Usage of megestrol acetate in the treatment of anorexia-cachexia syndrome in the elderly.

UNLABELLED: The aim of this review is to assess the efficacy and safety of megestrol acetate (MA) in geriatric cachexia. The paper presented here reviews a previously published study of MA use in 69 patients in a randomized double blind placebo-controlled trial. This paper will also address the underlying pathogenesis of cachexia (specifically, the role of cytokines) along with the use of MA, its mechanism of action and its side effects. OBJECTIVE: To compare the effects of MA oral suspension (O.S.), 800 mg/day, versus placebo on weight in geriatric nursing home patients with weight loss or low body weight. DESIGN: Twelve weeks, randomized, double-blind, placebo-controlled trial with a 13-week follow-up period. PATIENTS: Northport VAMC Nursing home patients with weight loss of * 5% of usual body weight over the past 3 months, or body weight 20% below their ideal body weight. INTERVENTIONS: Patients were randomly assigned to receive placebo or MA 800 mg/d for 12 weeks and were then followed for 13 weeks off treatment and mortality 4 years post treatment. MEASUREMENTS: Primary outcome- weight and appetite change. Secondary outcome-sense of well being, enjoyment of life, change in depression scale, laboratory nutrition parameters, energy intake counts, body composition, and adverse events. RESULTS: At 12 weeks there were no significant differences in weight gain between treatment groups, while MA-treated patients reported significantly greater improvement in appetite, enjoyment of life, and well being. At week 25 (3 months after treatment), 61.9% of MA-treated patients had gained * 1.82 kg (4 lbs) compared to 21.7% of placebo patients. There was no difference in survival between MA and placebo groups. Considering possible confounders, higher initial IL-6, initial TNFR-p75 levels, and final neutrophil percentage were associated with elevated mortality, whereas higher initial pre-albumin, initial albumin, final pre-albumin, final albumin and final weight gain were associated with decreased death.

A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults.

BACKGROUND: The incidence and severity of herpes zoster and postherpetic neuralgia increase with age in association with a progressive decline in cell-mediated immunity to varicella-zoster virus (VZV). We tested the hypothesis that vaccination against VZV would decrease the incidence, severity, or both of herpes zoster and postherpetic neuralgia among older adults. METHODS: We enrolled 38,546 adults 60 years of age or older in a randomized, double-blind, placebo-controlled trial of an investigational live attenuated Oka/Merck VZV vaccine ("zoster vaccine"). Herpes zoster was diagnosed according to clinical and laboratory criteria. The pain and discomfort associated with herpes zoster were measured repeatedly for six months. The primary end point was the burden of illness due to herpes zoster, a measure affected by the incidence, severity, and duration of the associated pain and discomfort. The secondary end point was the incidence of postherpetic neuralgia. RESULTS: More than 95 percent of the subjects continued in the study to its completion, with a median of 3.12 years of surveillance for herpes zoster. A total of 957 confirmed cases of herpes zoster (315 among vaccine recipients and 642 among placebo recipients) and 107 cases of postherpetic neuralgia (27 among vaccine recipients and 80 among placebo recipients) were included in the efficacy analysis. The use of the zoster vaccine reduced the burden of illness due to herpes zoster by 61.1 percent (P<0.001), reduced the incidence of postherpetic neuralgia by 66.5 percent (P<0.001), and reduced the incidence of herpes zoster by 51.3 percent (P<0.001). Reactions at the injection site were more frequent among vaccine recipients but were generally mild. CONCLUSIONS: The zoster vaccine markedly reduced morbidity from herpes zoster and postherpetic neuralgia among older adults.

The correlation of cytokine levels with body weight after megestrol acetate treatment in geriatric patients.

