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SNAP23 Is Selectively Expressed in Airway Secretory Cells and Mediates Baseline and Stimulated Mucin Secretion. - Bioscience reports
Airway mucin secretion is important pathophysiologically and as a model of polarized epithelial regulated exocytosis. We find the trafficking protein, SNAP23, selectively expressed in secretory cells compared to ciliated and basal cells of airway epithelium by immunohistochemistry and fluorescence activated cell sorting, suggesting that SNAP23 functions in regulated but not constitutive epithelial secretion. Heterozygous SNAP23 deletant mutant mice show spontaneous accumulation of intracellular mucin, indicating a defect in baseline secretion. However mucins are release from perfused tracheas of mutant and wild-type mice at the same rate, suggesting that increased intracellular stores balance reduced release efficiency to yield a fully compensated baseline steady state. In contrast, acute stimulated release of intracellular mucin from mutant mice is impaired whether measured by a static imaging assay 5 minutes after exposure to the secretagogue ATP or by kinetic analysis of mucins released from perfused tracheas during the first 10 minutes of ATP exposure. Together, these data indicate that increased intracellular stores cannot fully compensate for the defect in release efficiency during intense stimulation. The lungs of mutant mice develop normally and clear bacteria and instilled polystyrene beads comparable to wild-type mice, consistent with these functions depending on baseline secretion that is fully compensated.
Do adjunctive flap-monitoring technologies impact clinical decision making? An analysis of microsurgeon preferences and behavior by body region. - Plastic and reconstructive surgery
Multiple perfusion assessment technologies exist to identify compromised microvascular free flaps. The effectiveness, operability, and cost of each technology vary. The authors investigated surgeon preference and clinical behavior with several perfusion assessment technologies.A questionnaire was sent to members of the American Society for Reconstructive Microsurgery concerning perceptions and frequency of use of several technologies in varied clinical situations. Demographic information was also collected. Adjusted odds ratios were calculated using multinomial logistic regression accounting for clustering of similar practices within institutions/regions.The questionnaire was completed by 157 of 389 participants (40.4 percent response rate). Handheld Doppler was the most commonly preferred free flap-monitoring technology (56.1 percent), followed by implantable Doppler (22.9 percent) and cutaneous tissue oximetry (16.6 percent). Surgeons were significantly more likely to opt for immediate take-back to the operating room when presented with a concerning tissue oximetry readout compared with a concerning handheld Doppler signal (OR, 2.82; p < 0.01), whereas other technologies did not significantly alter postoperative management more than simple handheld Doppler. Clinical decision making did not significantly differ by demographics, training, or practice setup.Although most surgeons still prefer to use standard handheld Doppler for free flap assessment, respondents were significantly more likely to opt for immediate return to the operating room for a concerning tissue oximetry reading than an abnormal Doppler signal. This suggests that tissue oximetry may have the greatest impact on clinical decision making in the postoperative period.
Effect of chronic administration of hexane extract of Byrsonima crassifolia seed on B-cell and pancreatic oxidative parameters in streptozotocin-induced diabetic rat. - African journal of traditional, complementary, and alternative medicines : AJTCAM / African Networks on Ethnomedicines
In Mexican traditional medicine, the seeds of Byrsonima crassifolia have been used in the treatment of diabetes, rheumatism and for wound healing. The aim was to evaluate the effect of seeds of B. crassifolia on insulin release from the pancreatic beta cells in streptozotocininduced diabetic rats.In the present study, we evaluated the beneficial effect of seeds B. crassifolia streptozotocin-induced type 1 diabetic rats. Insulin level; insulin sensitivity index, insulin content in pancreas, malonaldehyde, nitric oxide contents, oxidative stress parameters were assayed. Serum glucose levels were determined by the glucose oxidase method. To determine the insulin releasing activity, after extract treatment, the pancreas was excised. Pancreatic sections were processed for examination of insulin-releasing activity using an imunocytochemistry kit.Administration of the hexane extract (200 and 400 mg/kg), exhibited a significant reduction in serum glucose. Administration of streptozotocin decreased the number of beta cells with insulin secretory activity in comparison with intact rats; but treatment with the B. crassifolia seed extract increased significantly the activity of the beta cells in comparison with the diabetic control rats. The extract decreased serum glucose in streptozotocin-induced diabetic rats and increased insulin release from the beta cells of the pancreas.These finding suggest that B. crassifolia seed has beneficial effect for diabetes through decreasing blood glucose and lipid levels, increasing insulin sensitivity index and insulin content, up-regulating antioxidant enzyme activity and decreasing lipid peroxidation.
