Ethical and legal aspects of enteral nutrition.

European ethical and legal positions with regard to EN vary slightly from country to country but are based on a common tradition derived from Graeco Roman ideas, religious thought and events of the 20th century. The Hippocratic tradition is based on 'beneficience' (do good) and 'non-maleficience' (do no harm). Religious thinking is based upon the presumption of providing food and drink by whatever means unless burden outweighs benefit. The concept of 'autonomy' (the patients right to decide) arose following in the decades after the Second World War and is enshrined in Human Rights law. The competent patient has the right to participate in decision making and to refuse treatment although the doctor is not obliged to give treatment which he or she considers futile or against the patient's interests. The incompetent patient is protected by law. The fourth principle is that of 'justice' i.e. equal access to healthcare for all. The law regards withholding and withdrawing treatment as the same. It also defines the provision of food and drink by mouth as basic care and feeding by artificial means as a medical treatment. It requires doctors to act in the best interests of the patient.

Estrogen receptor expression in benign breast epithelium and breast cancer risk.

BACKGROUND: Estrogen exposure is a major risk factor for breast cancer. Increased estrogen responsiveness of breast epithelium may enhance this effect. We examined the relationship between breast cancer diagnosis and 1) the presence and absence of estrogen receptor expression in benign breast epithelium, 2) the level of expression and 3) its variation during the menstrual cycle, and 4) other established risk factors. e.g., age, age at menarche, parity, and family history. METHODS: We measured estrogen receptor expression (as % of positive cells) by immunohistochemistry in normal breast epithelium from 376 women undergoing diagnostic or therapeutic breast surgery. Data on established risk factors were collected prior to surgery and those on menstrual cycle dates at the time of surgery. Logistic regression was used to assess risks (odds ratios [ORs]). RESULTS: The crude OR for breast cancer in women with estrogen receptor-positive breast epithelium versus those without was 3.16 (95% confidence interval [CI] = 1.89-5.28), with an OR of 2.49 (95% CI = 1.25-4.96) for premenopausal and an OR of 3.32 (95% CI = 1.43-7.68) for postmenopausal women. The ORs remained high and statistically significant after controlling for age and other breast cancer risk factors. The level of estrogen receptor expression was higher in patients with breast cancer than in control subjects and it was related to breast cancer risk in postmenopausal women (P trend <.005). Expression declined as expected in premenopausal control subjects as the menstrual cycle progressed but rose in breast cancer patients (P trend <.015). CONCLUSIONS: The overexpression of estrogen receptors in normal breast epithelium may augment estrogen sensitivity and hence the risk of breast cancer.

Studies on the regulation of food intake using rat total parenteral nutrition as a model.

Total parenteral nutrition (TPN) is essential for maintaining the nutritional status of patients who are unable to eat sufficiently to meet their metabolic needs. However, TPN suppresses appetite and ultimately diminishes food intake. Theories concerning the role(s) of peripheral metabolites as signals, acting via the liver and the hypothalamus, for the metabolic control of food intake, have been put forward to explain the anorectic effect of TPN. In addition, it is postulated that changes in peripheral metabolites during TPN may be translated into changes in the levels of brain neurotransmitters known to decrease food intake. This review summarizes studies concerning the effect of TPN on food intake. These studies have involved: (1) characterizing the changes in feeding activity due to TPN; (2) investigating the involvement of the central nervous system; and (3) investigating the role of the periphery and its metabolites in the regulation of food intake during TPN. Some insight into the mechanism of action of TPN on food intake is provided.

A critical appraisal of the usefulness of perioperative nutritional support.

