Identification of educational needs in the management of overweight and obesity: results of an international survey of attitudes and practice.

Despite the availability of a growing range of interventions to assist control of body weight for people with excess weight or obesity, only a small proportion of people achieve their weight loss goals and are able to maintain body weight reductions in the long term. Negative attitudes and beliefs are often found among physicians and others involved in treating obesity and may adversely impact the effectiveness of management. In this international study, healthcare professionals were invited to complete an online survey of their attitudes and practice in the management of excess body weight. A total of 335 clinicians completed the survey of whom approximately half were based in Europe. A key finding from the survey is that, while participants are generally confident in their ability to manage overweight and obesity effectively, they also report that most of their patients are not successful in achieving their weight loss goals. At the same time, participants tended to overestimate the effectiveness of current medical management in maintaining reductions in body weight. Educational initiatives addressing the real-life effectiveness of different weight control interventions may help to close the gap between clinicians' perceptions and reality in the management of excess body weight.

Alterations in key gluconeogenic regulators with age and endurance training.

The purpose of the present investigation was to examine changes in six potential regulators of hepatic gluconeogenesis with normal aging and endurance training: fructose 2,6-bisphosphate (F 2,6-P2), mitochondrial and cytosolic phosphoenolpyruvate carboxykinase (PEPCK) activity, PEPCK mRNA, and pyruvate carboxylase and malate dehydrogenase activity. Young (4 months), middle-aged (12 months), and old (22 months) male-Fischer 344 rats (N = 66) were divided into trained and sedentary groups. Trained animals were run 1 h/d, 5 d/wk for 10 weeks at treadmill speeds of 75% age-specific maximal running capacity. Animals were killed at rest, and the right main lobe of the liver was removed. F 2,6-P2 levels were significantly greater in old compared with young animals regardless of training condition (119% and 80% increase in old trained and untrained animals, respectively). No changes were found with training. Rates of cytosolic PEPCK activity declined significantly with age in both trained (1.3 +/- 0.1, 1.0 +/- 0.1, and 0.7 +/- 0.1 mumol/g/min in young, middle-aged, and old, respectively) and untrained (1.3 +/- 0.1, 1.1 +/- 0.1, and 0.8 +/- 0.2 mumol/g/min) groups. Training did not result in any significant differences between age groups. PEPCK gene expression (mRNA) determined by Northern blot analysis decreased 30% in trained and untrained old animals compared to the young counterparts; again, training had no effect in any age group. No significant differences were found in pyruvate carboxylase, mitochondrial PEPCK, or malate dehydrogenase activity with either age or training. These results suggest that previous age-related declines found in hepatic gluconeogenic capacity can be attributed, in part, to changes in F 2,6-P2, cytosolic PEPCK activity, and PEPCK mRNA, but not to alterations in the activities of mitochondrial PEPCK, malate dehydrogenase, or pyruvate carboxylase. Since training had no effect on any regulator studied, the factors responsible for attenuation in the age-related decline in gluconeogenesis with training remain to be determined.

Cerebrospinal fluid angiotensin converting enzyme levels in the diagnosis of neurosarcoidosis.

Cerebrospinal fluid angiotensin converting enzyme (CSF-ACE) level was measured in two patients considered to have neurosarcoidosis, three patients with possible neurosarcoidosis and in 38 control patients suffering from prolapsed intervertebral discs. Both neurosarcoidosis patients had elevated levels (1.8 and 5.4 mumol/l/min) while the possible neurosarcoidosis patients had values similar to the control patients (mean 0.59 +/- 0.42 mumol/l/min). We suggest that CSF-ACE values may be of use in some patients as a diagnostic test for neurosarcoidosis and provide a reference range of normal controls.

The effect of testosterone replacement on plasma lipids and apolipoproteins.

Ten men with Klinefelter's syndrome were studied to assess the effect of testosterone replacement on plasma lipids and apolipoproteins. Measurements taken before the insertion of a testosterone ester implant were compared with those obtained 1 week and 4 weeks later. Mean plasma testosterone, androstenedione, total cholesterol and calculated LDL-cholesterol increased significantly after 1 and 4 weeks. No significant changes were seen in total plasma concentrations of HDL-cholesterol, HDL-cholesterol subfractions 2 and 3 or in apoplipoproteins A-I, A-II or B. A significant correlation was seen between total cholesterol and plasma oestradiol concentrations (Rs = 0.61; P less than 0.001). A significant negative correlation was seen between the concentrations of total testosterone and total triglyceride (Rs = -0.56; P less than 0.005) but not with the other lipid parameters. Testosterone replacement is associated with slight but potentially adverse changes in plasma cholesterol levels.

