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Biomedical subjects

N Finer

Publications and source records attributed to N Finer.

At least 37 records · Page 2Linked to original sources
PubMed2000

One-year treatment of obesity: a randomized, double-blind, placebo-controlled, multicentre study of orlistat, a gastrointestinal lipase inhibitor.

OBJECTIVE: To assess the efficacy and tolerability of orlistat (Xenical) in producing and maintaining weight loss over a 12-month period. DESIGN: Patients were randomized to double-blind treatment with either orlistat 120 mg or placebo three times daily, in conjunction with a low-energy diet, for 12 months. SETTING: Five centres in the UK. SUBJECTS: 228 obese adult patients with body mass index between 30 and 43 kg/m2 and mean weight 97 kg (range 74-144 kg). INTERVENTIONS: All patients were prescribed a low-energy diet, providing 30% of energy from fat, designed to produce an individually tailored energy deficit of approximately 600 kcal/day, for a run-in period of 4 weeks and then 12 months, plus orlistat 120 mg or placebo three times daily. MAIN OUTCOME MEASURES: Change in body weight (the primary efficacy parameter), waist circumference and adverse events were reviewed regularly, together with serum lipids, insulin, glucose and plasma levels of fat-soluble vitamins and beta carotene. RESULTS: Based on an intent-to-treat analysis, after 1 y of treatment patients receiving orlistat had lost an average of 8.5% of their initial body weight compared with 5.4% for placebo-treated patients; 35% of the orlistat group lost at least 5% of body weight compared with 21% of the placebo group (P < 0.05), and 28% and 17%, respectively (P = 0.04) lost at least 10% of body weight. Orlistat-treated patients showed significant decreases (P < 0.05) in serum levels of total cholesterol, low density lipoprotein cholesterol, and in the low density lipoprotein: high density lipoprotein ratio in comparison with placebo. Both groups had similar adverse-event profiles, except for gastrointestinal events, which were 26% more frequent in the orlistat group but were mostly mild and transient. To maintain normal plasma levels of fat-soluble vitamins, supplements of vitamins A, D and E were given to 1.8%, 8.0% and 3.6%, respectively, of orlistat-treated patients, compared with 0.9% of placebo-treated patients for each vitamin type. After 1 y, the decrease in vitamin E and beta carotene was significantly greater in orlistat-treated patients compared with those receiving placebo (P < 0.001). No significant change was found in the mean vitamin E:total cholesterol ratio in either group after 52 weeks. CONCLUSIONS: Orlistat, in conjunction with a low-energy diet, produced greater and more frequent significant weight loss than placebo during 1 y of treatment. One-third of orlistat-treated patients achieved clinically relevant weight loss (> or = 5% initial body weight). There was also an improvement in relevant serum lipid parameters. Fat-soluble vitamin supplements may be required during chronic therapy. Orlistat was well tolerated and offers a promising new approach to the long-term management of obesity.

Adult↗
PubMed2000

Sibutramine is effective for weight loss and diabetic control in obesity with type 2 diabetes: a randomised, double-blind, placebo-controlled study.

