Naloxone suppresses buprenorphine stimulation of plasma prolactin

The effects of parenterally-administered buprenorphine and simultaneous injection of naloxone was evaluated in six healthy adult males. Each subject was studied on six occasions, an average of 10 days apart, and received either two simultaneous intramuscular injections of saline, buprenorphine 0.3 mg and saline, or buprenorphine 0.3 mg and 0.6 mg, 0.45 mg, 0.3 mg, or 0.15 mg of naloxone. Simultaneous injection of buprenorphine 0.3 mg and saline resulted in an average increase in plasma prolactin above baseline levels of approximately 10 and 25 ng/ml, 30 and 55 minutes after injection. Buprenorphine-induced stimulation of plasma prolactin levels was statistically significantly greater than basal prolactin values (p less than 0.01). When 0.6 mg of naloxone was simultaneously injected with 0.3 mg buprenorphine, peak plasma prolactin levels were significantly lower (p less than 0.05) than prolactin values after administration of 0.3 mg buprenorphine and saline. Simultaneous injection of 0.45 mg naloxone and 0.3 mg buprenorphine also resulted in a significant attenuation (p less than 0.05) of buprenorphine-stimulated prolactin levels. Injection of 0.3 mg or 0.15 mg of naloxone did not inhibit prolactin stimulation produced by buprenorphine 0.3 mg. These findings demonstrate a dose-effect relationship between naloxone concentration and suppression of the increase in plasma prolactin levels produced by administration of buprenorphine 0.3 mg. As prolactin stimulation occurs shortly after opioid agonist administration and is temporally concordant with the rapid induction of pharmacologic reinforcement associated with opiate abuse, naloxone added to buprenorphine parenteral preparations may reduce the abuse potential of buprenorphine.     

The determinants of mortality and morbidity after multiple-valve operations

The factors predictive of hospital mortality and morbidity after contemporary multiple-valve surgical procedures were identified to develop strategies to improve the results of such procedures. Preoperative, intraoperative, and postoperative information was collected prospectively on 90 consecutive patients undergoing surgical procedures between 1982 and 1984. The operative mortality was 5.6%, and the incidence of postoperative low-output syndrome was 16.7%. Multivariate logistic regression analysis identified tricuspid regurgitation (p less than .03, improvement-of-fit chi square) and the aortic valve lesion (p less than .03) as the independent predictors of postoperative complications (mortality or low-output syndrome). Patients with tricuspid regurgitation and right ventricular decompensation and those with aortic stenosis and left ventricular hypertrophy had limited ventricular functional reserve and faced an increased risk. Improved methods of myocardial protection may reduce the risk in these patients.     

Relationship between patent foramen ovale and ischemic cerebrovascular events in children

Objectives: The objective is to report the feasibility and technique of treating popliteal artery aneurysms (PAA) with a stent made of nitinol rings externally supported by thin polyester (Anaconda limbs). Background: PAA are the most common peripheral aneurysms. The main limitations of stents used in these settings are: short lengths, longitudinal and horizontal compliance mismatch; graft failure from angulation and movement at the joint level; and dislodgment. Methods: This is a prospective multicenter cohort study of consecutive symptomatic and asymptomatic PAA treated in tertiary vascular centers. Outcomes included patency of the stent and postoperative time‐to‐independent‐ambulation and to‐climb‐a‐flight‐of‐stairs. Results: Fourteen PAA were treated in 12 men, age 72 ± 3 years. The median ASA classification was 2.5. The length of artery covered was 147 ± 41 mm. The PAA diameter was 31 ± 5 mm, 6 were symptomatic. One stent was used in 6 aneurysms, two in 7, and three in 1. The average stent diameter was 10 ± 1 mm. The length of the proximal neck was 24 ± 6 mm with a diameter of 9.8 ± 1.9, and length of the distal neck 23 ± 3 mm with a diameter of 8.7 ± 1.2 mm. In 6 aneurysms, the stent crossed the knee joint. There was no mortality, and one stent occluded (primary patency 93% at 6 ± 3 months). The median hospital stay was 1.7 days, time to independent ambulation was 3 hr and the time to climbing a flight of stairs was 1 day. Conclusions: The use of Anaconda limbs for endovascular repair of PAA is feasible and safe. © 2008 Wiley‐Liss, Inc.     

