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Accurate information about weight loss is not available for most commercial weight-loss programs. Our objective was to obtain accurate assessments of weight outcomes, behavioral data, and side effects for an intensive behavioral weight-loss program using low-energy diets. Weights, behavioral data, and side effects for 173 consecutive patients were assessed. Treatment options were Medically Supervised, using a minimum of five meal replacements per day, and Healthy Solutions, using meal replacements, fruits, and vegetables. Both options included weekly classes, daily records, midweek phone calls, and a minimum physical activity goal of 2,000 kcal/week. The primary outcome was change in body weight with secondary outcomes related to behavioral changes and side effects. Intention-to-treat (ITT) and completer analyses (completed 9 weeks of treatment) were performed. During 13 months, 173 patients met criteria for analysis. They selected either Healthy Solutions: 56 patients (ITT) and 37 completers; or Medically Supervised: 117 patients (ITT) and 93 completers. Mean (+/-standard error) weight losses were: Healthy Solutions: ITT=12.8+/-1.3 kg in 13 weeks and completers=17.0+/-1.4 kg in 18 weeks; Medically Supervised: ITT=16.6+/-1.0 kg in 16 weeks and completers=19.7+/-1.0 kg in 19 weeks. Mean use of meal replacements, fruits, and vegetables exceeded goals. Most side effects were mild and did not affect program continuation. An intensive behavioral weight-loss program using low-energy diets, including five meal replacements daily, is safe and effective.

Recent studies suggest that obese individuals lose weight more rapidly and lose more total weight with soy protein than with animal protein as a major diet component. The purpose of the present study was to evaluate the weight-loss efficacy and changes in body composition, waist circumference, blood pressure, and levels of plasma glucose, insulin, serum lipids, C-reactive protein, and homocysteine from consumption of either 3 soy shakes or 3 casein shakes daily as part of a 16-week, energy-restricted diet for obese women. Forty-three women with body mass index values of 30 to 40 kg/m(2) were randomized to intensive dietary interventions using either casein (n = 21) or soy (n = 22) shakes. Subjects were instructed to consume 3 shakes, 1 prepackaged entrée, and 5 servings of fruits or vegetables daily to achieve an energy intake of 4.5 to 5.0 MJ/d. Subjects attended classes weekly or biweekly. Weight, body fat, lipid, and glucose measurements were obtained at baseline and at 8 and 16 weeks. For both groups combined, subjects lost 8.1% of initial body weight (7.7 kg) at 8 weeks and 13.4% (12.7 kg) at 16 weeks. Weight loss from baseline did not differ significantly by group and, for completing subjects, was 14.0% +/- 1.2% (mean +/- SE) for casein and 12.8% +/- 1.4% for soy. With the intention-to-treat analysis, weight losses at 16 weeks were 12.5% +/- 1.4% for casein and 11.3% +/- 1.2% for soy. Body fat losses were 23.7% +/- 2.0% for casein and 21.8% +/- 2.4% for soy and did not differ significantly. Both study groups lost significant amounts of weight with a highly structured behavioral program incorporating 4 meal replacements and vegetables and fruits. Differences in weight loss and body composition changes between casein and soy treatments were not significant.

Based on what is known of the components of plant-based diets and their effects from cohort studies, there is reason to believe that vegetarian diets would have advantages in the treatment of type 2 diabetes. At present there are few data on vegetarian diets in diabetes that do not in addition have weight loss or exercise components. Nevertheless, the use of whole-grain or traditionally processed cereals and legumes has been associated with improved glycemic control in both diabetic and insulin-resistant individuals. Long-term cohort studies have indicated that whole-grain consumption reduces the risk of both type 2 diabetes and cardiovascular disease. In addition, nuts (eg, almonds), viscous fibers (eg, fibers from oats and barley), soy proteins, and plant sterols, which may be part of the vegetarian diet, reduce serum lipids. In combination, these plant food components may have a very significant impact on cardiovascular disease, one of the major complications of diabetes. Furthermore, substituting soy or other vegetable proteins for animal protein may also decrease renal hyperfiltration, proteinuria, and renal acid load and in the long term reduce the risk of developing renal disease in type 2 diabetes. The vegetarian diet, therefore, contains a portfolio of natural products and food forms of benefit for both the carbohydrate and lipid abnormalities in diabetes. It is anticipated that their combined use in vegetarian diets will produce very significant metabolic advantages for the prevention and treatment of diabetes and its complications.

The subfornical organ (SFO) has been repeatedly identified as a CNS site that plays a critical role in sensing multiple physiological variables of the ‘milieu interieur’ and, through efferent projections to other CNS sites, initiating physiological responses to change. Many recent in vitro patch-clamp studies have examined the cellular mechanisms underlying the sensory abilities of these specialized CNS neurons. The primary limitation of these studies, however, has been the inability to identify homogeneous groups of SFO neurons for such investigation. We report here the development of techniques to permit patch clamp recording from dissociated SFO neurons identified according to their in vivo projection site. SFO neurons were labeled by injection of fluorescently labeled, retrogradely transported microspheres into the hypothalamic paraventricular nucleus (PVN) 3 days prior to cell dissociation. Patch-clamp recordings from these SFO-PVN neurons revealed both sodium currents, potassium currents, action potentials, input resistance and membrane potential which were all similar to SFO cells prepared from animals with no prior tracer injection. Labeled SFO→PVN cells were also found to be osmosensitive and responsive to angiotensin II, suggesting specific functional roles for this anatomically defined group of SFO neurons. Intriguingly, our post hoc analysis also demonstrated that all labeled neurons demonstrated a unique electrophysiological profile dominated by a large transient potassium conductance such that the transient/sustained potassium current ratio, or degree of inactivation was, on average, greater than 4.0. Utilization of these tracing techniques to permit the in vitro recording from cells with known in vivo connections will permit study of intrinsic mechanisms that underlie physiological responses of anatomically defined populations of neurons.

