Lifestyle change reduces cardiometabolic risk factors and glucagon-like peptide-1 levels in obese first-degree relatives of people with diabetes.

BACKGROUND: Preventing type 2 diabetes in a real-world setting remains challenging. The present study aimed to assess the effectiveness of a lifestyle-based programme for individuals at high risk of developing type 2 diabetes as assessed by achieved weight loss, cardiovascular risk factors and glucagon-like peptide-1 (GLP-1). METHODS: Sixty-six obese individuals with history of diabetes in first-degree relatives participated in an 8-month lifestyle programme consisting of 12 × 1.25 h group education sessions led by dietitian and a weekly exercise programme. Before and after comparisons were made of fasting blood glucose, insulin, HbA1c, lipids, GLP-1 and quality of life (QoL). RESULTS: Fifty-four participants of whom the majority were women [47 females; mean (SD) body mass index 35.3 (2.8) kg m-2 ; age = 52 (10) years] completed the 8-month programme. Mean (SD) weight loss was 10.1 (6.0) kg (P < 0.001). Out of 54 participants, 36 lost more than 7% of their body weight and 47 lost more than 5%, with significant improvements in cardiovascular risk factors, glycaemia and QoL scores. The fall was observed in basal (P < 0.05 versus baseline) but not stimulated GLP-1 levels. In the subgroup of participants losing >10 kg, a correlation was found between weight change and change in both basal (r = 0.61, P < 0.05) and stimulated (r = 0.49, P < 0.05) GLP-1. CONCLUSIONS: An evidence-based lifestyle programme achieved sustained weight loss in obese first-degree relatives of individuals with type 2 diabetes associated with improvements in cardiometabolic risk factors and QoL without the 'voltage drop' of less benefit commonly seen when moving from the clinical trial experience into the real world.

The acquisition of lysophosphatidylcholine by African trypanosomes.

Bloodstream forms of the African trypanosome, Trypanosoma brucei, can acquire substantial amounts of exogenous lysophospholipid. Lysophosphatidylcholine uptake is through a pathway consisting of three enzymes, phospholipase A1, acyl-CoA ligase, and lysophosphatidylcholine:acyl-CoA acyltransferase. The pathway enables the organism to acquire fatty acids and phospholipid head groups such as choline. Radiolabeling and 13C NMR studies show that two molecules of lysophosphatidylcholine are used to generate one molecule of cellular phosphatidylcholine. The three enzymes are associated with the trypanosomal plasma membrane and are accessible to exogenous substrates. The first enzyme, phospholipase A1, generates free fatty acid from exogenous lysophospholipid, which the second enzyme, a ligase, uses to form acyl-CoA. The fatty acyl-CoA formed by this route is in a separate pool from that derived from exogenous free fatty acid and is used by the third enzyme, acyltransferase, to acylate a second molecule of exogenous lysophospholipid. Acyltransferase is accessible to exogenous and endogenous acyl-CoA. The high activity of this pathway in bloodstream forms, compared with procyclic culture form trypanosomes, suggests that it may play a role in the acquisition of fatty acids for synthesis of the membrane form of the variant surface glycoprotein. Extracellular myristoyllysophosphatidylcholine can be used by trypanosomes as a source of myristate in remodeling the lipid anchor of the variant surface glycoprotein.

Complications following ventilation of the middle ear using Goode T tubes.

This is a 3.5-year retrospective review on the insertion of 210 Goode T tubes into 182 ears of 93 patients. Otorrhea was noted postoperatively in 35.2% of the ears treated, with chronic drainage lasting longer than 4 months developing in more than 7% of the cases. Perforations were found in 34 ears (18.7%) following removal or extrusion of the T tubes; in 13 (7.1%) of these patients, chronic perforations requiring tympanoplasties developed. The literature was screened for additional studies addressing the complications associated with tympanostomy tubes. The documented incidence of perforations between conventional tubes and Goode T tubes was emphasized, and comparisons were made. Our findings indicate that, even with the immediate placement of paper patches following removal of all Goode T tubes, the percentage of tympanic membrane perforations resulting from the use of Goode T tubes is significantly greater than previously reported.

Chondrosarcoma of the sphenoethmoid complex.