BACKGROUND: Cachexia is associated with elevated levels of cytokines in cancer and human immunodeficiency virus patients. Studies in cancer and acquired immunodeficiency syndrome patients showed that treatment with megestrol acetate (MA) is associated with improvement in appetite and weight gain. Reduction in the levels of cytokines is associated with weight gain in laboratory animals with cancer. This study evaluates the correlation between changes in cytokine (or their receptor) levels and weight following MA treatment in geriatric weight-loss patients. METHODS: Veterans Administration Medical Center nursing home patients (N = 69) with a weight loss of > or =5% of usual body weight over the past 3 months or body weight 20% below their ideal body weight participated in a 12-week, randomized, double-blind, placebo-controlled trial, with an additional 13-week follow-up period. Patients were randomly assigned to receive a placebo or MA oral suspension of 800 mg/d for 12 weeks. Levels of the following cytokines (or their receptors) were measured at baseline and after 12 weeks of treatment: tumor necrosis factor soluble receptor (TNFR) subunits. TNFR-p55 and TNFR-p75: interleukin 6 (IL-6); and the soluble interleukin-2 receptor (sIL-2R). The subjects' weight and body composition were measured at the start of the study. Weight and mortality were followed up for another 13 weeks after discontinuing the MA study drug. RESULTS: Elevated levels of IL-6 in almost all geriatric cachexic patients, compared with normal volunteers (mean, <4.6 pg/ml). were noted at baseline. At 12 weeks after the study drug treatment, there was a decrease in cytokine levels (or their receptors) in the MA group (mean change in IL-6, 3.63+/-6.62 pg/ml; TNFR-p55, -0.06+/-0.11 ng/ml; TNFR-p75. -0.01+/-0.29 ng/ml; and sIL-2R, 0.08+/-0.07 ng/ml) and the placebo group (mean change in IL-6, -2.08+/-3.92 pg/ml; TNFR-p55, -0.02+/-0.08 ng/ml; TNFR-p75, -0.20+/-0.18 ng/ml; and sIL-2R, 0.02+/-0.03 ng/ml). Although the change in cytokine levels was not statistically significant between the two groups, significant negative correlation (p < .05) was found. For example, increased weight correlated with decreased sIL-2R levels (r = .36) and TNFR-p75 (r = -.31; fat-free mass (FFM) gain and reduction of sIL-2R (r = -.39), TNFR-p75 (r = -.30). There was a significant correlation between weight gain and reduction of TNFR-p75 (r = .54), TNFR-p55 (r- = .47), and sIL-2R (r = -.53); FFM gain and reduction of sIL-2R (r = -.59), TNFR-p75 (r = -.41), TNFR-p55 (r = -.42); and fat gain and reduction of TNFR-p75 (r = -.41) in the MA group (p < .05), but not in the placebo group. CONCLUSIONS: Although there was no significant change in cytokine levels between the two groups, the reduction in cytokine levels after MA treatment correlated with improvement in weight, fat mass, and FFM at 12 weeks.

Improvement in quality-of-life measures and stimulation of weight gain after treatment with megestrol acetate oral suspension in geriatric cachexia: results of a double-blind, placebo-controlled study.

BACKGROUND: Weight loss among older patients is a severe problem, associated with an increased incidence of infections, decubiti, and death. Megestrol acetate (MA) causes weight gain in cachectic cancer and AIDS patients, but its effects in older cachectic patients are unknown. OBJECTIVE: To compare the effects of MA oral suspension (O.S.), 800 mg/day, versus placebo on weight in geriatric nursing home patients with weight loss or low body weight. DESIGN: Twelve-week, randomized, double-blind, placebo-controlled trial with a 13-week follow-up period. SETTING: Veterans Administration Medical Center (VMAC) nursing home. PATIENTS: Nursing home patients with weight loss of > or =5% of usual body weight over the past 3 months, or body weight 20% below their ideal body weight. INTERVENTIONS: Patients were randomly assigned to receive placebo or MA 800 mg/day for 12 weeks and were then followed for 13 weeks off treatment. MEASUREMENTS: Primary outcome was measured by weight and appetite change. Secondary outcome measures included sense of well-being, enjoyment of life, change in depression scale, laboratory nutrition parameters, energy intake counts, body composition, and adverse events. RESULTS: At 12 weeks there were no significant differences in weight gain between treatment groups, whereas MA-treated patients reported significantly greater improvement in appetite, enjoyment of life, and well-being. Body composition was not statistically different between the two groups. At Week 25 (3 months after treatment), 61.9% of MA-treated patients had gained > or =1.82 kg (4 lbs) compared to 21.7% of placebo patients. CONCLUSIONS: In geriatric patients with weight loss or low body weight MA improves appetite and well-being after 12 weeks of treatment. During the 3 months of MA treatment, there was no statistically significant weight gain (> or =4 lbs). Three months after treatment, weight gain (> or =4 lbs) was significantly increased in MA-treated patients.

