Perinatal asphyxia in the rat has lifelong effects on morphology, cognitive functions, and behavior

Perinatal asphyxia (PA) is a major determinant of neurological morbidity and mortality in the neonatal period. Many studies have been investigating neurological deficits following PA, including seizures, cerebral palsy, mental retardation, as well as psychiatric deficits. Most research performed so far has been focusing on acute or subacute sequelae and has uncovered a variety of morphological, neurochemical, behavioral, and cognitive changes following PA. However, information on long-term sequelae of animals that underwent a period of PA is scanty. Perinatally asphyxiated rats at the end of their life span present with immunohistochemical and synaptic changes as well as changes in brain protein expression. Furthermore, deficits in cognitive function tested in the Morris water maze and changes in social behavior were described. In this review, we are summarizing and discussing reported effects of global PA on morphology, cognitive functions, and behavior in rats at the end of their life span.     

A probabilistic functional atlas of the human subthalamic nucleus

This paper introduces a method for generation and validation of a probabilistic functional brain atlas of subcortical structures from electrophysiological and neuroimaging data. The method contains three major steps: (1) acquisition of pre, intra, and postoperative multimodal data; (2) selection of an accurate data set for atlas generation; and (3) generation of the atlas from the selected data set. The method is applied to construct the probabilistic functional atlas of the human subthalamic nucleus (STN). The STN atlas has been built from data collected during surgical treatment of 184 patients with Parkinson’s disease. It is based on preoperative X-ray ventriculography imaging, intraoperative electrophysiological measurements and X-ray imaging, and postoperative neurological assessment. The atlas features a high resolution of 0.25 mm³ and a high accuracy of 0.25 mm. It is dynamic and can be rapidly recalculated for arbitrary resolution and extended by adding new patient data. The atlas can easily be reformatted and warped to match patient-specific data. Its applications include planning of subthalamic stimulations and neuroscience research to study functional properties of the STN. The presented method is general and can be applied for constructing human and animal probabilistic brain atlases.     

Patient with partial trisomy 9q and learning disability but no pyloric stenosis

Partial trisomy of the long arm of chromosome 9 represents a very rare and heterogeneous group of chromosomal aberrations. Associated clinical features include learning disability and pyloric stenosis. We present the first patient to be reported with a duplication of the chromosome region 9q22.1-->q33. The patient (female, age 17 years) presented with growth retardation, microcephaly, facial dysmorphia, oesophageal atresia, aortic stenosis, ventricular septal defect, atrial septal defect II, hypothyroidism, and learning disability, but no pyloric stenosis. A review of all cases of partial trisomy 9q reported in the literature demonstrates that learning disability is a characteristic feature of this group of chromosomal aberrations. However, there are cases of duplications of the same chromosome 9 material, with and without pyloric stenosis. This study provides new information for future genetic counselling, especially in cases of prenatal diagnosis of partial trisomy 9q.     

Clozapine in drug induced psychosis in Parkinson's disease: a randomised, placebo controlled study with open follow up

OBJECTIVE: To compare the efficacy and safety of clozapine in drug induced psychosis in Parkinson's disease (PD). METHODS: A four week, randomised, double blind, parallel comparison of clozapine and placebo, followed by a 12 week clozapine open period, plus a one month period after drug discontinuation, in 60 patients with PD. The primary efficacy outcome was the "clinical global impression scale" (CGI); the positive subscore of the "positive and negative syndrome scale" (PANSS) was used as the secondary efficacy parameter and the "unified Parkinson's disease rating scale" (UPDRS) and the "mini mental test examination" (MMSE) as safety outcomes. RESULTS: The mean (SD) dosage of clozapine was 35.8 (12.5-50) mg at the end of the double blind period. The mean (SD) scores on the CGI improved by 1.8 (1.5) for the clozapine group compared with 0.6 (1.1) for the placebo group (p = 0.001). The mean (SD) positive subscore of PANSS improved by 5.6 (3.9) for the clozapine group (0.8 (2.8) for the placebo group; p < 0.0001). At the end of the open period, 25 patients had completely recovered from delusions and hallucinations, and 19 experienced a relapse within one month after the clozapine washout period. The UPDRS motor and MMSE mean scores did not change significantly in either group. Somnolence was more frequent with clozapine than with placebo. CONCLUSIONS: Clozapine at a mean dose lower than 50 mg/day improves drug induced psychosis in PD without significant worsening of motor function, and the effect wears off once the treatment stops.     

