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Biomedical subjects

L F Martin

Publications and source records attributed to L F Martin.

At least 37 records · Page 2Linked to original sources

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↗

Weight loss normalizes the inhibitory effect of N6-(phenylisopropyl)adenosine on lipolysis in fat cells of massively obese human subjects.

1. Fat cells were isolated from massively obese patients at or before gastric bypass, from other patients after normalization of body weight after gastric bypass or gastroplasty (post-bypass patients) and from control subjects of a stable normal body weight. 2. The inhibition of isoprenaline-stimulated lipolysis by N6-(phenylisopropyl)adenosine in the presence of adenosine deaminase was much attenuated in cells from the massively obese patients as compared with those from normal-weight control subjects, but was normal in cells from post-bypass patients. 3. Isolated fat cells of the massively obese patients were larger (913 +/- 197 pl, mean +/- SEM) than those of the normal-weight group (437 +/- 95 pl). The volume of cells from the post-bypass patients was only 125 +/- 49 pl, although the body mass index of this group was almost exactly the same as that of the normal-weight control subjects. 4. Although epidemiological studies have suggested that genetic factors are important in the development and maintenance of obesity, these results demonstrate that the changes observed in the inhibitory regulation of lipolysis in obesity are secondary.

Adenosine Deaminase↗

Stress ulcers and organ failure in intubated patients in surgical intensive care units.

This study compared prophylactic administration of either intragastric misoprostol (200 micrograms four times a day), a prostaglandin E1 analog, or bolus intravenous cimetidine (300 mg every 6 hours) in preventing stress lesions and stress bleeding in 127 adult postoperative patients who required mechanical ventilation and also had developed hypotension or sepsis. Both drug treatments were equally effective in preventing the development of diffuse gastritis (greater than 10 gastric hemorrhagic lesions) and in preventing upper gastrointestinal hemorrhage (UGIH). The combined data from both groups showed that for the 44 (35%) patients who died, death was significantly associated with the presence at study entry of renal failure (64% of 25 patients with renal failure died), hepatic failure (57% of 23 patients) or coagulopathy (62% of 29 patients) (p less than 0.02 for each), and with the number of organ system failures at study entry (48% of 69 patients with multiple organ system failures died, p less than 0.001). Death was also significantly associated with the presence of adult respiratory distress syndrome (ARDS) at study entry or the development of ARDS (63% of 24 patients with ARDS died, p less than 0.001), and the development of UGIH (5% of 93 patients with known bleeding outcome died, p less than 0.05). The number of stress lesions that developed was significantly associated with subsequent UGIH (p less than 0.001). Additional organ system failure developed during the study in 31% of the 127 patients, as did diffuse gastritis in 20% of 111 patients who had a follow-up endoscopy. These results demonstrate that postoperative patients who require mechanical ventilation and have hypotension or sepsis are at significant risk for the development of stress gastric lesions and multiple organ system failure even when prophylaxis for stress ulcers is provided. Furthermore, the presence of ARDS, renal failure, hepatic failure, coagulopathy, and UGIH are significantly associated with death.

Cause of Death↗

Pyruvate carboxylase in genetic obesity.

Immunoblotting and protein microsequencing were used to identify several adipocyte proteins expressed in an obesity-related fashion in the Zucker rat. One of these was a 116-kDa particulate protein (p116). The p116 levels in adipocytes from 5- to 7-wk-old obese Zucker rats were two- to fivefold higher on a per milligram of protein basis than levels in lean animals and decreased after the induction of streptozotocin-induced diabetes mellitus. This suggests the change may be related to the actions of insulin. Hepatic levels of p116 did not change. The p116 was purified to homogeneity from obese Zucker rat adipocytes, and polyclonal antisera were prepared against the purified protein in rabbits. Microanalysis of electroblotted p116 proteolytic fragments suggested that p116 was pyruvate carboxylase (PC). Other evidence that p116 was PC included the following: 1) p116 contained biotin, 2) p116 in particulate subcellular fractions was soluble after freeze-lysis, 3) antibodies to p116 reacted with purified hepatic PC, 4) p116 and purified hepatic PC had identical pI and relative molecular weight values, and 5) similar changes were detected in adipocyte p116 and PC enzyme activity during obesity and after the induction of streptozotocin-induced diabetes mellitus. Increased adipose tissue PC probably contributes to the increased lipogenic capacity of young obese Zucker rat adipocytes.

Amino Acid Sequence↗

Attenuated adenosine-sensitivity and decreased adenosine-receptor number in adipocyte plasma membranes in human obesity.

Fat-cells were isolated from patients of body-mass indices (BMIs) ranging from 17.9 to 83.9 kg/m2. Isoprenaline-stimulated cyclic AMP accumulation in cells prepared from obese subjects as compared with normal-weight subjects, was less sensitive to inhibition by the adenosine agonist N6-(phenylisopropyl)adenosine (PIA) (P = 0.047). The inhibition of 7 beta-desacetyl-7 beta-[gamma-(N-methylpiperazino) butyryl]-forskolin-stimulated adenylate cyclase by PIA in the presence of adenosine deaminase was also much attenuated in crude plasma membranes of adipocytes prepared from massively obese patients as compared with lean controls (P = 0.0143). This difference was probably not due to different cell size, because adenylate cyclase of crude plasma membranes of large adipocytes was actually more sensitive to PIA than was adenylate cyclase of membranes of smaller fat-cells co-isolated from the same individual. The stimulatory effect of PIA on glucose uptake in the presence of adenosine deaminase was depressed in adipocytes prepared from obese subjects and correlated with BMI at r = -0.626 (P = 0.007) at 100 nM-PIA. The adenosine receptors were studied by using the adenosine antagonist 1,3-[3H]dipropyl-8-cyclopentylxanthine. The binding was rapid and proportional to protein concentration. There was no difference in the affinities of receptors in membranes of obese and normal-weight subjects; Kd values of all patients averaged 3.3 nM. Bmax values were 54 and 130 fmol/mg of protein in membranes prepared from seven obese and five control patients respectively. The Bmax values calculated per mg of protein correlated with BMI at r = -0.539 (P = 0.047). The adenosine content of adipose tissue was higher in obese than in control subjects. These results demonstrate an attenuated response of cyclic AMP accumulation, adenylate cyclase and glucose uptake to adenosine in fat-cells prepared from obese subjects, and suggest that this change is at least partly due to changes in the amount of adenosine receptors, but not their affinity. The decreased receptor number could be due to higher adenosine content. A higher adenosine concentration in adipose tissue could explain why lipolysis is inhibited in situ in obesity, and the desensitization could explain the diminished response to adenosine analogues in isolated fat-cells.

Adenosine↗