Treatment of a transvestic fetishist with cognitive-behavioral therapy and supportive psychotherapy: case report.

Transvestic fetishism is a paraphilia marked by recurrent, intense sexually arousing fantasies, sexual urges, or behavior involving cross-dressing, in a heterosexual male. There are many explanations of the pathogenesis, but none are conclusive. Different treatments have been applied, but they generally remain obscure and disappointing. Transvestic fetishists rarely seek psychotherapy, because of their dynamic balance between perversion and intrapsychic disintegration. There are few studies, either qualitative or quantitative, associated with transvestic fetishism in Taiwan. This case report describes an adolescent transvestic fetishist who underwent a brief course of psychotherapy in the outpatient department of a psychiatric center in Taipei. After consultation for one year, he still maintained his deviant sexual behavior but also developed more severe moral anxiety. He was then referred for psychotherapy. Cognitive-behavioral and psychodynamic theories associated with transvestic fetishism were reviewed and applied in both understanding and treating this client. Some temporal effectiveness was achieved with combined cognitive-behavioral and dynamic-oriented supportive psychotherapy. After 18 sessions of psychotherapy over more than 4 months, the client was able to stop his perverse behavior and have fewer sexually arousing fantasies. The prognosis of transvestic fetishism is generally supposed to be pessimistic and have a high rate of recurrence. Some propose that adolescents have a better outcome after treatment. This case report reveals the possibility of change for a transvestic fetishist. However, the long-term effects of the brief course of psychotherapy require further evaluation in the future.

Characterization of the Bacillus macerans cyclodextrin glucanotransferase overexpressed in Escherichia coli.

Cyclodextrin glucanotransferase (CGTase, EC 2. 4. 1. 19) converts starch and related alpha-1,4-glucans to cyclodextrin (CD). Our previous studies of the enzyme have suggested that E344 on the polypeptide is crucial to the enzyme activity. Mutational analysis of CGTase was performed to confirm this idea. Three mutant CGTases containing either E344D, E344K or E344L substitution were overexpressed in Escherichia coli. However, only the wild-type and E344D CGTases became soluble when expressed at 20 degrees C. These two enzymes were purified to homogeniety from E. coli cells after beta-CD and Ni-NTA affinity chromatographies. The Km values of the authentic Bacillus macerans CGTase (2.10 mM), and of the wild-type (0.58 mM) and E344D (1.05 mM) CGTases purified from E. coli were different. The kcat values of the three CGTases were 99.8, 26.5 and 90.7 s-1, respectively. The percentage of alpha-CD production was 18.4% for the authentic CGTase, 24.9% for the wild-type and 14.5% for the E344D CGTases purified from E. coli. The changes of both the coupling and cyclization activities of CGTase caused by E344D suggest that E344 is important to the catalytic function of CGTase.

Geriatric cachexia: the role of cytokines.