AIM: To assess the efficacy and tolerability of sibutramine 15 mg once daily as a weight reduction agent in overweight and obese patients (body mass index (b.m.i.) > 26 kg/m2) with type 2 diabetes when given with a customised, reduced-calorie diet, and to evaluate the influence of weight loss on diabetic control. METHODS: Randomised, placebo-controlled, double-blind, parallel-group, 12-week study conducted at two hospital-based obesity/diabetes clinics. Patients were men and women aged 30-65 years, with b.m.i. > 26 kg/m2 and < or = 35 kg/m2 and treated or untreated type 2 diabetes diagnosed > or = 6 months previously. Each patient was given sibutramine 15 mg or placebo once daily and advised to follow a customised diet of 500 kcal/day less than the individual's energy needs. The principal measure of efficacy was change in body weight (b.w.). Additional efficacy measurements were changes in b.m.i., body composition as measured by dual-energy X-ray absorptiometry, and change in waist and hip measurements. Changes in diabetic control were assessed by blood glucose levels fasting and after a standard test meal, fasting insulin level, and glycosylated haemoglobin level. Adverse events (AEs) were monitored at each visit, and routine laboratory safety tests were done at 4-week intervals. RESULTS: Ninety-one patients were randomised into the study, 44 to placebo and 47 to sibutramine 15 mg once daily. Eighty-three patients (91%) completed the study, 40 (91%) on placebo and 43 (91%) on sibutramine. Mean weight reduction from baseline was statistically significantly greater with sibutramine than with placebo at every measurement and at the end of the study (2.4 vs. 0.1 kg at week 12; p < 0.001; intent-to-treat). The proportion of patients who lost > 5% of their baseline b.w. was 19% in the sibutramine group and 0% in the placebo group (p < 0.001; 95% confidence interval: 9, 30). Patients receiving sibutramine lost significantly more fat mass compared with those receiving placebo, as a percentage (1.0% vs. 0.1%; p < 0.05) and in absolute terms (1.8 vs. 0.2 kg, p < 0.001). Loss of lean mass was not significantly different between the groups. Mean peak blood glucose concentration after a standard test meal decreased by 1.1 mmol/l in the sibutramine treatment group but increased by 0.5 mmol/l in the placebo group (p = 0.04; difference in means, 1.6, 95% confidence interval: -3.3, -0.1). Mean fasting blood glucose decreased by 0.3 mmol/l with sibutramine and increased by 1.4 mmol/l with placebo. Mean glycosylated haemoglobin levels decreased by 0.3% units with sibutramine treatment, and were unchanged with placebo. However, more sibutramine-treated patients (33%) than placebo-treated patients (5%) achieved decreases in glycosylated haemoglobin of 1% unit or more (p < 0.05). Sibutramine 15 mg was safe and well tolerated, and AEs were mostly mild or moderate in severity. No significant differences were found between treatment groups in blood pressure. No clinically significant conduction or rhythm abnormalities were observed on ECG. CONCLUSIONS: Sibutramine 15 mg once daily with a customised, reduced-calorie diet significantly reduced weight compared with placebo in overweight and obese patients (b.m.i. > 26 kg/m2) with type 2 diabetes. Sibutramine was well tolerated, and significant improvement in diabetic control was seen in conjunction with weight reduction on sibutramine treatment.

Absorptiometry, Photon↗
PubMed2000

Redefining type 2 diabetes: 'diabesity' or 'obesity dependent diabetes mellitus'?

Type 2 diabetes is considered by diabetes physicians as a complex and heterogeneous disease with a poorly understood aetiology, apart from the fact that there is a strong genetic propensity that becomes overt when exposed to a typical Western lifestyle. Our clinical targets are now moving from controlling the disease to preventing it. Do we need to await more research on the aetiology and pathophysiology before establishing a preventive strategy? No, the pathophysiology may be poorly understood, but there is now solid evidence that type 2 diabetes is a disease of fatness. New, controlled, clinical trials show that as little as 5% weight loss is sufficient to prevent most obese subjects with impaired glucose tolerance developing type 2 diabetes. Since type 2 diabetes is obesity dependent, and obesity is the main aetiogical cause of type 2 diabetes, we propose the term 'diabesity' should be adopted.

Adipose Tissue↗
PubMed1997

Present and future pharmacological approaches.

There is evidence that drugs altering food intake such as dexfenfluramine, sibutramine and orlistat have useful therapeutic effects, with an acceptable side effect profile. 'Thermogenic' drugs, such as ephedrine and caffeine, are also effective, but less well tolerated and may, in any case, work by producing anorexia. The state of drug treatment for obesity now is similar to the early days of antihypertensive treatment in the 1960s when reserpine, ganglion blockers and nonselective adrenergic blocker were all that was available. There is considerable reason for optimism that the next 10 years will bring better treatments for the obese.

