Biomedical subjects
Publications and source records attributed to S Jonas.
Hemorrhage secondary to anticoagulant therapy is well documented. We report a patient who presented with acute vertigo and unilateral deafness while on warfarin and was found to have a probable hemorrhage in the labyrinth, identified on MRI.
The introduction of cyclosporine A (CsA) and FK506 significantly improved the outcome of liver transplantation. However, the postoperative course and outcome of liver transplant recipients in still compromised by rejection, over-immunosuppression-induced infection and immunosuppression-associated toxicity. In the present study, we evaluated the reason for conversion between immunosuppressive regimens in 121 patients, 60 treated with FK506 and 61 patients treated with CsA-based immunosuppression. Five patients treated primarily with CsA (8.3%) were converted to FK506 therapy because of refractory acute of chronic rejection within 12 months following liver transplantation (LTX). In 2 patients, conversion was performed after Re-LTX. In 4 of these 5 patients, rejection was successfully treated according to histological and laboratory investigations, while in the remaining patient, graft function improved with persisting histological evidence of chronic rejection. Moderate and severe neurologic symptoms during the early postoperative period, i.e. organic brain syndromes (OBS), seizures, hemiparesis, dysphasia, dysathria and cerebellar symptoms were observed in 21.3% of patients treated with FK506 and in 11.7% of patients treated with CsA (p = n.s.). Five patients treated primarily with FK506 were converted to CsA due to severe neurotoxicity. Early postoperative renal insufficiency was observed to a similar extent with 42.6% of FK506- and 36.7% of CsA-treated patients. 8.3% of FK506-treated patients and 11.7% of CsA-treated patients required hemodialysis (p = n.s.) There patients were converted from FK506 to CsA due to persisting renal insufficiency. Moderate and severe neurologic symptoms were observed more frequently under treatment with FK506 than CsA, and all conversions from FK506 to CsA (13.3%) were performed because of neuro- or nephrotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS)
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As part of a European multicenter study to investigate the potency of FK506 in primary immunosuppression after liver transplantation, this comparison with our conventional cyclosporine-based quadruple regimen was carried out as a controlled, prospective, randomized trial. The 121 patients entering the study were randomly assigned to receive immunosuppressive regimens consisting either of FK506 and prednisolone (FK/n = 61) or of cyclosporine, prednisolone, azathioprine, and a 7-day course of rabbit antithymocyte globulin (CsA/n = 60). Rejection was suspected in the case of scant production of light bile or biochemical graft dysfunction, without evidence of vascular, biliary, or infectious complications. A liver biopsy for confirmation of the diagnosis was obtained each time. Initial therapy entailed a 3-d course of high-dose methyl-prednisolone. Steroid resistant rejections were treated with OKT3 monoclonal antibody or, in the group of primary CsA administration, conversion to FK506 as another treatment option. One-year patient (FK: 90.2%; CsA: 96.7%) and graft survival (FK: 88.5%; CsA: 91.7%) did not differ significantly. Overall, 41 patients (33.9%) experienced 50 acute, cellular rejection episodes (RE) [FK: 25 RE in 21 patients (34.4%); CsA: 25 RE in 20 patients (33.3%)]. The histological grading ranged from mild (FK: 14/25; CsA: 8/25) to moderate (FK: 9/25; CsA: 16/25) and severe (FK: 2/25; CsA: 1/25): not significantly different between the two groups. In the CsA-based group, three additional rejection episodes were classified as early chronic (n = 1) and chronic rejection (n = 2).(ABSTRACT TRUNCATED AT 250 WORDS)
The disease and disability toll of drug use and certain features of current national drug use/abuse policy produce serious negative outcomes for the health and welfare of the United States and its people. Therefore, national drug policy should be the subject of serious review. Neither the central focus of present policy, the "Drug War," nor what is usually presented as the only alternative to this policy, "legalization," effectively deal with the U.S. drug use/abuse problem. In this commentary, we first examine the nature of the total drug problem. Then, an analysis of its causes is presented, followed by a discussion of present policy and how it does or does not address both the problem and its causes. Finally, a proposed new approach to the drug problem, based on well-known public health principles, is offered.
