Maternal antioxidant treatments prevent diabetes-induced alterations of mitochondrial morphology in rat embryos

OBJECTIVE: To investigate the bioavailability (extent and rate of absorption) of ketorolac from two cutaneous absorption sources, active electrotransport and passive transdermal, and to examine the enantiomeric selectivity of bioavailability for each source. METHODS: Based on a crossover study in 12 healthy volunteers, the extent and rate of absorption of ketorolac, delivered by a patch, were found by estimating the input rate function of the drug. For that purpose, deconvolution was used in two steps. First, intravenous data were analyzed to estimate the ketorolac disposition function, and second, postpatch data were deconvolved to estimate the unknown patch input profile given the disposition function estimated in the first step. Because the input rate function curves to be estimated for the patches may be of arbitrary shape, a spline was used to model the patch input function, whereas intravenous data were modeled with use of a sum of exponentials. Differences in the extent of absorption (F) for the four treatment-enantiomer combinations were further examined with a mixed-effect regression model, based on the sets of four individual estimates of bioavailability. RESULTS: On average, the F value for the active electrotransport treatment, which exhibited the faster absorption rate, was four times greater than the F for the passive transdermal treatment. Further, during the passive treatment, R-ketorolac yielded an average F that is 42% greater than that for S-ketorolac and also exhibited a smaller absorption lag-time. During the active treatment, there was no important enantiomeric difference in either extent or rate of absorption.     

Diagnosis of pulmonary embolism with spiral and electron-beam CT

PURPOSE: To compare spiral (SCT) and electron-beam CT (EBT) for the diagnosis of pulmonary embolism (PE). MATERIALS AND METHODS: From June 1997 to June 1998 188 patients with suspected acute or chronic thromboembolism of the pulmonary arteries were examined. A total of 108 patients were scanned using SCT and 80 patients using EBT. On each scanner two different scan protocols were evaluated. RESULTS: PE was diagnosed in 38 patients using EBT and in 49 patients using SCT. Especially with EBT, isolated peripheral emboli could be confidently diagnosed. When EBT and SCT were compared for the analysis of peripheral pulmonary arteries, some paracardiac segmental and subsegmental vessels were significantly better analyzable with EB. Additional or diseases other than PE were diagnosed in 112 patients. Other diagnoses included bronchial carcinoma and aortic dissection. CONCLUSIONS: Advanced CT scanning techniques allow the highly accurate diagnosis of central and peripheral PE. Other potentially life-threatening underlying diseases are also readily recognized.     

Loss of heterozygosity of BRCA1, TP53 and TCRD markers analysed in sporadic endometrial cancer

Genetic alterations of tumour suppressor genes, for which loss of heterozygosity (LOH) is one mechanism of gene inactivation, are important steps in the development of endometrial cancer. To investigate the clinical relevance of LOH of BRCA1 (17q21), TP53 (17p13) and TCRD (14q11) in endometrial cancer, polymerase chain reaction (PCR)-based fluorescent DNA technology for the detection of microsatellite polymorphisms was applied. One hundred and thirteen archival endometrial cancer samples with matched normal tissues were examined. Allele loss at three loci were correlated with age, tumour size, lymph node status, metastases, stage, histological types, grade, expression of oestrogen receptor (ER) and progesterone receptor (PgR), family history of cancer, previous history of cancer or precursor lesions, and previous history of hormone replacement therapy (HRT). LOH for BRCA1 was detected in 18.1%, of TP53 in 26.9%, and of TCRD in 26.3% of informative cases. LOH of BRCA1 correlated with medium grade, positive ER status, and family history of cancer; LOH of TP53 correlated with younger age, high grade, positive PgR status, and with tumours from patients without HRT; LOH of TCRD correlated only with family history of cancer. LOH at all three loci correlated only with grade and positive family history. Allele loss of one of the three tumour suppressor loci did not correlate with disease-free survival (DFS), but LOH of BRCA1 correlated significantly with decreased overall survival (OS). The latter, together with the correlation of LOH of BRCA1 locus with steroid hormone receptor expression, might give a hint to the potential involvement of the co-localised 17 beta-hydroxysteroid dehydrogenase (HSD) gene in the development of endometrial cancer.     

Contrast hysterosonography: an efficient means of investigation in gynecology. Review of the literature

The structure of WA8242B, a potent novel inhibitor against phospholipase A2, was fully characterized by spectroscopic methods and chemical degradation. The success of total synthesis of WA8242B confirmed the structure and allowed the pharmacological study of WA8242B. The structures of WA8242A1 and A2 were also described.     

