Biomedical subjects
Publications and source records attributed to M E Mitchell.
Bladder exstrophy remains one of the most challenging problems in pediatric urology. Recent efforts have focused on primary reconstruction rather than urinary diversion to treat exstrophy. Complete primary closure appears to offer improved continence and decreases the number of surgical procedures required to treat exstrophy.
We reviewed our experience with minimally invasive direct-access mitral valve surgery in 207 patients through February 1999. Three patients underwent associated procedures, a coronary artery bypass graft (CABG) with right internal mammary artery to right carotid artery (RIMA-RCA), a left ventricular outflow tract (LVOT) debridement for endocarditis, and a primum atrial septal defect (ASD) repair, and were excluded from analysis. Of the 204 remaining patients, 120 (59%) patients were men, aged 58.7 +/- 13.2 years, functional class of 2.3 +/- 0.5. The cause was myxomatous in 162 (79%) patients, rheumatic in 28 (14%) patients, endocarditis in 8 (4%) patients, congenital in 3 (2%) patients, and ischemic in 3 (2%) patients. Mean preoperative EF was 60% +/- 10%, with 184 (90%) patients showing ejection fraction (EF) greater than 50%. The valve was approached through a 5- to 8-cm right parasternal (n = 180, 88%) or right inframammary (n = 24, 12%) incision. One hundred nineteen (58%) patients had open femoral artery-femoral vein cannulation, and 85 (42%) patients had direct cannulation of the aorta and percutaneous cannulation of the femoral vein. One hundred seventy (83%) patients underwent successful valve repair, and 34 (17%) patients required valve replacement. The mean duration of aortic clamping and cardiopulmonary were, respectively, 100 +/- 34 and 146 +/- 44 minutes. There were 2 (1%) surgical deaths. Nonfatal perioperative complications included 3 (1.5%) ascending aortic complications, 3 (1.5%) reoperations for bleeding, 4 (2%) strokes, 2 (1%) transient ischemic attacks (TIAs), 2 (1%) myocardial infarctions, 3 (1.5%) pericardial effusions requiring drainage, 9 (4.5%) vascular complications, and 3 (1.5%) wound complications. Mean length of stay (LOS) was 6.1 +/- 3 days, with 63 (31%) patients being discharged in less than 5 days. One hundred twenty-nine (63%) patients did not require blood transfusions. Follow-up was complete in 165 (81%) patients, with mean follow-up of 13.2 +/- 8 months. Late complications included 1 (0.5%) myocardial infarction, 3 (1.5%) reoperations, all converting repairs to replacements, 3 (1.5%) wound hernias requiring reoperation and repair with mesh, 5 (2.5%) thromboembolic events, and 3 (1.5%) deaths of suicide, pneumonia, and sudden death, respectively. Mean follow-up New York Heart Association (NYHA) functional class was 1.2 +/- 0.5. We conclude that minimally invasive direct-access mitral valve surgery is safe, effective, and applicable for most patients presenting for isolated mitral valve surgery. We now consider it the standard of care for selected patients.
This study examined the efficacy of augmenting standard weekly cognitive-behavioral treatment for obesity with a self-monitoring intervention during the high risk holiday season. Fifty-seven participants in a long-term cognitive-behavioral treatment program were randomly assigned to self-monitoring intervention or comparison groups. During 2 holiday weeks (Christmas-New Years), the intervention group's treatment was supplemented with additional phone calls and daily mailings, all focused on self-monitoring. As hypothesized, the intervention group self-monitored more consistently and managed their weight better than the comparison group during the holidays. However, both groups struggled with weight management throughout the holidays. These findings support the critical role of self-monitoring in weight control and demonstrate the benefits of a low-cost intervention for assisting weight controllers during the holidays.