The effects of age to meet the standard production rate. - Work (Reading, Mass.)
This study evaluated the energy expenditure of workers in physical work tasks in order to determine if people of different ages and gender carry out repetitive activities according to the recommended limits of energy at work.Exploring whether age is a significant factor to achieve industrial production rates and determine its possible consequences.A laboratory experiment was conducted with people age 20 to 58 years split by gender into four age groups. Oxygen consumption and heart rate were measured as variables of response to the physical workloads.When carrying out repetitive moderate load operations, women aged over 30 years exceeded the recommended energy expenditure (95% CI). For heavy activities, only men in the age groups 20-39 and 30-40 years could perform these tasks without exceeding the recommended oxygen consumption (95% CI).The industrial predetermined motion time systems do not take into account the effects of age and gender difference on energy production when obtaining cycle times in activities with significant aerobic loads. Manufacturing processes have specific standard times that might be inappropriate if they are performed by individuals who do not meet the standard energy production capacity.
Targeting of rifamycin SV to the colon for treatment of travelers' diarrhea: a randomized, double-blind, placebo-controlled phase 3 study. - Journal of travel medicine
Rifamycin SV is under development for treatment of travelers' diarrhea (TD) in a new oral formulation, Rifamycin SV MMX (RIF-MMX; Santarus Inc., San Diego, CA, USA), which targets its delivery to the colon, making it a unique rifamycin drug.This was a randomized, double-blind, phase 3 study of adult travelers to Mexico or Guatemala experiencing acute diarrhea. A total of 264 patients received RIF-MMX (2â€‰Ã—â€‰200â€‰mg twice daily for 3â€‰days, nâ€‰=â€‰199) or placebo (nâ€‰=â€‰65) in a 3â€‰:â€‰1 ratio. The primary endpoint was the length of time between the administration of first dose of study drug and passage of the last unformed stool (TLUS; after which clinical cure was declared). Other endpoints included eradication of pathogens from the stools, pathogen minimum inhibitory concentration (MIC), and adverse events (AEs).TLUS was significantly shorter in the RIF-MMX group (median: 46.0â€‰hours) compared with placebo (median: 68.0â€‰hours; pâ€‰=â€‰0.0008) and a larger percentage of RIF-MMX treated patients (81.4%) achieved clinical cure compared with placebo patients (56.9%). TLUS was significantly shorter in the subgroups of patients with enteroaggregative, enterotoxigenic, or diffusely adherent Escherichia coli infections (pâ€‰=â€‰0.0035) with nonsignificant activity against invasive bacteria (pâ€‰=â€‰0.3804). Overall pathogen eradication rates were numerically higher in the RIF-MMX group (67.0%) compared with placebo (54.8%) but the difference did not reach significance (pâ€‰=â€‰0.0836). In vitro resistance to rifamycin SV was observed in some bacteria remaining after treatment of patients with RIF-MMX but was not associated with lower efficacy in them. AEs appeared to be more frequent with placebo (38.5%) than with RIF-MMX (29.6%).RIF-MMX shortened the duration of TD in patients with a broad range of pathogens and was well tolerated. The unique pharmacokinetic properties of the drug offer evidence that TD pathogens work at the level of the colon.Â© 2014 International Society of Travel Medicine.
