 83% and Sp, 78%. BAL with 3% infected cells was significantly better for predicting nosocomial pneumonia than direct examination of bronchial aspirate or PTC specimens (p = .0012). When the BAL showed 3% infected cells, neither direct examination of bronchial aspirate nor direct examination of PTC specimens was useful (p = .24 and p = .38, respectively). Combined use of direct examination of PTC specimens plus BAL with 3% infected cells markedly improved sensitivity. The total cost of each procedure was taken into account for the final evaluation. CONCLUSIONS: Our data suggest that BAL with 3% infected cells is currently the only test whose predictive value for nosocomial pneumonia is sufficiently high to be of use for guiding the initial choice of antimicrobial class while waiting for quantitative culture results.

Adult↗

Acute encephalopathy associated with vigabatrin in a six-month-old girl.

PURPOSE: Vigabatrin (VGB) is a new-generation anticonvulsant used in the treatment of partial seizures and West syndrome. Side effects of VGB treatment in adults and children are well described. Acute encephalopathy with VGB has recently been reported in eight adults. They developed stupor, confusion, and electroencephalographic abnormalities after starting VGB. Does the acute encephalopathy with VGB also occur in childhood? METHODS: We describe a 6-month-old girl with infantile Alexander disease with hydrocephalus who developed similar clinical symptoms with apathia, somnolence, and sopor, as well as slowing of the background activity in EEG, 3 days after starting VGB. After exclusion of shunt dysfunction, encephalitis, metabolic dysfunction, and renal failure, VGB was discontinued. RESULTS: During the next 2 days, symptoms subsided, and after 10 days, EEG background activity returned to the one before starting VGB. CONCLUSIONS: Acute encephalopathy associated with VGB in children seems to be very rare, but should not be ignored.

Acute Disease↗

Detection of thrombosis in the portal venous system: comparison of contrast-enhanced MR angiography with intraarterial digital subtraction angiography.

PURPOSE: To determine whether intraarterial digital subtraction angiography (DSA) can be replaced by contrast material-enhanced magnetic resonance (MR) angiography in the assessment of patency or thrombosis of the portal venous system in patients with portal hypertension. MATERIALS AND METHODS: Thirty-six patients with portal hypertension underwent contrast-enhanced MR angiography and intraarterial DSA for assessment of the portal venous system. The images were evaluated for vessel patency or thrombosis of the portal, splenic, or superior mesenteric vein. RESULTS: Of the 101 vessels evaluated, 42 were thrombosed. Overall sensitivity, specificity, and accuracy for the detection of thrombosis were 100%, 98%, and 99%, respectively, for MR angiography and 91%, 100%, and 96%, respectively, for DSA; differences between the imaging methods were not statistically significant. Only in four patients with six vessels (6%) were there discordant findings between MR angiography and DSA. CONCLUSION: Noninvasive contrast-enhanced MR angiography has the potential to replace intraarterial DSA as the standard method to assess the whole portal venous system.

Adolescent↗

Multicenter prospective study of ventilator-associated pneumonia during acute respiratory distress syndrome. Incidence, prognosis, and risk factors. ARDS Study Group.

We investigated the incidence, risk factors for, and outcome of ventilator-associated pneumonia (VAP) in patients with acute respiratory distress syndrome (ARDS). We compared 134 patients with ARDS with 744 patients without ARDS on mechanical ventilation. Fiberoptic bronchoscopic examination and quantitative bacterial cultures (protected brush or catheter sampling [threshold: 10(3) cfu/ml], or bronchoalveolar lavage [threshold: 10(4) cfu/ml]) were used to diagnose pneumonia. VAP occurred in 49 patients (36.5%). The incidence of pneumonia was 23% (173 of 744 patients) among patients without ARDS (p < 0.002). Nonfermenting gram-negative rods caused significantly more pneumonia in ARDS patients. Mortality rates were identical in ARDS patients with (28 of 49 patients, 57%) and without (50 of 85 patients, 59%) pulmonary infection (p = 0.8). VAP resulted in a considerable increase in attributable time on mechanical ventilation of both the overall population of ARDS patients and of survivors. Both the use of sucralfate (adjusted odds ratio [OR]: 4. 42; 95% confidence interval [CI]: 2.01 to 9.7, p = 0.0002) and the duration of exposure to sucralfate (adjusted OR: 1.206; 95% CI: 1. 095 to 1.328, p = 0.0002) were associated with an increased risk of VAP during ARDS. VAP considerably prolongs the time on mechanical ventilation without affecting survival. Patients given sucralfate may be at greater risk of developing pulmonary infection during ARDS.

Adult↗

Workshop to identify critical windows of exposure for children's health: cancer work group summary.

