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Biomedical subjects

K Lehmann

Publications and source records attributed to K Lehmann.

At least 55 records · Page 3Linked to original sources
PubMed1999

Treatment for human immunodeficiency virus with indinavir may cause relevant urological side-effects, effectively treatable by rehydration.

OBJECTIVE: To explore the occurrence of, and diagnostic and therapeutic procedures for urological side-effects (e.g. micro- and macrohaematuria, and kidney stone formation) in individuals treated with indinavir for the human immunodeficiency virus (HIV). PATIENTS AND METHODS: The study comprised a retrospective follow-up of 74 individuals infected with HIV-1 and who were treated with indinavir orally at a daily dose of 2.4 g. Data were collected at the outpatient department of our institution between March 1996 and November 1997. RESULTS: Of the 74 individuals treated with indinavir, 15 (20%) had indinavir-related urological side-effects (19 episodes), most commonly dull flank pain and dysuria. Microhaematuria occurred in 16 of the 19 episodes. Four patients showed urinary tract distension ultrasonographically as a possible indirect sign of urolithiasis and one patient passed a kidney stone. In four patients treatment had to be stopped permanently, but in the remaining 11 patients treatment was continued. Some patients required dose reduction and/or interruption of treatment; only conservative therapeutic measures were required, consisting of rehydration (fluid intake >1.5 L/day) and analgesics. CONCLUSIONS: Urological side-effects of indinavir may be apparent in 20% of patients so treated; some (5%) may require permanent withdrawal. In addition to a history and clinical examination, urine analysis and ultrasonography were the only diagnostic procedures required. Therapy is mainly conservative, using rehydration, analgesics and a brief discontinuation of therapy, according to the severity of the symptoms.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Synergistic effects of tetrahydroaminoacridine and lithium on cholinergic function after excitotoxic basal forebrain lesions in rat.

Effects of lithium and tetrahydroaminoacridine (THA), either alone or in combination, were tested in an animal model of excitotoxic cholinergic deafferentation of the cerebral cortex. Rats received ibotenic acid lesions of cholinergic basal forebrain nuclei resulting in a 30% to 40% depletion of both cortical choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activity. Lithium as well as THA, given separately either prior or subsequently to the development of the lesion, had small but significant effects on the recovery of cortical ChAT and AChE activity. Applied in combination, these drugs clearly showed synergistic effects. These potentiating actions might be due to neuroprotective/ neurotrophic mechanisms as well as to effects on acetylcholine turnover and muscarinic receptor-coupled phosphoinositide turnover. Similar approaches of combination therapy might prove useful for the management of mental disorders associated with cholinergic dysfunction.

Acetylcholinesterase↗
PubMed1998

Mutant alleles of the MRS2 gene of yeast nuclear DNA suppress mutations in the catalytic core of a mitochondrial group II intron.

Previous studies show that some yeast strains carrying point mutations of domain 5 that block splicing of a mitochondrial group II intron yield spontaneous revertants in which splicing is partially restored by dominant mutations of nuclear genes. Here we cloned and sequenced the suppressor allele of one such gene, and found it to be a missense mutation of the MRS2 gene (MRS2-L232F). The MRS2 gene was first implicated in group II intron splicing by the finding that overexpression of the wild-type gene weakly suppresses the splicing defect of a mutation of another intron. Tetrad analysis showed that independently isolated suppressors of two other domain 5 mutations are also allelles of the MRS2 gene and DNA sequencing identified a new missense mutation in each strain (MRS2-T230I and MRS2-L213M). All three suppressor mutations cause a temperature-sensitive respiration defect that is dominant negative in heterozygous diploids, but those strains splice the mutant intron at the elevated temperature. The three mutations are in a domain of the protein that is likely to be a helix-turn-helix region, so that effects of the mutations on protein-protein interactions may contribute to these phenotypes. These mutations suppress the splicing defect of many, but not all, of the available splicing defective mutations of aI5gamma, including mutations of several intron domains. Protein and RNA blot experiments show that the level of the protein encoded by the MRS2 gene, but not the mRNA, is elevated by these mutations. Interestingly, overexpression of the wild-type protein restores much lower levels of splicing than were obtained with similar elevated levels of the mutated Mrs2 proteins. The splicing phenotypes of these strains suggest a direct role for Mrs2 protein on group II intron splicing, but an indirect effect is not yet ruled out.