BACKGROUND Current perception is that participants of a structured weight-loss program regain all of their weight loss within 5 y. OBJECTIVE The objective was to examine the long-term weight-loss maintenance of individuals completing a structured weight-loss program. DESIGN Studies were required to 1) have been conducted in the United States, 2) have included participants in a structured weight-loss program, 3) have provided follow-up data with variance estimates for > or =2 y. Primary outcome variables were weight-loss maintenance in kilograms, weight-loss maintenance as a percentage of initial weight loss, and weight loss as a percentage of initial body weight (reduced weight). RESULTS Twenty-nine studies met the inclusion criteria. Successful very-low-energy diets (VLEDs) were associated with significantly greater weight-loss maintenance than were successful hypoenergetic balanced diets (HBDs) at all years of follow-up. The percentage of individuals at 4 or 5 y of follow-up for VLEDs and HBDs were 55.4% and 79.7%, respectively. The results for VLEDs and HBDs, respectively, were as follows: weight-loss maintenance, 7.1 kg (95% CI: 6.1, 8.1 kg) and 2.0 (1.5, 2.5) kg; percentage weight-loss maintenance, 29% (25%, 33%) and 17% (13%, 22%); and reduced weight, 6.6% (5.7%, 7.5%) and 2.1% (1.6%, 2.7%). Weight-loss maintenance did not differ significantly between women and men. Six studies reported that groups who exercised more had significantly greater weight-loss maintenance than did those who exercised less. CONCLUSIONS Five years after completing structured weight-loss programs, the average individual maintained a weight loss of >3 kg and a reduced weight of >3% of initial body weight. After VLEDs or weight loss of > or =20 kg, individuals maintained significantly more weight loss than after HBDs or weight losses of

The constancy of plasma osmolality demands that salt and water concentration within the extracellular fluid be constantly monitored and regulated within a few percentage points. The circumventricular organs in general, and the subfornical organ in particular, have long been proposed to be the site of the osmosensitivity. Isolated subfornical organ neurons of male rats were studied using the whole-cell patch-clamp technique and both action potential frequency and whole cell currents were measured as bath osmolality was changed, from 240 to 330 mOsm, by altering the amount of mannitol and maintaining the concentrations of electrolytes constant. Out of 64 cells, 66% responded to changes in bath osmolality in a predictable manner, exhibiting a hyperpolarization and decrease in spike frequency in hypo-osmotic solutions and a depolarization and increase in action potential frequency during hyperosmotic exposure. Cells (34%) defined as non-responders exhibited no significant modulation during identical changes in extracellular osmolality. The responses to changing extracellular osmolality were dose dependent; the activity of subfornical organ neurons was significantly modulated by changes in extracellular osmolality of less than 10 mOsm. By regression analysis, this osmosensitivity was approximately 0.1 Hz/mOsm change throughout a ±10 mOsm range and was maintained throughout the range of osmolalities studied (270–330 mOsm). The mechanism underlying this osmosensitivity remains unclear, although the non-selective cation conductance and the volume-activated chloride conductance do not seem to be involved. This intrinsic osmosensitivity of subfornical organ within the normal physiological range supports the view that this circumventricular structure plays a role in normal osmoregulation.

Background: Hypercholesterolemia is a major risk factor for coronary heart disease and nutrition management is the initial therapeutic approach. Objective: This multicenter study evaluated the long-term effectiveness of psyllium husk fiber as an adjunct to diet in the treatment of persons with primary hypercholesterolemia. Design: Men and women with hypercholesterolemia were recruited. After following an American Heart Association Step I diet for 8 wk (dietary adaptation phase), eligible subjects ts with serum LDL-cholesterol concentrations between 3.36 and 4.91 mmol/L were randomly assigned to receive either 5.1 g psyllium or a cellulose placebo twice daily for 26 wk while continuing diet therapy. Results: Serum total and LDL-cholesterol concentrations were 4.7% and 6.7% lower in the psyllium group than in the placebo group after 24-26 wk (P < 0.001). Other outcome measures did not differ significantly between groups. Conclusions: Treatment with 5.1 g psyllium twice daily produces significant net reductions in serum total and LDL-cholesterol concentrations in men and women with primary hypercholesterolemia. Psyllium therapy is an effective adjunct to diet therapy and may provide an alternative to drug therapy for some patients.