PURPOSE: The surgical correction of bladder exstrophy to achieve continence with voiding remains a challenging problem for the urologist. Since 1989 we have performed complete primary repair for exstrophy based on the concept that the primary defect of bladder and cloacal exstrophy is anterior herniation. Thus, the bladder and urethra must be treated as a single unit to move them posteriorly into the pelvis. We present this technique. MATERIALS AND METHODS: From 1989 to 1997, 18 patients with bladder exstrophy and 6 with cloacal exstrophy underwent complete primary repair of exstrophy. This procedure was done on day 1 of life in 18 patients. Mean followup is 44 months (range 4 months to 8 years). RESULTS: At a median followup of 48 months 4 boys and 4 girls have volitional voiding after complete primary repair of bladder exstrophy, 21 patients have continent intervals and 2 boys void with continent intervals after complete primary repair of cloacal exstrophy. No patient has had a loss of renal function in this series. Postoperative complications included urethrocutaneous fistula formation in 2 cases. No patient had primary closure dehiscence. CONCLUSIONS: The rate of urinary continence achieved with complete primary repair compares favorably to that of staged repair for exstrophy. Complete primary repair also minimizes the number of surgical procedures required to achieve urinary continence and potentiates bladder neck function that permits bladder cycling in year 1 of life. The complication rates of these techniques are significantly lower than those reported in previous series of primary closure of exstrophy.
Over the last 150 years, bladder exstrophy has undergone a transition from a primarily nonsurgically treated disease to a disease treated by urinary diversion or staged repair and now, possibly, primary newborn reconstruction. Our enthusiasm for primary reconstruction arises because of its potential to simplify the management of this disorder and optimize the return of normal bladder function for these patients. As with most new concepts, the evolution of our primary reconstruction techniques could not have been achieved without the prior efforts of others. Other surgeons such as H.H. Young and J. Ansell have shown us the possibility of achieving urinary continence with primary newborn exstrophy closure without sacrificing renal function, but the results have been inconsistent in the past. Staged reconstruction for bladder exstrophy demonstrates the possibility to achieve consistent successful rates of continence in these patients. However, multiple surgical procedures are required to attain this success. The preliminary results of our series of primary bladder exstrophy closures has encouraged us to perform it for all neonates referred to our institution with bladder exstrophy as well as to use it as part of staged reconstructive efforts for patients who have undergone primary surgical procedures for exstrophy elsewhere. We are hopeful and optimistic that newborn primary exstrophy closure performed as described herein will produce consistent rates of urinary continence and allow normal voiding function as well.
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OBJECTIVES: Visual inspection of the spermatic cord vessels and vas deferens during laparoscopy now frequently determines further treatment. We set out to explore the implications of atretic spermatic cord vessels and vas deferens entering the inguinal ring, a finding noted on laparoscopic examination in some patients with a nonpalpable testis, and that we refer to as the inguinal vanishing testis. METHODS: We reviewed our series of 35 patients with nonpalpable testes with regard to the laparoscopic, surgical, and histopathologic findings of the involved gonadal structures. RESULTS: We noted atretic vessels and vas deferens entering the inguinal ring in 14 patients in this series. All 14 patients underwent open inguinal exploration. Histopathologic findings revealed fibrosis and hemosiderin deposits alone in 13 patients. One specimen had a microscopic focus of residual seminiferous tubules. No specimen contained dysgenetic gonadal tissue. CONCLUSIONS: We submit that patients with inguinal vanishing testes do not need to undergo inguinal exploration to remove residual testicular tissue. Only rarely will viable seminiferous tubules be found, so the risk of malignant degeneration is remote. The histopathologic findings suggest that the inguinal vanishing testis occurs secondary to a vascular accident in utero or in the neonatal period.
PURPOSE: Brachial artery vasoactivity (BAVA) evaluation is a reliable, noninvasive method of assessing arterial endothelial function in vivo. We previously have shown that patients with peripheral vascular disease (PVD) and occult diabetes have abnormal BAVA results when fasting and after oral glucose intake during oral glucose tolerance test (OGTT). Troglitazone is an oral hypoglycemic agent that enhances the action of insulin. The effect of troglitazone on BAVA in patients with occult diabetes and PVD is not known. METHODS: Patients with PVD, normal fasting glucose levels, and abnormal OGTT results were identified. With a duplex ultrasound scan, BAVA was evaluated by measuring the brachial artery (BA) flow (in millimeters per minute) before and after 5 minutes of BA occlusion during fasting and at 30 minutes, 1 hour, and 2 hours after the administration of 75 g of glucose during OGTT. Troglitazone therapy (400 mg/day) was begun, and the BAVA evaluation was repeated after 2 and 4 months. These results were compared with the results of the control group who had normal fasting glucose levels, normal OGTT results, and no evidence of PVD. A paired t test was used to compare the BA flow before and after BA occlusion, with a P value of less than.05 considered significant. RESULTS: The control group had a normal hyperemic response with a significantly increased BA flow after 5 minutes of BA occlusion during fasting and at all stages of the OGTT. The occult diabetic group had an abnormal response to hyperemia before the treatment with troglitazone and showed little change in flow after BA occlusion. After 2 months of troglitazone therapy, BAVA results improved after oral glucose intake but not during fasting. After 4 months, BAVA results normalized both while fasting and after oral glucose intake during the OGTT. CONCLUSION: Patients with occult diabetes and PVD have impaired BAVA, which normalizes after treatment with troglitazone. Insulin-action enhancers may slow the progression of PVD in patients with diabetes by improving endothelial cell function. Agents that are aimed at enhancing the action of insulin may have an advantage over the other traditional therapies for diabetes.
