Serotonin 5-HT2C receptor-mediated phosphoinositide hydrolysis in rat choroid plexus after fluoxetine and citalopram treatments.

Selective serotonin reuptake inhibitors (SSRIs) bind directly to various neurotransmitter receptors. The clinical effects of SSRIs appear gradually during weeks of treatment, suggesting a role for adaptive changes in neurotransmitter receptors. Most clinically used antidepressants, e.g. fluoxetine, bind to 5-HT2C receptors. When administered chronically, many antidepressants elicit adaptive regulation of 5-HT2C receptors. The present study was conducted in order to determine the effects of acute and chronic fluoxetine and citalopram treatments on the density and function of 5-HT2C receptors in the rat choroid plexus. Acute and chronic treatments followed by phosphoinositide (PI) hydrolysis assays and quantitative receptor autoradiography were performed. Acute (single-dose) treatment with neither drug significantly affected basal or 5-HT-stimulated PI hydrolysis, but acute citalopram (20 mg/kg) treatment increased both agonist and antagonist binding to 5-HT(2C) receptors. Chronic (14 days) citalopram treatment (20 mg/kg) increased the maximal PI hydrolysis response by 40%, but fluoxetine lacked this effect. The present data suggest that sensitisation of 5-HT2C receptor-mediated intracellular signal transduction may play a role in the effects of citalopram. In contrast, fluoxetine treatment does not functionally sensitise 5-HT2C receptors. Thus, functional 5-HT2C receptor sensitisation is not a common effect of antidepressants, but the differential effects may explain some of the pharmacodynamic differences seen with these drugs, especially upon repeated administration.     

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.     

The role of dendritic cells during infection

The skin and the mucosa of the respiratory and gastrointestinal tracts are continuously exposed to microorganisms, but only a limited number of these enter the body and cause disease. To resist microbial infection, the host has developed a multitude of defense mechanisms involving the innate and adaptive immune systems. Dendritic cells (DCs) provide the link between these arms of the immune system. The initiation of an immune response is critically dependent on the activation of DCs, which can discriminate between different classes of microorganisms and elicit tailored antimicrobial immune responses. They have an extraordinary capacity to stimulate naive T cells and initiate primary immune responses. In turn, some pathogens interfere with DC function to block or delay their elimination by the host. Progress in understanding the role of DCs in the host response to microbes is reviewed.     

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     

Cardiac rehabilitation and return to work after coronary artery bypass surgery

The work situation of 66 male patients who underwent elective coronary artery bypass surgery (CABS) and who had been randomly allocated to receive cardiac rehabilitation (group R) was compared with the work situation of 59 similar patients allocated to receive only standard care (group H). The follow-up time was one year. The proportions of subjects working in groups R and H were 26% and 20% (p=ns) before the CABS, 45% and 34% (p=ns) 6 months and 56% and 38% (p=ns) 12 months after the CABS, repectively. The increase in proportion of subjects who worked was significant in both groups at both 6 and 12 months after the CABS (p<0.05 for all changes). The increases were not significantly different between the whole groups, but in patients younger than 55 years of age, return to work was more frequent in group R than in group H (at 12 months 60% vs. 35%, p for the difference in change=0.02). Stepwise logistic regression analysis of the factors influencing return to work showed that a patient's judgement of his own working capacity as good 6 months after CABS (odds ratio (OR) 8.5, confidence interval (CI) 2.3–32.0), functional class 16 months after the CABS (OR 6.7, CI 1.8–24.5), his desire to work (OR 6.4, CI 1.6–26.0) and absence from work of less than 3 months before the CABS (OR 4.9, CI 1.2–20.2) were significant positive predictors of return to work 1 year after the CABS.     

Enchondroma of the hand – clinical evaluation of diagnosis, surgical treatment, and outcome

Summary Enchondroma are benign cartilaginous tumors and are localized most often at the site of the phalanges. Between 1982 and 1993 73 patients with monostotic enchondroma and 5 patients with polyostotic enchondroma were operated at our clinic. Clinical signs of monostotic tumors were pathological fracture (38.4 %), pain or swelling. Eleven percent of cases were accidental findings. Surgical treatment was performed by complete removal of the tumors and filling the bone cavity with autologous spongiosa taken from the pelvic bones, the elbow, or the radius. Three patients (4.1 %) had to be operated a second time due to wound infections and hematoma. In one case Sudeck's dystrophy was diagnosed. One patient (1.4 %) developed a recurrent tumor. Our follow-up examination of 65 patients showed that 77 % of the patients with monostotic enchondroma achieve very good or good functional long-term results after this operation, but only 40 % of the patients with polyostotic enchondroma.