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Biomedical subjects

H Hoffmann

Publications and source records attributed to H Hoffmann.

At least 109 records · Page 6Linked to original sources

The molecular mode of action of the Ca agonist (-) BAY K 8644 on the cardiac Ca channel.

The primary drug action of (-) BAY K 8644 on whole-cell Ca current in atrial myocytes was measured under conditions where secondary Ca-mediated changes of Ca channel activity were minimized. The most direct action of (-) BAY K 8644 is the change of gating kinetics which results in a strictly voltage-dependent increase of the peak current in the voltage range between -40 and 0 mV. Peak currents were increased dose dependently in the concentration range from 1 to 30 nM. Analysis of peak current/voltage relations revealed a linear shift of the current activation by approximately 23 mV to more negative membrane potentials, without any change in its voltage dependence and in the current reversal potential or the maximum whole-cell conductance. Measurement of Ca current activation and deactivation time constants suggests that (-) BAY K 8644 prolongs the single-channel open time without affecting the closed time. From the shift of the open time function to more negative voltages by about 50 mV the energy transferred to the gating process is calculated to be 5.4 kJ/mol (1.3 kcal/mol). The drug-induced slow component of tail current has been used to estimate the true dose/response relation for (-) BAY K 8644. A KD value of 4.3 nM and a Hill coefficient of 1.25 were determined. Flash-induced competition experiments with the Ca antagonist nifedipine allowed the measurement of binding kinetics of (-) BAY K 8644. The association rate constant is estimated to about 5 x 10(6) mol-1.s-1 and dissociation time constant is approximately 50-70 s; both are in close agreement with receptor binding studies. Results are discussed in relation to models for drug action of dihydropyridine-type compounds and to implications for the structure of the Ca channel protein.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

On-line immunoanalysis for bioprocess control.

Immunoanalytical techniques such as ELISA are often used for the detection of proteins produced in cultivation processes. Owing to the difficulty of automating of the time-consuming traditional ELISA, there is an intense demand for a suitable on-line monitoring method. Combining well-known immunoassays with the FIA technique, we present the heterogeneous and the turbidimetric immuno-FIA methods. The following proteins were investigated with these FIA methods: thermostable pullulanase, IgG, antithrombin III, and recombinant tissue-type plasminogen activator. In the cases of pullulanase and monoclonal mouse IgG, the turbidimetric immuno-FIA was used for on-line analysis of the cultivation process. Results are presented here to demonstrate the effectiveness and application of these immunoanalysis.

Antithrombin III↗

[Low-dose midazolam reduces the alfentanil demand in elderly but not in young patients during extracorporeal shock wave lithotripsy].

To evaluate whether midazolam has analgesic properties in humans after intravenous injection we studied the influence of a subhypnotic dose of midazolam (50 micrograms/kg) on the cumulative alfentanil consumption in 53 patients during extracorporeal shock wave lithotripsy (ESWL) using a patient-controlled analgesia system (PCAS). In a randomised double blind fashion all patients received either midazolam or an equal volume of saline (placebo) prior to ESWL. Heart rate and arterial blood pressure were measured before and during ESWL. Alfentanil consumption was assessed 20 minutes after injection of midazolam or placebo, respectively. All patients received oxygen via face mask. In patients older than 60 years (median: 70 years, range: 61-88 years) pretreatment with midazolam resulted in a significantly lower cumulative alfentanil consumption (0.41 vs 0.97 mg; p = 0.027) compared with patients younger than 60 years after midazolam pretreatment (0.84 vs 0.71 mg; p = 0.27). Mean arterial pressure also was significantly lower in the former compared with the latter group, while heart rate remained unchanged. In contrast, in patients younger than 60 years (median: 47 years, range: 24-56 years) no significant differences were observed between the midazolam and the placebo group. Thus, low dose intravenous midazolam pretreatment led to a significant decrease of alfentanil consumption in patients beyond 60 years of age. We conclude that subhypnotic doses of midazolam are capable of reducing alfentanil demand in elderly but not in younger patients during ESWL.

Adult↗

The round table in a community-based outpatient service.

The community-based outpatient service of Berne has used the round table for 8 years. It has become a strong element of the care of long-term outpatients. The aim of the present study is to examine how the round table is used and estimated by the patients: whether it only fulfils the function of a psychosocial contact facility to reduce social isolation or whether it has other helpful functions of social relationship. Further, we were interested to find out which of the therapeutic factors in group therapy are of importance. Four major factors could be elaborated by factor analysis: the functions and the importance of the caretakers at the round table, the acceptance and social integration of the patients and psychotherapeutic factors such as self-disclosure and vicarious learning. The round table is not only a social contact facility but also a new form of an informal, open, socio-therapeutic group.

