SNP array mapping of chromosome 20p deletions: Genotypes,phenotypes, and copy number variation

The use of array technology to define chromosome deletions and duplications is bringing us closer to establishing a genotype/phenotype map of genomic copy number alterations. We studied 21 patients and five relatives with deletions of the short arm of chromosome 20 using the Illumina HumanHap550 SNP array to: 1) more accurately determine the deletion sizes; 2) identify and compare breakpoints; 3) establish genotype/phenotype correlations; and 4) investigate the use of the HumanHap550 platform for analysis of chromosome deletions. Deletions ranged from 95 kb to 14.62 Mb, and all of the breakpoints were unique. Eleven patients had deletions between 95 kb and 4 Mb and these individuals had normal development, with no anomalies outside of those associated with Alagille syndrome (AGS). The proximal and distal boundaries of these 11 deletions constitute a 5.4‐Mb region, and we propose that haploinsufficiency for only 1 of the 12 genes in this region causes phenotypic abnormalities. This defines the JAG1‐associated critical region, in which deletions do not confer findings other than those associated with AGS. The other 10 patients had deletions between 3.28 Mb and 14.62 Mb, which extended outside the critical region, and, notably, all of these patients had developmental delay. This group had other findings such as autism, scoliosis, and bifid uvula. We identified 47 additional polymorphic genome‐wide copy number variants (>20 SNPs), with 0 to 5 variants called per patient. Deletions of the short arm of chromosome 20 are associated with relatively mild and limited clinical anomalies. The use of SNP arrays provides accurate high‐resolution definition of genomic abnormalities. Hum Mutat 0,1–8, 2008. © 2008 Wiley‐Liss, Inc.     

Evaluation of growth hormone secretion and insulin-like growth factor-1 in prepubertal children with thalassemia.

Growth retardation is a clinical feature of patients with thalassemia major, and endocrine studies have frequently revealed the presence of normal growth hormone (GH) secretion. The present study was undertaken in 14 prepubertal thalassemic children (9 males and 5 females), aged 2(2/12) to 10(3/12) years, with the aim of evaluating GH response to i.v. arginine, oral L-dopa stimulation and insulin-like growth factor-1 (IGF-1) levels. Eleven patients had peak serum GH levels less than 7 ng/ml and two patients had peak serum GH levels of 7-10 ng/ml with arginine. Similarly, 10 patients had peak levels less than 7 ng/ml and one patient had a peak level of 7-10 ng/ml with L-dopa. Thus, nine of the patients had GH deficiency and two had partial GH deficiency. Three patients had elevated basal GH values. The serum IGF-1 levels in the patients were not statistically different from the levels in the controls, but three patients had low IGF-1 values. These findings suggest a defect in the regulatory mechanisms of GH secretion.     

Nitric oxide levels in rat cortex,hippocampus, cerebellum,and brainstem after impact acceleration head injury

Nitric oxide (NO) is a potential mediator of secondary brain injury in the settings of cerebral ischemia and inflammation. Traumatic brain injury (TBI) alters the levels of stable end products of NO metabolism. We investigated these changes and attempted to identify brain regions that were unique with regard to NO production in the period immediately after TBI. The experiment involved assaying nitrite-nitrate concentrations in the rat cortex, cerebellum, hippocampus, and brainstem after impact-acceleration head injury. Five rats comprised the sham-operated (control) group, five sustained mild head injury (MHI), and five sustained severe head injury (SHI). There was a uniform decline in the tissue concentrations of NO metabolites in all four brain regions in both injured groups. There were no significant differences in the concentrations of NO metabolites among the various sites tested in the MHI group; however, there appeared to be a relationship between degree of decline in NO levels and amount of trauma sustained by a given region in the SHI group. In these rats, NO dropped to the lowest levels in the brain region where the direct trauma was most severe. The results suggest that nitrite-nitrate levels in these four brain regions fall below normal in the first 5 min after impact trauma. This decrease may, in part, be related to reduced activity of all nitric oxide synthase isoforms, which would cause a drop in the levels of NO metabolites. We believe that this decline may be linked to, and may even cause, the global decrease in cerebral blood flow that occurs in the initial stages of TBI.     

