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Biomedical subjects

R A Forse

Publications and source records attributed to R A Forse.

At least 73 records · Page 4Linked to original sources
PubMed1993

Endotoxin-exposed atria exhibit G protein-based deficits in inotropic regulation.

BACKGROUND: Diminished response at the myocardial beta 1-adrenoceptor is established in endotoxemia. The myocardial muscarinic-2 acetylcholine receptor (M2ACHR) has not been investigated in endotoxemia, although it shares a G protein-mediated link to adenyl cyclase (AC). This study aimed to assess the contractile responses elicited at the M2ACH and beta 1 receptors, their respective G proteins, and the AC unit in endotoxemia. METHODS: Isometric force and rate of contraction were measured in atria from Sprague-Dawley rats after exposure to 24-hour continuous intravenous infusion of 0.2 mg/kg endotoxin or vehicle. The responses to isoproterenol, acetylcholine, sodium fluoride (NaF), and forskolin were studied. RESULTS: In a comparison of endotoxic versus control atria, diminished force response at the beta 1-adrenoceptor was confirmed (4.98 +/- 1.343 vs 7.26 +/- 1.568 gx10 [gx10 is unit of measure used for force], p = 0.0006, n = 10), and an analogous defect at the M2ACHR was identified (6.66 +/- 0.906 vs 8.16 +/- 1.307 gx10, p = 0.009, n = 10). NaF was able to directly activate Gs and G(i) in a dose-dependent differential manner. Both Gs (5.40 +/- 0.795 vs 7.81 +/- 1.057 gx10, p = 0.0015, n = 6) and G(i) (2.73 +/- 0.528 vs 3.76 +/- 0.332 gx10, p = 0.003) force responses were diminished in endotoxic atria. Stimulus of AC by forskolin yielded similar force increases (3.15 +/- 0.731 vs 3.21 +/- 0.667 gx10, p = 0.89, n = 9). CONCLUSIONS: In this model only contractile responses were altered by endotoxemia. The use of NaF revealed dysfunction distal to agonist receptor interaction and with the data from M2ACHR activation confirmed that this defect is not adrenergic specific. The preserved response at AC localized the site of this myocardial receptor dysfunction to the G proteins.

Acetylcholine↗
PubMed1993

A gastroplasty that avoids stapling in continuity.

BACKGROUND: Staple line perforations have been the principal cause of failure after vertical-banded gastroplasty in patients followed at least 4 years at our institution. In the present study an operation was devised that created a vertical-banded gastroplasty not dependent on staple lines to avoid this complication. METHODS: One hundred two patients with a body mass index (BMI) greater than 35 kg/m2 underwent vertical-banded gastroplasty from Jan. 1 to Dec. 30, 1986, with an orifice size of 45 to 47 mm external circumference and division between the vertical staple lines to prevent gastric pouch to gastric fundus fistula. RESULTS: Ninety-eight of the patients have been followed up for a minimum of 4 years. Sixty-two percent of patients obtained an excellent or good final result after 4.5 +/- 0.1 years. This was a BMI of less than 35 kg/m2 or less than 50% excess weight. This acceptable long-term result was achieved 90% of the time if the patient was obese (BMI, 35 to 40 kg/m2) before surgery and in 75% of patients who were morbidly obese (BMI, 40 to 50 kg/m2) but in only 30% of patients who were superobese (BMI > 50 kg/m2) before surgery. Staple line disruption was markedly reduced; however, stenosis or failure to lose weight or late weight gain required reoperation in 36% of the patients. CONCLUSIONS: Gastric bypass was superior to reversal or revision of the gastroplasty as a remedial operation. This study again questions the value of vertical-banded gastroplasty in the treatment of obesity even when staple line disruption is markedly diminished.

Adult↗
PubMed1992

Heart disease and hypertension in severe obesity: the benefits of weight reduction.

Severe obesity is associated with abnormalities of cardiac structure and function. These include an increased cardiac workload and ventricular hypertrophy. Hypertension in combination with severe obesity seriously burdens the heart because the increased preload and afterload compound cardiac work. Weight reduction induced by gastric operations for severe obesity is associated with resolution of hypertension, reduction in ventricular wall thickness and cardiac chamber size, as well as improved systolic function. Additional data are needed to predict when in the course of development of obese cardiomyopathy the changes in contractile function become irreversible. Additionally, the impact of coronary artery disease on the progression of obese cardiomyopathy and the effects of surgical weight reduction on cardiac structure and function need to be further clarified. Studies of the association between obesity, its treatment, and modification of cardiovascular risk are a major focus of preventive cardiology today.