Background: Soluble fibers, including those from psyllium husk, have been shown to augment the cholesterol-lowering effects of a low-fat diet in persons with hypercholesterolemia. As evidence of this, the US Food and Drug Administration recently authorized the use of health claims on food products containing soluble fiber from psyllium that state that they are associated with a decreased risk of coronary heart disease. Objective: This meta-analysis was conducted to more precisely define the hypolipidemic effects and safety of psyllium when used adjunctive to a low-fat diet in men and women with hypercholesterolemia. Design: The 8 studies in the meta-analysis included a total of 384 and 272 subjects receiving psyllium or cellulose placebo, respectively. All studies evaluated the hypocholesterolemic effects of 10.2 g psyllium/d adjunctive to a low-fat diet for ≥8 wk in individuals with mild-to-moderate hypercholesterolemia after a low-fat diet lead-in phase lasting ≥ 8 wk. The safety and adverse events associated with psyllium consumption were summarized from pooled data of 19 clinical studies ranging from 6 wk to 6 mo in duration. Results: Consumption of 10.2 g psyllium/d lowered serum total cholesterol by 4% (P < 0.0001), LDL cholesterol by 7% (P < 0.0001), and the ratio of apolipoprotein (apo) B to apo A-I by 6% (P < 0.05) relative to placebo in subjects already consuming a low-fat diet, with no effect on serum HDL or triacylglycerol concentrations. Conclusions: Psyllium supplementation significantly lowered serum total and LDL-cholesterol concentrations in subjects consuming a low-fat diet. Psyllium is well tolerated and safe when used adjunctive to a low-fat diet in individuals with mild-to-moderate hypercholesterolemia.

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death in the U.S. and in most developed countries. Many nutritional factors contribute to risk for ASCVD including total and saturated fat consumption, fruits and vegetables in the diet and dietary fiber intake. This review will focus on the relationship of dietary fiber intake to risk for coronary heart disease (CHD) and ASCVD (which includes, principally, CHD, cerebral vascular disease and peripheral vascular disease). Fiber-rich foods such as vegetables, fruits, whole-grain cereals and legumes are rich sources of nutrients, phytochemicals and antioxidants. For example, most high fiber foods contain soluble and insoluble fiber, minerals, vitamins, other micronutrients and phytochemicals. Cereals and legumes also contain complex carbohydrates and unsaturated fatty acids. Some high fiber foods are rich in monounsaturated fatty acids, whereas others provide (n-3) fatty acids. Legumes and certain vegetables provide oligosaccharides. When assessing the health benefits of dietary fiber, one should consider the potential effects of associated nutrients, micronutrients and phytochemicals. These interactions will be reviewed as we discuss relationships of dietary fiber to ASCVD.

Background: Long-term maintenance of weight loss remains a therapeutic challenge in obesity treatment. Objective: This multicenter, double-blind, placebo-controlled study was designed to test the hypothesis that orlistat, a gastrointestinal lipase inhibitor, is significantly more effective than a placebo in preventing weight regain. Design: Obese subjects who lost ≥8% of their initial body weight during a 6-mo lead-in of a prescribed hypoenergetic diet (4180-kJ/d deficit) with no adjunctive pharmacotherapy were randomly assigned to receive placebo, 30 mg orlistat, 60 mg orlistat, or 120 mg orlistat 3 times daily for I y in combination with a maintenance diet to help prevent weight regain. Of 1313 recruited subjects [body mass index (in kg/m 2 ): 28-43], 729 subjects lost ≥8% of their initial body weight during the 6-mo weight-loss lead-in period and were enrolled in the double-blind phase. Results: After 1 y, subjects treated with 120 mg orlistat 3 times daily regained less weight than did placebo-treated subjects (32.8 ± 4.5% compared with 58.7 ± 5.8% regain of lost weight; P < 0.001). Moreover, more subjects in the 120-mg orlistat group than in the placebo group regained ≤25% of lost weight (47.5% of subjects compared with 29.9%). In addition, orlistat treatment (120 mg 3 times daily) was associated with significantly greater reductions in total and LDL-cholesterol concentrations than was placebo (P < 0.001). Conclusion: The use of orlistat during periods of attempted weight maintenance minimizes weight readjustment and facilitates long-term improvement in obesity-related disease risk factors.

Levels of antioxidants, activities of free radical scavenging enzymes and extent of lipid peroxidation were determined in the blood of 37 elderly diabetic men and 30 control elderly men, 16 without cardiovascular disease (CVD) and 14 with CVD. The mean +/-S.D. of the ages of the diabetic men was 66+/-5 and those of the control men was 69+/-5, while serum glucose levels of diabetic men were 213+/-81 mg/dl and that of control subjects were 95+/-14 mg/dl. Among the diabetic men, 13 men were obese with body mass index>30, 26 men had poor control of diabetes (glycohemoglobin>7%) and 25 men had retinopathy. The diets of the control and diabetic men were evaluated. Blood samples were collected and analyzed for major endogenous antioxidant defense parameters and lipid peroxidation. The results show that diabetic men had significantly lower blood reduced glutathione levels (p

For > 150 y, clinicians and investigators have observed that high protein intakes accelerate the progression of renal disease and that low protein intakes have beneficial effects. Some studies suggest that the effects of soy-protein intake resemble those of a low-protein diet. The Brenner hypothesis suggests that high protein intakes by diabetic individuals create hyperfiltration and glomerular hypertension eventuating in renal damage. On the basis of the available evidence, we are proposing the soy-protein hypothesis, which states that substituting soy protein for animal protein in diabetes patients results in less hyperfiltration and glomerular hypertension and, therefore, resultant protection from diabetic nephropathy. Furthermore, substituting soy protein for animal protein should have therapeutic value in diabetic nephropathy with resultant slowing of deterioration of renal function and decreasing proteinuria. The preliminary results of the study of 8 type 2 diabetes patients with obesity, hypertension, and proteinuria are reported. Under the conditions of the study, providing soy protein as half of the daily protein intake had no distinct effects on renal function or proteinuria in these subjects. Soy-protein intake was associated with a significant reduction in serum cholesterol and triacylglycerol concentrations. Further studies are required to critically examine the effects of soy-protein intake on the renal function of diabetes patients.

