Search PubMed⌕ Search

Biomedical subjects

R Zimmermann

Publications and source records attributed to R Zimmermann.

At least 163 records · Page 9Linked to original sources
PubMed1999

[Prospective study of treatment of bullous pemphigoid by a class I topical corticosteroid].

INTRODUCTION: The high mortality at 1 year of patients with bullous pemphigoid is considered to be due mainly to systemic corticosteroids. We report 20 cases of bullous pemphigoid treated solely with class I topical corticosteroid. PATIENTS AND METHODS: Twenty patients with bullous pemphigoid grade 1 and grade 2 were treated with clobetasol propionate 0.05 p. 100 cream at the initial dose of 12 mg/m2/day, progressively tapered over months. Severe forms of bullous pemphigoid covering more than 60 p. 100 of total body area were excluded. RESULTS: 35 p. 100 of the patients obtained a remission and 35 p. 100 healed (62.5 p. 100 of the mild forms, 16.7 p. 100 of the moderate forms). The average follow up was 11 months after the end of treatment. Side-effects were mild (cutaneous infections, dermal atrophy). Transitory biological anomalies were observed, mainly related to systemic absorption of clobetasol propionate. Some systemic adverse reactions were noted not necessarily attributed to treatment. DISCUSSION: Topical steroid treatment was efficient in patients with mild bullous pemphigoid. Our results were comparable to those reported in the literature except for some cutaneous side effects.

Administration, Topical↗
PubMed1999

Mutational analysis of the N-ras, p53, p16INK4a, CDK4, and MC1R genes in human congenital melanocytic naevi.

Eighteen human congenital melanocytic naevi (CMN) from 17 patients were screened for activating point mutations in the oncogenes N-ras and CDK4 and for sequence variants in the MC1R gene by combined RFLP-PCR/SSCP analysis. In addition, all lesions were screened for deletions and point mutations in the tumour suppressor genes p53 and p16INK4a (CDKN2A) by combined multiplex PCR/SSCP analysis. Positive screening data were specified by sequencing of the corresponding PCR product. Activating point mutations in the N-ras gene (nine CAA (Gln) to AAA (Lys) transversions and one CAA (Gln) to CGA (Arg) transition at codon 61) were detected at high frequency (56%). Furthermore, three missense mutations (V92M) and two silent mutations (CGA (Arg) to CGG (Arg), codon 213, exon 6) were found in the MC1R and p53 genes, respectively. No mutations were found in p16 or CDK4. The activated N-ras oncogene, which is also found in human cutaneous melanomas, may constitute a potential risk factor for melanoma formation within CMN.

Adolescent↗
PubMed1999

[Brief report of the working group OPD-CA (children and adolescents) Axis II: interpersonal relations].

Operationalization of relations is tried out following an interpersonal circular model (SASB) using observation and description of behavior in dyadic and triadic relationship configurations. On a vertical and on a horizontal axis the amount of loving kindness versus hostile aggressivity and of independence versus control is determined. Different dyadic and triadic relationship configurations (e.g. child to mother or researcher to child) and also the emotional resonance of the investigating person will be rated according to anamnestic data, observed and videotaped sequences of interaction, play episodes or symbolic relationships in projective tests. Such ratings can be performed in a module like form and will be used not only in clinical practice but also in settings of scientific research. The minimal standard for a clinical examination consists of the evaluation of the child with his parents.

Adult↗
PubMed1998

Extended Electrokinetic Characterization of Flat Solid Surfaces.

