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K Mulligan

Publications and source records attributed to K Mulligan.

At least 19 recordsLinked to original sources
PubMed2000

Thalidomide for the treatment of AIDS-associated wasting.

A double-blind, placebo-controlled trial of efficacy and safety of thalidomide in AIDS-associated wasting was carried out. Ninety-nine of 103 male patients had at least one on-study measurement (intent-to-treat [ITT] cohort). Patients were randomized to thalidomide at 100 mg/day (T100) or 200 mg/day (T200), or placebo for 8 weeks. By ITT analysis, the mean change in body weight of the placebo, T100, and T200 treatment groups was 0.3 kg (0.4%), 2.0 kg (3.0%), and 0.9 kg (1.4%), respectively (p = 0.021 for T100 versus placebo; p = 0.53 for T200 versus placebo). Of the 64 patients who completed the 8 weeks of study treatment, significant weight gain was observed in both the T100 group (2.2 kg, [33%]; p = 0.008 versus placebo) and the T200 group (1.5 kg [2.5%]; p = 0.019 versus placebo). Approximately half the weight gain was fat-free mass (bioimpedance analysis). Patients in the T100 or T200 groups had no significant change in CD4+ cell counts, neutrophil counts, or TNF-alpha levels, compared with placebo. HIV viral load measured as log10 copies/ml decreased by a median of 0.07 in the placebo group, and increased by a median of 0.29 (T100 group) and 0.23 (T200 group) (p = 0.024 andp = 0.018 versus placebo, respectively). Thalidomide therapy was associated with mild to moderate rashes and fevers, but not peripheral neuropathy. Although the anabolic benefits of high-dose thalidomide are limited by drug intolerance, 8 weeks of low-dose thalidomide results in significant weight gain in patients with AIDS-associated wasting.

Adult↗
PubMed2000

Hyperlipidemia and insulin resistance are induced by protease inhibitors independent of changes in body composition in patients with HIV infection.

Although protease inhibitor (PI) therapy has improved the clinical status of patients with HIV infection, concerns have arisen that such treatment may have deleterious effects on glucose control, lipid metabolism, and body fat distribution. To determine whether initiation of PI therapy uniquely affects glucose and lipid metabolism, we analyzed paired data in HIV-infected patients before and after beginning antiretroviral therapy that included a PI (PI; N = 20) or lamivudine (3TC) but no PI (3TC; N = 9); and a control group on stable regimens that included neither of these agents (CONT: N = 12). Measurements included fasting glucose; insulin; triglycerides; total, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol; HIV RNA; CD4+ lymphocytes; weight; and total and regional body composition. Neither weight nor total or regional fat content changed significantly in any group during the period of observation. Nonetheless, in patients beginning PI therapy, there were significant increases in glucose (+9+/-3 mg/dl; p = .0136), insulin (+12.2+/-4.9 U/ml; p = .023), triglycerides (+53+/-17 mg/dl; p = .0069), and total and LDL cholesterol (+32+/-11 and +18+/-5 mg/dl; p = .0082 and .0026, respectively). None of these parameters changed significantly in the 3TC or CONT groups. The PI and 3TC groups experienced comparable increases in CD4+ lymphocytes, suggesting that the observed metabolic effects may be associated with PIs uniquely, rather than improvement in clinical status. However, it is also possible that the metabolic effects of PIs are associated with more effective viral suppression, because a greater proportion of patients in the PI group achieved undetectable levels of virus. We conclude that changes in glucose and lipid metabolism are induced by PI therapy in the absence of significant changes in weight or fat distribution. Longer periods of follow-up will be required to determine the clinical significance of these changes. However, at the moment, the risks associated with these metabolic effects do not appear to outweigh improvements in survival seen with PI therapy.

Adult↗
PubMed2000

Physical activity levels in patients on hemodialysis and healthy sedentary controls.