Cardiomyopathies↗
PubMed1992

Intra-abdominal sepsis and adrenergic receptor response.

This study measured the adrenergic receptor response of 13 patients with severe intra-abdominal sepsis, who required laparotomy and an open abdominal closure with Marlex mesh. The source of the sepsis was gram-negative organisms of intestinal origin. There were seven survivors and six nonsurvivors. When the patients were stratified into survivors and nonsurvivors, the Septic Severity Score, the APACHE II score, the Acute Physiological Score, and the Glasgow Coma Scale score results were not significantly different between groups. The alpha-2 and beta-1 adrenergic receptor responses were measured in the adipose tissue of the abdominal wall and the small bowel mesentery on day 1 of admission to the intensive care unit. The results demonstrated that the alpha-2 and beta-1 receptors of the nonsurvivors had a significantly decreased receptor response with desensitization and down regulation. The alpha-2 and beta-1 receptors of the survivors had an increased response with hypersensitization and up regulation. This study indicates that the adrenergic receptor pattern is distinctly different between survivors and nonsurvivors with severe abdominal gram-negative sepsis. The pattern differences occurred early (within 24 hours) when the patients had similar physiologic profiles. It is concluded that adrenergic receptor response may be a biologic indicator of the magnitude of the septic injury and a predictor of outcome.

Adipose Tissue↗
PubMed1992

Glutamine content of whole proteins: implications for enteral formulas.

In two recent clinical trials in surgical patients, supplementation of total parenteral nutrition with daily doses of 12 or 20 g of glutamine resulted in a diminished loss of free glutamine in skeletal muscle tissue. Studies in animals exploring the use of both enteral and parenteral glutamine supplementation suggest that glutamine may be an essential nutrient in the maintenance of gut structure and function during critical illness. These findings have led to heightened interest in the glutamine content of enteral formulas. This article describes a method for estimating the glutamine content of whole-protein enteral formulas. The average amount of glutamine in selected, whole-protein formulas ranges from a minimum of 3.55 g/4200 kJ to a maximum of 5.15 g/4200 kJ. Although it is still too early to define the safest and most effective dose of glutamine, there are two points regarding glutamine supplementation that clearly merit further investigation: no clinical trials have been conducted to assess the potential benefits of glutamine supplementation of an enteral diet or to assess the effects of using diets containing protein-bound glutamine rather than free glutamine.

Enteral Nutrition↗
PubMed1992

Tolerance to enteral tube feeding diets in hypoalbuminemic critically ill, geriatric patients.

Tolerance of elemental (for example, Peptamen [PEP]) or free amino acid (for example, Vivonex TEN [VIV]) tube feeding diets is controversial, especially in the critically ill patient who is hypoalbuminemic. A prospective, randomized trial was conducted to compare differences between feeding PEP (n = 8) or VIV (n = 8) in critically ill, elderly (average age of 66 years) patients. Diets were administered through nasogastric or postpyloric feeding tubes. Eleven patients had diseases of the gastrointestinal tract; all underwent surgical treatment. Patients were fed each diet at full strength, beginning with 20 to 30 milliliters per hour and advancing by 10 to 20 milliliters every day until goal rate was reached, usually on day 4. Assessment was made for ability to comply with rate of tube feeding ordered, compliance with caloric goal and tolerance (as evidenced by abdominal discomfort and diarrhea). Diarrhea was qualitatively defined as more than three stools per day and then quantitatively as the mean number of stools daily. There were no significant differences between the two groups in terms of compliance with prescribed tube feeding order or caloric goal or the presence of diarrhea and abdominal discomfort. There was a significant difference between the two groups in terms of the actual number of stools per day (PEP equals 1.38 versus VIV equals 2.25, p less than 0.02). Serum albumin concentrations upon initiation of the diets were 2.3 grams per deciliter in both groups. We conclude that tolerance to the two diets were similar because it was possible to feed enterally either PEP or VIV in critically ill, hypoalbuminemic patients (serum albumin concentrations of less than 2.5 grams per deciliter) successfully, irrespective of diet. Although there were more stools in the VIV group, this did not reduce compliance with the goals.

Aged↗
PubMed1992

Dietary enrichment with omega-3 fatty acids partially protects against lipopolysaccharide-induced atrial depression in rats.