An experimental setup has been developed and applied for the combined determination of the electrokinetic potential and the surface conductivity of flat surfaces. The key feature of the new device (designated as microslit electrokinetic setup) is the variability of the distance between two parallel flat sample surfaces (10 mm x 20 mm) forming a slit channel. The setup allows us to decrease this distance down to about 1 µm keeping the surfaces parallel. In consequence, streaming potential measurements can be performed at a given solid/liquid interface both at conditions where surface conductivity is negligible and at conditions where surface conductivity significantly contributes to the total channel conductivity. The zeta potential is calculated at different channel geometries based on streaming potential and channel conductivity data and, alternatively, based on streaming current measurements and the dimensions of the cross section of the slit channel. The results obtained were found to agree well if correct conductivity values for the calculation of the zeta potential based on the streaming potential data are used. The surface conductivity is determined from the extrapolation of the channel conductance values gained at a number of sufficiently small distances between the parallel sample surfaces to the distance zero. An additional feature of the developed microslit electrokinetic setup is the assessability of the hydrodynamic thickness of adsorbed layers of macromolecules or particles at the investigated flat surface. In a series of measurements a plasma-deposited fluoropolymer (PDFP) layer on top of a glass carrier and an adsorption layer of the blood protein fibrinogen on top of the PDFP layer were characterized by zeta potential and surface conductivity measurements in different aqueous electrolyte solutions (KCl, KOH, HCl). For the PDFP/solution interfaces zeta potential up to -100 mV were obtained in solutions of neutral pH exclusively due to preferential ion adsorption. After adsorption of fibrinogen the zeta potential is considerably reduced. For the PDFP/solution interfaces surface conductivities were determined in the range of (1-2) x 10(-9) S. The contribution of the diffuse layer to the surface conductivity has been calculated from the zeta potential according to the approach of Bikerman (Kolloid Z. 72, 100 (1935)) and compared with the experimentally determined surface conductivity. Based on this comparison ions in hydrodynamically immobile interfacial layers were concluded to contribute considerably to the surface conductivity in all investigated cases. This so-called additional surface conductivity is attributed to the accumulation of hydroxide and hydronium ions in the Stern layer. Both the high specific mobility of these ions (as compared to the potassium and the chloride ions) and the conductivity of the charge determining species may contribute to the experimental observations. After adsorption of fibrinogen onto the PDFP surface the additional surface conductivity is increased by about an order of magnitude. The latter fact is assumed to be caused by the presence of mobile ions in the interfacial volume of the adsorbed protein layer. In addition to the electrochemical characterization of the adsorbed protein layer its hydrodynamic thickness has been determined by means of liquid flow measurements with the microslit electrokinetic setup. The obtained value of 48 +/- 5 nm correlates well with the protein dimensions given in the literature and is in the order of magnitude of the optical layer extension determined by ellipsometry. Copyright 1998 Academic Press.

Journal Article↗
PubMed1998

Differential immune response to influenza and pneumococcal vaccination in immunosuppressed patients after heart transplantation.

INTRODUCTION: Patients after solid organ transplantation are at an increased risk for microbial infections. Due to therapeutic immunosuppression, the response to active immunizations may be reduced. The serological efficacy of pneumococcal and influenza vaccination was studied in heart transplant recipients. PATIENTS AND METHODS: Sixteen patients over 1 year after heart transplantation and control patients were immunized with a 23-valent pneumococcal vaccine and a triple-split influenza vaccine. Pre- and postvaccinal antibody titers were serologically determined, including quantitation of specific antibodies against nine pneumococcal serotypes. RESULTS: Both vaccines were well tolerated without systemic reactions or infectious complications. Median postvaccinal pneumococcal antibody titers in the transplant patients were comparable to controls (5513 U/ml, range: 694-41007, vs. 5490 U/ml, range: 1088-38042; P=NS); vaccination was successful in 23/23 (100%) of controls and in 15/16 (94% plus 1 borderline positive case) of the transplant recipients. Specific antibody titers were similar for eight of nine serotypes; only the immune response against serotype 3 was reduced after transplantation. The efficacy of influenza vaccination was significantly impaired in transplant patients against all three virus strains (62% vs. 97%, P<0.01/50% vs. 94%, P<0.001/37% vs. 80%, P<0.01), but 9/16 (56%) of patients still showed a sufficient immune response to two out of three virus strains. No clinical or demographic predictors of successful vaccination could be established. CONCLUSIONS: Pneumococcal vaccination under cyclosporine-based immunosuppression after heart transplantation is safe and equally effective as in healthy controls. In contrast, the immune response to influenza vaccination is significantly reduced, although not completely abolished. This differential response might be accounted for by T cell-independent antibody production against polysaccharide antigens contained in the pneumococcal vaccine.

Adult↗
PubMed1998

A general mechanism for regulation of access to the translocon: competition for a membrane attachment site on ribosomes.

