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Biomedical subjects

Amit Gupta

Publications and source records attributed to Amit Gupta.

At least 37 records · Page 2Linked to original sources

Cancer specific outcomes in patients with pT0 disease following radical cystectomy.

PURPOSE: We assessed clinical outcomes in patients found to have no evidence of disease, ie pT0, in the cystectomy specimen following radical cystectomy for transitional cell carcinoma. MATERIALS AND METHODS: Between 1984 and 2003, 955 consecutive patients underwent bilateral pelvic lymphadenectomy and radical cystectomy for bladder cancer at 3 institutions, namely The Johns Hopkins Hospital, University of Texas Southwestern Medical Center and Baylor College of Medicine. Excluding nonTCC histology and patients with missing data resulted in 888 evaluable cases. Primary end points were recurrence-free survival and bladder cancer specific survival. RESULTS: Final pathological evaluation revealed absent transitional cell carcinoma in the cystectomy specimen, ie pT0, in 59 patients (7%), of whom 2 (3%) had pathologically positive lymph nodes. Transurethral resection stage or clinical stage data were available on 56 patients (95%), including Tis in 5 (9%), Ta in 2 (4%), T1 in 18 (32%), T2 in 29 (52%) and T3 in 2 (4%). Overall 6 recurrences (10%) were noted, including cTis in 1 case, cT1 in 1, cT2 in 3 and cT3 in 1. Median followup in patients with pT0 disease was 56 months (range 3 to 183). Three patients (5%) died of bladder cancer and another 4 (7%) died of other causes. Five and 10-year bladder cancer progression-free and cancer specific survival estimates in patients with pT0 disease were 90% and 81%, and 95% and 85%, respectively. CONCLUSIONS: Despite excellent clinical outcomes in the majority of patients with no evidence of tumor on final pathological evaluation not all patients with pT0 disease in the cystectomy specimen are cured of bladder cancer. These events may even occur in patients with nonmuscle invasive or muscle invasive organ confined pathology at staging transurethral resection. Further study is needed to identify prognostic factors in this population.

Adult↗

Clinical outcomes following radical cystectomy for primary nontransitional cell carcinoma of the bladder compared to transitional cell carcinoma of the bladder.

PURPOSE: The effect of bladder cancer histological subtypes other than transitional cell carcinoma (nonTCC) on clinical outcomes remains uncertain. We conducted a multi-institutional retrospective study of patients with bladder cancer treated with radical cystectomy to assess the impact of nonTCC histology on bladder cancer specific outcomes. MATERIALS AND METHODS: A total of 955 consecutive patients underwent radical cystectomy with bilateral pelvic lymphadenectomy for bladder cancer at 3 academic institutions. TCC was present in the radical cystectomy specimen in 888 patients (93%). NonTCC histology was present in 67 patients (7%), including squamous cell carcinoma in 26, adenocarcinoma in 13, small cell carcinoma in 10 and other nonTCC subtypes (ie spindle cell carcinoma, carcinosarcoma and undifferentiated carcinoma) in 18. For patients alive at last followup median followup was 39 and 23 months for patients with TCC and nonTCC histologies, respectively. Bladder cancer specific progression and survival were assessed using Kaplan-Meier and multivariate Cox proportional hazards analyses. RESULTS: Bladder cancer specific progression and mortality did not differ significantly between patients with SCC and TCC histologies. Patients with nonTCC and nonSCC bladder cancer were at significantly increased risk for progression and death compared to patients with TCC or SCC (p <0.001). This association remained statistically significant in patients with organ confined disease (stage pT2 or lower) and patients with nonorgan confined disease (stage pT3 or higher) (p <0.001). In a multivariate analysis nonTCC and nonSCC histology was associated with an increased risk of bladder cancer progression and death (OR 2.272 and 2.585, respectively, p <0.001), even after adjusting for final pathological stage, lymph node status, lymphovascular invasion and neoadjuvant or adjuvant treatments. CONCLUSIONS: NonTCC and nonSCC histological subtype is an independent predictor of bladder cancer progression and mortality in patients undergoing radical cystectomy for bladder cancer. Patients with bladder TCC and SCC share similar stage specific clinical outcomes.