We considered whether there are discrete windows of vulnerability in the development of cancer and which time periods may be of the greatest importance. Cancer was considered broadly, including cancers in childhood as well as adult cancers that may have an in utero or childhood origin. We concluded that there was evidence from animal and epidemiologic studies for causal relationships for preconceptional, in utero, and childhood exposures and cancer occurrence in children and adults. However, the evidence is incomplete and all relevant critical windows may not have been identified. The comprehensive evaluation of the relative importance of specific time windows of exposure is limited. Improvements in the design of epidemiologic studies and additional animal studies of mechanisms are warranted.

Adolescent↗

[Prospective, randomized, comparative study of the efficacy, safety and cost of cefuroxime versus cephradine in acute pyelonephritis during pregnancy].

BACKGROUND: Second generation cephalosporins (CFPs) are more active in the treatment of acute pyelonephritis during pregnancy but their cost is considerably higher than their predecessors. Cefuroxime, a second generation CFP with oral and parenteral presentations, might offer significant advantages and become a first choice antimicrobial in this setting. AIM: To compare the efficacy, safety and cost of cefuroxime and cephradine in the treatment of acute pyelonephritis in pregnancy. PATIENTS AND METHODS: Hospitalized women with 12 to 34 weeks of pregnancy, with clinical and bacteriological diagnosis of acute pyelonephritis, were randomly assigned to receive cefuroxime (Curocef(r), Glaxo Wellcome) 750 mg t.i.d, i.v. or cephradine 1 g q.i.d., i.v. If the isolated organism was resistant to the assigned drug the patient was excluded. Once patients were afebrile, they were switched to an oral form of the same antimicrobial. They were discharged according to the clinical status and treated for a total of 14 days. laboratory tests, including urine culture were requested during controls and at the end of follow-up at 28 days. RESULTS: One hundred and one patients were randomized: 49 to receive cephradine and 52 to receive cefuroxime. Patients in the cefuroxime group hed fewer febrile days (mean 1.7 vs 2.2, p < 0.05), faster clinical recovery (mean 2.7 vs 3.1 days, p < 0.05), a higher rate of bacteriological cure at 28 days (78.8% and 59.2%, p < 0.05) and lower rate of failure (21.2% vs 40.8% p < 0.05). The rate of resistance of isolated uropathogens was 14% to cephradine and 1% to cefuroxime. CONCLUSIONS: Cefuroxime can be considered as a first choice option in the treatment of acute pyelonephritis during pregnancy due to its tolerance, microbiological activity and efficacy.

Acute Disease↗

[Impact of antiretroviral therapy in mortality of Chilean HIV (+) patients: a case control study].

BACKGROUND: Combined antiretroviral therapy (AVR) has shown a protective effect (PE) on morbidity and survival in HIV (+) patients of industrialised countries where triple-drug therapy (ARV-3) is standard. In Chile the public health system began providing double-drug therapy in 1997 (ARV-2) with 2 reverse transcriptase inhibitors. AIM: To assess the impact of ARV in morbimortality of HIV (+) patients in Chile after a year of follow up. PATIENTS AND METHODS: Retrospective case-control (1:1) study. Cases were 97 patients followed during 1997 for 6 or more months and dying during that period. Each case had a control of the same gender and CDC stage, similar age and CD4 count, but surviving a same period of follow up. A comparison of ARV before and during follow up (rate and type) was done. P carinii prophylaxis, pneumococcal immunization at baseline or follow up, frequency of hospital admissions and occurrence of opportunistic infections in both groups were assessed. Odds ratio (OR) for mortality, hospitalization and opportunistic infections in ARV user, as well as treatment PE were calculated. RESULTS: Twenty four (24.7%) cases and sixty six (68%) controls received ARV during follow up (p < 0.001), OR was 0.15 (CI 95% 0.08-0.3), p < 0.001, the PE was 6.6 for ARV users versus non users, among cases 19 patients received ARV-2 and five received ARV-3. Among controls, 41 patients received ARV-2 and 25 received ARV-3. These differences established an OR of 0.20 (CI 95% 0.09-0.04) and a PE of 5 for ARV-2 versus no ARV. For ARV-3 compared with no ARV the OR was 0.08 (CI 95% 0.003-0.26), and the PE 12.5. Fifty three (54.6%) cases and 13 (13.4%) controls required hospital admission, OR 0.49 (CI 95% 0.25-0.94), p = 0.03, and PE of 2.04 of ARV versus no ARV; 82 (85.3%) cases and 50 (51%) controls had opportunistic infections, OR 0.5 (CI 95% 0.26-0.96), p = 0.03 and PE of 2 for ARV versus no ARV. There were no significant differences in prior ARV, prophylaxis and immunisation between cases and controls. CONCLUSIONS: This study showed the high impact of ARV in short term morbimortality of HIV(+) patients and the need to implement antiretroviral therapy to all patients as an official health policy. This study did not answer the question of the role, if any, of weaker-than standard antiretroviral therapy.

AIDS-Related Opportunistic Infections↗