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Biomedical subjects

L F Martin

Publications and source records attributed to L F Martin.

At least 19 recordsLinked to original sources

Beta-adrenergic responsiveness of adenylate cyclase in human adipocyte plasma membranes in obesity and after massive weight reduction.

The aim of this study was to find out how beta-adrenergic responsiveness of adipocytes is altered in obesity and by weight loss and to investigate what mechanisms lead to potential alterations in responsiveness. Crude plasma membranes were prepared from adipocytes of massively obese and normal-weight individuals, as well as previously obese patients that had lost an average of 38% of their initial weight after bariatric surgery. Stimulation of adenylate cyclase by isoproterenol varied considerably in fat cell plasma membranes from different individuals. Crude fat cell plasma membranes from obese patients were less responsive to isoproterenol than those from normal-weight subjects, whereas those from postgastroplasty patients were hyperresponsive. The response was correlated negatively with cell size and positively with beta-adrenergic receptor density and with the ratio of beta-receptors and stimulatory G-proteins (Gs). There was no correlation with Gs content. However, differences in receptor density between small and large cells or normal-weight, obese, and post-bypass patients could not explain the observed differences in responsiveness to isoproterenol between the different groups.

Adenylyl Cyclases

A multicenter, placebo-controlled, randomized, double-blind, prospective trial of prophylactic ursodiol for the prevention of gallstone formation following gastric-bypass-induced rapid weight loss.

BACKGROUND: Previous studies have documented a high incidence of gallstone formation following gastric-bypass (GBP)-induced rapid weight loss in morbidly obese patients. This study was designed to determine if a 6-month regimen of prophylactic ursodiol might prevent the development of gallstones. METHODS: A multicenter, randomized, double-blind, prospective trial evaluated 3 oral doses of ursodiol: 300, 600, and 1,200 mg versus placebo beginning within 10 days after surgery and continuing for 6 months or until gallstone development, for patients with a body mass index (BMI) > or = 40 kg/m2. All patients had normal intraoperative gallbladder sonography. Transabdominal sonography was obtained at 2, 4, and 6 months following surgery, or until gallstone formation. RESULTS: Of 233 patients with at least one postoperative sonogram, 56 were randomized to placebo, 53 to 300 mg ursodiol, 61 to 600 mg ursodiol, and 63 to 1,200 mg ursodiol. Preoperative age, sex, race, weight, BMI, and postoperative weight loss were not significantly different between groups. Gallstone formation occurred at 6 months in 32%, 13%, 2%, and 6% of the patients on the respective doses. Gallstones were significantly (P < 0.001) less frequent with ursodiol 600 and 1,200 mg than with placebo. CONCLUSION: A daily dose of 600 mg ursodiol is effective prophylaxis for gallstone formation following GBP-induced rapid weight loss.

Adolescent

Can morbidly obese patients safely lose weight preoperatively?

BACKGROUND: Preoperative weight loss is often suggested as a means of reducing operative risk in obese patients requiring laparotomy but there are no large studies documenting that this is feasible or helpful. Although several commercial products are available that provide high levels of protein with low levels of carbohydrates in convenient liquid preparations, recommendations regarding the extent to which weight loss can be pursued preoperatively are not available. PURPOSE: To determine whether it is practical and safe to have obese patients lose weight preoperatively. PATIENTS AND METHODS: We asked 100 severely obese patients requesting gastric bypass surgery to diet before their operations. Seventy patients agreed to diet by consuming a 420 Kcal, 70 g protein liquid diet daily for at least 1 month. RESULTS: Forty-seven patients lost at least 7.5 kg (mean +/- SD 17.1 +/- 0.7). The patients who successfully lost weight preoperatively (dieters group) were significantly heavier than patients (nondieters group) who did not lose weight (251% +/- 45% of ideal body weight [IBW] versus 229% +/- 33% IBW, respectively; P < 0.01), had a significantly higher ratio of men to women, and had psychiatric evaluations and psychological test scores that suggested significantly more psychopathology. Other biosocial and medical characteristics were similar. Postoperatively, the dieters and nondieters had similar rates for morbidity. Dieters and nondieters had no differences in wound-healing complications, and subgroups who had collagen deposition measured experimentally had similar amounts of hydroxy-proline accumulation in their wounds. CONCLUSION: These results suggest that a preoperative diet program appeals more to certain subgroups of severely obese patients than to others. An aggressive preoperative weight loss program that encourages patients to lose an average of 17 kg is safe and can be accomplished practically using available commercial products.