Preoperative malnutrition is often associated with poor postoperative outcome, yet there is no consensus about whether perioperative nutritional support reduces postoperative complications to the level occurring in well-nourished patients undergoing similar procedures. This is partly because reports evaluating effect of perioperative nutritional support on postoperative outcome vary widely in number of patients studied, primary diagnosis, and duration and quality of perioperative nutritional support. These concerns warrant caution in interpreting reported results, even of randomized studies. However, analysis of published reports suggests that when total parenteral nutrition (TPN) is given to malnourished patients in adequate amounts for greater than or equal to 7-15 d preoperatively, significant improvements in both nutritional status and postoperative clinical outcome are likely to occur. Preoperative total enteral nutrition (TEN) is as effective as TPN in improving postoperative clinical outcome. Postoperative TPN, TEN, and ad libitum oral nutrition are equally effective in reducing postoperative complications. Potential candidates for surgery for whom prompt initiation of preoperative TPN or TEN may reduce operative morbidity and mortality irrespective of nutritional status can be identified on admission.

Valine kinetics at graded valine intakes in young men.

Twelve young men, six subjects in each group studied in two phases, participated in an experiment to explore the relationships between valine intake, plasma valine concentrations, and valine kinetics, using 1-[13C]valine as a tracer. Below a valine intake of about 20 mg.kg-1.day-1 plasma valine concentrations reached a low and relatively constant level. The rate of valine oxidation fell with the decline in the intake of amino acid. Below valine intakes of 16 mg.kg-1.day-1, the mean daily rate of oxidation was estimated to be generally higher than the intake level, implying a negative valine balance during the 24 h day. These findings indicate that an intake of 10 mg valine kg-1.day-1 would not be adequate to maintain protein nutritional status. Our results are discussed in relation to the currently accepted 1973 FAO/WHO value of 10 mg.kg-1.day-1 as being the upper range of the valine requirement in healthy adult humans.

Leucine kinetics at graded leucine intakes in young men.

A study was carried out with 12 young men to examine the relationships between the intake of leucine and indices of leucine kinetics, using L-[1-13C]leucine as a tracer. Six subjects received L-amino acid diets during 7-day periods supplying leucine in the range of 79 to 20 mg.kg-1.day-1 (Group I) and another six subjects (Group II) received leucine intakes ranging from 20 to 4 mg.kg-1.day-1. Estimations were made of leucine kinetics, at the end of each diet period, when subjects were receiving small isonitrogenous, isocaloric meals during the isotope infusion period. Leucine flux declined with reduced leucine intake and leucine oxidation tended not to change at intakes below 20 mg.kg-1.day-1 (slope not statistically different than zero). Plasma valine increased markedly with further restriction in leucine intake below this level. The daily mass balance of leucine, estimated from the difference between intake and oxidation, became negative at an intake of about 20 mg.kg-1.day-1. These findings are discussed in relation to the published mean and upper range of requirement for leucine in healthy adults, currently taken to be 11 mg.kg-1.day-1 and 14 mg.kg-1.day-1, respectively.

The normal breast epithelium of women with breast cancer displays an aberrant response to estradiol.

Breast epithelial response to estradiol may play an important role in breast cancer etiology. We have examined the relationship between serum estradiol and progesterone levels and normal breast epithelial expression of estrogen receptor (ER) alpha, progesterone receptor (PgR), and epithelial proliferation (as reflected by the Ki-67 labeling index) in 121 women (50 newly diagnosed breast cancer cases and 71 benign breast disease controls). Simultaneous samples of grossly normal breast tissue and venous blood were obtained from women undergoing breast surgery. Serum estradiol and progesterone levels were measured by radioimmunoassay; breast epithelial ER, PgR, and Ki-67 expression was measured by immunohistochemistry. Linear regression, controlled for patient age and ductal and lobular composition of the tissue, showed that the breast epithelium of control women displayed an inverse correlation between serum estradiol and ER-alpha, which was not seen in case women (P for the difference in regression slopes = 0.001). PgR expression displayed a significant positive correlation with serum estradiol in cases, but not in controls. Epithelial proliferation had no relationship to either estradiol or progesterone in both cases and controls but showed an inverse relationship with ER in controls and a direct relationship in cases (P for the difference in regression slopes = 0.066). These results suggest a dysregulation of hormonal response in the normal breast epithelium of high-risk women, with lack of regulation of ER by estradiol, increased estrogen responsiveness as reflected by PgR expression, and a dissociation of ER expression and proliferative response.