Weight loss in elderly patients is a common clinical problem. Wasting and cachexia are associated with severe physiologic, psychologic, and immunologic consequences, regardless of the underlying causes. Cachexia has been associated with infections, decubitus ulcers, and even death. Multivariate analyses of risk and prognostic factors in community-acquired pneumonia in the elderly have found that age by itself is not a significant factor related to prognosis. Among the significant risk factors, only nutritional status is amenable to medical intervention. Cachexia in the elderly may have profound consequences: medical, cognitive, and psychiatric disorders may diminish self-reliance in activities of daily living, thus reducing quality of life and increasing the frequency of secondary procedures, hospitalizations, and the need for skilled care. Cachexia is associated with higher-than-normal concentrations of tumor necrosis factor alpha (TNF-alpha), interleukin (IL) 1, IL-6, serotonin, and interferon gamma. The role of these proinflammatory cytokines has been established in the cachexia seen in cancer and AIDS patients. Reduction in the concentrations of these cytokines is associated with weight gain. Drugs that promote appetite stimulation and weight gain, such as progestational agents, cyproheptadines, pentoxifylline, and thalidomide may work by down-regulating these proinflammatory cytokines. An understanding of the relation between cachexia and negative regulatory cytokines may point to effective treatment of geriatric cachexia as well.

Hypertension in nursing home patients.

There have been few studies of hypertension in nursing home patients. To assess the prevalence, demographic characteristics, comorbidity and drug therapy in hypertensive nursing home patients compared with those who are normotensive, we reviewed all medical charts of patients in three nursing home facilities. Of the 804 patients, 355 (44.2%) have hypertension. Calcium channel blockers were the most frequently prescribed anti-hypertensive (30.3%) and together with diuretics (28.4%) and ACE inhibitors (27.7%) account for more than 85%. Hypertensive patients take more cardiac, hypoglycaemic, and analgesic drugs (P = <0.001, <0.001, and 0.004, respectively) than those who are normotensive. Overall patients take an average of 8.68 medications daily. In hypertensive patients, the average number of comorbid conditions (excluding hypertension) is 5.02 compared with 3.23 in normotensive patients. Hypertension is significantly associated with diabetes, heart disease, cerebrovascular disease, neoplasms, endocrine disorders, gastrointestinal diseases, psychiatric disorders, dementia, other central nervous system diseases, skin problems, blood diseases and inversely with hip fracture. Blood pressure control (<140/90 mm Hg) is achieved in 88.8%, is not related to age and is significantly more frequent in males than females (91.8% vs 82.6% P = 0.025). The problem of hypertension in nursing home patients is complex and has received insufficient study. Since studies demonstrating benefit from anti-hypertensive therapy in the elderly excluded the very elderly and those with significant comorbid conditions, additional research is needed.

Psychogenic vomiting: report of two cases.

Two patients were admitted to our hospital with the diagnosis of psychogenic vomiting of more than 9 months' duration. Both were treated with a combination of pharmacotherapy, relaxation training, cognitive therapy and supportive psychotherapy. Behavioral therapy and verbal catharsis were also used in one of the cases involving bereavement. The intervention was not directly aimed at the vomiting, but at the aspects of the patients' stress and emotional problems. Change in condition was assessed on basis of the frequency of vomiting and the severity of anxiety and depression. Vomiting was found to be positively related to anxiety but not to depression. These 2 patients improved to the extent that the disturbance caused by vomiting was significantly reduced, and the reduction was closely related to the severity of anxiety. Both were also found to have similar personality traits and family types, which have been reported to be related to psychogenic vomiting. We review the characteristics of psychogenic vomiting and relate some important considerations for treating Chinese psychogenic vomiting cases.

Withdrawal of antihypertensive medications.