For proteins to enter the secretory pathway, the membrane attachment site (M-site) on ribosomes must bind cotranslationally to the Sec61 complex present in the endoplasmic reticulum membrane. The signal recognition particle (SRP) and its receptor (SR) are required for targeting, and the nascent polypeptide associated complex (NAC) prevents inappropriate targeting of nonsecretory nascent chains. In the absence of NAC, any ribosome, regardless of the polypeptide being synthesized, binds to the endoplasmic reticulum membrane, and even nonsecretory proteins are translocated across the endoplasmic reticulum membrane. By occupying the M-site, NAC prevents all ribosome binding unless a signal peptide and SRP are present. The mechanism by which SRP overcomes the NAC block is unknown. We show that signal peptide-bound SRP occupies the M-site and therefore keeps it free of NAC. To expose the M-site and permit ribosome binding, SR can pull SRP away from the M-site without prior release of SRP from the signal peptide.

Animals↗
PubMed1998

A pancreas-specific glycosylated protein disulphide-isomerase binds to misfolded proteins and peptides with an interaction inhibited by oestrogens.

Using a cross-linking approach, we have demonstrated that radiolabeled model peptides or misfolded proteins specifically interact in vitro with two different luminal proteins in a crude extract from sheep pancreas microsomes. One of the proteins was identified as protein disulphide-isomerase (PDI), the other one was a related protein (PDIp). We have shown that PDIp was expressed exclusively in the pancreas. Interspecies conservation of PDIp was confirmed and, unlike other members of the PDI family, PDIp from various sources was found to be a glycoprotein. PDIp interacted with peptides and also a misfolded protein, but not with native proteins, suggesting that it might act as a molecular chaperone. The initial binding process was independent of the presence of Cys residues in the probed peptides. Certain oestrogens strongly inhibited the interaction between peptides and PDIp, with 17beta-oestradiol being the most potent inhibitor.

Animals↗
PubMed1998

In vitro characterisation of the interaction between newly synthesised proteins and a pancreatic isoform of protein disulphide isomerase.

The lumen of the endoplasmic reticulum (ER) contains an array of molecular chaperones and folding factors that modulate the folding and assembly of newly synthesised proteins entering the secretory pathway. One of these components, protein disulphide isomerase (PDI), facilitates the formation of the correct disulphide bonds within newly synthesised polypeptides, and is the archetype for a family of sequence related PDI-like proteins. We have investigated the interaction between a recently identified, pancreas-specific PDI-like protein (PDIp), and in vitro synthesised secretory and membrane proteins produced in the presence of ER-derived canine pancreatic microsomes. We have previously established that a second PDI-like protein, ERp57, interacts specifically with N-glycosylated proteins. In contrast, we find that the interaction of PDIp with newly synthesised proteins occurs independently of any requirement for N-linked glycosylation. In this respect, the properties of PDIp mirror those of archetypal PDI. When the carbohydrate-dependent interactions between glycoproteins and ERp57 are blocked by drug treatment, the association of these precursors with both PDIp and PDI is enhanced. We propose that PDI-like proteins have overlapping specificity and may exhibit some degree of functional redundancy.

Animals↗
PubMed1998

Differential immunosuppressive activity of monoclonal CD2 antibodies on allograft rejection versus specific antibody production.

CD2 is a co-stimulatory receptor involved in T cell activation. Here we report on immunosuppressive effects of three mouse CD2 monoclonal antibodies (OX34, OX54, OX55) directed against non-overlapping epitopes of the rat CD2 receptor on various modes of T cell activation in vitro and in vivo. Although non-ligand-blocking OX54 and OX55, in concert, activated T cells through CD2 in vitro, they individually suppressed the mixed lymphocyte reaction (MLR) and significantly prolonged allograft survival after rat heart transplantation in vivo. Phenotype analysis revealed that OX55 significantly down-modulated CD2 in vivo, whereas OX54 depleted T cells. Graft rejection coincided with re-expression of CD2 and clearance of OX55 from serum, whereas T cell depletion by OX54 outlasted the period of graft survival. The most suppressive antibody, OX34, down-modulated CD2 and inhibited T cell activation through the TCR or CD2 and the MLR and prolonged median allograft survival time from 7 days in controls to 45 days in the absence of any additional treatment. Graft survival was clearly dose dependent and correlated with the duration of CD2 down-modulation and the presence of circulating CD2 antibody in serum. Importantly, the specific antibody production to a T cell-dependent antigen as demonstrated by immunization with keyhole limpet hemocyanin in vivo remained unaffected after treatment with OX34. These results demonstrate the pivotal role of CD2 signaling in mediating allogeneic immune reactions after vascularized organ transplantation while allowing specific humoral immune responses in vivo.

Animals↗
PubMed1998

[First implantation of a totally implantable electronic hearing aid in patients with inner ear hearing loss].

