Design, synthesis, and characterization of polyintercalating ligands.
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Amino Acid Sequence↗
Biomedical subjects
M M Murr
Publications and source records attributed to M M Murr.
An octakis-intercalating molecule.
Herein we report the synthesis and characterization of a polyintercalator with eight potential intercalating l,4,5,8-naphthalenetetracarboxylic diimide (NDI) units linked in a head-to-tail arrangement via a peptide linker. UV spectroscopy and viscometry measurements indicated the molecule binds to double-stranded DNA with all eight NDI units intercalated simultaneously. Competition dialysis and DNAse 1 footprinting studies revealed a preference for GC-rich regions of DNA, and circular dichroism studies revealed significant distortion of B-form DNA upon binding. Our so-called "octamer" represents, to the best of our knowledge, the first intercalator that binds as an octakis-intercalator, capable of spanning at least 16 base pairs of DNA.
Animals↗
Clinical predictors of sleep apnea in patients undergoing bariatric surgery.
BACKGROUND: Sleep apnea is a frequent and unappreciated condition of morbidly obese patients. If unrecognized it could lead to significant postoperative complications. A clinical tool to assess the severity of sleep apnea is not available. We prospectively determined whether the Epworth Sleepiness Scale (ESS) or body mass index (BMI) predict the severity of sleep apnea in morbidly obese patients. METHODS: 66 consecutive patients evaluated for bariatric surgery from June to November 1999 were examined and prospectively administered a health questionnaire including the ESS. Patients with an ESS > or =6 were referred for polysomnography with calculation of Respiratory Disturbance Index (RDI). Sleep apnea was graded as mild (RDI 6-20), moderate (RDI 21-40) and severe (RDI>40). Clinical variables such as BMI and ESS score were compared using regression analysis. Data are mean +/- SEM. RESULTS: 4 men and 23 women (27/66) who scored >6 on the ESS completed a sleep study. Mean ESS was 13+/-4.5. Sleep apnea was mild in 13 patients, moderate in 7, severe in 6, and absent in 1. Mean age was 43+/-9.5 years. BMI was 52+/-10 kg/m2. Linear regression analysis did not demonstrate correlation between ESS score and severity of sleep apnea (r2=0.03, p>0.05). Multiple regression analysis demonstrated no correlation between BMI, patient snoring, and RDI score. CONCLUSIONS: Sleep apnea is frequent in candidates screened for bariatric surgery. ESS is a useful tool to investigate daytime sleepiness and other manifestations of sleep apnea. However, the ESS does not predict the severity of sleep apnea. Clinical suspicion of sleep apnea should prompt polysomnography.
Adult↗
Medical school curricula do not address obesity as a disease.
BACKGROUND: Obesity and its associated comorbidities have become an epidemic. However, medical school curricula do not address obesity as a disease. We undertook this study to assess medical students' knowledge about obesity before and after exposure to bariatric surgery. METHODS: A 10-item questionnaire that assesses knowledge of etiology, comorbidities, diagnosis, and management of obesity was mailed to all 201 2nd and 3rd year medical students enrolled in USF between 1999-2000. Data are mean +/- sem. Means were compared using t-test; p < or = 0.05 was significant. RESULTS: The overall response rate was 80%. The 3rd yr students who rotated on bariatric surgery (n = 24) answered correctly more questions than 55 students who did not rotate (90 +/- 2% vs 79 +/- 2%, p = 0.048). These differences were mainly noted in questions related to clinical management of obesity (p = 0.04). There were no significant differences among responses from 2nd yr students (n = 81) and the subset of 3rd yr students (n = 55) who did not rotate through bariatric surgery. CONCLUSIONS: Medical students' knowledge about obesity is significantly improved by rotation on a bariatric surgery program and not during rotations on other clinical disciplines. Medical school curricula should be changed to reflect the growing epidemic of obesity and enhance students' knowledge about obesity as a disease.
Clinical Clerkship↗
Delay in treatment of biliary disease during pregnancy increases morbidity and can be avoided with safe laparoscopic cholecystectomy.
