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Biomedical subjects

E Schweizer

Publications and source records attributed to E Schweizer.

At least 109 records · Page 6Linked to original sources
PubMed1990

[Small intestine transplantation--a causal therapy in short bowel syndrome].

The problems of surgical technique, graft physiology and immunological reactions in small-bowel transplantation have been investigated in extended animal experiments. In these experiments, the fundamentals of a successful clinical application of small-bowel transplantation could be laid. A successful human small-bowel transplantation could be carried out by the Kiel Group for the first time in 1988. A graft which had been removed from a related donor showed a complete adaptation after 22 months, so that the patient became completely independent from parenteral nutrition. After that, in several cases small-bowel and combined liver and small-bowel transplantation have been carried out. Thus, the clinical small-bowel transplantation represents the causal therapy of short-bowel syndrome and should be developed in further clinical trials.

Adult↗
PubMed1990

The multifunctional 6-methylsalicylic acid synthase gene of Penicillium patulum. Its gene structure relative to that of other polyketide synthases.

6-Methylsalicylic acid synthase (MSAS) from Penicillium patulum is a homomultimer of a single, multifunctional protein subunit. The enzyme is induced, at the transcriptional level, during the end of the logarithmic growth phase. After approximately 150-fold purification, a homogeneous enzyme preparation was obtained exhibiting, upon SDS gel electrophoresis, a subunit molecular mass of 188 kDa. By immunological screening of a genomic P. patulum DNA expression library, the MSAS gene together with its flanking sequences was isolated; 7131 base pairs of the cloned genomic DNA were sequenced. Within this sequence the MSAS gene was identified as a 5322-bp-long open reading frame coding for a protein of 1774 amino acids and 190,731 Da molecular mass. Transcriptional initiation and termination sites were determined both by primer extension studies and from cDNA sequences specially prepared for the 5' and 3' portions of the gene. The same cDNA sequences revealed the presence of a 69-bp intron within the N-terminal part of the MSAS gene. The intron contains the canonical GT and AG dinucleotides at its 5'- and 3'-splice junctions. An internal TACTGAC sequence, resembling the TACTAAC consensus element of Saccharomyces cerevisiae introns is suggested to represent the branch point of the lariat splicing intermediate. When compared to other known polyketide synthases, distinct amino acid sequence similarities of limited lengths were observed with some, though not all, of them. A comparatively low degree of similarity was detected to the yeast and Penicillium FAS or to the plant chalcone and resveratrol synthases. In contrast, a significantly higher sequence similarity was found between MSAS and the rat fatty acid synthase, especially at their transacylase, 2-oxoacyl reductase, 2-oxoacyl synthase and acyl carrier protein domains. Besides several dissimilar, interspersed regions probably coding for MSAS- and FAS-specific functions, the sequential order of the similar domains was colinear in both enzymes. The low similarity between the two P. patulum polyketide synthases, MSAS and FAS, possibly supports a convergent rather than a divergent evolution of both multienzyme proteins.

Acyltransferases↗
PubMed1990

Long-term therapeutic use of benzodiazepines. I. Effects of abrupt discontinuation.

We compared the effect of abrupt discontinuation of therapeutic doses of short half-life and long half-life benzodiazepines in 57 benzodiazepine-dependent patients (daily use, greater than 1 year). Despite the use of a mean daily dose of 14.1 mg of diazepam equivalents, there were notable residual symptoms of anxiety and depression present at intake (Hamilton Rating Scale for Anxiety score, 17.0; Hamilton Rating Scale for Depression score, 14.0). Benzodiazepine intake was stabilized for 3 weeks before double-blind assignment to placebo (n = 47), or continued benzodiazepine use (n = 10). Clinical assessments were performed daily, including benzodiazepine plasma levels. Depending on the outcome criteria used, anywhere from 58% to 100% of patients were judged to have experienced a withdrawal reaction, with a peak severity at 2 days for short half-life and 4 to 7 days for long half-life benzodiazepines. Relapse onto benzodiazepines occurred in 27% of patients who were receiving long half-life benzodiazepines and in 57% of patients who were receiving short half-life benzodiazepines. Baseline predictors of relapse were nonpanic diagnoses, a higher benzodiazepine dose, and a higher Eysenck neuroticism score. A short half-life and higher daily doses were associated with greater withdrawal severity, as were personality traits, such as dependency and neuroticism, less education and higher baseline levels of anxious and depressive symptoms. Patients who were able to remain free of benzodiazepines for at least 5 weeks obtained lower levels of anxiety than before benzodiazepine discontinuation. These results provide a detailed picture of the symptoms, time course, and multidimensional determinants of the benzodiazepine withdrawal syndrome.