BACKGROUND: Patients on dialysis have reduced exercise tolerance compared with age-matched sedentary controls. The reasons for this debility have not been fully elucidated, but physical inactivity could be a contributing factor. The purpose of the current study was to determine whether patients on hemodialysis are less active than healthy sedentary controls and to explore clinical correlates of physical activity level in a group of hemodialysis patients. METHODS: Thirty-four hemodialysis patients and 80 healthy sedentary individuals participated in the study. Physical activity was measured for seven days with a three-dimensional accelerometer and with an activity questionnaire. RESULTS: Vector magnitude values from the accelerometer for the dialysis and control subjects were 104,718 +/- 9631 and 161,255 +/- 6792 arbitrary units per day, respectively (P < 0.0001, mean +/- SEM). The estimated energy expenditure values derived from the questionnaire were 33.6 +/- 0.5 kcal/kg/day and 36.2 +/- 0.5 kcal/kg/day (P = 0.002). The difference between patients on dialysis and controls increased with advancing age. Among the dialysis subjects, some measures of nutritional status correlated with physical activity level, including serum albumin concentration (r = 0.58, P = 0.003), serum creatinine concentration (r = 0.37, P = 0. 03), and phase angle derived from bioelectrical impedance analysis (r = 0.40, P = 0.02). CONCLUSIONS: Patients on hemodialysis are less active than healthy sedentary controls, and this difference is more pronounced among older individuals. There is an association between the level of physical activity and nutritional status among patients on dialysis. These findings are of great concern, given the trend toward increasing age in incident dialysis patients and the well-known association between inactivity and increased mortality in the general population.

Adult↗
PubMed1999

Anabolic effects of nandrolone decanoate in patients receiving dialysis: a randomized controlled trial.

CONTEXT: Patients receiving dialysis commonly experience malnutrition, reduced muscle mass (sarcopenia), and fatigue for which no effective treatment has been identified. Anabolic steroids are known to increase muscle mass and strength in healthy individuals, but their effect on the sarcopenia and fatigue associated with long-term dialysis has not been evaluated. OBJECTIVE: To assess the effects of an anabolic steroid, nandrolone decanoate, on lean body mass (LBM), functional status, and quality of life in dialysis patients. DESIGN: Randomized, double-blind, placebo-controlled trial conducted between April 1996 and July 1997. SETTING: Hospital-based outpatient dialysis unit. PATIENTS: Twenty-nine patients undergoing dialysis for at least 3 months. INTERVENTION: Nandrolone decanoate, 100 mg (n = 14), or placebo (n = 15) by intramuscular injection once a week for 6 months. MAIN OUTCOME MEASURES: Weight, LBM, fatigue, grip strength, walking and stair-climbing times, and treadmill performance after 3 and 6 months of treatment. RESULTS: Lean body mass increased significantly in patients given nandrolone compared with patients given placebo (mean change [SD], +4.5 [2.3] kg; P<.001 compared with baseline). This effect was significantly greater than the change in LBM in the placebo group (mean change [SD], +1.9 [1.6] kg; P = .003 compared with baseline; P = .005 compared with nandrolone group). Serum creatinine levels increased in the nandrolone group (+168 [203] mmol/L [1.9 [2.3] mg/dL]; P = .02) but not in the placebo group (-4.0 [177] mmol/L [0.04 [2.0] mg/dL]; P = .95), suggesting an increase in muscle mass. Time to complete the walking and stair-climbing test decreased from 36.5 to 32.7 seconds in the nandrolone group, while those in the placebo group increased from 38.7 to 42.1 seconds (P = .05). Peak oxygen consumption increased in the individuals in the nandrolone group who performed treadmill tests, but not to a statistically significant degree. Grip strength did not change in either group. CONCLUSIONS: Treatment with nandrolone for 6 months resulted in a significant increase in LBM associated with functional improvement in patients undergoing dialysis.

Absorptiometry, Photon↗
PubMed1999

Plasma platelet-activating factor acetylhydrolase activity in human immunodeficiency virus infection and the acquired immunodeficiency syndrome.