Chondrosarcoma of the nose and paranasal sinuses is extremely rare. We report a case of a child with a massive chondrosarcoma of the sphenoethmoid complex who presented with a change of visual acuity. Clinical and histologic characteristics of this lesion are discussed, along with treatment options and factors affecting prognosis.

Neck masses: benign or malignant? Sorting out the causes by age-group.

Differential diagnosis of cervical masses varies with the age of the patient. In children, neck masses are most likely to be inflammatory or congenital, and evaluation may include routine laboratory evaluation, skin tests, chest films, computed tomography and/or magnetic resonance imaging of the neck, and, possibly, fine-needle aspiration of the mass. The workup in young adults is similar to that in children. In older patients (greater than 40 years), however, the likelihood of malignant disease increases significantly. These patients should have formal endoscopy with biopsy of any suspicious lesions before an open biopsy of the neck mass is performed.

Brain herniation and space-occupying lesions eroding the tegmen tympani.

Technological advances in neuroradiology and the development of skull base surgery in neurotology have improved diagnosis and management of lesions eroding the tegmen tympani. The diagnosis of brain hernia is to be suspected in patients with a history of complicated chronic ear surgery and a slowly developing pulsatile mass with CSF leak. Patients are best evaluated in the upright position, with an otomicroscope and by magnetic resonance imaging (MRI). Over 6 years, our group has treated seven patients with eight space-occupying lesions eroding the tegmen. Five of the lesions were repaired with a temporalis muscle flap, 2 with fascia and bone, and 1 with Marlex. A review of new technology in the diagnosis of brain hernia and a modification of previous techniques is given.

Croup and epiglottitis: a radiologic study.

Because of the controversy regarding the benefits of the lateral neck and chest radiographs in the evaluation of croup and epiglottitis, a two-part retrospective study was initiated. Part I consisted of a retrospective chart review of 44 patients with a final diagnosis of croup and epiglottitis. Part II consisted of the 42 lateral neck and chest x-rays from patients in part I presented to six radiologists who knew only the patients age and the history of respiratory distress. Two hundred forty-six responses were obtained. The results of the part I study showed that 64% of patients with documented epiglottitis had a positive radiologic diagnosis. Only 33% of patients with croup had a positive radiologic diagnosis and importantly 27% had a diagnosis of possible epiglottitis. The results of part II showed 38% of the documented epiglottitis patients had a positive lateral neck radiograph. The croup patients had a lateral neck and/or chest x-ray positive in 38%. Of interest, 24% had readings consistent with possible epiglottitis. Based on this two-part study, it is our conclusion that the lateral neck and chest x-ray may be unreliable and inaccurate in the diagnosis of croup and epiglottitis. Caution and good clinical judgement should be utilized when interpreting these x-rays.

Platelet associated complement components (PAC3c and PAC3d) in patients with autoimmune thrombocytopenia.

Platelet associated C3c and C3d (PAC3c and PAC3d) were quantitated by enzyme linked assay in 105 patients with idiopathic autoimmune thrombocytopenia (AITP) in whom elevated platelet associated immunoglobulins (IgG and IgM) had previously been documented. Increased levels of complement components were demonstrated in 46 of 105 patients (43.8%). In 11 of these patients, PAC3d alone was abnormal implying that C3b had been inactivated after cleavage by C3 inactivator in vivo. Complement binding was seen in two of 16 patients (12.5%) with raised PAIgG alone, four of 19 patients (21.0%) with raised PAIgM alone and in 40 of 70 patients (57.1%) in whom PAIgG and PAIgM were raised together. This difference was highly significant (P = 0.01). The clinical implication of these findings are discussed.

The effect of storage in different anticoagulants on platelet associated IgG.