Ambulatory Care↗
PubMed1990

Long-term therapeutic use of benzodiazepines. II. Effects of gradual taper.

We compared the effect on withdrawal severity and acute outcome of a 25% per week taper of short half-life vs long half-life benzodiazepines in 63 benzodiazepine-dependent patients. Patients unable to tolerate taper were permitted to slow the taper rate. Ninety percent of patients experienced a withdrawal reaction, but it was rarely more than mild to moderate. Nonetheless, 32% of long half-life and 42% of short half-life benzodiazepine-treated patients were unable to achieve a drug-free state. The most difficulty was experienced in the last half of taper. Baseline personality, high Eysenck neuroticism, female sex, and mild-to-moderate alcohol use were found to be more significant predictors of withdrawal severity than the daily benzodiazepine dose or benzodiazepine half-life. These findings suggest that personality factors contribute significantly to the patient's difficulties with gradual benzodiazepine discontinuation of therapeutic doses of benzodiazepines.

Adult↗
PubMed1990

Small bowel transplantation.

Small intestinal transplantation has had several clinical attempts based on extensive experimental work during the past two decades. Several models, such as auxiliary (heterotopic) or orthotopic models, have been developed in regard to problems with graft immunology and function. The question of mesenteric-portal or mesenteric-caval graft drainage was raised, and the answer seems to be open. Concerning lipid absorption, interest was directed to the reconstitution of lymphatic vessels, because orally administered cyclosporine A is absorbed by the lipid mechanism. Carbohydrate digestion and absorption are used for determination of graft function and for monitoring graft rejection. This article summarizes these problems and deals with the surgical procedure of small bowel transplantation in the rat.

Anastomosis, Surgical↗
PubMed1990

Lorazepam vs. alprazolam in the treatment of panic disorder.

Sixty-seven patients with panic disorder were treated with single-blind placebo for one week before being randomized to 6 weeks of double-blind treatment with either lorazepam or alprazolam. Both drugs showed significant and comparable antipanic efficacy throughout the course of the study. With the exception of sedative effects, both drugs were well-tolerated at a mean daily dose of 7 mg for lorazepam and 3 mg for alprazolam. Lorazepam appeared to be as effective as alprazolam in the acute treatment of panic disorder.

Adult↗
PubMed1990

Benzodiazepine dependence: management of discontinuation.

This article discusses the management of benzodiazepine (BZ) withdrawal in patients who are chronically benzodiazepine dependent. Gradual benzodiazepine discontinuation is preferable to abrupt discontinuation, particularly for patients on short half-life benzodiazepines. For a small number of patients, replacement of short half-life with long half-life benzodiazepines may also be helpful. Finally, we present new preliminary data from a controlled, double-blind study that suggest that adjunctive use of such drugs as carbamazepine, imipramine, and buspirone may be helpful in managing gradual benzodiazepine discontinuation. Initiating adjunctive medication prior to, and continuing it during and after benzodiazepine discontinuation led to significantly higher discontinuation success rates for carbamazepine (91%), buspirone (85%), and imipramine (79%) than for placebo (58%) (p less than .05). Careful followup for an extended period of time is needed after benzodiazepine discontinuation because, frequently, emerging psychiatric symptoms may again necessitate psychiatric intervention.

Anti-Anxiety Agents↗
PubMed1990

The clinical course and long-term management of generalized anxiety disorder.

Evidence suggests that generalized anxiety disorder (GAD) has a fairly chronic course marked by significant long-term distress and comorbidity. Research has focused on short-term treatment of GAD, and long-term outcome studies after either short- or long-term treatment have been relatively neglected. The authors discuss the benefits and risks of various drug and nondrug therapies used in the long-term management of generalized anxiety disorder and suggest avenues for future research.