Atrial activity during cardioplegia and postoperative arrhythmias

Cardioplegia provides excellent protection for the left ventricle, but the right atrium may be poorly protected. Myocardial temperatures, right atrial electrical activity, and postoperative arrhythmias were assessed in 103 patients participating in two consecutive randomized trials comparing blood cardioplegia (n = 36), crystalloid cardioplegia (n = 38), and diltiazem crystalloid cardioplegia (n = 29). Both right atrial and right ventricular temperatures were significantly warmer (p less than 0.05) during delivery of the blood cardioplegic solution than during delivery of either the crystalloid or the diltiazem crystalloid cardioplegic solutions; the aortic root temperatures were 9 degrees +/- 2 degrees C with blood cardioplegia and 5 degrees + 1 degrees C with both crystalloid and diltiazem crystalloid cardioplegia. Atrial activity during cardioplegic arrest was greatest with blood cardioplegia (12 +/- 3 beats/min), lower with crystalloid cardioplegia (10 +/- 2 beats/min), and minimal with diltiazem crystalloid cardioplegia (5 +/- 1 beats/min, p less than 0.05). Perioperative ischemic injury (by creatine kinase MB isoenzyme analysis) was greatest with crystalloid cardioplegia (p less than 0.05). Postoperative supraventricular arrhythmias (both treated and untreated) were more frequent after crystalloid cardioplegia (crystalloid, 63%; blood, 40%; diltiazem, 47%; p less than 0.05). Patients in whom supraventricular arrhythmias developed had significantly more postoperative ischemic injury (by creatinine kinase MB isoenzyme analysis, p less than 0.05). Blood cardioplegia reduced supraventricular arrhythmias by reducing ischemic injury despite warmer intraoperative temperatures and more right atrial activity. Diltiazem crystalloid cardioplegia reduced postoperative arrhythmias by improving intraoperative myocardial protection and suppressing intraoperative and postoperative atrial activity. Crystalloid cardioplegia cooled but did not arrest the right atrium intraoperatively, resulted in the most perioperative ischemic injury, and yielded the highest incidence of postoperative supraventricular arrhythmias.     

Epirubicin,Cisplatin and Protracted Venous Infusion 5-Fluorouracil Chemotherapy for Advanced Salivary Adenoid Cystic Carcinoma

AimsAdenoid cystic carcinoma (ACC) is a rare tumour that usually arises in the salivary glands. Initial management is surgery often combined with adjuvant radiotherapy. Chemotherapy is reserved for treatment of symptomatic recurrence. We evaluated the combination of epirubicin, cisplatin and protracted venous infusion 5-fluorouracil (ECF) in the management of ACC.Materials and methodsPatients referred for treatment of advanced, symptomatic ACC were considered. The drugs given were epirubicin 50 mg/m² 3-weekly, cisplatin 60 mg/m² 3-weekly and protracted venous infusion 5-fluorouracil 200 mg/m²/day.ResultsEight patients (median age 46 years) received a median of five cycles of chemotherapy. All patients had had previous surgery, seven had had previous radiotherapy and one had had previous chemotherapy. One patient showed a partial response (duration 34 months) and five showed stable disease (median duration 13.6 months [6.8–15.9+ months]). Median survival was 27 months (3.5–62.3 months).ConclusionsThe activity of ECF in ACC of the head and neck seems to be similar to the combination of cisplatin and 5-fluorouracil and single-agent epirubicin.     

Malignant peripheral nerve sheath tumour in the ischio-rectal fossa

Primary sarcomas in the ischiorectal fossa are occasionally reported and represent a significant challenge due to the proximity of rectum, levator muscles and pudendal neurovascular structures. We report a case in which the diagnosis changed between biopsy (desmoid tumour) and resection (malignant peripheral nerve sheath tumour), requiring a multidisciplinary surgical approach involving different sub-specialties. It also illustrates the importance of undertaking sarcoma surgery in a recognized sarcoma centre with sarcoma expertise available across a range of disciplines.     