Death patterns during the 1918 influenza pandemic in Chile. - Emerging infectious diseases
Scarce information about the epidemiology of historical influenza pandemics in South America prevents complete understanding of pandemic patterns throughout the continent and across different climatic zones. To fill gaps with regard to spatiotemporal patterns of deaths associated with the 1918 influenza pandemic in Chile, we reviewed archival records. We found evidence that multiple pandemic waves at various times of the year and of varying intensities occurred during 1918-1921 and that influenza-related excess deaths peaked during July-August 1919. Pandemic-associated mortality rates were elevated for all age groups, including for adults >50 years of age; elevation from baseline was highest for young adults. Overall, the rate of excess deaths from the pandemic was estimated at 0.94% in Chile, similar to rates reported elsewhere in Latin America, but rates varied â‰ˆ10-fold across provinces. Patterns of death during the pandemic were affected by variation in host-specific susceptibility, population density, baseline death rate, and climate.
Studying the complex expression dependences between sets of coexpressed genes. - BioMed research international
Organisms simplify the orchestration of gene expression by coregulating genes whose products function together in the cell. The use of clustering methods to obtain sets of coexpressed genes from expression arrays is very common; nevertheless there are no appropriate tools to study the expression networks among these sets of coexpressed genes. The aim of the developed tools is to allow studying the complex expression dependences that exist between sets of coexpressed genes. For this purpose, we start detecting the nonlinear expression relationships between pairs of genes, plus the coexpressed genes. Next, we form networks among sets of coexpressed genes that maintain nonlinear expression dependences between all of them. The expression relationship between the sets of coexpressed genes is defined by the expression relationship between the skeletons of these sets, where this skeleton represents the coexpressed genes with a well-defined nonlinear expression relationship with the skeleton of the other sets. As a result, we can study the nonlinear expression relationships between a target gene and other sets of coexpressed genes, or start the study from the skeleton of the sets, to study the complex relationships of activation and deactivation between the sets of coexpressed genes that carry out the different cellular processes present in the expression experiments.
Neoadjuvant chemotherapy and short-term morbidity in patients undergoing mastectomy with and without breast reconstruction. - JAMA surgery
Neoadjuvant chemotherapy (NC) is increasingly being used in patients with breast cancer, and evidence-based reports related to its independent effects on morbidity after mastectomy with immediate breast reconstruction are limited.To determine the effect of NC on 30-day postoperative morbidity in women undergoing mastectomy with or without immediate breast reconstruction.All women undergoing mastectomy with or without immediate breast reconstruction from January 1, 2005, through December 31, 2011, at university and private hospitals internationally were analyzed using the American College of Surgeons National Surgical Quality Improvement Program 2005-2011 databases. Patients who received NC were compared with those without a history of NC to estimate the relative odds of 30-day postoperative overall, systemic, and surgical site morbidity using model-wise multivariable logistic regression.Neoadjuvant chemotherapy.Thirty-day postoperative morbidity (overall, systemic, and surgical site).Of 85,851 women, 66,593 (77.6%) underwent mastectomy without breast reconstruction, with 2876 (4.3%) receiving NC; 7893 patients were excluded because of missing exposure data. The immediate breast reconstruction population included 19,258 patients (22.4%), with 820 (4.3%) receiving NC. After univariable analysis, NC was associated with a 20% lower odds of overall morbidity in the group undergoing mastectomy without breast reconstruction (odds ratio [OR], 0.80; 95% CI, 0.71-0.91) but had no significant effect in the immediate breast reconstruction group (OR, 0.98; 95% CI, 0.79-1.23). After adjustment for confounding, NC was independently associated with lower overall morbidity in the group undergoing mastectomy without breast reconstruction (OR, 0.61; 95% CI, 0.51-0.73) and the immediate tissue expander reconstruction subgroup (OR, 0.49; 95% CI, 0.30-0.84). Neoadjuvant chemotherapy was associated with decreased odds of systemic morbidity in 4 different populations: complete sample (OR, 0.59; 95% CI, 0.49-0.71), mastectomy without breast reconstruction (OR, 0.59; 95% CI, 0.48-0.72), any immediate breast reconstruction (OR, 0.57; 95% CI, 0.37-0.88), and the tissue expander subgroup (OR, 0.41; 95% CI, 0.23-0.72).Our study supports the safety of NC in women undergoing mastectomy with or without immediate breast reconstruction. Neoadjuvant chemotherapy is associated with lower overall morbidity in the patients undergoing mastectomy without breast reconstruction and in those undergoing tissue expander breast reconstruction. In addition, the odds of systemic morbidity were decreased in patients undergoing mastectomy with and without immediate breast reconstruction. The mechanisms behind the protective association of NC remain unknown and warrant further investigation.
