Search

Studies comparing the accuracy of clinical diagnosis in unselected patients who died in hospital in different medical eras have shown no decline of errors in the main diagnosis. We assessed changes in diagnostic accuracy over 20 years.We analysed retrospectively diagnostic errors, with use of necropsy as the gold standard for diagnosis. We randomly selected 300 patients who died at a tertiary-care teaching hospital in Switzerland--100 in each of 1972, 1982, and 1992. We classified discrepancies between clinical diagnosis and necropsy findings as major and minor errors.The overall necropsy rate at the hospital stayed at around 90% for the whole period. During the study, the frequency of major discrepancies declined significantly (1972, 30%; 1982, 18%; 1992, 14%; p=0.007). The rate of minor diagnostic errors increased significantly from 23% in 1972 to 46% in 1992 (p0.001). The increase in overall diagnostic accuracy occurred mainly because of a significant improvement in specificity for cardiovascular diseases (1972, 85%; 1982, 82%; 1992, 97%; p=0.034) and non-significantly improved sensitivity (1972, 69%; 1982, 82%; 1992, 86%; p=0.061). Sensitivity also improved for infectious diseases (1972, 25%; 1982, 67%; 1992, 86%; p=0.036). Sensitivity and specificity for neoplastic diseases were high originally and did not change. The total number of diagnostic procedures per year increased from 191 in 1972 to 259 in 1992, mainly because of non-invasive techniques, such as ultrasonography, and endoscopies.The frequency of major diagnostic errors in unselected patients who died in hospital was halved over 20 years, probably because of improved clinical skills and new diagnostic procedures.

A systematic review of the second half of the last century suggested that diagnostic errors have decreased over time. Our previous study covering the years 1972-1992 was then the only time series showing a significant reduction of diagnostic errors from a single institution. We report here the results of a follow-up study a decade later. We analyzed discrepancies between clinical and autoptic diagnoses in 100 randomly selected medical patients who died in the wards and in the medical intensive care unit at a tertiary-care teaching hospital in Switzerland in the year 2002. Autopsy rate declined from around 90% in the years from 1972 to 1992 to 54% in the present study. Major diagnostic errors (class I and II) declined significantly from 30 to 7% (P

Summary OBJECTIVE Adults with long-standing GH deficiency have a decreased lean body mass and an increased fat mass. We investigated the effects of the abnormal body composition on glucose turnover and fuel metabolism. DESIGN Cross-sectional analysis. PATIENTS Twenty-four adults with acquired GH deficiency and a wide range of adiposity (body mass index from 18·8 to 42·3 kg/m2). MEASUREMENTS In the post-absorptive state glucose turnover was measured following intravenous injection of 3-3H-glucose and leucine oxidation was assessed following intravenous injection of 1-14C-leuclne. Glucose and fat oxidation were calculated from indirect calorimetry using protein oxidation derived from leucine oxidation. RESULTS Total glucose turnover was 692 ± 146 μmol/min (mean ± SD) and Increased with height (r= 0·70, P= 0·0003) and with lean body mass (LBM) (r= 0·80, P < 0·0001). Glucose turnover expressed per kg LBM was in the published normal range (14·2 ± 2·1 pmol/kg LBM min). Glucose oxidation was 47 ± 27% of glucose turnover and increased with LBM (r= 0·59, P= 0·008) but not with height (r= 0·32, NS). Glucose turnover increased with increasing fat oxidation (r= 0·61, P= 0·006). The non-oxidative part of glucose turnover was positively correlated with fat oxidation (r= 0·82, P= 0·0001) and inversely with the respiratory quotient (r= -0·81, P < 0·0001). Ketone body concentration (r= 0·55, P= 0·03), but not free fatty acid levels (r= 0·21, NS), correlated with fat oxidation. Fasting plasma glucagon levels were elevated (35 ± 13 vs 9 ± 19pmol/l (published controls) and inversely related to lean body mass (r= -0·44, P= 0·04). CONCLUSIONS Adults with GH deficiency studied after an overnight fast have changes In glucose and fuel metabolism seen In normal subjects after more prolonged fasting suggesting that adults with hormone deficiency have reduced carbohydrate stores.

