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Biomedical subjects

M Wolff

Publications and source records attributed to M Wolff.

At least 145 records · Page 8Linked to original sources

[Antiretroviral therapy. Announcement of the Advisory Committee of the Chilean Society of Infectology on AIDS].

There are treatments to induce the long term suppression of viral replication and that delays the progression of HIV disease. To be effective, these treatments require the uninterrupted use of a combination of drugs (ideally three), patients must be highly compliant, must be instituted in early stages of the disease and drugs must be used for prolonged periods and given by specialists. These treatments are indicated in all symptomatic patients and in those with early immunologic deterioration or high viral load. Recent infection and acute primary retroviral infections should also be considered for treatment. The treatment sponsored and financed by the ministry of health for its beneficiaries is insufficient at this time, since it is received by a minority of eligible patients due to budgetary reasons, and only two drugs are given which is considered such optimal by most experts. The committee considers that the responsibility for financing, providing and delivering these treatments in proper combination and dosages exceeds the duty of the Ministry of Health and should include all the involved parties. However, the state and its official institutions have a special responsibility to provide with adequate treatments to the poorer segments of our population. They also should promote, supervise and control the proper access of the rest of the population to efficient treatments. The committee also considers that the efforts to prevent new infections must not be neglected and that individuals under successful treatment should not consider themselves as non infectious.

Acquired Immunodeficiency Syndrome↗

[Portal hypertension and variceal bleeding: shunt in concomitant or general prehepatic block].

Thrombosis of the portal system should be ruled out in all patient with esophagogastric varices. Such patients with no evidence of concomitant liver disease and with a high risk of rebleeding (e.g. gastric varices, low platelet counts, endoscopic criteria) should be referred to decompressive shunt surgery. The type of shunt is dictated by the patent segments of the portal system. Splenectomy should be avoided. The results show a low operative mortality, a zero encephalopathy and a low rebleeding rate. Patients with prehepatic thrombosis and liver cirrhosis represent a more severe problem since the risk and mortality of variceal hemorrhage is high and on the other hand TIPS procedure and liver transplantation may be impossible. In case of a high risk of rebleeding or endoscopic therapy failure we advocate surgical shunting as the risk of encephalopathy appears to be low when portal flow diversion already exists.

Adolescent↗

[Value of diagnostic laparoscopy in primary malignant liver tumors].

The advent of new imaging modalities such as CT-AP and MRT has markedly improved the diagnosis and staging of primary liver tumors and will change the diagnostic impact of laparoscopy. Diagnostic laparoscopy in this retrospective study was not found to add information in regard to tumor staging and resectability, and there was no clear benefit by avoiding diagnostic laparotomies when all imaging and biopsy techniques available were used preoperatively. Therefore, we advocate the use of diagnostic laparoscopy only in selected cases suspicious for superficial small tumor lesions and cirrhosis with impact on the treatment modality.

Adult↗

Safety profile of phase I and II preventive HIV type 1 envelope vaccination: experience of the NIAID AIDS Vaccine Evaluation Group.

The NIAID-sponsored AIDS Vaccine Evaluation Group was established in 1988 to perform phase I/II clinical trials with candidate preventive HIV-1 vaccines. This report includes safety data from 1398 HIV-negative, healthy volunteers who were enrolled into 25 phase I and 1 phase H multicentered, randomized, double-blind studies evaluating seven recombinant HIV-1 envelope vaccines, two V3 loop synthetic peptide vaccines, and two live poxvirus-vectored recombinant envelope vaccines. All studies but three were placebo controlled; the placebo was either the adjuvant alone or, in studies of recombinant poxvirus vaccines, it was the vector with no gene insert or a non-HIV gene insert. All candidate vaccines were generally well tolerated. The only adverse effects that were clearly related to vaccination were occasional acute local and systemic reactions that were associated with the adjuvants. Three adjuvants in particular were associated with moderate to severe local reactions: alum plus deoxycholate (ImmunoAg), MTP-PE (Biocine Corp.), and QS21 (Genentech, Inc.). MTP-PE was also associated with self-limited severe systemic reactions. There were no serious adverse laboratory toxicities and no evidence of significant immunosuppressive events after receipt of the candidate vaccines. A few volunteers experienced symptoms that might relate to an underlying immunopathologic mechanism (rash, hemolytic anemia, arthralgia), but their presentations were mild and their incidence was low. Eleven volunteers were diagnosed with malignancies during or after their participation, which was within the 95% confidence interval of the number of cases predicted by the National Cancer Institute SEER (Program for cancer surveillance, epidemiology, and end result reporting) database. In conclusion, the envelope-based recombinant or synthetic candidate HIV-1 vaccines appear to be safe and this work has prepared the way for the testing of increasingly complex candidate HIV-1 vaccines.

AIDS Vaccines↗

Functional distribution of three types of Na+ channel on soma and processes of dorsal horn neurones of rat spinal cord.