Platelet-activating factor (PAF) acetylhydrolase (PAF-AH) catalyzes the hydrolysis of PAF, a mediator of inflammation, as well as other biologically active oxidized phospholipids. In humans, plasma PAF-AH activity is bound to low-density lipoprotein (LDL) and high-density lipoprotein (HDL). Higher levels of plasma PAF-AH activity have been found in a variety of diseases, and are thought to be a defense mechanism against the toxic effects of PAF and oxidized phospholipids. We studied plasma PAF-AH activity in patients with human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS), a disease characterized by chronic HIV infection and a systemic host response. Plasma PAF-AH activity was significantly greater in AIDS patients compared with control subjects (25.2 +/- 2.0 v 17.0 +/- 0.8 nmol/min/mL, P < .001). The higher levels of plasma PAF-AH activity were found in LDL (28.2 +/- 2.2 v 18.3 +/- 1.0 nmol/min/mL for AIDS v controls, respectively, P = .0005), but not in HDL. Plasma PAF-AH activity in AIDS correlated with circulating interferon alfa (r = .575, P = .005) and plasma triglycerides (r = .556, P < .0025). The presence of secondary infection in AIDS did not significantly change plasma PAF-AH activity. The initiation of a new antiretroviral regimen with either a protease inhibitor or the nucleoside analog lamivudine did not significantly decrease plasma PAF-AH activity, despite successful suppression of HIV RNA levels. Plasma PAF-AH activity may be a sensitive marker of the host response to infection, and the higher levels of plasma and LDL-associated PAF-AH activity in patients with HIV infection and AIDS may be a physiological response to protect the host against oxidative injury from PAF and oxidized phospholipids.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1998

"Buffalo hump" in men with HIV-1 infection.

BACKGROUND: Enlargement of the dorsocervical fat pad ("buffalo hump") has been reported in numerous HIV-1-infected patients. Some investigators have speculated that this finding is associated with protease-inhibitor treatment. METHODS: Between June, 1995, and October, 1997, we studied eight HIV-1-infected men who had developed a buffalo hump while otherwise stable on antiretroviral therapy. Measurement of 24 h urinary free cortisol excretion and an overnight low-dose dexamethasone suppression test were done to screen for Cushing's syndrome. In one patient, plasma cortisol concentrations were measured every 4 h for 24 h to assess the circadian rhythm of cortisol. Results of total and regional body-composition analysis by dual-energy X-ray absorptiometry, and glucose, cholesterol, triglyceride, and cortisol concentrations were compared with those obtained in a control population of 15 HIV-1-positive men whose age, body-mass index (BMI), and CD4-lymphocyte count were within the range of values in the eight study patients. FINDINGS: The eight patients with a buffalo hump were clinically stable on various antiretroviral regimens, four of which included a protease inhibitor. No other signs of Cushing's syndrome were observed, and plasma cortisol values did not differ significantly from those of controls. 24 h urinary free cortisol excretion was normal in seven patients and slightly raised in one (248 nmoles). In this patient, a repeat 24 h urinary free cortisol was 175 nmoles and plasma cortisol concentrations over 24 h showed a normal circadian pattern (nadir 83 nmol/L at 2400 h). All eight patients had normal suppression of cortisol values after dexamethasone 1 mg (plasma cortisol less than 83 nmol/L). When compared with HIV-1-positive controls, men with a buffalo hump had a significantly greater proportion of fat in the trunk region, suggesting central fat accumulation. Triglyceride but not cholesterol values were higher in the patients than in controls but this difference was not significant. Fasting glucose values did not differ significantly. INTERPRETATION: The development of a buffalo hump cannot be attributed to hypercortisolism in these eight men. Furthermore, its occurrence is not unique to patients on protease inhibitors. Although the mechanism for dorsocervical fat accumulation is unclear, we speculate that regional abnormalities in lipogenesis and lipolysis occur, possibly influenced by the hormonal and metabolic changes seen with HIV-1 infection and its treatment.

Adipose Tissue↗
PubMed1998

Patients report positive nutrition counseling outcomes.

