Subcellular concentrations of estrone, estradiol, androstenedione and 17 beta-hydroxysteroid dehydrogenase (17-beta-OH-SDH) activity in malignant and non-malignant human breast tissues

Total and subcellular (cytosol and nuclear) concentrations of estrone (E1), estradiol (E2), and androstenedione were determined in non-malignant (n = 61) and malignant (n = 65) human breast tissues obtained from post-menopausal women. The 17 beta-hydroxysteroid dehydrogenase (17 beta-OH-SDH) activity was determined in 800g supernatant fraction. Total estrogens, E1 and E2 levels and 17 beta-OH-SDH activity were significantly (p less than 0.005, 0.0005, 0.001, respectively) higher in malignant than in non-malignant breast tissues. We failed to observe significant changes in subcellular steroid concentrations or enzyme activity associated with patients' obesity or tumor estrogen receptor status. When the steroid levels were analyzed in relation to clinical staging of the disease, nuclear contents of estradiol were significantly higher (p less than 0.005) in Stage-IV patients than in those with less advanced disease (Stages I to III). 17 beta-OH-SDH activity was significantly (p less than 0.001) lower in patients with advanced disease than in those with relatively less advanced (Stages I to III) disease and was positively correlated with tissue concentration of androstenedione. Our present data indicate that differential intracellular metabolism of steroid hormones may have some influence on availability of estradiol at nuclear sites. In postmenopausal women, local interconversion of estrogens may provide sufficient estrogenic stimulus to enhance the growth and progression of breast tumors.     

Comparative effects of pilocarpine in different vehicles on pupil diameter in albino rabbits and squirrel monkeys

Several commercial pilocarpine preparations have been compared for their efficacy of drug delivery as evaluated by changes in pupil diameter, and return to base-line pupil size, in rabbits and squirrel monkeys. Adsorbocarpine, Isoptocarpine, Pilocar, all at 2%, and Pilopine HS gel, 4%, were used. In albino rabbits the order of efficacy, as judged by area under the curve, or maximal pupil diameter change, was Pilopine greater than Isoptocarpine = Adsorbocarpine greater than Pilocar = saline (prepared in this laboratory). In general, greater areas under the curve were associated with greater changes in pupil diameter. Pupil diameter had returned to normal by a maximum of 5 hours after drop instillation. In squirrel monkeys, the maximum pupillary change was statistically (P greater than 0.05) the same for all preparations, as was the percentage change in pupil diameter at 6 hours since pupils were still somewhat constricted at this time after drop instillation. The differences in area under the curve were minor. The greater response in primates compared to rabbits may be due to differences in pigment, intraocular kinetics and a far more active ciliary muscle in primates. Also studied were newly developed, non-surfactant containing, preservative-free polymer- and microparticle-based vehicles. Some of the vehicles, based on cyanoacrylate, modified hyaluronate, anionic copolymers, polyvinyl-pyrrolidone, cross-linked gelatin and microparticles showed greater pupillary changes and areas under the curve in rabbits compared to saline vehicle. When compared to commercial preparations in the monkey eye cyanoacrylate block copolymer and modified hyaluronate showed an increase in efficacy. Polyvinylpyrrolidone, anionic copolymer and cross-linked gelatin were equal to the commercial preparations.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation of the Ca 1 monoclonal antibody in distinguishing oral squamous cell carcinoma from non-malignant or premalignant oral lesions

The Ca antigen has been reported to be present on the surface of malignant but not, with few exceptions, non-malignant cells. We investigated the potential usefulness of the monoclonal Ca 1 antibody in differentiating oral squamous cell carcinoma from non-malignant or premalignant oral neoplasms. Paraffin-embedded sections from 33 biopsy specimens of 12 hyperplastic and 21 neoplastic oral lesions were examined by immunohistochemical staining. Seven of the 33 specimens showed positive staining for Ca antigen. Fifteen of 21 specimens of oral squamous cell carcinoma were negative for Ca antigen, and one case of focal keratosis was positive. The results indicate that the use of the Ca 1 antibody to distinguish oral squamous cell carcinoma from non-malignant or premalignant oral lesions is highly unreliable.     

Family History of Alcoholism Does Not Predict Neuropsychological Performance in Alcoholics

We examined the relationship of history of alcoholism in first-degree relatives to neuropsychological performance of alcoholics abstinent from several weeks to several years. Eighty-four men were assigned to four groups based on "strength" of family history of alcoholism. The groups were: (1) "strong history," a parent plus another first-degree relative positive; (2) "moderate," parent only positive; (3) "weak," nonparent first-degree relative only positive; and (4) "negative," no first-degree relative positive. There were no significant between-group differences in NP performance. In other analyses there were no NP differences between alcoholics classified positive or negative purely on basis of paternal alcoholism, and no differences between subjects who had multigenerational versus unigenerational versus negative familial histories of alcoholism. It is concluded that genetic loading for alcoholism does not significantly affect the NP status of abstinent alcoholic groups equated for education, drinking history, and medical risk.     