1. Voltage-gated Na+ channels and their distribution were studied by the patch-clamp technique in intact dorsal horn neurones in slices of newborn rat spinal cord and in neurones isolated from the slice by slow withdrawal of the recording pipette. This new method of neurone isolation was further used to study the roles of soma and axon in generation of action potentials. 2. Tetrodotoxin (TTX)-sensitive Na+ currents in intact neurones consisted of three components. A fast component with an inactivation time constant (tau f) of 0.6-2.0 ms formed the major part (80-90%) of the total Na+ current. The remaining parts consisted of a slowly inactivating component (tau s of 5-20 ms) and a steady-state component. 3. Single fast and slow inactivating Na+ channels with conductances of 11.6 and 15.5 pS, respectively, were identified in the soma of intact neurones in the slice. Steady-state Na+ channels were not found in the soma, suggesting an axonal or dendritic localization of these channels. 4. In the whole-cell recording mode, the entire soma of a dorsal horn neurone could be isolated from the slice by slow withdrawal of the recording pipette, leaving all or nearly all of its processes in the slice. The isolated structure was classified as: (1) 'soma' if it lost all of its processes, (2) 'soma+axon' complex if it preserved one process and at least 85% of its original peak Na+ current or (3) 'soma+dendrite' complex if it preserved one process but the remaining Na+ current did not exceed those observed in the isolated 'somata'. 5. The spatial distribution of Na+ channels in the neurone was studied by comparing Na+ currents recorded before and after isolation. The isolated 'soma' contained 13.8 +/- 1.3% of inactivating Na+ current but no steady-state Na+ current. 'Soma+axon' complexes contained 93.6 +/- 1.4% of inactivating and 46% of steady-state Na+ current. 6. In current-clamp experiments, the intact neurones and isolated 'soma+axon' complexes responded with 'all-or-nothing' action potentials to current injections. In contrast, isolated 'somata' showed only passive or local responses and were unable to generate action potentials. 7. It is concluded that dorsal horn neurones of the spinal cord possess three types of TTX-sensitive voltage-gated Na+ channels. The method of entire soma isolation described here shows that the majority of inactivating Na+ channels are localized in the axon hillock and only a small proportion (ca 1/7) are distributed in the soma. Steady-state Na+ channels are most probably expressed in the axonal and dendritic membranes. The soma itself is not able to generate action potentials. The axon or its initial segment plays a crucial role in the generation of action potentials.

Action Potentials↗

[Max Brödel (1870-1941): his life and contribution to the development of modern surgery].

Max Brödel (1870-1941), from Leipzig, Germany, is often referred to in the USA as the father of modern medical illustration and mentioned in the same breath as Leonardo da Vinci or Andreas Vesal. After a classical formal art education in Leipzig he worked in Carl Ludwig's laboratory of physiology and anatomy, where he came in contact with American physicians. In 1894, the anatomist F.P. Mall convinced him to work for the recently inaugurated Johns Hopkins School of Medicine in Baltimore, where he collaborated with world-famous surgeons such as H.A. Kelly, W.S. Halsted, and H. Cushing. His illustrations were characterized by meticulous observation, both realistic and explanatory intention, technical superiority, and artistic merit. In 1911 he established the first "Department of Art as applied to Medicine". Here, he proved to be an innovative artist, a creative scientist, and an inspiring and skillful instructor. By the time of Brödel's retirement in 1939, 160 students had graduated as medical illustrators. His pupils spread his principles and style throughout the USA and Canada, and several similar academic programs for medical illustration have been founded in these countries.

Anatomy, Artistic↗

Shock complicating severe falciparum malaria in European adults.

OBJECTIVE: To study adult patients with severe falciparum malaria who developed shock. DESIGN: Retrospective study from 1987 to 1993. SETTING: Medical intensive care unit in a university hospital. PATIENTS: 14 patients admitted with severe falciparum malaria who developed shock. All received intravenous quinine. MEASUREMENTS AND RESULTS: The mean Simplified Acute Physiology Score II was 59.5 +/- 7.1; 2.6 +/- 0.4 criteria defining severe disease were present on admission in 12 patients; and initial parasitemia was 21 +/- 6%. Twelve patients received inotropic drugs. Pulmonary artery catheterization showed the following results in 7 patients: mean arterial pressure 57 +/- 4 mmHg; pulmonary artery occlusion pressure 11 +/- 1 mmHg; cardiac index 5.5 +/- 0.91.min-1.m-2, and systemic vascular resistance index 783 +/- 122 dyne.s.cm-5.m-2. Seven patients had evidence of bacterial infection at the time of shock. Of the 7 deaths (50%), 5 were due to shock, with documented bacterial infection in all patients and persistent parasitemia in 4. CONCLUSIONS: Shock complicating severe falciparum malaria in adults is associated with peripheral vasodilation and carries a poor prognosis. In falciparum malaria with shock, bacterial coinfection should be suspected immediately and treated empirically with broad-spectrum antibiotics. Nevertheless, Plasmodium falciparum may contribute directly or indirectly to the onset of shock.

Adult↗

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↗