Synchronized release of dopamine and serotonin in the medial and lateral hypothalamus of rats.

A positive linear correlation between dopamine and serotonin release was found in the ventromedial hypothalamus and in the lateral hypothalamic area in fasting rats and in fed rats during intermeal intervals. Dopamine release in the ventromedial hypothalamus positively correlated with dopamine and serotonin release in the lateral hypothalamic area, which occurred only during intermeal intervals and was non-significant during the meal consumption periods or during fasting. Meal size correlated significantly only with a decrease in serotonin release in the lateral hypothalamic area. The study was designed to evaluate the relationship between dopamine and serotonin release in these hypothalamic areas and their dependence on feeding status. Microdialysis was performed simultaneously via two probes, one in the ventromedial hypothalamus and the other in the contralateral lateral hypothalamic area, of freely moving male lean Zucker rats over 24h with preserved light and dark phase, either with ad libitum access to food and water, or when no food was available. Dopamine and serotonin concentrations were measured by high-performance liquid chromatography with electrochemical detection in 20-min dialysis samples. Time-series analysis was applied to determine linear correlations between monoamines and in relation to food intake. Data showed that release of dopamine and serotonin is synchronized within the ventromedial hypothalamus and lateral hypothalamic area, particularly in the dark phase and when no food was ingested. However, synchronized release of monoamines between these nuclei occurred only during intermeal intervals: the periods of satiety. These findings suggest a tight relationship between dopaminergic and serotonergic systems of the lateral hypothalamic area and ventromedial hypothalamus, which is influenced by the feeding state and which may be involved in maintaining the balance within and between the centers of the parasympathetic and sympathetic nervous systems. The data also illustate that food intake is coupled unequivocally to the release of dopamine and serotonin in the hypothalamus, suggesting it as a mechanism of activation of postsynaptic neurons associated with new metabolic status.

VMN hypothalamic dopamine and serotonin in anorectic septic rats.

During sepsis, catabolism of proteins and associated changes in plasma amino acids occur. Tryptophan and tyrosine, and their derivatives serotonin (5-HT) and dopamine (DA), influence hypothalamic feeding-related areas and are associated with the onset of anorexia. We hypothesized that anorexia of sepsis is associated with changes in serotonin and dopamine in the ventromedial nucleus (VMN) of the hypothalamus. The aim of this study was to test our hypothesis by measuring intra-VMN changes of these two neurotransmitters at the onset of anorexia during sepsis. Fischer 344 male rats had an intracerebral guide cannula stereotaxically implanted into the VMN. Ten days later, in awake, overnight-food-deprived rats, a microdialysis probe was inserted through the in situ VMN cannula. Two hours thereafter, serial baseline serotonin and dopamine concentrations were measured. Then cecal ligation and puncture to induce sepsis or a control laparotomy was performed under isoflurane anesthesia. VMN microdialysis samples were serially collected every 30 min for 8 h after the surgical procedure to determine 5-HT and DA changes in response to sepsis. During the hypermetabolic response to sepsis, a strong association occurred between anorexia and a significant reduction of VMN dopamine concentration (P < 0.05; constant rate of dopamine decrease in the Study group of 0.99 pg per 2 h); no changes occurred in 5-HT in association with anorexia of sepsis. Six hours after operation, a single meal was offered for 20 min to assess the response of neurotransmitters to food ingestion. Food intake was minimal in anorectic septic rats (mean size of the after food-deprived meal in the Septic group was 0.03+/-0.01 g, that of the Control group was 1.27+/-0.14 g; P = 0.0001), while Control rats demonstrated anticipated changes in neurotransmitters in response to eating. We conclude that the onset of anorexia in septic rats is associated with a reduction in VMN dopamine.

