Differential effects of inhibitors of monoamine oxidase Types A and B on the adrenergic system of the rabbit iris.

Topical instillation of inhibitors of monoamine oxidase Types A and B into the rabbit eye, followed by the administration of a releaser of monoamines (Ro 4-1284), induces strong and sustained dilation of the iris. The mydriatic pattern differs markedly with A- and B-inhibitors and with the duration of the inhibitor treatment. The Type B inhibitor, deprenyl, prevents the degradation of exogenous 2-phenylethylamine and possibly of the endogenous amine X capable of releasing monoamines from a compartment less accessible to Ro-1284.     

Chemotherapy of autochthonous leukemias induced by 7,12-dimethylbenz(a)anthracene in long evans rats

Summary A total of 111 autochthonous (primary) acute rat leukemias of the diffuse-hepatic type which had been induced by 7,12-dimethylbenz(a)anthracene were treated with mono- and combination chemotherapy. The survival time of treated rats increased significantly compared to untreated controls. A combination of vincristine (VCR), adriamycin (ADR), and cytosine arabinoside (Ara-C) was superior to a combination of VCR and ADR as well as to a monotherapy with Cyclophosphamide, BCNU, VCR, ADR, and Ara-C.     

Influence of ischemia on heart-rate variability in chronic hemodialysis patients

BACKGROUND: Sudden cardiac death occurring in patients with end-stage renal disease (ESRD) may be related to poor autonomic function with a significant decreased heart-rate variability (HRV). In addition, coronary artery disease has a high prevalence in this population and accounts for 50% of deaths. In the present study, relationships between HRV and myocardial ischemic abnormalities revealed by myocardial scintigraphy (MS) were evaluated in 32 chronic hemodialysis patients. METHODS: We prospectively studied 32 chronic hemodialysis patients. Each underwent MS and 24 h electrocardiography at baseline for analysis of time and frequency domain the day of dialysis. Three periods were analyzed: during dialysis session, the morning after (nondialytic period), and in a 24 h period. Patients were included in group 1 (seven women, 11 men; mean age: 62+/-19 years) when MS revealed no ischemia, whereas patients were included in group 2 (seven women, seven men; mean age: 63.1+/-20 years) when MS revealed ischemic lesions. RESULTS: A student+/-test revealed that during the nondialytic period, two important markers of HRV, percentage of delta RR>50 ms (pNN50) (4.5+/-4.04 in group 1 versus 1.7+/-1.4 in group 2), and root mean square of delta RR (rMSSD) (27.7+/-13.4 versus 19.7+/-6.8) were significantly reduced in group 2 compared with values in group 1. No significant difference appears between the two groups for standard deviation of normal to normal intervals (SDNN), mean heart rate, and spectral analysis. CONCLUSION: Patients with ESRD and myocardial ischemia revealed by MS have reduced parasympathetic activity during the nondialytic period. Correlations between parameters of HRV and ischemic lesions revealed by MS have been shown for the first time.     

Chemotherapy of meningeal leukemia in rats (L5222)

An experimental model of meningeal leukemia in syngenic BDIX rats was developed by intracerebral inoculation of leukemic cells from the transplantable acute leukemia L5222. Using the bioassay technic, the proliferation of the L5222 in the central nervous system and in the body was studied. According to the number of leukemic cells in the meninges and brain, an early, advanced, and preterminal stage of meningeal leukemia can be distinguished. Chemotherapeutic studies with BCNU and cyclophosphamide yielded cures in a high percentage of cases when treatment began at an early stage of meningeal leukemia. In advanced and preterminal stages, only BCNU showed a large number of cures. This model for meningeal leukemia was used as a screening system for new nitrosoureas. Preliminary results on chemotherapeutic activity showed a marked superiority of the water-soluble 1-(2-hydroxyethyl)-3-(2-chloroethyl)-3-nitrosourea in comparison to BCNU.     

Childhood idiopathic thrombocytopenic purpura in the Nordic countries: epidemiology and predictors of chronic disease

AIM: To describe the epidemiology of idiopathic thrombocytopenic purpura (ITP) in the Nordic countries, to define clinical subgroups and to investigate factors predicting chronic disease. METHODS: A prospective registration was done from 1998 to 2000, including all children with newly diagnosed ITP aged 0-14 y and at least one platelet count <30 x 10(9)/l. RESULTS: 506 children were registered and 423 followed for 6 mo. The incidence was 4.8/10(5) per year. Most children were aged 0-7 y (78%), with a predominance of boys, while patients aged 8-14 y had equal representation of the two sexes. There were seasonal variations determined by variations in postinfectious cases with sudden onset. The platelet count was <10 x 10(9)/l in 58%, but bleeding manifestations were mild or moderate in 97%. The insidious form (symptoms for more than 2 wk) was more frequent in older children and girls, showed little seasonal variation, had milder manifestations and ran a chronic course in more than half the cases. Intracranial haemorrhages did not occur in the first 6 mo after diagnosis. Chronic ITP developed in 25%. The strongest predictor of chronic disease was insidious onset of symptoms (OR 5.97). CONCLUSION: In the Nordic countries, ITP mainly affects children aged 0-7 y, with a winter bulk of postinfectious cases superimposed on a steady occurrence of non-infectious cases. Clinically, it may be useful to distinguish between children with sudden versus insidious onset of symptoms rather than between different age groups.     

