A randomized controlled trial evaluating nutrition counseling with or without oral supplementation in malnourished HIV-infected patients.

OBJECTIVE: To evaluate the effects of nutrition counseling with or without oral supplementation in malnourished patients infected with the human immunodeficiency virus (HIV). DESIGN: Randomized controlled trial. SUBJECTS: HIV-infected men (n=118) who were less than 90% of usual weight for height or who had lost more than 10% of body weight. INTERVENTION: Nutrition counseling alone (control group) vs nutrition counseling plus enteral supplementation (supplement group) for 6 weeks. All patients were instructed to consume a diet that exceeded estimated total energy expenditure by 960 kcal/day. MAIN OUTCOME MEASURES: Weight, skinfold thickness, fat-free mass, grip strength, quality of life, and cognitive function (Buschke test). STATISTICAL ANALYSES: Differences in baseline variables and outcomes were evaluated using analysis of variance or the Wilcoxon rank sum test. RESULTS: Ninety-nine men completed at least 4 weeks of treatment, 49 in the supplement group and 50 in the control group. Half the patients in each treatment group achieved at least 80% of their energy target. No differences in weight, skinfold thickness measurements, or quality of life were observed. Compared with the control group, the supplement group had larger increases in fat-free mass and grip strength, although the differences did not reach statistical significance. APPLICATIONS: In the short term, nutrition counseling with or without oral supplementation can achieve a substantial increase in energy intake in about 50% of malnourished HIV-infected patients. Although further study is needed to evaluate long-term effects, these findings suggest that nutrition counseling has an important role in the management of malnourished HIV-infected patients.

The risk of Helicobacter pylori infection among U.S. military personnel deployed outside the United States.

To determine whether military personnel deployed outside the United States are at increased risk of Helicobacter pylori infection, 1,000 male U.S. Navy and Marine Corps personnel (mean age 22 years) were evaluated. Study subjects included 200 recruits, 500 shipboard personnel deployed for six months to South America, West Africa, and the Mediterranean, and 300 ground troops deployed for five months to Saudi Arabia. Among all 1,000 subjects, 247 (25%) were seropositive for H. pylori IgG antibody by an enzyme-linked immunosorbent assay; 24% of new recruits and 25% of troops who had been on active duty for a mean of four years. The prevalence of H. pylori antibody was higher among subjects who were older, nonwhite, foreign-born, and seropositive for antibody to hepatitis A virus. Among the 601 initially seronegative subjects evaluated before and after a 5-6 month deployment outside the United States, five seroconverted, for a rate of infection of 1.9% per person-year of exposure. As found in other populations in developed countries, these data indicate that among U.S. military personnel a large proportion of H. pylori infections occur before adulthood and infection is related to demographic factors. These preliminary findings also suggest that deployed U.S. military personnel may be at increased risk of H. pylori infection compared with adult populations in developed countries either from exposure in developing countries or from crowding.

Discontinuation of total parenteral nutrition in a patient with acquired immunodeficiency syndrome: a Canadian perspective.

Provision of nourishment to terminally ill patients has been a controversial topic in clinical medicine. Determination of the limits of palliative care requires an understanding of the disease process, as well as the boundaries of patient self-determination. With the advent of living wills, the determination of the patient to limit care, including nutrition support, has become socially acceptable. Difficulties arise when there are differences of opinion between the caregiver and the patient. The solutions to these conflicts are often decided in the courtroom, as demonstrated by the Cruzan and Quinlan cases. Living wills are often written to prevent unnecessary financial burdens in hopeless situations. As well, financial considerations influence the decisions made by caregivers in providing care to terminally ill patients. The following case report illustrates the conflict between patient self-determination and limitation of care for financial reasons. The use of substituted judgment within the Canadian health care system and the role of team meetings to resolve ethical decisions are discussed.

Rapid eye movement latency and mood following a delay of bedtime in healthy subjects: do the effects mimic changes in depressive illness?