For the majority of patients with sensorineural hearing loss (SNHL) many available hearing aids often do not achieve satisfactory results. For these patients partially implantable hearing devices have been developed, allowing distortion-free hearing and speech intelligibility that may be superior to conventional hearing aids. The external parts of partial implants, however, may result in a patient's stigmatization. Furthermore, they do not use the acoustic properties of the external auditory canal. Recently, we published the successful development of the first totally implantable hearing device for the treatment of SNHL (HNO 46 [1998] 853-863). Here we report the first implantations of this unique, totally implantable electronic hearing system in patients with SNHL: Implex TICA LZ 3001. The implant microphone is implanted subcutaneously in the outer ear canal near the ear drum. The signal is processed by a digitally programmable multichannel audioprocessor located subcutaneously on the bony skull behind the ear. A piezoelectric transducer is coupled to the body of the incus and drives the ossicular chain by vibratory actions. Energy is provided by an implantable battery. Implanted patients describe hearing as being distortion-free and transparent. Speech intelligibility and the hearing of music are improved. Patients may achieve better speech discrimination, especially in the presence of background noise. The aid can be used during sports, including swimming. To our knowledge, this is the first report of the implantation of a totally implantable electronic hearing system in patients. These results encourage further implantations of the totally implantable hearing system in the course of an ongoing clinical study.

Audiometry, Speech↗
PubMed1998

[Distal, metaphyseal compression fractures of the radius. Results of open reposition, stable defect replacement with cortico-cancellous iliac crest bone and plate osteosynthesis].

Conservative treated distal radius fractures with extended metaphyseal void and missing cortical support resulted in loss of reduction. From 1988 till 1994 117 fractures of the distal radius were treated by open reduction, filling the metaphyseal void with a corticocancellous iliac bone graft and plate fixation. In this retrospective study results after surgical reconstruction were evaluated radiologically and clinically and were discussed to conservative treatment. 30 patients suffering from extraarticular metaphyseal distal radius fracture were evaluated after a mean of 42 months (minimum 20, maximum 68 months) after surgery. Ulnar variance was restored in 70% to the uninvolved side. Ulnar minus variance up to 2 mm persisted in 30%. Radial joint angles were restored to normal in 53%. In 40% of the patients a loss of reduction up to 10 degrees and in 7% up to 25 degrees occured. Active range of motion in the sagittal and frontal plane was equivalent to the non involved side in 30%. 70% of the patients showed reduced range of motion up to 20%. Rotation was unlimited in 77%, reduced up to 10% in 23%. Subjective results were excellent in 90%, good in 10%. Compared to conservative therapie, surgery showed superior results.

Adolescent↗
PubMed1998

L-arginine: effect on reperfusion injury after heart transplantation.

Global myocardial ischemia and reperfusion injury play a major role in early postoperative myocardial graft dysfunction. The aim of the present study was to investigate the effects of the nitric oxide (NO) precursor L-arginine on myocardial and endothelial function after hypothermic ischemia and reperfusion in a heterotopic rat heart transplantation model. After 1 hour ischemic preservation, reperfusion was started after application of placebo (control, n = 12) or L-arginine (L-Arg 40 mg/kg, n = 12), a substrate of NO synthesis. Myocardial blood flow (MBF) was assessed by the hydrogen clearance method. An implanted balloon was used to obtain pressure-volume relations of the transplanted heart. Left ventricular developed pressure (LVDP), rate of pressure development (dP/dt), end-diastolic pressure (LVEDP), isovolumic relaxation constant (TE), and MBF were measured after 60 minutes and 24 hours of reperfusion. endothelium-dependent vasodilatation in response to acetylcholine (ACh) and endothelium-independent vasodilatation in response to sodium nitroprusside (SNP) were also determined. After 1 hour the MBF was significantly higher in the L-Arg group (3.6 +/- 0.6 vs. 1.9 +/- 0.2 ml/min/g, p < 0.05). The L-Arg group showed better recovery of systolic function and myocardial relaxation (LVDP 106 +/- 6 VS. 70 +/- 7 mmHg, p < 0.05; maximal dP/dt 5145 +/- 498 vs. 3410 +/- 257 mmHg/s, P < 0.05; TE 12.1 +/- 0.9 vs. 16.1 +/- 1.5 ms, p < 0.05, at an intraventricular volume of 80 microliters). LVEDP was similar in the two groups. After 24 hours no difference was found between the groups for basal MBF, LVP dP/dt, TE, LVEDP, or the response of MBF to SNP. However, ACh led to a significantly higher increase in MBF in the L-Arg group (52 +/- 8% vs. 29 +/- 7%, p < 0.05). These results indicate that (1) NO donation improves myocardial and endothelial functional recovery during early reperfusion after heart transplantation; and (2) initial treatment with L-Arg has a persisting beneficial effect against reperfusion-induced graft coronary endothelial dysfunction during late reperfusion.

