Antoine A Makhlouf’s research while affiliated with Southwest Minnesota State University and other places

To determine whether shock wave lithotripsy (SWL) increases the prevalence of hypertension (HTN) at intermediate follow-up. All patients were treated with the Medstone STS electrohydraulic lithotripter, and the data were recorded prospectively in a centralized database. The data on the development of HTN after SWL was obtained from a questionnaire mailed to the patients who had undergone SWL from November 1999 and January 2002. Controls matched for age, sex, and body mass index were obtained from the National Health and Nutrition Examination Survey, using the demographic, body measurements, medical conditions, and blood pressure data sets. Two sets of matching controls were used to compare the prevalence of HTN between our patients and the NHANES population at SWL and at the follow-up point. A total of 2041 patients responded to the questionnaire, with a median follow-up of 6 years. No statistically significant difference was found in the HTN prevalence between the patients and matched controls at SWL (26.7% vs 28.0%). At the follow-up point, the prevalence of HTN was greater in our patients (37.8%) than in the controls (32.5%, P=.0009). Of our patients, 15% have developed de novo HTN compared with the predicted rate of 6.25% from the matched controls. Male gender, age, and a greater body mass index were associated with the development of HTN, but none of the SWL parameters (number of shocks, bilateral vs unilateral, and multiple SWL sessions) were significantly associated with HTN. The results of our study have indicated a small, but significant, increase in the risk of developing HTN after SWL using a third-generation electrohydraulic lithotripter at intermediate follow-up.

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Though cryopreservation of mouse sperm yields good survival and motility after thawing, cryopreservation of rat sperm remains a challenge. This study was designed to evaluate the biophysics (membrane permeability) of rat in comparison to mouse to better understand the cooling rate response that contributes to cryopreservation success or failure in these two sperm types. In order to extract subzero membrane hydraulic permeability in the presence of ice, a differential scanning calorimeter (DSC) method was used. By analyzing rat and mouse sperm frozen at 5 degrees C/min and 20 degrees C/min, heat release signatures characteristic of each sperm type were obtained and correlated to cellular dehydration. The dehydration response was then fit to a model of cellular water transport (dehydration) by adjusting cell-specific biophysical (membrane hydraulic permeability) parameters L(pg) and E(Lp). A "combined fit" (to 5 degrees C/min and 20 degrees C/min data) for rat sperm in Biggers-Whitten-Whittingham media yielded L(pg) = 0.007 microm min(-1) atm(-1) and E(Lp) = 17.8 kcal/mol, and in egg yolk cryopreservation media yielded L(pg) = 0.005 microm min(-1) atm(-1) and E(Lp) = 14.3 kcal/mol. These parameters, especially the activation energy, were found to be lower than previously published parameters for mouse sperm. In addition, the biophysical responses in mouse and rat sperm were shown to depend on the constituents of the cryopreservation media, in particular egg yolk and glycerol. Using these parameters, optimal cooling rates for cryopreservation were predicted for each sperm based on a criteria of 5%-15% normalized cell water at -30 degrees C during freezing in cryopreservation media. These predicted rates range from 53 degrees C/min to 70 degrees C/min and from 28 degrees C/min to 36 degrees C/min in rat and mouse, respectively. These predictions were validated by comparison to experimentally determined cryopreservation outcomes, in this case based on motility. Maximum motility was obtained with freezing rates between 50 degrees C/min and 80 degrees C/min for rat and at 20 degrees C/min with a sharp drop at 50 degrees C/min for mouse. In summary, DSC experiments on mouse and rat sperm yielded a difference in membrane permeability parameters in the two sperm types that, when implemented in a biophysical model of water transport, reasonably predict different optimal cooling rate outcomes for each sperm after cryopreservation.