Cold preservation of the porcine pancreas with histidine-tryptophan-ketoglutarate solution

OBJECTIVES: To describe the prescribing and use of antiepileptic drug (AED) therapy in nursing facility residents. DESIGN: A retrospective, multicenter drug use evaluation. SETTING: A total of 85 nursing facilities (average size, 119 beds) in five states. PARTICIPANTS: 1132 residents of the total 10,168 residents screened were prescribed at least one AED. MEASURES: Demographic information, primary indication for AED, comorbid conditions, prescribing physician's specialty, concomitant medications, and AED dosage regimen information were collected. Laboratory tests obtained in the most recent 6 months and seizure occurrence and seizure-related diagnostic assessments made in the most recent 3 months were also recorded. RESULTS: Of 1132 residents receiving AED therapy, 892 (78.8%) were prescribed AED therapy for a seizure-related diagnosis although 86% of seizure types were unspecified. Another 215 residents (19.0%) were prescribed AEDs for nonseizure diagnoses, and 25 (2.2%) had no indication for AED therapy. AEDs most frequently prescribed were phenytoin (56.8%), carbamazepine (23.0%), phenobarbital (15.6%), and valproic acid (13.1%). For residents with a seizure diagnosis, the most frequently prescribed monotherapy agents were phenytoin (52.0%), carbamazepine (12.2%), and phenobarbitol (7.1%). Almost 25% of residents with a seizure diagnosis took a combination of AEDs; more than 50% of all combinations included phenobarbital. About 9% of residents with a seizure diagnosis had one or more documented seizures during a 3-month review period. CONCLUSION: Among the substantial percentage of residents treated with AEDs, the lack of diagnosis of seizure type has serious implications for the choice of AED therapy. Opportunities exist for prescribing physicians, consultant pharmacists, and nursing staff to improve the medical management of nursing facility residents with seizures and of others receiving AEDs.     

Responses of neurons of the nucleus of the optic tract and the dorsal terminal nucleus of the accessory optic tract in the awake monkey

The in vitro effect of recombinant human Granulocyte Macrophage Colony Stimulating Factor (rh-GMCSF) on the leishmanicidal activity and superoxide anion productivity of macrophages derived from human blood monocytes (MOs) were investigated. MOs treated with 25, 125, or 250 U/mL of rh-GMCSF for 72 h prior to infection with leishmania parasites, manifested significant dose-dependent increase in its leishmanicidal activities against Leishmania major and Leishmania donovani parasites. The percentage of increase in leishmanicidal activity of L. major-infected MOs were 22.71, 64.34 and 81.34, respectively while in L. donovani-infected MOs, it reached 3.01, 32.28 and 74.38, respectively. Treatment of leishmania-infected MOs with rh-GMCSF (250 U/mL) for different periods of time up to 96 hours, induced a significant time-dependent reduction in the percentage of infected cells and the parasitic load (No. of amastigotes/100 MOs). After 96 h of treatment with rh-GMCSF, the percentages of reduction in the infection rates were 82.45 in L.major-infected MOs (p < 0.001) and 39.65 in L. donovani-infected cells (p < 0.01). The percentage of reduction in the parasitic load reached 90.82 (p < 0.001) and 36.6 (p < 0.05) in MOs infected with L. major and L. donovani, respectively. The priming effect of rh-GMCSF on superoxide anion production by human MOs stimulated with phorbol myristate acetate (PMA) was both dose-dependent and time-dependent. In 72 hour-old human MOs, the maximum superoxide anion release was generated by MOs primed for 45 min with 500 U/mL of rh-GMCSF. These cells produced 8.960 +/- 2.075 nmol/5 x 10(4) MOs/ 180 min as compared to 4.563 +/- 1.773 nmol/5 x 10(4) unprimed cell control/180 min (p < 0.001).     

Aging and the use of perceptual and temporal information in source memory tasks

A number of studies have reported age differences in memory for the source of information. S.A. Ferguson, S. Hashtroudi, and M.K. Johnson (1992) suggested that older adults do not efficiently use multiple distinctive characteristics of sources to distinguish between sources in source memory tasks. In the study reported here, participants heard information from 2 sources and later decided whether test items had been presented by Source A, by Source B, or were new. The distinctiveness of both perceptual and temporal characteristics of sources were independently manipulated. Older adults benefited more than young adults from multiple distinctive characteristics of sources. These results question the generality of S.A. Ferguson et al.'s hypothesis.