A review of the psychopharmacology of panic disorder: individual differences and non specific factors

This paper critically examines the pharmacological provocation and treatment of panic disorder. An analysis of research findings on how panic attacks are induced indicates that there are psychological and non specific factors that may mediate biochemical etiological models, and these individual differences need to be investigated further. This has important implications for the psychopharmacological management of panic. A review of studies on treating panic disorder with imipramine and alprazolam emphasizes the importance of several non specific factors that include the role of self-directed in vivo exposure and changes in dysphoria and self-efficacy (subjective beliefs regarding personal competency) in predicting outcome. It is recommended that any treatment of panic-related disorders include self-directed, in vivo exposure.     

Candidate genetic risk factors of stroke: results of a multilocus genotyping assay

BACKGROUND: Epidemiological studies indicate that genetic factors play a role in the risk of stroke, particularly in younger individuals, but the role of single-nucleotide polymorphisms (SNPs) is controversial. We tested the possible association of a number of previously described SNPs with stroke risk. METHODS: We investigated the prevalence of 60 polymorphisms located in 35 genes in 450 white patients who suffered an acute stroke or transient ischemic attack before the age of 60 years and in 817 healthy control individuals by a multilocus PCR-based assay. The controls were randomly selected from attendees of a health service program. Genetic variations were detected by hybridization to nylon strips (Roche Molecular Systems) containing detection oligonucleotides for the SNPs. We used P values of <0.05 for confirmatory analysis of the SNPs in the genes for APOE (allele 4), angiotensin converting enzyme, factor V, prothrombin, and methylenetetrahydrofolate reductase. To account for multiple testing we defined a P value of <0.001 as statistically significant for all exploratory tests. The genes represented in the test panel by more than 1 SNP were also evaluated by haplotype analysis. RESULTS: Frequencies of all 60 tested SNPs among patients and controls were very similar. No SNP reached an odds ratio of 2, and no association with stroke risk was statistically significant. CONCLUSIONS: Our results do not indicate a clinically relevant role of any of the investigated SNPs for stroke risk in individuals hospitalized for ischemic stroke/transient ischemic attack before or at 60 years of age. These results are in accordance with previous metaanalyses showing at most a very modest or no significant effect of these SNPs on stroke risk.     

Elevated tryptase levels selectively cluster in myeloid neoplasms: a novel diagnostic approach and screen marker in clinical haematology

Background  Recent data suggest that tryptase, a mast cell enzyme, is expressed in neoplastic cells in myeloid leukaemias. In several of these patients, increased serum tryptase levels are detectable.
Materials and methods  We have determined serum tryptase levels in 914 patients with haematological malignancies, including myeloproliferative disorders ( n  = 156), myelodysplastic syndromes (MDS, n  = 241), acute myeloid leukaemia (AML, n  = 317), systemic mastocytosis (SM, n  = 81), non-Hodgkin's lymphoma ( n  = 59) and acute lymphoblastic leukaemia ( n  = 26). Moreover, tryptase was measured in 136 patients with non-neoplastic haematological disorders, 102 with non-haematological disorders and 164 healthy subjects.
Results  In healthy subjects, the median serum tryptase was 5·2 ng mL⁻¹. Elevated serum tryptase levels were found to cluster in myeloid neoplasm, whereas almost all patients with lymphoid neoplasms exhibited normal tryptase. Among myeloid neoplasms, elevated tryptase levels (> 15 ng mL⁻¹) were recorded in > 90% of patients with SM, 38% with AML, 34% with CML and 25% with MDS. The highest tryptase levels, often > 1000 ng mL⁻¹, were found in advanced SM and core-binding-factor leukaemias. In most patients with non-neoplastic haematological disorders and non-haematological disorders analysed in our study, tryptase levels were normal, the exception being a few patients with end-stage kidney disease and helminth infections, in whom a slightly elevated tryptase was found.
Conclusions  In summary, tryptase is a new diagnostic marker of myeloid neoplasms and a useful test in clinical haematology.     