Intrathecal gadolinium (gadopentetate dimeglumine) enhanced magnetic resonance myelography and cisternography: results of a multicenter study

RATIONALE AND OBJECTIVES: This cooperative multicenter human study was designed to evaluate the safety, magnetic resonance (MR) imaging characteristics, and clinical response to a single gadolinium contrast agent: gadopentetate dimeglumine. MATERIAL AND METHODS: Ninety-five patients (age range: 1 month to 78 years; sex: 50 males, 45 females) were included in this prospective study. The patients presented clinically with a variety of cranial or spinal signs and symptoms for which an intrathecal contrast myelogram or cisternogram was requested by clinical staff. Via lumbar puncture (20-25 g needle), 3 to 5 mL/ml of cerebrospinal fluid were withdrawn and mixed with a single volume of 0.5 (n = 63), 0.7 (n = 13), 0.8 (n = 12), or 1.0 (n = 7) cc/mL of gadopentetate dimeglumine (Magnevist; Schering, Berlin, Germany). This was then injected into the subarachnoid space, and the needle was removed. Immediate and delayed (up to 96 hours) T1- and T2-weighted MR imaging was performed on super conductive, high-field (1.0-1.5 tesla) imaging units in two or three planes. All patients were hospitalized for an observation period of 24 hours following the procedure, and follow-up neurologic examinations were performed serially for 6 to 12 months afterward. RESULTS: No patient manifested gross behavioral changes, neurologic alterations, or seizure activity at any time following the procedure. Nineteen patients (20%) experienced postural postlumbar puncture headache, six patients had nausea (6%), and two patients had episodes of vomiting (2%), all which resolved within the first 24 hours of the lumbar puncture with conservative bed rest. CONCLUSION: This cooperative study demonstrates the general safety and feasibility of low dose (0.5-1.0 mL/ml) intrathecal gadopentetate dimeglumine administration. The potential useful clinical applications include the evaluation of obstructions and communications of the various subarachnoid spaces, spontaneous or traumatic/postsurgical craniospinal cerebrospinal fluid leaks, and subarachnoid space CSF flow and parenchymal CNS interstitial diffusion dynamics. This worldwide cooperative study seeks to progressively perform human studies for further definitive evaluation of the practical clinical applications, of the relationship of this technique to other imaging studies and modalities, and the long-term safety of the procedure in a larger number of subjects.     

Is 100% beating heart coronary by-pass justified?

Coronary by-pass on a beating heart may provide a safer form of surgical revascularization by avoiding the well-documented side effects of cardiopulmonary by-pass. In addition, off-pump bypass is suggested to be a good alternative to on-pump especially in high risk patients. This study reviews the feasibility of coronary by-pass on the beating heart in all patients referred to surgery. Two hundred and ninety-four patients operated on the beating heart were prospectively followed and compared to the control group of 100 consecutive patients operated with the conventional method. There were no significant differences between the groups with respect to risk factors, except the incidence of chronic obstructive pulmonary disease and ejection fraction which were higher in the conventional group, whereas peripheral vascular disease was higher in the beating heart group. There was more distal anastomosis in the conventional group. Postoperative inotrope requirement, peak creatine phosphokinase- MB, ventilation time, blood loss in the first 24 h, transfusion needs, new atrial fibrillation and length of hospital stay were significantly lower in the beating heart operations. However, there were no significant differences between the groups in terms of neurological complications, chest infection, intraaortic balloon pump usage and mortality. In conclusion, multivessel off pump coronary by-pass is feasible with the same or better results as it is observed in the conventional technique when postoperative bleeding, neurogenic complications, arrythmias, hospital stay, overall morbidity and mortality are compared.     

The acute effects of sildenafil on tear functions

The acute effects of 50 mg of sildenafil on tear functions were evaluated in 12 impotent patients. Mean tear breakup time, cotton thread, and Schirmer I tests were 19.42±6.45 s, 13.92±6.63 mm, and 16.58±12.19 mm, respectively before sildenafil and 20.33±10.40 s, 10.92±6.14 mm, and 18.08±12.36 mm, respectively, 1 hour after sildenafil. The results suggest that sildenafil does not adversely affect tear functions. The authors have stated that they do not have a significant financial interest or other relationship with any product manufacturer or provider of services discussed in this article. The authors also do not discuss the use of off-label products, which includes unlabeled, unapproved, or investigative products or devices.     

Phase II study of gemcitabine plus paclitaxel in metastatic breast cancer patients with prior anthracycline exposure