In the present study we measured fasting lipid profiles in over 8,500 community-living men with coronary artery disease (CAD) to determine the distribution of lipid abnormalities in this population: 81% were white and 16% black; mean age 62.9 +/- 8 years; mean total cholesterol 214 +/- 41 mg/dl; low-density lipoprotein (LDL) cholesterol 140 +/- 37 mg/dl; high-density lipoprotein (HDL) cholesterol 39 +/- 11 mg/dl; and triglycerides 190 +/- 142 mg/dl. After adjusting for age, the only significant difference between blacks and whites was a higher HDL cholesterol in blacks (45 vs 38 mg/dl, p or = 100 mg/dl), 38% had low HDL cholesterol ( 200 mg/dl). We estimated that 42% of men with CAD would be definite candidates for cholesterol-lowering medication according to the National Cholesterol Education Program guidelines and that 41% of those in whom cholesterol-lowering medication would not be definitely indicated had low levels of HDL cholesterol. We conclude that (1) black men with CAD have substantially higher HDL cholesterol than white men, (2) almost 90% of male patients with CAD are candidates for dietary intervention and > 40% may need medications to lower LDL cholesterol, and (3) 40% of patients without a definite indication for cholesterol-lowering medications have low levels of HDL cholesterol.

Over the past 20 y dietary fiber has emerged as a leading dietary factor in the prevention and treatment of chronic diseases. High fiber intakes are associated with lower serum cholesterol concentrations, lower risk of coronary heart disease, reduced blood pressure, enhanced weight control, better glycemic control, reduced risk of certain forms of cancer, and improved gastrointestinal function. Dietary fiber can be categorized into water-soluble and water-insoluble components. Dried beans, oat products, and certain fruits and vegetables are good sources of soluble fiber. Most plant foods are good sources of insoluble fiber and wheat bran is a concentrated form of insoluble fiber. Current guidelines advise a doubling of dietary fiber intake for Americans. Inclusion of ample servings of fruits and vegetables, whole grains, and dried beans and peas will help individuals meet these guidelines.

We investigated the effects of halothane, enflurane, and isoflurane on the activity of 43 tracheo-bronchial slowly adapting stretch receptors (SARs) and 16 rapidly adapting irritant receptors (RARs) in 5 anesthetized, vagotomized, paralyzed, and artificially ventilated dogs. The 43 SARs were classified into 2 subtypes: (i) 17 low-threshold SARs with an expiratory discharge at FRC that were active throughout the respiratory cycle and (ii) high-threshold SARs active only in respiration. Ventilating the lungs with 5% of each anesthetic caused a significant increase in the inspiratory discharge of low-threshold SARs, whereas the expiratory discharge was inhibited or altogether silenced. While the activity of the majority of high-threshold SARs increased during the administration of the three volatile anesthetics, it decreased in those with a particulary high recruitment threshold. There was however, a consistent increase in the pressure threshold at which all SARs were recruited. Ventilating the lungs with 5% of each anesthetic cuased a significant decrease in activity of RARs. Our results indicate that all three halogenated anesthetics inhibit RAR at concentrations rangig from 1% to 5%.

The effects of halothane, enflurane, and isoflurane on laryngeal receptors were investigated in 6 anesthetized dogs breathing spontaneously through a tracheostomy. Single unit action potentials were recorded from the peripheral cut end of the superior laryngeal nerve (SLN) while different concentrations of volatile anesthetics (1.25, 2.5, 5.0%) were administered in the expiratory direction at a constant air-flow (6 l/min) for 1 min through the functionally isolated upper airway. A total of 21 respiratory-modulated mechanoreceptors, 18 "irritant" receptors, and 7 cold receptors were studied. The overall results obtained from the 16 respiratory-modulated mechanoreceptors challenged with the 3 anesthetic gases disclosed a prevalent inhibitory effect and halothane proved to be the most effective of the 3 gases. The activity during both the inspiratory and expiratory phase was significantly reduced only by halothane (inspiratory phase, P0.01; expiratory phase, P0.05), while neither isoflurane nor enflurane caused significant changes in receptor activity. Of the 18 irritant receptors, 14 receptors increased their activity in a dose-related manner in response to one or more of the anesthetics although the effect of halothane was more pronounced than those of enflurane and isoflurane. All of the 7 cold receptors consistently increased their activity in a dose-related manner in response to halothane whereas 3 of 7 receptors were insensitive to enflurane and 4 of 7 receptors were insensitive to isoflurane. Our results indicate that, while all three commonly used anesthetics can have an effect on different types of laryngeal receptors, the effects of halothane are more pronounced than those of the other two gases in terms of changes in receptor activity.

It has been previously found that volatile anesthetics significantly affect the activity of laryngeal receptors. In this study we have investigated the respiratory effects of these volatile anesthetics delivered into the upper airway of newborn and adult dogs. Experiments were performed on 17 5-14-day-old, 3 26-28-day-old and 3 adult dogs, anesthetized and breathing spontaneously through a tracheostomy. In the youngest age group, halothane decreased ventilation (VE) to 37.6 +/- 6.8% of control (mean +/- SE; P0.01) due to a decrease in both frequency and tidal volume. Peak inspiratory and expiratory flows, and esophageal pressure (Pes) were depressed also (60.8 +/- 6.5%, 51.6 +/- 7.1% and 66.5 +/- 8.1% of control, respectively; P0.01). Superior laryngeal nerve (SLN) section abolished the changes in VE, but residual significant decreases in peak flows and Pes were still present and disappeared only after topical anesthetization of the nasal cavities. Isoflurane had similar but weaker effects on VE (74.2 +/- 2.8% of control; P0.01), accompanied by a decrease in peak inspiratory and expiratory flows and Pes. SLN section abolished these changes. In the 26-28 day age group there was only a decrease in peak inspiratory airflow with the halothane challenge; isoflurane did not have any effect. In the adult dogs halothane caused only a marginal decrease in inspiratory time. The depressive effects of halothane and isoflurane should be considered when they are used for induction of anesthesia in newborns.