Diagnosis of atheroembolic disease (AD) is challenging, because no specific test is available and AD often masquerades as other clinical conditions. We conducted the current study to investigate the relative frequency of autopsy-proven AD over time, to describe its clinical presentation, and to identify risk factors for AD. We screened 2066 autopsy reports from 1995 to 2006 for AD. For each AD case, a control patient without AD was matched for age, sex, and autopsy year. Diagnostic and therapeutic interventions (surgery, catheter interventions, and drug treatment) in the last 6 months before death, as well as clinical and laboratory parameters during the last hospitalization, were retrieved from electronic charts. We identified 51 patients with AD. Among these only 6 (12%) had been diagnosed clinically. The organs most often affected were kidney (71%), spleen (37%), and lower gastrointestinal tract (22%). The relative AD frequency decreased over time from 3.5 to 0.5 per 100 autopsies, whereas the frequency of clinically suspected and biopsy-proven AD remained constant. Among clinical signs, skin lesions such as livedo reticularis and blue toe (33% vs. 14%; p = 0.04) were significantly increased in AD patients compared with the matched controls. We also observed a trend for higher incidence of eosinophilia and proteinuria in AD patients. Vascular interventions within 6 months before death were highly associated with AD (55% vs. 29%; p = 0.01), and in a multivariable analysis this remained the only significant risk factor for AD. Thus, the diagnosis of AD is frequently missed. Vascular interventions represent the most important risk factor for AD and should be performed restrictively in high-risk patients.

1. The relationship of lean body mass, plasma insulin concentration and leucocyte active sodium transport with basal metabolic rate was investigated in 24 adults with growth hormone deficiency before and after treatment with recombinant human growth hormone and in 10 patients with untreated acromegaly. 2. Based on total-body potassium determined by whole-body 40K counting, patients with acromegaly had increased lean body mass, whereas lack of growth hormone was associated with decreased lean body mass. 3. By indirect calorimetry, patients with acromegaly had increased basal metabolic rates and patients with growth hormone deficiency had decreased values when expressed as percentages of values predicted from the WHO/FAO/UNU equations. Basal metabolic rate expressed in terms of lean body mass was similar in acromegaly and growth hormone deficiency, but was higher than normal in both patient groups. 4. The leucocyte ouabain-sensitive sodium efflux rate constant was decreased in both patients with acromegaly and patients with growth hormone deficiency, and there was no correlation with basal energy expenditure, fasting plasma insulin level or serum growth hormone level. 5. There was no increase in the sodium efflux rate constant in patients with growth hormone deficiency after 1 month on treatment with recombinant human growth hormone. 6. Apparent differences in basal metabolic rate in growth hormone deficiency and acromegaly are due to changes in lean body mass. Both adults with growth hormone deficiency and patients with acromegaly have increased energy expenditure, probably owing to changes in fuel metabolism which are not reflected in the leucocyte sodium pump activity.

The effect of recombinant DNA human growth hormone (rhGH) treatment in adults with growth hormone (GH) deficiency was studied in 24 patients in a double-blind placebo-controlled trial. The dose was 0.07 U/kg body wt daily. After 6 mo of treatment, significant increases were noted in the rhGH group for total cross-sectional area of thigh muscle (+11.2 +/- 3.1 vs. -0.5 +/- 3.0 cm2; P = 0.015 vs. placebo) and quadriceps muscle (+4.1 +/- 0.8 vs. +0.4 +/- 1.2 cm2; P = 0.031) measured by computerized tomography. Strong correlations were noted between lean body mass (measured as total body potassium) and total thigh muscle area in normal and GH-deficient adults both before and after rhGH treatment. Strength of hip flexors (+1.25 +/- 0.27 vs. +0.25 +/- 0.12 z-scores; P = 0.004) and limb girdle muscles increased (P = 0.02) in the rhGH group. We conclude that 1) rhGH increases lean tissue and skeletal muscle mass in adults with human GH deficiency, 2) this suggests a role for GH in the regulation of body composition of adult humans, 3) the increase in strength of limb girdle muscles after rhGH treatment suggests that adults with GH deficiency may have a proximal myopathy, and 4) the failure to demonstrate an increase in strength in other muscle groups may require the study of larger numbers of patients.