Female

Comparison of the costs associated with medical and surgical treatment of obesity.

BACKGROUND: We compared the long-term costs and outcomes of gastric bypass versus medical therapy (very low-calorie diet plus weekly behavioral modification) for obese patients. METHODS: A successful outcome was defined as the loss of at least one third of excess weight that was maintained for the duration of the study. A minimal cost was assigned: $3000 for medical and $24,000 for surgical treatment. A cost per pound of weight lost for all patients successfully monitored was calculated. The Federal Trade Commission recently asked all weight loss programs to report this cost for patients at least 2 years after therapy. RESULTS: A total of 201 patients entered surgical and 161 entered medical therapy. The surgical group was initially heavier (mean body mass index [kg/m2] +/- SE = 49.3 +/- 0.6 versus 41.2 +/- 0.7, p < 0.01), but each group's lowest mean body mass index was similar (31.8 versus 32.1, respectively). A significantly higher percentage of patients in the surgical versus the medical group were still successful at year 5: 89% versus 21%. The cost per pound lost for medical therapy exceeded the cost of surgical therapy in the sixth posttreatment year (both more than $250/pound). CONCLUSIONS: Surgical treatment appears to be more cost-effective at producing and maintaining weight loss. It is imperative that long-term follow-up studies be funded to definitely establish this finding.

Adolescent

Severe obesity: expensive to society, frustrating to treat, but important to confront.

Obesity is a major contributor to chronic and costly diseases and disabilities. More than 30% of American adults are obese, and the percentage has been rising for 20 years. A recent estimate placed the direct economic costs of obesity at more than $39.3 billion, or 5.5% of all medical expenditures in the mid-1980s. These numbers underestimate prevalence and cost because the studies designed to monitor our nation's health problems have ignored the most obese segment of the population-individuals weighing more than 350 pounds. The methods used to treat obesity are controversial, some of them lacking appropriate evaluation. Physicians have been reluctant to treat obese people because of the intensity and duration of an effective treatment program. Finally, many treatments fail in the long term and therefore are not considered cost effective. Multiple treatment options are currently available, and this review presents data to aid physicians in selection of the best therapy to help their patients. As cost advantages of comprehensive care of obese patients become more obvious under capitated financing systems, further investigation should focus on mechanisms of choosing more individualized care plans to defined subsegments of the obese population to make care more cost effective.

Health Care Costs

Are learning objectives useful in evaluating medical school course and instructor performance?

We tested the hypothesis that learning objectives could be used to evaluate course and instructor effectiveness. Ninety-seven third-year medical students who had their surgical clerkship or their medical clerkship as their first clinical rotation were compared. The surgery clerks received 171 urologic learning objectives. Students taking the surgical clerkship had significantly higher postclerkship recognition of the learning objectives than did medical clerkship students. One year later, these students were again surveyed to determine whether they still knew the correct response to the learning objective. The follow-up survey showed that 50% of the students recognized objectives covered in five of the eight urology lectures, while the other lectures were not effective. Students who recognized the objective on the postclerkship evaluation were more likely to think the objective had been taught on this follow-up survey. These data suggest that learning objectives are useful for evaluating course and instructor effectiveness.

Adult

Cyclic AMP and glycerol concentrations in freeze-clamped human omental and subcutaneous adipose tissues.

OBJECTIVE: To compare intracellular concentrations of cyclic AMP, GTP, ATP, AMP and glycerol in omental and abdominal subcutaneous adipose tissues. DESIGN: Samples of omental and/or abdominal subcutaneous adipose tissues of 14 women undergoing elective surgery were freeze-clamped, deproteinized with perchloric acid and neutralized. All subjects were obese since it was not possible to freeze-clamp lean individuals. MEASUREMENTS: The concentrations of ATP and GTP were determined by ion-paired high performance liquid chromatography and AMP and glycerol enzymatically. Cyclic AMP was determined by radioimmunoassay. Intracellular nucleotide concentrations were calculated from tissue weights, water contents and relative amounts of sodium and potassium. RESULTS: The intracellular concentration of cyclic AMP in omental adipose tissue (31 mumol/l) was twice as high as that in subcutaneous fat while those of ATP, GTP and AMP were similar at the two sites. Glycerol concentrations were higher in subcutaneous (472 mumol/l) than in omental (325 mumol/l) adipose tissue. CONCLUSION: The results suggest higher relative stimulation of lipolysis by cyclic AMP in omental adipose tissue than in the subcutaneous region in situ. However, probably because of differences in blood flow and possibly in the lipolytic machinery, this is not reflected as a higher glycerol concentration.