We tested the hypothesis that pretreatment with a diet enriched with omega-3 fatty acids can prevent lipopolysaccharide (LPS)-induced atrial dysfunction. Sprague-Dawley rats were fed a diet containing 20% safflower oil (control diet; CD) or 19.5% menhaden/0.5% safflower oil (experimental diet; ED). After 28 days, the animals were injected I.V. with LPS (20 mg/kg) or normal saline (S). Two hours later, the atria were harvested, connected to a force displacement transducer-amplifier-recorder system and maintained in vitro in oxygenated 37.5 degrees C Krebs-Henseleit buffer. Force of contraction indexed to body weight (FOCI; g/kg) and maximal rate of rise of contraction (dF/dt, g/sec) and relaxation (-dF/dt, g/sec) were similar in the CD-S (n = 6) and ED-S (n = 6) groups. FOCI, dF/dt, and -dF/dt were lower (P less than 0.05) in rats injected with LPS compared with rats injected with S irrespective of diet, but were significantly higher (P less than 0.05) in LPS-ED rats (n = 11) compared with LPS-CD rats (n = 11). Chronotropic and inotropic responses to graded doses (0.1, 0.5, 1.0, and 5.0 microM) of isoproterenol were not significantly different among groups. LPS-induced production of thromboxane B2 but not 6-keto-prostaglandin F1 alpha, was inhibited in ED fed rats. The ED did not enhance survival when rats were challenged with a 20 mg/kg I.V. dose of LPS. These results indicate that dietary enrichment with omega-3 fatty acids in rats partially protects against LPS-induced alterations in atrial function but does not change mortality after an LD100 dose of LPS.

6-Ketoprostaglandin F1 alpha↗
PubMed1991

Elective intrahospital admissions versus acute interhospital transfers to a surgical intensive care unit: cost and outcome prediction.

After a decade of intense fiscal scrutiny, appropriate utilization of intensive care resources remains controversial. In particular, the financial impact of patients transferred to a tertiary surgical intensive care unit (SICU) from a community hospital (interhospital) is unknown, especially when compared with elective (intrahospital) SICU admissions admitted from the tertiary center itself. We prospectively studied outcome and costs in 82 consecutive tertiary SICU admissions. Half were transferred acutely from community hospitals and half were transferred from within the hospital or postoperatively. Severity of illness (APACHE II) was scored on day 1, at the same time of the day (9:00-10:00 AM) and by one attending surgeon (BCB). Acute transfer patients had a significantly elevated mortality (36%) when compared with elective admissions (12%) (p less than 0.05). When stratified by APACHE II score, acute transfers had twice the mortality for equivalent APACHE II scores (p less than 0.05). Acute transfer patients with APACHE II scores greater than 19 had an 89% mortality; those nonsurvivors cost $128,652 each. From these results we conclude the following: (1) Acute transfer patients have a significantly elevated mortality when compared with elective intrahospital admissions with equivalent APACHE II day-1 scores; (2) patients transferred acutely to tertiary SICUs are significantly more costly, irrespective of outcome; (3) admission source (elective vs. acute transfer) should be seriously considered when evaluating patient outcome and cost in a SICU.

Acute Disease↗
PubMed1991

Surgical intensive care unit resource use in a specialty referral hospital: I. Predictors of early death and cost implications.

The rationing of medical care prioritizes the need for early predictors of death in the surgical intensive care unit (SICU). We prospectively studied 100 consecutive SICU admissions, looking for predictors of early death in the SICU and the cost implications of these findings. Serial APACHE II scores on days 1, 3, and 5 were subjected to multinomial logistic regression analysis to determine significant predictors of death in the SICU on day 1. Survivors had significantly lower (p less than 0.05) mean day-1 APACHE II scores than had nonsurvivors (13.6 vs 22.1). Half of the patients with scores greater than 18 died, and all patients with scores on day 1 of 25 or greater died. Significant predictors of death on SICU day 1 were APACHE II scores, Acute Physiology Score, Glasgow Coma Score, creatinine level, and Chronic Health Evaluation Score. Forty-one patients had been transferred from community hospitals as a results of acute illness; this population accounted for two thirds of the deaths in the SICU. Ten of 18 nonsurvivors were predicted on day 1, with these patients incurring a total cost of approximately $1 million. If therapy had been modified on days 5, 10, or 15, the potential cost savings would have been $340,000, $240,000, or $140,000, respectively. Integration of the results of this study into the management decision-making process and treatment guidelines may reduce the cost of care in the SICU.

Costs and Cost Analysis↗
PubMed1990

Effects of glucose on nitrogen balance during high nitrogen intake in malnourished patients.