A Retrospective Review of the Use and Safety of Droperidol in a Large, High-risk, Inner-city Emergency Department Patient Population

Droperidol (DROP) is used in the emergency department (ED) for sedation, analgesia, and its antiemetic effect. Its ED safety profile has not yet been reported in patients (pts). OBJECTIVES: To document the use of DROP in high-risk pts (those with head injury, alcohol or cocaine intoxication, and/or remote or recent seizures), and to determine the number of serious and minor adverse events (AEs)-seizures, hypotension, extrapyramidal side effects (EPSEs)-after DROP. METHODS: The ED database (EmSTAT) was queried to determine who received intramuscular or intravenous DROP in the ED in 1998; further chart review was done if the patient was considered high risk for or had experienced an AE. Multiple regression analysis using a random-effects model determined the significance of each variable in the occurrence of AEs. RESULTS: 2,468 patients (aged 20 months to 98 years; 112 < or =17 years; 141 > or =66 years) received DROP for agitation (n = 1,357), pain (1,135), anxiety (99), vomiting (173), or other reasons (50). There were 945 pts considered high risk; 933 charts were reviewed (DROP mean dose 4.1 +/- 2.0 mg); of these, 50 patient visits did not meet the criteria for high risk. There were 622 pts with head trauma (401 with alcohol use), including 47 with computed tomography (CT) scans positive for brain injury, 64 with cocaine use, and 197 with recent or remote seizures (137 with alcohol use). Minor AEs such as transient hypotension occurred in 96 pts after DROP (73 with alcohol use); 20 received intravenous fluids, while an additional 28 pts (8 with alcohol use) received rescue medications for EPSEs. Six possible serious AEs occurred in pts with serious comorbidities; 2 cases of respiratory depression, 3 post-DROP seizures, and 1 cardiac arrest (resuscitated) 11 hours after DROP in a cocaine-intoxicated pt (normal QT interval). There was no significant difference among high-risk groups in the occurrence of AEs. CONCLUSIONS: The vast majority of pts who received DROP in the ED did not experience an AE. A few serious AEs were noted following DROP in patients with serious comorbidities; it is not clear that DROP was causative.     

Assessing Health Disparities in Rural Hawaii Using the Hoshin Facilitation Method

CONTEXT: Health disparities between rural and urban communities are well documented. There are many suggested causes and many proposed solutions but no one-size-fits-all answer. The most successful community interventions have been introduced by communities themselves. However, before communities invest in such interventions, each group must identify and prioritize their needs. PURPOSE: This article describes the Hoshin facilitation method as a practical option assisting communities in assessing their needs and gaining consensus for future steps. METHODS: Thirty-four meetings were held in 11 rural communities in Hawaii using the Hoshin process to identify factors that impact rural health. Themes were identified by constant comparative analysis and thematic frequency described. Commonality of responses between communities was examined. Informal feedback was collected from meeting participants. FINDINGS: There was a great deal of commonality between community responses, with economic factors, drug use, lack of community leadership, lack of health care services and access to services, lack of healthy activities for youth, and poor public education being the most common issues noted. Group involvement in the meetings was high, and the facilitation method received positive feedback from participants. CONCLUSIONS: The Hoshin facilitation method is a very useful tool to help communities rapidly identify and prioritize areas for programmatic attention.     

Wisconsin Card Sorting Test performance in schizophrenia: remediation of a stubborn deficit.

OBJECTIVE: Schizophrenic patients typically perform poorly on the Wisconsin Card Sorting Test, which is a putative index of prefrontal functioning. The authors attempted to remediate the deficits of schizophrenic patients on this measure by giving detailed instructions and monetary reinforcement. METHOD: Forty-six inpatients with chronic schizophrenia and 20 control subjects with other psychiatric illnesses were given the Wisconsin Card Sorting Test under four conditions that varied in monetary reinforcement and level of instructions. The schizophrenic patients were given the Brief Psychiatric Rating Scale (BPRS) and three information processing measures (the Continuous Performance Test, Span of Apprehension, and Pin Test). RESULTS: Schizophrenic patients performed worse than psychiatric control subjects across most conditions. Monetary reinforcement had little effect on performance, but detailed instructions significantly improved the scores for both groups. When instructions were withdrawn and monetary reinforcement was maintained, both groups continued to show improved performance over baseline. Symptoms were not significantly associated with Wisconsin Card Sorting Test performance. One measure (the Pin Test) correlated significantly with performance on the Wisconsin Card Sorting Test. CONCLUSIONS: The results suggest the importance of combining motivational with instructional factors for training psychiatric patients in problem solving.     

Truncus Arteriosus With Patent Ductus Arteriosus and Normal Aortic Arch

In hearts with a common arterial trunk (truncus arteriosus), there is almost always an inverse development of the aortic arch and the ductus arteriosus. Truncus with a normal aortic arch and a patent ductus is a rare echocardiographic and surgical finding. In this report, we describe 2 neonates in whom truncus arteriosus with a normal aortic arch and a medium or large patent ductus was diagnosed by preoperative echocardiography (without catheterization) and confirmed intraoperatively.