Accelerated myocardial metabolic recovery with terminal warm blood cardioplegia

Although blood cardioplegia provides excellent protection, myocardial metabolic recovery is delayed. To evaluate the benefits of a terminal warm cardioplegic infusion after cold blood cardioplegia, we performed a prospective randomized trial in 20 patients undergoing elective coronary bypass grafting. Eleven patients received cold blood cardioplegia and nine patients received cold blood cardioplegia and warm blood cardioplegia before cross-clamp removal (hot shot). The hot shot provided oxygen and removed excess lactate from the arrested heart. After the hot shot lactate was extracted by the heart and tissue adenosine triphosphate and glycogen concentrations were preserved. Atrial pacing and volume loading 3 and 4 hours postoperatively decreased myocardial lactate extraction after cold blood cardioplegia but increased lactate extraction after the hot shot. Left atrial pressures were higher at similar end-diastolic volumes (by nuclear ventriculography), which suggested decreased diastolic compliance after cold blood cardioplegia. Terminal warm blood cardioplegia accelerated myocardial metabolic recovery, preserved high-energy phosphates, improved the metabolic response to postoperative hemodynamic stresses, and reduced left atrial pressures.     

The 86-kD subunit of Ku autoantigen mediates homotypic and heterotypic adhesion of multiple myeloma cells.

Previous studies have shown that triggering multiple myeloma (MM) cells via CD40 induces IL-6-mediated autocrine growth as well as increased expression of cell surface adhesion molecules including CD11a, CD11b, CD11c, and CD18. In this study, we generated the 5E2 mAb which targets an antigen that is induced upon CD40 ligand (CD40L) activation of MM cells. Immunofluorescence, immunoprecipitation, and protein sequencing studies identified the target antigen of 5E2 mAb as the 86-kD subunit of the Ku autoantigen. We demonstrate that increased cell surface expression of Ku on CD40L-treated cells is due to migration of Ku from the cytoplasm to the cell surface membrane. Moreover, cell surface Ku on CD40L-treated MM cells mediates homotypic adhesion of tumor cells, as well as heterotypic adhesion of tumor cells to bone marrow stromal cells and to human fibronectin; and 5E2 mAb abrogates IL-6 secretion triggered by tumor cell adherence to bone marrow stromal cells. These data suggest that CD40L treatment induces a shift of Ku from the cytoplasm to the cell surface, and are the first to show that Ku functions as an adhesion molecule. They further suggest that cell surface Ku may play a role in both autocrine and paracrine IL-6-mediated MM cell growth and survival.     

Alcohol effects on hCG-stimulated gonadal hormones in women

Chronic alcohol abuse is associated with derangements of reproductive function in women. The mechanism of increased risk for alcohol-related abortions and fetal alcohol syndrome is unknown. The goal of this study was to determine if acute alcohol administration affected gonadal steroid hormone levels after administration of human chorionic gonadotropin (hCG) to normal healthy women. hCG was used to simulate the hormonal milieu during the first trimester of pregnancy. Ten women were studied during the mid-luteal phase (between days 17 and 23) of their menstrual cycle. Plasma estradiol, progesterone and prolactin were measured before and after simultaneous administration of 5000 I.U. of hCG (Profasi) and alcohol or placebo solution under double-blind conditions. There was a significant increase in plasma estradiol (P less than .001) and prolactin levels (P less than .01) after hCG and alcohol administration but not after hCG and placebo administration. Plasma progesterone increased significantly (P less than .001) above base line after hCG and placebo administration but this was not observed after hCG and alcohol administration. Since progesterone is essential for the maintenance of pregnancy, alcohol's attenuation of the expected progesterone response to hCG stimulation could increase the risk of spontaneous abortion. An alcohol-induced increase in estradiol after hCG administration could contribute to risk for fetal dysmorphology during the first trimester of pregnancy.