Appetite-suppressant drugs and primary pulmonary hypertension.
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Appetite Depressants↗
Biomedical subjects
R L Atkinson
Publications and source records attributed to R L Atkinson.
Long-term drug treatment of obesity in a private practice setting.
This study evaluated the long-term efficacy and safety of the combination of phentermine and fenfluramine for the treatment of obesity in a private practice setting. A total of 1388 consecutive, qualified patients presenting to a private general internal medicine practice in Charlotte, NC, were enrolled with eligibility criteria including: age 18 years to 60 years, 20% over "desirable" bodyweight or body mass index > 27, no serious medical or psychiatric disease, and no contraindications to drug therapy. Patients were instructed in diet, exercise, and behavior modification techniques and received phentermine (15 mg/day to 30 mg/day) and fenfluramine (20 mg/day to 60 mg/day) continuously for over 3 years. Average duration of treatment was 15.9 months, and average weight loss at the last visit was 11.6 kg, or 11.7% of initial bodyweight. For patients completing 1 year of drug treatment, mean weight loss was 16.5 kg, or 16% of initial weight. Weight loss persisted for 2 years, but partial regain was seen at 3 years. The dropout rates were 18% at 6 months, 39% at 1 year, 68% at 2 years, and 78% at 3 years. At 1 year, blood pressure of hypertensive patients fell from 151/95 mm Hg to 127/78 mm Hg, and serum cholesterol and triglycerides of hyperlipidemic patient fell by 0.750 mmol/L (29 mg/dL) and 0.937 mmol/L (83 mg/dL), respectively. Adverse events were modest. We conclude that, in a private practice setting, long-term treatment of obesity with the combination of phentermine, fenfluramine, and a weight maintenance program is generally safe and effective. More research is needed to determine efficacy and safety for longer than 3 years.
Adolescent↗
Association of adenovirus infection with human obesity.
We previously reported that chickens infected with the avian adenovirus SMAM-1 developed a unique syndrome characterized by excessive intra-abdominal fat deposition accompanied by paradoxically low serum cholesterol and triglyceride levels. There have been no previous reports of avian adenoviruses infecting humans. We screened the serum of 52 humans with obesity in Bombay, India, for antibodies against SMAM-1 virus using the agar gel precipitation test (AGPT) method. Bodyweights and serum cholesterol and triglyceride levels were compared in SMAM-1-positive (P-AGPT) and SMAM-1-negative (N-AGPT) groups. Ten subjects were positive for antibodies to SMAM-1, and 42 subjects did not have antibodies. The P-AGPT group had a significantly higher bodyweight (p < 0.02) and body mass index (p < 0.001) (95.1 +/- 2.1 kg and 35.3 +/- 1.5 kg/m2, respectively) compared with the N-AGPT group (80.1 +/- 0.6 kg and 30.7 +/- 0.6 kg/m2, respectively). Also, the P-AGPT group had significantly lower serum cholesterol (p < 0.02) and triglyceride (p < 0.001) values (4.65 mmol/L and 1.45 mmol/L, respectively) compared with the N-AGPT group (5.51 mmol/L and 2.44 mmol/L, respectively). Two subjects positive for SMAM-1 antibodies had antibodies against each others' serum, suggesting the presence of antigens in one or both. When these two serum samples were inoculated into chicken embryos, macroscopic lesions compatible with SMAM-1 infection developed. The inoculation of serum from N-AGPT subjects did not produce such lesions. The presence of increased obesity, antibodies to SMAM-1, reduced levels of blood lipids, and viremia that produces a typical infection in chicken embryos suggests that SMAM-1, or a serologically similar human virus, may be involved in the cause of obesity in some humans.
Adenoviridae↗
Metyrapone pre-treated inferior petrosal sinus sampling in the differential diagnosis of ACTH-dependent Cushing's syndrome.