Effect of general anesthesia on fertilization and cleavage of human oocytes in vitro

To determine whether anesthesia affects in vitro fertilization (IVF), the authors examined 3 1/2 years' experience with IVF. Anesthesia length significantly predicted fertilization and cleavage at stage 0 of stepwise multiple logistic regression analysis, but not at the final step. Oocyte grade, retrieval order, and a quadratic term for grade remained significant for fertilization; cleavage, order, the interaction of order and grade, and the quadratic term for grade remained significant. Order correlated with anesthesia (r = 0.675, P less than 0.001). Also inherent in order are CO2 pneumoperitoneum, increased prolactin, decreased gonadotropins, ovarian trauma, and time. First oocytes of equivalent grade from contralateral ovaries were compared. Fertilization rates were equivalent, but significantly fewer mature oocytes from the second ovary cleaved. Anesthetic agents and CO2 appear to adversely affect fertilization and cleavage in vitro.     

Interleukin-1 receptor antagonist genotype is associated with coronary atherosclerosis in patients with type 2 diabetes

Recently, inflammation has received considerable attention in the pathogenesis of both type 2 diabetes and atherosclerosis. The interleukin-1 receptor antagonist (IL-1ra) is a major modulator of the interleukin-1 pro-inflammatory pathway. We studied the relationship between a variable number tandem repeat (VNTR) polymorphism in intron 2 of the IL-1ra gene (IL1RN) and coronary artery disease (CAD) in patients with and without type 2 diabetes, following 787 consecutive patients admitted for suspected CAD. According to the current criteria of the American Diabetes Association, 250 patients had type 2 diabetes. In this group of patients, allele 2 carriers (n = 108) had an increased prevalence of CAD compared with noncarriers (85.2 vs. 73.2%), a difference that remained significant in a multivariate logistic regression model (odds ratio 2.2, 95% CI 1.1-4.3, P = 0.02). No association of CAD with allele 2 carrier status was present among nondiabetic patients (n = 537). Enzyme-linked immunosorbent assays showed decreased baseline plasma levels of IL-1ra in patients with type 2 diabetes, which may in part explain the role of the IL1RN VNTR in these patients.     

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Treatment of coxa magna in Perthes disease by pelvic osteotomy (author's transl)

In M. Perthes a progressive deformation and flattening of the epiphysis is caused by the stress in the hip. In the beginning stages a varisation osteotomie gives a sufficient reduction of the joint pressure and a modelling of the enlarged head by the acetabulum is possible. In later stages a detoriation of the head deformity with fixed adduction contracture can be caused by varisation osteotomie. Enlarging the acetabulum laterally and ventrally and medializing the hip-joint by means of a Chiari pelvic-osteotomy reduces the joint pressure so far, that a restitution of the hip joint with round and congruent joint surfaces can be expected. A lateralisation of the deformed femoral head with a secondary insufficiency of the acetabulum should also be treated by an additional pelvic osteotomy, if in the arthrography the lateral part of the head does not enter the acetabulum in abduction position. In secondary osteochondritis in hip luxation the treatment should be equal. Even an advanced secondary osteoarthritis after M. Perthes could be stopped by pelvic osteotomy over years.     

Loss of normal circadian profile of urine excretion in idiopathic restless legs syndrome

BACKGROUND: This study was performed to elucidate preliminary observations of excessive nighttime urine excretion in idiopathic restless legs syndrome (iRLS). METHODS: Seventeen patients, with normal serum creatinine, blood urea nitrogen, and urate, and 11 healthy controls were examined. We measured excretory renal function parameters (urine volume, osmolarity, sodium, chloride, potassium, calcium, phosphate, microalbumin, aldosterone, creatinine) between 7:00 am and 10:00 pm and between 10:00 pm and 7:00 am. RESULTS: During the nighttime, volume (P=0.006), sodium (P=0.009), and chloride excretion (P=0.001) were significantly higher, and osmolarity (P=0.025) was significantly lower in patients as compared to controls. In comparing daytime to nighttime, controls showed the physiological reduced nocturnal excretion of volume (P=0.009) and chloride (P=0.023), and an increased osmolarity (P=0.026), but patients showed similar excretion rates of these parameters (all differences ns). CONCLUSIONS: These data indicate a loss of normal circadian profile of urine excretion in iRLS. The elevated nighttime excretion, with values similar to those in the daytime, hint at a possibly elevated fluid, sodium, and chloride intake during daytime.