Aged↗

Treatment of erectile dysfunction with sildenafil citrate in renal allograft recipients: a randomized, double-blind, placebo-controlled, crossover trial.

BACKGROUND: Erectile dysfunction (ED) is observed frequently in patients with end-stage renal disease, hemodialysis patients, and renal allograft recipients. There are few studies of sildenafil use in renal allograft recipients. METHODS: The study is designed as a randomized, double-blind, placebo-controlled, crossover trial. Efficacy was assessed by using the self-administered International Index of Erectile Function (IIEF), a 15-question validated measure of ED, and a global efficacy question (Did the treatment improve your erection?). RESULTS: Thirty-two eligible renal transplant recipients were included in this study. After treatment with sildenafil citrate, patients had significantly better scores in 13 of 15 questions, except for questions 11 (desire frequency; P = 0.39) and 12 (desire level; P = 0.61). Treatment efficacy assessed through questions 3 (penetration ability; P < 0.001) and 4 (maintenance frequency; P < 0.001) was significantly better after sildenafil therapy. There were no significant differences between baseline and post-placebo treatment scores, except for question 13 (relationship satisfaction). Patients treated with sildenafil had significantly better scores in 4 domains compared with baseline, but a difference was not observed in the sexual desire domain (P = 0.32). There were no significant differences in scores between placebo and baseline in any domain. On the global efficacy question, 81.3% of patients showed improvement compared with 18.7% with placebo. There were no differences in areas under the curve and maximum cyclosporine concentrations before and after sildenafil therapy. No patient discontinued the drug because of side effects except for 1 patient with visual hallucination. CONCLUSION: Treatment with sildenafil in renal transplant recipients is a valid option with an effective response.

Adult↗

Dioxin exposure and benign prostatic hyperplasia.

OBJECTIVE: Dioxins decrease prostate weight, reduce androgen responsiveness, and inhibit prostate morphogenesis in rats. We assessed the association of dioxins and benign prostatic hyperplasia (BPH) in participants in the National Health and Nutritional Examination Survey 1999-2000. METHODS: Forty-two participants were classified as having BPH and 99 were classified as controls. Dioxin exposure was expressed as dioxin toxic equivalents (TEQ). Age, body mass index, waist circumference, race/ethnicity, smoking, physical activity, and education were assessed as potential confounders. RESULTS: After age adjustment, men without BPH had 20.9% higher TEQs (95% confidence interval [CI] = 5.4-38.7%) as compared with men with BPH. On weighted, multivariate, logistic regression analyses, men with higher dioxin levels had lower odds of having BPH (odds ratio = 0.22, 95% CI = 0.08-0.62). CONCLUSIONS: Dioxin exposure in the general population may be associated with decreased odds of BPH. Our study findings need to be confirmed.

Aged↗

Serum dioxin, testosterone, and subsequent risk of benign prostatic hyperplasia: a prospective cohort study of Air Force veterans.

BACKGROUND: Operation Ranch Hand veterans were involved in spraying herbicides, including Agent Orange, during the Vietnam War in 1962-1971; Agent Orange was contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). It has been hypothesized that dioxins may be partially responsible for an increase of male reproductive tract disorders such as testicular cancer, cryptorchidism, and hypospadias. OBJECTIVES: In this study, our objective was to assess the effect of serum TCDD concentration on the risk of development of benign prostatic hyperplasia (BPH) and on serum testosterone levels. METHODS: This study was a longitudinal, prospective cohort study made up of U.S. Air Force veterans involved in Operation Ranch Hand. Other Air Force veterans who did not spray herbicides were included as comparisons. BPH was determined by medical record review and by medical examinations conducted during the study. Data were available for 971 Ranch Hand and 1,266 comparison veterans. We investigated the relationship between BPH and serum TCDD level using the Cox proportional hazards models adjusted for testosterone levels, body mass index (BMI), and the percentage change in BMI per year. RESULTS: In univariate and multivariate analyses, the risk of BPH decreased with increasing serum TCDD in the comparison group. The multivariate risk ratio for BPH in the comparison group was 0.84 (95% confidence interval, 0.73-0.98). Excluding men with prostate cancer, inflammatory or other prostatic diseases did not substantially alter the association. Serum testosterone levels were inversely associated with serum TCDD levels in both Ranch Hand and comparison groups. CONCLUSIONS: TCDD exposure at general population levels is associated with a decreasing risk of BPH with higher exposure levels. TCDD exposure is also negatively associated with serum testosterone levels.