BACKGROUND: Inferior petrosal sinus sampling (IPSS) is a useful investigative technique in the differential diagnosis of ACTH-dependent Cushing's syndrome. Diagnostic accuracy is improved by the administration of corticotrophin releasing-factor (CRF) during the procedure to stimulate ACTH secretion. We hypothesized that, given the unavailability of CRF in Australia, stimulation of ACTH secretion from tumorous corticotrophs with metyrapone treatment before IPSS may be useful. AIMS: To describe our clinical experience with a novel diagnostic test, and to compare results between IPSS with and without metyrapone pre-treatment. SETTING: Metropolitan, Australian university teaching hospital. PATIENTS: 18 patients were studied on 21 occasions: three with Cushing's disease without metyrapone treatment prior to IPSS (M-), 11 with Cushing's disease with metyrapone pretreatment (M+), three with ectopic ACTH syndrome, and one with pseudo-Cushing's syndrome. TREATMENT: Patients received oral metyrapone, median dose 750 mg 6 hourly, for 24 h before IPSS. RESULTS: No major side effects were noted. Metyrapone increased serum 11-deoxycortisol concentration to a median of 400 nmol/l (range 36-1310) on the morning of the test. Radiological confirmation of correct catheter placement was shown in 36/42 inferior petrosal sinuses (86%). Median peak central: peripheral ACTH ratios were 9.8 for M- pituitary adenomas (range 5.7-13.6), 12.9 for the technically successful M+ pituitary adenomas (range 8-54.1), and 1.6 for M+ ectopic ACTH syndrome cases (range 1.2-3.4). Repeat studies in unoperated patients with ectopic ACTH syndrome showed ratios < 1.6. IPSS showed median peak ACTH concentrations of 190 ng/l for M- pituitary adenomas (range 83-205), 595 ng/l for the technically successful M+ pituitary adenomas (range 80-7630; P = 0.035 compared to M-), and 62 ng/l for M+ ectopic ACTH syndrome cases (range 47-220). IPSS correctly identified the pituitary source of ACTH production in all cases of Cushing's disease (except one technical failure where MRI revealed a lesion). MRI scanning correctly identified a lesion in 3/14 operated Cushing's disease cases. IPSS correctly lateralized 1/3 M- and 7/8 M+ Cushing's disease cases where the procedure was technically successful and surgical descriptions adequate. Pituitary exploration revealed a visible lesion in 75% of cases corresponding to the side predicted by IPSS; 'blind' hemi-hypophysectomy was performed on the side predicted from IPSS in the remainder. All cases of Cushing's disease were cured or improved following surgery, with a median follow-up of 2.8 years (range 0.7-5.9). CONCLUSIONS: Metyrapone pre-treated inferior petrosal sinus sampling is safe, and appears to induce high ACTH output from pituitary corticotroph adenomas. The technique has allowed accurate localization and treatment of pituitary corticotroph microadenomas.
ACTH Syndrome, Ectopic↗
Obesity surgery as a model for understanding the regulation of food intake and body weight.
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Body Weight↗
Use of drugs in the treatment of obesity.
Obesity has become an epidemic in the United States and in many other countries of the world. Obesity is a chronic disease, not a failure of willpower. Diet, exercise, and behavioral modification of lifestyle are rarely successful over the long term. Medications have been used sparingly, because of concerns about addiction and ineffectiveness, but used chronically, obesity drugs are effective. The two main categories of obesity drugs are centrally active adrenergic and serotonergic agents. These drugs reduce appetite, enhance satiety, and increase energy expenditure. Use of single agents produces modest weight loss and use of combinations increases loss, but few patients reach their goal weight. Co-morbidities associated with obesity resolve or are reduced in severity with weight loss. Adverse events of major concern are changes in brain biochemistry and primary pulmonary hypertension. Published guidelines for use of obesity medications recommend they be used only for medically significant obesity.
Adrenergic Agents↗
Differential regulation of the p80 tumor necrosis factor receptor in human obesity and insulin resistance.
Previous studies have shown that tumor necrosis factor (TNF)-alpha production from adipose tissue is elevated in rodent and human obesity and plays an important role in insulin resistance in experimental animal models. In this study, we examined the adipose expression of both TNF receptors (TNFR1 and TNFR2) in human obesity and demonstrated that obese female subjects express approximately twofold more TNFR2 mRNA in fat tissue and approximately sixfold more soluble TNFR2 in circulation relative to lean control subjects. In contrast, TNFR1 expression and protein levels were similar in these subjects. TNFR2 expression levels in adipose tissue were strongly correlated with BMI (r = 0.65, P < 0.001) and level of hyperinsulinemia (P < 0.001), an indirect measure of insulin resistance, as well as level of TNF-alpha mRNA expression in fat tissue (r = 0.56, P < 0.001). These results suggest that TNFR2 might play a role in human obesity by modulating the actions of TNF-alpha.
Adipose Tissue↗
Role of nutrition planning in the treatment for obesity.
The most sensible eating plans are those that involve a wide selection of foods with a modest percentage of kilocalories as fat. The dietary pyramid developed by the US Government is an excellent basis for the construction of an eating plan for life. Patients should be encouraged to develop healthy eating habits that they can maintain indefinitely, as the early inevitable consequence of finishing a diet is regain of any weight that has been lost when the patient goes back to their old eating habits. The unfortunate fact is that individuals with the disease of obesity must behave differently than those who do not. This usually means that obese persons must eat differently than lean persons, and they must do this for their entire lives. Food is a critical part of the social fabric of our society. The physician, usually in combination with a knowledgeable and empathetic dietitian or other nutritional education resource, can help obese patients choose the series of compromises in eating plans and activity levels that can be maintained for life but still allow a reasonable quality of life.