Clinical outcomes in cranioplasty: risk factors and choice of reconstructive material. - Plastic and reconstructive surgery
Continuing advances in cranioplasty have enabled repair of increasingly complicated cranial defects. However, the optimal materials and approaches for particular clinical scenarios remain unclear. This study examines outcomes following cranioplasty for a variety of indications in patients treated with alloplastic material, autogenous tissue, or a combination of both.a retrospective analysis on 180 patients who had 195 cranioplasties performed between 1993 and 2010.Materials used for cranioplasty included alloplastic for 42.6 percent (83 of 195), autologous for 19.0 percent (37 of 195), and both combined for 38.5 percent (75 of 195). Mean defect size was 70.5 cm. A subset of patients had undergone previous irradiation (12.2 percent; 22 of 180) or had preoperative infections (30.6 percent; 55 of 180). The most common complication was postoperative infection (15.9 percent; 31 of 195). Factors that significantly predisposed to complications included preoperative radiation, previous infection, and frontal location. Preoperative radiation was the strongest predictor of having any postoperative complications, with an adjusted odds ratio of 6.91 (p < 0.005). Irradiated patients (OR, 7.96; p < 0.05) and patients undergoing frontal cranioplasties (OR, 2.83; p < 0.05) were more likely to require repeated operation. Preoperative infection predisposed patients to exposure of hardware in alloplastic reconstructions (OR, 3.13; p < 0.05).Despite the evolution of cranioplasty techniques and materials, complications are not uncommon. The choice of reconstructive material may modify the risk of developing postoperative complications but appears less important than the clinical history in affecting outcome.Risk, III.
The participation of varicella zoster virus in relapses of multiple sclerosis. - Clinical neurology and neurosurgery
Recent studies have documented the apparent participation of varicella zoster virus (VZV) in the etiopathogenesis of multiple sclerosis (MS). The present study aimed to corroborate the possible presence of VZV during exacerbations of MS.Fifty-three patients with definite MS were included; of them, 31 were studied during the first week of a clinical relapse, whereas 16 were studied during remission; 6 patients with progressive MS were also studied. Genes from 5 herpes viruses: varicella zoster, herpes simplex 1 and 2, Epstein-Barr and herpes 6 were studied by polymerase chain reaction in cerebrospinal fluid and in peripheral blood mononuclear cells (PBMC). As controls 21 patients with inflammatory or functional neurological disorders were included.DNA from varicella zoster virus was found in the CSF from all MS patients studied during relapse (100%) and in the PBMC from 28 of them (90%). However, VZV DNA was found in the CSF only in 5 MS patients studied during remission (31%) and in the PBMC from 3 of them (19%). VZV DNA was also found, but in lower amounts, in the CSF (83%) and PBMC (33%) from patients with progressive MS. In contrast, VZV was not found either in CSF or in PBMC from controls. Results from the other herpes viruses tested were similar in MS patients and in controls.Our results corroborate the conspicuous, but ephemeral presence of VZV during relapses of MS and support the idea of VZV involvement in the etiopathogenesis of MS. Recent epidemiological and molecular studies as well as reports of severe VZV infections triggered by specifically induced immunosuppression during therapy of MS give additional support to this potential association.Copyright Â© 2014 Elsevier B.V. All rights reserved.
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