Recent reports indicate that laparoscopic cholecystectomy in pregnancy is safe. The aim of this study was to evaluate whether delays in definitive treatment of symptomatic cholelithiasis increase morbidity. We reviewed the records of 16 women who underwent laparoscopic cholecystectomy during pregnancy between 1992 and 1999. Mean age was 24 +/- 5 years (mean +/- standard error). Symptom onset was during the first trimester in nine patients, second trimester in six patients, and third trimester in one patient. Patients had abdominal pain (93%), nausea (93%), emesis (80%), and fever (66%) for a median of 45 days (range 1-195 days) before cholecystectomy. Nine of 11 women who underwent cholecystectomy more than 5 weeks after onset of symptoms experienced recurrent attacks necessitating 15 hospital admissions and four emergency room visits. Moreover four women who developed symptoms in the first and second trimesters but whose operations were delayed to the third trimester had 11 hospital admissions and four emergency room visits; three of those four (75%) women developed premature contractions necessitating tocolytics. Cholecystectomy was completed laparoscopically in 14 women. There was no hospital infant or maternal mortality or morbidity. We recommend prompt laparoscopic cholecystectomy in pregnant women with symptomatic biliary disease because it is safe and it reduces hospital admissions and frequency of premature labor.
Adult↗
Location, not staging, of cholangiocarcinoma determines the role for adjuvant chemoradiation therapy.
The role of adjuvant chemoradiation therapy (CT/XRT) in the treatment of cholangiocarcinoma is controversial. We undertook this study to determine whether CT/XRT is appropriate after resection of cholangiocarcinomas. One hundred ninety-two patients with cholangiocarcinomas were treated from 1988 to 1999. After resection, patients were assigned a stage (TNM) and were stratified by location of the tumor as intrahepatic, perihilar, and distal tumors. Data are presented as mean +/- standard deviation. Of 192 patients 92 (48%) underwent resections of cholangiocarcinomas. Thirty-four patients had liver resections, 25 had bile duct resections, and 33 underwent pancreaticoduodenectomies. Thirty-four patients had adjuvant CT/XRT, three had adjuvant chemotherapy, four had neoadjuvant CT/XRT, and 50 had no radiation or chemotherapy. Mean survival of resected patients with adjuvant CT/XRT was 42 +/- 37.0 months and without CT/XRT it was 29 24.5 months (P = 0.07). Mean survival of patients with distal tumors receiving or not receiving CT/XRT was 41 +/- 21.8 versus 25 +/- 20.1 months, respectively, (P = 0.04). Adjuvant chemoradiation improves survival after resection for cholangiocarcinoma (P = 0.07) particularly in patients undergoing resection for distal tumors (P = 0.04). Benefits of adjuvant CT/XRT are apparent when stratified by location of cholangiocarcinomas rather than staging.
Aged↗
What prognostic factors are important in duodenal adenocarcinoma?
HYPOTHESIS: Survival of patients with adenocarcinoma of the duodenum depends on the ability to perform a complete resection and the tumor stage DESIGN: Retrospective case series. SETTING: Tertiary care referral center. PATIENTS: A cohort of 101 consecutive patients (mean age, 62 years), undergoing surgery for duodenal adenocarcinoma from January 1, 1976, through December 31, 1996. Patients with ampullary carcinoma were specifically excluded. Mean duration of follow-up was 4 years. INTERVENTIONS: Surgery was curative in 68 patients (67%) and palliative in 33 patients (33%). Of the curative group, 50 patients (74%) underwent radical surgery, ie, 30 (60%), pancreaticoduodenectomy; 15 (30%), pylorus-preserving pancreaticoduodenectomy; and 5 (10%), total pancreatectomy. A more limited resection procedure was used in 18 patients (26%) involving a segmental duodenal resection in 15 (83%) and a transduodenal excision in 3 (17%). patient survival, and correlation with patient and tumor variables using univariate and multivariate analysis. RESULTS: Actuarial 5-year survival for the curative group was 54%. Only 1 patient in the unresected group survived beyond 3 years. Nodal metastasis (P = .002), advanced tumor stage (P<.001), positive resection margin (P = .02), and weight loss (P<.001) had a significant negative impact on survival in multivariate analysis. Tumor grade, size, and location within the duodenum had no impact on survival. Patient age and tumor depth of invasion influenced survival in univariate analysis, but lost their prognostic significance in multivariate analysis. CONCLUSIONS: Metastasis to lymph nodes, advanced tumor stage, and positive resection margins are associated with decreased survival in patients with duodenal adenocarcinoma. An aggressive surgical approach that achieves complete tumor resection with negative margins should be pursued. Pancreaticoduodenectomy is usually required for cancers of the first and second portion of the duodenum. Segmental resection may be appropriate for selected patients, especially for tumors of the distal duodenum.