Dietary Services↗
High prevalence of gastric trichobezoars (hair balls) in Wistar-Kyoto rats fed a semi-purified diet.
Gastric trichobezoars (hair balls) are frequently found in rabbits but are rarely reported in rats. Several Wistar-Kyoto rats fed a semi-purified diet developed anorexia and abdominal tenderness. Proteolysis therapy with fresh papaya and commercially prepared enzyme was attempted in these rats but was not successful. The prevalence of trichobezoars at necropsy was 100%. We conclude that semi-purified diets contribute to trichobezoar formation in rats, but proteolysis therapy is not effective in dissolving the trichobezoars.
Animals↗
Combined drug treatment of obesity.
Pharmacological treatment of obesity has been neglected as a viable therapeutic option for many years. Recent long term studies with combinations of obesity drugs gives promise that drugs may play a role in weight maintenance, which classically has been the most difficult aspect of treating obesity. Currently available obesity drugs include centrally acting adrenergic agents and serotonin agonists. Drugs still in development include a lipase inhibitor that produces fat malabsorption, a combined adrenergic-serotonergic reuptake inhibitor, various gut-central nervous system peptides, and a number of beta-3 agonists. Any of these obesity drugs given alone produces modest weight loss, and for most, weight loss continues for as long as medication is given. The most successful drug regimens to date are combinations of phentermine and fenfluramine or of ephedrine, caffeine, and/or aspirin. The former combination produces reduction in body weight and complications of obesity for 2 to almost 4 years in clinical trials to date. More research is needed to document long term efficacy and particularly the long term safety of these and other combinations.
Adrenergic Agents↗
1995: clinical nutrition--a medical specialty in transition.
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Humans↗
Dietary fat and adiposity: a dose-response relationship in adult male rats fed isocalorically.
This study examined the effects of increasing levels of dietary fat fed isocalorically on body weight, body composition, and adipose distribution. Adult male rats were weight matched into four groups. One group that was fed a low-fat diet (12%) served as reference controls. The other three groups were fed diets of 24, 36, or 48% fat in amounts to equal the energy intake of the control group. After 6 wk, body weights of the four groups were not significantly different. Intrascapular brown fat did not differ between groups. Total body fat and adipose depot weights, however, increased in proportion to the level of fat in the diet. Total body fat and retroperitoneal and mesenteric depot weights of the 48% fat group were greater than controls (P < 0.05). Mesenteric fat in this group was also significantly increased over all other groups (P < 0.05). These results show that high-fat diets fed to adult animals cause increased body fat in the absence of significant changes in body weight and that mesenteric fat is increased disproportionately.
Adipose Tissue↗
Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance.
Obesity is frequently associated with insulin resistance and abnormal glucose homeostasis. Recent studies in animal models have indicated that TNF-alpha plays an important role in mediating the insulin resistance of obesity through its overexpression in fat tissue. However, the mechanisms linking obesity to insulin resistance and diabetes in humans remain largely unknown. In this study we examined the expression pattern of TNF-alpha mRNA in adipose tissues from 18 control and 19 obese premenopausal women by Northern blot analysis. TNF-alpha protein concentrations in plasma and in conditioned medium of explanted adipose tissue were measured by ELISA. Furthermore, the effects of weight reduction by dietary treatment of obesity on the adipose expression of TNF-alpha mRNA were also analyzed in nine premenopausal obese women, before and after a controlled weight-reduction program. These studies demonstrated that obese individuals express 2.5-fold more TNF-alpha mRNA in fat tissue relative to the lean controls (P < 0.001). Similar increases were also observed in adipose production of TNF-alpha protein but circulating TNF-alpha levels were extremely low or undetectable. A strong positive correlation was observed between TNF-alpha mRNA expression levels in fat tissue and the level of hyperinsulinemia (P < 0.001), an indirect measure of insulin resistance. Finally, body weight reduction in obese subjects which resulted in improved insulin sensitivity was also associated with a decrease in TNF-alpha mRNA expression (45%, P < 0.001) in fat tissue. These results suggest a role for the abnormal regulation of this cytokine in the pathogenesis of obesity-related insulin resistance.
Adipose Tissue↗
Intravascular ultrasound imaging of coarctation of the aorta: animal and human studies.