Previous studies examining the hypocholesterolemic effects of high-soluble-fiber diets have not been designed to control for dietary fat intake. Serum cholesterol reductions may therefore be accounted for by differences in consumption of fat. Moderately hypercholesterolemic, nonobese, Caucasian men and women, 30-50 y old were randomly assigned to low-fat, low-fat plus high-fiber, or usual-diet groups and followed for 12 mo. At 12 mo the high-fiber group consumed significantly more soluble fiber than both the low-fat and usual-diet groups (P = 0.0063 and P = 0.0001); the high-fiber group did not differ from the low-fat group in quantity of dietary fat consumed. The high-fiber group experienced a greater average reduction (13%) in serum cholesterol than did the low-fat (9%) and usual-diet (7%) groups. After adjustment for relevant covariates, the reduction in the high-fiber group was significantly greater than that in the low-fat group (P = 0.0482). Supplementation with soluble fiber reduces serum cholesterol beyond the reduction observed with low-fat diet alone.

Mechanisms for the hypocholesterolemic effects of oat bran remain unclear. Soluble fibers such as oat bran are fermented in the colon to short-chain fatty acids (SCFAs), which may enter the portal vein and attenuate hepatic cholesterol synthesis. To compare effects of oat bran and wheat bran on serum SCFA concentrations, 20 hypercholesterolemic men entered a metabolic ward and received control diets for 1 wk followed by oat-bran or wheat-bran diets for 3 wk. Oat bran decreased serum cholesterol 12.8% (P less than 0.001) whereas wheat bran had no effect. Peripheral serum SCFA concentrations were measured seven times over 14 h at the end of each diet. Serum acetate values from 1200 to 2200 were significantly higher in subjects fed oat-bran vs wheat-bran diets. Peak and incremental peak acetate values were also significantly higher than control values in subjects fed oat bran but not in subjects fed wheat bran. SCFA responses may contribute to the hypocholesterolemic effects of oat bran.

The metabolic effects of high-carbohydrate (70%), high-fiber (70 g) (HCHF) and low-carbohydrate (39%), low-fiber (10 g) (LCLF) diets were examined for 10 subjects with insulin-dependent diabetes mellitus (IDDM). After a 1-wk control period subjects on a metabolic ward were randomly allocated to HCHF or LCLF diets for 4 wk. After a 6-wk washout period subjects re-entered the metabolic ward for 4 wk on the alternate diet. Artificial-pancreas studies were performed on each diet for measurement of insulin requirements. Compared with the LCLF diet, the HCHF diet reduced basal insulin requirements (P less than 0.025), increased carbohydrate disposed of per unit insulin (P less than 0.0008), and lowered total (P less than 0.0004) and high-density-lipoprotein cholesterol (P less than 0.0013). Glycemic control and other lipid fractions did not differ significantly. These results suggest that in IDDM patients, HCHF diets enhance peripheral glucose disposal, decrease basal insulin requirements, and lower total cholesterol without altering glycemic control or triglycerides.

The hypocholesterolemic effects of oat bran (OB) have been recently challenged. To carefully document the hypocholesterolemic effects of OB, 20 hypercholesterolemic men admitted to a metabolic ward were randomly allocated to either OB or wheat bran (WB) for 21 d after a 7-d control-diet period. Control and treatment diets were designed to be identical in energy content and nutrients, differing only in the amount of soluble fiber. After 21 d, OB significantly decreased total cholesterol by 12.8% (P less than 0.001), low-density-lipoprotein cholesterol by 12.1% (P less than 0.004), and apolipoprotein B-100 by 13.7% (P less than 0.001) whereas WB had no significant effect. High-density-lipoprotein cholesterol and apolipoprotein A-I did not change significantly in either group. Serum triglycerides decreased by 10% in both groups but the decrease was only significant (P less than 0.04) in WB subjects. OB but not WB significantly reduced total cholesterol and other atherogenic lipoprotein fractions independent of other dietary changes.

Although constant airflow through the upper airway has been shown to induce ventilatory depression in anesthetized newborn animals, the role of laryngeal temperature in this response has not been studied. Experiments were performed in fourteen 1-5 day-old anesthetized puppies breathing through a tracheostomy. Tidal volume and laryngeal temperature were recorded while a constant stream of air (15-25 ml/sec) at room temperature was passed in the expiratory direction for 20 sec through the isolated upper airway. Warm (35-37 degrees C), humidified air at the same flow served as control. When laryngeal temperature was decreased by 7.5 +/- 0.9 degrees C, a marked change in breathing pattern was observed (VT = 54 +/- 5, TI = 187 +/- 33, TE = 636 +/- 179, VT/TI = 45 +/- 10% of control; n = 9). Warm air at the same flow induced no significant changes. Superior laryngeal nerve section abolished the effects of cooling on breathing pattern. In 5 puppies we compared the effect of 'fast' and 'slow' laryngeal cooling. Fast trials altered breathing pattern earlier than slow trials. We conclude that the depressant effect of airflow through the upper airway is entirely due to a decrease in laryngeal temperature and is mediated by superior laryngeal nerve afferents.

