Goitre: a cause of obstructive sleep apnoea in euthyroid patients

While hypothyroidism is considered to predispose to obstructive sleep apnoea (OSA), the presence of a goitre itself is not a recognized cause of OSA. We present the cases of two euthyroid patients with large goitres and clinical evidence of OSA, whose OSA symptoms significantly improved following partial thyroidectomy. This finding suggests that the goitre contributed to their symptoms.     

Neuroradiologic diagnosis and treatment of vasospasm

For survivors of aneurysmal subarachnoid hemorrhage, cerebral vasospasm significantly contributes to its morbidity and mortality by causing delayed ischemic neurological deficit. Noninvasive evaluation with computed tomography, transcranial doppler and single photon emission computerized tomography helps guide clinical decisions. Endovascular therapy of symptomatic vasospasm with balloon angioplasty and to a lesser extent with intraarterial papaverine infusion has emerged as an important treatment adjunct to neurosurgical medical and operative management. Early and aggressive treatment with balloon angioplasty has resulted in sustained clinical improvement in about two-thirds of patients suffering from neurological deficits attributable to vasospasm. Encouraging long-term clinical and transcranial artery damage following angioplasty. Despite balloon angioplasty's 2% to 5% peri-procedure mortality rate, it remains under used.     

Investigation of the selenium status of aborted calves with cardiac failure and myocardial necrosis

Lesions of heart failure, specifically cardiac dilation or hypertrophy along with a nodular liver (chronic passive congestion) and ascites, have been found in 4-5% of aborted bovine fetuses. In this study, a group of 22 such fetuses was compared with groups of aborted fetuses without lesions of heart failure and with nonaborted fetuses obtained from a slaughterhouse. The fetuses were necropsied, tissues were taken for histopathology, and samples were collected for routine bacteriologic and virologic examinations. Liver and kidney tissue was saved for selenium analysis. Histopathologic examinations of myocardium of fetuses with cardiac failure revealed myocardial necrosis and mineralization in 7 fetuses, lymphocytic myocarditis in 5 fetuses, myocardial fibrosis in 5 fetuses, or no microscopic lesions in 5 fetuses. Mean liver selenium levels were 5.5 mumol/kg in the fetuses with heart lesions, 6.5 mumol/kg in the fetuses without heart lesions and 7.5 mumol/kg in fetuses from the slaughterhouse; these differences were statistically significant. The results suggest that selenium deficiency in bovine fetuses may cause myocardial necrosis and heart failure. This study also provides data on normal liver and kidney selenium levels in bovine fetuses from the analyses of 19 nonaborted fetuses.     

Relationships between cell density, glutathione and proliferation of A549 human lung adenocarcinoma cells treated with acrolein

Acrolein is a highly electrophilic alpha,beta-unsaturated aldehyde to which humans are exposed in various situations. Acrolein reacts rapidly with and depletes cellular glutathione (GSH), and is toxic to various types of cells. In the current study, the ability of acrolein to alter proliferation of A549 cells was found to be dependent on cell density as well as total cell number. Thus, 'doses' must be expressed per cell rather than as a concentration, and all related studies need to be performed by plating a constant number of cells. A549 cells were plated at various densities and treated with acrolein after 48 h. Acrolein doses up to 47 fmol/cell at the time of treatment did not cause cell lethality. However, growth of A549 cells (as shown by thymidine incorporation, alamarBlue and total protein) was inhibited at acrolein levels > 34 fmol/cell in 6-well plates seeded at 5000 cells/cm2 48 h prior to treatment. Cellular GSH levels were decreased 34% by 2 h at acrolein levels of 6.7 fmol/cell and by 65% at 47 fmol/cell. Recovery of GSH was rapid at 6.7-47 fmol/cell acrolein, returning to control levels or above by 12 h post-treatment. These data show a strong correlation between cellular GSH and proliferation. The apparent conflict with a previous study of Ramu et al., suggesting that sublethal concentrations (up to 10 microM) of acrolein inhibited the proliferation of A549 cells without a decline in total cellular GSH, arose because, while the acrolein concentration was the same in cells used for proliferation and GSH assays, GSH measurements were done in cells plated at a higher density, resulting in a much lower acrolein dose per cell. Interestingly, very low dose levels of acrolein with cells seeded at low densities stimulated cell growth despite an initial decline in GSH content. Preliminary studies with the stress genes hsp70 and gadd153 suggest that acrolein at 35 fmol/cell does not stimulate formation of their mRNA beyond the level stimulated by a 2 h incubation in serum-free medium but may actually delay or decrease the induced expression. The mechanism(s) of the inhibitory and mitogenic effects of acrolein remains to be determined, but could be due to changes in gene expression induced by this electrophile, perhaps mediated by changes in GSH.     

Human B cells secreting immunoglobulin G to glutamic acid decarboxylase-65 from a nondiabetic patient with multiple autoantibodies and Graves' disease: a comparison with those present in type 1 diabetes