Adenosine Monophosphate

Sleep apnea and sleep disruption in obese patients.

OBJECTIVES: To describe the frequency and severity of sleep apnea in obese patients without a primary sleep complaint and to assess the sleep patterns of obese patients without apnea and compare them with the sleep patterns of nonobese controls. DESIGN AND SETTING: Prospective case series with historical controls in an obesity and sleep disorders clinic. SUBJECTS: Two hundred obese women and 50 obese men (mean body mass index, 45.3) consecutively referred for treatment of their obesity and 128 controls matched for age and sex. MAIN OUTCOME MEASURES: Eight-hour sleep laboratory recording, including electroencephalogram, electro-oculogram, electromyogram, and respirations. Subjectively reported sleep-related symptoms and signs were also recorded. RESULTS: Twenty men (40%) and six women (3%) demonstrated sleep apnea warranting therapeutic intervention. Another four men (8%) and 11 women (5.5%) showed sleep apneic activity that warranted recommendation for evaluation in the sleep laboratory. In contrast, none of the 128 controls demonstrated sleep apneic activity severe enough for therapeutic intervention. The best clinical predictors of sleep apnea in the obese population were severity of snoring, subjectively reported nocturnal breath cessation, and sleep attacks. Obese patients, both men and women, without any sleep-disordered breathing demonstrated a significant degree of sleep disturbance compared with nonobese controls. Wake time after sleep onset, number of awakenings, and percentage of stage 1 sleep were significantly higher in obese patients than in controls, while rapid eye movement sleep was significantly lower. CONCLUSION: Severely or morbidly obese men are at extremely high risk for sleep apnea and should be routinely evaluated in the sleep laboratory for this condition, while for severely or morbidly obese women the physician should include a thorough sleep history in the clinical assessment.

Adolescent

Abnormal A1 adenosine receptor function in genetic obesity.

Obesity is increasingly recognized as an important health problem in developed, industrialized countries. As a large proportion of the variance in individual adiposity is based on genetic factors (1-3), recent efforts have focused on identifying genes involved in regulating the percentage of body fat in a given individual. This effort is helped by the existence of rodent models of genetic obesity. Many strains of mice and at least three rat strains have been identified thus far that exhibit inherited obesity accompanied by a similar set of endocrine abnormalities (4). Although the symptoms of the disease are similar in different strains, different genes appear to be involved in causing the syndrome, as the mutation responsible for the obesity maps to different chromosomal sites in the different strains. Efforts to find the products of the mutated genes over the past 30 years have generally been unsuccessful. However, the available data imply that many obesity mutations may involve genes that code for proteins in a single signal transduction pathway or one particular cascade of covalent modification. Reasonable theories are plentiful about the identity of such a pathway, but current studies in the laboratories of the authors suggest that the A1 adenosine receptor signaling pathway may be involved. Evidence of abnormal A1 receptor function has been obtained from studies of Zucker rats and obese (ob/ob) mice (5-7). These strains are obese because of a single recessive mutation. Measurements of adenylyl cyclase activity and regulation in isolated adipocytes and isolated plasma membranes suggest that the receptor is unusually and tonically active in obese rats. Because signaling from this receptor inhibits lipolysis in white and brown fat, induces insulin resistance in skeletal muscle (8, 9), but increases insulin sensitivity in adipose tissue (10, 11), the possibility arises that the excessive activity of the A1 adenosine receptor may induce obesity. Data from human volunteers are also compatible with the possibility that the activity of the receptor is unusually high in vivo in obese individuals (12).

Adenylyl Cyclases

Are there effective treatments for the severely obese?