PURPOSE: Peripheral vascular disease involving the infragenicular arterial tree is common in patients with diabetes mellitus (DM). Accelerated proliferation of vascular smooth muscle cells (VSMCs) plays an important role in the development of atherosclerosis. Insulin and glucose stimulate VSMC proliferation and are elevated in patients with non-insulin-dependent DM. We have previously described the mitogenic effect of insulin on VSMCs in vitro; the effects of insulin and glucose separately and in combination on the proliferation of VSMCs grown in serum-free media were studied. METHODS: Human infragenicular VSMCs isolated from diabetic patients with end-stage peripheral vascular disease undergoing below-knee amputation were used. Cells from passages 3 to 5 were grown in serum-free media with varying glucose (0.05%, 0.1%, 0.2%, 0.4%, 0.6%, and 0.8%) and insulin (no added insulin, 100 ng/mL, and 1000 ng/mL) concentrations for 6 days. RESULTS: Insulin stimulated VSMC growth at glucose concentrations more than 0.2% (0.4% glucose with no added insulin resulted in 13,073 +/- 336 cells/mL, 0.4% glucose with 100 ng/mL insulin resulted in 16,536 +/- 1175 cells/mL, 0.4% glucose with 1000 ng/mL insulin resulted in 17,500 +/- 808 cells/mL, 0.6% glucose with no added insulin resulted in 14,167 +/- 1062 cells/mL, 0.6% glucose with 100 ng/mL insulin resulted in 18,984 +/- 1265 cells/mL, 0.6% glucose with 1000 ng/mL insulin resulted in 20,450 +/- 1523 cells/mL, 0.8% glucose with no added insulin resulted in 15, 853 +/- 1650 cells/mL, 0.8% glucose with 1000 ng/mL insulin resulted in 26,302 +/- 1919 cells/mL; P <.05 compared with glucose with no added insulin). Glucose stimulated VSMC proliferation up to a concentration of 0.2% (42% and 117% higher growth at 0.1% and 0.2% glucose, respectively, compared with the baseline, P <.05), regardless of the insulin concentration in the media. The greatest growth (26,302 +/- 1919 cells/mL) occurred in the group with the highest concentration of both insulin (1000 ng/mL) and glucose (0.8% glucose; P <.05). CONCLUSION: Both insulin and glucose stimulate the growth of diabetic infragenicular VSMCs. The mitogenic effects of insulin and glucose are additive and may contribute to the development of atherosclerosis in patients with DM.
