Smallpox vaccine stability after maintenance at temperatures not recommended for shipping

Two distinct smallpox vaccine formulations were exposed to temperatures beyond the ranges specified by the manufacturers for vaccine maintenance and shipping. Under the conditions investigated, titers of both Dryvax smallpox vaccine and Aventis Pasteur smallpox vaccine remained at or above the titers recommended for successful vaccination. From these data it can be inferred that vaccine efficacy would not be expected to be adversely affected by unintended fluctuations of temperature, within the ranges studied, for a 4-day period.     

Cognitive behavioral therapy vs zopiclone for treatment of chronic primary insomnia in older adults: a randomized controlled trial

Context  Insomnia is a common condition in older adults and is associated with a number of adverse medical, social, and psychological consequences. Previous research has suggested beneficial outcomes of both psychological and pharmacological treatments, but blinded placebo-controlled trials comparing the effects of these treatments are lacking. Objective  To examine short- and long-term clinical efficacy of cognitive behavioral therapy (CBT) and pharmacological treatment in older adults experiencing chronic primary insomnia. Design, Setting, and Participants  A randomized, double-blinded, placebo-controlled trial of 46 adults (mean age, 60.8 y; 22 women) with chronic primary insomnia conducted between January 2004 and December 2005 in a single Norwegian university-based outpatient clinic for adults and elderly patients. Intervention  CBT (sleep hygiene, sleep restriction, stimulus control, cognitive therapy, and relaxation; n = 18), sleep medication (7.5-mg zopiclone each night; n = 16), or placebo medication (n = 12). All treatment duration was 6 weeks, and the 2 active treatments were followed up at 6 months. Main Outcome Measures  Ambulant clinical polysomnographic data and sleep diaries were used to determine total wake time, total sleep time, sleep efficiency, and slow-wave sleep (only assessed using polysomnography) on all 3 assessment points. Results  CBT resulted in improved short- and long-term outcomes compared with zopiclone on 3 out of 4 outcome measures. For most outcomes, zopiclone did not differ from placebo. Participants receiving CBT improved their sleep efficiency from 81.4% at pretreatment to 90.1% at 6-month follow-up compared with a decrease from 82.3% to 81.9% in the zopiclone group. Participants in the CBT group spent much more time in slow-wave sleep (stages 3 and 4) compared with those in other groups, and spent less time awake during the night. Total sleep time was similar in all 3 groups; at 6 months, patients receiving CBT had better sleep efficiency using polysomnography than those taking zopiclone. Conclusion  These results suggest that interventions based on CBT are superior to zopiclone treatment both in short- and long-term management of insomnia in older adults. Trial Registration  clinicaltrials.gov Identifier: NCT00295386      

Further evidence for glycocalicin being derived from a larger amphiphilic platelet membrane glycoprotein

Lysis of platelets by freezing and thawing in the absence of enzyme inhibitors leads to the solubilization of glycocalicin with the concomitant loss of a glycocalicin-related membrane protein. As evidenced by crossed immunoelectrophoresis and SDS-PAGE, this loss was counteracted by EDTA and leupeptin which are inhibitors of the calcium-activated protease. Charge shift crossed immunoelectrophoresis demonstrated the hydrophilic nature of glycocalicin and the amphiphilic character of the precursor protein previously described. Combination of crossed immunoelectrophoresis and SDS-PAGE showed that the glycocalicin-related protein was larger than the soluble glycocalicin and belonged to the GP I family of platelet glycoproteins.     

Gynaecological problems related to anatomical changes after conventional proctocolectomy and ileostomy