Although the use of balloon dilation for treatment of native and recurrent coarctation of the aorta (coA) has become widespread, the optimal balloon size and postdilation vessel wall changes remain undetermined. Intravascular ultrasound (IVUS) imaging has emerged as a an important adjunct in the treatment and follow-up of patients with coronary artery and peripheral vascular lesions, and has been used for evaluation in a limited number of patients with CoA. We used a combination of balloon dilation/ultrasound imaging catheter in animals with experimentally-induced CoA. We used a combination balloon dilation/ultrasound imaging catheter in animals with experimentally-induced CoA . This technique provided real-time data regarding aortic wall morphology and luminal diameter during balloon angioplasty of the CoA. In humans, we used IVUS to study CoA before and after both transcatheter and surgical therapy. IVUS was more sensitive than angiography in the detection of intimal tears post-balloon dilation and in the evaluation of vessel wall changes and remodelling observed at follow-up after relief of CoA. IVUS may provide valuable information regarding vascular wall changes that predict aneurysm format ion, restenosis, or a successful result after balloon dilation.
Animals↗
Maxillofacial biomodelling.
The authors report the clinical applications of biomodelling with the stereolithography apparatus, a computer-controlled manufacturing technique that builds anatomically accurate skeletal models from sectional radiological data. Reference to several individual cases demonstrates how pre-operative 3-D modelling can refine the accuracy of diagnostic information, facilitate preoperative planning and surgical technique, and reduce operating time.
Acrylic Resins↗
Report on the NIH Workshop on Pharmacologic Treatment of Obesity.
A National Institutes of Health workshop on pharmacologic treatment of obesity concluded that pharmacologic agents may be effective in reducing body weight over an extended period of time. Drugs should be used as only one component of a comprehensive weight-reduction program, and additional research is needed on the long-term efficacy and safety of drugs for obesity, and especially for combinations of drugs. Improvement in comorbidities and risk factors of obesity should be used along with weight reduction as an outcome measure in clinical trials. Industry, professional societies, and governmental agencies should work together to explore the potential for drugs for obesity and to reassess the regulatory and administrative controls on the use of currently available drugs for obesity and on the approval process for future drugs.
Animals↗
Treatment of trigeminal neuralgia by posterior fossa microvascular decompression.
A series of 109 cases of microvascular decompression for intractable trigeminal neuralgia was reviewed. Operations were performed by a single surgeon and cases were reviewed independently by the one author. The failure rate in this study was 17.6%. A further 6.5% of cases endured brief recurrences not requiring treatment. Two-thirds of significant recurrences occurred within the initial 12 months. Long-term complications were experienced in 7.4% of cases. There was one postoperative mortality occurring in a patient with a large fibroblastic meningioma invading the brain stem. The classic Jannetta approach was modified following the first 32 cases allowing the cerebellum to be depressed inferiorly with a subsequent decline in the rate of loss of hearing from 12.5 to 3.7%. In over 70% of cases an aberrant superior cerebellar artery was found compressing the fifth cranial nerve. Patients had dental work performed in an attempt to control the pain prior to operation in 44% of cases.
Adult↗
Insulin sensitivity of adipocytes from inbred mouse strains resistant or sensitive to diet-induced obesity.
We evaluated insulin sensitivity in epididymal adipocytes from two mouse strains shown to be either sensitive (AKR/J, n = 14) or resistant (SWR/J, n = 12) to the development of obesity when fed a high-fat diet. Half of each strain was fed a chow (CH) diet (12% fat), and half received a sweetened condensed milk (CM) diet (33% fat). After 1 wk, epididymal adipose depots were removed and digested with collagenase, and glucose transport was measured with labeled 2-deoxyglucose. Plasma glucose and insulin were slightly higher in AKR/J than SWR/J mice (glucose: 139.7 vs. 118.8 mg/dl, P < 0.06; insulin: 3.45 vs. 2.99 ng/ml, P < 0.04). One week of high-fat feeding increased adipose depot mass and carcass lipid in both strains to approximately the same extent. Adipocytes from AKR/J mice had greater insulin-stimulated glucose transport compared with SWR/J mice at both submaximal and maximal insulin levels (P < 0.0001). Short-term feeding of the high-fat diet increased AKR/J adipocyte insulin sensitivity but decreased the sensitivity of SWR/J adipocytes to insulin. The differences in adipocyte insulin sensitivity between strains were not explained by differences in adipocyte cell size. Access to the high-fat CM diet for 12 wk increased total dissected adipose depot size by 209% in the AKR/J mice and 82% in the SWR/J mice. These data clearly demonstrate that the two strains differ in adipocyte insulin sensitivity as well as sensitivity to dietary obesity. Increased adipocyte insulin sensitivity could contribute to a predisposition to increase adipose tissue lipid stores with diets high in fat content.
Adipocytes↗