Brachial artery vasoactivity is a well known non-invasive method of assessing arterial endothelial function in vivo. Brachial artery vasoactivity has been found to be impaired in overt diabetes and in patients with coronary artery disease. Impaired brachial artery vasoactivity is felt to be an early indicator of atherosclerosis. The authors identified a group of patients with lower extremity peripheral vascular disease, who had normal fasting glucose level and were not known to be diabetics. An oral glucose tolerance test was performed in this group of patients. Brachial artery vasoactivity was assessed at each step of the oral glucose tolerance test to examine their occult diabetic status and correlate brachial artery vasoactivity to that status. The authors studied 23 randomly selected patients from the vascular surgery clinic between the ages of 50 and 79 years. Serum glucose level was assessed after a 10-h fast and at 30, 60 and 120 min after a 75-g oral glucose challenge. Any patient with two serum glucose values > 140 mg/dl was considered to have a positive oral glucose tolerance test. Using duplex ultrasound, the brachial artery diameter (cm) and blood volume (ml/min) were assessed before and after tourniquet occlusion at each step of the oral glucose tolerance test. Paired and unpaired t-tests were used to evaluate the results, P < 0.05 was considered significant. Nine patients had abnormal oral glucose tolerance test for a prevalence of 39%. There was no significant difference in fasting glucose levels between positive and negative oral glucose tolerance test patients (97.4+/-16.7 versus 88.5+/-5.8, P = 0.23). Patients with a positive oral glucose tolerance test had impaired vasoactivity at fasting and at each step of the test with no significant changes in brachial artery diameter or blood flow in response to brachial artery occlusion. Patients with a negative oral glucose tolerance test exhibited increased brachial artery diameter at fasting in response to brachial artery occlusion (0.43+/-0.02 versus 0.46+/-0.02, P = 0.03), but not after oral glucose challenge. In patients with a negative oral glucose tolerance test, brachial artery flow volume increased significantly in response to hyperemia at fasting (240+/-61 versus 578+/-262, P = 0.001) and at 30 min after glucose intake (260+/-53 versus 358+/-72, P = 0.01). At 60 and 120 min after glucose intake, brachial artery flow volume did not significantly increase in response to brachial artery occlusion. These results indicate that individuals with PVD and normal fasting glucose levels have a high prevalence of positive oral glucose tolerance test (39%). Patients with normal fasting glucose levels and abnormal oral glucose tolerance test have impaired brachial artery vasoactivity at fasting and after oral glucose challenge, this is in contrast to patients with normal oral glucose tolerance test who have normal fasting hyperemic response to brachial artery occlusion. However, this normal brachial artery vasoactivity is lost in the negative oral glucose tolerance test group in response to oral glucose load. These results suggest that endothelial function in diabetics is impaired in the early stages of the disease even before overt hyperglycemia occurs. Tight control of blood glucose level in glucose-intolerant patients prior to occurrence of overt fasting hyperglycemia may prove protective.
The vitamin B-6 requirement of young women consuming a constant high-protein diet (1.55 g/kg body wt) and the effect of various ratios of vitamin B-6 to protein on this requirement were studied. Eight women were fed a lactoovovegetarian basal diet containing 0.45 mg vitamin B-6 (2.66 micromol as pyridoxine) and 30 micromol carnitine for 92 d. The protocol consisted of successive baseline adjustment (9 d), depletion (27 d), and repletion (two 21-d and then one 14-d) periods. Vitamin B-6 intakes were 1.60, 0.45, 1.26, 1.66, and 2.06 mg, resulting in ratios of vitamin B-6 (in mg) to protein (in g) for the five periods of 0.016, 0.005, 0.013, 0.017, and 0.021, respectively. Direct and indirect as well as short- and long-term vitamin B-6 status measures were assessed weekly. Regression analysis revealed that the amount of dietary vitamin B-6 required to normalize urinary 4-pyridoxic acid, plasma pyridoxal-P, erythrocyte pyridoxal-P and pyridoxal, and erythrocyte alanine and aspartate aminotransferase activity coefficients to predepletion baseline values was 1.94 mg vitamin B-6/d (0.019 mg vitamin B-6/g protein). This study suggests that the current vitamin B-6 recommended dietary allowance of 1.6 mg/d based on 0.016 mg/g protein is not an adequate intake and may require reevaluation.
The purpose of the present study was to determine whether vitamin B-6 depletion and repletion influence carnitine concentrations in the plasma, erythrocytes, and urine of young adult women consuming a low-carnitine (30 micromol/d), lactoovovegetarian diet. Doses of vitamin B-6 were administered sequentially as follows: 1.60 mg/d during adjustment for 9 d, 0.46 mg/d during depletion for 27 d, 1.26 mg/d during the first repletion for 21 d, 1.66 mg/d during the second repletion for 21 d, and 2.06 mg/d during the third repletion for 14 d. Urinary carnitine tended to decline but was not significantly different throughout the 92-d study period. Plasma short-chain acylcarnitine and total carnitine decreased during vitamin B-6 depletion; however, the ratio of plasma acylcarnitine to total carnitine was not significantly different during changes in vitamin B-6 intake. Erythrocyte long-chain acylcarnitine increased during vitamin B-6 depletion, but the ratio of erythrocyte acylcarnitine to total carnitine did not respond to changes in vitamin B-6 intake. Plasma free and total carnitine concentrations were only weakly correlated with plasma pyridoxal-P concentration (r = 0.28 and r = 0.29, respectively; P < 0.01). No significant correlations were observed between urinary carnitine excretion or erythrocyte carnitine concentrations and plasma or erythrocyte pyridoxal-P concentrations. Thus, a vitamin B-6 intake of 0.5 mg/d does not affect carnitine concentrations in biological fluids and therefore is unlikely to affect endogenous carnitine synthesis over 27 d. The changes in carnitine indexes that we observed were probably due to adaptation to a vegetarian pattern of exogenous carnitine consumption.