Primary care residents' characteristics and motives for providing differential medical treatment of cervical cancer screening

BACKGROUND: Cervical cancer screening rates in the United States are sub-optimal. Physician factors likely contribute to these lower rates. Previous studies provide inconclusive evidence about the association between physician characteristics and the likelihood of addressing cervical cancer. This report assesses potential mechanisms that explain why certain providers do not address cervical cancer screening. METHODS: One hundred primary care residents from various specialties were asked to indicate the preventive topics they would address with a hypothetical white female in her early 20s, who was portrayed as living a "high risk" lifestyle, and visiting her provider only for acute care reasons. RESULTS: Among the provider characteristics assessed, only residents' ethnicity was associated with the likelihood of and time spent addressing cervical cancer screening. In particular, Asian-American residents were least likely to address cervical cancer, while African-American residents were most likely. A mediation analyses revealed that perceived barriers for addressing cervical cancer accounted for this difference. CONCLUSIONS: Study results suggest that there may be cultural factors among health care providers that may account for differential referral and treatment practices. Findings from this study may help identify factors that explain why cervical cancer screening rates are not higher.     

Effect of genital prolapse on assessment of bladder neck mobility by the Q-tip test

OBJECTIVE: To investigate the effect of vaginal prolapse and bladder fullness on Q-tip test assessment of urethral mobility. METHODS: Twenty-six women with genital prolapse to or beyond the hymen and undergoing urodynamics for urogynecologic dysfunction were assessed by the Q-tip test. Measurements were obtained with the bladder empty, with and without the prolapse reduced by the posterior blade of a Graves speculum. Angles were repeated at bladder capacity. Measured Q-tip angles were compared using the Wilcoxon signed rank test. RESULTS: Q-tip angles were significantly altered by vaginal prolapse and bladder fullness. With an empty bladder, the median Q-tip angle measured with the prolapse reduced was significantly less than that measured without reduction (53 degrees, interquartile range 25-65, versus 68 degrees, interquartile range 45-75; P <.001). With a full bladder, similar but lesser results were obtained (33 degrees, interquartile range 15-55 [reduced] versus 48 degrees, interquartile range 31-60 [unreduced]; P <.001). The median Q-tip angle with an empty bladder was greater than that with a full bladder. With the prolapse reduced, the Q-tip angle was 53 degrees (interquartile range 25-65) with an empty bladder versus 33 degrees (interquartile range 15-55) with a full bladder (P <.001). Without the prolapse reduced, the median Q-tip angle was 68 degrees (interquartile range 45-75) with an empty bladder and 48 degrees (interquartile range 31-60) with a full bladder (P <.001). CONCLUSION? Measurement of urethral mobility by the Q-tip test is significantly affected by genital prolapse. Q-tip angles are less with the reduction of vaginal prolapse and with the bladder full. Standardization of measurement technique is necessary for the development of clinical management recommendations.     

Pharmacokinetics and pharmacodynamics of single-chain recombinant human follicle-stimulating hormone containing the human chorionic gonadotropin carboxyterminal peptide in the rhesus monkey

Objective: To compare the pharmacokinetics of a long-acting FSH analog containing the hCG-β carboxyterminal peptide (recombinant hFSH–CTP) with native recombinant hFSH and describe the pharmacodynamics of recombinant hFSH–CTP after SC injection in female rhesus monkeys.

Design: Rhesus monkey study.

Setting: Academic research environment.

Animal(s): Ten female rhesus monkeys.

Intervention(s): Recombinant hFSH and recombinant hFSH–CTP were administered via a single SC or IV dose to rhesus monkeys, and serial phlebotomy was performed (n = 2 and N = 4 for SC recombinant hFSH and recombinant hFSH–CTP, respectively; for IV dosing, N = 1 in each group). An additional two monkeys were pretreated with SC ganirelix and received SC recombinant hFSH–CTP after confirmation of pituitary suppression.