Antibodies to glutamic acid decarboxylase-65 (GAD65) are present in a number of autoimmune disorders, such as insulin-dependent (type 1) diabetes mellitus (IDDM), stiff man syndrome, and polyendocrine autoimmune disease. Antibodies to GAD in IDDM patients usually recognize conformation-dependent regions on GAD65 and rarely bind to the second isoform, glutamic acid decarboxylase-67 (GAD67). In contrast, those present in stiff man syndrome and polyendocrine disease commonly target the second isoform (GAD67) and include antibodies that are less dependent on the conformation of the molecule. By immortalizing peripheral blood B cells with Epstein-Barr virus, we have generated three human IgG autoantibodies, termed b35, b78, and b96, to GAD65 from one patient with multiple autoantibodies to endocrine organs and Graves' disease. All three autoantibodies are of the IgG1 isotype, with islet cell activity, and do not react with GAD67. The regions on GAD65 recognized by the three autoantibodies have been investigated by immunoprecipitation with a series of chimeras, by binding to denatured and reduced antigens, and using protein footprinting techniques. Using chimeric GAD proteins, we have shown that b35 targets the IDDM-E1 region of GAD65 (amino acids 240-435) whereas both b78 and b96 target the IDDM-E2 region of GAD65 (amino acids 451-570). Furthermore, examination of binding to recombinant GAD65 and GAD67 by Western blotting revealed some differences in epitope recognition, where only b78 bound denatured and reduced GAD65. However, b35, b78, and b96 autoantibodies had different footprinting patterns after trypsin treatment of immune complexes with GAD65, again indicating different epitope recognition. Our results indicate that antibodies to GAD65 present in nondiabetic patients with multiple autoantibodies to endocrine organs show similarities to those in IDDM (by targeting IDDM-E1 and IDDM-E2 regions of GAD65) as well as subtle differences in epitope recognition (such as binding to denatured and reduced GAD65 and by protein footprinting). Thus, the GAD65 epitopes recognized by autoantibodies in different autoimmune diseases may overlap and be more heterogeneous than previously recognized.     

Pharmacotherapy for Delusional Disorder and Associated Conditions.

Delusional disorder, according to current psychiatric nosology, is the presence of one or more nonbizarre delusions (i.e., false beliefs that nonetheless may be plausible or derived from ordinary life experiences) that do not occur in the context of schizophrenia and often exist in the presence of generally acceptable levels of psychosocial functioning. Currently recognized subtypes of delusional disorder are erotomanic (a delusion that another is in love with the patient), grandiose, jealous, persecutory, or somatic (Manschreck, 2000). As Manschreck noted, the diagnosis is complicated by disagreements over the distinction between bizarre and nonbizarre delusions, as well as the fact that the features of certain subtypes of delusional disorder may closely resemble those found in other conditions. Very little data, aside from anecdotal or case reports, exist to inform practice regarding the treatment of delusional disorder. Much of the recent literature addresses delusions that exist in the context of dementia or another underlying neurological disorder. It is important to recognize the substantial differences between these conditions and a primary delusional disorder. This brief review examines not only pharmacological management of primary delusional disorder but also delusions in the context of dementia and related disorders. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The Time Dependence of the Detachment Force of Ground Micrometer-Size Particles from a Planar Substrate: Effect of Particle Rotation

The time dependence of the detachment force applied to 7 µm ground polyester particles coated with silica nanoparticles was determined by ultracentrifugation. It was found that the force required to separate the particles from the substrate increased during the first 24 hours and changed very little thereafter. Scanning electron microscopy (SEM) results suggest that the increase in adhesion is due to the particles rotating from their initial positions obtained during deposition. The role of the silica nanoparticles in determining the time dependence of the detachment force is discussed in terms of the JKR and Fuller-Tabor models.     

Junior doctors and clinical audit

OBJECTIVES: To assess the extent of junior doctor involvement in clinical audit, the degree of support from audit staff, and the perceived value of the resulting audits. DESIGN: Postal survey of National Health Service (NHS) junior doctors. SUBJECTS AND SETTINGS: 704 junior doctors in central Leeds hospitals, June 1996. RESULTS: Questionnaires were returned by 232 respondents (33%), 211 (31%) were completed; 157 respondents (74%) had personally performed audit. Mean (+/- SD) duration since last audit project was 14.9 (14.1) (range 0-84) months. Of the respondents who had personally performed audit, 88 (56%) did not use the hospital audit department, 60 (38%) received no guidance and only 19 (12%) were involved in re-auditing the same project. Mean (+/- SD) time spent per audit project was 27.8 (37.7), (range 2-212) hours. Seventy-five junior doctors (48%) were aware of subsequent change in clinical practice, 41 (26%) perceived a negative personal benefit from audit, 33 (21%) perceived a negative departmental benefit, and 42 (27%) felt that audit was a waste of time. CONCLUSIONS: A large proportion of junior doctors are involved in audit projects that do not conform to established good practice and which have a low impact on clinical behaviour. Although junior doctors feel that there is inadequate assistance and poor supervision whilst performing audit, they still support the principle of audit. There is a need to improve the quality and supervision of audit projects performed by junior doctors.     

A longitudinal study of circulating lymphocyte subsets in the peripheral blood during the acute stage of Guillain-Barré syndrome

We investigated sequential changes in bile flow, serum and biliary biochemical parameters in phalloidin-induced cholestasis in rats. Intrahepatic cholestasis was induced by administration with phalloidin (500 microg/kg) for 7 days, and then the animals were allowed to survive for 1, 2, 4, 7, 14 and 28 days after the last treatment. In phalloidin-treated rats, bile flow significantly decreased up to 4 days of recovery, compared with the control animals. In contrast, serum ALP activity, LAP activity, cholesterol concentration and phospholipid concentration exhibited a marked elevation throughout the recovery periods. For biliary parameters, bilirubin excretion rate was unchanged but, cholesterol excretion rate showed a marked decrease throughout the recovery periods. These results demonstrate that some parameters, particularly important indexes of cholestasis (serum ALP, cholesterol, bile flow and so on), continued significant changes at least 4 days after the last administration of phalloidin. These results demonstrate that successive treatment with phalloidin can cause damage in most of serum and biliary parameters at a chronic stage of cholestasis. Thus, our findings may provide useful information for diagnosis of drug-induced cholestasis and help to further elucidate the biochemical mechanisms of drug-induced cholestasis in humans.