RNA as a source of biomarkers for amyotrophic lateral sclerosis

Metabolic Brain Disease - Amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease, leads to the loss of motor neurons. There are currently no effective therapies to treat this...     

Vascular endothelial growth factor expression and bone formation in posterior glenoid fossa during stepwise mandibular advancement.

This study assessed the amount of vascular endothelial growth factor (VEGF) expression and related the findings to new bone formation in the posterior glenoid fossa during stepwise mandibular advancement. A total of 250 female Sprague-Dawley rats, 35 days old, were randomly divided into 10 groups, each including 5 control and 20 experimental rats. Within each group, 10 experimental rats were fitted with functional appliances with a 1-step advancement of 3.5 mm. Another 10 were fitted with stepwise appliances with an initial advancement of 2 mm and a subsequent increase to 3.5 mm on day 30. The rats in the experimental groups were killed on days 3, 7, 14, 21, 30, 33, 37, 44, 51, and 60, respectively. The matched controls were killed on the same time points. Sections (7 microm) were cut through the glenoid fossa sagittally and stained with anti-VEGF antibody. VEGF expression in the posterior glenoid fossa was evaluated with a computer-assisted image-analyzing system. Both VEGF expression and new bone formation were greater in the experimental rats than in the controls. During stepwise advancement, initial VEGF expression was less than that of 1-step advancement, but the second advancement elicited another peak on day 44. New bone formation was also less than that of 1-step advancement during early stages of stepwise advancement but then began to increase from day 37 onward. The maximum increase was observed on day 60. Stepwise advancement of the mandible delivers mechanical stimuli that produce a series of tissue responses that lead to increased vascularization and bone formation.     

Antiproliferative Activity Against MCF‐7 Breast Cancer Cells by Diamino‐Triazaspirodiene Antifolates

Two triazaspirodienes, having similar phenoxy propyloxy side chain, were identified as potent mammalian dihydrofolate reductase inhibitors; one having a 6,5‐spiro bicyclic ring system (IC₅₀ = 2.3 nm ) and the other a 6,6‐spiro bicyclic system (IC₅₀ = 6.9 nm ). They also showed more than 50% antiproliferative activity against the MCF‐7 breast cancer cells at 20 μm . This study demonstrated the potential lead of the diamino‐triazaspirodienes in anticancer chemotherapeutical agents’ discovery.     

Pulmonary resection for metastases from colorectal cancer

Aim: The prognosis of patients with disseminated colorectal carcinoma is poor except for those with single organ pulmonary or hepatic metastases. The objective of the present study was to evaluate the result of pulmonary metastasectomy for colorectal secondary and to identify the prognostic factors. Methods: This was a retrospective study of 80 patients who had pulmonary metastasectomy for pulmonary secondary from colorectal carcinoma in Queen Elizabeth Hospital, Hong Kong. Results: The overall 5‐year and 10‐year survival rates of the entire cohort were 42.5% and 35.5%, respectively. High premetastasectomy carcinoembryonic antigen (> 20 μg/dL), short disease‐free interval (< 12 months) and incomplete resection were the independent prognostic factors. Neither the characteristics of the primary colorectal tumour nor the number of metastatic nodules had a significant contribution to the long‐term survival. Six patients underwent second pulmonary metastasectomy and three were still free from tumour recurrence after the second operation. Conclusion: Patients with pulmonary metastases from colorectal carcinoma would benefit from pulmonary metastasectomy. High premetastasectomy carcinoembryonic antigen and short disease‐free interval were negative predictive factors for survival. Long‐term follow‐up study is required, as recurrence can occur more than 5 years after pulmonary metastasectomy. Also, whether the survival benefit is due to surgical treatment effect or lead‐time bias remains undecided.     

The efficacy of 2 different dosages of methylphenidate in treating adults with attention-deficit hyperactivity disorder.