Seventy-one women who had a proctocolectomy for ulcerative colitis (n=41) or Crohn's disease (n=30) were interviewed in the follow-up clinic about gynaecological problems and fertility. All women were examined by an independent gynaecologist and abnormalities of the internal genital tract were registered. Forty-nine per cent (35/71) of the women had a distressing vaginal discharge after proctocolectomy, compared with 9% (6/71) before surgery. At the gynaecological examination 45% (32/71) had a heavy vaginal secretion with-out any signs of an acute vaginal infection. In 68% (30/44) fluid retention in the vagina was associated with a caudally firmly fixed and dilatated posterior vaginal fornix. Twelve per cent (8/66) of the women reported dyspareunia before surgery. After surgery, 27% (18/66) complained of this symptom. Fertility was significantly reduced after surgery since only 37% (10/27) of the women who attempted to become pregnant succeeded within 5 years follow-up. The corresponding figure before surgery was 72% (39/54). Those who conceived went through pregnancy and parturition without any incident, 6 of 21 delivered by caesarean incision. In conclusion, conventional proctocolectomy in women will result in distressing vaginal discharge, and dyspareunia in a considerable proportion of the patients. The operation also seems to decrease their chances of becoming pregnant.     

Mutations in the HERG K+-ion channel: a novel link between long QT syndrome and sudden infant death syndrome

In a 7-week-old infant who experienced sudden infant death syndrome (SIDS), a novel missense mutation was identified in KCNH2, causing a lysine-to-glutamic acid amino acid substitution at position 101 (K101E). KCNH2 codes for the HERG ion channel and mutations in the gene are associated with congenital long-QT syndrome (LQTS), and in the family of this case of SIDS, the mutation was associated with Torsades de pointes tachycardia, making SIDS the most likely outcome of congenital LQTS.     

Prehospital chest tube thoracostomy: effective treatment or additional trauma?

BACKGROUND: The use of prehospital chest tube thoracostomy (TT) remains controversial because of presumed increased complication risks. This study analyzed infectious complication rates for physician-performed prehospital and emergency department (ED) TT. METHODS: Over a 40-month period, all consecutive trauma patients with TT performed by the flight physician at the accident scene were compared with all patients with TT performed in the emergency department. Bacterial cultures, blood samples, and thoracic radiographs were reviewed for TT-related infections. RESULTS: Twenty-two patients received prehospital TTs and 101 patients received ED TTs. Infected hemithoraces related to TTs were found in 9% of those performed in the prehospital setting and 12% of ED-performed TTs (not significant). CONCLUSION: The prehospital chest tube thoracostomy is a safe and lifesaving intervention, providing added value to prehospital trauma care when performed by a qualified physician. The infection rate for prehospital TT does not differ from ED TT.     

Inhibition of dipeptidyl-peptidase IV catalyzed peptide truncation by Vildagliptin ((2S)-{[(3-hydroxyadamantan-1-yl)amino]acetyl}-pyrrolidine-2-carbonitrile)

Vildagliptin (NVP-LAF237/(2S)-{[(3-hydroxyadamantan-1-yl)amino]acetyl}-pyrrolidine-2-carbonitrile) was described as a potent, selective and orally bio-available dipeptidyl-peptidase IV (DPP IV, EC 3.4.14.5) inhibitor [Villhauer EB, Brinkman JA, Naderi GB, Burkey BF, Dunning BE, Prasad K, et al.1-[[(3-Hydroxy-1-adamantyl)amino]acetyl]-2-cyano-(S)-pyrrolidine: a potent, selective, and orally bioavailable dipeptidyl peptidase IV inhibitor with antihyperglycemic properties. J Med Chem 2003;46:2774-89]. Phase III clinical trials for the use of this compound in the treatment of Type 2 diabetes were started in the first quarter of 2004. In this paper, we report on (1) the kinetics of binding, (2) the type of inhibition, (3) the selectivity with respect to other peptidases, and (4) the inhibitory potency on the DPP IV catalyzed degradation of glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and substance P. Vildagliptin behaved as a slow-binding DPP IV inhibitor with an association rate constant of 1.4x10(5)M(-1)s(-1) and a K(i) of 17nM. It is a micromolar inhibitor for dipeptidyl-peptidase 8 and does not significantly inhibit dipeptidyl-peptidase II (EC 3.4.11.2), prolyl oligopeptidase (EC 3.4.21.26), aminopeptidase P (EC 3.4.11.9) or aminopeptidase M (EC 3.4.11.2). There was no evidence for substrate specific inhibition of DPP IV by Vildagliptin or for important allosteric factors affecting the inhibition constant in presence of GIP and GLP-1.