Appetite Regulation↗
PubMed1996

Predischarge respiratory recordings in very low birth weight newborn infants.

PREMISE: There may be a relationship between undiagnosed, ongoing apnea occurring at discharge in infants of very low birth weight and sudden infant death syndrome. OBJECTIVE: To describe patterns of apnea in former very low birth weight (< 1251 gm) infants thought to be ready for hospital discharge, and to determine the relationship between apnea at discharge and later adverse events-in particular, apparent life-threatening events (ALTEs) and sudden infant death syndrome. METHODS: One hundred eighty-seven infants had 24-hour (four-channel) recordings scored for apnea (> 12 seconds in duration) frequency, type, and duration. Infants were followed by telephone interview at 2, 4, and 6 months after discharge from the hospital. RESULTS: Ninety-one percent of recordings displayed significant apnea, the majority of episodes of apnea were obstructive, and about half occurred during feedings. Infants had as many as 43 episodes in a 24-hour period, with a maximum duration of 62 seconds. There was no relationship between severity of pre-discharge episodes of apnea and ALTEs. No infants died during follow-up. CONCLUSIONS: Predischarge multichannel recordings may identify infants with apnea that is not otherwise clinically apparent but do not predict the risk of an ALTE.

Apnea↗
PubMed1995

Timing of repair of congenital diaphragmatic hernia requiring extracorporeal membrane oxygenation support.

Treatment of congenital diaphragmatic hernia (CDH) has undergone a revolutionary change in philosophy, from previous urgent repair to the present practice of stabilization and delayed repair. However, when extracorporeal membrane oxygenation (ECMO) is required, many people believe that the risk of postoperative pulmonary hypertension (PPHN) mandates hernia repair while on ECMO. This report details the experience in two ECMO centers with stabilization, ECMO if required, and CDH repair post-ECMO. All CDH patients symptomatic in the first hour of life with a gestational age of at least 34 weeks during the period were reviewed retrospectively. Standard criteria were used to select patients for ECMO. High-frequency jet or oscillating ventilators and nitric oxide were not routinely available throughout the study period, but were used in some of the more recent patients. A total of 60 patients presented to the two centers; 24 cases were stabilized with conventional management, repair of the CDH was done elective, and survival was 100%. Eight patients were referred after having repair elsewhere; six survived (75%). The two deaths were attributable to associated lethal lesions--complex cyanotic heart disease and alveolar capillary dysplasia. Eight patients who required ECMO were managed with the intention of repairing the defect on ECMO. Four survived (50%). Two patients died before repair. Twenty patients were managed with ECMO, with the intention of repairing the defect after decannulation. Overall survival was 13 (65%), deaths were caused by pre-ECMO hypoxia, pulmonary insufficiency, and associated cardiac disease. No patient had recurrent pulmonary hypertension after late repair.(ABSTRACT TRUNCATED AT 250 WORDS)

Capillaries↗
PubMed1995

Effects of two rescue doses of synthetic surfactant in 344 infants with respiratory distress syndrome weighing 750 to 1249 grams: a double-blind, placebo-controlled multicenter Canadian trial. Canadian Exosurf Neonatal Study Group.

In a multicenter, double-blind, placebo-controlled rescue trial conducted at 13 Canadian hospitals, two 5 ml/kg doses of a synthetic surfactant or air placebo were administered to 344 infants with birth weights of 750 to 1249 gm who had established respiratory distress syndrome and an arterial/alveolar oxygen tension ratio less than 0.22. The first dose was given between 2 and 24 hours of age, and the second dose was given 12 hours later to the infants remaining on mechanical ventilation. Infants were stratified at study entry by birth weight and gender. The trial was terminated short of the targeted sample size because significant reductions in mortality were observed in another rescue trial completed in the United States in the same weight class of infants. Despite premature termination of the trial, the rate of survival without bronchopulmonary dysplasia was increased (61% vs 52%; p = 0.046) in infants treated with surfactant. In addition, there was a significant reduction in the incidence of overall pulmonary air leak (46% vs 32%; p = 0.009), pneumothorax (27% vs 17%; p = 0.023), and pulmonary interstitial emphysema (40% vs 28%; p = 0.018) in infants treated with synthetic surfactant. There was no difference in the incidence of bronchopulmonary dysplasia, apnea, or pulmonary hemorrhage. Significant improvements in alveolar-arterial oxygen tension gradient, arterial/alveolar oxygen tension ratio, and oxygen and ventilator requirements through day 7 were present. These findings indicate that rescue therapy with synthetic surfactant can improve outcome for premature infants weighing 750 to 1249 gm with respiratory distress syndrome.

