Effect of sequential administration of an opioid and cholecystokinin on gallbladder ejection fraction: brief communication.

This study was undertaken to test the effect of sequential administration of an opioid and intravenous cholecystokinin (CCK) on gallbladder ejection fraction. METHODS: Forty-nine patients who had received an opioid underwent quantitative cholescintigraphy with octapeptide of CCK (CCK-8). Gallbladder ejection fraction and CCK-8-induced paradoxical filling were calculated. RESULTS: In the basal state, more of the hepatic bile entered the gallbladder (67%) than the small intestine (33%). After CCK-8 infusion, gallbladder ejection fraction was low in 37 (76%) of 49 patients and normal in 12 (24%). All 5 types of opioids lowered ejection fraction. CCK-induced paradoxical filling of the gallbladder was noted in 7 patients, but only one showed paradoxical filling of greater than 20% and none had a normal gallbladder ejection fraction. The lowering effect of opioids on gallbladder ejection fraction may last as long as 18 h after intake. CONCLUSION: CCK-8 produced a normal gallbladder ejection fraction in 24% of patients who had received an opioid and thus could exclude both acute and chronic cholecystitis during a single hepatobiliary study.     

An update on the overnight dexamethasone suppression test for the diagnosis of Cushing's syndrome: limitations in patients with mild and/or episodic hypercortisolism.

The overnight one-mg dexamethasone suppression test has been used for many years to screen for Cushing's syndrome. This test has usually been evaluated in controls versus patients with severe hypercortisolism. Under these conditions, the overnight dexamethasone suppression test has been reported to have high sensitivity and specificity. The objective of this study was to determine the sensitivity of the one mg overnight dexamethasone suppression test in patients with mild and/or periodic Cushing's syndrome. Therefore, an overnight dexamethasone suppression test was performed in 17 consecutive patients presenting to an endocrinology clinic with signs and symptoms of hypercortisolemia who were later proven to have Cushing's syndrome. The majority of patients were found to have both mild and periodic hypercortisolism. One mg of dexamethasone was given at midnight and a plasma cortisol was measured by radioimmunoassay at 08:00 the following morning. Using a cut-off for a morning cortisol following overnight dexamethasone of > 5 microg/dL, only three of 17 patients failed to suppress to a value less than this cut-off (sensitivity 18 %). A cut-off of > 2 microg/dL gave similar sensitivity. Even with a stringent cut-off point of > 1.8 microg/dL, only seven of 17 patients failed to suppress to a value less than this cut-off point (sensitivity of 41 %). These results demonstrate that the great majority of patients with mild and/or periodic Cushing's syndrome suppress to overnight dexamethasone. Since patients with mild and/or periodic Cushing's syndrome are the patients in whom the identification of hypercortisolism is difficult, our results from this relatively small study suggest that this test should no longer be used to exclude these patients from further workup for Cushing's syndrome.     

Role of tumour necrosis factor-alpha receptor p75 in cigarette smoke-induced pulmonary inflammation and emphysema.

Chronic obstructive pulmonary disease (COPD) is characterised by a local pulmonary inflammatory response to respiratory pollutants and by systemic inflammation. Tumour necrosis factor (TNF)-alpha has been implicated in systemic effects of COPD and operates by binding the p55 (R1) and p75 (R2) TNF-alpha receptors. To investigate the contribution of each TNF-alpha receptor in the pathogenesis of COPD, the present study examined the effects of chronic air or cigarette smoke (CS) exposure in TNF-alpha R1 knockout (KO) mice, TNF-alpha R2 KO mice and wild type (WT) mice. CS was found to significantly increase the protein levels of soluble TNF-alpha R1 (by four-fold) and TNF-alpha R2 (by 10-fold) in the bronchoalveolar lavage of WT mice. After 3 months, CS induced a prominent pulmonary inflammatory cell influx in WT and TNF-alpha R1 KO mice. In TNF-alpha R2 KO mice, CS-induced pulmonary inflammation was clearly attenuated. After 6 months, no emphysema was observed in CS-exposed TNF-alpha R2 KO mice in contrast to WT and TNF-alpha R1 KO mice. CS-exposed WT and TNF-alpha R1 KO mice failed to gain weight, whereas the body mass of TNF-alpha R2 KO mice was not affected. These current findings suggest that both tumour necrosis factor-alpha receptors contribute to the pathogenesis of chronic obstructive pulmonary disease, but tumour necrosis factor-alpha receptor-2 is the most active receptor in the development of inflammation, emphysema and systemic weight loss in this murine model of chronic obstructive pulmonary disease.     

Energy cost of activity and exercise in children and adolescents with cystic fibrosis.