Stable isotope dilution gas chromatographic-mass spectrometric (GC-MS) measurement of tricyclic antidepressants (TCA) is a useful alternative to high-performance liquid chromatography (HPLC) methods when interfering substances prevent accurate quantitation by HPLC. For satisfactory GC-MS analysis, secondary amine TCA must be derivatized. Commonly employed trifluoroacetyl and heptafluorobutyryl derivatives are relatively unstable and cause rapid deterioration of capillary GC columns. Therefore we examined 4-carbethoxyhexafluorobutyryl chloride (CHFB-CI) as an alternative derivatizing agent and developed a stable isotope dilution GC-MS method employing ring-labeled [2H4]-desipramine and [2H4]-imipramine internal standards, which permits measurement of desipramine, nortriptyline, imipramine, and amitriptyline in plasma samples containing one or all of these analytes. The GC-MS assay is linear for each analyte from the lower limit of quantitation (25 ng/mL) up to 1500 ng/mL and correlates well with HPLC measurements. The GC-MS analytic coefficient of variation was 9.7 +/- 1.3% for all analytes considered together. Although interferences are observed in the HPLC assay, thioridazine, perphenazine, cyclobenzaprine, and norcyclobenzaprine do not interfere with GC-MS measurements of the TCA examined here. The stability of the CHFB derivative of secondary amine TCA was found to be superior to that of the trifluoroacetyl derivatives of these compounds.
PURPOSE: Voiding dysfunction has been reported after bilateral extravesical ureteral reimplantation. We evaluate the incidence and duration of voiding dysfunction, and the effects of minimizing surgical dissection in a cohort of children after bilateral extravesical reimplantation. MATERIALS AND METHODS: A retrospective chart review was performed on 33 consecutive children who underwent bilateral extravesical ureteral reimplantation for reflux. Preoperative and postoperative radiological studies, and postoperative post-void residuals were reviewed. Of the 33 patients 11 underwent ureteroneocystostomy using a modified Lich-Gregoir technique with ureteral advancement and 22 underwent a modified procedure in which the detrusor dissection was minimized and the obliterated umbilical artery was preserved. Both groups had similar preoperative characteristics. Postoperative surgical success and signs of voiding dysfunction were evaluated and compared between groups. RESULTS: The average length of time until patients were able to void at least half of the bladder volume was 5.9 +/- 3.1 days. The average length of time until successful postoperative Foley catheter or suprapubic tube removal was 7.4 +/- 4.2 days. All children were able to void adequately eventually. Postoperative voiding cystourethrogram demonstrated that reflux was cured in 97% of the ureters. There was no postoperative vesicoureteral obstruction. There was no significant difference in length of time necessary to void, the duration of catheterization or operative success between the children who underwent standard versus limited detrusor dissection procedures. CONCLUSIONS: Extravesical ureteral reimplantation is an effective method for repairing reflux without ureteral obstruction but it can also result in a high rate of transient postoperative urinary retention even when detrusor dissection is minimized.