Alleles↗
PubMed1998

Phosphoinositide 3-kinase induces scattering and tubulogenesis in epithelial cells through a novel pathway.

Hepatocyte growth factor/scatter factor (HGF/SF) treatment of the Madin-Darby canine kidney epithelial cell line causes scattering of cells grown in monolayer culture and the formation of branching tubules by cells grown in collagen gels. HGF/SF causes prolonged activation of both the mitogen-activated protein (MAP) kinase extracellular signal-regulated kinase 2 (ERK2) and the phosphoinositide 3-OH kinase (PI 3-kinase) target protein kinase B (PKB)/Akt; inhibition of either the MAP kinase pathway by the MAP kinase/ERK kinase inhibitor PD98059 or the PI 3-kinase pathway by LY294002 blocks HGF/SF induction of scattering, although in morphologically distinct ways. Expression of constitutively activated PI 3-kinase, Ras, or R-Ras will cause scattering, but activated Raf will not, indicating that activation of the MAP kinase pathway is not sufficient for this response. Downstream of PI 3-kinase, activated PKB/Akt and Rac are both unable to induce scattering, implicating a novel pathway. Scattering induced by Ras or PI 3-kinase is sensitive to PD98059, as well as to LY294002, suggesting that basal MAP kinase activity is required, but not sufficient, for the scattering response. Induction of MDCK cell tubulogenesis in collagen gels by HGF/SF is inhibited by PD98059; expression of activated Ras and Raf causes disorganized growth in this system, but activated PI 3-kinase or R-Ras causes branching tubule formation similar to that seen with HGF/SF treatment. These data indicate that multiple signaling pathways acting downstream of Met and Ras are needed for these morphological effects; scattering is induced primarily by the PI 3-kinase pathway, which acts through effectors other than PKB/Akt or Rac and requires at least basal MAP kinase function. Elevated PI 3-kinase activity induces tubulogenesis, but total inhibition and excess activation of the MAP kinase pathway both oppose this effect.

Animals↗
PubMed1998

Prostate-specific antigen in the cerebrospinal fluid leads to diagnosis of solitary cauda equina metastasis: a unique case report and review of the literature.

A 79-year-old male patient presented with a subacute cauda syndrome caused by an intradural metastasis of the lumbosacral caudate fibres from an adenocarcinoma of the prostate, which had been treated 5 years earlier with external beam radiation therapy. Diagnosis could not be established by repeated magnetic resonance images (MRIs) during a 2-year period of increasingly severe radicular pain. Eventually, a small tumour mass could be visualized on the fourth MRI. Repeated normal serum prostate-specific antigen (PSA) did not hint at a prostate cancer metastasis (range 2.4-5.1 ng ml(-1)); however, PSA in the cerebrospinal fluid was found to be elevated (29.1 ng ml(-1)). Empirical radiation therapy of the caudate region did not improve radicular pain. Therefore, an exploratory surgical procedure was conducted, which confirmed the suspicion of an intradural prostate cancer metastasis. In conclusion, PSA in the cerebrospinal fluid provides a useful diagnostic tool for detecting intradural prostate cancer metastasis.

Adenocarcinoma↗
PubMed1998

[Ambulatory treatment of erectile dysfunction].

Intracavernous injection of vasodilating agents and vacuum constriction devices are the therapeutic alternatives in outpatients with secondary erectile dysfunction in Europe. The agents commonly used include papaverine, alprostadil and phentolamine, singly or in combination. Quality of erectile response has agent related characteristics and is dose-dependent. Optimal clinical response ranges from full response for adequate sexual performance to a duration exceeding patient's and partner's wishes. Therefore, the adequate response must be titrated for every patient individually. Vacuum erection devices are efficacious and well accepted from patients and their partners if they can accept the artificial aspect of this approach. Vacuum erection devices are not suitable for men in unstable relations. Injection therapy and vacuum device interfere with spontaneity. The medicated urethral system for erection (MUSE) is a new approach to deliver alprostadil to the corpus cavernosum. The application is more user-friendly than with injections but response rates for adequate satisfactory sexual performance are lower than with intracavernous injections. Therefore indications may be limited to specific etiologies such as neurogenic erectile dysfunction. There is currently no efficient pill on the market although a wide range of therapies are used. Approval and introduction of new oral treatments like Sildenafil and others are awaited by patients and physicians. The availability of new and highly efficient treatment options does not simplify evaluation and treatment of patients with ED. In the contrary they request refinements in the diagnostic process for etiologic diagnosis with subsequently least invasive treatment and minimal side effects.

