Lack of effect of 5HT3 antagonist in mediating subjective and behavioral responses to cotinine

Previous studies have shown that cotinine, a metabolite of nicotine, may antagonize some of the therapeutic effects of nicotine. The mechanisms underlying cotinine's effects are unclear, but cotinine has been observed to increase serotonin levels in the brain. Thus, it is possible that blocking serotonin effects may antagonize the actions of cotinine, thereby reducing its impact on responses to nicotine. This study determined whether granisetron, a 5HT(3) receptor antagonist, would enhance the efficacy of the nicotine patch. Subjects were randomly assigned to one of the three granisetron conditions (N=43 for 2 mg/day; N=43 for 1 mg/day; N=42 for 0 mg/day) and asked to take the assigned medication daily during 15 days of tobacco abstinence. Because we were interested in interactions between cotinine and serotonin, all groups were also treated with a 21-mg nicotine patch. Assessments of withdrawal symptoms were made for 1 week during baseline smoking and several times during the experimental period. There was a near but nonsignificant difference among groups on a measure of tobacco withdrawal and no significant differences on global measures of drug effects or physiological measures. The data do not strongly support the hypothesis that 5HT(3) agonism is the mechanism by which cotinine offsets the effects of nicotine.     

The seroprevalence of varicella zoster antibodies in Behçet's and other skin diseases

The purpose of this study was to investigate the association of the varicella zoster virus (VZV) IgG, and IgM antibodies with Behçet's and other skin diseases (group 1: recurrent aphthos stomatitis, fungal infections, psoriasis; group 2: vitiligo, lichen planus). Twenty eight patients with Behçet's disease (BD), and 117 patients with dermatological disorders other than BD were evaluated for specific VZV IgG and IgM antibodies by using a third generation enzyme-linked immunosorbent assay (ELISA). The Mantel Heizshel ² method was used to adjust the confounding of age and sex of the patients. The serological positivity for VZV IgG and IgM antibodies in BD was not statistically different from other skin diseases. When we considered the age of the patients, ² = 2.64, CI (0.27–1.65), odds ratio (1, 1.25, 2.21) (p = 0.10) and when we considered the sex of the patients, ² = 0.31, CI (0.81–1.28), odds ratio (1, 1.45, 1.41), (p = 0.57).     

Comparison of alpha-stat and pH-stat cardiopulmonary bypass in relation to jugular venous oxygen saturation and cerebral glucose-oxygen utilization

Jugular venous oxygen saturation (SJVO(2)) reflects the balance between cerebral blood flow and metabolism. This study was designed to compare the effects of two different acid-base strategies on jugular venous desaturation (SJVO(2) <50%) and cerebral arteriovenous oxygen-glucose use. We performed a prospective, randomized study in 52 patients undergoing cardiopulmonary bypass (CPB) at 27 degrees C with either alpha-stat (n = 26) or pH-stat (n = 26) management. A retrograde internal jugular vein catheter was inserted, and blood samples were obtained at intervals during CPB. There were no differences in preoperative variables between the groups. SJVO(2) was significantly higher in the pH-stat group (at 30 min CPB: 86.2% +/- 6.1% versus 70.6% +/- 9.3%; P < 0.001). The differences in arteriovenous oxygen and glucose were smaller in the pH-stat group (at 30 min CPB: 1.9 +/- 0.82 mL/dL versus 3.98 +/- 1.12 mL/dL; P < 0.001; and 3.67 +/- 2.8 mL/dL versus 10.1 +/- 5.2 mL/dL; P < 0.001, respectively). All episodes of desaturation occurred during rewarming, and the difference in the incidence of desaturation between the two groups was not significant. All patients left the hospital in good condition. Compared with alpha-stat, the pH-stat strategy promotes an increase in SJVO(2) and a decrease in arteriovenous oxygen and arteriovenous glucose differences. These findings indicate an increased cerebral supply with pH-stat; however, this strategy does not eliminate jugular venous desaturation during CPB. IMPLICATIONS: A prospective, randomized study in 52 patients during cardiopulmonary bypass revealed that pH-stat increased jugular venous oxygen saturation and decreased arteriovenous oxygen-glucose differences. There was no difference in the incidence of jugular venous desaturation. These findings suggest an increased cerebral blood flow with no protection against jugular venous desaturation during pH-stat.     

