Monoclonal anti-tuberculosis antibodies react with DNA, and monoclonal anti-DNA autoantibodies react with Mycobacterium tuberculosis.

Classical models of experimental autoimmune diseases, such as adjuvant arthritis entail the use of mycobacteria. Furthermore, BCG immunotherapy may be followed by arthritic symptoms. To test the infection-autoimmunity relationship of mycobacteria, we used monoclonal antibodies raised against M. tuberculosis and against DNA. Murine monoclonal anti-TB antibodies were found to react with ssDNA, dsDNA and other polynucleotides. Monoclonal anti-DNA autoantibodies derived from patients and mice with SLE bound to three glycolipids shared among all mycobacteria and derived from mycobacterial cell wall. Prior incubation of the antibodies with ssDNA and other polynucleotides or with glycolipid antigens inhibited binding. These results indicate that infecting mycobacteria share antigens with human tissue, thus accounting in part for the production of autoantibodies in mycobacterial infections.     

Venous ischemia as a cause of ureteral necrosis in transplanted ureters

BACKGROUND: Urologic complications after pediatric renal transplantation can adversely effect the outcome and may result in decreased graft survival. Efforts to prevent these complications are worthwhile. This study investigates the incidence of these complications in a clinical transplant program and reports on an animal model used to investigate one possible cause. METHODS: In the clinical study, the results of a pediatric renal transplant program at a large children's hospital for a 5(1/2)-year period were reviewed with special attention paid to patients suffering ureteral necrosis. In the experimental study, 9 swine underwent laparotomy, bilateral complete infrahilar ureteric dissection, and extravesical ureteroneocystostomy. On the left side only, the renal and adrenal veins were ligated. The arterial supply remained intact. The right side did not undergo vessel ligation and served as the control. Three pigs each were killed at 3, 8, and 15 days. Kidneys, ureters and a cuff of bladder were examined histologically. RESULTS: In the clinical study 75 renal transplants were performed with a total of 5 cases of early ureteral necrosis. Two of these 5 displayed venous congestion and ischemia, and 2 were associated with kidneys displaying primary nonfunction of the graft. Seventy-one of 75 grafts are continuing to function. One of the 4 early graft losses also had an ischemic ureter. In the experimental study all right kidneys and ureters were normal. All left kidneys had complete hemorrhagic necrosis. Necrosis also was found in 5 of 9 proximal left ureters and in 7 of 9 distal left ureters. Viable left ureters displayed moderate to severe submucosal and periureteric hemorrhage. Four of 9 ureters displayed more damage distally than proximally. The extent of necrosis was similar at 3, 8, and 15 days. CONCLUSION: In both clinical and experimental studies, venous congestion and subsequent ischemia have been shown to be important causes of ureteral necrosis after renal transplantation.     

Effect of Flumazenil on Ventilatory Drive during Sedation with Midazolam and Alfentanil

Background: Patients who receive a combination of a benzodiazepine and an opioid for conscious sedation are at risk for developing respiratory depression. While flumazenil effectively antagonizes the respiratory depression associated with a benzodiazepine alone, its efficacy in the presence of both a benzodiazepine and an opioid has not been established. This study was designed to determine whether flumazenil can reverse benzodiazepine-induced depression of ventilatory drive in the presence of an opioid.

Methods: Twelve healthy volunteers completed this randomized, double-blind, crossover study. Ventilatory responses to carbon dioxide and to isocapnic hypoxia were determined during four treatment phases: (1) baseline, (2) alfentanil infusion; (3) combined midazolam and alfentanil infusions, and (4) combined alfentanil, midazolam, and "study drug" (consisting of either flumazenil or flumazenil vehicle) infusions. Subjects returned 2-6 weeks later to receive the alternate study drug.

Results: Alfentanil decreased the slope of the carbon dioxide response curve from 2.14 +/- 0.40 to 1.43 +/- 0.19 l [dot] min sup -1 [dot] mmHg sup -1 (x +/- SE, P < 0.05), and decreased the minute ventilation at PET CO2 = 50 mmHg (V with dotE 50) from 19.7 +/- 1.2 to 14.8 +/- 0.9 l [dot] min sup -1 (P < 0.05). Midazolam further reduced these variables to 0.87 +/- 0.17 l [dot] min sup -1 [dot] mmHg sup -1 (P < 0.05) and 11.7 +/- 0.8 l [dot] min sup -1 (P <0.05), respectively. With addition of flumazenil, slope and V with dot sub E 50 increased to 1.47 +/- 0.37 l [dot] min sup -1 [dot] mmHg sup -1 (P < 0.05) and 16.4 +/- 2.0 l [dot] min sup -1 (P < 0.05); after placebo, the respective values of 1.02 +/- 0.19 l [dot] min sup -1 [dot] mmHg sup -1 and 12.5 +/- 1.2 l [dot] min sup -1 did not differ significantly from their values during combined alfentanil and midazolam administration. The effect of flumazenil differed significantly from that of placebo (P < 0.05). Both the slope and the displacement of the hypoxic ventilatory response, measured at PET CO2 = 46 +/- 1 mmHg, were affected similarly, with flumazenil showing a significant improvement compared to placebo.     

