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Biomedical subjects

E Lang

Publications and source records attributed to E Lang.

At least 127 records · Page 7Linked to original sources

[Significance of arrhythmias in advanced age].

Tachycardiac and bradycardiac arrhythmias increase with age. Because cardiac arrhythmias at an advanced age are almost always caused by organic disease, one must face more frequently electrical complications (e.g. ventricular fibrillation). Owing to the decrease of arterial flow volume as well as mean arterial pressure, bradycardiac and tachycardiac arrhythmias result in cerebral symptoms more often in elderly than younger persons. The causes of this observation are the disturbed cerebral autoregulation of blood pressure, but also the insufficient capacity of adaptation of the ageing circulation. In this situation it is more frequently necessary in old people than in younger ones to treat cardiac arrhythmias by antiarrhythmic drugs. The cardiodepressant effect of most antiarrhythmic drugs must be taken into account in this context.

Aged↗

A clinical trial on efficacy and safety of teicoplanin in combination with beta-lactams and aminoglycosides in the treatment of severe sepsis of patients undergoing allogeneic/autologous bone marrow transplantation.

Early institution of empiric therapy with a broad-spectrum antibiotic has markedly reduced the morbidity and mortality from infections complicating severe or prolonged cytopenia in patients receiving either an allogeneic or autologous bone marrow transplant. Ceftazidime in combination with an aminoglycoside, i.e. netilmicin, has been established as a combination schedule offering low or even avoiding therapy-related toxicity. We evaluated teicoplanin for suspected Gram-positive infections after inadequate response to initial beta-lactam and aminoglycoside combination therapy. All 11 patients so far included in this study received either an allogeneic (five patients) or an autologous (six patients) bone marrow transplant for acute myeloid leukaemia (AML), non-Hodgkin lymphoma (NHL, high grade) or other malignant diseases. All patients developing a primary septicaemia of unknown origin (10 patients) or a catheter related septicaemia (one patient) were treated with 400 mg teicoplanin, administered i.v. once daily in combination with a cephalosporin and an aminoglycoside (ceftazidime 2 g, i.v., t.i.d., netilmicin 400 mg once daily). All 11 patients responded to therapy, 10 patients were clinically cured, one patient improved under therapy. The therapeutic regimen was well tolerated and adverse drug reactions did not occur. We have not observed any delayed take of prolonged neutropenia or thrombocytopenia with this therapeutic regimen when compared to other bone marrow transplant patients who did not receive this antimicrobial therapy. Our preliminary results suggest that teicoplanin is a potentially effective and well-tolerated antimicrobial agent in bone marrow transplant patients with infections not responding primarily to beta-lactams and aminoglycosides.

Adolescent↗

Chemosensitivity of fine afferents from rat skin in vitro.

1. Properties of sensory receptors with slowly conducting nerve fibers (less than 10 m/s) were studied using a rat skin-saphenous nerve in vitro preparation where receptive fields of identified single units can be isolated and superfused at the corium side with defined chemical solutions. 2. With mechanical search stimuli, 150 slowly adapting units were identified, 88% C-fibers, and the remainder, A delta-fibers. The majority of these units (65%) were categorized as mechano-heat sensitive ("polymodal") with controlled radiant heat stimulation. The remaining units were classified as low- or high-threshold mechanoreceptors according to their von Frey thresholds. 3. Bradykinin (BK), in concentrations of 10(-8) to 10(-4) M, was repeatedly applied for 1 min at 10-min intervals. Fifty-six percent of the polymodal C-fibers responded to BK (up to 10(-5) M), in contrast to 17% of the heat-insensitive units (P less than 0.01). No correlation between BK sensitivity and conduction velocity or von Frey threshold was found. 4. The BK "threshold concentrations" to excite C- and A delta-fibers were about equally distributed over a range from 10(-8) to 10(-5) M. 5. There was a large interindividual variability in pattern and magnitude of the response to BK. Intraindividually, a marked tachyphylaxis upon repeated BK stimulation was observed. 6. In fibers with a slow development of tachyphylaxis, the effects of conditioning application of different chemicals on BK responsiveness were studied. Norepinephrine in 10(-7) M concentration did not produce a significant effect, whereas 10(-5) M and 10(-4) M seemed to increase the BK responses. 7. Prostaglandin E2 (10(-6) M) caused a weak sensitization to BK on average (n.s.), but serotonin (10(-6) M) was clearly effective (P less than 0.05). 8. The strongest sensitization to BK (P = 0.01) resulted from conditioning heat stimulation, which also uncovered a responsiveness in some units initially insensitive to BK. 9. In some experiments the calcium concentration in the superfusate of receptive fields was lowered to 0.3 mM, which induced ongoing activity in C-fibers and markedly increased the BK responses in two polymodal units tested. Increasing the calcium concentration to 3.0 mM reversed these effects. 10. After completing the BK test protocol, polymodal C-fibers were exposed to other chemicals.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗

High spinal anesthesia does not depress central nervous system function as measured by central conduction time and somatosensory evoked potentials.

Short-latency somatosensory evoked potentials (SSEPs) in response to median nerve stimulation were recorded from the neck and the scalp before and during diagnostic high spinal anesthesia (touch T3, pinprick C8) in six patients with chronic pain. The central conduction time--the time difference between the neck-recorded N13 and the scalp-recorded N20--and the amplitudes of the SSEPs did not change in a statistically significant way during high spinal anesthesia. However, latencies of the neck-recorded N13 and the scalp-recorded N20 and P25 increased slightly. This may have been due to a local anesthetic effect on those spinal roots of the median nerve in which segmental pinprick analgesia occurred. Because high spinal anesthesia did not depress central nervous function, as measured by central conduction time, and SSEP amplitudes, it is concluded that scalp-recorded SSEPs during high spinal anesthesia measure the effects of local anesthetics in the cerebrospinal fluid on neuronal pathways outside the brain.

Adult↗

Comparison of efficacy and safety of teicoplanin in gram-positive infections: a multicentre study.

A multicentre open trial included 219 hospitalized patients suffering from various Gram-positive infections. Previous antimicrobial therapy had been carried out in 37% of patients. The initial teicoplanin dose was 400 mg for 77.6% and 800 mg for 12.6% of the patients, 9.8% received other initial doses. The dose on subsequent days was 200 mg or less for 63% of patients and 400 mg for the remaining 27%. The mean duration of treatment was 11 days. Concomitant antibiotic treatment was given in 35% of cases. The overall clinical success rate was 86.9%. Therapy failure or recurrence of infection was seen in 5% and 2%, respectively. Elimination of pathogens was seen in 85.1% of all evaluable cases. Adverse drug reactions were observed in 14 patients. From these results, we conclude that teicoplanin is safe and effective in the therapy of many different infections caused by Gram-positive bacteria.

Adolescent↗

Antibody 12-15 cross-reacts with mouse Fc gamma receptors and CD2: study of thymus expression, genetic polymorphism and biosynthesis of the CD2 protein.

Previously we described a monoclonal antibody (mAb 12-15) that reacted with murine Fc receptor proteins (beta 1, beta 2 and alpha) and an undefined molecule of 37 kDa (beta 3) on certain types of cells. Here we present serological and biochemical evidence that the beta 3 chain is expressed on mouse thymocytes and that it is identical to the CD2 antigen. By immunofluorescence staining and cytofluorographic analysis greater than 95% of thymocytes were positive. Brightly staining cells coincided with cortisone-resistant thymocytes suggesting that mature thymocytes expressed higher levels of the antigen. Biosynthetic labeling of DBA/2 thymocytes with [35S]methionine showed that the size of the CD2 precursor molecule was 43 kDa which was processed to approximately 55-65 kDa in the mature molecule. mAb 12-15 was also reactive with the tunicamycin-treated form of the CD2 antigen suggesting that the cross-reactive epitope was of protein nature. Comparison of different mouse strains indicated that two molecular forms of CD2 exist. On BALB/c thymocytes, the relative mass of the native molecule was approximately 60-70 kDa (CD2.1) and slightly larger than in DBA/2 (CD2.2). Following endoglycosidase F treatment both proteins still showed a slight difference in electrophoretic mobility. Several inbred mouse strains were analyzed for expression of CD2 forms. When mAb 12-15 was used in cytotoxic T lymphocyte inhibition experiments using specific CTL and tumor target cells it was found that the antibody could specifically inhibit CTL-mediated lysis presumably by interfering with CD2 function.