Air↗
PubMed1995

Two cases of Wegener's granulomatosis involving the pituitary.

We describe two patients with Wegener's granulomatosis involving the pituitary. The diagnosis of Wegener's granulomatosis was inferred from the histological appearance of biopsy tissue and the presence of anti-neutrophil cytoplasmic antibodies with cytoplasmic distribution in the first case, in which disease remained confined to the pituitary, causing anterior and posterior pituitary dysfunction. In the second case the diagnosis was made by the progressive involvement of other organ systems, compatible histology and the presence of anti-neutrophil cytoplasmic antibodies with cytoplasmic distribution. In neither patient did posterior pituitary dysfunction respond to immunosuppressive therapy, despite remission of other features of systemic vasculitis. Panhypopituitarism in association with isolated pituitary Wegener's granulomatosis has not previously been described.

Adult↗
PubMed1992

Pulmonary hemorrhage in premature infants after treatment with synthetic surfactant: an autopsy evaluation. The American Exosurf Neonatal Study Group I, and the Canadian Exosurf Neonatal Study Group.

In an across study analysis of five multicenter, placebo-controlled trials of the synthetic surfactant, Exosurf Neonatal in infants weighing at least 700 gm, the incidence of clinical pulmonary hemorrhage was 1.9% in treated infants and 1.0% in control infants. To investigate whether a similar increase was also present histologically at postmortem examination, a blinded retrospective review of all autopsy reports from infants dying during these five trials was conducted. Pulmonary hemorrhage was present in 55% of 159 infants undergoing autopsy; the incidence was not different in infants treated with surfactant or air placebo. Birth weight was inversely related to the incidence of pulmonary hemorrhage in both groups. Pulmonary pathologic findings significantly associated with pulmonary hemorrhage included pulmonary interstitial emphysema and necrotizing laryngotracheitis in both groups. In the surfactant group, patent ductus arteriosus, intraventricular hemorrhage, and pneumothorax were significantly more frequent among those who developed pulmonary hemorrhage. In contrast to clinical diagnosis, pathologic diagnosis of pulmonary hemorrhage at autopsy was not more common in infants treated with Exosurf Neonatal.

Autopsy↗
PubMed1992

Drug therapy after very-low-calorie diets.

Very-low-calorie diets (VLCDs) are effective at reducing weight, even in patients who have often failed with conventional diets. Maintaining weight lost by means of a VLCD remains a clinical challenge. Attempts to prevent weight regain by dietary reeducation or by more formal behavior-modification techniques are not easily applicable to large numbers of patients and are not always successful; the use of drugs to maintain and improve upon initial VLCD success could be of real clinical value. Pharmacological treatment of obesity has evolved in recent years with the development and licensing of potent serotonin agonists, such as dexfenfluramine (dF), acting as nonstimulant anorectic agents. Thermogenic drugs are not yet as advanced in clinical development and evaluation but offer the prospect of increasing energy output in the reduced obese patient. Drugs used to treat obesity need to be effective, to be safe, not to exhibit drug tolerance, and ideally, to be shown to reduce morbidity or mortality from obesity, particularly because treatment will need to be prolonged. Such requirements are not unique for treating obesity, they are similar for drugs used to treat other metabolic diseases such as hypercholesterolemia or diabetes. VLCD followed by dF has been shown to be effective. A double-blind trial randomized 45 patients who had successfully completed 8 wk of treatment on the Cambridge diet to either placebo or dF 15 mg twice daily for 26 wk. Patients continued on a diet giving 60-75% of daily energy needs.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Ceftazidime versus aminoglycoside and (ureido)penicillin combination in the empirical treatment of serious infection.

