BMP-2 gene polymorphisms and osteoporosis: the Rotterdam Study.

After reported associations of variations in the BMP-2 gene with osteoporosis in small populations, we studied the association of the BMP-2 gene polymorphisms Ser37Ala and Arg190Ser with osteoporosis in 6353 men and women from the Rotterdam Study. We did not observe an association of these variants with BMD, bone loss, hip structural analysis parameters, and fracture risk. INTRODUCTION: Bone morphogenetic protein 2 (BMP-2) plays a role in osteoblast differentiation. BMP-2 gene variation has previously been associated with osteoporosis in various small populations, but current evidence remains inconclusive about the exact association with osteoporosis. Therefore, we studied the association of two polymorphisms located in the BMP-2 gene (Ser37Ala and Arg190Ser) and haplotypes defined by these polymorphisms with BMD, rates of bone loss, parameters of hip structural analysis (HSA), and fractures in the Rotterdam Study, a large prospective cohort study of diseases in the elderly. MATERIALS AND METHODS: Databases were searched for polymorphisms and haplotype blocks in the BMP-2 gene region. Allele frequencies for Ser37Ala and Arg190Ser were determined in 60 blacks and 110 Chinese from Coriell panels. Genotype data on Ser37Ala and Arg190Ser were available for 6353 individuals from the Rotterdam Study population. Haplotype alleles defined by Ser37Ala and Arg190Ser were inferred using PHASE software. Genotype and haplotype analyses for BMD (measured at the lumbar spine and femoral neck), bone loss per year (measured at the femoral neck), and HSA were performed using AN(C)OVA. Fractures were analyzed using a Cox proportional-hazards model and logistic regression. All outcomes were adjusted for age, height, and weight. RESULTS: Allele frequencies were 2.5% for Ala37 and 40.2% for Ser190, whereas haplotype allele frequencies were 57.28% (Ser37Arg190), 40.19% (Ser37Ser190), 2.50% (Ala37Arg190), and 0.02% (Ala37Ser190). For BMD, bone loss, HSA outcomes, and (incident) fractures, no differences could be seen between genotype and haplotype groups. Conclusions: In this large population-based cohort of Dutch whites, we conclude that the BMP-2 Ser37Ala and Arg190Ser polymorphisms or haplotypes thereof are not associated with parameters of osteoporosis.     

Long-term neurotoxicity of chlorpyrifos: spatial learning impairment on repeated acquisition in a water maze.

Organophosphate compounds are cholinesterase inhibitors widely used in agriculture, industry, household products, and even as chemical weapons. Their major mechanism of acute toxic action is the inhibition of acetylcholinesterase, which is responsible for the degradation of the neurotransmitter acetylcholine. An organophosphorus ester-induced chronic neurotoxicity (OPICN) syndrome has been proposed. The OPICN syndrome could result from both long-term exposure to subclinical doses of OPs and after acute poisoning. Development of animal models for the cognitive decline are required and could later help to elucidate the mechanisms involved in this long-term effect on the central nervous system. Previously, we have found performance decrements in a four-trial repeated acquisition spatial task in a water maze. The present study includes two experiments to extend the long-term behavioral effects observed. Rats were injected either once or twice with chlorpyrifos (CPF) and then tested months after in a two-trial repeated acquisition task in a water maze. Our results confirm and extend the long-term behavioral effects of subcutaneous administration of CPF. The two treatments used produced performance decrements that suggest functional central nervous system alterations.     

Non-epithelial neoplasms of the stomach.

Non-epithelial neoplasms of the stomach are rare in all countries, in contrast to neoplasms of epithelial origin. They can be either benign or malignant. The distinction between these two groups is based entirely on histopathology. This paper reports a series of 27 patients managed during the period June 1978 to March 1991.     