1. The effects of increasing glucose intake on nitrogen balance, energy expenditure and fuel utilization were measured in 12 malnourished adult patients receiving parenteral nutrition with constant, very high nitrogen intake (500 mg of N/kg), high (105 kJ/kg) or low (30 kJ/kg) glucose intake and constant fat intake (7 kJ/kg). Each patient received each diet for 8-day periods in random order. 2. Energy balance and nitrogen balance were determined daily. Blood samples, taken at admission, during 5% (w/v) dextrose (D-glucose) infusion and at the end of days 7 and 8 of each diet, were analysed for urea, glucose, lactate, triacylglycerols, fatty acids, glycerol, 3-hydroxybutyrate, insulin and glucagon. 3. The effect of increasing glucose intake was to increase nitrogen balance by 0.60 +/- 0.25 (SEM) mg/kJ. At zero energy balance, nitrogen balance was 48 mg day-1 kg-1. This confirms findings of previous studies: that the effects of glucose on nitrogen balance are greater at high than at low nitrogen intakes, and that, in malnourished patients, unlike in normal adults, markedly positive nitrogen balance can be achieved at zero or negative energy balances. 4. Changes in nitrogen balance were due almost entirely to changes in urea excretion. 5. The high nitrogen intake markedly increased plasma insulin and glucagon concentrations and reduced glycerol, fatty acid and 3-hydroxybutyrate concentrations, independent of any glucose effect. Glucagon concentrations were significantly decreased by added glucose intake, an effect not previously seen at low nitrogen intakes. At this high nitrogen intake, the effects of added glucose appear to be mediated by both insulin and glucagon.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxybutyric Acid↗
PubMed1990

Protein metabolic effects of a prolonged fast and hypocaloric refeeding.

In a study of the mechanism of adaptation to protein deficiency, 10 moderately obese women underwent a 3-wk fast followed by random allocation to a 1-wk refeeding regimen providing 80 g carbohydrate or protein. Protein metabolism was studied by means of nitrogen (N) balance, urinary 3-methylhistidine excretion, and postabsorptive plasma leucine flux using L-[1-13C]leucine infusions. After the 3-wk fast, plasma leucine flux and 3-methylhistidine excretion both decreased by 31% from control diet values (P less than 0.01), and N balance was -5.9 g/day. After protein refeeding, N balance was positive (+1.7 g/day, P less than 0.05) whereas leucine flux was unchanged from prolonged fasting values. After carbohydrate refeeding, N balance improved to -3.1 g N/day, whereas leucine flux decreased by a further 18% (P less than 0.05). Protein and carbohydrate refeeding were associated with further 23 and 31% reductions of 3-methylhistidine excretion compared with prolonged fasting (P less than 0.05). The results support the hypothesis that improved efficiency of protein retention in starvation is intimately associated with a decreased rate of protein turnover.

3-Hydroxybutyric Acid↗
PubMed1990

Assessment of cardiac function in patients who were morbidly obese.

Cardiac function of 30 patients who were morbidly obese was studied before bariatric surgery. Twelve patients were studied 13 +/- 4 months after surgery. These patients had a mean age of 37.1 +/- 2.9 years and a body mass index of 50.0 +/- 1.4 kg/m2. Cardiac function was measured by echocardiography, radionuclide angiography scanning, and right heart catheterization. To determine the degree of cardiac dysfunction, the patients were studied with exercise and intravenous fluid challenges. Ultrasonography produced evidence of myocardial thickening with an increased interventricular septum in eight patients (32%) and increased left ventricular mass in 17 patients (53%). The radionuclide scan suggested that morbid obesity was associated with a significantly (p less than 0.05) increased end-diastolic volume and decreased left ventricular ejection fraction as compared with patients who were of normal weight. With exercise the patient who was of normal weight had an increase in the end-diastolic volume, stroke volume, and heart rate, but the patient who was morbidly obese only increased heart rate to produce the necessary increase in cardiac output. Right heart catheterization indicated that the relationship of the pulmonary wedge pressure and the left ventricular stroke work index was abnormal in 14 of 29 patients (48.3%) and depressed in six of 29 patients (20.7%) with exercise. One liter of fluid caused an abnormal relationship of the pulmonary wedge pressure and the left ventricular stroke work index in 12 of 30 patients (40%) and a depressed response in 10 of 30 patients (33.3%). Cardiac studies were repeated in 12 patients after a 54.8 +/- 1.9 kg weight loss. Echocardiography indicated a decrease in dilatation (27.3% to 9.1%) and a significant (p less than 0.05) decrease in hypertrophy (45.5% to 0%). After the weight loss, radionuclide and right heart catheterization studies indicated improved cardiac function with reduced filling pressures and increased left ventricular work during fluid and exercise challenges. These results support the presence of obesity-related cardiomyopathy with ventricular dysfunction, which appears to be caused by a noncompliant ventricle. Significant weight loss achieved with gastroplasty results in increased ventricular compliance and improved cardiac function.