Urgent treatment of serious infections with broad spectrum antibiotics usually starts before bacteriological evidence of the infective organism(s) becomes available. In this study 471 patients with a clinical diagnosis of sepsis were treated empirically with ceftazidime (CAZ) monotherapy (249 patients), or with an aminoglycoside+(ureido)penicillin combination (AG+PEN) (222 patients) to establish clinical outcome and bacteriological response. Up to 72 h post-treatment 94.5% of patients in the CAZ group and 93.8% in the AG+PEN group were treated successfully (treatment difference 0.7%, P < 0.01, 95% confidence interval -3.8%, 5.2%); 2-4 weeks after treatment neither regimen proved clinically superior. The differences in bacteriological response up to 72 h, and at 2-4 weeks after treatment, were 5.6% and 12.4% in favour of CAZ, however, these were not statistically significant. Overall, 56 patients reported 72 adverse events in the CAZ group, compared with 33 patients reporting 41 adverse events in the AG+PEN group. Deaths, 40 on CAZ and 21 on AG+PEN, were mainly related to their underlying condition. The two regimens were shown to be clinically equivalent in seriously ill patients treated empirically.

Adult↗
PubMed1992

Body weight evolution during dexfenfluramine treatment after initial weight control.

While very low calorie diets (VLCD) can lead to rapid weight loss, even in patients who have often failed with conventional diets, maintaining this loss remains a clinical challenge. Since dietary re-education or more formal behaviour modification techniques are not easily applicable to large numbers of patients and are not always successful, drugs to maintain and improve upon initial VLCD success would be of clinical benefit. Pharmacological treatment of obesity has evolved in recent years with the development and licensing of potent serotonin agonists, such as dexfenfluramine (D-F). VLCD followed by D-F has been shown to be effective. A double-blind trial randomized 45 patients who had successfully completed eight weeks' VLCD treatment, to either placebo or D-F 15 mg b.d. for 26 weeks. Patients continued on a diet giving 60-75% of daily energy needs. Patients treated with D-F had lost 14.9 +/- 0.9 kg on the Cambridge diet and a further 5.8 +/- 1.8 kg during the drug treatment. In contrast, patients who received placebo regained 2.9 +/- 1.3 kg of the 13.5 +/- 1.0 kg they had lost during VLCD. The total weight loss after 34 weeks in total was thus 21.3 +/- 2.6 versus 11.3 +/- 1.9 kg. Patients were offered the option of continuing on D-F, or switching from placebo, in an open continuation of the trial. Ten patients, regaining weight on placebo, stabilized their weight without further regain over the next 24 weeks when switched to D-F.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

The natural history of the appearance of apnea of prematurity.

Twenty healthy preterm infants of less than 34 wk gestation were studied with continuous recordings, commencing within 8 h of birth, for up to 1 wk of age to determine the usual time course of the appearance of apnea and to classify apnea types. Airway occlusion studies were also performed on a regular basis to determine whether apneic spells were preceded or followed by a reduction in central respiratory drive. Apneic spells of greater than 15 s duration accompanied by hypoxia or bradycardia occurred in all infants before 24 h of age. The frequency of apneic spells was highest in the first 24 h after birth with a mean frequency of 0.9/h and gradually reduced thereafter, falling to 0.2/h by 5 d of age (p less than 0.01). Apneic spells were more likely to be obstructive in the first 2 d of life than thereafter (p less than 0.05). Central apnea was proportionately significantly less frequent during this time period. Reduced respiratory drive, as demonstrated by airway occlusion pressures, was associated with more frequent apnea and was evident at the first occlusion study, which frequently preceded the first significant apnea.

Age Factors↗