Ambulatory Care↗
PubMed1998

[Priapism].

Priapism is the persistence of an erection that does not result from sexual desire. Diagnosis is based on history, clinical examination, diagnostic aspiration of blood and measurement of blood gas levels. The purpose of treatment is to increase corporeal outflow by aspiration and injection of alpha stimulating agents. In some rare cases selective angiographic embolisation or surgical resection of a bleeding intracavernous artery is required. Prognosis is good if diagnosis and treatment are not delayed.

Diagnosis, Differential↗
PubMed1997

Potentiation of aflatoxin B1-induced hepatocarcinogenesis in the rat by pretreatment with buthionine sulfoximine.

A single i.p. dose of aflatoxin B1 (AFB1) (1.0 and 2.0 mg/kg body wt)-induced hepatocarcinogenesis with phenobarbital as a promoter has been examined in young male Fischer rats. Immunohistochemical method has been employed to detect AFB1-induced glutathione S-transferase placental form (GST-P)-positive hepatic foci observed from 3 week and 10 week to 40-48 week periods. With 2.0 mg AFB1 dosing, the number, area and volume occupied by GST-P-positive hepatic foci increased significantly and progressively from 3 week, 10 week and 48 week periods. In long term studies (40-48 weeks), 1.0 mg and 2.0 mg AFB1 dose levels yielded linear response in area and volume occupied by AFB1-induced hepatic foci. Pretreatment of rats with L-buthionine sulfoximine (BSO), a GSH depleter, at a dose of 4 mmol/kg body wt 4 and 2 h before 1.0 or 2.0 mg AFB1 treatment enhanced the number, area and volume of GST-P-positive hepatic foci, increases being the largest at shorter time periods (3 and 10 weeks) compared to longer time periods (40 and 48 weeks). This report appears to be the first example of an enhanced chemical induced hepatocarcinogenesis in a long term study in any experimental animals species by a GSH depleting agent.

Aflatoxin B1↗
PubMed1997

Cloning of minisatellite-containing sequences from two-dimensional DNA fingerprinting gels reveals the identity of genomic alterations in low-grade gliomas of different patients.

Two-dimensional (2-D) DNA fingerprinting was used to investigate genomic changes in human low-grade gliomas of different subtypes. DNA variations were identified in the 2-D hybridization patterns as spot losses or gains. Computer-aided matching of spot patterns from different patients revealed a clustering of spot changes at particular areas in the gel. Representative spots of each cluster were cloned using a spot cloning protocol which includes the preparation of a duplicate and a master gel. The DNA fragments of the 2-D gels were transferred to DEAE and nylon membrane, respectively. After hybridization of the master blot with a minisatellite core probe, the position of a particular spot was determined with reference to the lambda DNA fragments used as external markers in both gels. The gel spot DNA was recovered from the DEAE membrane by high salt elution and was polymerase chain reaction (PCR)-amplified after ligation of adaptor oligo cassettes. The PCR products were cloned and used as locus-specific probe for the rehybridization of the 2-D blots. One of these probes detected a spot loss in 7 of 28 low-grade gliomas of different subtypes analyzed. Another probe revealed a characteristic intensity shift in 8 of 9 pilocytic astrocytomas between two neighboring spots. The target sequence of this highly specific effect was assigned to chromosome 11q14 by in situ hybridization of a P1 clone harboring the affected genomic region. Thus, we successfully established a spot cloning procedure for the generation of locus-specific probes that may be instrumental in the discovery of the critical early events of glioma pathogenesis.

Chromosome Mapping↗
PubMed1997

Mumps orchitis: report of a mini-epidemic.