In vitro studies upon the release of gamma-glutamyltransferase from human liver.

Samples of human liver have been incubated in different fluids for up to 48 h and the released gamma-glutamyltransferase studied by gel chromatography on Sephacryl S-300 and polyacrylamide gradient gel electrophoresis. When human liver is incubated in serum, most of the released enzyme is of high Mr (greater than 1,000,000). Incubation in hepatic bile, or in a solution of glycochenodeoxycholate, results in the release of enzyme that is hydrophobic in nature and which reaggregates to a varying extent after the removal of bile salts. In contrast, incubation in saline, or in a solution of human albumin results in the release of a hydrophilic low Mr (about 120,000) form of the enzyme. These observations are discussed in relation to possible mechanisms for the release of these multiple forms.

Lactate dehydrogenase as a marker for testicular germ-cell tumours.

One hundred and eighty-four patients with testicular germ-cell tumours, 92 with seminoma and 92 with non-seminomatous germ-cell tumours (NSGCT) had total lactate dehydrogenase (LD) assay performed at the time of initial staging following orchidectomy. The proportion of patients with elevated plasma LD and the mean plasma LD increased with advancing stage and increasing tumour bulk for both seminoma and NSGCT. Of patients receiving cytotoxic chemotherapy, 87.5% with seminoma and 63% with NSGCT had elevated plasma LD with subsequent levels reflecting regression or progression of disease. Elevated plasma LD levels were seen in four of seven seminoma, and in 18 of 30 NSGCT patients relapsing after primary treatment. The LD assay provides useful information, and complements the routine measurement of alphafetoprotein (AFP) and beta human chorionic gonadotrophin (beta hCG) in the management of patients with testicular germ-cell tumours.

Multiple forms of gamma-glutamyltransferase: a clinical study.

We have measured the amounts of different molecular forms of gamma-glutamyltransferase (EC 2.3.2.2), leucine aminopeptidase (EC 3.4.11.2), and alkaline phosphatase (EC 3.1.3.1) in serum of patients with different types of liver disease. A high-molecular-mass (greater than 1 000 000 Da) form of gamma-glutamyltransferase and of each of the other enzymes is present in greatest amounts in patients with jaundice from extrahepatic obstruction. A gamma-glutamyltransferase form of intermediate molecular mass (250 000 to 500 000 Da) is present in the serum from most patients with liver disease and can be separated by electrophoresis into several bands. We found that one of these bands predominated in patients with extrahepatic obstructive jaundice, whereas the others predominated in patients with other liver diseases. Electrophoresis of serum gamma-glutamyltransferase may be of clinical value in distinguishing extrahepatic from intrahepatic causes of jaundice.

Physical properties of gamma-glutamyltransferase in human serum.

Using gel chromatography on Sephacryl S300 we have separated serum gamma-glutamyltransferase into three fractions with estimated relative molecular masses of (a) greater than 1000 000, (b) 250 000-500 000 and (c) about 120 000. Similarly, serum leucine aminopeptidase has been separated into three fractions. We have studied, particularly, the gamma-glutamyltransferase fraction of intermediate relative molecular mass (250 000-500 000) in serum from patients with a number of liver diseases. We have shown, both by polyanion and immuno-precipitation, that it consists significantly of a complex between gamma-glutamyltransferase and high density lipoprotein. The physical properties of this fraction, namely its mass and charge, can be altered by incubating serum with either bile or bile salts.

The nature of gamma-glutamyltransferase and other hepatocyte plasma membrane enzymes in human bile.