Partial Portal Vein Ligation Plus Thioacetamide: A Method to Obtain a New Model of Cirrhosis and Chronic Portal Hypertension in the Rat

To obtain a new model of chronic portal hypertension in the rat, two classical methods to produce portal hypertension, partial portal vein ligation and the oral administration of thioacetamide (TAA), have been combined. Male Wistar rats were divided into four groups: 1 (control; n?=?10), 2 [triple partial portal vein ligation (TPVL); n?=?9], 3 (TAA; n?=?11), and 4 (TPVL plus TAA; n?=?9). After 3 months, portal pressure, types of portosystemic collateral circulation, laboratory hepatic function tests (aspartate aminotransferase, alanine aminotransferase, bilirubin, alkaline phosphatase, and gamma-glutamyl transpeptidase) and liver histology were studied. The animals belonging to group 2 (TPVL) developed extrahepatic portosystemic collateral circulation, associated with mesenteric venous vasculopathy without hepatic destructurization or portal hypertension. Animals from group 3 (TAA) developed cirrhosis and portal hypertension but not extrahepatic portosystemic collateral circulation, or mesenteric venous vasculopathy. Finally, the animals from group 4 (TPVL?+?TAA) developed cirrhosis, portal hypertension, portosystemic collateral circulation, and mesenteric venous vasculopathy. The association of TPVL and TAA can be used to obtain a model of chronic portal hypertension in the rat that includes all the alterations that patients with hepatic cirrhosis usually have. This could, therefore, prove to be a useful tool to study the pathophysiological mechanisms involved in these alterations.     

Tityus perijanensis González-Sponga (Scorpiones, Buthidae): molecular assessment of its geographical distribution and venom lethality of Venezuelan populations.

An extensive field survey allowed us to expand the geographical distribution of the scorpion Tityus perijanensis in the Perijá range, western Zulia State, Venezuela, including areas where adult cases of severe scorpionism have been reported. 16S ribosomal RNA (rRNA) gene sequencing, DL(50) determination, and native PAGE suggest low genetic and venom proteomic divergence across the distribution range. The results also indicate phylogenetic divergence between T. perijanensis and T. discrepans, the species prevalent in northcentral Venezuela. T. perijanensis venom lethality (0.91-0.94 mg/kg) is comparable to that of the Brazilian T. serrulatus and ranks highest among toxic Venezuelan Tityus studied so far. The data indicate that the Perijá range should be included amongst the endemic areas of scorpionism of Venezuela and Colombia.     

Detection of Porphyromonas gingivalis, Porphyromonas endodontalis, Prevotella intermedia, and Prevotella nigrescens in chronic endodontic infection.

Black-pigmented anaerobic rods such as Prevotella spp. and Porphyromonas spp. are involved in the etiology and perpetuation of endodontic infections. The aim of this study was to evaluate the prevalence of these species in chronic endodontic infections by using culture and polymerase chain reaction (PCR) techniques. Samples of 100 patients with root canals displaying chronic endodontic infections were obtained by sterilized paper points. Bacterial identification was performed by using culture and PCR techniques. By culture, in 33% of the samples, P. intermedia-P. nigrescens (75.8%), P. gingivalis (27.3%), and P. endodontalis (9.1%) were identified, and by PCR 60% of the samples harbored P. nigrescens (43.3%), P. gingivalis (43.3%), P. intermedia (31.7%), and P. endodontalis (23.3%). The presence of these black-pigmented anaerobic rods alone or in association in chronic endodontic infections seems to be frequent. PCR is a very sensitive technique for detecting DNA from bacterial cells. Culturing is only able to reveal living bacteria and is less sensitive for the identification of low numbers of bacterial cells.     

Evaluation of bone height and bone density after tooth extraction: an experimental study in minipigs.

OBJECTIVE: The objective of this study was to radiographically quantify bone density and bone height preservation in tooth extraction alveolus filled with xenograft. STUDY DESIGN: The maxillary and mandibular fourth deciduous molars and fourth premolars of 6 minipigs were removed. Randomly, in 3 animals the right side was used as the test side and in the other 3 animals the left side was the test side. Intraoral radiographs were performed to compare the condition at the initial time and 3 months later. Measurements of bone height and bone density were performed using KS300 (Zeiss) software. RESULTS: After 3 months, there was a statistically significant smaller bone height loss for the test group. The test group presented a statistically greater bone density immediately after tooth extraction. However, after 3 months there was no statistically significant difference between the groups. CONCLUSIONS: The results suggest that treatment of postextraction alveolus with xenograft can preserve bone height initially but differences in bone density compared to when no xenograft is used are not sustained.     