PURPOSE: The incidence of mumps orchitis has declined dramatically since the introduction of vaccination. While in the past cases of mumps have only been seen occasionally at our institution, recently there has been a sharp increase in the number of confirmed cases. MATERIALS AND METHODS: Between June 1995 and April 1996, 11 patients with severe mumps orchitis were hospitalized at our clinic. Medical history, therapeutic measures and clinical outcome were recorded for each patient. RESULTS: All patients showed marked scrotal swelling with a temperature above 38.5 C. Serum C-reactive protein was significantly elevated (mean 140 mg./l.). The vaccination status of 1 of the 11 patients (9%) was unknown. Medical records from the remaining 10 patients indicated that they had not been vaccinated. Nine patients (82%) had a typical mumps parotitis preceding the orchitis. In 2 patients the clinical diagnosis of parotitis was uncertain but mumps serology was positive. None of the patients showed other manifestations of mumps. Antibodies to the mumps virus (IgG and IgM) were determined in 6 patients and positive in all cases. The average interval between parotitis and onset of orchitis was 10 days. All patients were hospitalized for an average of 6 days. Treatment included bed rest with local cooling, scrotal support and systemic treatment with nonsteroidal anti-inflammatory drugs. Ciprofloxacin or clavulanic acid/amoxicillin was administered as bacterial orchitis could not be excluded at initial presentation. The mean time to cessation of fever was 3.6 days (range 3 to 5). Antibiotics were administered for an average of 8.8 days (range 7 to 13) and anti-inflammatory drugs were given an average of 8.6 days (range 7 to 11). One patient required scrotal exploration. CONCLUSIONS: Since the introduction of a vaccine against the mumps virus there is a diminished risk for mumps and its complications. However, in case of scrotal swelling mumps orchitis should still be considered. Despite vaccination mumps has not been erradicated. Therefore, continued vaccination should be considered an important step in minimizing clinical outbreaks and working towards a possible eradication of this disease in the future.

Adolescent↗
PubMed1997

On the problems of switching from intravenous to oral administration in drug treatment of endogenous depression--a placebo-controlled double-blind trial with doxepin.

In the treatment of depressive disorders the onset of action can be accelerated if the antidepressant drug is initially administered by intravenous infusion. It is not clear whether this effect is due to pharmacological or to psychological effects of the infusion setting. The necessary switch to oral administration may be problematic. Uncontrolled observations indicate that it could be associated with a remarkable deterioration in the course of the disease. This randomized double-blind placebo-controlled study on doxepin is the first investigation of the effect of the switch from parenteral to oral administration on symptoms of endogenous depression. The hypothesis to be tested, that there is a significant worsening of treatment response during the switch, must be rejected on the basis of objective and subjective psychometric tests. There was in fact a continuous improvement. Precondition was a selection of patients with typical "endogenous" depressions and maintenance of at least constant plasma levels of the active antidepressants. In patients under the age of 65 years this can generally be achieved by switching in a ratio of 125 mg i.v. to 250 per os in the case of doxepin. Individual case studies indicated that a worsening in the patient's progress after switching was correlated with a decreasing plasma level of the active drug. Low plasma level already during the infusion period, insufficient response, and questionable compliance on oral medication were associated. Due to large interindividual differences of plasma levels by a factor of 10, measurements before and after switching are required.

Administration, Oral↗
PubMed1996

Inhibition of poly(ADP-ribose) formation by 4-hydroxynonenal in primary cultures of rabbit synovial fibroblasts.

The formation of poly(ADP-ribose) in primary cultures of rabbit synovial fibroblasts after treatment with active oxygen released by xanthine/xanthine oxidase is inhibited by addition of 1 and 10 microM 4-hydroxy-2,3-trans-nonenal (HNE). The endogenous formation of HNE by the xanthine/xanthine oxidase system is not responsible for the inhibitory effect of the aldehyde, owing to the low accumulation rate of the lipid peroxidation product in the system used. HNE is able to inhibit the isolated nuclear enzyme ADP-ribosyltransferase, as shown by an in vitro assay with an Ki of 4 mumol/litre. Therefore the molecular basis of HNE-mediated effects on cell proliferation, differentiation and transformation might be due to the inhibitory effect of poly(ADP-ribos)ylation.

Aldehydes↗
PubMed1996

[The value of color-coded duplex ultrasound as standard assessment in erectile dysfunction].