Appropriate timing of surgical intervention after transmural acute myocardial infarction

OBJECTIVE: Recommended timing of coronary revascularization after transmural acute myocardial infarction ranges from immediate surgical intervention to repair 4 weeks after infarction. Such wide variation has created a dilemma in the management of these patients. The objective of this study was to delineate the optimal timing of revascularization after transmural acute myocardial infarction in a large and contemporary patient population. METHODS: We performed a retrospective multicenter analysis of 32,099 patients who underwent coronary artery bypass grafting as the sole procedure after transmural myocardial infarction between 1991 and 1996 by 179 surgeons at 33 hospitals in New York State. RESULTS: Overall hospital mortality for all patients who underwent coronary revascularization with a history of transmural myocardial infarction was 3.3%. Hospital mortality decreased with increasing time interval between revascularization and transmural acute myocardial infarction: 14.2%, 13.8%, 7.9%, 3.8%, 2.9%, and 2.7% for less than 6 hours, 6 hours to 1 day, 1 to 3 days, 4 to 7 days, 7 to 14 days, and greater than 15 days, respectively. Multivariate analyses of 43 potential risk factors suggests that revascularization within 3 days of transmural acute myocardial infarction is independently associated with mortality. CONCLUSIONS: Coronary revascularization within 3 days of a transmural acute myocardial infarction might be an added risk for mortality. In the absence of absolute indications for emergency surgical intervention, such as structural complications and ongoing ischemia, a 3-day waiting period before surgical revascularization should be considered.     

Prolonged donor ischemic time does not adversely affect long-term survival in adult patients undergoing cardiac transplantation

OBJECTIVE: With liberalization of donor eligibility criteria, organs are being harvested from remote locations, increasing donor ischemic times. Although several studies have evaluated the effects of prolonged donor ischemic times on short-term survival and graft function, few have addressed concerns regarding long-term survival. METHODS: Over the last 11 years, 819 consecutive adults underwent cardiac transplantation at Columbia Presbyterian Medical Center. Recipients were separated into the following 4 groups based on donor ischemic time: <150 minutes, 150 to 200 minutes, 200 to 250 minutes, and >250 minutes. Statistical analysis included Kaplan-Meier survival and Cox proportional hazard models to identify predictors of long-term survival. RESULTS: Donor ischemic time was 120.1 +/- 21.1 minutes for group 1 (n = 321), 174.1 +/- 14.7 minutes for group 2 (n = 264), 221.7 +/- 14.6 minutes for group 3 (n = 154), and 295.5 +/- 37.1 minutes for group 4 (n = 80) (P <.001). There were no significant differences in recipient age, donor age, etiology of heart failure, United Network for Organ Sharing status, or history of previous cardiac surgery among the groups (P = NS). Prolonged donor ischemic time did not adversely affect long-term survival, with actuarial survival at 1, 5, and 10 years of 86.9%, 75.2%, and 56.4% for group 1; 86.2%, 76.9%, and 50.9% for group 2; 86.4%, 71.0%, and 43.7% for group 3; and 86.7%, 70.1%, and 50.9% for group 4 (P =.867). There was no significant difference in freedom from transplant coronary artery disease among the 4 groups (P =.474). CONCLUSIONS: Prolonged donor ischemic time is not a risk factor for decreased long-term survival. Procurement of hearts with prolonged donor ischemic time is justified in the setting of an increasing recipient pool with a fixed donor population.     

Failure strength of bioabsorbable interference screws: effects of in vivo degradation for 12 weeks

We investigated the effect of in vivo degradation for 6-12 weeks on the fixation strength of polylactide bioabsorbable interference screws. Ten bioabsorbable interference screws were used to fix the patellar tendon autograft in ten live sheep knees, which were equally divided into two groups and killed in the 6th or 12th week. The control group consisted of four cadaveric knees. Following the killing of the animals the screws were retrieved and reused to fix patellar tendon grafts in cadaveric sheep knees. Tendon pull-out tests were performed for the partially degraded screws, for the control group, and for the reused screws of the control group. Macroscopic and microscopic examinations of the 6- and 12-week specimens were performed. Tendons pulled-out with an average force of 357+/-30 N in the cadaveric control group on the first use and with 465+/-118 N on the second use. The partially degraded screws failed with a mean load of 399+/-119 N in the 6-week group, and 12-week screws at 447+/-72 N. No macroscopic sign of degradation was observed on the retrieved screws. Histological examination of the 6 week specimens showed necrotic changes in the tendon around screw contact areas. Healing with granulation tissue was present in the same area in the 12th week. Foreign body reaction or an excessive inflammatory reaction was not observed. In vivo degradation of poly- l-lactide interference screws for 12 weeks thus causes neither a loss in the fixation strength of the screws nor an obvious inflammatory reaction.