The phase advance hypothesis proposes that a phase advance of certain circadian rhythms (such as rapid eye movement (REM) sleep propensity) relative to the sleep-wake cycle is implicated in the pathophysiology and pathogenesis of depression. In an earlier study, we reported that a 6-h delay of sleep in normals produced REM changes that resembled the depressive pattern. Mood change was generally modest, although 2 of the 10 subjects became noticeably depressed. This study assessed the replicability of these results, and introduced a phase advance control condition. Predicted changes were observed in REM parameters. Modest but reliable mood change was confined to the first night of the phase delay, and was attributed to sleep loss. These results suggest that the effects of the phase shift were relatively benign, except in a minority of cases. Such individuals may have a susceptibility to depression that manifests itself under certain conductive physiological conditions.

Age-related changes in sleep in depressed and healthy subjects. A meta-analysis.

In this article we demonstrate that the difference in sleep between depressives and healthy controls varies systematically as a function of the mean age of the sample studied. The data were taken from 27 studies that had compared the sleep of drug-free depressed patients and age-matched healthy controls. In all, the studies give data for 822 patients (in 41 samples) and 621 healthy controls (in 37 samples). The mean age of the samples varied between 9 and 72 years. For total sleep time, minutes awake, sleep efficiency, minutes of slow-wave sleep, and REM latency, there are reliable age-related trends in both sets of samples. These trends follow a progressively diverging course such that, within studies, the mean difference and the standardized mean difference (d) between patients and controls increases as a linear function of the mean age of the former (i.e., the older the patients, the greater the difference). Possible reasons for the interaction are discussed.

Variation in process S: effects on sleep continuity and architecture.

Given the two-process model of sleep regulation, and the hypothesis that the sleep disorder in depressive illness is a consequence of a deficient Process S, it was predicted that relatively high levels of S would result in enhanced sleep continuity, increased slow-wave sleep (SWS), prolonged rapid-eye-movement (REM) latency, and less REM sleep. These predictions were tested in two studies. In Study 1, the level of Process S (at 0900 h prior to a 3-h sleep episode) was varied by altering the time and duration of prior nocturnal sleep (2400-0300 h, 0300-0600 h, 2400-0600 h). In Study 2, the leve of Process S (at 2400 h prior to an 8-h sleep episode) was varied by studying subjects when they had not napped or had taken 2-h naps beginning at either 1000 or 1900 h. As predicted by the model, SWS varied reliably depending on the level of S at bedrest, as did indices of sleep continuity at night. Contrary to prediction, however, REM sleep was either increased (Study 1) or did not change reliably (Study 2). It is suggested that, contrary to the other aspects of sleep, REM sleep is strongly influenced by circadian and homeostatic processes and that Process S plays a relatively minor role in its regulation.

Effect of lactose or its component sugars on jejunal calcium absorption in adult man.

The effect of lactose vs glucose plus galactose on jejunal calcium absorption was studied in 10 subjects using a triple-lumen perfusion technique. In each, 30 cm of jejunum was perfused with two test solutions. The comparisons made were lactose (Lac) vs mannitol (Man), Lac vs glucose and galactose (GG), and Man vs GG. Compared with Man, Lac, and GG caused a significant increase in net water and sodium absorption and luminal calcium concentration. In subjects receiving both Lac and GG, water and sodium absorption were greater with GG. The only statistically significant increase in net calcium absorption occurred with Man vs GG in which water absorption increased from 16 to 350 mL.h-1.30 cm-1. However, by use of data from all test solutions, water and sodium absorption were found to be significantly correlated with calcium absorption (p less than 0.05). These results suggest that lactose or its component sugars enhance jejunal calcium absorption in proportion to their effect on fluid absorption.

Pulmonary deposition of calcium phosphate crystals as a complication of home total parenteral nutrition.

A patient on home total parenteral nutrition (TPN) developed a diffuse granulomatous interstitial pneumonitis secondary to calcium phosphate deposition. Calcium and phosphorus concentrations in the TPN formula were not unusually high, indicating that other factors contributed to calcium phosphate crystallization. The effects of duration of storage of the TPN formulation, solution temperature, pH, and magnesium concentration on calcium phosphate precipitation are discussed.

Response of fractional calcium absorption in women to various coadministered oral glucose doses.