To evaluate the efficacy of celecoxib as an analgesic and medical expulsive agent in acute renal colic. A prospective randomized double-blind study was conducted on patients presenting with an obstructing ureteral calculus < 10 mm in largest diameter. Patients were randomized to 400 mg of celecoxib, followed by 200 mg every 12 hours for 10 days, or to placebo. Patients with a solitary kidney, renal insufficiency (CR > 1.8), urinary tract infection, or significant cardiovascular disease were excluded. A total of 57 patients provided consent of which 53 completed the study. Four patients were excluded from the analysis because of stone passage or withdrawal of consent before the first dose of study medication. No significant difference was noted in the spontaneous stone passage rate (celecoxib 55.2%, placebo 54.2%) and between celecoxib and placebo with regard to days to stone passage (7.0 vs 9.0, P = .6) or size of stone passed (3.9 vs 4.6 mm, P = .18). No significant difference was noted in pain analog scores (2.6 vs 3.5, P = .71) or narcotic doses (13.2 vs 13.6, P = .74). Furthermore, a 25% decrease in narcotic use (or 19 mg based on placebo mean) was outside the 80% one-sided confidence interval for the change in mean narcotic use between the 2 groups. Thus, it is unlikely (< 20%) that we missed a clinically significant beneficial effect of celecoxib on narcotic consumption because of sample size. Celecoxib does not facilitate stone passage or decrease narcotic requirements in patients with acute renal colic.

To investigate the hypothesis that extracorporeal shock wave lithotripsy (ESWL) increases the incident risk of new-onset diabetes mellitus (DM). Studies have suggested that ESWL predisposes to DM. Using a mail survey, we collected data on the presence and onset of DM in 1947 patients treated with the Medstone-STS electrohydraulic lithotripter from 1999 to 2002. These patients were matched by age, sex, and body mass index to controls from the National Health and Nutrition Examination Survey (NHANES) database. Of the 1947 patients, 4% could not be matched and were excluded, leaving 1869 for analysis, of whom 60.0% were men. The mean age was 51.9 years at ESWL and the median follow-up was 6 years. The mean body mass index at the end of the study was 28.6 kg/m(2). At ESWL, 8.67% of matched patients had a diagnosis of DM. This had increased to 13.9% at the time of survey. In the NHANES group, 8.34% had DM at the time the ESWL group underwent treatment, and this had increased to 14.1% at the NHANES survey. Therefore, the rate of new DM cases in the ESWL group was similar to that in the NHANES group (5.2% vs 5.8%, respectively; P = .47). Multivariate analysis of the patient cohort confirmed that age, sex, body mass index, and family history correlated with development of DM and that the laterality of treatment and number of treatments or shocks given were not significant predictors of DM. The results of our study have shown that patients treated with ESWL do not develop DM at a greater rate than does the general population at 6 years of follow-up.

We previously developed a computational model to predict vesicoureteral reflux resolution 1 and 2 years after diagnosis. Previous studies suggest that an abnormal renal scan may be a predictor of the failure of vesicoureteral reflux to resolve. We investigated whether the addition of renal scan data would improve the accuracy of our computational model. Medical records and renal scans were reviewed on 161 children, including 127 girls and 34 boys, with primary reflux between 1988 and 2004. In addition to the 9 input variables from our prior model, we added renal scan data on decreased relative renal function (40% or less in the refluxing kidney) and renal scars. Resolution outcome was evaluated 1 and 2 years after diagnosis. Data sets were prepared for 1 and 2-year outcomes, and randomized into a modeling set of 111 and a cross-validation set of 50. The model was constructed using neUROn++. A logistic regression model had the best fit with an ROC area of 0.945 for predicting reflux resolution in the 2-year model. This was improved compared to our previous model without renal scan data. A prognostic calculator using this model can be deployed for availability on the Internet, allowing input variables to be entered and calculating the odds of resolution. This computational model uses multiple variables, including renal scan data, to improve individualized prediction of early reflux resolution with almost 95% accuracy. The prognostic calculator is a useful tool for predicting individualized vesicoureteral reflux resolution.