In cystic fibrosis (CF), perturbations of total daily energy expenditure (TDEE) may be a major determinant of altered nutrition and growth. Measurement of TDEE is problematic, though the flex-heart rate method (FHRM) provides a close estimation of TDEE, as compared to the cost-prohibitive, gold standard, the double-labeled water method, and permits estimates of the energy cost of daily activities (ECA) above resting energy expenditure (REE). We hypothesize that alterations in ECA affects TDEE in CF. PURPOSE: To measure components of TDEE in adolescents with CF and normal lung function compared with controls, and to determine whether ECA can be improved by diet and exercise. METHODS: Clinically stable CF subjects (aged 9-13, n=12) and age- and gender-matched controls (n=13) had repeated measurements of TDEE by FHRM, REE, and maximal cardiopulmonary exercise testing (CPET) during a 6-week exercise and diet program. RESULTS: While the mean REE was similar in both groups, ECA was significantly lower in CF adolescents as compared to controls (p=0.02). During CPET, maximal exercise in CF was characterized by hyperventilation, which was unrelated to ventilation-perfusion mismatching. There were no changes in REE after dietary intervention. CONCLUSION: ECA in CF adolescents with normal lung function is lower when compared to healthy controls. These findings support the hypothesis that clinically stable patients with CF have inefficient energy metabolism or alternatively conserve energy during activities of daily living.     

Case Report: Second case of a successful pregnancy in maternal isovaleric acidaemia

Summary: A female patient with isovaleric acidaemia had a successful outcome from pregnancy.     

Soluble triggering receptor expressed on myeloid cells-1 in acute respiratory infections.

Levels of the soluble form of the triggering receptor expressed on myeloid cells (sTREM)-1 are elevated in severe sepsis. However, it is not known whether sTREM-1 measurements can distinguish milder bacterial infections from noninfectious inflammation. The present authors studied whether serum sTREM-1 levels differ in community-acquired pneumonia, exacerbations of chronic obstructive pulmonary disease (COPD), asthma and controls, and whether sTREM-1 may be used as a surrogate marker for the need for antibiotics. Serum sTREM-1 levels in 150 patients with pneumonia, COPD and asthma exacerbations and 62 healthy controls were measured. Serum sTREM-1 levels were significantly elevated in pneumonia (median 295.2 ng x mL(-1)), COPD (280.3 ng x mL(-1)) and asthma exacerbations (184.0 ng x mL(-1)) compared with controls (83.1 ng x mL(-1)). Levels were higher in pneumonia and Anthonisen type 1 COPD exacerbations than in type 2 and 3 COPD and asthma exacerbations. The area under the receiver operating characteristics curve for sTREM-1 as a surrogate marker for the need for antibiotics was 0.77. Serum levels of the soluble form of the triggering receptor expressed on myeloid cells-1 were elevated predominantly in pneumonia and Anthonisen type 1 COPD exacerbations versus type 2 and 3 chronic obstructive pulmonary disease exacerbations, asthma and controls. Serum levels of the soluble form of the triggering receptor expressed on myeloid cells-1 has moderate but insufficient accuracy as a surrogate marker for the need for antibiotics in lower respiratory tract infections.     

Prognostic factors for surgical resection in patients with multidrug-resistant tuberculosis.

Although surgical lung resection could improve prognosis in some patients with multidrug-resistant tuberculosis (MDR-TB), there are no reports on the optimal candidates for this surgery. The aim of the present study was to elucidate the prognostic factors for surgery in patients with MDR-TB. Patients who underwent lung resection for the treatment of MDR-TB between March 1993 and December 2004 were included in the present study. Treatment failure was defined as greater than or equal to two of the five cultures recorded in the final 12 months of treatment being positive, any one of the final three cultures being positive, or the patient having died during treatment. The variables that affected treatment outcomes were identified through univariate and multivariate logistic regression analysis. In total, 79 patients with MDR-TB were included in the present study. The treatment outcomes of 22 (27.8%) patients were classified as failure. A body mass index <18.5 kg x m(-2), primary resistance, resistance to ofloxacin and the presence of a cavitary lesion beyond the range of the surgical resection were associated with treatment failure. Low body mass index, primary resistance, resistance to ofloxacin and cavitary lesions beyond the range of resection are possible poor prognostic factors for surgical lung resection in multidrug-resistant tuberculosis patients.     

Response to treatment with rosiglitazone in familial partial lipodystrophy due to a mutation in the LMNA gene

Background Familial partial lipodystrophy (FPLD) is a monogenic form of diabetes characterised by a dominantly inherited disorder of adipose tissue associated with the loss of subcutaneous fat from the limbs and trunk, with excess fat deposited around the face and neck. The lipodystrophy causes severe insulin resistance, resulting in acanthosis nigricans, diabetes, dyslipidaemia, and increased risk of cardiovascular disease. Preliminary results from animals and man suggest that increasing subcutaneous fat by treatment with thiazolidinediones should improve insulin resistance and the associated features of this syndrome. Case report We report a 24-year-old patient with FPLD caused by a mutation in the LMNA gene (R482W) treated with 12 months of rosiglitazone. Subcutaneous fat increased following rosiglitazone treatment as demonstrated by a 29% generalised increase in skin-fold thickness. Leptin levels increased from 5.8 to 11.2 ng/ml. Compared with treatment on Metformin, there was an increase in insulin sensitivity (HOMA S% 17.2–31.6) but no change in glycaemic control. The lipid profile worsened during the follow-up period. Conclusion This initial case suggests that, for modification of cardiovascular risk factors, there are no clear advantages in treating patients with FPLD with rosiglitazone despite increases in subcutaneous adipose tissue. Larger series will be needed to identify moderate beneficial effects and treatment may be more effective in patients with generalised forms of lipodystrophy.