Blood was collected from nine normal volunteers into each of four different anticoagulants and in order to simulate transport conditions, was stored at room temperature for 96 h. The platelet associated IgG (PAIgG) was determined from aliquots thereof over this period. Blood in EDTA gave slightly higher initial values (day 0) than in other anticoagulants. PAIgG levels increased at different rates in all anticoagulants thereafter. In contrast to recent reports which suggested that falsely elevated levels were likely to be seen after storage in EDTA, we found little difference in these values in blood in different anticoagulants at 72 h and all PAIgG measurements remained within our quoted normal range at this time. After 96 h storage however, one of nine (11%) in CPD-A, two of nine (22%) in EDTA, two of nine (22%) in Na-citrate and six of nine (66%) in EDTA paraformaldehyde gave falsely elevated results. The possible mechanisms of these changes are discussed. The assay system employed in this study measures 'total' platelet IgG in a platelet extract in contrast to some other assays which quantify surface platelet IgG alone and it is possible that this difference in technique is responsible for the relatively smaller percentage changes after storage than reported by others. All anticoagulants tested in this study proved satisfactory both for handling and for the measurement of PAIgG at 48 h, with the proviso that normal ranges should be established for each.

Platelet associated IgG and immune thrombocytopenia in lymphoproliferative and autoimmune disorders.

Thrombocytopenia is frequently encountered in patients with lymphoproliferative disorders (LPD) and systemic erythromatosus (SLE) and to a lesser extent in association with other diseases such as rheumatoid arthritis (RA), pernicious anaemia (PA) and autoimmune haemolytic anaemia (AIHA). This report attempts to document the incidence of thrombocytopenia in these disorders, other than that overtly due to malignant infiltration or marrow suppression by drugs and to demonstrate, that in a significant proportion antibody mediated immune destruction of platelets can be confirmed by positive platelet antibody tests. Platelet associated IgG (PAIgG) was measured in all patients by a quantitative enzyme linked assay. Platelet antibodies were found in 11 of 24 (46%) thrombocytopenic patients with LPD, 10 of 16 (62%) patients with SLE and thrombocytopenia, and in all patients with RA and PA who had low platelet counts at the time of study. In addition, elevated PAIgG levels were found in the following non-thrombocytopenic patients: 9 of 43 (21%) patients with LPD, 2 of 12 (17%) with SLE, 2 of 12 (17%) with AIHA, 2 of 39 (5%) with PA and 5 of 61 (8%) patients with RA. The nature and the role of raised PAIgG levels in diseases other than autoimmune thrombocytopenia is controversial. Our reasons for interpreting these as true platelet autoantibodies in this selected group of disorders and the clinical implications of our results are discussed.

Detection of platelet-bound and serum antibodies in autoimmune thrombocytopenia by enzyme-linked assay.

Platelet antibodies were looked for in 47 patients with autoimmune thrombocytopenia using a modification of the enzyme-linked assay previously described. Surface-bound antibodies measured as increased platelet-associated IgG were found in 32 (68%) of the patients. After incubation in test sera, the platelet-associated IgG of normal donor platelets was significantly increased in 27 of the 47 patients (57%), thus demonstrating the presence of platelet antibodies free in their sera. 6 patients had antibodies only in the serum without any elevation of their platelet-associated IgG. When both tests are evaluated together no antibody was detected by either the direct or the indirect test in 9 of the 47 patients (29%) studied. The technique used is described and the interpretation of our results discussed.

Enzyme linked immunoassay for the detection of platelet associated IgG.

An enzyme linked immunoassay incorporating antihuman globulin coupled with alkaline phosphatase has been developed to measure platelet associated IgG (PAIgG). Using a method in which platelet IgG is extracted into the fluid phase after appropriate procedures, we were able to bind the 'solubilized' PAIgG to commercially obtained antihuman IgG (AHG) which had previously been coated onto polystyrene. The amount of PAIgG thus bound was subsequently measured by the addition of the enzyme reagent using p-nitro phenyl phosphate as substrate. With this technique platelets from normal donors were found to have 2.6-17.4 ng/10(6) platelets (mean +/-2 SD). These values are higher than those obtained when assay systems using intact platelets are employed. Platelets from patients with immune thrombocytopenia had PAIgG values of 8.2-98.0 ng/10(6) platelets. In a few patients with disorders other than autoimmune thrombocytopenia (AITP) increased levels of PAIgG were also demonstrated. The assumption that increased PAIgG always represents platelet autoantibody may not be valid. The relevance of PAIgG as a parameter in the diagnosis and clinical management of patients with AITP is discussed.