OBJECTIVE: Assess outcomes of patient nutrition counseling. DESIGN: A descriptive study based on the results of a telephone interview performed 2 to 8 weeks after counseling. SUBJECTS/SETTING: Subjects were 400 adult patients referred for nutrition counseling at 2 academic health centers. Of these, 274 patients received nutrition counseling during hospitalization and 126 as outpatients. STATISTICAL ANALYSIS: Descriptive statistics were used to summarize data and the Mann-Whitney U statistic and logistic regressions were used to test significant differences (P < .05) between inpatient and outpatient counseling outcomes. RESULTS: Most patients (83%) gave a partial or full description of their diet modifications and 79% had a moderate or good understanding of their diet. Most patients reported that the dietitian's advice was suited to their special needs (88%) and that they knew what to eat (83%). A majority (62%) had made dietary changes, but 17% said they had had trouble changing their diets as suggested. After talking with a dietitian, 57% felt better emotionally, 37% felt better physically, 64% felt in control of their condition, and 43% noticed improved health indicators. Initial analysis indicated that outpatients reported better outcomes than inpatients; further analysis showed that these differences could be attributed to younger ages among the outpatient sample. APPLICATIONS/CONCLUSIONS: Patient nutrition counseling has positive outcomes. Therefore, key counseling points should be introduced or reinforced in inpatient settings, in conjunction with multiple-session protocols during the pre- and/or posthospitalization continuum of care. Dietitians, managers, administrators, and credentialing agencies should work together to secure and promote the necessary physical, personnel, and financial resources to make this happen.

Adult↗
PubMed1998

Effects of chronic growth hormone treatment on energy intake and resting energy metabolism in patients with human immunodeficiency virus-associated wasting--a clinical research center study.

In previous studies, treatment with recombinant human GH (rhGH) produced sustained increases in weight and lean body mass (LBM) and decreases in fat mass in patients with human immunodeficiency virus (HIV)-associated wasting. To evaluate the effects of chronic rhGH treatment on components of energy balance, we recruited separate subgroups of HIV-positive patients with an involuntary weight loss of 10% or more to undergo paired measurements of resting energy metabolism (n = 6) or food intake (n = 11) before and during the final week of a 3-month rhGH (0.1 mg/kg.day) treatment period. In the energy metabolism subset, resting energy expenditure (REE) and substrate oxidation rates were measured by indirect calorimetry during brief admissions to a metabolic ward. Patients in the energy intake subset prepared written 4-day food intake diaries. Body composition was measured in both groups by bioelectrical impedance analysis. Changes in weight (+2.2 +/- 0.9 and +2.2 +/- 0.6 kg), LBM (+3.2 +/- 0.6 and +3.8 +/- 0.5 kg), and fat (-1.0 +/- 0.5 and -1.6 +/- 0.5 kg) in the energy metabolism and energy intake subsets, respectively, did not differ between groups and were comparable to changes seen in a larger group of patients who received rhGH in a randomized, double blind, placebo-controlled multicenter study. In the energy metabolism subset, REE (+232 +/- 69 Cal/day; P = 0.020) and lipid oxidation (+3.1 +/- 1.0 Cal/kg LBM.day; P = 0.016) increased, whereas protein oxidation decreased (-1.3 +/- 1.0 Cal/kg LBM.day; P = 0.027) during rhGH therapy. These changes in REE and substrate oxidation are comparable to changes we noted previously in a study of the effects of short term rhGH treatment in patients with HIV-associated wasting. Moreover, the sustained increases in lipid oxidation are consistent with the decreases in body fat content that occur with rhGH treatment. In the energy intake subset, a trend for increased daily energy intake (+203 +/- 262 Cal; P = 0.456) is obviated when adjustments for changes in weight or LBM are made (+1.3 +/- 4.0 and -0.5 +/- 5.0 Cal/kg BW and LBM, respectively). Taken together, these results demonstrate that increases in weight and LBM that occur with chronic rhGH therapy are accompanied by sustained increases in REE and lipid oxidation and decreases in protein oxidation. These changes in body composition occur without a significant increase in energy intake and may, instead, represent a redistribution of body energy stores.

Adult↗
PubMed1998

Leptin, body composition, and indices of malnutrition in patients on dialysis.