Adult↗
PubMed1990

Late results of vertical banded gastroplasty for morbid and super obesity.

Two hundred one patients who underwent vertical banded gastroplasty have been followed up for a minimum of 2 years to more than 5 years. Staple line perforations occurred in 48% of patients, and 36% underwent reoperation. The instability of the operation becomes apparent only with careful follow-up. More than 50% of patients who maintained a small orifice of less than or equal to 11 mm in diameter and an intact staple line over 3 to 5 years achieved an excellent result (0% to 25% excess weight), which equals the best results in the literature for any gastric-limiting operation, whether bypass or gastroplasty. The results of this operation for super obesity (a body mass index greater than or equal to 50 kg/m2) are disappointing. Only 8% of these patients achieve an excellent result. Failure of vertical banded gastroplasty in the morbidly obese (body mass index of 40 to 50 kg/m2) is frequently technical, and a method that eliminates dependence on integrity of staples should be evaluated. Results should be reported so that unsatisfactory results are apparent. Mean weight loss and mean percent excess weight loss are both highly satisfactory in this study, whereas unsatisfactory results ranged from 10% to 21% for each of the 5 years of follow-up.

Body Mass Index↗
PubMed1989

The effect of ASP on the adipocyte of the morbidly obese.

The control of triglyceride synthesis within the adipocyte is not fully understood. Insulin is considered to be the most potent stimulant of triglyceride synthesis. In this paper, we report on the effect of a small (14000 Da), basic (pI 9.0) protein isolated from human serum. This protein has been called acylation stimulating protein (ASP). It is a potent stimulant of triglyceride synthesis in adipocytes from both normal weight and morbidly obese subjects. Its stimulatory effect on adipocytes is both rapid, occurring between 15-30 min after the start of incubation, and prolonged, lasting for up to 3 hr. Compared to insulin, it is sixfold more potent in its effect on triglyceride synthesis. As well as acting on isolated cells, ASP also has a fourfold stimulatory effect on triglyceride synthesis in human adipose microsomes at a concentration of 25 micrograms/ml. This study indicates that ASP is a potent stimulant of triglyceride synthesis and therefore may play a role in the pathogenesis of morbid obesity.

Adipose Tissue↗
PubMed1989

The effect of Escherichia coli endotoxin on the adrenergic control of lipolysis in the human adipocyte.

We investigated the effect of Escherichia coli O127:B8 endotoxins on the adrenergic control of lipolysis in the human adipocyte. Adipose tissue was incubated in vitro with isoproterenol to stimulate the beta-1 receptors, clonidine to stimulate the alpha-2 receptors, and theophylline to stimulate the subreceptor mechanism. Using a dual radioisotope technique, a lipolysis factor was calculated for each sample. The basal lipolysis factor was significantly (P less than 0.006) decreased 31% with endotoxin. beta-1 adrenergic receptor stimulation (isoproterenol, 1 X 10(-8) to 1 X 10(-4) M) was significantly decreased an average of 31% with E. coli endotoxin. The beta-1 receptor responsiveness was also significantly (P less than 0.02) decreased but not the receptor sensitivity. This indicated an alteration in the post beta receptor mechanism. The various components of the post beta-1 adrenergic mechanism were stimulated including the beta-1 receptor, the G protein, adenylase cyclase, and the lipase phosphorylase. The results indicated a significant 24.2% reduction of the beta-1 receptor and a 25.4% reduction in G protein stimulation. Thus the E. coli endotoxin effect on the beta adrenergic mechanism is at the G protein. The endotoxin had no effect on the alpha-2 receptor stimulation nor the theophylline stimulation of the subreceptor lipolysis. This study indicates that E. coli endotoxin (O127:B8) decreases in vitro beta adrenergic stimulation of human adipocyte lipolysis, and this effect can be partially reversed by theophylline.

Adipose Tissue↗
PubMed1989

DNA marker studies show that Machado Joseph disease is not an allele of the Huntington disease locus.

Machado Joseph Disease (MJD) is a progressive spinocerebellar atrophy (SCA) with an autosomal dominant mode of inheritance. On the basis of some similarities in the clinical features and in the abnormal profiles of brain proteins, it has been suggested that MJD might be an allele of the Huntington Disease (HD) locus. Using the DNA probe (pK082), we analyzed the linkage between the DNA marker locus D4S10 and the MJD locus in two large kindreds. The data exclude linkage between these two loci at a distance of 10 cm (Z = - 2.02). Since the D4S10 locus is linked to the HD locus at a distance of approximately 4 cm, we conclude that MJD is not an allele of the HD locus.

Alleles↗