Dioxins↗

Steroid resistant nephrotic syndrome: role of histopathology.

This study was conducted to (1) see the histopathological distribution of different subtypes in steroid resistant nephrotic syndrome (SRNS) and (2) compare the clinical, biochemical parameters and outcome between Minimal Change Disease (MCD) with non-MCD subtypes in response to immunosuppressive therapy. A retrospective analysis was done of data on all biopsy proven children with idiopathic SRNS (no response to 4 weeks of standard prednisone therapy (60 mg/m(2)/day)) referred to our institute over last 12 years. They were treated with one of the following medications: oral or intravenous cyclophosphamide, cyclosporine or combination of dexamethasone and azathioprine. A comparison was done of the demographic clinical and biochemical features different histopathologies. We studied 136 children with SRNS (100 M, 36 F). They accounted for 15.1%(136/900) of all children with idiopathic nephrotic syndrome. Focal segmental glomerulosclerosis (FSGS) was the commonest 80/136 (59%), followed by MCD (17.6%). Children with non-MCD had a significantly greater prevalence of microhematuria as compared to MCD. The other baseline clinical and biochemical features including the glomerular filtration rate (GFR) were similar. After a mean follow up of 46 (8-148) months, a significantly greater children with non-MCD 65/112) continued to be proteinuric as compared to the MCD (3/24) (p=0.0001). FSGS was the commonest cause of SRNS in our patient population. Children with SRNS secondary to MCD are more likely to achieve remission as compared to non-MCD subtypes and have a better long-term prognosis. Hence kidney biopsy is of significant prognostic value in SRNS.

Adolescent↗

Continuous peritoneal dialysis in children: a single-centre experience in a developing country.

Continuous peritoneal dialysis (CPD) is the most commonly used modality of dialysis in children. Continuous ambulatory peritoneal dialysis (CAPD) has been an established form of therapy in adult patients with end-stage renal failure in India for more than a decade. There is a paucity of published experience of CPD in children from developing countries. We retrospectively studied children with end-stage renal failure (ESRD) that had been on CAPD over the past 10 years. Thirty patients with ESRD, mean age 13+/-8 years (range 5-21 years), male 18, were started on CAPD from 1994 to October 2004. The mean break-in period was 12+/-3 days. Of these 30 patients, 15 had a total of 21 episodes of peritonitis. The peritonitis rate was 0.58 episodes per patient year. E. coli was the commonest organism causing peritonitis. On outcome analysis, 7/30 (23.3%) patients received a renal transplant, while 11/30 (36.6%) continued on CAPD, awaiting a kidney transplant. Of the rest, eight (26.6%) patients died, two (6.7%) suffered technique failure and were changed to haemodialysis, and two (6.7%) were lost to follow-up after 2 months. The mean cumulative survival time of patient on CPD was 42 months. We conclude that CPD is a viable option for dialysis in ESRD children in a developing country and is a successful bridge between ESRD and renal transplantation.

Adolescent↗

Immediate corticocancellous bone autografting in segmental bone defects of the hand.

We performed a retrospective analysis of 12 type III open hand fractures in seven patients with segmental bone loss and associated soft tissue injuries to determine the effectiveness of immediate autologous corticocancellous bone grafting. Radical débridement and fracture fixation were performed prior to bone grafting. Results were interpreted according to clinical and radiologic time of bony healing, rate of infection, time to return to regular work duty, grip strength, rate of complications and range of motion. The final union rate was 92%, with a mean time to bony union of 18 weeks. The infection rate was 0%. The mean time to return to regular work duty, including recovery time after secondary surgeries, was 5 months and 21 days. All patients returned to their pre-injury employment. The mean total active motion of the combined metacarpophalangeal proximal interphalangeal and distal interphalangeal joints in bone-grafted digits was 178 +/- 53 degrees at final follow-up.