Obesity is a major contributor to the costs of several chronic diseases and disabilities. Over 30% of adults in Louisiana are moderately to severely obese (defined as a body mass index > 28). As weight increases so do sick days and bedridden days. The estimated direct economic costs of not treating obesity effectively are over $40 billion nationwide, or 5.5% of all medical costs. Even though weight loss reduces the medication needs of obese individuals with hypertension, diabetes, and osteoarthritis, physicians have been reluctant to treat obese people because many treatments fail and are not considered cost effective. We present the available treatment options including their advantages and disadvantages. These treatments help between 25% and 85% of those referred to special centers specializing in obesity treatments. All physicians can help their obese patients by being aware of the costs, risks, and benefits of modern medically-supervised weight management programs.

Gastric Bypass

Prediction of postoperative complications after elective aortic surgery using stepwise logistic regression analysis.

Perioperative risk factors that contribute to postoperative morbidity have been identified for various forms of vascular disease, but it is not clear to what degree each type of disease contributes to morbidity when these diseases are seen in combination. We used stepwise logistic regression analysis to determine the relative importance of 25 risk factors in predicting postoperative complications in 100 consecutive patients undergoing elective intra-abdominal aortic surgery (59% aneurysmal disease, 37% occlusive disease, 26% renal artery lesions). Thirty-one patients developed postoperative complications, including three deaths. The most common complication was deterioration in renal function (17 patients, 24% of those at risk) followed by the need for prolonged endotracheal intubation (> 48 hours, 8%). All other events occurred uncommonly (4% or less). Stepwise logistic regression demonstrated four criteria that were significantly associated with complications. In descending order of importance these were: renal artery occlusive disease, intraoperative blood replacement, the preoperative APACHE II score, and a history of heavy smoking. Since both physiologic status and comorbid conditions contribute to morbidity and costs of elective vascular surgery, outcome studies must be adjusted to account for these preoperative characteristics. Additionally, since two-thirds of patients who have renal artery occlusive disease develop complications that prolong hospitalization, our current methods of protecting the kidney during ischemia should be improved to potentially reduce this cause of morbidity.

Adult

Stress ulcers are common after aortic surgery. Endoscopic evaluation of prophylactic therapy.

Defining who is at risk for the development of postoperative gastric mucosal ulcers and subsequent hemorrhage is an important task when deciding what type of prophylactic treatment is appropriate. We asked 100 consecutive patients requiring aortic surgery to participate in a randomized, double-blind, double-dummy study to compare the effectiveness of antacid titration with fixed doses of a synthetic prostaglandin E1 analog (misoprostol) as prophylaxis against stress gastritis and bleeding. Forty-six of the 100 patients agreed to participate in the study, and 23 were randomized to each arm. The other 54 patients were treated with cimetidine and followed as if they were study participants. Approximately half of the patients had aneurysmal disease, while the other half had occlusive disease. Thirty-one patients developed postoperative complications, and three patients died. Eighty per cent of the 42 patients who volunteered to undergo endoscopic evaluation developed stress ulcers postoperatively. Development of stress ulcers did not correlate with the development of the other complications or with the type of treatment. Only one of the 100 patients (in the cimetidine group) required operative therapy for hemorrhage from stress ulcers, and this occurred after a protocol violation. The endoscopic exams demonstrated that misoprostol and antacid therapy were equally effective in preventing stress ulcers. Patients who refused to participate in the study had significantly more complications than those who did participate by stepwise logistic regression analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Continuous intravenous cimetidine decreases stress-related upper gastrointestinal hemorrhage without promoting pneumonia.