High molecular mass gamma-glutamyltransferase in human bile is converted by physiological concentrations of the bile salts glycocholate and glycochenodeoxycholate to a form with a molecular mass estimated by gel chromatography to be 165,000. A molecule of intermediate molecular mass estimated to be 330,000 is obtained following treatment with the non-ionic detergent Triton X-100. When human bile is centrifuged at 150,000 X g, between 25-73% of gamma-glutamyltransferase activity is recovered in the supernatant. This proportion is increased following prior addition of bile salts to the bile. Analogous results are obtained for the high molecular mass enzymes alkaline phosphatase and leucine aminopeptidase, present in human bile, and also considered to originate from the hepatocyte plasma membrane. From these results it is suggested that these high molecular mass enzymes found in bile may, in part at least, represent artefacts following aggregation of the enzymes in aqueous media containing no bile salts.

Gamma-glutamyltransferases in bile and sera from patients with extrahepatic biliary obstruction.

Gamma-glutamyltransferase has been studied in bile and sera from patients with extrahepatic biliary obstruction. In both fluids gamma-glutamyltransferase activity is found largely in the high molecular mass fraction present in the void volume following G200 gel chromatography and which remains at the origin after 7% polyacrylamide gel electrophoresis. When bile, sera and liver microsomes are treated with deoxycholate, a different form of gamma-glutamyltransferase, with an approximate molecular mass of 157 000 estimated by gel chromatography and of 125 000 by gradient gel electrophoresis, is obtained. After treatment with papain, all three types of specimen gave rise to a form of gamma-glutamyltransferase with a molecular mass of 115 000 estimated by gel chromatography and of 98 000 by gradient gel electrophoresis. The possible relationship between these various forms of gamma-glutamyltransferase, and their relevance to the increases in activity in serum seen in extrahepatic biliary obstruction, are discussed.

TSH response to TRH in substantial obesity.

TSH response to TRH stimulation was studied in 40 non-obese control females and in 40 obese female subjects 40-148 per cent in excess of their ideal weight prior to receiving dietary advice. One patient was found to be hypothyroid and was excluded from further study. There was no significant difference between the basal serum TSH concentration in the subjects and controls. Obese subjects however had significantly greater serum TSH concentrations at 20 and 60 min following TRH stimulation. The implciations of these findings are at present unexplained.

The significance of gross elevations of the erythrocyte sedimentation rate in a general medical unit.

One hundred consecutive patients with an ESR of 100 mm or more in the first hour admitted to a general medical unit were studied. Their mean age was 67 years and forty-seven were male. Three patients recovered without a satisfactory diagnosis. In thirty-three of the remainder a single diagnosis was considered responsible for the elevation of the ESR, and in the others multiple diagnoses were found. Infection was found in 60% of patients, malignancy in 28% (including 7% with myelomatosis), rheumatoid disease in 20% and renal disease in 11%. 34% of patients died within 6 months of entry into the study. In the absence of rheumatoid disease or a paraproteinaemia, elevation of the ESR in excess of 60 mm in the first hour at 1 month or longer was associated with a particularly poor prognosis. This study has shown the diagnostic implications of an ESR of 100 mm or more in the first hour and the prognostic significance of a persistent elevation of the ESR.

Hypothalmic-pituitary adrenal responsiveness to dexamethasone-insulin tolerance test in acromegalic patients before and during treatment with bromocriptine.

Insulin tolerance tests were carried out in 10 acromegalic patients after 1 mg dexamethasone had been given the previous evening (DEX-ITT). Nine patients showed a rise in plasma 11-OHCS and four patients showed a rise in plasma growth hormone (GH) levels. These responses were unaltered after treatment with bromocriptine 10 mg daily for two months. Basal plasma GH levels fell in 6 of the patients and the mean plasma GH levels of the 10 patients during an oral glucose tolerance test (OGTT) fell from 63.2 +/- 25.5 ng/ml before treatment to 53.0 +/- 27.1 ng/ml (mean +/- sem; p less than 0.05). These data fail to confirm a previous report of abnormal hypothalmic-pituitary-adrenal suppressibility during a DEX-ITT in acromegalic patients. They also indicate that bromcriptine does not alter the responses of plasma 11-OHCS and plasma GH to the DEX-ITT despite lowering plasma GH levels.

Serum protein analysis and bone marrow cytology in patients with an extreme elevation of the erythrocyte sedimentation rate.