Adult↗

Isolation, characterization and biological evaluation of datura lactones as potential immunomodulators.

Phytochemical investigation of Datura quercifolia (Solanaceae) plant yielded a new datura lactone, 1beta,5alpha,12alpha-trihydroxy-6alpha,7alpha,24alpha,25alpha-diepoxy-20S,22R with-2-enolide (1), along with two known compounds, 2 and 3. The structure of 1 was established on the basis of spectral analysis, as well as by its chemical transformation into known datura lactones. These compounds have been evaluated for immunomodulatory activity by observing their effect on antibody production, T-cell and B-cell activation, and cytokine production from splenocytes. Compound 2 was found to be the most promising immunostimulator in the present study.

Animals↗

Lymphovascular invasion is independently associated with overall survival, cause-specific survival, and local and distant recurrence in patients with negative lymph nodes at radical cystectomy.

PURPOSE: We hypothesized that bladder cancer patients with associated lymphovascular invasion (LVI) are at increased risk of occult metastases. METHODS: A multi-institutional group (University of Texas Southwestern [Dallas, TX], Baylor College of Medicine [Houston, TX], Johns Hopkins University [Baltimore, MD]) carried out a retrospective study of 958 patients who underwent cystectomy for bladder cancer between 1984 and 2003. Of patients with transitional-cell carcinoma (n = 776), LVI status was available for 750. LVI was defined as the presence of tumor cells within an endothelium-lined space. RESULTS: LVI was present in 36.4% (273 of 750) overall, involving 26% (151 of 581) and 72% (122 of 169) of node-negative and node-positive patients, respectively. Prevalence of LVI increased with higher pathologic stage (9.0%, 23%, 60%, and 78%, for T1, T2, T3, and T4, respectively; P < .001). Using multivariate Cox regression analyses including age, stage, grade, and number of pelvic lymph nodes removed, LVI was an independent predictor of local (HR = 2.03, P = .049), distant (HR = 2.60, P = .0011), and overall (HR = 2.02, P = .0003) recurrence in node-negative patients. LVI was an independent predictor of overall (HR = 1.84, P = .0002) and cause-specific (HR = 2.07, P = .0012) survival in node-negative patients. LVI maintained its independent predictor status in competing risks regression models (P = .013), where other-cause mortality was considered as a competing risk. LVI was not a predictor of recurrence or survival in node-positive patients. CONCLUSION: LVI is an independent predictor of recurrence and decreased cause-specific and overall survival in patients who undergo cystectomy for invasive bladder cancer and are node-negative. These patients represent a high risk group that may benefit from integrated therapy with cystectomy and perioperative systemic chemotherapy.

Age Distribution↗

A study of pore blockage in silicalite zeolite using free energy perturbation calculations.

Binary systems consisting of large coadsorbed molecules (n-hexane, cyclohexane, and benzene) with smaller penetrant molecules (methane) were simulated to investigate the mechanisms of pore blockage in the zeolite silicalite. Benzene and cyclohexane trap the methane molecules in the zeolite channels on the time scales of molecular dynamics simulations. Minimum energy paths for methane diffusion past the blocking molecules were determined, and free energy perturbation calculations were carried out along the paths to get the rate constants of methane hopping past coadsorbed benzene and cyclohexane molecules, which adsorb in the channel intersections. Three principal diffusion pathways were found in both the methane/benzene and methane/cyclohexane systems. Minima which were connected by low-energy pathways were grouped together into macrostates. Using the calculated hopping rates between macrostates, kinetic Monte Carlo was then used to obtain the diffusivity of methane with a coadsorbate benzene loading such that all channel intersections are filled by benzene - conditions where molecular dynamics simulations fail. Passage of methane across cyclohexane molecules involved pushing the cyclohexane molecules into the channels from their preferred channel intersection positions.