Animals↗

Leishmania major: histopathological responses before and after topical treatment in experimental animals.

The cellular response in the cutaneous leishmaniasis lesion (CL), of BALB/c mice treated topically with an ointment composed of 15% paromomycin and 12% methylbenzethonium chloride (PR-ointment) was studied. In the infected, untreated control group, the lesion showed progressive necrosis with an increase in the number of parasites, macrophages, lymphocytes, and polymorphonuclear cells over a period of 18 weeks. In the PR ointment-treated group, complete healing of the lesion was observed 4 weeks after termination of treatment, but total elimination of the parasites from the lesion was observed only 2 weeks later. A marked reduction in the number of macrophages and polymorphonuclear cells was observed during the healing process. A similar phenomenon was observed with mice inoculated intraperitoneally with paromomycin alone, although total elimination of the parasites from the lesions of these mice was not demonstrated over a period of 18 weeks. Neither L3T4 helper T cells nor Ly2 cytotoxic suppressor T cells were detected in the CL lesion, either before or after treatment.

Administration, Topical↗

States of developmental commitment of a mouse embryonal carcinoma cell line differentiating along a neural pathway.

The embryonal carcinoma cell line PCC7-S-AzaR1 (clone 1009) has been shown to differentiate in the presence of all-trans retinoic acid and dibutyryl cAMP into cells of predominantly neural properties (Paulin, D., H. Jakob, F. Jacob, K. Weber, and M. Osborn. 1982. Differentiation. 22:90-99). By analyzing the marker expression of derivatives in further detail, we characterized the two major cell phenotypes as neuron- and fibroblast-like and the two minor ones as astroglia- and endothelial-like. The stability of developmental commitment of clone 1009 was tested by recloning. The isolated subclones exhibited different patterns of chemically induced derivatives, with some of them (denoted N-clones) producing only a single (neuronal) cell type. As shown by long-term cultures in the absence of retinoic acid, the properties of isolated subclones remained essentially stable. In contrast to the clones producing neuron-like and other derivatives upon induced differentiation, the (exclusively neuronal) derivatives of N-clones detached and died within a few days in culture. If maintained in the presence of other neural cell types, however, their survival was dramatically extended indicating a requirement for specific interactions with other cells of the same tissue. The patterns of derivatives obtained from N-clones depended on the chemical nature of the substrate on which they were grown. Thus, when seeded on laminin-coated surfaces before induced differentiation, N-clones developed not only to neuron-like derivatives but rather to the same four derivatives observed with the original cell pool. These and further results suggest a common cell lineage of the identified phenotypes. The isolated subclones of uninduced cells probably represent different states of commitment within the same developmental pathway. Their stability offers the opportunity to analyze the nature of cellular commitment on the cellular, molecular, and genetic levels. This makes the family of clones derived from PCC7-S-AzaR1 (clone 1009) cells an advantageous in vitro model of mammalian brain early ontogenesis.

Animals↗

Crusted scabies: a case report and review of the literature.

Crusted (Norwegian) scabies, a highly contagious variant of classical scabies, has traditionally been associated with mentally retarded and physically debilitated patients. Recent reports have increasingly linked scabies with immunosuppression, as in acquired immunodeficiency syndrome (AIDS) and in transplant recipients. Lesions may mimic those of a wide variety of skin diseases. The patient presented is a 41-year old male with signs of systemic illness and atypical dermatitis. This case illustrates the pitfalls in recognition of crusted scabies and the importance of rapid diagnosis. Diagnostic technique and treatment are briefly reviewed.

Acquired Immunodeficiency Syndrome↗

Spinal cord transmission of impulses during high spinal anesthesia as measured by cortical evoked potentials.