We assessed the accuracy of C-reactive protein (CRP) levels and lymphocyte counts to predict a mechanical complication (MC) after myocardial infarction (MI). Within 10 years, we identified 36 patients with 39 echocardiographically confirmed MC within 30 days of MI: ventricular septal defect (17 cases), papillary muscle rupture (10 cases), and left ventricular free wall rupture (12 cases). They were compared to 41 controls with an uncomplicated hospital course after MI. Peak CRP levels and minimum relative lymphocyte counts obtained within 96 h of the acute MI (AMI) and before diagnosis of the complication were compared with clinical parameters. Prior to the MC, peak CRP levels were significantly higher (p < 0.001) and relative lymphocyte counts lower (p < 0.001) than in controls while creatine kinase levels did not differ (p = nonsignificant). Using multivariate logistic regression, the following score was identified to have excellent prognostic significance for MC: CRP (mg/l) – 10 × Lyc (%). The area under the receiver-operating characteristic curve was 0.90 ± 0.05 (p < 0.001). Combined use of CRP levels and relative lymphocyte counts may be helpful in accurately predicting an MC after AMI and should therefore be routinely assessed.

The long term effects of GH replacement in adult GH-deficient (GHD) patients have not yet been clarified. We studied 21 GHD adults who originally took part in a randomized, double blind, placebo-controlled trial of GH treatment in 1987. After completion of that trial, 10 patients received continuous GH replacement for the subsequent 10 yr, whereas 11 did not. A group of 11 age- and sex-matched normal controls were also studied in 1987 and 1997. Lean body mass, as assessed by total body potassium measurement and computed tomography scanning of the dominant thigh, increased in the GH-treated group (P < 0.01 for both) only (P < 0.05 between groups for total body potassium). Low density lipoprotein cholesterol decreased in the GH-treated group (P < 0.05) only. Carotid intima media thickness was significantly greater (P < 0.05) in the untreated group than in the GH-treated group. Assessment of psychological well-being using the Nottingham Health Profile revealed improvement in overall score, energy levels, and emotional reaction in the GH-treated group compared with those in the untreated group (P < 0.02). In conclusion, GH treatment for 10 yr in GHD adults resulted in increased lean body and muscle mass, a less atherogenic lipid profile, reduced carotid intima media thickness, and improved psychological well-being.

1. Adults with growth hormone deficiency have an abnormal body composition. Alterations in body composition are closely related to substrate concentrations and insulin action. The lack of growth hormone has been associated with increased insulin sensitivity. 2. We investigated the correlations of body composition with fasting insulin levels and substrate concentrations in 24 adults with growth hormone deficiency over a wide range of adiposity (body mass index 18.8-42.3 kg/m2). 3. Lean body mass was measured by total body potassium, computer tomography of the thigh and urinary creatinine excretion. Muscle fibre distribution was evaluated from vastus lateralis biopsies. Fat mass was assessed by skinfold thickness measurements, computer tomography of the thigh, and waist and hip girth. 4. Fasting plasma insulin level increased with fat mass (r = 0.67, P = 0.0004) and with waist girth (r = 0.76, P = 0.0001). Fasting plasma insulin level increased with fasting plasma glucose level (r = 0.53, P = 0.01). Fasting plasma glucose level in turn was positively correlated with lean body mass (r = 0.49, P = 0.01) and with total thigh muscle area (r = 0.54, P = 0.01). There was no correlation between lean body mass and fat mass (r = 0.17, not significant) nor between muscle fibre types and fat mass or fat distribution. Fasting plasma insulin level showed no correlation with any measurement of lean body mass or muscle fibre type. 5. These data demonstrate that the presence of obesity is associated with hyperinsulinaemia as the result of insulin resistance in adults with growth hormone deficiency, which could contribute to the increased cardiovascular mortality in adults with growth hormone deficiency.

Exercise-induced anaphylaxis (EIA) is a rare form of physical allergy. Although histamine release is a feature of EIA, and histamine provocation of coronary spasm has been described, serious cardiac arrhythmias in EIA have not been reported. Exercise-induced anaphylaxis was diagnosed in a survivor of out-of-hospital cardiac arrest due to ventricular fibrillation after ECG signs of coronary spasm. Coronary artery disease was excluded. Ergonovine provocation induced coronary spasm in this patient. This is, to the authors' knowledge, the first description of ventricular fibrillation in EIA, possibly due to coronary spasm.

Involvement of endocrine organs is frequent in patients with HIV infections. We report the first case of symptomatic hypoparathyroidism in a patient in the course of HIV infection. He presented with tetany and hypocalcemia in the presence of decreased levels of parathyroid hormone, which persisted after correction of hypomagnesemia. The family history was negative and none of the autoimmune diseases associated with hypoparathyroidism was present. No local destruction by tumor or infection could be demonstrated apart from HIV infection. We propose a causal role of HIV infection in the development of hypoparathyroidism and discuss the possible mechanisms of parathyroid involvement in AIDS.