Robotic-assisted heller myotomy versus laparoscopic heller myotomy for the treatment of esophageal achalasia: multicenter study

Laparoscopic Heller myotomy (LHM) has become the standard treatment option for achalasia. The incidence of esophageal perforation reported is about 5%–10%. Robotically assisted Heller myotomy (RAHM) is emerging as a safe alternative to LHM. Data comparing the two approaches are scant. The aim of this study was to compare RAHM with LHM in terms of efficacy and safety for treatment of achalasia. A total of 121 patients underwent surgical treatment of achalasia at three institutions. A retrospective review of prospectively collected perioperative data was performed. Patients were divided into two groups: group A (RAHM), 59 patients, and group B (LHM), 62 patients. All the operations were completed using minimally invasive techniques. There were 63 women and 58 men, with a mean age of 45 ±19 years (14–82 years). Fifty-one percent of patients in group A and 95% of patients in group B reported weight loss. Duration of symptoms was equal for both groups. Dysphagia was the main complaint in both groups (P = NS). There was no difference in preoperative endoscopic treatment in both groups (44% versus 27%, P = NS). Operative time was significantly shorter for LHM in the first half of the experience (141 ± 49 versus 122 ± 44 minutes, P < .05). However, in the last 30 cases there was no difference in operative time between the groups (P = NS). Intraoperative complications (esophageal perforation) were more frequent in group B (16% versus 0%). The incidence of postoperative heartburn did not differ by group. There were no deaths. At 18 and 22 months, 92% and 90% of patients had relief of their dysphagia. This study suggests that RAHM is safer than LHM, because it decreases the incidence of esophageal perforation to 0%, even in patients who had previous treatment. At short-term follow-up, relief of dysphagia was equally achieved in both groups. Presented at the Forty-Sixth Annual Meeting of The Society for Surgery of the Alimentary Tract, Chicago, Illinois, May 14–18, 2005 (oral presentation). This study was supported in part by a grant provided by Intuitive Surgical, Inc. and Ethicon Endo-Surgery, Inc.     

Mechanisms of progression and regression of coronary artery disease by PET related to treatment intensity and clinical events at long-term follow-up.

Changes in regional myocardial perfusion throughout the entire coronary vascular tree, as opposed to changes in the worst regional perfusion defect, have not been described during long-term regression or progression of coronary artery disease (CAD) or related to clinical outcomes. METHODS: Four-hundred nine patients with CAD undergoing dipyridamole PET at baseline and after 2.6 +/- 1.4 y were followed over 5 more years for coronary events. PET images were objectively quantified by automated software for changes in severity of the (i) baseline worst quadrant, indicating the worst flow-limiting stenosis at baseline PET; (ii) follow-up worst quadrant, indicating the worst stenosis on follow-up PET; and (iii) maximal change quadrant, indicating the largest change of any same quadrant pair from baseline-to-follow-up images. RESULTS: At follow-up PET, new regional perfusion defects were seen in 40% of patients. In 77% of patients, the greatest change was in a quadrant different from the worst baseline defect. The maximal change quadrant improved in 70% of patients on intense lifestyle and pharmacologic lipid treatment, in 48% on moderate treatment, and in 39% on poor treatment (P < 0.0001). Combined quadrant changes integrated throughout the heart independently predicted cardiovascular events at long-term follow-up. In contrast, changes of any single baseline-to-follow-up quadrant pair did not. CONCLUSION: By PET, 77% of patients with CAD had the greatest perfusion changes in areas different from the baseline worst perfusion defect and 40% had new perfusion defects. Changes in perfusion defects throughout the entire coronary vascular tree predicted coronary events, whereas changes in the worst flow-limiting stenosis at baseline or in any one segment of myocardium did not. To our knowledge, these data provide the first direct evidence on mechanisms for disproportionately greater reduction in cardiac events than changes in single stenosis severity with lipid treatment.