A new technique for performing Syed-Neblett template interstitial implants for gynecologic malignancies using transrectal-ultrasound guidance

The authors review the literature on intra-adenomatous pituitary apoplexy with special emphasis on pathophysiology, diagnosis and therapeutic approach. They present five cases, from a series of 86 patients with pituitary tumors, that developed this syndrome. The patients were diagnosed and followed by the Neurosurgery and Endocrinology Services of Hospital Universitario Clementino Fraga Filho, Universidade Federal do Rio de Janeiro. Diagnosis was confirmed by CT-Scan and MRI in all cases, and the treatment of choice was surgical. Conclusions point to the diagnostic difficulties and the urgency of treatment in this clinical setting.     

The surgical treatment of a large postoperative ventral hernia in patients over 60

Breech presentation occurs in 3-5% of deliveries and can be managed by either a trial of vaginal breech delivery (TOVBD), external cephalic version (ECV) or Caesarean section. A postal questionnaire was completed by 82% of Scottish consultant obstetricians and revealed wide variations in practice. Eighteen percent never offered ECV. Among those who did consensus was lacking on some contraindications. One-quarter sometimes performed ECV before 37 weeks gestations despite the possibility of spontaneous version. Only 70% restricted ECV to one or more designated operators thereby maintaining levels of expertise. Variations were demonstrated in the use of tocolytics, and pre and post procedure investigations. Following failed ECV 28% considered a repeat attempt and 56% a TOVBD. TOVBD was not offered as first line management by one-fifth of respondents. Those who did varied in the pre-procedure investigations performed. Guidelines are required to ensure safe, consistent practice and avoid unnecessary Caesarean sections.     

Dehydroepiandrosterone in systemic lupus erythematosus: relationship between dosage, serum levels, and clinical response

OBJECTIVE: To examine in women with systemic lupus erythematosus (SLE) who participated in a clinical trial the relationship between daily dose of dehydroepiandrosterone (DHEA), serum levels of DHEA and DHEA sulfate (DHEAS), clinical effectiveness, and side effects. METHODS: Twenty-three women with mild to moderate SLE were treated with DHEA for a 6 month period. The starting dose was 50 mg/day, and monthly stepwise increases were allowed. Subjects were assessed monthly by the Systemic Lupus Erythematosus Disease Activity Index, Systemic Lupus Activity Measure (SLAM), Health Assessment Questionnaire, and other outcomes. Serum testosterone, DHEA, and DHEAS levels were obtained and side effects noted monthly. RESULTS: Statistically significant improvements were found in all lupus outcomes over 6 months. Serum DHEA and DHEAS levels correlated with the dose of DHEA. Serum DHEA and DHEAS correlated negatively with SLAM score. A second order regression analysis of serum DHEAS level versus SLAM score suggested that the optimal serum level of DHEAS was 1000 microg/dl. The most common side effect was acne. CONCLUSION: The clinical response to DHEA was not clearly dose dependent. Serum levels of DHEA and DHEAS correlated only weakly with lupus outcomes, but suggested an optimum serum DHEAS of 1000 microg/dl. Monitoring these serum levels appears to have limited clinical utility.     

A randomized comparison of the efficacy and toxicity of epirubicin and doxorubicin in the treatment of patients with non-Hodgkin's lymphoma

BACKGROUND: Combination chemotherapy consisting of methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisolone, and bleomycin (MACOP-B) has been frequently used for the treatment of non-Hodgkin's lymphoma. This randomized study was undertaken to assess the efficacy and toxicity of this regimen when either doxorubicin or epirubicin was used as the anthracycline drug. METHODS: Between April 1989 and December 1993, 211 previously untreated patients with intermediate grade and high grade non-Hodgkin's lymphoma were randomized to receive either doxorubicin (n=106) or epirubicin (n=105) with the MACOP-B regimen. These patients were followed through December 1996. Numerous clinical features predictive of response and survival were analyzed. Cardiac and noncardiac toxicity in the two treatment arms were compared. RESULTS: The median age of the patients was 48 years. Complete remission was experienced by 122 patients (58.3%); 62 patients (58.5%) achieved complete remission in the doxorubicin arm and 60 (58.1%) in the epirubicin arm. Response rates, time to treatment failure, relapse data, and overall survival were comparable between the two arms. Morbidity due to mucositis, vomiting, peripheral neuropathy, and cardiotoxicity were also comparable. The overall mortality was 10%. Mortality due to neutropenic sepsis was considerably higher among patients who received epirubicin (10 patients) than among those who received doxorubicin (5 patients). Cardiac evaluation revealed no difference in toxicity between the two arms. CONCLUSIONS: Epirubicin was as effective as doxorubicin in terms of patients' responses to therapy. There was no difference in cardiotoxicity between the two treatment arms. However, in this study, the mortality due to neutropenic sepsis was significantly higher among patients treated with epirubicin.     

