CNS-active substances: synthesis of epoxybenzoxocines

The 2-(2-Bromophenyl)-acetaldehyde acetals 8 are treated with n-BuLi and the aldehydes 7 and 11 to form the hydroxyacetales 9 and 12, respectively. 9 is cyclized under acidic conditions to the epoxybenzoxocine 2; analogously 12 yields the epoxydibenzoxocine 14.     

Features of head injury in a developing country--Taiwan (1977-1987)

Certain features of head-injured patients admitted to the Chang Gung Memorial Hospital in Taiwan during the period 1977 to 1987 were reviewed. The most common causes of injury were motorcycle accidents (56.3%) and street accidents with pedestrian injury (29.47%). The age groups with the greatest incidence of injury were aged 16-20 years, 21-25 years, and 25-30 years. The pedestrian group involving the highest incidence of injury was less than 10 years of age. Overall mortality was 17.26%. The injured pedestrian group had the highest mortality (19.1%). Initial clinical assessment was recorded using the Glasgow Coma Scale. Head-injured patients with a GCS less than 8 had a mortality in the injured pedestrian group of 46%, whereas the mortality rate in the motorcycle accident group was 41%. Additional features studied were time of occurrence of injury and pattern of injury. Information gathered from this study would suggest the need to establish a Head Injury Prevention Program in Taiwan. This of course implies major cooperation among the providers of health care delivery, the medical profession, legislators, and the government at all levels.     

8-OH-DPAT and buspirone analogs inhibit the ketanserin-sensitive quipazine-induced head shake response in rats

Behavioral syndromes mediated by serotonergic mechanisms may reflect interactions between distinct effects initiated by specific 5-HT receptors, such as the 5-HT1A and the 5-HT2 receptor. This hypothesis was tested by examining the effect of various 5-HT1A agonists on the 5-HT2 receptor-mediated quipazine-induced head shake response in rats. Subcutaneous administration of 8-OH-DPAT, buspirone, gepirone, and ipsapirone produced a dose-dependent inhibition of the ketanserin-sensitive quipazine-induced head shake response. These effects were produced by doses of agonists which did not induce reciprocal forepaw treading. Furthermore, pretreatment with a partial 5-HT1A agonist (+/-)pindolol blocked the inhibitory effects of 8-OH-DPAT to the level of inhibition produced by (+/-)pindolol itself. These results suggest that stimulation of central 5-HT1A receptors can modulate the expression of a central 5-HT2 receptor-mediated behavior.     

Is protection of ischemic neonatal myocardium by cardioplegia species dependent?

Hypothermia combined with pharmacologic cardioplegia protects the globally ischemic adult heart, but this benefit may not extend to children, resulting in poor postischemic recovery of function and increased mortality. The relative susceptibilities to ischemia modified by hypothermia alone and by hypothermia plus cardioplegia were assessed in isolated perfused neonatal (3- to 4-day-old) rabbit and pig hearts. Hearts were perfused aerobically with Krebs buffer solution in the working mode for 30 minutes and aortic flow was recorded. This was followed by 3 minutes of hypothermic (14 degrees C) coronary perfusion with either Krebs or St. Thomas' Hospital cardioplegic solution No. 2 followed by hypothermic (14 degrees C) global ischemia (rabbits 2, 4, and 6 hours; pigs 2 and 4 hours). Hearts were reperfused for 15 minutes in the Langendorff mode and 30 minutes in the working mode, and recovery of postischemic aortic flow was measured. Hypothermia alone provided excellent protection of the ischemic neonatal rabbit heart, with recovery of aortic flow after 2 and 4 hours of ischemia at 91% +/- 4% and 87% +/- 5% (mean +/- standard deviation) of its preischemic value. Recovery after 6 hours of ischemia was depressed to 58% +/- 9% of its preischemic value. Ischemic neonatal pig hearts protected with hypothermia alone recovered 94% +/- 3% of preischemic aortic flow after 2 hours; none was able to generate flow after 4 hours. St. Thomas' Hospital solution No. 2 decreased postischemic aortic flow after 4 hours of ischemia in rabbit hearts from 87% +/- 5% to 70% +/- 7% (p less than 0.05, hypothermia alone versus hypothermia plus cardioplegia) but improved postischemic recovery of aortic flow in pig hearts after 4 hours of ischemia from 0 to 73% +/- 13% (p less than 0.0001, hypothermia alone versus hypothermia plus cardioplegia). This effect was dose related in both species. We conclude that the neonatal pig heart is more susceptible to ischemia modified by hypothermia alone than the neonatal rabbit and that St. Thomas' Hospital solution No. 2 improves postischemic recovery of function in the neonatal pig but decreases it in the neonatal rabbit. This species-dependent protection of the neonatal heart may be related to differences in the extent of myocardial maturity at the time of study.     

Removal of famotidine by haemodialysis in elderly anuric patients

Summary The effect of haemodialysis on the pharmacokinetics of oral famotidine has been studied in five elderly anuric patients. Famotidine 20 mg was administered in a cross-over design to patients on and not on haemodialysis.The elimination rate constant of haemodialysis (k) was 4.6-fold larger than the systemic elimination rate constant (k_e). Although the mean maximum serum concentration of famotidine during haemodialysis (141.5 ng·ml^–1) was not significantly lower than that without haemodialysis (195.6 ng·ml^–1), the AUC up to 5 h during haemodialysis was significantly decreased to 58.1% of the value without it.The data suggest that famotidine is dialysable by haemodialysis.     