Acetylcholine↗
PubMed1998

[Emotional status of patients on the waiting list for heart transplantation].

Although heart transplantation is by now considered an established procedure in patients with terminal heart failure, there has been a stagnation or even a decline in the number of transplantations performed due to the decreased willingness of the public to provide organs. As a consequence of this development patients have to wait for a donor organ for a much larger time. The aim of this study was to examine patients especially during this very stressful period. From July 1995 to February 1997, 62 patients who had been continuously added to the waiting list were examined regarding their quality of life and emotional state. Completely assessed were 53 patients (participation rate: 85%). As compared to a healthy control group, patients with terminal heart failure on the waiting list reported their quality of life in the physical as well as the psychological area as significantly lower (p < 0.001). The areas of depression (p < 0.001) and anxiety (p < 0.001) also showed a significant difference. There was an obvious correlation (p < 0.01) between the key symptom of terminal heart failure-- dyspnoea--and the measured level of depression. This served to support the notion that there is a connection between the psychological and the somatic state in these severely ill patients. These results point to the necessity of supportive psychotherapeutic treatment during this very stressful time.

Adult↗
PubMed1998

Upregulated and downregulated transcription of myocardial genes after pulmonary artery banding in pigs.

BACKGROUND: Acute or chronic pressure overload may occur during or after cardiac surgical procedures. Typical examples are aortic cross-clamping and pulmonary artery banding. It is well known that mechanical stress induces transcription of different myocardial genes. However, these results were mainly obtained from in vitro studies and experiments with rodents. This experiment was carried out to investigate molecular alterations after pressure overload in porcine hearts. METHODS: The study was performed with 35 Landrace pigs with a mean weight of 32+/-1.2 kg. The five groups consisted of 7 pigs each, 3 sham-operated pigs and 4 banded pigs. The hearts were exised after different time intervals. We investigated messenger RNA expression of sarcoplasmic reticulum adenosine triphosphatase, phospholamban, alpha-/beta-myosin heavy chain, and atrial natriuretic factor by Northern blot analysis. RESULTS: The ratio of right ventricular weight to body weight increased significantly after 7 and 24 days in banded pigs (p < 0.05). Atrial natriuretic factor messenger RNA was significantly upregulated in banded pigs versus sham-operated pigs after 1 day (240%+/-7% versus 100%+/-6%; p < 0.01) and 3 days (520%+/-8% versus 100%+/-8%; p < 0.01). There was insignificant downregulation of sarcoplasmic reticulum adenosine triphosphatase and phospholamban after 1, 3, and 7 days. Myosin heavy chain messenger RNA expression remained unchanged. CONCLUSIONS: Pulmonary artery banding results in hypertrophic response of the porcine right ventricle; however, the weight increase is not the result of myosin heavy chain messenger RNA upregulation. Atrial natriuretic factor messenger RNA is locally expressed in mechanically stressed myocytes. Furthermore, pressure overload downregulates transcription of calcium-binding proteins that can influence ventricular contractility. These results may have an impact on cardiac surgical procedures.

Adenosine Triphosphate↗
PubMed1998

Psychological distress in patients awaiting heart transplantation.

Heart transplantation has become an established procedure for the treatment of terminal heart failure. However, due to a shortage of donor organs, the waiting period for a donor organ is increasing. Cross-sectional and retrospective studies have indicated that there is tremendous psychological distress during this waiting period. The aim of this study was to assess this phase systematically and longitudinally. At the beginning of their waiting period, 62 patients at the Heidelberg Transplantation Centre were examined with regard to their physical complaints, quality of life, and level of depression. Four months later the remaining 42 patients were re-examined. The sample showed a significant increase (p<0.001) in subjective physical symptoms and an impairment in social activities (p<0.05) and everyday life (p<0.05), and a significant increase in depression (p<0.001), despite the relatively short time period. These results show the necessity of supportive psychotherapy for patients undergoing heart transplantation.

Adult↗