A retrospective analysis of 462 consecutive orthotopic liver transplantations was undertaken to evaluate incidence, risk factors, clinical course, and outcome of fungal infections. Infections involving Aspergillus (6 cases), Candida (5 cases), Mucor (1 case), and Cryptococcus (1 case) were observed in 2.8% (13/462) of our patients. Twelve of the 13 episodes developed during the first 2 postoperative months. None of the potential risk factors for fungal infections described by other authors (i.e., age, rejection treatment, dialysis, mechanical ventilation, graft failure, long operation time, second transplant, serious non-fungal infection) correlated significantly with the episodes in our patients. However, in patients who exhibited three or more of these potential risk factors the incidence of fungal infections was elevated (P < 0.001). Six of seven exogenous infections (Aspergillus, Mucor) began before July 1991 when our department moved from Charlottenburg to Wedding, thus indicating that the incidence of these infections is highly influenced by exposure (P = 0.01). Exposure prophylaxis should therefore by meticulously followed, particularly when severely compromised patients are involved, in order to prevent exogenous infections (i.e., Aspergillus/Mucor). Infections involving such patients are combined with a very high mortality (57%). We observed Candida infection as a pathological overgrowth of physiological oropharynx flora into the esophagus and/or trachea in five patients. In each case treatment led to full recovery.
The early outcome of 201 liver grafts transplanted consecutively between September 1988 and November 1991 was investigated retrospectively. Donors were categorized according to their hospitalization periods in an intensive care unit (ICU) prior to harvesting, their causes of death, and the variables generally believed to be critical in liver donation, such as arterial hypotension (n = 69; 34.3%), cardiopulmonary resuscitation (n = 20; 9.9%), elevated serum-aminotransferases (s-AT) (n = 11; 5.5%), or an age over 50 years (n = 16; 8.0%). Ninety-one donors (45.3%) spent less than 24 h in an ICU; 29 donors (14.4%) and 14 donors (7.0%) had hospitalization periods generally considered critical of 4-6 days and more than 6 days, respectively. The most common causes of death were subarachnoidal bleeding (n = 70; 34.8%), isolated head injuries (n = 68; 33.8%), and polytraumata (n = 33; 16.4%). The postischemic hepatocellular damage was evaluated comparing peak post-transplant s-AT, which did not differ significantly between groups; nor did donor and recipient ages or cold ischemia times. Fourteen grafts (7.0%) showed a reversible preservation injury presenting with post-transplant s-AT elevated above 2000 IU/l. Five cases (2.5%) of a primary non-functioning graft (PNF) underwent early retransplantation successfully. Serum-aminotransferases (AST: 4944 +/- 2280 IU/l; ATL: 3186 +/- 1918 IU/l) were significantly (P < 0.01) elevated as compared to primary functioning grafts (AST: 699 +/- 935 IU/l; ALT: 620 +/- 701 IU/l). The donor structure of both groups reflected the distribution of variables in the entire collective. No significant overrepresentations were observed.(ABSTRACT TRUNCATED AT 250 WORDS)
In order to evaluate a combination of yellow fever and typhoid fever vaccine, we conducted a controlled trial comparing reactogenicity and immunogenicity of Vi polysaccharide (ViPS) vaccine and yellow fever 17D (YF) vaccine after single, simultaneous and combined administration. The combined YF/ViPS vaccine was prepared by using the liquid ViPS vaccine as a diluent for the YF vaccine. The stability of such a reconstitution had been assessed in vitro. Safety was evaluated using a self-surveillance form and by repeated clinical visits. Immunogenicity was evaluated by a plaque reduction test for YF and by radioimmunoassay for ViPS. Tolerability was satisfactory in all groups. There was no increase in local or general reactions in groups receiving both vaccines, whether given simultaneously or combined. The serological response to ViPS was similar after single and simultaneous or combined administration. Interestingly, the immune response to YF was significantly enhanced in groups receiving the vaccines simultaneously or combined, suggesting a potential adjuvant effect of ViPS.
