The proapoptotic 9-2 isozyme of 2-5 (A) synthetase cannot substitute for the sperm functions of the proapoptotic protein, Bax.

The 9-2 isozyme of 2-5 (A) synthetase has cellular proapoptotic functions that are mediated not by enzyme activity but by the Bcl-2 homology domain 3 present in its unique carboxyl-terminal region. Another proapoptotic cellular protein is Bax, whose absence in the Bax(-/-) mice causes male sterility due to abnormal sperm differentiation. In this study, we examined whether transgenic 9-2 expression can substitute for the in vivo reproductive function of Bax. To achieve this goal, a sperm-specific promoter was used to drive the expression of 9-2 in the sperm of transgenic mice. By selective cross-breeding, the transgene was transferred to Bax(-/-) mice to generate the experimental mouse line (Bax(-/-), 9-2(+/+)). The male experimental mice were sterile, and their testes maintained the structural abnormality found in Bax(-/-) mice. Thus, the male reproduction functions of Bax could not be replaced by the 9-2 isozyme of 2-5 (A) synthetase.     

Quality in Clinical Practice

This paper reports the proceedings of the discussion panel assigned to look at clinical aspects of quality in emergency medicine. One of the seven stated objectives of the Academic Emergency Medicine consensus conference on quality in emergency medicine was to educate emergency physicians regarding quality measures and quality improvement as essential aspects of the practice of emergency medicine. Another topic of interest was a discussion of the value of information technology in facilitating quality care in the clinical practice of emergency medicine. It is important to note that this is not intended to be a comprehensive review of this extensive topic, but instead is designed to report the discussion that occurred at this session of the consensus conference.     

Postoperative convalescence after inguinal hernia surgery: Prospective randomized multicenter study of laparoscopic versus Shouldice inguinal hernia repair in 1042 patients

Interest in inguinal hernia surgery has increased significantly with the introduction of new operating techniques during the past decade. This multicenter study compared short-term results in patients treated by the laparoscopic transabdominal preperitoneal patch technique (TAPP; n=518) and the Shouldice technique (n=524). We evaluated demographics, operative data, complications, hospital stay, postoperative pain, use of analgesics, functional status, sick leave, and complaints up to 3 months postoperatively. The median operating time was shorter in the Shouldice group (55 vs. 65 min), but there were no significant differences in complication rates, and major complications were rare. The hospital stay was 1 day or less in over 98% of cases in both groups, but more operations were performed on outpatient basis in the Shouldice group. In the TAPP group postoperative pain and analgesic consumption were less, postoperative functional status was better, and sick leave was shorter (10 vs. 14 days). These results show that the two methods are equally safe and have few major complications. The TAPP operation is associated with less postoperative pain, better postoperative functional status, and shorter sick leave, but at the price of a longer operating time. Electronic Publication     

Cough and paradoxical vocal fold motion

OBJECTIVES: The differential diagnosis and treatment of patients with chronic cough, paradoxical vocal fold motion, and disordered breathing can be a challenge to most practicing otolaryngologists. Tracheobronchial (ie, asthma, bronchitis, and tracheal stenosis), laryngeal (ie, vocal fold paralysis and neoplasms), and rhinologic (ie, allergies and rhinosinusitis) etiologies are commonly diagnosed and treated effectively. However, occasionally one is faced with patients who are refractory to medical treatment and have no obvious rhinologic, laryngeal or pulmonary cause. STUDY DESIGN AND SETTING: We conducted a review of the literature. METHODS: We present a thorough review of the current medical literature exploring the complex neurologic mechanisms involved in the production of cough and the relationship between gastroesophageal reflux disease, vagal neurapathy, and paradoxical vocal fold motion. RESULTS: The diagnosis and successful treatment of chronic cough can be complex. It requires a thorough understanding of the neurologic mechanisms behind cough excitation and suppression. Successful treatment strategies include aggressive management of the patient's reactive airway disease, gastroesophageal reflux disease, and, in select cases, paradoxical vocal fold motion. This may involve a well-coordinated effort among pulmonologists, otolaryngologists, gastroenterologists, and speech pathologists. CONCLUSION: Gastroesophageal reflux disease, vagal neuropathy, and paradoxical vocal fold motion are additional causes of chronic cough and disordered breathing that need to be considered, in the absence of obvious laryngotracheal and/or rhinologic pathology. A high index of suspicion is essential in making the diagnosis and formulating an effective multidisciplinary treatment plan for these patients.     

