Scaling of movement velocity: a measure of neuromotor retardation in individuals with psychopathology

The combination of ifosfamide, carboplatin and etoposide (modified ICE), was evaluated for its toxicity and activity in relapsed or refractory aggressive non-Hodgkin's lymphoma. Twenty patients, 14-69 years of age, with relapsed (19 cases) or refractory (one case) aggressive non-Hodgkin's lymphoma were treated with modified ICE therapy, consisting of ifosfamide 6 g/m2 (1.2 g/m2 day 1-5), carboplatin 400 mg/m2 (day 1) and etoposide 500 mg/m2 (100 mg/m2 day 1-5). The regimen was repeated at approximately 28-day intervals. All patients had undergone a doxorubicin-containing regimen before modified ICE therapy. Median total dose of previously received doxorubicin was 406 mg/m2 (range: 200-825 mg/m2). The median interval from diagnosis to modified ICE therapy was 9.4 months (range: 3.6-121 months). Two patients achieved CR and five achieved PR out of 16 patients with measurable lesions (response rate 43.8%; 95% confidence interval 19.0-68.6%). Median overall survival was 227 days (range: 41-552 days) from the start of modified ICE therapy. Myelosuppression was the most serious toxicity, namely 16 patients (80%) and 11 patients (55%) showed grade 4 neutropenia and grade 4 thrombocytopenia after the first course, respectively. Modified ICE therapy might be an active regimen with acceptable toxicity as a salvage chemotherapy in aggressive non-Hodgkin's lymphoma.     

The Drosophila Medea gene is required downstream of dpp and encodes a functional homolog of human Smad4

The Transforming Growth Factor-beta superfamily member decapentaplegic (dpp) acts as an extracellular morphogen to pattern the embryonic ectoderm of the Drosophila embryo. To identify components of the dpp signaling pathway, we screened for mutations that act as dominant maternal enhancers of a weak allele of the dpp target gene zerkn?llt. In this screen, we recovered new alleles of the Mothers against dpp (Mad) and Medea genes. Phenotypic analysis of the new Medea mutations indicates that Medea, like Mad, is required for both embryonic and imaginal disc patterning. Genetic analysis suggests that Medea may have two independently mutable functions in patterning the embryonic ectoderm. Complete elimination of maternal and zygotic Medea activity in the early embryo results in a ventralized phenotype identical to that of null dpp mutants, indicating that Medea is required for all dpp-dependent signaling in embryonic dorsal-ventral patterning. Injection of mRNAs encoding DPP or a constitutively activated form of the DPP receptor, Thick veins, into embryos lacking all Medea activity failed to induce formation of any dorsal cell fates, demonstrating that Medea acts downstream of the thick veins receptor. We cloned Medea and found that it encodes a protein with striking sequence similarity to human SMAD4. Moreover, injection of human SMAD4 mRNA into embryos lacking all Medea activity conferred phenotypic rescue of the dorsal-ventral pattern, demonstrating conservation of function between the two gene products.     

Medical marijuana

To evaluate the use of high-resolution magnetic resonance imaging (MRI) for the differentiation of skin tumors in the maxillofacial region, 60 patients (25 female) were examined in a 1.5-T whole-body MR imager with a 2.5-cm surface coil. Plain transverse T1-(TR 500 ms, TE 25 ms), T2-(2200 ms, TE 80 ms), fat-(TR 500 ms, TE 28 ms), and water-suppressed (TR 500 ms, TE 38 ms) SE sequences were used. Following the application of the paramagnetic contrast agent Gd-DTPA, transverse T-weighted and fat suppression sequences were repeated. Before and after contrast administration, tumor signal intensities and percent contrast enhancement were determined by a ROI technique. All tumors were classified by standard histologic technique and evaluated with regard to their response to contrast medium. Quantitative evaluation was performed by three independent radiologists. Additionally, signal- and contrast-to-noise ratios were calculated for each tumor type. All MRI findings were compared with histology. Significant contrast enhancement occurred in most tumors; malignant tumors displayed inhomogeneous enhancement. The optimal pulse sequences for tumor delineation are plain T1-weighted, water-suppressed, and contrast-enhanced fat-suppressed sequences. Tumors could not be specified by signal intensities or percent contrast enhancement, and CNR did not allow for malignant lesions to be differentiated from benign tumors. High-resolution MRI proved to be an adequate method for imaging skin tumors and their inner structure. Tumor typing was not possible by either contrast-administration or modification of sequence parameters. In this regard, further innovations in contrast agent design seem to be necessary.     