Adult↗

Young adult chronic patients: empirical results on subgroups and age.

The discussion about young adult chronic patients (YACPs) started in the literature in the early eighties. However, the insufficient operationalization of the YACP concept provoked some criticism. The aim of the present study was to examine whether there were operational differences between YACPs and older chronic patients, as well as between hypothesized subgroups. The results show, as expected, that the differences between YACPs and older patients correlate with age. But only the 'high-energy, high-demand' subgroup differs not only from the other YACPs but also from the older chronic patients concerning psychopathology, social functioning and their interaction with the social environment. After 35 they grow out of their typical behavior which is strongly determined by traits of borderline and antisocial personality disorder. The stigmatizing YACP label should therefore be replaced by a more precise description such as 'young long-term patients with borderline or antisocial personality traits'.

Adolescent↗

[Extended resections in bronchial cancer: complications and late results].

From 1982 through April 1992, 192 patients underwent extended resection for non-small cell carcinoma of the lung (NSCLC) invading the chest wall (n = 52) or the mediastinum (n = 140). Complete resection of the tumor was possible in 81 (58%) patients with invasion of mediastinum and in 34 (65%) patients with invasion of the chest wall. The operative mortality was 9%, respiratory complications causing most of the postoperative morbidity and mortality. Incomplete resection was associated with poor prognosis. The mean survival of these patients was 10 month. The 5 year actuarial survival rate of patients having curative resection was 20%. In these patients the presence of lymphatic metastases significantly reduced survival, with a 3 year actuarial survival rate of 40% of patients with No disease, and 30% or 5% for those with N1 or N2 disease, respectively. In conclusion, extended resection for advanced NSCLC offers a significant chance for long-term survival in the absence of N2 lymphatic metastases. In the presence of N2 metastases and poor overall prognosis however, reasonable palliation is the primary goal of surgical management.

Carcinoma, Bronchogenic↗

[Expandable metal mesh stents for treatment of tracheal stenoses and tracheomalacia].

The treatment of tracheo-bronchial stenosis or tracheomalacia is mainly carried out by means of resection or tracheoplastic operative strategies. Since the introduction of metal-mesh stents, a definitive endoluminal therapy has to be considered under new aspects. Six patients with malignant stenosis or tracheomalacia due to compression were treated by implantation of Palmaz- or Wallstents. Immediately after the implantation, patients were relieved from dyspnoea, the forced inspiratory volume-1 (FIV1) was normalized. All implanted stents were well tolerated, even in the long-time follow-up (19 months). Bronchoscopic control showed overgrowth of the metal meshes by respiratory epithelium. The implantation of metal-mesh stents is an adequate alternative in the treatment of malignant stenosis and tracheomalacia.

Aged↗

[Young chronic psychiatric patients. A new focus in research and practice].

This paper tries to show how stimulating the mutual effects of modeling, providing a network of psychiatric facilities and research can be in the care of young adult chronic patients. However, they do not behave all the same and require various strategies in therapy. Under the influence of a new model of Sheets et al. (1982), the young adult chronic patients are classified into three subgroups: the "High-Functioning, High-Aspiration"-, "Low-Energy, Low-Demand"- and the "High-Energy, High-Demand"-group. With the example of the situation in Berne it can be shown that each group needs different facilities. The own research allows conclusions about the efficacy of the therapeutic offers. On the other hand, it stresses the point that especially the group of "High-Energy, High-Demand"-patients are a major challenge for us in psychiatry. Finally some reflections are presented how we professionals can deal with these patients in future to do more justice to them.

Activities of Daily Living↗

[Young chronic patients: how can we better manage the most difficult cases among them? A review of the literature].

The term "Young Adult Chronic Patients" (YACPs) was first used in the early eighties in the American literature. It describes a new generation of young mentally ill persons who become chronic, no longer in the clinic but in the community. They are characterized less by a common psychopathology than by their social deficits and their behaviour, which frustrates caregivers and makes them feel helpless. Possible causes of the YACP phenomenon and shortcomings of the care provided for them are discussed. The authors consider that a flexible, individually tailored and comprehensive multi-program system of services including case-management is needed to treat the YACPs better in future. Finally, advantages and problems of the YACP concept are discussed.

Adult↗

Sensitive detection of the activation state of blood coagulation in porcine DIC models by a new fibrin immunoassay.