Anti-Anxiety Agents↗
PubMed1990

Clinical overview of serotonin reuptake inhibitors.

The clinical pharmacology, adverse event profiles, and clinical efficacy of several serotonin reuptake inhibitors are summarized and compared with those of the classic tricyclic antidepressants. Serotonin reuptake inhibitors discussed are sertraline, zimelidine, fluoxetine, fluvoxamine, and paroxetine. While they do not differ from tricyclics in efficacy or onset of action, the serotonin reuptake inhibitors clearly have a different side effect potential. Unlike tricyclics, serotonin reuptake inhibitors provide effective antidepressant activity without sedating, anticholinergic, or cardiotoxic reactions. In comparison, tricyclics lower the seizure threshold, have anticholinergic and hypotensive effects, affect cardiac conduction, are dangerous in overdose, and may cause weight gain. The primary adverse events associated with serotonin reuptake inhibitors involve the gastrointestinal system, although side effects may be less frequent at lower dosage levels. It is important to choose antidepressant therapy on the basis of a patient's ability to tolerate the specific adverse reactions that may occur with a given agent. Although serotonin reuptake inhibitors have not replaced the tricyclics, they are a useful addition to the variety of drugs currently used for the treatment of depression.

1-Naphthylamine↗
PubMed1990

Buspirone in depressed outpatients: a controlled study.

One hundred fifty-five outpatients suffering from major depression with significant anxiety entered a double-blind study comparing 8 weeks of treatment with buspirone or placebo. Twenty-nine percent of buspirone and 40 percent of placebo patients discontinued treatment before 8 weeks. Major efficacy measures were the Hamilton Rating Scale for Depression (HAM-D) total score, the HAM-D retardation and anxiety factors, the HAM-D Rickels and Bech core depression clusters, the Clinical Global Impressions (CGI), and the Hopkins Symptom Checklist (HSCL). Results were consistent across all outcome measures, including the two core depression clusters, with treatment response to buspirone significantly better than to placebo at treatment endpoint. Seventy percent of buspirone and 35 percent of placebo patients (p less than .01) were rated moderately or markedly improved after 8 weeks of therapy. Buspirone was found to be safe and well-tolerated by patients with major depression and concomitant anxiety at doses of up to 90 mg/day.

Anxiety Disorders↗
PubMed1990

A placebo-controlled study of enciprazine in the treatment of generalized anxiety disorder: a preliminary report.

Enciprazine is a propanolamine derivative with a preclinical profile similar to buspirone but with less affinity for the postsynaptic dopamine receptor (Linden et al. 1988). We report on the outcome, using intent-to-treat data, of a 5-week, double-blind trial comparing three dose strengths of enciprazine (5 mg t.i.d., 10 mg t.i.d., and 20 mg t.i.d.) to placebo. A dose escalation was permitted after 2 weeks of active drug treatment, which 61 percent of patients overall took advantage of. A "last observation carried forward" (LOCF) analysis found a mean improvement in Hamilton Anxiety Scale (HAM-A) scores by Week 5 of -11.0 for the combined enciprazine treatment groups, and -4.4 for the placebo group (p less than .05). Fifty-two percent of enciprazine patients were judged to be "much" or "very much" improved, whereas none of the placebo patients were judged to have comparable improvement. Enciprazine was well-tolerated, with low levels of sedative and asthenic side effects reported. The compound appears to have promise as an anxiolytic agent.

Adult↗
PubMed1990

Results of a brief survey on the prescribing practices for monoamine oxidase inhibitor antidepressants.

Four hundred eighty-five psychiatrists in Pennsylvania and Delaware responded to a survey of prescribing practices for the monoamine oxidase inhibitor (MAOI) antidepressants. Although the low response rate (34%) limited the generalizability of the results, the similarity between respondents and the total sample surveyed argued against gross sampling bias. The authors found that only a minority of psychiatrists (25%) prescribe MAOIs regularly, despite a relatively low rate of reports of serious sequelae from hypertensive crises or other side effects. They also found that a substantial number of psychiatrists who regularly prescribe MAOIs also report prescribing high doses and combining therapy with tricyclics, lithium, neuroleptics, and psychostimulants. These findings have implications for postmarketing research on psychotropic drugs.

Anxiety Disorders↗