Journal Article↗

Relationship between prostate specific antigen and indexes of prostate volume in Japanese men.

PURPOSE: We determined the relationship between serum prostate specific antigen (PSA) and indexes of prostate volume in Japanese men, and compared that relationship with the one in white men. MATERIALS AND METHODS: Data on a clinical cohort of 535 Japanese men with at least moderate lower urinary tract symptoms (LUTS) and clinical benign prostatic hyperplasia were examined. PSA, and total and transition zone prostate volume were related to age and linear regression analyses were performed to analyze the relationship between PSA and volume indexes. RESULTS: The group of 535 men with a median age of 68 years had a median serum PSA of 1.5 ng/ml, and a median total and transition zone volume of 26.8 and 8.8 ml, respectively. PSA, total prostate volume and transition zone volume increased almost linearly with age. On univariate regression with age with each successive decade total prostate volume increased by 10.65% (95% CI 5.4 to 16.2), transition zone volume increased by 20.84% (95% CI 11.84 to 30.56) and the transition zone index increased by 3.1% (95% CI 1.66 to 4.57). On multivariate analysis the PSA-total prostate volume relationship was statistically independent of age. The study suggests that Japanese men might produce or release more PSA per unit prostate volume than white men. CONCLUSIONS: Japanese men with LUTS and clinical benign prostatic hyperplasia but no evidence of prostate cancer might produce and/or release more PSA per unit prostate volume than white men. To our knowledge the cutoffs for PSA and prostate volume to predict the response to LUTS therapy and the development of complications in Japanese men are unknown. Future studies in Japanese men are needed to identify these cutoffs.

Adult↗

The reproducibility of urodynamic findings in healthy female volunteers: results of repeated studies in the same setting and after short-term follow-up.

AIM: To assess the immediate (same testing period) and short-term (within 6 months) repeatability of urodynamic (UD) testing in asymptomatic healthy female volunteers. MATERIALS AND METHODS: Twenty asymptomatic women with a mean age of 41.8 years (30-55) agreed to undergo a UD assessment which consisted of noninvasive uroflowmetry, post-void residual (PVR) measurement, medium-fill cystometry, and pressure flow study with perineal surface electromyographic (EMG) electrodes. The UDS evaluation was repeated immediately without removing the catheters (a two-fill and void study). Sixteen women returned for an identical UD assessment 1-5 months later. Immediate and short-term repeatability of UD parameters was assessed by calculating the coefficient of repeatability (COR). RESULTS: The repeatability of certain parameters of immediate UD testing could not be calculated since there was an apparent influence of the first test on the second (i.e., an apparent accommodation noted in bladder filling volumes). Other immediate UD values (maximum flow, detrusor pressure at maximum flow, voided volume) had high COR values, as did all UD values on short-term testing, indicating relatively poor repeatability. Picking the 'best' pressure flow value (highest flow rate with accompanying detrusor pressure) did not consistently improve the COR values. CONCLUSIONS: The lack of repeatability of UD studies likely stems from a combination of the true physiological fluctuations in bladder function and the inherent relative insensitivity of our instruments in conducting these testing. Knowledge of the limitations of current technology is essential in allowing us to better utilize these studies in evaluating our patients and further improving diagnostic strategies.

Adult↗

Anatomic study of variations of hypothenar muscles and arborization patterns of the ulnar nerve in the hand.

