Plasma concentrations and bioavailability of propranolol by oral, rectal, and intravenous administration in man

Eight normal male volunteers received 80 mg doses of propranolol by the oral and rectal routes and 2.2 mg by intravenous administration in a crossover fashion. Plasma concentrations of propranolol were measured by a gas chromatographic method using an electron capture detector. Individual subject concentration-time data were analysed and results indicated that the data fit a two compartment model with first order absorption. An approximately two-fold higher plasma propranolol concentration was observed after rectal administration as compared with oral dosing. Statistical analysis of the difference in the total AUCs indicates a significantly higher bioavailability of propranolol administered by the rectal route. The reduced bioavailability after oral administration indicates a substantial first pass effect but that it is possible to bypass the liver, at least partially, by giving the drug rectally to man.     

善宁治疗顽固性大咯血疗效观察

目的 评价善宁对顽固性大咯血的疗效。方法 将55例传统药物抢救无效或有禁忌的大咯血分为治疗组（善宁）与对照组（立止血组），观察24—72h的止血效果。结果 治疗组总有效率为92％，对照组为70％，两组比较有显著差异p〈0．05（x^2=4．125）。结论 善宁治疗大咯血疗效显著，使用安全，不良反应少，值得临床推广应用。     

Gadolinium ring enhancement and mass effect in acute disseminated encephalomyelitis

A 9-year-old boy presented with a subacute history of optic neuritis followed by brainstem involvement, with fever and a lymphocytic pleocytosis in the cerebrospinal fluid. Gadolinium-enhancing ring lesions were demonstrate in the white matter of the cerebrum, brainstem and cerebellum on day 17 of the illness, all appearing simultaneously as part of a monophasic illness. A parietal lesion exerted mass effect. Needling and biopsy yielded no evidence of a pyogenic lesion, tumour or tuberculosis and showed vasculitis. There was insufficient material for myelin staining. Dexamethasone therapy lead to rapid improvement of the radiological lesions: MRI and CT on day 34 of the illness showed complete clearing of the lesions except for residual abnormality at the biopsy site.     

Evidence for differential effects of 8-OH-DPAT on male and female rats in the Anxiety/Defense Test Battery

The Proxemics/Activity test and the Eat/Drink test, two components of the Anxiety/Defense Test Battery, were developed to measure defensive reactions to situations associated with a natural predator (cat). In the present studies the behavioral effects of 8-OH-DPAT treatment (0.01–1.0 mg/kg, SC) were entirely consistent with anxiety/fear reduction. These effects included an increase in time spent near the cat compartment, and a complimentary decrease in time spent farthest from this compartment, together with an increase in transits and locomote behavior. 8-OH-DPAT (1.0 mg/kg) also increased eat frequencies and durations (highly preferred food) both during and following cat presentation, without influencing drinking. This finding is discussed with reference to previous findings with 8-OH-DPAT in studies assessing both food intake and anxiolysis. Interestingly, 8-OH-DPAT was more potent in a majority of its effects in female subjects, a finding consistent with recent neurochemical data. These findings provide important behavioral evidence for a sexual differentiation in 5-HT function, and support the case for greater emphasis on female subjects in animal models of anxiety.Supported by NIH MH42803 and RCMI Grants RR03061 and RR01825     

Late Effects of Childhood Acute Leukemia and Its Treatment

Late effects of childhood acute leukemia and its treatment were studied in 766 patients (684 ALL, 73 ANLL, and 9 others) in Japan who had remained in remission for more than 1 year after their first complete remission. Delayed adverse sequelae involve a wide variety of organs and their functions. Short stature was present in 2.61%, obesity in 3.79%, abnormalities of growth hormone secretion in 1.5%, delayed secondary sex characteristics in 1.5% of males and 0.6% of females, motor disturbances in 1.17%, sensory disturbances in 0.91%, intellectual and learning disabilities in 2.48%, abnormal findings in routine neurologic examinations in 1.31%, EEG abnormalities in 4.30%, brain CT abnormalities in 5.09% and cardiac dysfunction in 1.07%. Various other disorders were seen in 20 patients. Many of these delayed adverse sequelae are caused by or related to central nervous system prophylaxis and systemic combination chemotherapy. The results suggest that it is needed to improve therapeutic methods through the stratification of patients by risk factors and detailed analysis of prognostic factors. Moreover it is important to render medical and psychosocial support to long-term survivors of childhood leukemia through interactions between the patient, parents and medical staff.     