The purpose of this study was to relate the carbon dioxide (CO2) response of laryngeal receptors to their behavior during the breathing cycle (i.e, their response to transmural pressure changes, laryngeal movement or decreases in temperature)_or during exposure to irritant stimuli (water or cigarette smoke). In 9 anesthetized mongrel dogs breathing spontaneously through a tracheostomy, unit activity from the superior laryngeal nerve was recorded while warmed and humidified gas mixtures (air or 10% CO2 in O2) were passed, for 1 min, through the functionally isolated upper airway in the expiratory direction. None of the 10 cold receptors studied were affected by CO2. Eleven of 20 laryngeal non-modulated mechanoreceptors were stimulated (from 0.3 to 1.6 imp/sec) by exposure to CO2. These CO2-responsive receptors were also stimulated by known irritant stimuli (cigarette smoke, water), although not all receptors which responded to these irritants were stimulated by CO2. Twelve of 33 respiratory-modulated receptors were affected by CO2; 4 were stimulated and 8 inhibited. Receptors inhibited by CO2 were also inhibited by negative pressure while receptors stimulated by CO2 were also stimulated by negative pressure. These results show that CO2-responsive laryngeal receptors are not specialized endings. Although it is not clear to what extent each separate group of laryngeal receptors is involved, each may contribute to the reflex bradypnea which has been observed during exposure of the upper airway to elevated levels of CO2. However, the importance of CO2-responsive laryngeal receptors in physiological conditions remains unclear.

Oat bran lowers serum lipid concentrations in healthy and hyperlipidemic subjects. To determine the effects of a ready-to-eat oat-bran cereal on lipid concentrations, we fed control (corn flakes) and oat-bran cereal diets for 2 wk to 12 men with undesirably high serum total-cholesterol concentrations. Subjects were randomly assigned to one of the two diets upon admission to the metabolic ward. After completing the first diet, subjects completed 2 wk on the alternate diet. Intakes of carbohydrate, protein, fat, and cholesterol were virtually identical on the two diets. The oat-bran cereal provided 25 g oat bran/d. The oat-bran cereal diet compared with the corn flakes diet lowered serum total-cholesterol and serum LDL-cholesterol concentrations significantly by 5.4% (p less than 0.05) and 8.5% (p less than 0.025), respectively. Final body weights on each of the diets were similar. Ready-to-eat oat-bran cereal provides a practical means to incorporate soluble fiber into the diet to lower serum cholesterol.

Dried beans lower serum lipid concentrations in healthy and hyperlipidemic subjects. To determine the effects of canned beans on serum lipid concentrations, 24 hyperlipidemic men ate one of three bean diets for 21 d in a metabolic ward. Diets A and B included 227 g canned beans (120 g beans with 107 g tomato sauce) daily, in a single dose for diet A and in a divided dose for diet B. Diet C included 182 g canned beans (162 g beans with 20 g tomato sauce) daily in a divided dose. All bean diets combined lowered serum cholesterol and triglyceride concentrations 10.4% (p less than 0.001) and 10.8% (p less than 0.025), respectively. Diet B was as effective as diet C, and the groups on those diets had greater cholesterol reductions than did the group on diet A. Serum cholesterol reduction was positively correlated (p less than 0.01) with intake of total dietary fiber and soluble fiber. The ratios of low- to high-density-lipoprotein cholesterol remained constant for all groups. Body weight decreased 1.0-1.5 kg for all groups despite constant energy intakes. Canned beans may make an important contribution to hyperlipidemia management.

To investigate whether osmoreceptor mechanisms or the renin-angiotensin system might be involved in respiratory regulation of H+ homeostasis, plasma osmolality was acutely lowered by approximately 10 mOsm in 7 awake mongrel dogs by a gastric water load (20 ml.kg-1 distilled, deionized water). Plasma renin activity (PRA) was measured as an indicator of angiotensin II levels. During these studies PaCO2 and [H+]a reflected the spontaneous level of ventilation (VE); higher levels of VE were correlated with lower PaCO2 and [H+]a, indicating a nonchemical drive to breathe. Stimulation of ventilation to lower PaCO2 following the water load was positively correlated with increase in PRA and decrease in plasma osmolality, but not with change in osmolality alone. An increased VE, a decreased ventilatory response curve (VRC) threshold for PaCO2, and a lower PaCO2 occurred with increase in PRA. Conversely, a lower or acutely decreased PRA, due to administration of arginine vasopressin, was correlated with a lower VE, an increase in the VRC threshold for PaCO2, and a higher PaCO2. Ventilatory control of PaCO2 during acute lowering of osmolality may be related to a central inter-action between osmolality and the renin-angiotensin system.

Eighty morbidly obese individuals consecutively enrolled in a comprehensive very-low-calorie diet (VLCD) program were evaluated. Patients' mean initial body mass index was 45.5 kg/m2 and they lost 35.3 kg in 26 wk. Serum total cholesterol, low-density-lipoprotein cholesterol, and triglycerides decreased by 15.0%, 17.0%, and 14%, respectively. Systolic and diastolic blood pressure decreased by 8.7% and 10.0%, respectively. The 46 individuals completing 2-y follow-up were maintaining 48.0 +/- 7.6% (means +/- SE) of their weight loss. Morbidly obese persons lost substantial amounts of weight using a comprehensive VLCD program, reduced risk factors associated with obesity, and had encouraging long-term results, with 48% of weight loss maintained at 2 y of follow-up.

