Estramustine and estrone analogs rapidly and reversibly inhibit deoxyribonucleic acid synthesis and alter morphology in cultured human glioblastoma cells

Estramustine is an estradiol-based agent that has been shown to accumulate in human glioma cells, resulting in a concentration-dependent alteration in cell size and shape within minutes and an inhibition of proliferation over 3 to 6 days. We evaluated human glioblastoma cultures with [3H]thymidine incorporation assays to determine estramustine's early effects on deoxyribonucleic acid synthesis in these tumors. Because estramustine shares a common structural motif with other antimicrotubule drugs, we synthesized four A-ring conjugates of estrone that contained a carbamate moiety but lacked nitrogen mustard. These analogs were examined by [3H]thymidine incorporation and compared with vinblastine. Greater than 70% inhibition of [3H]thymidine incorporation occurred within 1 hour of treatment with estramustine at 10(-5) mol/L, which increased to 80% inhibition at 4 hours. Ethyl carbamate JE208 was nearly as effective as estramustine in inhibiting deoxyribonucleic acid synthesis, and both were more effective than vinblastine. The inhibitory effects of estramustine and estrone analogs were reversible; vinblastine was not reversible. Although estramustine and JE208 induced similar antiproliferative and morphological changes in glioblastoma cells that persisted for at least 4 days, there was a modest recovery of morphology and thymidine incorporation with JE208 after prolonged treatment. The common findings with estramustine and JE208 suggest that these agents may have a similar mechanism of action and form the basis for the investigation of new agents that may rapidly and reversibly inhibit glioblastoma.     

The therapeutic effect of intralesional interferon in classical Kaposi's sarcoma

Interferon alpha-2a, which has antineoplastic, antiviral, immunomodulatory, and antiangiogenic effects, was evaluated in a prospective study, treating 10 lesions of patients with classical Kaposi's sarcoma. Ten patients received injections of interferon alpha-2a intralesionally in a dose of 3 million units three times weekly for 4 weeks, and in a variable dose for 4 more weeks. Two of the patients had a complete response, and in one of these, distant lesions also responded. Seven had a partial response, and one did not respond. The treatment was generally well tolerated. The results of our study support the use of interferon in the therapy of classical Kaposi's sarcoma, although it would appear that to achieve maximum efficacy, a longer period of treatment is needed.     

Morphological changes induced by colchicine in the chick optic cup in early stages of development. A stereological study

In this study chick embryo optic cups at HH stage 13 of development were analyzed under normal conditions and after inoculation with colchicine for 1, 2, 4, and 8 h. Several changes were seen after these periods of treatment: 1) modifications of the structure, with thicker regions in the cup and a general decrease in the total volume according to the duration of exposure to the drug (about 4 times less than normal, 5,035 x 10(3) microns 3 vs 1,334 x 10(3) microns 3 after 8 h of treatment); 2) enlargement of the ventricular cavity and its closure, due to failure of approximation of retinal and pigmentary layers; 3) failure of lens development, with delay and impairment of pit formation and deformation of all structures; lens volume was less than normal (about 4 times less, 2,148 x 10(3) microns 3 vs 658 x 10(3) microns 3 after 8 h of treatment); 4) a general segregation of the cells making up the structure, principally in the more active proliferating zones. The local alterations found are described.     

Disaster-readiness of medical facilities in Aichi Prefecture

One month following the Great Hanshin Earthquake of January 17, 1995, we conducted a survey of 173 hospitals in Aichi Prefecture to pinpoint problems related to their actual disaster-readiness and the medical backup systems in place to deal with such disasters. This study revealed that staff at 50% of the surveyed hospitals could reach the hospital within an hour, but that communication is almost entirely dependent on phone lines, suggesting that cordless/portable/mobile phones, radio systems, Internet, communications satellites and the like should be studied in the days to come for possible use as effective communication alternatives in times of disaster. Whereas 92% of the surveyed hospitals had manuals dealing with fire outbreaks, other areas were less well represented. For example, only 36.9% of surveyed hospitals had manuals for earthquakes, 31.7% had manuals for power outages and 14.2% had manuals to deal with flooding and water disasters. New manuals must be developed incorporating the key points garnered from experience (especially Hanshin) and be ready for use immediately. It is the time for each hospital to seriously rethink the measures it should take to deal with disasters.     

