Coping strategies and individual meanings of illness.

Every person has a subjective understanding of their own illness. The personal attitude towards disease and the corresponding coping mechanisms go beyond biomedical factors to influence the course of the disease. Lipowski described eight different disease concepts which were supplemented by the theory of control conviction (external-internal control). Several hypotheses about disease concepts, coping strategies and psychopathology were globally confirmed in a study of 205 chronic patients: Ability to control and acceptance lead to a more active and problem-related coping, whereas emotional coping modi occur more often in persons who do not accept their illness or do not consider it to be controllable. Results confirm the necessity of a differentiated analysis.     

Detection of the Arg702Trp, Gly908Arg and Leu1007fsinsC polymorphisms of the NOD2/CARD15 gene by real-time PCR with melting curve analysis.

Crohn's disease is a complex disorder, with multiple genetic traits. A frameshift mutation (Leu1007fsinsC) and two missense mutations (Gly908Arg and Arg702Trp) in the NOD2/CARD15 gene are strongly associated with susceptibility to Crohn's disease. The presence of one of these risk alleles confers a 2- to 4-fold increase in the risk of developing Crohn's disease, and the presence of two mutant alleles increases the risk over 20-fold. To facilitate the analysis of these polymorphisms, we developed three LightCycler assays to detect the missense mutations Arg702Trp and Gly908Arg and the frameshift mutation Leu100fsinsC in the NOD2/ CARD15 gene. All three assays can be run simultaneously on one LightCycler using identical cycling parameters. Analysis of 53 DNAs from Crohn's patients helped to identify carriers at allele frequencies similar to other Caucasian populations. The sequencing of such DNAs confirmed the accuracy of the assays. In conclusion, we present three rapid and robust assays to detect the Arg702Trp, the Gly908Arg and the Leu1007fsinsC ins mutations in the NOD2/CARD15 gene [corrected]     

Amitriptyline pharmacokinetics and clinical response: II. Metabolic polymorphism assessed by hydroxylation of debrisoquine and mephenytoin

A subgroup of 16 out of 30 endogenous depressive inpatients (cf. part I), treated for 3 weeks with 150 mg amitriptyline (AT) daily, participated in a pharmacogenetic study: all were phenotyped with debrisoquine and 3 of them with mephenytoin. Four patients were found to be poor metabolizers (PMs) of debrisoquine and one of mephenytoin. Plasma levels of AT + NT (nortriptyline) were highest in the PMs of debrisoquine, but the ratio of hydroxylated metabolites to the parent compounds appeared to be lower in these subjects. From these data, it is speculated that, in the PM of mephenytoin, the demethylation of AT is impaired. In 12 patients, free plasma 10-hydroxy-AT (ATOH) and 10-hydroxy-NT (NTOH) were found to be bound to a similar extent to plasma proteins, but not so firmly as their parent compounds, by a factor of 6 and 4 respectively. While mean total plasma ATOH reached only 15% of the value of AT, total plasma NTOH was as high as NT. ATOH correlated significantly with its parent compound, but NTOH did not correlate with NT. No drug plasma levels/clinical relationship was found in this small group of patients, even when the hydroxylated metabolites were taken into account. Both poor and extensive metabolizers of debrisoquine responded to treatment. The debrisoquine-test appears to be a useful clinical tool for detecting in patients a genetic deficiency in the hydroxylation of AT-type drugs.     

Isolation and interspecies-transfer of a plasmid from Pasteurella multocida encoding for streptomycin resistance

A plasmid encoding streptomycin-resistance could be detected in 13 of 32 Pasteurella multocida-cultures isolated from cattle and swine. The plasmid of these cultures proved to be similar upon Southern blot hybridization. It could be transformed into Escherichia coli 490A, where it also expressed streptomycin resistance.     

Development of glutamate neurotoxicity in cortical cultures: induction of vulnerability by insulin.