A prospective randomized study of the optimal source of nonprotein calories in total parenteral nutrition.

We previously showed that providing 30% of nonprotein calories as lipid eliminated glucose intolerance and ameliorated the other troublesome metabolic complications of total parenteral nutrition (TPN): hepatic abnormalities and hypertriglyceridemia. Whether such a mixed-fuel system is as effective as a hypertonic glucose-only TPN fuel system in achieving an anabolic state was tested in 88 consenting patients randomized to either conventional TPN (25% dextrose and 4.25% amino acids) or modified TPN (15% dextrose, fat, and 5% amino acids). Treatment groups were: group A, no surgery, TPN only; group B, postoperative TPN starting 48 hours after surgery; and group C, preoperative TPN, surgery on day 7 and with continued postoperative TPN. In all groups TPN was given for 14 days while patients were given nothing by mouth. Changes in the indexes of body protein metabolism, reflected by nitrogen balance, serum albumin, blood urea nitrogen, and weight, were measured on days 1 and 14. Nitrogen balance improved in patients randomized to either regimen, but there was no significant difference in the degree of improvement. Albumin levels were maintained, and differences between initial and final values were not significant. Blood urea nitrogen increased in all groups (p less than 0.05); however there was no significant difference between regimens. Patients maintained their weight, and fluid balance data indicated no water retention. Observed weight changes were not statistically significant. In each treatment group an anabolic state occurred and gains in measured protein indexes were similar. Isocaloric replacement of 30% of TPN glucose calories with fat was as effective as glucose-only TPN in achieving an anabolic state without the metabolic complications associated with glucose-only TPN.

Parenteral nutrients in rat suppresses hepatic vagal afferent signals from portal vein to hypothalamus.

BACKGROUND: Parenteral nutrition (PN) suppresses spontaneous food intake in rats by stimulating dopamine in lateral hypothalamic area (LHA), which is attenuated by vagotomy. Sensors for glucose and for some individual amino acids exist in hepatoportal areas sending signals via hepatic vagal afferents to LHA. Hypothesizing that the decrease in spontaneous food intake occurs because a PN amino acid solution is recognized by portal vein sensors, we measured afferent nerve discharges in hepatic vagus in response to PN. METHODS: Hepatic vagus was divided in 11 rats, and an isolated nerve filament was placed on recording electrodes. Afferent firing rate was recorded before and after injecting during 1 minute a well-balanced crystalline amino acid mixture into either the portal or peripheral vein. Isotonic glucose was used as standard solution. RESULTS: A significant decrease in hepatic vagal afferent discharge rate was recorded after both intraportal and intravenous injection of the PN amino acid mixture. The mean discharge rate was inversely related to the concentration of the solution. Successive injections produced further decreases in discharge rate, and the effect was more sustained. CONCLUSIONS: The observed decrease in discharge rates suggests that the crystalline amino acid PN solution is sensed in hepatoportal areas informing LHA via hepatic afferents. This effect may play a role in regulating food intake during PN.

Lateral hypothalamic dopaminergic neural activity in response to total parenteral nutrition.

BACKGROUND: The lateral hypothalamic dopaminergic neurons dominate modulation of food intake. Changes in lateral hypothalamic synaptic dopaminergic release before and during total parenteral nutrition (TPN) and its components were measured in vivo with microdialysis probes. METHODS: Rats had an intracerebral guide cannula and an internal jugular catheter placed. Ten days after recovery, rats were fasted for 24 hours. A 2 mm microdialysis probe was inserted into the lateral hypothalamus neurons via the guide cannula. Dopamine level was measured by high-performance liquid chromatography in three 60-minute baseline dialysis samples. TPN, glucose, fat, or amino acid was then infused via the internal jugular catheter, and dopamine level was measured in three more 60-minute dialysate samples. Single nutrients were infused for 24 hours, and dopamine was measured during the 3 hours after the infusions were stopped. Data were analyzed by paired t test (mean +/- standard error) and represented percentage change from baseline. RESULTS: Dopamine levels rose significantly (p < 0.05) and remained so during infusions in TPN (26% +/- 3%), glucose (26.5% +/- 4.6%), fat (36.2% +/- 6.7%), and amino acids (9.6% +/- 4.2%). After infusions were stopped, dopamine levels decreased to -35.4% +/- 1.5% in glucose but remained unchanged with fat and amino acids. CONCLUSIONS: Increase in lateral hypothalamic dopamine level occurs with TPN and its components, and changes persist temporarily after stopping the infusions, explaining in part the slow recovery of food intake after TPN is stopped.