Erectile dysfunction has taken on increasing importance in urologic practice. Still open is the question of which tests are mandatory for adequate clinical assessment of erectile dysfunction. One accepted standard modality is the intracavernous pharmacotest with vasoactive agents. In contrast, color duplex sonography is not considered mandatory although it reveals detailed information about penile vessels and functional implications. The question remains whether the information gained by color duplex sonography is relevant for therapy, making it an indispensable standard procedure. Patients with erectile dysfunction were evaluated, without preselection, by extensive history, clinical evaluation, laboratory tests, tumescence and rigidity measurements, intracavernous administration of vasoactive drugs and color duplex sonography. Seventy-nine patients were available for final analysis. Color duplex sonography revealed 39 normal tests, 16 arterial impairments. 19 venous leakages and 5 arteriovenous fistulae. Intracavernous vasoactive agents (pharmacotest) revealed 44 reactions sufficient for intercourse and 35 insufficient responses. In 89% of patients, the diagnoses on color duplex sonography and intracavernous pharmaco-testing were similar. The accuracy of the two methods in diagnosing erectile dysfunction was not statistically different (McNemar's test). In contrast to intracavernous pharmaco-testing, color duplex sonography permitted further etiologic subdivision into arterial disease, venous leakage, arteriovenous fistula and normal result. This was made possible by measuring significantly (P < 0.01) different arterial peak flow velocities, end-diastolic velocities and calculated resistance index. These data did not imply direct clinical consequences. Color duplex sonography and intracavernous pharmacotesting reveal comparable results concerning the diagnosis of an erectile dysfunction. In contrast to pharmacotesting, color duplex sonography reveals details of the nature of the erectile dysfunction. Because this information has no profound implications for the choice of therapeutic procedure, color duplex sonography can not be recommended as a standard procedure in the evaluation of erectile dysfunction.

Adolescent↗
PubMed1996

Intraurethral prostaglandin improves quality of vacuum erection therapy.

OBJECTIVE: The aim of this study was to investigate whether intraurethral prostaglandin E1 (PGE1) improves vacuum-induced penile rigidity. METHODS: Nineteen patients with a mean age of 55 years (range 30-66 years) complaining of erectile dysfunction for 24 months (range 3-156 months) were investigated. The penile diameter was measured and a mark was made 50 mm proximal of the coronary sulcus on the flaccid penis. Twenty micrograms of liquid PGE1 (pH 4.5; 308 mosm/l) were instilled intraurethrally; thereafter the meatus was occluded for 10 min. Penile diameter and increase in length of the initially 50-mm line were measured with both pure vacuum-induced erection as well as combined with PGE1. RESULTS: The vacuum erection device alone lengthened the distance by 26 mm (range 18-64 mm) and the diameter by 4 mm (range 2-10 mm). Combined with PGE1, 36 mm (range 27-70 mm; p = 0.016) and 7 mm (range 2-11 mm; p = 0.04) were found, respectively. CONCLUSION: We conclude that PGE1 significantly increases vacuum-induced tumescence. Optimized pharmacological preparations for intraurethral application are a new way to further improve vacuum-assisted erection.

Adult↗
PubMed1996

[Acute inpatient treatment of manias. Effects of independent variables on neuroleptic dosage and length of stay].

Investigations of drug therapy regimens in the treatment of acute mania are rare, selective, methodically problematic, and contradictory. The goal of the present study is to describe the practice of mania treatment in a large unselected collective of patients for the first time, and, following reduction of the data to global parameters such as length of stay, neuroleptic daily and total doses, to determine sources of variance and the strength of their effects by means of explorative data analysis. In contrast to widely held opinions, neuroleptics are used as primary medication in all grades of severity of manic illness. The daily dose comprises 496 +/- 379 mg of chlorpromazine (CPZ) equivalents; this result supports the first dose determination study and is at odds with other studies with much higher dosages. The amount of mean daily medication is only influenced by the severity of illness according to variance analysis, the effect is moderately strong. Neuroleptics appear to have causal effects, a property that has so far only been attributed to prophylactic medication, which is given in 80% of cases; the different application forms have no effect on the neuroleptic dosage, although they do affect the length of stay slightly. The mean length of stay is 46.6 +/- 35.7 days and is slightly affected by age, sex, severity of illness and compliance.

Acute Disease↗