Cytostatic and immunosuppressive treatment of ocular Beh?et syndrome

Ocular symptoms of Beh?et's syndrome in 16 patients and the results of cytostatic and immunosuppressive therapy with cyclosporin A (6 patients), chlorambucil (6 patients), and a combination of cyclophosphamide and procarbacin (4 patients) are described. The clinical course and therapeutic outcome were compared to the patients' visual acuity and the duration of the disease prior to institution of cytostatic therapy. Average follow-up was 4.6 years, maximum 9 years. The principal ocular symptom in all patients was hemorrhagic, occlusive periphlebitis. Other symptoms, in descending order of frequency, were chorioretinitis, iridocyclitis, complicated cataract, secondary glaucoma and exudative retinal detachment. The patients in whom cytostatic therapy was instituted no later than 6 months after onset of the disease showed an improvement in or stabilization of visual acuity, as well as a clear reduction in signs of intraocular inflammation and frequency of recurrence. No improvement in visual acuity or ocular symptoms was achieved in cases where the disease was very advanced, despite cytostatic-immunosuppressive therapy. The results support early institution of immunosuppressive therapy in cases with Beh?et's syndrome where severe, irreversible damage has not yet occurred and in which vision is threatened in both eyes. However, due consideration must be given to the potential risks of immunosuppressive therapy, in particular the risk of a malignant tumor.     

D-[3H]galactose incorporation into glycogen in retinal cone cells

Previous studies have shown that bovine retinas incubated with [3H]galactose incorporated it, unmodified, into large molecules. Light and electron microscope autoradiography showed a significant proportion of the label to be in cone inner segments, and pulse-chase studies showed it was subsequently transported to the synaptic pedicles. In this report, evidence is presented to show that the galactose-labelled macromolecules are resistant to hydrolysis by proteolytic enzymes, testicular hyaluronidase, chondroitinase ABC, beta-glucosidase and beta-glucuronidase, but are readily degraded by alpha-amylase and beta-galactosidase, and to a lesser extent by beta-amylase. Treatment with alpha-amylase also leads to specific removal of radioactivity from cone inner segments and pedicles, as judged by light-microscopic autoradiography. These studies appear to indicate that the cone-specific galactose label is in glycogen or glycogen-like molecules.     

Four years' experience with a clinical intervention program: cost avoidance and impact of a clinical coordinator

Four years of data are reported on the drug cost avoidance and the net cost savings associated with a clinical pharmacy intervention program. In 1986 the pharmacy department at a 324-bed nonprofit community medical center began a clinical intervention program by adding one full-time equivalent for providing clinical services. A new clinical pharmacist position was created in 1988. A reorganization in 1989 resulted in further increases in staffing, including the creation of a clinical coordinator position to oversee the intervention program, and in administrative time. Staff pharmacists self-report a broad range of interventions on a clinical documentation form. During the period 1986-1989, monthly data on the number of types of interventions recommended, the percentage of recommendations accepted by the medical staff, and drug cost avoidance were tabulated. Cost avoidance was calculated by subtracting the cost of therapy ordered by the physician from the cost of therapy initiated as a result of the intervention. Net drug cost savings were calculated by subtracting from cost avoidance the cost of pharmacist time required for performing the interventions. The average number of interventions per month ranged from 170 in 1986 to 292 in 1990. During an 18-month period before the clinical coordinator was added, average monthly cost avoidance and net savings were $4932 and $3739, respectively. Average monthly cost avoidance increased to $6244 and savings to $4644 in a 12-month period after the clinical coordinator was added. A four-year study of a clinical intervention program showed that the dollar value and impact outlasted the initial success expected for such programs.     

Origins of heterogeneous ovarian carcinomas. A molecular cytogenetic analysis of histologically benign, low malignant potential, and fully malignant components.

It is unclear whether ovarian carcinomas develop from malignant transformation of benign precursors or whether they arise de novo. Thus, histologically benign or low malignant potential components found in heterogeneous ovarian carcinomas may be remnants of pre-existing lesions that progressed to malignancy or, alternatively, elements that arose independently (de novo). In a third possible interpretation, they represent areas of malignant epithelium that matured. We evaluated clonal relationships of histological components in 10 heterogeneous ovarian carcinomas using fluorescence in situ hybridization and confocal microscopy. Detailed analysis of aneuploidy for chromosomes 8, 12, and 17 on intact paraffin sections revealed that two tumors were aneuploid in all components, two lacked abnormalities in benign-appearing components, and one lacked aneuploidy in both histologically benign and low malignant potential components. Histological appearance was significantly related to aneuploidy (P < 0.05). The distribution of aneuploidy among tumor components strongly supports the tumor progression theory and demonstrates that the de novo hypothesis is highly unlikely (P < 0.001). Results also indicate that benign-appearing components in heterogeneous ovarian carcinomas do not represent maturation of malignant tissue and suggest that some benign tumors that become cancerous may have genetic aberrations that predispose them to malignant transformation.