The effect of severe trauma on urine loss of insulin.

Six trauma patients and five healthy volunteers were given an intravenous glucose infusion (5 Gm. per hour) for 6 hours. The serum insulin response and urine insulin excretion were measured and compared in the two groups. Glucose intolerance and serum insulin levels which were elevated but inappropriately low for the degree of glycemia characterized the trauma patients. Urine insulin concentrations and total urine insulin were increased significantly in the trauma patients. Renal function was similar in both groups, as determined by serum creatinine, blood urea nitrogen, and creatinine clearance. The increase in urine insulin concentration in the trauma patients reflected the higher serum insulin concentrations, but no correlation existed between serum insulin and urine insulin concentrations. A negative correlation was found between "insulin clearance" and serum insulin in both groups, indicating altered renal handling of insulin following injury which may be a contributory factor to the relative hypoinsulinemia of trauma.

Indomethacin decreases carrageenan-induced peritoneal adhesions.

For evaluation of a rat intra-abdominal adhesion model, 48 study rats were each given an intraperitoneal injection of 1 ml of 1.5% carrageenan solution and 48 control rats were each given 1 ml of sterile saline solution. Thereafter, 6 control and 6 study rats were killed on days 2, 3, 4, 5, 7, 9, 14, and 21 for assessment of the temporal nature of adhesion formation. No peritoneal reaction or adhesions occurred from saline solution. Carrageenan induced a generalized peritonitis between days 2 and 7. The frequency of adhesions from day 5 onward was 66%. The effects of celiotomy and of systemic indomethacin on carrageenan-induced adhesion formation were then examined. Rats underwent a standardized celiotomy and, on closure of the abdomen, received either an intraperitoneal injection of saline solution (n = 72) or an intraperitoneal injection of carrageenan solution (n = 96). Both groups were then randomized to receive either no indomethacin (IND-0), a single preoperative dose of indomethacin (IND-1), or four perioperative doses of indomethacin (IND-4). Then, 2, 5, 14, and 21 days later, rats from each group were killed, the extent of intraperitoneal adhesions was assessed, and the nature of any adhesions was histologically examined. Celiotomy plus intraperitoneal saline solution produced no adhesions. Celiotomy plus intraperitoneal carrageenan solution (IND-0) significantly increased adhesions to 83%. Preoperatively and perioperatively administered indomethacin significantly decreased the adhesion formation rate to 49%.

The benefits of Isolator cultures in the management of suspected catheter sepsis.