Adenocarcinoma↗
Bariatric surgery. Surgery for weight control in patients with morbid obesity.
Morbid obesity has become a health crisis in the United States. Medical programs developed at nonoperative attempts to lose (and maintain) an adequate weight loss are largely unsuccessful. Bariatric surgery has been proven to be effective at inducing and maintaining a satisfactory weight loss to decrease weight-related comorbidity. Bariatric operations include procedures that decrease mechanically the volume capacitance of the proximal stomach (vertical banded gastroplasty, laparoscopic gastric banding) or decrease the proximal gastric capacitance and establish a partial selective malabsorption (gastric bypass and its modifications, partial biliopancreatic bypass, and duodenal switch with partial biliopancreatic bypass). These operations should induce a loss of at least 50% (or more) of excess body weight. Not all patients are candidates for these procedures, and the best results are obtained by a multidisciplinary team (including nutritionist, physician, dietitian, psychologist or psychiatrist interested in eating disorders, and surgeon).
Adult↗
Role of nitric oxide, vasoactive intestinal polypeptide, and ATP in inhibitory neurotransmission in human jejunum.
BACKGROUND: Inhibitory neurotransmission in the human intestine is poorly understood. This study was undertaken to determine the role of nitric oxide (NO), adenosine triphosphate (ATP), and vasoactive intestinal polypeptide (VIP) in inhibitory neurotransmission in human jejunal circular muscle strips. METHODS: In vitro response of precontracted (10(-5) M substance P) normal human jejunal muscle strips to electric field stimulation (EFS) under adrenergic and cholinergic receptor blockade was evaluated. Selective neural blockade was obtained by the NO synthase inhibitor l-NG-nitroarginine methyl ester (l-NAME, 10(-3) M), VIP receptor antagonist (4-Cl-d-Phe6Leu17-VIP, 10(-7) M), P2 purinergic receptor blocker suramin (3 x 10(14) M), or the calcium-dependent potassium channel blocker apamin (10(-6) M). Force generated in response to EFS was quantitated and analyzed statistically. RESULTS: Exogenous NO and ATP dose-dependently inhibited contractile activity and relaxed muscle strips with a concentration yielding a 50% effect (ED50) of 4.5 +/- 2.9 x 10(-6) M and 3.3 +/- 1.3 x 10(-4) M, respectively. EFS resulted in relaxation of precontracted muscle strips in all groups. When compared with controls, relaxation was decreased but not abolished by l-NAME (-0.12 +/- 0.03 vs -0.33 +/- 0. 05, -0.07 +/- 0.03 vs -0.34 +/- 0.05, and 0.04 +/- 0.03 vs -0.30 +/- 0.04 at 2, 5, and 10 Hz, respectively, P < 0.011). d-NAME (inactive stereoisomer of l-NAME), 4-Cl-d-Phe6Leu17-VIP, suramin, and apamin did not alter EFS-induced relaxation. CONCLUSIONS: Inhibition of NO synthesis by l-NAME reduced the inhibitory response to EFS, whereas blocking ATP and VIP receptors or other effector pathways had no effect. Our findings indicate that although NO plays a predominant role in inhibitory neurotransmission in human jejunal circular muscle, another neurotransmitter(s) appears to be involved as well. These data may impact on understanding mechanisms of disorders of gut dysmotility.
Adenosine Triphosphate↗
Long-term results of biliary reconstruction after laparoscopic bile duct injuries.