BACKGROUND: Treatments for acute ischemic stroke have evolved as knowledge about the pathophysiology of ischemic brain injury has advanced. Treatment strategies under development are aimed at offering neuroprotection acutely after focal cerebral ischemic injury, but delayed initiation of therapy may reduce efficacy. Pretreatment before ischemia begins could offer distinct advantages in patient groups at high risk for ischemic stroke. SUMMARY OF REVIEW: If a neuroprotective drug were available orally, safe, and relatively inexpensive, it could be considered for prophylactic use in high-risk populations. Prophylactic neuroprotection would include (1) short-term neuroprotection before and after high-stroke risk procedures, (2) long-term neuroprotection for primary and secondary intervention in populations at high risk for stroke, and (3) concomitant neuroprotection with agents that have multiple treatment effects. Patients undergoing procedures such as cardiac surgery, endarterectomy, or endovascular therapy, which have a risk of cerebral ischemic events during a defined period, might be considered for short-term, periprocedure prophylactic neuroprotection. Several populations at high long-term risk for initial ischemic stroke have been identified and include those with combinations of vascular risk factors, transient ischemic attacks, atrial fibrillation, and asymptomatic carotid stenosis. Such people, as well as those at risk for stroke recurrence after minor strokes, are readily identifiable and perhaps appropriate for long-term prophylactic neuroprotection. Patients with hypertension and cerebrovascular atherosclerosis have a high stroke risk, and therapies directed at these underlying disorders are available that also have concomitant neuroprotective effects. An ideal drug for trials in these patient groups has not yet been developed, and establishing its efficacy may prove to be an arduous and lengthy task. CONCLUSIONS: The possibility of ameliorating the consequences of an acute ischemic stroke by pretreating high-risk patients with appropriate neuroprotective agents needs to be explored. Several types of high-risk population for prophylactic neuroprotection can be envisioned and then studied in clinical trials.
Between September 1988 and November 1991, 201 donor hepatectomies and transplantations were performed. Fifty-four livers (26.9%) were harvested by other teams and shipped for transplantation; 147 livers (73.1%) were procured by teams from our transplant center. Comparing the maximal postoperative serum-aminotransferases (s-AT), we evaluated the postischemic damage of shipped organs (AST 951 +/- 931 IU/l; ALT 820 +/- 666 IU/l) and nonshipped organs (AST 753 +/- 1256 IU/l; ALT 636 +/- 896 IU/l); this did not differ significantly. Donor-related factors, such as critical parameters (i.e., cardiac arrest, arterial hypotension, age over 50 years, or elevated preoperative s-AT), length of stay in the intensive care unit before harvesting, and cause of death showed similar patterns in both groups. The mean cold ischemia time in the group of shipped livers (12 h 10 min +/- 4 h 22 min) and in the nonshipped livers (10 h 6 min +/- 3 h 53 min) did not differ significantly. Five cases (2.5%) of a primary non-functioning graft presenting with significantly (P < 0.001) elevated s-AT (AST 4944 +/- 2280 IU/l; ALT 3186 +/- 1918 IU/l) necessitated an early retransplantation. One organ was shipped and four organs were nonshipped, thus corresponding to their portion of all grafts. These data indicate that the transplantation of shipped livers is a safe procedure procedure, provided that procurement is done by experienced centers.
Continuous ambulatory ECG (CAECG) monitoring has been advocated as an effective low-cost preoperative method for detecting silent myocardial ischemia in patients undergoing peripheral vascular surgery. In addition, silent ischemic events are associated with an increased incidence of postoperative myocardial infarctions. Ninety-six patients (mean age 73 years) admitted for elective aortic (24) or infrainguinal (72) operations over a 2-year period underwent 24-hour two- or three-lead CAECG monitoring. Results were reviewed by a single cardiologist blinded to the study. The criterion for ischemia was ST segment depressions of 1 mm or greater for 40 seconds or more 60 msec after the J point. Postoperative myocardial infarction was determined by ECG changes and/or elevated serum creatinine phosphokinase with positive MB isoenzymes. Risk factors included hypertension (71%), history of coronary artery disease (66%), smoking (61%), and diabetes mellitus (47%). Nine out of 96 patients (9.4%) had a positive CAECG test for silent myocardial ischemia. Only one patient (11.1%) developed postoperative myocardial infarction and there were no deaths in this group. The incidence of postoperative myocardial infarction in the nonischemic group was 16.1% (14/87). However, the mortality in this group was 6.9% (6/87). New and malignant arrhythmias requiring preoperative medical intervention were observed in seven patients (7.4%): two cases of ventricular tachycardia and five cases of atrial flutter/fibrillation. Contrary to previous reports, CAECG monitoring for silent ischemia was not a significant predictor of postoperative myocardial infarction or mortality in our patient population. However, we continue to recommend the preoperative use of CAECG monitoring as a diagnostic tool for unsuspected malignant arrhythmias.