PURPOSE: To show the variations in the hypothenar muscles and the arborization patterns of the ulnar nerve and to investigate the relationship between the hypothenar muscles and the ulnar nerve. METHODS: We performed an anatomic study of 35 hands from embalmed cadavers. After dissecting the ulnar side of the hand we recorded the number of hypothenar muscles and their variations, the site of the hiatus for the deep branch of the ulnar nerve, and the branching patterns of the ulnar nerve in each hand. We then investigated the relationship between the variations in the hypothenar muscles and the arborization patterns of the ulnar nerve. RESULTS: The abductor digiti minimi (ADM) had 1 belly in 6 hands, 2 bellies in 28 hands, and 3 bellies in 1 hand. The flexor digiti minimi brevis was absent in 8 hands, had 1 belly in 24 hands, and had 2 bellies in 3 hands. The opponens digiti minimi had 2 layers of origin and the deep branch of the ulnar nerve passed between these 2 layers in all hands. We classified the structural patterns of the hiatus into 3 types, the arborization patterns of the ulnar nerve into 5 types, and the branching patterns of the motor branch to the ADM into 4 types according to their morphologic characteristics. We found variations of the arborization pattern in which the deep branch originated from the ulnar trunk of the ulnar nerve distal to bifurcation in 3 hands, a communicating branch was present between the 2 sensory branches to the fingers in 3 hands, and the ulnar sensory branch pierced the ADM in 2 hands. CONCLUSIONS: We confirmed that the anatomic relationship between the ulnar nerve and the hypothenar muscle is complex and that the formation of the hiatus varies. This knowledge can assist the surgeon in the diagnosis and treatment of conditions associated with the ulnar aspect of the hand.

Aged↗

Analysis of prognostic factors in ring avulsion injuries.

PURPOSE: To report 105 cases of ring avulsion injuries, examine the factors affecting rate of survival and functional outcome after reconstruction, and evaluate whether these data provide enough evidence to support attempts to repair these injuries. METHODS: A retrospective cohort study was conducted in 105 patients with 105 ring avulsion injuries of all grades of severity treated at our center between 1977 and 2003. Factors that could affect the outcome included personal (gender, age, smoking history, vascular disease, diabetes mellitus, alcohol abuse), injury (finger affected, level of skeletal injury, presence of tendon and nerve injury, Urbaniak class as modified by Kay et al, presurgery time), and surgery features (number of arteries and veins reconstructed primarily and with vein grafts). Results were interpreted based on survival and final function. Function was measured by the presence of pain, range of motion, and 2-point discrimination. RESULTS: Of the 86 digits with inadequate circulation, 11 digits had primary amputation. Reconstruction was attempted in 75 digits. Fourteen digits had secondary amputation because of revascularization failure. Failure was attributed to artery problems in 5 digits and to vein problems in 5 digits and was unknown in 4 digits. The overall survival rate was 81%. CONCLUSIONS: Cigarette smoking is not associated with higher risk of revascularization failure. Reconstruction of 2 or more veins resulted in higher survival rates compared with reconstruction of only 1 vein. Level of bone injury is not an accurate indication of whether to attempt reconstruction. Primary nerve repair does not lead to a good sensory recovery in most digits. Patients who had their digits finally amputated had variable periods of hypersensitivity at the stump, which prolonged their convalescence time.

Adolescent↗

Verification and incorporation biases in studies assessing screening tests: prostate-specific antigen as an example.

OBJECTIVES: Prostate-specific antigen (PSA) measurement is a widely used screening test for prostate cancer. However, studies assessing the performance of PSA suffer from verification bias and incorporation bias, because men with PSA levels less than 4 ng/mL do not undergo biopsy unless the digital rectal examination findings are suspicious for prostate cancer. We have reviewed how these biases have influenced such studies. METHODS: We compared the results of three studies that reported on the test characteristics of PSA, taking into account the types of bias present. We applied approximate verification bias corrections to previously reported age-specific reference ranges, based on the reported 22% cancer detection rate in the PSA range 2.5 to 4 ng/mL. To adjust for incorporation bias, we removed PSA from the criteria establishing the absence of prostate cancer and recalculated the test characteristics of PSA. RESULTS: Verification bias led to an elevation in the sensitivity estimates of PSA. The specificity increased or decreased depending on the type of bias present. After accounting for incorporation bias, the sensitivity of PSA testing at a 4-ng/mL cutoff level was less than 67%, and the specificity was more than 80.6%. CONCLUSIONS: Studies evaluating PSA testing have been biased because of the presence of verification and incorporation biases. Future studies must consider the possibility of these biases to obtain valid results.

Adenocarcinoma↗