Previous studies found an enhancing effect of glucose on fractional calcium absorption in humans but little information is available on the effect of different amounts of carbohydrate on Ca absorption. Thus, we studied the response of fractional Ca absorption to various loads of oral glucose coadministration with Ca in ten female subjects. After an overnight fast, 47Ca was administered orally on four occasions in solutions that contained varying doses of glucose (0 control, 56, 222, and 444 mmol). Seven of the ten subjects showed a positive response to glucose. In this group of responders there was a linear response to glucose between 0 and 222 mmol. No further increase was achieved at the higher dose of glucose. The response to 222 mmol glucose represented a 49% increase in Ca absorption compared with absorption without carbohydrate.

The time course of 'process S': comparison of visually scored slow wave sleep and power spectral analysis.

The sleep of 4 groups (N = 8) of young healthy subjects was recorded during naps at either 09.00, 14.00, 19.00 or 24.00 h. For the first hour of sleep, conventionally scored slow wave sleep (SWS) and computed EEG power density (0-25 Hz) were found to increase exponentially as a function of prior wakefulness (range 3-18 h). The equations based on SWS and spectral analysis of the sleep EEG gave values for r' (the growth rate of the function) that were similar to each other (0.038 and 0.039, respectively) and to that reported by Daan et al. (1984; 0.055). These data are consistent with the proposal that process S, 1 of 2 processes believed to regulate sleep and wakefulness, increases exponentially during the waking day (Daan et al. 1984). In addition, they indicate that in this context SWS and spectral analysis provide measures of slow wave activity that are equally sensitive to changes in prior wakefulness.

Dietary supplementation and respiratory muscle performance in patients with COPD.

We studied the effects of oral nutritional supplementation on respiratory muscle (RM) performance in 25 ambulatory patients with severe chronic obstructive pulmonary disease (COPD). There was a relationship between body weight and anthropometric parameters of nutritional status (triceps skinfold thickness [r = 0.67; p less than 0.005], midarm muscle circumference (r = 0.53; p less than 0.005), but body weight did not correlate with daily caloric intake, serum albumin, transferrin, or blood lymphocyte count. None of these measurements of nutritional status correlated with any measure of RM strength or endurance. In a randomized observer-blinded crossover trial, patients were allocated to one of two groups. In the first eight weeks of the study, group A received nutritional supplementation, and patients in group B were control subjects. In the second eight weeks, patients in group A were control subjects, and group B received supplement. Mean daily caloric intake and body weight increased in both groups while receiving supplement (both p less than 0.05). Calories provided by the supplement were frequently substituted for normal dietary calories. Any increases in RM performance in the group receiving supplement were matched by increases (due to learning) in controls. We conclude that oral dietary supplements have no important effects on RM performance in ambulatory patients with COPD.

Intestinal absorption of Ca(H2PO4)2 and Ca citrate compared by two methods.

The purpose of this study was to compare the absorption of calcium from two soluble Ca salts and determine if the oral Ca load test can be used as a simple measure of relative Ca bioavailability. Eight normal subjects ingested 750 mg Ca as solution of Ca(H2PO4)2 or Ca citrate (two occasions) tagged with 47Ca tracer. Absorption of Ca from the two salts was estimated from both the increase in forearm radioactivity and rise in urinary Ca (oral Ca load test). Both measures indicated that Ca was absorbed at least twice as well from Ca citrate as from Ca(H2PO4)2. However, the increment in urinary Ca 2-4 h after the oral load correlated with fractional absorption when only Ca citrate (r = 0.803, p less than 0.02) was ingested. For group comparisons the oral Ca load test is a rough index of Ca availability but cannot substitute for more direct measures of absorption in an individual.

Mood change following an acute delay of sleep.

A phase advance of some circadian rhythms (e.g., body temperature and rapid eye movement [REM] sleep propensity) relative to the sleep-wake cycle is thought to be implicated in the pathophysiology and pathogenesis of some affective disorders. Since this phase disturbance can be induced in normal subjects by acutely delaying their sleep onset, it follows that the outcome of this experimental procedure should resemble the symptoms of depressive illness. This hypothesis was tested by imposing a 6-hour phase delay of sleep in 10 young male subjects. There were reliable changes in observers' ratings of mood and in some self-report measures. For the most part, the effect was modest, being largely confined to variations within normal limits. Two of the subjects, however, were noticeably depressed when interviewed after either the first or the second night of phase shift.

The influence of prior wakefulness on REM sleep.