Until recently, when a patient receiving total parenteral nutrition (TPN) was suspected of having catheter-related sepsis, the catheter was removed and the tip and the patient's blood was cultured. Using this method at our institution, greater than two thirds of the central venous catheters (CVC) removed were sterile, or if colonized, proved not to be the source of sepsis. This practice led to the unwarranted removal of numerous catheters and posed a clinical dilemma because it necessitated replacement of the catheter with its attendant risks, cost, and inconvenience. To address this problem, we instituted a protocol for determining in situ catheter-related sepsis based on a quantitative blood culture method using lysis centrifugation (Isolator; Dupont Co., Wilmington, Del.). When catheter-related sepsis was clinically suspected, quantitative blood cultures were obtained simultaneously via a peripheral (PER) vein and through the CVC suspected as the source of sepsis. The CVC, however, remained in situ pending culture results (approximately 16 to 24 hours). A CVC colony of greater than or equal to five times the PER colony count was considered significant and the catheter was removed. Equivocal colony counts between the CVC and PER cultures were interpreted as incriminating a source of sepsis other than the CVC. An 8-month prospective study was undertaken to evaluate the efficacy of this method for determining in situ catheter sepsis. One hundred third-eight patients received TPN by means of 160 catheters. In 113 patients no sepsis-related problems were noted. In the remaining 25 patients, 28 catheters were suspected as the source of sepsis. Twenty-six catheters were evaluated by the Isolator culture method. In eight instances significant differences in colony counts between the CVC and PER cultures were seen, implicating the CVC as the source of infection. In all these cases the CVC was removed and the patients underwent defervescence. In 18 cases, the CVC samples revealed either no growth or insignificant differences between the CVC and PER colony counts. Nine of these CVCs were removed without clinical improvement. The remaining nine catheters were left in place, and another source of sepsis was ultimately identified and treated. These results confirm the use of the quantitative blood culture method for determining in situ catheter-related sepsis. In all cases, when the catheter was incriminated by culture data, removal of the CVC led to patient improvement.(ABSTRACT TRUNCATED AT 400 WORDS)

Pathogenesis-based treatment of recurring subareolar breast abscesses.

BACKGROUND: When a subareolar breast abscess (SBA) is incised and drained, an extraordinarily high frequency of recurrence is noted. METHODS: To develop a pathogenesis-based treatment plan, 24 women with a total of 84 abscesses were monitored. RESULTS: In nine women SBA was under the left areola, under the right, in 7 and in eight the SBA occurred either simultaneously or sequentially under both areolae. In 11 of 24 patients a chronic lactiferous duct fistula also existed. In four of 24 patients four SBAs were treated with antibiotics; alone; all recurred. In 16 of 24 patients initial treatment was incision and drainage plus antibiotics; all recurred. When the abscess plus the plugged lactiferous duct was excised, there were no recurrences; however, in four patients a new abscess in a different duct occurred, which was treated by en bloc resection of all subareolar ampullae, without further recurrence. Patients with a fistulous tract had the fistula, its feeding abscess, and its plugged lactiferous duct excised, without recurrence. In first time SBA the organism was usually staphylococcus; in recurrences mixed flora was isolated. Pathologic findings ranged from squamous metaplasia with keratinization of lactiferous ducts to chronic abscess. CONCLUSIONS: The cause of SBA is plugging of lactiferous duct within the nipple by keratin. To prevent recurrence the abscessed ampulla with its plugged proximal duct needs excision.

Role of hypothalamic monoamines in nicotine-induced anorexia in menopausal rats.

BACKGROUND: Nicotine reduces body weight by reducing appetite. Estradiol modulates food intake. Menopause or ovariectomy (Ovx) increases food intake and body weight. Nicotine and estradiol individually influence hypothalamic dopamine (DA) and serotonin (5-HT), whose interaction influences food intake and body weight. We investigated whether lower weight gain in menopausal smokers is mediated via changes in hypothalamic DA/5-HT. METHODS: Ovx or sham-operated female rats had 2 microdialysis guide cannulas simultaneously implanted in ipsilateral ventromedial nucleus of hypothalamus (VMN) and contralateral lateral hypothalamic area (LHA). Rats were divided into 4 groups and received a continuous subcutaneous infusion of nicotine or saline Ovx and sham. DA and 5-HT in LHA and VMN were measured by in vivo microdialysis. RESULTS: Nicotine infusion decreased food intake and body weight in Ovx and sham groups. Increase in LHA-DA and VMN-5-HT in sham group occurred with nicotine, whereas an increase in VMN-DA in Ovx groups with and without nicotine and VMN-5-HT in Ovx group with nicotine was observed. CONCLUSIONS: In the presence of estradiol (ovary intact sham-operated rats), nicotine lowers food intake and body weight via increased LHA-DA and VMN-5-HT. In menopause (Ovx rats), nicotine lowers food intake and body weight only via increased VMN-DA and 5-HT. Data show that lower weight gain is mediated via changes in hypothalamic monoamines, primarily via ventromedial hypothalamus.