Chemotherapy provides palliation and modest prolongation of symptom-free survival in metastatic breast cancer. Taxane containing regimens are commonly considered to be among the initials in metastatic setting due to earlier use of anthracyclines in the course of breast cancer. Therefore, we conducted this Phase II study to assess efficacy and safety of gemcitabine plus paclitaxel (GT) combination therapy in anthracycline pretreated metastatic first-line setting. Patients and Methods: The study enrolled 26 women with pathologically confirmed and measurable metastatic breast cancer who were previously treated with anthracycline but no prior chemotherapy for metastatic disease. Twenty six and twenty four patients were eligible for toxicity and efficacy evaluations respectively. Mean age was 47.3 years and median ECOG performance status was 0. Twenty patients (76.9 percent) had visceral metastases, most commonly located in liver and lung. Treatment schedule was as follows: paclitaxel 175 mg/m² was administered intravenously in 3 hours on Day 1 and gemcitabine 1000 mg/m² was administered intravenously in 30 minutes on Day 1 after paclitaxel application, and on Day 8 every 21 days. Results: Objective response rate was 41.7 percent (95 percent CI: 21.9-61.4) with 16.7 percent (95 percent CI: 1.7-31.6 percent) CR, and 25.0 percent (95 percent CI: 7.6-42.3 percent) PR. Median time to progression and overall survival were 9.6 and 14.5 months, respectively. Grade 3-4 toxicity was observed in 34.6 percent (9) patients. Treatment of two patients was discontinued due to toxicity, consisting of Grade 3 hypersensitivity reactions and Grade 4 infections in one patient each. Dose reductions due to myelotoxicity were performed in 4 (15.3 percent) patients. Hematologic toxicities were generally manageable with appropriate dose modifications and supportive care. Conclusion: Gemcitabine and paclitaxel combination regimen is effective and has manageable toxicity profile as first line metastatic setting.     

Comparison of the factors that influence obesity prevalence in three district municipalities of the same city with different socioeconomical status: a survey analysis in an urban Turkish population

BACKGROUND: To evaluate the obesity status, factors and comorbidities related to it in three district municipalities (DM) that compose city center of Bursa with inhabitants of different socioeconomic status. METHODS: A total of 1632 inhabitants >/=18 years of age were interviewed. The number of sample in each DM was obtained proportional to their populations by stratified sampling method. Among 1632, a total of 1543 subjects were included by random sampling and a questionnaire was filled in including demographic, social and behavioral features. RESULTS: The participants living in DM with the highest socioeconomical status (SES) score and level of education had the lowest body mass index (BMI) and body fat percentage (%BF) compared to other DMs. The lowest obesity prevalence (30.8% vs. 36.4% and 39.3%) in that DM was possibly due to younger age, lower female ratio, more active professional, higher percentage of smoking, more consumption of vegetables, olive or corn oil, and less carbohydrate. For the evaluation of the factors that may influence obesity risk, we investigated the effects of these factors in men and women separately with logistic regression model. Sedentary life style and dyslipidemia (DL) in men, being unemployed, having lower level of education and having hypertension (HT) in women and familial obesity in both gender were found to be related to increased obesity risk. CONCLUSIONS: The prevalence of obesity in Bursa is increasing although inhabitants are taking some precautions parallel to their socioeconomical and educational levels. Obesity is becoming a more alarming public health problem in Bursa and Turkey like in most other parts of the world, which forces us to invent new prevention policies. Besides, the results of our study highlight the fact that especially female education requires more attention for decreasing obesity prevalence in coming generations.     

Effectiveness of vardenafil versus papaverine in penile Doppler ultrasonography

PURPOSE: To evaluate erectile dysfunction, penile color Doppler ultrasound is currently considered the best method. But intracavernous injection is invasive and has adverse effects, such as prolonged erection and risk of priapism. In our study we want to evaluate whether vardenafil can be used instead of papaverine in penile Doppler ultrasonography. MATERIALS AND METHODS: A total of 24 patients with erectile dysfunction underwent color Doppler ultrasound before and after intracavernous injection of 60 mg papaverine with genital and audiovisual sexual stimulation. Peak flow and end diastolic velocity were measured in the recorded waveforms obtained 0, 1, 5, 10 and 20 min after injection. The patients also underwent color Doppler ultrasound after a 10-mg oral dose of vardenafil with genital and audiovisual sexual stimulation and at least 5 days after the prior examination. The same parameters were measured at 30, 45, 60, 75 and 90 min after the drug administration. We compared the results with the values obtained after papaverine injection. RESULTS: After oral vardenafil mean peak flow velocity significantly increased starting at 30 min and achieving a maximum value at 60 min. There were no significant differences in the 2 methods in mean peak velocity 1, 5, 10 and 20 min after papaverine injection, and 30, 45, 60, 75 and 90 min after oral vardenafil administration. Although papaverine injection is the gold standard for penile color Doppler ultrasound, it has severe adverse effects such as prolonged erection which we observed in 3 patients (12.5%) and required pharmacological detumescence. After vardenafil no severe adverse effects were observed. CONCLUSIONS: Vardenafil administration achieved increased peak flow velocity comparable to that after intracavernous papaverine injection. With no prolonged erection vardenafil is a safer alternative compared to more invasive intracavernous injection and is also an alternative for patients who fear injections.