A cross-sectional study was performed in a group of dialysis patients and control subjects to identify the determinants of serum levels of leptin, the protein product of the obese (ob) gene. Twenty-eight patients on dialysis (19 patients on hemodialysis [HD] and nine patients on peritoneal dialysis [PD]) and 41 healthy control subjects were studied. For each subject, blood was drawn for measurement of serum leptin levels and body composition was analyzed by dual-energy x-ray absorptiometry. Regression analyses were performed to determine the predictors of leptin levels, the independent contribution of HD and PD, and the relationship between leptin levels and markers of malnutrition and protein intake in the patients on dialysis. As expected, percentage of body fat was strongly correlated with leptin levels in the group as a whole and in each subgroup when analyzed separately. However, the slope of the relationship was significantly greater for dialysis patients than for control subjects (P < 0.05). Multivariate regression analysis showed that patients on HD and PD had higher leptin levels than control subjects even after adjustment for age, gender, and percentage of body fat. Univariate analyses were performed to assess the relationship between leptin levels and markers of nutritional status such as albumin, blood urea nitrogen, protein catabolic rate (PCR), transferrin, cholesterol, and lean body mass per height. There was a significant negative correlation between leptin levels and serum albumin (r = -0.598, P < 0.001) and between leptin and PCR (r = -0.433, P < 0.05) in the patients on dialysis. It is concluded that leptin levels adjusted for percentage of body fat are increased in dialysis patients compared with control subjects, particularly in those on PD. In addition, increased leptin levels are associated with low serum albumin levels and PCR in dialysis patients.

Adult↗
PubMed1998

Energy expenditure and protein metabolism in human immunodeficiency virus infection and cancer cachexia.

Malnutrition and weight loss are clinically significant complications of both human immunodeficiency virus (HIV) infection and cancer. Over the last two decades, multiple abnormalities in energy and protein metabolism have been documented in patients with cancer and, more recently, in HIV infection. In HIV infection, studies of the components of energy balance have demonstrated that weight loss results primarily from decreased energy intake, coupled with a failure to consistently reduce resting energy expenditure. Although several studies have shown that resting energy expenditure is elevated in many patients with HIV infection, other studies have shown that not all patients with HIV infection are hypermetabolic. Likewise, protein turnover is increased, decreased, or unchanged in patients with HIV infection and varies with the physiologic state of the patient. In cancer patients, studies of resting energy expenditure have produced similarly varying results, depending in part on tumor type and dietary intake. Protein turnover studies in patients with cancer suggest that support of the tumor may occur at the expense of host skeletal muscle. Abnormalities of glucose and lipid metabolism have been noted as well. Thus, pharmacologic intervention may be needed to restore weight and lean tissue in patients with weight loss associated with either HIV infection or cancer.

Cachexia↗
PubMed1998

Clinical trials update in human immunodeficiency virus wasting.

The major acquired immunodeficiency syndrome (AIDS) clinical trials groups in the Division of AIDS of the National Institutes of Health have been investigating weight loss and wasting in persons with the human immunodeficiency virus (HIV) and AIDS. Both the AIDS Clinical Trials Group (ACTG) and the Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA) have developed research projects to study the pathogenesis, diagnosis, prevention, and treatment of HIV-related malnutrition and wasting. This article reviews multicenter trials concerning HIV-related malnutrition and wasting conducted by the AIDS clinical trials groups. CPCRA trials will examine the effects of caloric supplements and triglycerides, or the use of megestrol acetate, oxandrolone, and progressive resistance training, on weight loss in patients with HIV-associated wasting. Planned ACTG trials will study the effects of the combination of megestrol acetate and testosterone, the testosterone derivative nandrolone decanoate, or highly active antiretroviral therapy on weight loss. Results from these studies may also have relevance to clinical oncologists who are treating patients with cancer-related cachexia.

Anabolic Agents↗
PubMed1997

Cross-sectional and longitudinal evaluation of body composition in men with HIV infection.