CMV disease (CMVD) is a recognized problem of the early post-transplant period (PTP) in renal transplant recipients. Information on CMVD in the late (or = 2 years) PTP is scarce. We have observed 5 cases of CMVD during late (3-8 years) PTP during the last 15 years. Three of these patients died from CMVD. One of the patients with late-onset CMVD recovered spontaneously from mild pneumonitis, 1 patient with severe CMVD after therapy with ganciclovir/anti-CMV-IgG. CMVD was ascribed to primary infection in 4/5 patients, and transmission was attributed to blood products in 2 cases. At the time of CMVD, 4/5 patients were on stable immunosuppression with azathioprine/prednisone; 1 patient who died had received prednisone pulses 1 month prior to CMVD. Late onset CMVD is an underreported disease in renal transplant recipients, which warrants preventive measures and consideration of antiviral therapy.

The effects of 6 months' treatment with recombinant human growth hormone (rhGH) on serum lipids and lipoproteins were assessed in 24 adult patients with GH deficiency in a double-blind, placebo-controlled trial. Compared with age-, weight-, and sex-matched controls, the patients had significantly higher serum concentrations of total cholesterol (P = .002), low-density lipoprotein (LDL) cholesterol (P < .001), apolipoprotein B ([apoB] P = .011), and triglyceride (P = .017), and lower concentrations of high-density lipoprotein (HDL) cholesterol (P < .001). The prevalence of elevated serum cholesterol, triglyceride, LDL cholesterol, and apo B levels was 39%, 26%, 39%, and 25%, respectively; 75% of patients had decreased concentrations of HDL cholesterol. Treatment with rhGH (0.07 U/kg daily) resulted in decreases in total cholesterol level (5.8 +/- 0.3 to 5.1 +/- 0.3 mmol.L-1 over 6 months; P = .01 compared with placebo), LDL cholesterol level (4.22 +/- 0.25 to 3.19 +/- 0.23 mmol.L-1; P = .0003), LDL:HDL cholesterol ratio (5.57 +/- 0.47 to 3.29 +/- 0.33; P = .03), apo B level (1.07 +/- 0.06 to 0.84 +/- 0.07 g.L-1; P = .003), and apo B: A-1 ratio (0.73 +/- 0.05 to 0.69 +/- 0.05; P = .01). HDL cholesterol and apo A-1 levels did not change following rhGH treatment. The changes in lipid and lipoprotein levels were not significantly related to changes in insulin, thyroid hormones, insulin-like growth factor-1 (IGF-1), or indices of adiposity.(ABSTRACT TRUNCATED AT 250 WORDS)

The histology of needle biopsy specimens of skeletal muscle from the vastus lateralis was quantitatively assessed in a group of adults with growth hormone (GH) deficiency, most of whom had hypopituitarism treated with conventional pituitary hormone replacement. The mean age of the 21 patients (16 males and 5 females) was 39 +/- 2 (SEM). Comparisons were made with age- and sex-matched controls following six months double-blind, placebo-controlled treatment with recombinant human GH (rhGH) in the GH-deficient patients. Before treatment, needle muscle biopsies from patients with GH deficiency showed mean type I and II fibre areas of 5,153 +/- 273 and 4,828 +/- 312 microns 2 respectively, which did not differ from the controls (4,482 +/- 306 and 4,699 +/- 310 microns 2). Percentages of type I fibres were similar in the two groups (47.2 +/- 2.5% in GH deficiency and 45.3 +/- 2.2% in controls). No difference in the variability of type I or II fibre areas was demonstrated between the groups. Correlations between the relative contribution to total fibre area by type I fibres (mean fibre area x percent) and maximal oxygen uptake (p = 0.006), and between type II fibres and quadriceps force (p = 0.035) were noted in GH-deficient adults before treatment. Following rhGH treatment, no change was noted in mean fibre areas, variability of fibre areas, or percentage of either fibre type.(ABSTRACT TRUNCATED AT 250 WORDS)

