Myoblast transfer in duchenne muscular dystrophy

One biceps muscle of 8 patients with Duchenne muscular dystrophy was injected at 55 sites with a total of 55 million viable, purified, and contamination-free normal myoblasts (myoblast transfer). The other biceps of each patient was injected with a placebo to serve as a control. The procedure was blinded to the patients, parents, and investigators. Myoblasts derived from a biopsy specimen of the fathers were cultured and purified under strict conditions and carefully screened for microbial contamination. All patients received cyclophosphamide for immunosuppression for 6 or 12 months. No serious complications were observed after myoblast transfer, indicating that the procedure is safe. The overall therapeutic efficiency of myoblast transfer was poor as judged by the results in maximal voluntary force generation, dystrophin content of the muscle, magnetic resonance imaging of the muscle, and the lack of donor-derived DNA and dystrophin messenger RNA in the injected muscle. An improved efficiency of the take of myoblasts might be achieved by using younger cells and injecting the myoblasts with a myonecrotic agent (to increase the prevalence of regeneration) and a basal laminal fenestrating agent.     

The Dartmouth Health Promotion Study: A Failed Quest for Synergy in School Health Promotion

ABSTRACT: The Dartmouth Health Promotion Study was a longitudinal, quasi-experimental field study with a qualitative research arm, designed to learn whether coordinating school health instruction, health services, and a healthful environment enhanced the program's effect on the heart health and mental health of children. The research strategy — the Coordinated Approach — was applied to approximately 300 children in each of two cohorts in grades four to six attending nine trial schools; a further 600 children attended 10 comparison schools in Dartmouth and nine distal comparison schools. Although the qualitative analysis demonstrated that positive feelings were engendered in most areas of the study, when either the classroom or the individual was used as the unit of analysis, the Coordinated Approach did not have a more favorable effect on the heart or mental health of children than did the standard school health program. Thus, the effect of an existing school health program was not directly enhanced through coordinating its components.     

The dietary intake of homeless males sleeping rough in Central London

Data concerning the food and beverage intake (including alcohol) of 79 males, aged 19–50 years, sleeping rough in Central London, who did not appear to be under the influence of drink, drugs or suffering from mental illness were collected by prompted 24-h recall and food-frequency questionnaire (FFQ). The source of food was noted and the subjects were asked about food availability and food needs. The group had intakes significantly lower than Dietary Reference Values (DRV) for the UK for energy, carbohydrate, non-starch polysaccharides (NSP), folate, zinc and magnesium. Significantly higher values were seen for protein, fat, vitamin B₁₂, calcium and iron. Alcohol intake was higher than that assumed to approximate current intakes of the UK population. Mean macronutrient intakes for the group were similar to means for British adult men (OPCS, 1990), only protein and NSP were significantly lower. The FFQ showed very low consumption/week of fruit, vegetables, salad, fruit juice and wholewheat/brown products. Organized charities provided the major source of food energy for the group as a whole. Self-supplied sources provided the major source of total energy. It is suggested that the group may benefit from an increase in dietary fibre and energy, with an increase in the proportion of energy supplied by carbohydrate and a reduction in energy from fat and alcohol. A varied supply of food and hot meals during weekends as well as during the week may benefit the group both aesthetically and nutritionally. It may be advisable to increase the supply of wholemeal/brown bread, fruits, vegetables and salad foods without decreasing the energy content of the food available.     

Down-Regulation of Estrogen Receptor Immunoreactivity by 17β-estradiol in the Guinea Pig Forebrain

Low amplitude pulses of estradiol-17β (E₂-17β) are more effective than large single bolus injections or constant exposure to E₂-17β in inducing progesterone-facilitated sex behavior in female rats and guinea pigs. The present study examined whether the increased responsiveness to E₂-17β is due to an increase in the number of estrogen receptors in the estrogen receptor rich areas of the hypothalamus and amygdala. Initial studies examined the rapid effects (20 min) of a high dose of E₂-17β (50 μg) on estrogen receptor immunostaining using either the H222 antibody or the ER 21 antiserum. ER 21 immunostaining was not affected by the E₂-17β treatment suggesting that it binds to both occupied and unoccupied estrogen receptors. Therefore the ER 21 antiserum was used to characterize the regulation of estrogen receptor immunoreactivity (ER-IR) by E₂-17β. ER-IR was examined for 48 h and serum E₂-17β for 24 h following a 2 μg s.c. injection of E₂-17β (a dose similar to that used in multiple pulse paradigms). Serum E₂-17β peaked 15 to 30 min following the injection and returned to baseline values by 1 h. In all but one area maximal suppression of ER-IR occurred at 12 h. In summary, 1) decreases in estrogen receptor immunoreactivity following E₂-17β are consistent with studies in which estrogen receptors were assayed by binding assays and estrogen receptor mRNA was determined by in situ hybridization; 2) the ER 21 antiserum is able to detect both occupied and unoccupied estrogen receptors and 3) H222 immunoreactivity is influenced by the presence of E₂-17β, so that the level of H222-IR is a reflection of ligand/receptor binding dynamics. The data suggest that up-regulation of estrogen receptors does not account for the increase in behavioral sensitivity which is observed following multiple pulses of E₂-17β.     

Recurrent aphthous ulcers in association with HIV infection. Diagnosis and treatment.

Recurrent aphthous ulcers in patients with HIV infection can cause significant morbidity, which makes successful diagnosis and treatment imperative. We have found that the diagnostic paradigm for recurrent aphthous ulcers in HIV-seronegative patients, which is based on the ulcers' clinical appearance, location, absence of other ulcer-causing pathogens or pathogenic processes, and response to therapy, may be successfully applied to recurrent aphthous ulcers in HIV-infected patients. However, one must be alert for ulcers with uncommon causes as well as ulcers with common causes that have atypical clinical appearances that may mimic recurrent aphthous ulcers. The topical glucocorticoids, which are used to treat recurrent aphthous ulcers in HIV-seronegative patients, proved very effective in HIV-infected patients for treatment of herpetiform and minor ulcers and most major ulcers and were without notable side effects. A few severe cases of major recurrent aphthous ulcers required treatment with systemic prednisone, and some side effects were encountered.     

Methotrexate for the treatment of unruptured tubal pregnancy: a prospective nonrandomized study.

BACKGROUND AND OBJECTIVES: The aim of this study was to compare in a prospective nonrandomized study, the efficacy of 2 methods of administering methotrexate (MTX) in the treatment of ectopic pregnancy (EP): transvaginal injection under sonographic control or intramuscular injection (IM). METHODS: Patients with EP who met specific inclusion criteria for medical treatment were treated with MTX: 63 patients (group 1) were treated by IM and 47 patients (group 2) by transvaginal local injection. In group 1, 50 mg/m2 of MTX was injected intramuscularly; in group 2, transvaginal injection of 1 mg/kg of MTX was injected into the ectopic sac under sonographic control. When an additional dose of MTX was required, it was administrated IM at the dosage of 50 mg/m2 in both groups. RESULTS: The overall success rate, defined by a posttreatment normal hCG level (< 10 mUI/mL) was 71.4% in group 1 versus 91.5% in group 2 (P < 0.01); for patients with hCG levels < 2000 mUI/mL, 83% and 96%, respectively (not significant); for patients with hCG > or = 2000 mUI/mL, 37.5% and 86.4%, respectively (P < 0.01). CONCLUSION: In the medical treatment of EP, the efficacy of MTX is greater when administered by local transvaginal injection than by IM injection. We propose local treatment every time EP can be punctured, especially when hCG levels are > or = 2000 mUI/mL.