Main Outcome Measure(s): Plasma disappearance rate of recombinant hFSH and recombinant hFSH–CTP and serum estradiol levels.

Result(s): The elimination half-life of recombinant hFSH–CTP was twofold and fourfold longer than that for recombinant hFSH after SC and IV dosing, respectively. The absorption half-life was approximately threefold longer for recombinant hFSH–CTP than for recombinant hFSH after SC administration. Recombinant hFSH–CTP stimulates estradiol secretion for 5–7 days after an isolated SC dose.

Conclusion(s): Addition of the hCG-β carboxyterminal peptide to hFSH-β results in an FSH analog with longer absorption and elimination half-lives compared with native hormone. This analog is capable of prolonged ovarian stimulation in rhesus monkeys after an isolated SC injection.     

Soy isoflavones in the treatment of prostate cancer

Epidemiological studies suggest an inverse association between soy intake and prostate cancer (Pca) risk. We have previously observed that soy isoflavone genistein induces apoptosis and inhibits growth of both androgen-sensitive and androgen-independent Pca cells in vitro. To determine the clinical effects of soy isoflavones on Pca we conducted a pilot study in patients with Pca who had rising serum prostate-specific antigen (PSA) levels. Patients with Pca were enrolled in the study if they had either newly diagnosed and untreated disease under watchful waiting with rising PSA (group I) or had increasing serum PSA following local therapy (group II) or while receiving hormone therapy (group III). The study intervention consisted of 100 mg of soy isoflavone (Novasoy) taken by mouth twice daily for a minimum of 3 or maximum of 6 mo. Forty-one patients were enrolled (4 in group I, 18 in group II, and 19 in group III) and had a median PSA level of 13.3 ng/ml. Thirty-nine patients could be assessed for response. Soy isoflavone supplementation was given for a median of 5.5 (range 0.8-6) mo per patient. Although there were no sustained decreases in PSA qualifying for a complete or partial response, stabilization of the PSA occurred in 83% of patients in hormone-sensitive (group II) and 35% of hormone-refractory (group III) patients. There was a decrease in the rate of the rise of serum PSA in the whole group (P = 0.01) with rates of rise decreasing from 14 to 6% in group II (P = 0.21) and from 31 to 9% in group III (P = 0.05) following the soy isoflavone intervention. Serum genistein and daidzein levels increased during supplementation from 0.11 to 0.65 microM (P = 0.00002) and from 0.11 to 0.51 microM (P = 0.00001), respectively. No significant changes were observed in serum levels of testosterone, IGF-1, IGFBP-3, or 5-OHmdU. These data suggest that soy isoflavones may benefit some patients with Pca.     

The efficacy and safety of Dermagraft in improving the healing of chronic diabetic foot ulcers: results of a prospective randomized trial

OBJECTIVE: To determine if a human fibroblast-derived dermal substitute could promote the healing of diabetic foot ulcers. RESEARCH DESIGN AND METHODS: A randomized, controlled, multicenter study was undertaken at 35 centers throughout the U.S. and enrolled 314 patients to evaluate complete wound closure by 12 weeks. Patients were randomized to either the Dermagraft treatment group or control (conventional therapy). Except for the application of Dermagraft, treatment of study ulcers was identical for patients in both groups. All patients received pressure-reducing footwear and were allowed to be ambulatory during the study. RESULTS: The results demonstrated that patients with chronic diabetic foot ulcers of >6 weeks duration experienced a significant clinical benefit when treated with Dermagraft versus patients treated with conventional therapy alone. With regard to complete wound closure by week 12, 30.0% (39 of 130) of Dermagraft patients healed compared with 18.3% (21 of 115) of control patients (P = 0.023). The overall incidence of adverse events was similar for both the Dermagraft and control groups, but the Dermagraft group experienced significantly fewer ulcer-related adverse events. CONCLUSIONS: The data from this study show that Dermagraft is a safe and effective treatment for chronic diabetic foot ulcers.