Patients treated for obesity with jejunoileal bypass (JIB) experienced a marked increased risk of hyperoxaluria, nephrolithiasis, and oxalate nephropathy developing. Jejunoileal bypass has been abandoned and replaced with other options, including Roux-en-Y gastric bypass (RYGB). Changes in urinary lithogenic risk factors after RYGB are currently unknown. Our purpose was to determine whether RYGB is associated with elevated risk of developing calcium oxalate stone formation through increased urinary oxalate excretion and relative supersaturation of calcium oxalate. A prospective longitudinal cohort study of 24 morbidly obese adults (9 men and 15 women) recruited from a university-based bariatric surgery clinic scheduled to undergo RYGB between December 2005 and April 2007. Patients provided 24-hour urine collections for analysis 7 days before and 90 days after operation. Primary outcomes were changes in 24-hour urinary oxalate excretion and relative supersaturation of calcium oxalate from baseline to 3 months post-RYGB. Compared with their baseline, patients undergoing RYGB had increased urinary oxalate excretion (31 +/- 10 mg/d versus 41 +/- 18 mg/d; p = 0.026) and relative supersaturation of calcium oxalate (1.73 +/- 0.81 versus 3.47 +/- 2.59; p = 0.030) 3 months post-RYGB in six patients (25%). De novo hyperoxaluria developed. There were no preoperative patient characteristics predictive of development of de novo hyperoxaluria or the magnitude of change of daily oxalate excretion. This prospective study indicates that RYGB is associated with an earlier increase in urinary oxalate excretion and relative supersaturation of calcium oxalate than previously reported. Additional studies are needed to determine longterm post-RYGB changes in urinary oxalate excretion and identify patients that might be at risk for hyperoxaluria developing.

To our knowledge baseline lithogenic risk factors in the morbidly obese population are currently unknown. Prior studies evaluated known stone formers and correlated risk with increasing body mass index. We describe risk factors for urinary stone formation in a group of unselected morbidly obese patients. Patients scheduled for gastric bypass provided a 24-hour urine collection before surgery. Patient demographics, medications and supplement consumption were recorded. A dietary intake diary was converted into daily kcal, Ca, Na and protein consumption. Differences between groups based on gender, history of diabetes or nephrolithiasis, diuretic use and Ca supplementation were evaluated. Correlation of stone risk parameters with body mass index was evaluated. A total of 45 patients provided samples for analysis. Mean +/- SD body mass index was 49.5 +/- 9.1 kg/m(2) and mean age was 47.0 +/- 10.5 years. Overall 97.8% of patients had at least 1 lithogenic risk factor identified. Low urinary volume was the most common abnormality, affecting 71.1% of patients. Male patients excreted significantly more Ox (p = 0.0014), Na (p = 0.020), PO(4) (p = 0.0083) and SO(4) (p = 0.0014) than females. Patients with a history of nephrolithiasis excreted significantly more oxalate (p = 0.018) and had higher relative Na urate supersaturation (p = 0.00093) than nonstone formers. Hydrochlorothiazide use was associated with significantly increased Na urate relative supersaturation (p = 0.0097). Increasing body mass index was inversely associated with Mg (r = -0.38, p = 0.01) and brushite (r = -0.30, p = 0.04). Of our cohort of morbidly obese patients 98% had at least 1 lithogenic risk factor identified on 24-hour urine collection. This study identified a high urinary stone risk in the morbidly obese and suggests possible avenues for dietary and/or pharmacological preventive measures. Future studies will determine how bariatric surgery alters these risk factors.

Erectile dysfunction (ED) and androgen deficiency in aging men are two separate clinical entities that often overlap. Controversy exists regarding the most appropriate total testosterone level that defines androgen deficiency in aging men, and its prevalence in men with ED is still uncertain. We evaluated the prevalence and risk factors of low and low-normal testosterone levels in men presenting for an initial ED evaluation. The computerized charts from 1987 to 2002 of 2794 men aged 25 to 80 years and presenting with a primary complaint of ED who also had serum total testosterone levels measured were retrospectively reviewed. Multiple testosterone level cutpoints and a linear regression model (including age, diabetes, cholesterol, anemia, creatinine, and prostate-specific antigen) were used to analyze the factors that correlated with hypogonadism. The prevalence of androgen deficiency was 7%, 23%, 33%, and 47% for testosterone levels of less than 200, less than 300, less than 346, and less than 400 ng/dL, respectively. An abrupt increase in hypogonadism prevalence occurred in men aged 45 to 50, beyond which a plateau of prevalence was maintained until older than 80 years of age. Age, the presence of uncontrolled diabetes, high total cholesterol, and anemia all correlated with significantly decreased testosterone levels in men with ED. The prostate-specific antigen level and creatinine did not affect the testosterone levels. Androgen deficiency was quite common in men presenting with ED and correlated significantly with age, uncontrolled diabetes, hypercholesteremia, and anemia. Although additional prospective studies evaluating the effect of testosterone supplementation in this population are needed, clinicians, including urologists, should be keenly aware of the large overlap of patients with ED who might also have the entity, androgen deficiency in the aging male.