Management-related risk factors for M. paratuberculosis infection in Michigan, USA, dairy herds

A cross-sectional study was conducted from June through December 1996 to identify management-related risk factors for herd-level M. paratuberculosis infection. Data were collected from 121 participating herds. A two-part questionnaire was administered to gather data on current and previous management practices and herd productivity. A random sample of cows aged > or = 24 months was selected from each herd and tested for antibodies to M. paratuberculosis using the IDEXX Antibody ELISA (sensitivity 64%, specificity 96%). A positive herd was one in which > or = 2 animals tested positive for antibodies to M. paratuberculosis. A negative herd was one in which no animal tested positive. Herds in which only one animal tested positive were dropped from statistical analysis to reduce the risk of including false-positive herds in the statistical analyses. There were 80 herds with one or more positive animals and 41 herds with no positive animals in the sample (66% herd-level prevalence). Twenty-six herds (21%) were dropped from further analyses because they had only one positive cow. Twelve herds (10%) were dropped from analysis because of missing data. The resulting sample used for statistical modeling included 46 positive herds and 37 negative herds (55% herd-level prevalence). A multi-variable logistic-regression model was used to evaluate the results. The variable 'use of an exercise lot for lactating cows' was associated with a three-fold increase in odds of a herd being positive for M. paratuberculosis infection (O.R. = 3.01, C.I. = 1.03-8.80); 'cleaning of maternity pens after each use' was associated with a three-fold reduction in odds of a herd being positive for M. paratuberculosis infection (O.R. = 0.28, C.I. = 0.08-0.89); 'application of lime to pasture areas in 1993' resulted in a ten-fold decrease in odds of a herd being positive for M. paratuberculosis infection (O.R. = 0.10, C.I. = 0.02-0.56).     

Effects of aging, diet, and sex on plasma glucose, fructosamine, and lipid concentrations in barrier-raised Fischer 344 rats

We studied the relationships of plasma glucose, fructosamine, triglycerides, and cholesterol as a function of age, gender, and diet in barrier-raised Fischer 344 rats aged 5 to 26 months, fed a diet either ad libitum or restricted to 60% of the ad libitum caloric intake. The complex relationships of these plasma levels to age, gender, and diet led to the development of a model with age, diet, and sex as covariates. Overall, fasting plasma glucose concentrations were reduced by approximately 25% in rats on the restricted diet, compared to ad libitum-fed animals. There was a significant age-dependent decline in glucose levels in male animals, whereas in females there was an increase in plasma glucose with aging. Plasma fructosamine levels in calorie-restricted animals, overall, were reduced by 7% compared to levels in animals fed ad libitum. There was a significant positive correlation between plasma glucose and fructosamine levels. Mean plasma triglyceride content was decreased by 50% in calorie-restricted rats compared to ad libitum-fed animals. A significant decrease in triglyceride levels with increasing age was seen in male animals, and an increase with aging in females. There was a significant positive correlation between plasma glucose and triglyceride levels. Plasma cholesterol levels in calorie-restricted animals were reduced by 7% compared to levels in ad libitum-fed animals. An increase of cholesterol concentration with aging was significant in both males and females. Analysis of the data showed that there were significant differences between male and female Fischer 344 rats in the response of plasma glucose and fructosamine to aging and calorie restriction. Changes of plasma triglyceride and cholesterol with aging and dietary calorie restriction were also different in males and females. Studies of the effect of aging on glycemia and blood lipid content should take into account the contributions of animal sex.     

Nasopharyngeal carcinoma with intracranial spread: CT and MR characteristics

PURPOSE: Nasopharyngeal carcinoma (NPC) frequently spreads intracranially. We compare CT and MRI in identifying intracranial spread and reexamine the route of infiltration. METHOD: One hundred fourteen consecutive patients with proven NPC were evaluated prospectively with T1-, T2-weighted, contrast-enhanced MRI and CT. RESULTS: MRI showed 35 (31%) patients with middle cranial fossa involvement. Twenty-nine (25%) patients had cavernous sinus infiltration, while six (5%) showed only dural thickening. The most common route of spread is through the foramen ovale (FO) (12/35 patients, 34%), followed by skull base destruction (6/35 patients, 17%), foramen lacerum (FL) (6/35 patients, 17%), sphenoid sinus (6/35 patients, 17%), and combined FO and FL (5/35 patients, 14%). Using MRI as a standard, CT demonstrated the following involvement: cavernous sinus in 26 of 29 (90%) patients, FO in 9 of 12 patients, skull base in 6 of 6 patients, FO and FL in 3 of 5 patients, FL in 6 of 6 patients, sphenoid sinus in 6 of 6 patients and dura in 0 of 18 patients. CONCLUSION: It is believed that NPC most commonly spreads intracranially via the FL or by direct erosion. Perineural spread through the FO is an important route, which explains why with CT evidence of cavernous sinus involvement there may be no skull base erosion. These findings are best seen on MRI.     

Gene therapy for malignant gliomas

Malignant gliomas are attractive targets for gene therapy because of their relatively well-localized distribution. Several new strategies have been devised that target different aspects of glioma biology. Gene transfer can be used to synthesize chemotherapy drugs that block DNA synthesis within these highly mitotic tumors. New genes can be introduced that restore the functions of mutated tumor suppressor genes or block the molecular pathways needed for tumor angiogenesis. Alternatively, the immune response to these tumors can be augmented by the local production of cytokines. Finally, viruses themselves can be used as tumoricidal agents by designing viruses that selectively replicate and destroy tumor cells. The advantages and limitations of these approaches are discussed in the context of their possible application to the treatment of these highly lethal malignancies.