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Hepatitis A and hepatitis B are endemic in many countries and must be considered as serious health risks for large parts of the world population. Simultaneous or combined vaccination against these two diseases would therefore be most advantageous. In order to investigate possible interactions between these vaccines with respect to their tolerability and immunogenicity, we conducted a randomized prospective study comparing single and simultaneous administration of the two vaccines. Three groups of healthy volunteers, each with 55 persons, were included in the study. All were negative for hepatitis A and hepatitis B markers and had normal serum liver enzyme values. Group I received hepatitis A vaccine (720 ELISA units) into the left deltoid muscle, group II received hepatitis B vaccine (20 micrograms) into the right deltoid muscle and group III received hepatitis A vaccine into the left, and hepatitis B vaccine into the right deltoid muscle. Three doses of the vaccines were administered at 0, 1 and 6 months. Local and systemic reactions were monitored by means of questionnaires. Blood samples for determination of antibody to hepatitis A virus (anti-HAV) and antibody to hepatitis B surface antigen (anti-HBs) and of serum SGOT and SGPT levels were drawn at months 0, 1, 2, 6 and 7. There were no serious general and only mild local reactions. The mean serum SGOT and SGPT values remained in the normal range in all groups. The seroconversion rates and mean geometric titres of the anti-HAV and anti-HBs antibodies were similar when the vaccines were administered separately or simultaneously. There were no significant differences between the compared groups.(ABSTRACT TRUNCATED AT 250 WORDS)
BACKGROUND: Volatile crude oil derivates (hydrocarbons) are becoming more and more widely used in homes and during leisure activities. This leads to a high rate of intoxications with these products in children (5% of all pediatric intoxications, 25% of all lethal intoxications). Clinical courses, pathophysiology, and therapy of these intoxications are referred and studied. METHODS: Based on a literature review and 3 cases reports with different clinical courses, intoxications with volatile hydrocarbons are analyzed. RESULTS: The inhalation of volatile hydrocarbons causes an ARDS. This explains the high mortality. Early oxygen-treatment with PEEP-ventilation, however, facilitates a favourable outcome without residual defects as we demonstrate in one case. Another patient needs prolonged ventilatory support after a delayed start of therapy. A third patient cannot be saved even with ECMO. CONCLUSIONS: Initial pulmonary symptoms after hydrocarbon intoxication, such as coughing and cyanosis, are signs for a severe course. Immediate hospitalization with repetitive chest x-rays and adequate instant therapy are the only option to reduce the high mortality of this intoxication.
In a two years retrospective study we analyzed neonates from a US and a German neonatal center with pulmonary hypertension (persistent fetal circulation--PFC). The US patients were treated with Extracorporeal Membrane Oxygenation (ECMO) the german patients with conventional methods as hyperventilation, catecholamines, and vasodilators. Both groups fulfilled the classical ECMO entrance criteria: an alveolar-arterial oxygen difference greater than 610 mmHg and an oxygenation index (i.e. mean airway pressure x FiO2 x 100/paO2 of greater than 40 mmHg. We compared anamnestic and respiratory parameters with the t-test for independent groups or the chi-square test accordingly. With one patient in each group the mortality was not significantly different and the rate of meconium aspirations was the same. The APGAR score at 5 min was significantly lower in the US group, prenatal care was undertaken in significantly less US than german patients. Time intervals between delivery and important therapeutic interventions as intubation, hyperventilation, first catecholamines were not significantly different between both groups. Also worst paO2, pH, and paCO2 were not significantly different. Mechanical ventilation was more aggressive in the US group, i.e. higher intermittent-mandatory-ventilation-rate and peak inspiratory pressure. On the one hand our studies demonstrate that even patients fulfilling ECMO criteria still have a good chance with conventional treatment. On the other hand differences in APGAR scores and prenatal care might indicate that hypoxic-ischemic influences alter the US-group morbidity.
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The antioncogram is an aid to the selection of cytostatic drugs in the treatment of oral cavity carcinomas. In comparison with drug selection based on clinical experience, the antioncogram-oriented choice of the most promising drug in vitro results in improved survival rates.
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