BACKGROUND: Pharmacologic treatment of hypertension reduces risks of stroke, congestive heart failure, renal failure, and mortality, but whether medications, once begun, need to be continued for life is uncertain. METHODS: Several search strategies on MEDLINE using key words "medication," "withdrawal," "discontinuance," and "therapy" in several combinations, nested within "hypertension," were not productive. Accordingly, articles known to the authors and citations within them were reviewed. A survey of a random sample of members of the New York Academy of Family Practice was conducted to ascertain current practice of practicing physicians. RESULTS: Eighteen studies of antihypertensive medication withdrawal were located and all were reviewed. In 12 trials average success rates of 40.3 percent after 1 year of follow-up and 27.7 percent after 2 years were achieved. In six studies limited to elderly patients, an average success rate of 26.2 percent was obtained for periods of 2 or more years. The trials, however, were heterogeneous in design, patient selection criteria, and follow-up. The survey of family physicians indicated that 79.1 percent attempt withdrawal of antihypertensive medications in hypertensive patients whose blood pressure is controlled and who are without symptoms from medication. CONCLUSIONS: We conclude that successful withdrawal of antihypertensive medications can have substantial benefits with few or no adverse consequences and might be successful in about one third of patients. Additional research is required to substantiate rates of successful medication withdrawal, to define the best method of withdrawing medications, and to delineate characteristics of patients in whom withdrawal is most likely to succeed.

[The present status of psychiatric consultation in Chang Gung Memorial Hospital, Keelung: a report of clinical characteristics].

One hundred and sixty three inpatients (84 males and 79 females) were referred for psychiatric consultation through the year of 1994. The referal rate (0.71%) was considerably low when compared with the rates (0.72-2.05%) reported by other hospitals in Taiwan. Most of the referrals were the patients of internal medicine (64.78%), especially the nephrology department. And the most common psychiatric diagnoses were organic mental syndrome. The primary reason of referals was suicidal attempt (evaluation of suicidal risk) (33.14%). In a general hospital, psychoactive substance use disorders and induced mental disorders tended to be an most usual task of psychiatric consultation. The rate of execution of suggested medication was 72.68%. Most psychotic patients and nearly overall suicidal patients had higher rate of execution of pharmacotherapy. The rate of follow-up compliance was 39.58%. The development of consultation-liaison psychiatry is in the initial stage in our hospital. The results of our study could provide reference in clinical practice and stimulate further investigation.

ATP-AMP phosphotransferase from Paracoccus denitrificans.

Adenylate kinase has been extracted from Paracoccus denitrificans by toluene treatment and purified 370-fold (overall yield of 44%, 554 U/mg, Mr 22 000, pI 4.7; pH optimum 7.5-8.0) by using successive column chromatography on DEAE-cellulose DE-52, Matrex-Blue A and Sephadex G-75. The enzyme was homogeneous by dodecylsulfate gel electrophoresis and constancy of specific activity across the single peak found in Sephadex G-75 chromatography. Crystals in the form of heavy needles have been obtained in poly(ethylene glycol)-400. The enzyme is specific for adenine (deoxyadenine) nucleotides with Km values for ATP, ADP and AMP of 340 microns, 980 microM and 93 microM respectively and dissociation constants, for ATP, MgATP and AMP of 7.3 microM, 7.1 microM and 6.9 microM respectively. The enzyme was noted to have no disulfide bond, two free sulfhydryl groups and a total of 208 residues. Aboe 50 mM KCl the enzyme activity drops off gradually. The enzyme is stable at neutral pH and below a temperature of 44 degrees C. Adenylate kinase from P. denitrificans resembles adenylate kinases from other sources with respect to such properties as the dependence on specific divalent cations, maximal activities at a ratio of Mg2+:ATP of about 1:1 and the ratio of Mg2+:ADP of 1:2, in having MgATP (or MgADP) binding site and another substrate binding site for AMP (or ADP), and in requiring an intact histidine and one or more arginine residues for enzymatic activity. Adenylate kinase from P. denitrificans appears to resemble the so-called muscle-type (cytoplasmic) rather than the mitochondrial-type adenylate kinase by comparisons of the following properties: low molecular weight, having --SH groups and no disulfide bonds, pH-optimum of 8.0 for formation of ADP, positive cross-reaction by ELISA test and in requiring a low concentration of Ap5A to inhibit 95% activity.