Cortical evoked potentials (CEPs) resulting from posterior tibial nerve stimulation could be recorded before, but not during, diagnostic high spinal anesthesia to T2-3 in six patients with chronic pain. In contrast, spinal cord stimulation at T8-9 during high spinal anesthesia resulted in CEPs with reduced peak amplitudes and increased P1 and N2 latencies. Amplitudes of the CEPs evoked by spinal cord stimulation increased with increases in stimulus intensity before and during high spinal anesthesia (N = 3). During spinal anesthesia, higher stimulus intensities were required to evoke CEPs of similar amplitudes as before. Because CEPs evoked by stimulation of the posterior tibial nerve disappeared, but those evoked by spinal cord stimulation did not, it is concluded that spinal anesthesia is a result of blockade of nerve roots, not blockade of neural transmission within the cord. Therefore, diagnostic high spinal anesthesia cannot exclude an origin of pain within the spinal cord.

Adult↗

Murine Fc gamma receptor proteins: identification of a previously unrecognized molecule with a monoclonal antibody (12-15).

Previously we studied differential expression of cell surface molecules between the metastatic murine lymphoma ESb and an adhesion variant ESb-MP. Here we describe the specificity of a monoclonal antibody (12-15) that showed strong binding to the adhesion variant and weak reactivity against ESb cells. The antibody also reacted to lymphoid but not to macrophage-derived cell lines and immunoprecipitated a molecule of approx. 60-69 kDa from ESb-MP cells. N-terminal sequencing of the antigen revealed identity to the beta protein of mouse Fc gamma receptors. Using monoclonal antibodies against Fc gamma receptors (2.4G2 and K9.361) in immunofluorescence assays and cDNA probes specific for alpha, beta 1 and beta 2 Fc receptor transcripts in Northern blot experiments the differential expression of Fc receptors in ESb and ESb-MP cells was confirmed. Biochemical analysis of endoglycosidase F-treated precipitates revealed that antibody 12-15 reacted to products of all three transcripts with molecular masses for the protein core of 38.5 kDa (beta 1), 34 kDa (beta 2) and 31 kDa alpha). In addition, an unknown protein of 37 kDa (termed beta 3) was identified by antibody 12-15 which could also be detected in ESb cells and EL4 cells. Antibodies 2.4G2 and K9.361 did not react to the beta 3 chain but reacted to varying extents to the other Fc proteins in macrophage and lymphoid cells. Comparison by peptide mapping of the novel beta 3 chain to beta 1, beta 2 and alpha proteins revealed similar, but also distinct peptides. The tissue-specific reactivity of monoclonal antibody 12-15 is likely to be due to a carbohydrate epitope associated with all Fc gamma receptors in lymphoid but not macrophage cell lines.

Animals↗

Comparison of the antianginal efficacy of isosorbide dinitrate (ISDN) 40 mg and verapamil 120 mg three times daily in the acute trial and following two-week treatment.

Fourteen male patients with exertion-related angina pectoris and reproducible ST-segment depression on stress testing were each treated with isosorbide dinitrate (ISDN) 40 mg three times daily, verapamil 120 mg three times daily and placebo three times daily for two weeks according to a double-blind cross-over protocol. The mean improvement of exercise-induced ST-segment depression amounted to 73% on the first day of ISDN treatment (P less than 0.001) and to 54% following acute administration of verapamil (P less than 0.001). On the last day of continuous treatment, the antianginal efficacy of ISDN was somewhat mitigated (reduction of ST-segment depression: 54%; P less than 0.001), while the effect of verapamil remained unchanged (55%, P less than 0.001). The double product (heart rate x systolic blood pressure) at the end of stress testing decreased most pronouncedly on day 1 of ISDN treatment (-21%; P less than 0.01). On chronic testing, both drugs similarly influenced this parameter: 10-11% (P less than 0.05). The mean global ejection fraction (EF) assessed by gated blood pool scintigraphy on day 13 showed a stress-induced fall from 49 to 44% (P less than 0.05) after the administration of placebo. The respective values with ISDN were 53% at rest and 52% on exercise (n.s.), and after giving verapamil 50% and 47% (n.s.). Thus, ISDN 40 mg and verapamil 120 mg displayed beneficial anti-ischaemic effects in patients with stable exertion-related angina pectoris after acute and chronic administration. The efficacy of ISDN declined somewhat in the course of the two-week treatment, whereas that of verapamil remained unchanged. Beneficial effects of both drugs were also demonstrated with regard to the rate-pressure product. Isosorbide dinitrate 40 mg and verapamil 120 mg administered three times daily can be recommended for the acute and chronic therapy of patients with stable angina.