PURPOSE: Little is known about the developmental effects of high urinary diversion and bladder defunctionalization in infancy. Although clinical experience shows that a poorly functional bladder may result from urinary diversion in infancy, the mechanisms of change and specific bladder wall alterations have not been well characterized. We hypothesized that cyclic filling and emptying are necessary for normal bladder development. To investigate this important question we created a new animal model. MATERIALS AND METHODS: We designed a new method of hemibladder urinary diversion in 3-week-old New Zealand white rabbits. After vertical midline bladder division half of the bladder was formed into a functional reservoir, which remained in continuity with the ipsilateral ureter and urethra. The other bladder half was defunctionalized and isolated from the urine flow by ureteral ligation. Diversion was created for 3, 7, 14 and 28 days. Urodynamic evaluation was done in the functionalized hemibladders and age matched normal rabbit bladders to test the validity of the functionalized hemibladder as an internal control. Functional and defunctionalized hemibladders as well as age matched, nonoperated normal rabbit bladders were weighed, sectioned and stained to demonstrate muscle and connective tissue components. RESULTS: In 22 of the 27 healthy rabbits (81%) good quality diverted and functional bladder specimens were obtained after diversion. Defunctionalized hemibladders grew more slowly than functionalized bladders and normal age matched control bladders. Histological staining of the bladder wall demonstrated increased connective tissue between the muscle bundles within the diverted specimens than in functional bladders. CONCLUSIONS: Our successful model of urinary diversion may be used to study the developmental and histological effects of urinary diversion in the young bladder. Bladder growth and histological appearance are altered when the stimulus of cyclic filling and emptying is removed. Further studies using this model are warranted to define fully bladder changes that result from diversion and investigate the mechanism of the observed changes.
Complications resulting from advanced atherosclerosis are the most common indication for vascular reconstructive surgery. Atherosclerosis is a systemic disease affecting the entire arterial tree, but lesions involving the coronary, extracranial cerebral, and lower extremity circulations have the most clinical significance for surgeons. The pathogenesis of atherosclerosis involves a complex series of events, similar to a chronic inflammatory process, with the formation of atherosclerotic plaque as the end result. Injury to the endothelial cell of the artery, resulting in endothelial cell dysfunction, is the first step in the process. Activated endothelial cells attract leukocytes and vascular smooth muscle cells (VSMC), which accumulate and proliferate in the arterial wall. These cellular components produce an excessive amount of connective tissue matrix. The ultimate end point is the formation of a mature fibrous plaque. Symptoms occur when advanced lesions are complicated by plaque rupture, hemorrhage into the plaque, emboli, or thrombosis. A thorough understanding of the pathogenesis of atherosclerosis is essential for the development of strategies for the prevention of the disease, and for the development of new and effective treatments.
Cell differentiation and proliferation are influenced by peptide growth factors. These peptide molecules are important in maintaining the normal development and growth of animal cells; in addition, they have been found to play a major role in disease states. The role of growth factors in the development of arteriosclerosis and intimal hyperplasia is of great interest to us as physicians taking care of patients with peripheral vascular disease. Factors such as platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), insulin, insulin-like growth factor-I (IGF-I), and transforming growth factors alpha and beta (TGF alpha and beta) have been found to play important roles in controlling the progression of cells in the cell cycle. Furthermore, various growth factors have been found to influence the motility of cells, particularly vascular smooth muscle cells (VSMCs).
PURPOSE: The successful use of stomach for bladder augmentation and substitution is well documented. Gastric tissue has been used more recently to create continent catheterizable tubes. We describe 2 new techniques of gastric tube construction, and report our long-term followup of catheterizable gastric tubes in children and adults undergoing complex urinary tract reconstruction. MATERIALS AND METHODS: A retrospective chart review of 6 male and 4 female patients 5 to 43 years old was done. Primary diagnoses included bladder exstrophy, cloacal exstrophy, rhabdomyosarcoma and neurogenic bladder. Five patients underwent gastrocystoplasty with simultaneous creation of a continent gastric tube from the anterior gastric flap. In 2 patients who had undergone previous gastrocystoplasty a continent gastric tube was created from an anterior flap raised from the existing gastric bladder. Isolated gastric tubes were constructed in 3 patients. RESULTS: Followup ranged from 2 to 9 years (median 3.5). All patients demonstrated easy reliable catheterization. One patient required revision of the proximal end of the tube for incontinence. At followup all tubes were continent. Complications occurred only in flush or protuberant stomas, and resolved after stomal revision with recessed skin flaps. CONCLUSIONS: Several techniques can be used to create a continent gastric tube. Long-term followup reveals reliable catheterization and good continence rates. Recession of the gastric tube stoma with a skin flap prevents peristomal complications.