HYPOTHESIS: The Hepp-Couinaud approach to biliary enteric reconstruction for laparoscopic bile duct injuries provides a durable, long-term result in most patients. DESIGN: Retrospective study of patients who underwent operative repair of laparoscopic bile duct injuries from January 1990 through December 1997. SETTING: Academic tertiary referral center. MAIN OUTCOME MEASURES: Outcome was assessed using a grading system based on clinical symptoms, liver function tests, and need for reintervention for anastomotic stricture. The Kaplan-Meier method was employed to estimate stricture-free survival. RESULTS: Fifty-nine consecutive patients underwent operative repair of the following laparoscopic bile duct injuries (Strasberg classification): B: n = 2 (3%), C: n = 1 (1%), D: n= 2 (3%), E1: n= 5 (8%), E2: n= 16 (27%), E3: n= 25 (42%), E4: n = 5 (8%), and E5: n = 3 (5%). Forty-seven patients (80%) had 1 or more interventions prior to the index repair. The extrahepatic left bile duct (Hepp-Couinaud approach) was used in 46 of 53 patients who underwent a Roux-en-Y hepaticojejunostomy. Follow-up (mean+/-SEM, 3.7+/-0.3 years) was complete in 54 of the 57 patients still alive. Five patients developed subsequent anastomotic strictures and were treated with percutaneous transhepatic dilation (n = 3), endoscopic dilation (n = 1), and operative revision (n= 1). Excellent to good long-term results were achieved in the remaining 49 patients (91%). Life-table analysis yielded 95% and 88% chances of stricture-free survival at 2 and 5 years, respectively. CONCLUSIONS: Complex iatrogenic proximal bile duct injuries and strictures are amenable to operative repair using the extrahepatic left bile duct. The Hepp-Couinaud approach offers a durable result in more than 90% of patients, even after previous interventions have failed.
Bile Ducts↗
An end-to-end pancreaticojejunostomy using a mechanical purse-string device.
Pancreatic-jejunal anastomosis leaks are a major cause of morbidity and mortality after pancreaticoduodenectomy. We have used a mechanical purse-string device to secure the jejunum to the intussuscepted pancreatic stump in 17 patients. A major leak developed in 1 patient and minor leaks developed in 2 patients, all of which were managed nonoperatively. This technique is expeditious and safe.
Humans↗
Financial status does not predict weight loss after bariatric surgery.
BACKGROUND: Lower socioeconomic status and poor funding are thought to be associated with suboptimal outcome after bariatric surgery. We undertook this study to determine if funding status is a predictor of outcome in patients undergoing bariatric surgery. METHODS: The medical records of 131 consecutive patients who underwent vertical banded gastroplasty (VBG) for clinically severe obesity (BMI >40 kg/m2) were reviewed. Patients were divided into three groups based on insurance status: (1) commercially insured/traditional indemnity programs; (2) entitlement programs (Medicare), and (3) medically indigent (Medicaid or no funding). Data is mean +/- SD. Data was analyzed using ANOVA and Student t-test. RESULTS: The three groups had similar preoperative weight. Mean BMI was 39 +/- 13, 42 +/- 15, 41 +/- 11 at 1 year, and 40 +/- 13, 43 +/- 16, 45 +/- 16 at 2 years postoperatively for the insured, entitlement, and indigent groups, respectively. CONCLUSION: After standard preoperative evaluation and screening, patients loss weight following VBG independent of insurance status. Source of funding should, therefore, not preclude patients from undergoing bariatric surgery. Patients with limited financial resources can expect similar outcomes as patients with commercial insurance.
Adult↗
In situ neural isolation of the entire canine upper gut: effects on fasting and fed motility patterns.
BACKGROUND: Multiorgan upper gut transplantation is becoming clinically feasible; however, the effects of multivisceral transplantations on gastrointestinal motility are unknown. Our aim was to determine the neural and hormonal mechanisms controlling motility patterns after complete extrinsic denervation of the upper gut as a model of multivisceral upper gut autotransplantation. METHODS: Seven dogs successfully underwent in situ neural isolation of the stomach, entire small intestine, proximal colon, liver, and pancreas by transecting all connections (distal esophagus, midcolon, all nerves, lymphatics) to this multivisceral complex except the celiac artery, superior mesenteric artery, and the suprahepatic and infrahepatic vena cava; these vessels were meticulously stripped of adventitia under optical magnification. Blood flow was not disrupted to prevent confounding effects of ischemia-reperfusion injury. After 1- to 2-week recovery, myoelectric and manometric recordings of stomach and myoelectric recordings of small bowel were obtained from conscious animals. RESULTS: During fasting the characteristic cycling migrating motor complex (MMC) was observed in the stomach and small intestine. The gastric component of the MMC was absent in one of the seven dogs. Regular cycling of the MMC during fasting, however, was intermittently disrupted and replaced by a noncyclic pattern of intermittent contractions in two of seven dogs 43% of the recording time. A small meal (50 gm liver) did not abolish the MMC as occurs in normal dogs; in contrast, a large meal (500 gm liver) did abolish the MMC. CONCLUSIONS: Extrinsic innervation to the upper gut modulates but is not requisite for interdigestive and postprandial motility of the stomach. Because relatively normal global motility patterns are preserved, multivisceral upper gut transplantation should be a viable option in selected patients.