Body wasting is an increasingly prevalent AIDS-defining condition and an independent risk factor for mortality in patients infected with HIV. Largely on the basis of studies conducted early in the epidemic, HIV-associated wasting has been assumed to feature a disproportionate loss of lean tissue. We report the results obtained from cross-sectional and longitudinal studies that differ from these earlier observations. In a cross-sectional analysis, weight and body composition determined by dual-energy x-ray absorptiometry and bioelectrical impedance analysis in 32 HIV-infected men with documented weight loss of > or = 10% were compared to those in 46 HIV-positive men without significant weight loss and 32 HIV-negative controls. Fat, lean body mass (LBM), and body cell mass (BCM) were significantly lower in men with weight loss relative to controls (p < 0.001 for fat and BCM; p = 0.01 for LBM). Two thirds of the difference in weight was fat. For the longitudinal analysis, the composition of weight lost over time was evaluated in paired measurements in men grouped by body fat content (<15% or >15%, n = 10 per group). Weight loss in patients with baseline fat of more than 15% was only 16% LBM, but the composition of weight lost in men with baseline fat of less than 15% was 70% LBM. We conclude that progressive decreases in fat and lean tissue occur in men with HIV infection, with the composition of weight lost depending on baseline fat content. These results argue against the widely held notion that HIV-associated wasting is characterized by preservation of fat at the expense of lean tissue.

Adipose Tissue↗
PubMed1997

Simulated optic flow and extrastriate cortex. I. Optic flow versus texture.

A locomoting observer sees a very different visual scene than an observer at rest: images throughout the visual field accelerate and expand, and they follow approximately radial outward paths from a single origin. This so-called optic flow field is presumably used for visual guidance, and it has been suggested that particular areas of visual cortex are specialized for the analysis of optic flow. In the cat, the lateral suprasylvian visual area (LS) is a likely candidate. To test the hypothesis that LS is specialized for analysis of optic flow fields, we recorded cell responses to optic flow displays. Stimulus movies simulated the experience of a cat trotting slowly across an endless plain covered with small balls. In different simulations we varied the size of balls, their organization (randomly or regularly dispersed), and their color (all one gray level, or multiple shades of gray). For each optic flow movie, a "texture" movie composed of the same elements but lacking optic flow cues was tested. In anesthetized cats, > 500 neurons in LS were studied with a variety of movies. Most (70%) of 454 visually responsive cells responded to optic flow movies. Visually responsive cells generally preferred optic flow to texture movies (69% of those responsive to any movie). The direction in which a movie was shown (forward or reverse) was also an important factor. Most cells (68%) strongly preferred forward motion, which corresponded to visual experience during locomotion.

Animals↗
PubMed1997

Simulated optic flow and extrastriate cortex. II. Responses to bar versus large-field stimuli.

In the preceding paper we described the responses of cells in the cat's lateral suprasylvian visual area (LS) to large-field optic flow and texture movies. To assess response properties such as direction selectivity, cells were also tested with moving bar stimuli. We expected that there would be good agreement between response properties elicited with optic flow movies and those revealed with bar stimuli. We first asked how well bar response properties predicted responsiveness to optic flow movies. There was no correlation between responsiveness to movies and the degree of end-stopping, length summation, or preference for bars that accelerated and expanded. We then considered only the 322 cells that responded to both bars and optic flow or texture movies and asked how well the strength of their response to movies could be predicted from the direction-tuning curves generated with bar stimuli. One-third of these cells responded much more strongly to movies than could be predicted from their direction-tuning curves. Generally, such cells were rather well tuned for the direction of bar motion and preferred a direction substantially different from what they saw in optic flow movies. Optic flow movies shown in the forward direction were the most effective variety of movie for two-thirds of these cells. To see whether this outcome stemmed from differential direction tuning for bars and large multielement displays, in a second series of experiments we compared direction tuning for bars and large-field texture movies. Many cells showed substantially different direction tuning for the two kinds of stimulus: almost 1/3 of 409 cells had tuning curves that overlapped each other by < 50%. But only a small number of cells (< 10%) responded much better to texture movies than to bars in the predominant direction of image motion in optic flow movies. This result, like that reported in the preceding paper, suggests that cells in LS respond differently to optic flow than to texture displays lacking optic flow motion cues.

Animals↗