OBJECTIVES: To determine whether a continuous i.v. infusion of cimetidine, a histamine-2 (H2) receptor antagonist, is needed to prevent upper gastrointestinal (GI) hemorrhage when compared with placebo and if that usage is associated with an increased risk of nosocomial pneumonia. Due to the importance of this latter issue, data were collected to examine the occurrence rate of nosocomial pneumonia under the conditions of this study. DESIGN: A multicenter, double-blind, placebo-controlled study. INTERVENTIONS: Patients were randomized to receive cimetidine (n = 65) as an iv infusion of 50 to 100 mg/hr or placebo (n = 66). SETTING: Intensive care units in 20 institutions. PATIENTS: Critically ill patients (n = 131), all of whom had at least one acute stress condition that previously had been associated with the development of upper GI hemorrhage. MEASUREMENTS AND MAIN RESULTS: Samples of gastric fluid from nasogastric aspirates were collected every 2 hrs for measurement of pH and were examined for the presence of blood. Upper GI hemorrhage was defined as bright red blood or persistent (continuing for > 8 hrs) "coffee ground material" in the nasogastric aspirate. Baseline chest radiographs were performed and sputum specimens were collected from all patients, and those patients without clear signs of pneumonia (positive chest radiograph, positive cough, fever) at baseline were followed prospectively for the development of pneumonia while receiving the study medication. Cimetidine-infused patients experienced significantly (p = .009) less upper GI hemorrhage than placebo-infused patients: nine (14%) of 65 cimetidine vs. 22 (33%) of 66 placebo patients. Cimetidine patients demonstrated significantly (p = .0001) higher mean intragastric pH (5.7 vs. 3.9), and had intragastric pH values at > 4.0 for a significantly (p = .0001) higher mean percentage of time (82% vs. 41%) than placebo patients. Differences in pH variables were not found between patients who had upper GI hemorrhage and those patients who did not, although there was no patient in the cimetidine group who bled with a pH < 3.5 compared with 11 such patients in the placebo group. Also, the upper GI hemorrhage rate in patients with one risk factor (23%) was similar to that rate in patients with two or more risk factors (25%). Of the 56 cimetidine-infused patients and 61 placebo-infused patients who did not have pneumonia at baseline, no cimetidine-infused patient developed pneumonia while four (7%) placebo-infused patients developed pneumonia. CONCLUSIONS: The continuous i.v. infusion of cimetidine was highly effective in controlling intragastric pH and in preventing stress-related upper GI hemorrhage in critically ill patients without increasing their risk of developing nosocomial pneumonia. While the number of risk factors and intragastric pH may have pathogenic importance in the development of upper GI hemorrhage, neither the risk factors nor the intragastric pH was predictive. Therefore, short-term administration of continuously infused cimetidine offers benefits in patients who have sustained major surgery, trauma, burns, hypotension, sepsis, or single organ failure.

Adolescent

Potentiation of decreased pyruvate dehydrogenase activity by inflammatory stimuli in sepsis.

The effect of inflammation and chronic sepsis on the activity of pyruvate dehydrogenase complex (PDH) in skeletal muscle was investigated in rats. Inflammation was induced by the placement of a catheter in the carotid artery. Sepsis was induced by repeated (every 48 hr) injections of an inoculum composed of Staphylococcus aureus, Escherichia coli, and Bacteroides fragilis organisms into a preformed subcutaneous abscess. Hindlimb muscle was sampled 7 or 14 days following the initial injection of the inoculum into the abscess. Total PHD activity was not altered by any of the conditions examined. There were no differences in the proportion of active PDH complex after 7 days in any of the conditions examined. In contrast, 14 days after the initial bacterial injection, the concentration of active PDH complex in skeletal muscle was reduced by 50% in the septic rats. The combination of intravascular catheterization and infection resulted in a further decrease in the concentration of active PDH complex. The decreased concentration of active PDH complex was associated with increased plasma lactate concentrations in septic rats. Catheterization exacerbated the rise in plasma lactate in sepsis. In this model of chronic sepsis, the magnitude of the hyperlactatemia and the inhibition of the PDH complex in skeletal muscle appear dependent upon the length of time of the septic insult and are potentiated by addition of an intravascular focus of inflammation.

Animals

31P-NMR evaluation of postischemia renal ATP and pH levels after ATP-MgCl2 treatment in rabbits.

Phosphorus-31 (31P) nuclear magnetic resonance (NMR) spectroscopy was used to measure adenosine triphosphate (ATP) concentration and pH in vivo in rabbits subjected to a 40-minute period of unilateral renal ischemia to determine the effect of infusing ATP-magnesium chloride (MgCl2, 100 mumol/kg) versus saline at the initiation of reperfusion. Data were compared initially by analysis of variance and then analyzed further using a general linear model with covariate adjustment. ATP-MgCl2-treated animals did not have higher ATP levels during recovery but did have significantly higher renal blood flow (p less than 0.05), a significantly decreased rate of recovery from acidosis (p less than 0.05), and significantly higher urinary output (p less than 0.01) than saline-treated animals during the recovery period. Therefore, treatment with ATP-MgCl2 improves postischemic functional parameters in this model of moderate injury without functioning as a direct source of ATP or its precursors. These data add support to the emerging concept that intracellular acidosis protects cells from reperfusion injury.

Adenosine Triphosphate