Normal and streptozotocin-diabetic rats were fed a low carbohydrate diet or one of two high carbohydrate diets (sucrose or starch-bran). High carbohydrate diets were associated with slightly higher plasma glucose levels in both control and diabetic rats. However, glucose tolerance tests were not altered by the diets in either the control or diabetic rats. Plasma and liver triglyceride values for control and diabetic rats fed the high sucrose diet were similar to those of rats fed the low carbohydrate diet. The starch-bran diet was associated with lower plasma and liver triglyceride values in both control and diabetic rats. Plasma triglyceride values of diabetic rats fed the high sucrose diet or the low carbohydrate diet were significantly higher than values of control rats fed the same diets. On the other hand, plasma triglyceride values of diabetic rats fed the starch-bran diet were similar to values for control rats fed the same diet. These studies suggest that a high carbohydrate diet containing starch and wheat bran is associated with a reduction in plasma triglyceride values in both normal and diabetic rats. Liver glycolytic enzyme activities were significantly lower in diabetic rats than in control rats in all three dietary groups.

Dietary fiber measurements are essential to assessment of the potential therapeutic and preventive effects of fiber intake. Ideally, dietary fiber analyses should measure all components--soluble polysaccharides, noncellulosic polysaccharides, cellulose, and lignin--and the constituent sugars of the soluble and noncellulosic polysaccharides. We modified existing techniques to measure reproducibly the total dietary fiber, polysaccharide, and lignin components and the sugar constituents of selected foods. Soluble-fiber content as percentage of total dietary fiber for groups of foods averaged 32% for cereal products, 32% for vegetables, 25% for dried beans, and 38% for fruits. Lignin content, estimated gravimetrically, was approximately 1.4 g/100 g dry wt for 24 foods. Detailed fiber measurements are critical for evaluating the potential health benefits of dietary fiber intake.

Dietary fiber has important hypocholesterolemic effects and may reduce risk for coronary artery disease. Careful clinical studies indicate that foods such as oat bran or beans, rich in water-soluble fiber, can decrease serum total cholesterol by 19% while decreasing serum low density lipoprotein cholesterol by 22%. Food supplements rich in soluble fiber such as psyllium mucilloid are well tolerated and may lower serum cholesterol by 15%. Thus, high fiber foods or soluble fiber food supplements may decrease serum cholesterol by 15% to 19% and decrease estimated risk for coronary heart disease by greater than 30%.

High carbohydrate diets rich in dietary fiber were fed to 13 hyperglycemic diabetic men; five men required IS to 28 units of insulin per day, five men required sulfonylureas, and three men required 40 to 55 units of insulin. All 13 men were fed weight maintaining American Diabetic Association diets contining 43% of calories as carbohydrate for I week and then were fed 75% carbohydrate diets with I 5 g of crude dietary fiber for approximately 2 weeks. After 2 weeks on the 75% carbohydrate diet, sulfonylureas were discontinued in all five men, insulin was discontinued in four men and decreased from 28 to 15 units in I man from the group requiring less than 30 units pen day. Fasting plasma glucose values were significantly lower (P < 0.001) in all 10 men. However, insulin requirements and fasting plasma glucose values were not changed in the three men requiring 40 to 55 units of insulin. Fasting serum cholesterol values were significantly (P < 0.001) lower and mean fasting serum triglyceride values were 15% lower on the high carbohydrate diet than on the American Diabetic Association diet in these 13 men. Thus, a high carbohydrate diet with generous amounts of dietary fiber may be the treatment of choice of diabetic patients requiring sulfonylureas or less than 30 units of insulin per day. Diabetes mellitus is a major health prob- lem in the United States because it affects 5% of the population, its prevalence is rapidly increasing, and it is associated with major complications and shortened life span (1). "Few substantial improvements in therapy have occurred since the discovery of insulin more than 50 years ago" (1). A "diabetic" diet is an essential feature in the treatment of diabetes and traditionally this diet has been restricted in carbohydrate (2, 3). Although recently it has been recommended that the carbohydrate content of the diabetic diet be increased (4), no data are available that pro- vide compelling evidence for increasing the carbohydrate content of the diabetic diet. However, several studies (5-9) suggest that a high carbohydrate diet may be beneficial in treating some diabetic patients. Because diets containing 75 to 85% of calories as carbohy- drate have been associated with improved glucose metabolism of normal individuals (8, 10) and patients with mild diabetes (6, 8, 9), we have studied the therapeutic utility of a 75% carbohydrate diet in treating diabetic patients requiring either insulin or oral hypo- glycemic agents.

The effects of guar gum and wheat bran on blood and liver lipid levels of rats were measured. In experiment 1, rats were fed ad libitum a 55% sucrose diet containing 0, 15 or 25% wheat bran for 3 weeks. Postprandial plasma triglyceride, liver triglyceride and liver cholesterol values in rats fed the sucrose diet with wheat bran were significantly lower than values for rats fed the diet without wheat bran. Neither fasting plasma triglyceride nor cholesterol values were altered by wheat bran. In experiment 2, rats were meal-fed one of four experimental diets for 3 weeks: sucrose, sucrose-cholesterol, sucrose-cholesterol-bran or sucrose-cholesterol-guar gum. Rats fed sucrose-cholesterol-guar gum diet had significantly lower fasting plasma total cholesterol, liver triglyceride and liver cholesterol values, but higher plasma high density lipoprotein (HDL) cholesterol values than those fed sucrose-cholesterol diet. These values were similar for the sucrose-cholesterol and sucrose-cholesterol-bran groups. Fasting plasma triglyceride levels were not altered by wheat bran or guar gum. These studies indicate that while guar gum lowers fasting plasma total cholesterol and raises HDL cholesterol, wheat bran does not.