Treatment of sex offenders with antiandrogenic medication: conceptualization, review of treatment modalities, and preliminary findings

Sexual deviation disorders, or paraphilias, are diagnosable psychiatric syndromes manifested by 1) recurrent fantasies about deviant sex, 2) intense associated cravings, and 3) stereotypic behavioral responses. Pedophiles seek out children in response to their erotic thoughts and urges, whereas exhibitionists expose themselves. Paraphiliac syndromes ordinarily follow a chronic course and may be associated with biological pathology, but etiological factors are poorly understood. Treatment becomes a consideration when the well-being or rights of others are compromised. Proposed treatments have included psychotherapy, behavior therapy, surgery, and medication. Medroxyprogesterone acetate, which reduces testosterone, may diminish sexual preoccupation and urges, making self-control easier.     

Progress toward re‐engineering non‐ribosomal peptide synthetase proteins: a potential new source of pharmacological agents

Many important pharmaceutical agents, including vancomycin, bleomycin, cyclosporin, and several antibiotics, are produced by non‐ribosomal peptide synthetase (NRPS) enzymes in microorganisms. The NRPS pathway produces an extensive library of products using multienzyme complexes acting in an assembly‐line fashion. Engineering an NRPS system to produce an even greater variety of products, some of which may also have beneficial therapeutic value, would be an enormous advantage. Several approaches have been successful in generating novel NRPS products: mutational biosynthesis during which nonnatural substrates are fed to an organism; domain and module swapping between different species to generate hybrid enzymes; and rational site‐directed mutagenesis, based either on phylogeny or computational prediction, intended to switch substrate specificity and produce altered products. This review will highlight the progress in these areas and describe research in the future that will extend the capacity for re‐engineering NRPS systems. Drug Dev. Res. 66:9–18, 2006. © 2006 Wiley‐Liss, Inc.     

Use of the inferior epigastric artery as a free graft for myocardial revascularization

From March 1990 through January 1991, 47 patients undergoing myocardial revascularization had one (37) or both (10) inferior epigastric arteries (IEA) used as a conduit for bypass with 62 distal anastomoses. The internal thoracic artery (ITA) was used bilaterally in 41 patients and unilaterally in 6 with 100 distal anastomoses. Five patients had a single saphenous vein graft. In total, 167 anastomoses (3.55 per patient) were performed. Single IEA grafts were harvested through a paramedian incision and bilateral grafts, a midline incision. Harvest time was 36.5 minutes for IEA grafts and 29.6 minutes for ITA grafts (p less than 0.0001). Graft length was 11.9 cm for IEA grafts and 16.5 cm for ITA grafts (p less than 0.0001). Distal graft diameter was 2.0 mm for IEA grafts and 2.1 mm for ITA grafts (p less than 0.01). Graft flow was 49.7 mL/min for IEA grafts and 48.7 mL/min for ITA grafts. Microscopic assessment of segments of both the IEA and ITA from 14 patients revealed similar internal elastic laminae and an equal number of fenestrations. Combined intimal and medial thickness was comparable in both conduits. Medial elastic tissue was more prominent in ITA grafts and lacking in eight of the 14 IEA grafts. Gross plaque formation was noted in the proximal 1 to 3 cm of 50% of IEA grafts, but the lumen was not compromised and microscopic thickening was minimal. An unexpected finding was medial calcifications (M?nckeberg's disease) in two of the 14 IEAs without associated atherosclerosis. There was one hospital death, one abdominal wound infection, and one instance of fat necrosis superficial to the sternum.(ABSTRACT TRUNCATED AT 250 WORDS)