Elevated levels of soluble fibrin in plasma indicate that thrombin converts fibrinogen to fibrin without sufficient inhibitory control. Therefore, measurement of soluble fibrin (SF) in plasma may be considered as a laboratory test for intravascular coagulation. We have demonstrated that a new immunoassay for detection of SF in human plasma (Lill et al., Blood Coag Fibrinol 1993; 4: 97-102), based on a fibrin specific monoclonal antibody, also detects porcine SF with high sensitivity. Thrombin-dependent generation of SF in porcine plasma in vitro resulted in increased reactivity of the assay system, which was time and dose dependent. Dextran sulphate (DXS) and bacterial lipopolysaccharide (LPS) were used as stimuli in in vivo experiments in pigs. Plasma levels of SF increased steadily after intravenous administration of DXS (5 mg/kg for 1 h) to 38 +/- 7.8 micrograms/ml (mean +/- SEM) at 2 h, whereas LPS (2 micrograms/kg/h for 6 h) markedly increased plasma SF levels to over 120 micrograms/ml (at 6 h) after a lag phase of 2 h. In conclusion, this new immunoassay for human fibrin allows specific and sensitive detection of soluble fibrin in porcine plasma.

Animals↗

Ecological vocational rehabilitation.

Chronicity in serious mental disorders emanates from deficient ecological resources interacting with vulnerable individuals. Rehabilitation can succeed if an integrated and individualized approach is augmented by appropriate ecological supports.

Adaptation, Psychological↗

Long-term experience with transurethral rigid ureteroscopy as a complementary method to extracorporeal shockwave lithotripsy.

Between May 1985 and September 1990, 291 ureteroscopies were performed either for primary or secondary stone therapy or for diagnostic purposes. Rigid ureteroscopes (12.5 or 9.5 French) were used without dilation of the ureteral orifice. 83% of the stones could be removed either by direct extraction or electrohydraulic or ultrasound lithotripsy. The highest failure rates (25.6%) occurred in stones located in the upper ureter, the lowest failure rate (9.6%) resulted from treatment of lower ureteral stones. 3.4% complications were observed such as perforation, leakage, stenosis and septicemia. After an average follow-up of 4.5 months, 1 in 70 patients revealed an ureteropelvic stricture which was treated with open surgery. The ureterorenoscopy represents an effective and low-risk primary and secondary method for treatment of ureteral stones in stone centers using extracorporeal lithotriptors which are exclusively equipped with ultrasound detection devices.

Combined Modality Therapy↗

Chronic psychoses and rehabilitation: an ecological perspective.

Traditional explanatory models, based on core psychological deficits, vulnerability-stress models or distinctions between negative and positive symptoms, may not be sufficient to understand the phenomenon of chronicity. This linear thinking, looking for monocausal explanations, should be replaced by exploring multicausal and circular processes over time, including the individual ecological context of a given patient. Thus, chronicity appears to result much more from endless loops and irreversible bifurcations in its dynamics over time than to be a stable state. Furthermore, the current views on psychopathology and prognosis need to be fundamentally reexamined in the light of this new way of thinking. For understanding and treatment of chronic psychoses, this ecological perspective implies programs which do not focus only on the patient, but look for 'ecological niches' and interventions favoring synergetics and self-organization within the social networks and at the worksite of a given patient. A recently implemented five-step program for vocational rehabilitation and the corresponding research plan will be presented and discussed.

Chronic Disease↗

Effects of protease inhibitors in experimental septic shock.

Endotoxin shock and contact system activation were used to study effects of hirudin, antithrombin III, eglin C, aprotinin, and [Arg15]-aprotinin in anesthetized pigs. Alterations in the systemic and pulmonary circulation were in part prevented by administration of the inhibitors.

Animals↗

Effect of the elastase inhibitor eglin C in porcine endotoxin shock.

We wanted to demonstrate that the neutrophil elastase inhibitor eglin C reduces the loss of intravascular protein in endotoxin (LPS) shock and that effective concentrations are present in lymph. We used 45 anesthetized miniature pigs in a randomized, controlled trial. LPS 10 micrograms/kg/hr was given for 6 hr. Recombinant eglin C was given before LPS (250 nmol/kg) and continuously at 250 nmol/kg/hr (n = 18); septic controls received saline (n = 18); nine nonseptic controls were used. Eglin C significantly reduced the loss of intravascular protein (plasma volume times plasma protein concentration) from -0.79 g/kg in septic controls to 0.42 g/kg in eglin C-treated animals and reduced plasma concentration of neutrophil elastase, bound to the leukocyte neutral protease inhibitor (LNPI), but systemic hypotension was unchanged. Six additional pigs were anesthetized, prepared with a thoracic lymph fistula, and received eglin C at 475 nmol/kg/hr; three received saline; three received LPS. Eglin C concentrations in lymph were comparable to those in plasma. We conclude that eglin C reduced the loss of intravascular protein during LPS shock and attained effective concentrations in lymph.

Animals↗