High-carbohydrate, high-fiber (HCF) diets provide short-term benefits for selected individuals with diabetes. Long-term effects of HCF diets, however, have not previously been documented. The effectiveness and acceptability of HCF diets for 14 men with diabetes followed for 4 years as outpatients were assessed. Hospital HCF diets with 70% of energy as carbohydrate and 65 gm plant fiber daily lowered insulin doses, serum cholesterol, and triglycerides. Home HCF diets with 55% to 60% carbohydrate and 50 gm plant fiber daily sustained improvements throughout the observed period of up to 86 months. Of the 11 patients for whom diet adherence was evaluated, 9 had good to excellent adherence, 1 had fair adherence, and 1 had poor adherence.

Few studies accurately report total-dietary-fiber (TDF) content of current and alternative diets. In this study we analyzed and calculated TDF content of a simulated American diet with household Nationwide Food Consumption Survey data. We also analyzed the fiber content of four research diets: control; bean; high fiber, maintenance (HFM); and high carbohydrate, high fiber (HCF). Analyzed and calculated fiber values for the simulated diet were similar. The simulated, control, bean, HFM, and HCF diets provided 5.6, 8.1, 12.2, 17.4, and 22.8 g TDF/1000 kcal, respectively. Soluble-fiber content ranged from 1.7 g/1000 kcal for the simulated diet to 6.1 g/1000 kcal for the HCF diet. Cereal products contributed the most to total fiber content of the simulated diet, followed in order by vegetables, legumes, fruits, and miscellaneous foods. Fiber content of the simulated diet was below recommended levels. The HFM diet is suggested for individuals desiring to increase their dietary fiber intake.

Diet remains the cornerstone in the management of diabetes mellitus. A prudent nutrition plan reduces the exaggerated risk for atherosclerotic heart disease and metabolic complications of diabetes by improving lipid and glycemic control. The current consensus diabetes diet recommends 55 to 60 percent of energy as carbohydrate, 12 to 20 percent as protein, and less than 30 percent fat. Total cholesterol intake should be less than 300 mg per day. Fiber appears to have distinct benefits in improving glucose and lipid levels; therefore, an intake of up to 40 g per day or 15 to 25 g/1,000 kcal of food is recommended. Other considerations in meal planning for diabetes include alternative sweeteners, salt intake, alcohol consumption, and vitamin and mineral needs. Individualized and flexible nutrition plans, designed within established guidelines, promote adherence. Persons with diabetes can change their eating patterns and closely adhere to a diet plan if the entire health care team is enthusiastic, supportive, and instructive.

A luteinizing hormone (LH)-like molecule has been described in the rodent central nervous system and has been shown to have immunologic, chromatographic, and biologic activity similar to that of pituitary LH. In this communication we report that a depolarizing stimulus, high potassium concentration in the presence of calcium, causes in vitro release of LH from hypothalamic explants containing the pars tuberalis. Release from other brain areas containing LH was not seen nor was release of LH, in vitro, significantly provoked from dorsal segments of the hypothalamus, thus suggesting that most, if not all, of the releasable LH from intact hypothalamic explants may come from cells of the pars tuberalis.

Diabetes takes an enormous human and monetary toll each year. Current treatment too often revolves around insulin and drug therapy, neglecting diet and exercise. A comprehensive review was undertaken to assess and summarize the effects of dietary fiber on diabetes. Fiber supplement studies with guar, wheat bran, and apple fiber produced mixed results; some studies reported lowered fasting glucose and cholesterol values and less glycosuria. However, many available fiber supplements cause side effects. High-carbohydrate, high-fiber diets providing 55% to 60% of energy as carbohydrates, 15% to 20% as protein, and 20% to 25% as fat and including 50 gm or more fiber daily hold the most potential for long-term use. These diets reduce insulin requirements, improve glycemic control, lower fasting serum cholesterol and triglyceride values, and promote weight loss. Studies show good long-term adherence with these diets. Dietitians assume primary responsibility for educating individuals on the benefits and use of high-carbohydrate, high-fiber diets. Diets must be individualized, with special modifications for obesity, hyperlipidemia, or physiological states such as pregnancy and lactation. Widespread use of high-fiber diets will ultimately improve metabolic control and decrease health care costs for thousands of diabetic and non-diabetic individuals.

The isozyme composition and subcellular distribution of hexokinase in intestinal mucosa were studies. Only 19% of total jejunal hexokinase was in the supernatant fraction whereas 44% of ileal activity was soluble. Four isozymes, including glucokinase, were demonstrated by cellulose acetate electrophoresis of intestinal mucosal supernatant fractions. The type IV isozyme we demonstrated in intestine closely resembled hepatic glucokinase, and thus only intestine and liver appear to contain this specific isozyme. Glucose feeding significantly increased hexokinase activity of the particulate fraction of jejunal mucosa but increased, only slightly, the supernatant activity. Alterations in the intracellular distribution of hexokinase were seen more clearly when serial time studies were done in fasted, glucose-refed rats. Refeeding was associated with a specific increase, seen at days 1 and 2, in particulate activity without alterations in supernatant activity. After 5 days of refeeding, however, comparable increases in particulate and supernatant fractions were seen. These studies indicate that the adaptive responses of jejunal mucosa to dietary alterations include specific changes in the intracellular compartmentation of hexokinase.