OBJECTIVE: To evaluate the efficacy of methylphenidate in treating adults with attention-deficit hyperactivity disorder (ADHD), using subjective (self-report) and objective (computerized test) measures. METHOD: This double-blind crossover trial of placebo vs methylphenidate included subjects with childhood and current ADHD symptoms, IQs above 80, no other psychiatric condition explaining their difficulties or requiring other treatment, and no substance abuse in the previous 6 months. We administered 10 mg 3 times daily of medication (that is, placebo or methylphenidate) for 2 weeks. On the final day, subjects completed self-report measures and were tested on computerized tests. We then increased dosage to 15 mg 3 times daily for 2 weeks and administered a complete reassessment on the final day. Following a 1-week washout, we repeated this process on the second medication (that is, placebo or methylphenidate). RESULTS: Thirty adults with ADHD participated. Self-report measures and computerized tests showed significant improvements in ADHD symptoms on methylphenidate, compared with placebo. Other psychiatric symptoms (notably, anxiety and depression) were alleviated with methylphenidate. There was no significant difference between the 2 dosages of methylphenidate. CONCLUSION: Methylphenidate is effective in improving ADHD symptoms in adults with ADHD, is well tolerated, and has minimal side effects.     

Effect of intravenous sedation on the outcome of transvaginal oocyte retrieval: a comparative study of propofol- and methohexital-based techniques

This study retrospectively compares patients who underwent outpatient transvaginal follicle aspiration with either a propofol- or methohexital-based intravenous sedation technique. Data collected from patient charts (n = 212) over a 46-month period were analyzed to determine the effects of each sedation technique on procedure and recovery times, number of retrieved ova, as well as rates of nausea, fertilization, cleavage, pregnancy, and delivery. All patients were included in the study, regardless of age or diagnosis. procedure time was lower in the propofol group (51 t 18 min) than in the methohexital group (61 I 20 min) (p > 0.01). Patients in the methohexital group (139 2 51 min) spent more time in the recovery room than did those in the propofol group (71 ? 34 min) (p > 0.01). The nausea rates were significantly lower in the propofol group compared with the methohexital group (1.9% vs. 14.4%, respectively) (p > 0.02). Fertilization rate in the propofol group was 77.7% and was 62.9% in the methohexital group (p > 0.01). The numbers of retrieved ova and the cleavage rates were similar in both groups. The rate of pregnancy in patients sedated with propofol (46.1%) was higher than the methohexital group (26.9%) (p > 0.02). Delivery rate was 38.5% in the propofol group and 20.6% in the methohexital group (p > 0.02). In summary, propofol intravenous sedation for transvaginal follicle aspiration was associ- ated with an improved outcome. Pregnancy and delivery rates were higher while nausea, an unpleasant side effect, was sharply reduced.     

Rabbit Liver Class III Alcohol Dehydrogenase: A Cathodic Isoform with Formaldehyde Dehydrogenase Activity

Electrophoresis of rabbit liver homogenate on starch gel followed by activity staining revealed multiple forms of alcohol dehydrogenase (ADH) which, based on their electrophoretic mobilities, had been tentatively labeled as class "I," class "II," and dass "III" ADHs. The class II enzyme has now been purified to homogeneity by ion exchange and affinity chromatography and, except for an isoelectric point of 7.7, close: resembles human class III ADH. It is a homodimer of molecular weight near 80,000 with a similar amino acid composition and comparable kinetic parameter for the oxidation of primary alcohols. Like the rat, human, and Escherichia coli class III ADHs, the rabbit enzyme is a glutathione-dependent formaldehyde dehydrogenase, and catalyzes the oxidation of S-hydroxymethylglutathione and the hemithiolacetal of 8-thiooctenolc acid. Ethanol up to 3 M does not saturate the enzyme, whereas longer chain primary alcohols exhibit Michaelis-Menten kinetics. Key Words: XX-ADH, FDH.     

Which treatment for whom for ADHD? Moderators of treatment response in the MTA

Using receiver operating characteristics, the authors examined outcome predictors (variables associated with outcome regardless of treatment) and moderators (variables identifying subgroups with differential treatment effectiveness) in the Multimodal Treatment Study of Children with Attention-Deficit/Hyperactivity Disorder (ADHD; MTA). Treatment response was determined using parent- and teacher-reported ADHD and oppositional defiant symptoms, with levels near or within the normal range indicating excellent response. Among 9 baseline child and family characteristics, none predicted but 3 moderated treatment response. In medication management and combined treatments, parental depressive symptoms and severity of child ADHD were associated with decreased rates of excellent response; when these 2 characteristics were present, below-average child IQ was an additional moderator. No predictors or moderators emerged for behavioral and community comparison treatments. The authors discuss conceptual and clinical implications of research on treatment moderators.