Effects of raloxifene in a guinea pig model for leiomyomas

OBJECTIVE: Chronic exposure of oophorectomized guinea pigs to 17beta-estradiol causes leiomyoma formation. Our aims were to determine whether these leiomyomas can become estradiol independent after exposure to estradiol and if raloxifene inhibits leiomyoma growth when given concomitantly with estradiol. STUDY DESIGN: To induce leiomyoma development, 6 oophorectomized animals received two estradiol implants for 140 days. Next, the estradiol implants were replaced with empty implants in 3 animals, whereas the other 3 received 2 new estradiol implants and raloxifene given per os 10 mg/kg per day for 60 days. Tumor size was monitored biweekly by ultrasonography. RESULTS: On estradiol removal, abdominal wall leiomyomas regressed within 15 to 30 days; when estradiol implants were reintroduced, leiomyomas redeveloped. Within 30 days on raloxifene, all abdominal leiomyomas (n = 9) regressed as determined by ultrasonography and verified at laparotomy. Serum raloxifene and estradiol levels were 432 +/- 46 pg/mL and 78 +/- 13 pg/mL (mean +/- SEM, n = 3), respectively, after 60 days of treatment. CONCLUSIONS: Leiomyomas did not become estradiol independent, even after long exposure to estradiol; ultrasonography allowed frequent, noninvasive assessment of leiomyoma size, and raloxifene rapidly regressed leiomyomas in this animal model.     

Effects of readiness for drug abuse treatment on client retention and assessment of process

AIMS: This study examined client motivation as a predictor of retention and therapeutic engagement across the major types of treatment settings represented in the third national drug abuse treatment outcome study (DATOS) conducted in the United States. DESIGN: Sequential admissions during 1991-93 to 37 programs provided representative samples of community-based treatment populations. Based on this naturalistic non-experimental evaluation design, hierarchical linear model (HLM) analysis for nested data was used to control for systematic variations in retention rates and client attributes among programs within modalities. SETTING: The data were collected from long-term residential (LTR), outpatient methadone (OMT) and outpatient drug-free (ODF) programs located in 11 large cities. PARTICIPANTS: A total of 2265 clients in 18 LTR, 981 clients in 13 OMT and 1791 clients in 16 ODF programs were studied. MEASUREMENTS: Pre-treatment variables included problem recognition and treatment readiness (two stages of motivation), socio-demographic indicators, drug use history and dependence, criminality, co-morbid psychiatric diagnosis and previous treatment. Retention and engagement (based on ratings of client and counselor relationships) served as outcome criteria. FINDINGS: Pre-treatment motivation was related to retention in all three modalities, and the treatment readiness scale was the strongest predictor in LTR and OMT. Higher treatment readiness also was significantly related to early therapeutic engagement in each modality. CONCLUSIONS: Indicators of intrinsic motivation--especially readiness for treatment--were not only significant predictors of engagement and retention, but were more important than socio-demographic, drug use and other background variables. Improved assessments and planning of interventions that focus on stages of readiness for change and recovery should help improve treatment systems.     

Differential expression of extracellular matrix remodeling genes in a murine model of bleomycin-induced pulmonary fibrosis

PURPOSE: To prospectively analyze the value of fast, dynamic, subtraction magnetic resonance (MR) imaging in the characterization of musculoskeletal tumors. MATERIALS AND METHODS: In 175 consecutive patients with a musculoskeletal mass, dynamic contrast-enhanced subtraction MR imaging was performed after administration of 0.1 mmol per kilogram of body weight gadopentetate dimeglumine or gadoteridol. A turbo gradient-echo technique was used, with a temporal resolution of 1-3 seconds. The interval between arterial and early tumor enhancement, the pattern (peripheral or diffuse) of enhancement, and the progression of tumor enhancement, as visualized on time-signal intensity curves, were assessed. MR enhancement features were related to the histopathologic diagnoses. RESULTS: Differentiation of benign from malignant soft-tissue masses was possible with a sensitivity of 91% and specificity of 72% based on start of enhancement, a sensitivity of 73% and specificity of 97% based on peripheral or diffuse enhancement, and a sensitivity of 86% and specificity of 81% based on progression of enhancement. Benign bone tumors could not be accurately differentiated from malignant bone tumors on the basis of the three defined parameters (sensitivity, 63%-76%; specificity, 50%-76%). CONCLUSION: Dynamic, contract-enhanced, subtraction MR images may be useful to differentiate malignant from benign soft-tissue masses.     

Dominant host range selection of vaccinia recombinants by rescue of an essential gene

The intergeniculate leaflet (IGL) is a distinct division of the lateral geniculate complex that participates in the regulation of the circadian rhythm through its projections to the circadian pacemaker located in the suprachiasmatic nuclei of the hypothalamus. A high number of neuropeptide Y (NPY) cell bodies has been described in the IGL by immunohistochemistry and in situ hybridization. The present study investigated whether NPY in the IGL is influenced by the length of the daily photoperiod. By using in situ hybridization we show a significant increase of the number of NPY mRNA containing neurons in the mid-part of the IGL of Syrian hamsters maintained in a short photoperiod compared to those kept in a long photoperiod. On the other hand, NPY mRNA expression per cell in the IGL is similar in both photoperiods tested.     