Synthesis and pharmacology of conformationally restricted raloxifene analogues: highly potent selective estrogen receptor modulators

The 2-arylbenzothiophene raloxifene, 1, is a selective estrogen receptor modulator (SERM) which is currently under clinical evaluation for the prevention and treatment of postmenopausal osteoporosis. In vivo structure-activity relationships and molecular modeling studies have indicated that the orientation of the basic amine-containing side chain of 1, relative to the stilbene plane, is an important discriminating factor for the maintenance of tissue selectivity. We have constructed a series of analogues of 1 in which this side chain is held in an orientation which is orthogonal to the stilbene plane, similar to the low-energy conformation predicted for raloxifene. Herein, we report on the synthesis of these compounds and on their activity in a series of in vitro and in vivo biological assays reflective of the SERM profile. In particular, we describe their ability to (1) bind the estrogen receptor, (2) antagonize estrogen-stimulated proliferation of MCF-7 cells in vitro, (3) stimulate TGF-beta3 gene expression in cell culture, (4) inhibit the uterine effects of ethynyl estradiol in immature rats, and (5) potently reduce serum cholesterol and protect against osteopenia in ovariectomized (OVX) rats without estrogen-like stimulation of uterine tissue. These data demonstrate that one of these compounds, LY357489,4, is among the most potent SERMs described to date with in vivo efficacy on bone and cholesterol metabolism in OVX rats at doses as low as 0.01 mg/kg/d.     

Hemodynamic effect of plasma DNA

To reveal the hemodynamic effect of plasma DNA, the authors measured the concentrations of plasma DNA, the length of its molecular fragments, and hemodynamic resistance/Toms effect. The Toms effect was detected in all blood samples from 10 healthy donors and 39 patients without acute stroke caused by atherosclerosis of the head great arteries with and without arterial hypertension. There was a clear inverse relationships between the plasma concentrations of DNA which had only long-molecular fragments in healthy persons and the hemodynamic resistance of its blood flow samples. The patient blood plasma had significant increased DNA concentrations but their molecular fragments were long and short. Inverse relationships between the plasma DNA concentration and the hemodynamic resistance of the patients' blood flow samples had a less correlation coefficient due to the high proportion of short DNA molecular fragments. The Toms effect was shown in the DNA solution prepared only from human funic blood where the DNA molecular fragments were long. The Toms effect was absent in the solutions prepared from the commercial cattle or salmon sperm DNA which contained shorter DNA molecular fragments. It is concluded that plasma DNA has a hemodynamic effect and the origin of long-molecular fragments of DNA which is typical for healthy young persons and short DNA molecular fragments that additionally appear in patients with vascular disorders is different.     

The concepts of quantum theory can be introduced into psychophysiology

Changes in the structural proteins and hydration during aging is responsible for altered skin morphologic and mechanical properties manifested as wrinkling, sagging, loss of elasticity, or apparent dryness. To gain insight into the age-related alterations in protein conformation and water structure, we obtained Raman spectra from the sun-protected buttock skin representing chronologic aging and the sun-exposed forearm skin representing combined effects of photoaging and chronologic aging. Ten aged individuals (five men, five women; age range 74-87) and 10 control young individuals (five men, five women; age range 22-29) entered the study. In the photoaged forearm skin the positions of protein-specific amide I, amide III, and CH stretching bands were shifted, suggesting increased protein folding. In contrast, major changes were seen only in the amide I peak in chronologically aged skin. The intensity of the 3250 cm(-1) OH stretching band was increased in photoaged skin (but not in chronologically aged skin) indicating an increased water content. R(v) representation of the low-frequency region of Raman spectra was applied to determine water structure. In the young skin and chronologically aged skin water was mostly present in the bound form. In the photoaged skin, however, an increase in intensity at 180 cm(-1) was noted, which reflects an increase in the not-protein bound water (tetrahedron water clusters). In conclusion, it seems that proteins in the photoaged skin are more compact and interact with water to limited degree. Impairment in protein hydration may add to the understanding of ultrastructural, mechanical, and biochemical changes in structural proteins in the aged skin.     

Gap junctional intercellular communication contributes to the contraction of rat osteoblast populated collagen lattices

The contraction of native collagen lattices by resident mesenchymal cells mimics the organization of collagen during development and repair. Lattice contraction is cell density dependent, suggesting that cell-to-cell communications may contribute to the process. This possibility was investigated by comparing lattice contraction by four rat osteoblastic cell lines: ROS 17/2.8 cells (ROS); ROS transfected with an antisense cDNA sequence of the gap junctional protein connexin 43 (RCx16); ROS transfected with connexin 45 cDNA, a connexin not normally expressed in ROS cells (ROS/Cx45); and ROS transfected with cDNA encoding carboxy-terminal truncated Cx45 (ROS/Cx45tr). The cell coupling indices, which reflect gap junctional communication, were quantitated by the fluorescent dye scrape loading. ROS cells were well coupled (index 3.0), ROS/Cx45tr were better coupled (index 4.2), ROS/Cx45 were poorly coupled (index 1.7), and RCx16 showed no coupling (index 1.1). As determined by immunoblotting, the level of connexin 43 protein was increased in both ROS/Cx45tr and ROS/Cx45 cell lines compared with ROS cells, while the level in RCx16 cells was reduced. ROS populated collagen lattices (PCLs) contracted significantly more at day 5 (177 mm2 to 67 mm2) than ROS/Cx45tr (84 mm2), ROS/Cx45 (108 mm2), or RCx16 (114 mm2). Myosin ATPase activity, which is required for lattice contraction, was equivalent in all four cell lines, indicating that it was not responsible for inhibiting PCL contraction. ROS cells in collagen appeared elongated compared with the other cell lines which were more rounded. These experiments suggest gap junctional communication contributes to PCL contraction by resident osteoblasts.