The effect of insulin on the development of excitotoxic vulnerability in primary cultures of the rat cerebral cortex was examined. Cells were maintained for two weeks in serum-supplemented culture media, in the presence or absence of increasing insulin concentrations. Excitotoxic cell death was induced by 1 mM glutamate. The vulnerability of cells was evaluated by phase contrast microscopy and by the measurement of lactate dehydrogenase (LDH) release due to cytotoxic injury. In addition to a moderate (less than 50%) stimulation of protein and DNA synthesis, insulin produced more than a twofold increase in the excitotoxic vulnerability of cells. The effect of insulin was specific, concentration-dependent and required an intact molecular structure of insulin. Our findings indicate that insulin induces significant changes in cerebral neurons by increasing the lethal vulnerability of cortical cells to excitatory amino acids (EAAs).     

Pressure stability of nasal CPAP and bilevel devices

Summary Question of the study   Nasal continuous positive airway pressure (CPAP) prevents collapse of the upper airway during sleep in patients with obstructive sleep apnea provided that a positive transmural pressure can be maintained during inspiration. We examined pressure-flow characteristics in seven CPAP and bilevel devices during spontaneous breathing.
Methods   The CPAP devices were set to a pressure level of 9.8  hPa (10  cm H₂O) and adapted to a pneumotachograph using a standard CPAP hose and an outlet valve. We continuously measured flow, volume and pressure during resting ventilation and increasing voluntary hyperventilation and analysed the dependence of the variables on a breath-to-breath basis.
Results   Mean CPAP pressures differed between the devices (9.9 – 10.6  hPa) despite the same settings. In all machines pressure fell during inspiration to 8.4 – 9.8  hPa and increased during expiration to 11.1 – 11.7  hPa. This effect increased with higher flow rates. Maximum expiratory pressures rose to 12 – 19  hPa at peak flow rates of 2 l/s, mean expiratory pressures to 9.5 – 16  hPa. Inspiratory pressures dropped to 8.5 – 4.5  hPa (minimum) and 10.5 – 6.0 (mean). Bilevel devices showed a higher stability than CPAP devices. Pressure swings during the respiratory cycle increased the additional work of breathing.
Conclusions   Due to differences in mean and effective CPAP levels CPAP devices are not simply exchangeable but should be individually adapted. Patients with higher minute ventilation might benefit from more stable CPAP machines. The impact on patients' compliance remains to be evaluated.     

Memory search for faces and digits in patients with unilateral brain lesions.

To clarify whether the impairment of right-brain-damaged (RBD) patients in face recognition is related to perceptual or mnestic processing stages, we tested unilaterally lesioned patients and controls in a Sternberg-type memory search task. Subjects had to memorize sets of 1, 2, or 3 faces (or, in a control condition, digits) and were then to recognize these memorized stimuli among new ones by speeded choice reactions. In this task, deficits in stimulus encoding and memory search should show up in increased intercepts and slopes, respectively, of the RT function over memory set size. A face-specific impairment of the RBD patient group, consisting in longer reaction times and higher error rates, was confirmed but could not be unequivocally attributed to either stimulus encoding or memory search. However, inspection of individual data suggested that (1) some RBD patients are virtually unimpaired in face recognition and (2) if impairment after right hemisphere damage is present, it may selectively affect either stimulus encoding or memory search.     

HLA-DR7 predicts the response to alkylating agents in steroid-sensitive nephrotic syndrome

There is a lack of reliable predictors of the response to alkylating agents in children with idiopathic nephrotic syndrome (NS). HLA-DR7 is strongly associated with the frequency of relapses in steroid-sensitive NS before cytostatic therapy. We therefore examined retrospectively the time to the first relapse and the incidence of subsequent relapses in 54 HLA-typed children with frequently relapsing NS, after treatment with cyclophosphamide (n = 49) or chlorambucil (n = 5) for 8 or 12 weeks; 38 patients were HLA-DR7 positive and 16 negative with 80% in both groups being steroid dependent. HLA typing was performed using serological or DNA typing methods. Renal biopsy showed minimal glomerular changes. A lower proportion of HLA-DR7 positive than negative patients remained in remission after 3 years (36% vs. 81%, P<0.02) and 5 years (36% vs. 72%, P<0.03). In the first 3 years after cytostatic therapy the mean number of prednisone-treated relapses was 1.3/patient per year in HLA-DR7-positive patients compared with 0.4 in negative patients (P<0.025). There was no statistically significant difference in the proportion of relapse-free patients with and without steroid dependency. The HLA status predicts the response of NS patients to alkylating agents better than the rate of previous relapses. Received September 19, 1995; received in revised form and accepted April 16, 1996