Technical advances in pediatric laparoscopy have had a beneficial impact on splenectomy

PURPOSE: The aim of this study was to demonstrate the effects of recent technical advances on the safety and benefits of pediatric laparoscopic splenectomy. METHODS: A retrospective review was conducted of patients undergoing laparoscopic splenectomy from January 1998 to January 2000. Technical advances utilized during this period included the harmonic scalpel, a specialized flexible hilar retractor, a larger, wire-rimmed specimen bag, and lateral patient positioning. RESULTS: Laparoscopic splenectomy was performed successfully on 18 patients aged 3 to 17 years (median, 9). The indications were hereditary spherocytosis (n = 10), idiopathic thrombocytopenic purpura (n = 5), and other (n = 3). Eight patients had concomitant procedures including cholecystectomy (n = 3), resection of an accessory spleen (n = 3), and other (n = 2). The median operating time, including the concomitant procedures, was 125 minutes (range, 70 to 235). Patients tolerated a regular diet on median postoperative day 1 (range, 1 to 3), and 16 were discharged home on or before postoperative day 2. None of the patients required blood product transfusion or conversion to an open technique. There were no complications, and all patients had returned to usual activity by 2 weeks. CONCLUSION: With recent technological advances, the laparoscopic approach has become easy to perform, safe, and should be considered the procedure of choice for pediatric splenectomy.     

Characteristics and Outcome of Minority Group Patients in Methadone Maintenance Treatment

Minority status is associated with mental and physical morbidity, substance dependence, and poor outcomes. To compare characteristics and treatment outcomes between patients from two minority groups in Israel (Christians and Muslims) and patients from the majority population (Jews) in methadone maintenance treatment (MMT), we prospectively studied all patients admitted to our clinic between 1993 and 2012 and followed up until 2013; 655 Jews, 67 Christians, and 37 Muslims. Christian patients differed from Jews and Muslims by younger age at admission to MMT, greater prevalence of drug injectors, and a higher proportion of Hepatitis-C and HIV sera positive. Muslims had comparatively less education and a lower proportion of females. The three groups had similar rates of one-year retention (75.9%) and opiate abstinence (68.1%). They also did not differ in long-term retention (up to 20 years): Muslims 5.5 years (95%CI 3.6-7.4), Christians 7.5 years (95%CI 6-9.1), and Jews 7.6 years (95%CI 7-8.2, p = .3). The Hepatitis-C incidence, however, was higher among the 21 admitted Hepatitis-C seronegative minorities (5.0/100 person years) than the 207 Hepatitis-C seronegative non-minority patients (1.7/100 person years, p=0.03). All groups had good treatment outcomes, except for Hepatitis-C seroconversion, which necessitates a specific preventive intervention among the minority groups.     

Bioethics Consultation Practices and Procedures: A Survey of a Large Canadian Community of Practice

The literature fails to reflect general agreement over the nature of the services and procedures provided by bioethicists, and the training and core competencies this work requires. If bioethicists are to define their activities in a consistent way, it makes sense to look for common ground in shared communities of practice. We report results of a survey of the services and procedures among bioethicists affiliated with the University of Toronto Joint Centre for Bioethics (JCB). This is the largest group of bioethicists working in healthcare organizations in Canada. The results suggest there are many common services and procedures of JCB bioethicists. This survey can serve as a baseline for further exploration of the work of JCB bioethicists. Common practices exist with respect to the domains of practice, individual reporting relationships, service availability within business hours and the education and training of the bioethicist.     

The Relationship Between Vulnerable Attachment Style,Psychopathology, Drug Abuse,and Retention in Treatment Among Methadone Maintenance Treatment Patients

The relationship between vulnerable attachment style, psychopathology, drug abuse, and retention in treatment among patients in methadone maintenance treatment (MMT) was examined by the Vulnerable Attachment Style Questionnaire (VASQ), the Symptom Checklist-90 (SCL-90), and drug abuse urine tests. After six years, retention in treatment and repeated urine test results were studied. Patients with vulnerable attachment style (a high VASQ score) had higher rates of drug abuse and higher psychopathology levels compared to patients with secure attachment style, especially on the interpersonal sensitivity, anxiety, hostility, phobic anxiety, and paranoid ideation scales. Drug abstinence at baseline was related to retention in treatment and to higher rates of drug abstinence after six years in MMT, whereas a vulnerable attachment style could not predict drug abstinence and retention in treatment. Clinical Implications concerning treatment of drug abusing populations and methodological issues concerning the VASQ’s subscales are also discussed.     

Enlarged meristems and delayed growth in plp mutants result from lack of CaaX prenyltransferases

Meristems require a myriad of intercellular signaling pathways for coordination of cell division within and between functional zones and clonal cell layers. This control of cell division ensures a constant availability of stem cells throughout the life span of the meristem while limiting overproliferation of meristematic cells and maintaining the meristem structure. We have undertaken a genetic screen to identify additional components of meristem signaling pathways. We identified pluripetala (plp) mutants based on their dramatically larger meristems and increased floral organ number. PLURIPETALA encodes the alpha-subunit shared between protein farnesyltransferase and protein geranylgeranyltransferase-I. plp mutants also have altered abscisic acid responses and overall much slower growth rate. plp is epistatic to mutations in the beta-subunit of farnesyltransferase and shows a synergistic interaction with clavata3 mutants. plp mutants lead to insights into the mechanism of meristem homeostasis and provide a unique in vivo system for studying the functional role of prenylation in eukaryotes.