Efficacy and functionality of silver-coated textiles in patients with atopic eczema

BACKGROUND: Microbial skin colonization with Staphylococcus aureus is known to play an important role in atopic eczema (AE). Recently, an antibacterial effect of silver-coated textiles on S. aureus colonization has been demonstrated. OBJECTIVES: To investigate clinical efficacy and functionality of silver-coated textiles in AE, a multicentre, double-blind, placebo-controlled trial was conducted. PATIENTS/METHODS: From November 2001 to August 2002, 68 consecutive outpatients clinically diagnosed with generalized AE were included in the study. Inclusion criteria were the clinical diagnosis of AE with a moderate severity as measured by the scoring of atopic dermatitis (SCORAD) index with at least 20. Patients were instructed to wear either silver-coated (verum, 35 patients + 2 dropouts) or cotton garments (placebo, 22 patients + 9 dropouts) directly on the skin for 2 weeks. Only basic skin care and ongoing therapy with topical steroids or oral antihistamines was permitted. Clinical severity was assessed using the 'SCORAD' before, during and at the end of study. Quality of life (QOL), wearing comfort (WC) and functionality (FU) of study clothes were measured in parallel. Patients documented their subjective and objective symptoms daily. RESULTS: In the verum group, eczema improved significantly after 1 week with further enhancement until the end of study (P = 0.03 and P < 0.001). Silver-coated textiles were comparable to cotton in WC and FU. Pruritus and self-assigned skin condition improved significantly more than with placebo (P < 0.001 and P = 0.003). CONCLUSIONS: In conclusion, silver-coated textiles are able to improve objective and subjective symptoms of AE significantly within 2 weeks, showing a good wearing comfort and functionality comparable to cotton.     

An Evaluation of the Residual Activity of Antiseptic Handrub Lotions: An ‘In Use’ Setting Study

An evaluation of the residual activity of quick-drying agents (alcoholic solutions) used for hygienic hand disinfection is described. We looked for residual efficacy following hand disinfection with soap and water alone or followed by one of two alcoholic handrub lotions supplied from an automatic hand washing machine. The bacterial counts on the hands obtained before and within 2 successive hours after disinfection showed that alcoholic chlorhexidine was the most effective for 10 minutes after contamination of the hands. WELPAS® (alcoholic chlorbenzarconium) followed this in its immediate effect and was better than soap and water alone. There were no significant differences after 30‘ or 120‘ between the three disinfecting methods.     

Long-lasting effect of ceruletide on dyskinesia and monoaminergic neuronal pathways in rats treated with iminodipropionitrile

In a model of dyskinesia induced by the administration of iminodipropionitrile (IDPN) in the rat, we evaluated the effects of ceruletide, an analogue of cholecystokinin, on behavioral abnormalities and monoaminergic neuronal function. Vertical head twitching in the IDPN-treated animals was inhibited for over 5 h following a single subcutaneous dose of 160 micrograms/kg ceruletide. In animals dosed daily for 2 or 3 days, the number of head twitches at 24 h after the last dose was about one-third of the number before treatment. After repeated daily doses of ceruletide for 6 days, the number of head twitches was reduced to low levels and remained significantly below pretreatment levels until the 4th posttreatment day. These results indicate that the inhibition of dyskinesia by ceruletide was long-lasting. Assays of monoaminergic neurotransmitters and their metabolites in various brain regions indicate that an imbalance between dopaminergic and serotonergic neuronal systems plays a major role in the pathogenesis of the IDPN-induced dyskinesia, i.e. the ratio of (DOPAC+HVA)/5-HIAA was significantly greater in the striatum but significantly smaller in the hippocampus of the IDPN-treated vs normal animals. This initially abnormal ratio of (DOPAC+HVA)/5-HIAA in the striatum and hippocampus of IDPN-treated animals returned to normal following treatment with ceruletide, corresponding with the reduction of the head twitching. The alterations in monoaminergic neuronal function induced by repeated administration of ceruletide persisted for at least 3 days, even though its plasma half-life is several minutes. Ceruletide also exerted a marked effect on monoaminergic neuronal function in the IDPN-treated rats, in contrast to only a slight effect in normal animals.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sex cord-stromal tumors of the ovary

The developmental relationship between granulosa and stromal cells in the fetal ovary was reviewed. The proliferation and expression of basic fibroblast growth factor (bFGF) and luteinizing hormone receptor (LHR) of both the granulosa and theca cells was examined in the adult ovary. Ovarian granulosa cell tumors were then studied under light and electron microscopy and for immunohistochemical expression of bFGF and LHR. In the follicular development of the adult ovary, bFGF expression in the granulosa cells was correlated with theca cell proliferation. In ovarian granulosa cell tumors, estrogen-producing tumors showed a stratified or microfollicular pattern being accompanied by theca cells which had ultrastructural features of steroid-production, and these tumor cells exhibited immunoreactivity for bFGF. In contrast, tumors with no apparent hormone-production showed a solid or gyriform pattern without admixture of theca cells, and were negative for bFGF. LHR was expressed in both types of tumor. Accordingly, bFGF may play an important role in association with the theca cell component in granulosa cell tumors.