Comparison of clinical characteristics of influenza and respiratory syncytial virus infection in hospitalised children and adolescents

While significant morbidity due to respiratory syncytial virus (RSV) infection in the paediatric population has been well acknowledged, little is known about the burden of influenza in primarily healthy children in Europe. In our institution, a University Childrens Hospital in Switzerland, medical staff were encouraged to take nasopharyngeal specimens for multiplex polymerase chain reaction assays for influenza A and B, RSV and several other pathogens from patients hospitalised with respiratory symptoms. We took advantage of this strategy and performed a retrospective study to compare specific characteristics of influenza virus infections with those of RSV during two consecutive winter seasons. Overall, 126 patients were positive for RSV and 60 patients were positive for influenza (type A: 45; type B: 15). The median age of children with RSV, influenza A, and influenza B infection was 4 months; 2 years and 4 months; and 6 years and 2 months, respectively (P<0.001). Fever and cough predominated in children with influenza infection whereas cough, rhinorrhoea, feeding difficulties and dyspnoea were the major symptoms in children with RSV infection. Of patients with influenza, 41% suffered from lower respiratory tract infection compared to 91% of those with RSV infection (P<0.001). Of 60 patients hospitalised with influenza, 12 (20%) experienced febrile convulsions. None of the patients with influenza had been immunised in the respective winter season, although 27% of them had at least one underlying medical condition that would have counted as an indication for immunisation in Switzerland. Conclusion: influenza virus infections, like respiratory syncytial virus infections, are a major cause of hospitalisation in children with respiratory illness during the winter season. Since it is impossible to make an aetiological diagnosis on clinical grounds, it is important to apply specific diagnostic tools in children hospitalised with respiratory illness in order to better characterise the relative burden of disease caused by the respective agents.Abbreviations LRTI lower respiratory tract infection - NPS nasopharyngeal specimens - RAT rapid antigen test - RSV respiratory syncytial virusThis work forms the medical thesis of Susanne Meury at the Medical Faculty, University of Basel, Switzerland.     

Anxiolytic-like effects of the corticotropin-releasing factor1 (CRF1) antagonist DMP904 [4-(3-pentylamino)-2,7-dimethyl-8-(2-methyl-4-methoxyphenyl)-pyrazolo-[1,5-a]-pyrimidine] administered acutely or chronically at doses occupying central CRF1 receptors in rats

Corticotropin-releasing factor(1) (CRF(1)) antagonists may be effective in the treatment of anxiety disorders with fewer side effects compared with classic benzodiazepines. The behavioral effects of DMP904 [4-(3-pentylamino)-2,7-dimethyl-8-(2-methyl-4-methoxyphenyl)-pyrazolo-[1,5-a]-pyrimidine] and its effects on the hypothalamic-pituitary-adrenal (HPA) axis were related to its levels in plasma and estimated occupancy of central CRF(1) receptors. DMP904 (10-30 mg/kg, p.o.) and alprazolam (10 mg/kg, p.o.) increased time spent in open arms of an elevated-plus maze. In addition, acutely or chronically (14 days) administered DMP904 (1.0-30 mg/kg, p.o.) and acute alprazolam (1.0-3.0 mg/kg, p.o.) significantly reduced exit latency in the defensive withdrawal model of anxiety in rats, suggesting that tolerance may not develop to the anxiolytic-like effects of DMP904 in this model of anxiety. Acutely, DMP904 reversed the stress-induced increase in plasma corticosterone levels in defensive withdrawal at doses of 3.0 mg/kg and higher. These doses also resulted in levels of DMP904 in plasma similar to (for anxiolytic-like effects) or 4-fold higher (for effects on the HPA axis) than the in vitro IC(50) value for binding affinity at CRF(1) receptors and greater than 50% occupancy of CRF(1) receptors. Unlike alprazolam, DMP904 did not produce sedation, ataxia, or chlordiazepoxide-like subjective effects (as measured by locomotor activity, rotorod performance, and chlordiazepoxide discrimination assays, respectively) at doses at least 3-fold higher than anxiolytic-like doses. In conclusion, anxiolytic-like effects and effects on the stress-activated HPA axis of DMP904 in the defensive withdrawal model of anxiety required 50% or greater occupancy of central CRF(1) receptors. This level of CRF(1) receptor occupancy resulted in fewer motoric side effects compared with classic benzodiazepines.     

Platelet–leukocyte interaction and platelet activation in migraine: a link to ischemic stroke?

OBJECTIVES: Migraine has been identified as an independent risk factor for ischemic stroke. Both neurogenic inflammation and platelet activation have been linked to the pathophysiology of migraine. Increased platelet activation results in up-regulation of specific binding to leukocytes which promotes pro-inflammatory leukocyte secretion and their tethering to endothelium, a mechanism that has been demonstrated in stroke and which could provide a link to migraine. We aimed to determine whether platelet-leukocyte aggregation is increased in migraine patients outside an acute attack. METHODS: Seventy two patients with migraine according to IHS criteria were compared to a control group (n = 72). Whole blood flow cytometry was used to quantify the activation dependent P selectin on the platelet, and to assess the fraction of platelets bound to the different leukocyte subsets. RESULTS: Migraine patients showed significantly more platelet-leukocyte aggregates compared to the control subjects (p = 0.003). This effect was driven by an increased polymorphonuclear cell-platelet aggregation (p = 0.003) whereas platelet aggregation with monocytes and lymphocytes was not. Platelet activation was also increased (p = 0.001). CONCLUSIONS: In migraine pro-inflammatory platelet adhesion to leukocytes occurs during the headache free interval similar to that seen in acute coronary and cerebrovascular syndromes. This may suggest a link between migraine and stroke on a cellular level.