Effect of pneumatic dilation on gastroesophageal reflux in achalasia

The aims of this study were to assess the effect of pneumatic dilation on gastroesophageal reflux in achalasia, differentiate esophageal acid due to lactate from acid due to gastroesophageal reflux, and determine if chest pain and heartburn are reliable indicators of gastroesophageal reflux. Eight untreated achalasia patients underwent pre- and postdilation esophageal fluid/food residue lactate and pH analysis, esophageal manometry, 24-hr pH monitoring, and symptom assessment. All patients had a successful clinical outcome and a decrease in lower esophageal sphincter pressure from 29.1 +/- 12.7 to 14.7 +/- 3.8 mm Hg (mean +/- SD; P = 0.04). Abnormal acid exposure was present in two patients before and two patients after dilation. Postdilation acid exposure was mild. Lactate was detected before dilation in all patients. A lactate concentration >2 mmol/liter was associated with acidic residue and one abnormal 24-hr pH profile. There was no correlation between an abnormal 24-hr pH test and age, lower esophageal sphincter pressure, or duration of symptoms prior to treatment. Chest pain and heartburn were unrelated to drops in pH. Gastroesophageal reflux is rare in untreated achalasia and esophageal acidity may result from ingestion of acidic foods or production of lactate. Mild gastroesophageal reflux occurs after dilation but is of no clinical significance. Chest pain and heartburn are not indicators of acid reflux in achalasia.     

Estimation of fiber diameters in the spinal dorsal columns from clinical data

In the rat cerebellar slice preparation in vitro, excessive DL-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA)-receptor activation elicits a characteristic type of excitotoxicity of Purkinje cells (PCs) known as dark cell degeneration (DCD). DCD models neurotoxicity of PCs and hippocampal pyramidal neurons in vivo following hyperexcitable states. The intent of this study was to: a) determine whether AMPA-induced neurotoxicity of PCs is correlated with temporally and spatially restricted rises in intracellular Ca2+ and b) whether GYKI 52466 and nominal external Ca2+, conditions that reduced expression of AMPA-elicited DCD, altered the induced Ca2+ patterns. Employing the Ca2+-sensitive dye Fluo-3 and a confocal laser scanning microscope, we evaluated changes in intracellular Ca2+ within PCs in a cerebellar slice preparation. AMPA application alone (30 microM for 30 min) caused a significant initial rise in perinuclear and cytoplasmic Ca2+ that returned to control levels during the latter part of the AMPA exposure period. Following removal of AMPA (expression period), perinuclear and cytoplasmic Ca2+ displayed a significant delayed rise peaking transiently 60 min after AMPA removal. The efficacy of GYKI 52466 and nominal external Ca2+ conditions to attenuate AMPA-induced DCD was correlated to reductions in AMPA-induced transient elevations in perinuclear and cytoplasmic Ca2+ levels during the expression phase and to a lesser extent during the exposure period. The present data suggest that during the expression phase, the delayed perinuclear and cytoplasmic Ca2+ transient may be the harbinger of impending loss of Ca2+ homeostasis and cell damage.     

Cerebral ischemia in patients with hepatitis C virus infection and mixed cryoglobulinemia

We describe two women (ages 35 and 36 years) with cerebral ischemia, hepatitis C virus, and mixed cryoglobulinemia. One patient (case 1) was in otherwise good health when left parietal cerebral infarction developed, and she was found to have narrowing of the supraclinoid internal carotid artery siphon, anterior cerebral artery A1, and middle cerebral artery M1 segments bilaterally. Subsequent evaluation revealed abnormal liver enzymes, mixed cryoglobulinemia (type III), hypocomplementemia, and a high positive test result for rheumatoid factor. In the other patient (case 2), cerebral ischemia and seizures developed in the setting of previously documented mixed cryoglobulinemia (type II), membranoproliferative glomerulonephritis, and hypocomplementemia. In this patient, a brain biopsy demonstrated cerebral infarction. Hepatitis C virus infection was confirmed in both patients by polymerase chain reaction detection of hepatitis C virus RNA. These two cases document the occurrence of cerebral ischemia in patients with hepatitis C virus infection and mixed cryoglobulinemia. Testing for hepatitis C virus and cryoglobulins should be considered in selected patients with cerebral ischemia of inobvious cause.     

The role of dornase alfa in the treatment of cystic fibrosis

For morphometric studies, sections have been stained with the Luxol fast blue-PAS-Hematoxylin (LPH) staining method after secondary fixation with chromic acid followed by embedding in Celloidin to measure the area of nerve cells or axons with the help of an image analyzer and a microscope. However, the manufacture of Celloidin has been suspended in Japan. Therefore, we studied the use of Shiojirin E-10 (10% nitrocellulose ether alcohol solution) as a substitute embedding material, and compared it with Celloidin from the viewpoint of tissue shrinkage and staining characteristics. Regarding the shrinkage ratio of LPH-stained sections of human cauda equina, there was no practical difference in the axonal areas (p < 0.01) between Celloidin sections (4.31 +/- 2.55 microns2) and Shiojirin E-10 sections (4.14 +/- 2.20 microns2). Regarding staining characteristics, we introduced a hue analysis method using computerized digital signals converted from pictures of stained sections taken by a videocamera. For the evaluation of hue, we examined the H-E sections of mouse liver and kidney, and the LPH sections of the human cauda equina. The hematoxylin hues of the H-E sections were 295 degrees for Celloidin and 294 degrees for Shiojirin E-10. Eosin hues of the E-E sections were 320 degrees for both embedding material. The axonal hues of the LPH stain were 254 degrees for Celloidin and 251 degrees for Shiojirin E-10. Myelin sheath hues were 224 degrees for both embedding material. According to our results, Shiojirin E-10 can be substituted for Celloidin from the qualitative and quantitative viewpoints in the morphologic studies.