1. In adult humans with growth hormone deficiency, treatment with growth hormone has recently been shown to have major anabolic effects and to improve exercise performance. The cardiovascular effects of growth hormone in adults with growth hormone deficiency were examined in 24 patients treated with recombinant human growth hormone (0.07 units/kg at night) in a double-blind, placebo-controlled trial lasting 6 months. 2. Compared with placebo, resting M-mode echocardiography showed increases in left ventricular end-diastolic dimension and stroke volume in the group treated with recombinant human growth hormone. No differences were noted between the groups with respect to left ventricular end-systolic dimension, fractional shortening, wall thicknesses or mean arterial blood pressure. Left ventricular myocardial mass increased in the group given recombinant human growth hormone. 3. The supine plasma renin activity was increased and remained elevated over the 6 months, whereas the plasma aldosterone concentration was unchanged, after treatment with recombinant human growth hormone. Clinical signs of sodium retention were evident during the first 3 months of treatment with recombinant human growth hormone. 4. We conclude that treatment with recombinant human growth hormone in adults with growth hormone deficiency resulted in small increases in left ventricular pre-load, due to the sodium-retaining action of growth hormone. Activation of the renin-aldosterone system was involved in such changes. Myocardial hypertrophy was observed without changes in mean arterial pressure, reflecting the anabolic action of growth hormone.

Growth hormone (GH) treatment in adults with GH deficiency increases lean body mass and thigh muscle cross-sectional area. The functional significance of this was examined by incremental cycle ergometry in 24 GH-deficient adults treated in a double-blind placebo-controlled trial with recombinant DNA human GH (rhGH) for 6 mo (0.07 U/kg body wt daily). Compared with placebo, the rhGH group increased mean maximal O2 uptake (VO2max) (+406 +/- 71 vs. +133 +/- 84 ml/min; P = 0.016) and maximal power output (+24.6 +/- 4.3 vs. +9.7 +/- 4.8 W; P = 0.047), without differences in maximal heart rate or ventilation. Forced expiratory volume in 1 s, vital capacity, and corrected CO gas transfer were within normal limits and did not change with treatment. Mean predicted VO2max, based on height and age, increased from 78.9 to 96.0% in the rhGH group (compared with 78.5 and 85.0% for placebo; P = 0.036). The anaerobic ventilatory threshold increased in the rhGH group (+159 +/- 39 vs. +1 +/- 51 ml/min; P = 0.02). The improvement in VO2max was noted when expressed per kilogram body weight but not lean body mass or thigh muscle area. We conclude that rhGH treatment in adults with GH deficiency improves and normalizes maximal exercise performance and improves submaximal exercise performance and that these changes are related to increases in lean body mass and muscle mass. Improved cardiac output may also contribute to the effect of rhGH on exercise performance.

Skeletal muscle mass and function were assessed in 24 adults (16 males, 8 females) with severe, long-standing GH deficiency. Compared to 41 untrained controls (26 males, 15 females), adults with GH deficiency had reduced cross-sectional area of thigh muscle/body weight (p = 0.01), reduced quadriceps force/weight (males: p = 0.002; females: p less than 0.0001), and reduced quadriceps force/muscle area (males: p = 0.005). This suggests (a) that adults with GH deficiency have reduced skeletal muscle mass due, in part, to the absence of the anabolic effects of GH, and (b) that skeletal muscle force may be reduced due to altered muscle mass, contractile elements/muscle fibre, anaerobic energy supply, neural recruitment of fibres, or a combination of these.

In a double-blind, placebo-controlled trial, we studied the effects of six months of growth hormone replacement in 24 adults with growth hormone deficiency. Most of the patients had acquired growth hormone deficiency during adulthood as a consequence of treatment for pituitary tumors, and all were receiving appropriate thyroid, adrenal, and gonadal hormone replacement. The daily dose of recombinant human growth hormone (rhGH) was 0.07 U per kilogram of body weight, given subcutaneously at bedtime. The mean (+/- SE) plasma concentration of insulin-like growth factor I increased from 0.41 +/- 0.05 to 1.53 +/- 0.16 U per liter during rhGH treatment. Treatment with rhGH had no effect on body weight. The mean lean body mass, however, increased by 5.5 +/- 1.1 kg (P less than 0.0001), and the fat mass decreased by 5.7 +/- 0.9 kg (P less than 0.0001) in the group treated with growth hormone; neither changed significantly in the placebo group. The basal metabolic rate, measured at base line and after one and six months of rhGH administration, increased significantly; the respective values were 32.4 +/- 1.4, 37.2 +/- 2.2, and 34.4 +/- 1.6 kcal per kilogram of lean body mass per day (P less than 0.001 for both comparisons). Fasting plasma cholesterol levels were lower (P less than 0.05) in the rhGH-treated group than in the placebo group, whereas plasma triglyceride values were similar in the two groups throughout the study. We conclude that growth hormone has a role in the regulation of body composition in adults, probably through its anabolic and lipolytic actions.