Acute Disease↗

[Distal biceps tendon rupture. Clinical aspects--therapy--results].

Between 1980 and 1986 16 male patients of between 30 and 65 years of age were treated operatively because of distal biceps tendon ruptures. The operative procedures are reported and the results of a follow-up examination two years later are communicated. The good results of the applied operative treatment allow to recommend the operative procedure. A special method of measurement of muscle power is presented.

Adult↗

Changes in tumor cell adhesiveness affecting speed of dissemination and mode of metastatic growth.

Adhesion variants can be isolated from suspension growing highly metastatic murine ESb tumor cells under reproducible conditions from uncloned as well as from cloned ESb tumor cells. One such variant, ESb-MP, has been analyzed in detail. In vitro it had similar growth properties and high invasive capacity as the parental ESb cells. In vivo, ESb-MP cells showed a reduced growth capacity as compared to ESb cells. This was seen at the site of tumor cell transplantation (increased latency period) as well as at the site of secondary tumor growth in internal organs. ESb-MP tumor cells disseminated much later than ESb cells from the primary tumor into the blood stream. Both tumor lines metastasized to the liver but they affected liver functions in a different way: ESb cells infiltrated the liver diffusely and exerted toxic effects on liver parenchyma very quickly. This resulted in early increase of liver enzyme activity in the blood. In contrast, liver infiltrated by ESb-MP cells showed a more focal type of colonization and the organs seemed to be functioning for much longer periods. In fact, animals inoculated with ESb-MP cells subcutaneously or intravenously had an increased life expectancy compared to ESb-tumor-bearing animals of about 300%. The organotropism of both tumor lines remained similar although there were kinetic and quantitative differences, especially with regard to the kidney. In late stages of tumor growth, ESb-MP-tumor-bearing animals developed a high percentage of metastases in the kidney and around and within the spinal cord, thereby causing a syndrome of hind-leg paralysis. This syndrome was remarkable in its reproducibility, especially after intravenous tumor cell inoculation. The changed adhesiveness thus seemed to have affected the tumor latency period, the speed of dissemination into blood and internal organs, the mode of organ infiltration (focal vs. diffuse) and of metastatic growth, parameters which all might contribute to the greatly reduced overall malignancy.

Animals↗

Structural basis for altered soybean agglutinin lectin binding between a murine metastatic lymphoma and an adhesive low malignant variant.

By selection for plastic adhesiveness we have previously established a variant tumor line (ESb-MP) from the metastatic murine lymphoma ESb. In contrast to the parental line, the adhesion variant is significantly decreased in malignancy and is altered in the capacity to bind soybean agglutinin (SBA) lectin. Here we show biochemically that the major SBA-binding cell-surface component of ESb-MP cells is the T200 glycoprotein. In ESb cells, T200 antigens bind SBA only after sialidase treatment. Enzymatic studies suggested that glycans detected by the lectin with or without sialidase treatment are different. Inhibition of N-glycosylation by tunicamycin and biosynthetic labeling revealed two T200 chains for ESb-MP cells that were larger in size than the single chain detected in ESb cells. Studies on the biosynthesis revealed that ESb-MP cells expressed two precursor chains for T200 whereas ESb cells displayed only one. There was no size difference detectable in the mature T200 molecules of ESb and ESb-MP cells. Our data suggest that the molecules differ in expression of O-linked glycans that can be recognized by SBA. Additional O-linked sugars on ESb-MP T200 molecules seem to be expressed in particular after trimming of the second T200 precursor chain.

Animals↗