Cardiac tamponade as a presentation of primary hypothyroidism in a young woman

Pericardial effusion (PE) as a hypothyroidism associated sign, is something that can be found with relative frequency; nevertheless, cardiac tamponade (CT) as the first sign of this disease may be considered exceptional especially in young patients. We report a 31 years old woman with clinical symptoms and signs of CT that in the forward workshop was diagnosed of primary hypothyroidism as cause of the CT. We shortly describe the case and review the literature, emphasizing the importance of the knowledge of CT trigger factors in myxedematous PE, as well as its usual benign evolution with hormonal treatment, without recurrences of the CT after pericardiocentesis is performed. This justify a conservative approach, in spite of the slow resolution of the PE what can take as long as 1.5 years.     

Diagnostic value of the study of caffeine elimination in chronic liver diseases

Data from the past few years have shown that as caffeine metabolizes solely in the liver, caffeine elimination can serve as a liver function test. We have collected data by monitoring 40 persons with liver diseases (11 chronic alcoholic hepatitis, 24 liver cirrhosis, 5 non-cirrhotic liver disease). Eight subjects served as controls. The patients with liver cirrhosis were classified according to the Child--Pugh scoring system. To determine caffeine elimination blood samples were collected before and at 3, 6, 9 and 12 hours after oral administration of 0.2 g caffeine. Fasting serum caffeine concentration and concentration 12 hours after administration, serum clearance, half life, peak concentration and volume of distribution have been compared. The respective values measured in patients with non-cirrhotic liver diseases did not differ significantly from the controls. The disappearance of caffeine was significantly decreased in cirrhotics. Our results demonstrated a good correlation between impairment of caffeine elimination and assessment of severity of liver disease by the Child--Pugh classification. Measuring serum levels in samples taken 12 hours after caffeine administration is a simple and useful method in the diagnosis of liver diseases at cirrhotic stage.     

Enantioselective antiplatelet actions of nipecotamides

This investigation retrospectively examined changes in marital satisfaction following stroke. The relationship between such changes and other pertinent factors were also examined, including severity of aphasia, knowledge of aphasia, number of months after stroke, and length of the marriage. The subjects were 40 spouses of patients with aphasia grouped according to severity of the aphasia (mild, moderate, severe). Spouses completed two different measures of marital satisfaction--the Marital Satisfaction Scale (MSS) and the Marital Comparison Level Index (MCLI). These measures were completed in both a prestroke (retrospective reporting) and a poststroke format to allow for change to be assessed. In addition, a Knowledge of Aphasia questionnaire was completed by the normal spouses to evaluate their understanding of the disorder of aphasia. There was a significant difference between prestroke and poststroke scores on both the MSS and the MCLI, indicating a lower level of satisfaction following the stroke. The amount of change between prestroke and poststroke MSS and MCLI scores was not related to either number of months poststroke or number of years married. Although there was no relationship between changes in prestroke and poststroke scores on the MCLI and Knowledge of Aphasia scores, there was a significant correlation between changes in these scores on the MSS and Knowledge of Aphasia scores. Hence, the more knowledge spouses had regarding aphasia, the less the negative impact the stroke had on marital satisfaction, as measured by the MSS. Results are discussed in terms of the interdisciplinary treatment needs of aphasic patients and the implications for future investigations.     

Low birth weight as an additional indication for chromosomal analysis

INTRODUCTION: Even though there are few epidemiological studies evaluating the birth weights of different groups of malformed babies with chromosomal abnormalities, it is widely known that infants with trisomy 18, and to a lesser degree those with trisomy 13 and other chromosomal alterations, have low birth weights. PATIENTS AND METHODS: In this study we present the analysis of the birth weights and gestational ages of a large sample of babies (23,155 malformed and a similar number of nonmalformed babies), separating the different groups of chromosomal anomalies and comparing the weight in the clinical groups of malformed infants. RESULTS: Most of the groups with chromosomal abnormalities present lower birth weights in comparison to the other groups. CONCLUSIONS: The results of our study support the conclusion that the relationship between chromosomal alterations and low birth weight is sufficiently important that such a low birth weight in children with minor or major anomalies should be considered as one more indication to perform chromosomal analysis.