One hundred patients in whom an Erythrocyte Sedimentation Rate (ESR) in excess of 100 mm. in the first hour was found on 2 consecutive occasions were investigated. Serum protein electrophoresis was performed on 96 of these patients and bone marrow examination on 55 patients. Acute infection was the commonest diagnosis though the majority of patients had 2 or more separate conditions each contributing to the elevation of the ESR. Quantitive serum protein electrophoresis was abnormal in all but one patient and was of limited diagnostic value. A definite band in the globulin region was detected in 11 patients, 7 of whom were found to have myelomatosis. Bone marrow examination was useful only in patients with a discrete band in the globulin fraction or with a specific haematological abnormality. It is suggested, therefore, that bone marrow examination be confined to patients with such abnormalities irrespective of an elevation of their ESR.

Plasma and urinary digoxin in thyroid dysfunction.

The response to a single oral dose of 0.5 mg digoxin has been studied in eight patients, of whom four were hyperthyroid and four were hypothyroid, both before and after treatment for their thyroid dysfunction. The post-dose plasma digoxin levels were significantly lower in the hyperthyroid patients when they were thyrotoxic than when they became euthyroid. In only one hypothyroid patient was the post-dose plasma digoxin level significantly higher before treatment than it was after and in the others the digoxin values reached were either the same as, or lower than, before treatment. There was a significant correlation between the creatinine clearance and the urinary concentrations of digoxin and these both altered with change in thyroid status. Total urinary digoxin excretion did not change. Pharmacokinetic analysis suggested that digoxin was distributed in a way compatible with a two-compartment model and that the volume of the central compartment was high in thyrotoxic patients and low in hypothyroid patients. In both cases it reverted to a median value after treatment. It is recommended that plasma digoxin levels should be monitored in all patients with thyroid dysfunction who require therapeutic digoxin.

Thyroxine and triiodothyronine levels in hyperthyroid patients during treatment with propranolol.

Serum triiodothyronine (T3) and thyroxine (T4) levels were measured in twelve hyperthyroid patients before and after treatment with propranolol, 40 mg four times daily, for 2 weeks. There was a significant fall in serum T3 and a significant rise in serum T4 concentrations in the group as a whole and it was concluded that the clinical effectiveness of propranolol in hyperthyroidism may be mediated in part by its action on the peripheral metabolism of thyroid hormones. Propranolol treatment should be withdrawn gradually as removal of the suppressive action of the drug on thyroid hormone metabolism is potentially hazardous, particularly in patients with ischaemic heart disease.

Evidence of osteomalacia in an outpatient group of adult epileptics.

A review of 50 adult epileptics who had taken anticonvulsant drugs for 10 or more years showed a decrease in the concentration of serum phosphate and calcium and an increase in the activity of alkaline phosphatase in 22% of the patients. Plasma albumin and gamma-globulin levels were higher than in control subjects. All the patients lived at home and the dietary intake of calcium and vitamin D was often borderline normal or low. Six patients were submitted to bone biopsy and of these, 4 showed histological osteomalacia. Gastrointestinal disease did not appear to be a significant factor. None of the patients had symptoms or signs attributable to osteomalacia which does not seem to be of serious significance. All the patients were taking at least two drugs and it was not possible to assess the relative importance of the various drugs. A prospective study is needed. Measurements of serum calcium, phosphorus, and alkaline phosphatase should be performed at intervals on patients who are receiving anticonvulsant therapy. Treatment with calciferol may be indicated.

Plasma renin activity in diabetic autonomic neuropathy.

Postural changes in plasma renin activity were studied in three groups of age and duration-matched male diabetics (potent, impotent and with postural hypotension) and in non-diabetic control subjects. Those diabetic subjects with postural hypotension due to automatic neuropathy had no increase in plasma renin activity to the erect posture whereas both the potent and impotent groups had similar plasma renin activity responses to the control subjects. There was a significant inverse correlation between the rise in plasma renin activity on standing and the postural drop in blood pressure (r = 0.476, P less than 0.01) but no correlation with other tests of autonomic reflex function such as the Valsalva manoeuvre and blood pressure response to sustained handgrip. The results suggested that the lesion responsible for the postural hypotension is in the efferent sympathetic pathway. However, neuropathy per se did not wholly explain the decreased postural plasma renin activity response. Diabetic nephropathy, with involvement of cells of juxtaglomerular apparatus, may also be implicated.