Animals↗
Contractile properties of enteric smooth muscle after small bowel transplantation in rats.
BACKGROUND: The effects of small bowel transplantation (SBTx) on the function of enteric smooth muscle are not understood. PURPOSE: To study the contractile properties of enteric smooth muscle after SBTx in rats. METHODS: Five groups of inbred Lewis rats (n > or = 8 each group) were studied: unoperated, naive controls; operated controls 1 week (OC1) and 8 weeks after intestinal transection/reanastomosis of the proximal jejunum and distal ileum; and 1 week (TX1) and 8 weeks (TX8) after syngeneic orthotopic SBTx. Contractile activity of circular muscle strips of jejunum was evaluated in tissue chambers. Spontaneous contractile activity (force per wet weight tissue) increased in TX1, TX8, and OC1 rats (P < or = 0.01). Frequency of contractions doubled in OC1 rats (P < or = 0.001) but was unchanged in the other groups. In the presence of nonadrenergic noncholinergic (NANC) blockade, spontaneous contractile activity increased in TX1 and OC1 (P < or = 0.005) without a change in frequency of contractions. Inhibition of neural activity with tetrodotoxoin increased amplitude and frequency in all groups. Bethanechol (3 x 10(-6) to 3 x 10(-4) mol/L) increased, and norepinephrine (1 x 10(-6) to 1 x 10(-4) mol/L) dose-dependently decreased the amplitude and frequency of contractions in all groups; equi-effective concentrations, however, did not differ among groups. CONCLUSIONS: The increase in contractile activity after intestinal transection/reanastomosis is secondary to an increase in frequency of contractions and not amplitude. SBTx increases contractile amplitude of circular muscle due, in part, to downregulation of NANC nerves but not via muscarinic or adrenergic hypersensitivity. These alterations in enteric physiology of intestinal contractile activity may have important implications in clinical SBTx.
Animals↗
The surgeon's role in the treatment of chronic intestinal pseudoobstruction.
OBJECTIVE: The surgeon's role in the treatment of patients with chronic intestinal pseudoobstruction (CIP) is under-appreciated. Our aim was to determine the effects of operative treatment on symptomatic relief of CIP. METHODS: Records of all 21 patients who underwent surgery for CIP from 1980 to 1990 were reviewed. CIP was diagnosed by a combination of manometric, radiological, and/or histological examinations. RESULTS: Six of the nine patients who underwent resection or bypass of presumably localized disease are currently maintained on oral intake; one patient with multiple sclerosis who cannot eat is fed via a gastrostomy tube. Enterostomy tube(s) were placed in the other 12 patients; four no longer use the enterostomy tube(s), and eight rely on these decompressive tube enterostomies for symptomatic relief. After operative treatment, hospital readmissions decreased from a mean of 0.5 to 0.1 admission/year. All 19 patients currently alive report improved quality of life. CONCLUSIONS: Selective and directed operative treatment of patients with CIP can result in therapeutic and palliative benefits. The surgeon should have an active role in the evaluation and possible treatment of patients with CIP.
Adolescent↗
Diagnosis and treatment of pancreatic and ampullary cancer.
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Adenocarcinoma↗
Spinal epidural abscess complicating an ileal J-pouch-anal anastomosis. Report of a case.
A 42-year-old man developed recurrent epidural abscesses from an enteroepidural fistula arising from a J pouch. Lower-extremity neurologic deficit in patients with an ileal pouch-anal anastomosis should alert the physician to this rare complication.
Abscess↗
Case of multivertebral anomalies, cloacal dysgenesis, and other anomalies presenting prenatally as cystic kidneys.
We describe a newborn boy on whom prenatal ultrasonography demonstrated intrauterine growth retardation, multiple vertebral anomalies, cystic kidneys, and oligohydramnios. Autopsy findings included multiple vertebral anomalies, cloacal dysgenesis (imperforate anus, vesicorectal fistula, and bilateral renal dysplasia), sacral absence, single umbilical artery, pulmonary hypoplasia, scoliosis, and hexadactyly of the left thumb. Although our case resembles a previously described case, a definitive diagnosis could not be made. The differential diagnosis included a variant of spondylocostal dysostosis and the VATER association.
Abnormalities, Multiple↗