Data from studies of naps and of shifted sleep were used to determine the relationship between two measures of rapid eye movement (REM) sleep (percentage of REM in the first 2 hr of sleep and REM latency) and prior wakefulness. For each sample, we calculated the difference between the observed value and that predicted by a cosine function that estimated the circadian rhythm of REM sleep propensity. The difference values were found to correlate reliably with hours and log hours of prior wakefulness. We conclude that while REM sleep is regulated in part by an endogenous circadian oscillator, it is also influenced by the duration of prior wakefulness.

Monoclonal antibodies against the M-protein and carbohydrate antigens of histoplasmin characterized by the enzyme-linked immunoelectrotransfer blot method.

Monoclonal antibodies (MAbs) of two different specificities were produced by immunizing mice with the semipurified M antigen of histoplasmin. One type, from clone CB4, was an immunoglobulin M that precipitated a polysaccharide present in histoplasmin and also formed immunoprecipitates with a cross-reactive polysaccharide present in extracts of Blastomyces dermatitidis and Coccidioides immitis. The second type of MAb, from clone EC2, was an immunoglobulin G that reacted in the enzyme-linked immunoelectrotransfer blot (EITB) assay with a doublet of proteins with an apparent molecular size of 70 to 75 kilodaltons. This molecule is proposed as the authentic M protein antigen that is recognized by M antibodies in sera from mice and rabbits immunized with Histoplasma capsulatum and from persons with histoplasmosis. The M factor also occurs in an abundant disulfide-bridged dimer which has a molecular size of 150 kilodaltons and is nonimmunoreactive under the conditions of sodium dodecyl sulfate-polyacrylamide gel electrophoresis.

REM sleep and depression: further use of computer simulation to test the phase-advance hypothesis.

A phase advance of the circadian rhythm of rapid eye movement (REM) sleep propensity relative to the sleep-wake cycle has been proposed to account for the abnormalities of REM sleep commonly found in depressed patients. One implication of this hypothesis is that a phase delay of sleep in normal subjects should produce the same abnormalities of REM sleep. The hypothesis was tested by computer simulation using equations based on data derived from normal subjects who had experienced phase shifts of their bedtime. At phase delays of between 4 and 6 hours (an estimate of the putative phase advance in depressed patients), the mean REM latency and the mean duration of the first REM period predicted by the equations did not differ significantly from those observed in depressed patients. The findings with respect to the distribution of REM latency were more equivocal.

The sleep of remitted bipolar depressives: comparison with sex and age-matched controls.

The sleep of 10 bipolar patients was recorded for five consecutive nights following their recovery from a depressive episode. In all respects except the number of arousals, their sleep did not differ reliably from that of 10 sex and age-matched control subjects. We conclude that sleep measures are unlikely to be useful as trait markers of a depressive diathesis in bipolar disorder.

Slow-wave sleep in daytime and nocturnal sleep: an estimate of the time course of "Process S".

Daan et al. (1984) have proposed that sleep and wakefulness are regulated, in part, by a "Process S" that increases during wakefulness and declines during sleep. Data derived from several studies were taken to determine the time course of Process S during both wakefulness and sleep. As required by the model, slow-wave-sleep (SWS; an index of Process S) was found to increase exponentially as a function of prior wake time (equation 1) and to decline exponentially as a function of time asleep (equation 2). The equations accounted for 91% and 96% of the variance, respectively. In addition, equation 1 accurately predicted the amount the amount of SWS in the first hour of nocturnal sleep.

REM latency and depression: computer simulations based on the results of phase delay of sleep in normal subjects.

A phase advance of the circadian rhythm of rapid eye movement (REM) sleep propensity relative to the sleep-wake cycle has been hypothesized to account for the abnormalities of REM sleep in depression. One implication of this hypothesis is that an acute phase delay of sleep in normal subjects should produce the same abnormalities of REM sleep. A further implication is that changes in REM sleep that occur in normal subjects with delay shifts of sleep of progressively greater magnitude describe those that occur during the course of a depressive episode. This hypothesis was tested by computer simulation using two equations which, given the data derived from normal subjects experiencing phase delays of sleep, generated the REM latencies expected during successive stages of a depressive episode. For severely depressed patients, the computer-generated data matched those found empirically. The known correlation between severity of depression and REM latency, and the REM latencies of recovered patients, are consistent with the hypothesis.