Rapid bedside method to assess changes in postoperative fluid status with bioelectrical impedance analysis.

BACKGROUND: Estimates of daily postoperative fluid balance usually rely on properly recorded inputs, outputs, and daily weights or clinical signs. These may be imprecise (when poorly done) and are often considered tedious to perform. METHODS: We used bioelectric impedance analysis (BIA) to assess changes in body water shifts in cardiac patients after surgery. Nine consecutively admitted patients undergoing coronary artery bypass (seven men and two women; age range, 43 to 67 years) were studied. Body weight, fluid intake and output, and BIA variables (resistance and reactance) were measured daily. Relationships between body weight and changes in resistance and reactance and net change in fluid balance (in liters per day) were evaluated statistically by regression analysis. RESULTS: Mean body weights changed significantly, reflecting early operative fluid accumulation and later postoperative diuresis; net fluid balance correlated poorly (r = 0.48; p less than 0.05) with body weight, whereas both resistance (r = -0.82; p less than 0.001) and reactance (r = -0.92; p less than 0.0001) correlated highly with net fluid balance. CONCLUSIONS: BIA is useful as an accurate, rapid bedside method for assessing changes in hydration status sequentially after surgery in cardiac patients with complicated fluid shifts.

Nicotine's effect on hypothalamic neurotransmitters and appetite regulation.

BACKGROUND: Tobacco smoking reduces appetite and body weight. Cessation of smoking leads to hyperphagia and weight gain. Food intake is a function of meal number (MN) and meal size (MZ) (i.e., Food intake = MN x MZ). The effect of nicotine on these feeding components and their relationships to dopamine and serotonin in the lateral hypothalamic area (LHA) were determined. METHODS: In Fischer-344 rats the effect of 7 days of systemic nicotine infusion on the feeding patterns was measured by rat eater meter and changes in serotonin (5HT) and dopamine (DA) in the LHA were measured by in vivo microdialysis. RESULTS: Nicotine infusion caused hypophagia through a significant decrease in MN with a smaller decrease in MZ, resulting in a body weight reduction. 5HT and DA concomitantly increased in LHA. Stopping nicotine resulted in hyperphagia by a significant increase in MZ. Body weight normalized. 5HT and DA in LHA decreased after nicotine was stopped. CONCLUSION: Nicotine's hypophagic effect was associated with increased 5HT and DA in LHA, whereas hyperphagia after nicotine cessation was accompanied by decreased concentrations of the neurotransmitters. These findings suggest that nicotine affects appetite regulation, in part by modulation of LHA-DA and 5HT.

Insulin half-life in man after trauma.

To explore the possibility that the half-life of insulin changes after trauma, five control subjects and 19 severe trauma patients received intravenous glucose (0.5 gm/kg) in 5 minutes to raise rapidly the insulin levels, followed immediately by 300 mg of intravenous diazoxide over 5 minutes to inhibit any further insulin secretion. Serial blood samples were analyzed for immunoreactive insulin, and insulin half-life was calculated. The baseline insulin level was 13.4 +/- 3.8 microU/ml in the trauma group 10.4 +/- 3.1 microU/ml in the control group. During the glucose infusion, insulin levels rose to 177.0 +/- 56.0 microU/ml in the controls and to 127.0 +/- 27.0 microU/ml in the trauma group. The rise in the control subjects was greater (P less than 0.03) than the rise in the trauma patients. After diazoxide, insulin levels fell to 25.0 +/- 6.2 microU/ml and 25.0 +/- 6.6 microU/ml, respectively. Insulin half-life in the control subjects was 5.2 +/- 0.3 min and 3.9 +/- 0.2 min in the trauma group (P less than 0.019).