Four-year follow-up of a prospective randomized trial of mycophenolate mofetil with cyclosporine microemulsion or tacrolimus following liver transplantation

BACKGROUND: This is a 4-yr follow-up of a trial using mycophenolate mofetil (MMF) induction in orthotopic liver transplantation (OLT). The goal of this study was to evaluate a multidrug approach that would reduce both early and long-term morbidity related to immunosuppression while maintaining an acceptable freedom from rejection. METHODS: This was a prospective, randomized, intent to treat study designed to compare the primary endpoints of rejection and infection, and secondary endpoints of liver function, renal function, bone marrow function, cardiovascular risk factors, and the recurrence of hepatitis C. Ninety-nine consecutive patients with end stage liver disease who underwent OLT were randomized to receive either cyclosporine microemulsion (N) (50 patients) or tacrolimus (FK) (49 patients) starting on postoperative day 2, with MMF and an identical steroid taper begun preoperatively. RESULTS: Ninety of 99 patients (N 46, FK 44) completed the 4-yr follow-up. The overall 4-yr patient and graft survivals were 93 and 89%, respectively. There was no significant difference in 4-yr patient (N 96% vs. FK 90%, p = ns) or graft (N, 90% vs. FK, 88%, p = ns) survival between groups. The 4-yr rejection rate was not significantly different in either arm (N = 34%, FK = 24%; p = 0.28). There were no differences in infection rates in either arm. The patients with hepatitis C had no differences in the viral titers or Knodell biopsy scores between groups. However, in the hepatitis C subgroup (37 patients), the FK patients had a significantly lower rejection rate (p = 0.0097) and a significantly lower clinically recurrent hepatitis C rate (p = 0.05) than the N patients. No difference was seen in the percent of patients weaned off of steroids after 4 yr (N 51%, FK 49%). There were no differences in the incidences of diabetes mellitus and hypertension. When renal dysfunction was analyzed, a significant difference in the number of patients whose creatinine had increased twofold since transplant was seen (N 63%, FK 38%, p = 0.04). CONCLUSIONS: Use of MMF induction and maintenance following OLT in conjunction with either N or FK and an identical steroid taper, resulted in an acceptable long-term incidence of rejection and infection, without an increase in long-term graft or patient morbidity.     

Practical considerations in future psoriasis therapies

Exciting new therapies are becoming available that allow dermatologists and patients safe and effective alternatives to traditional psoriasis therapy. Because these new biologic drugs are parenterally administered, practical aspects of their integration into clinical practice must be addressed. This article offers guidelines for incorporating subcutaneous,intramuscular, and intravenous injectables into dermatology offices. Several tiers of psoriasis care are outlined to encourage individual physicians to choose the optimum level of service compatible with their individual practices.     

Surveillance of influenza in Apulia, Italy, 1999-2000, 2000-2001, 2001-2002, and 2002-2003 seasons

BACKGROUND: The objective of this study was to evaluate, within the Italian National Influenza Epidemiological and Virological Surveillance, the rate of vaccination coverage, the incidence of Influenza Like-Illness (ILI), the incidence of Acute Respiratory Illness (ARI), and to identify the virus strains circulating in Apulia from 1999 to 2003. METHODS: Vaccination coverage rates were calculated based on the number of doses administered to individuals > 65 years of age. Every week, sentinel physicians reported ILI and ARI cases having occurred among their patients. Voluntary general practitioners (GPs) and paediatricians (Ps) collected oropharyngeal swab samples from patients suspected with ILI. Influenza viruses were isolated and identified by cell culture (MDCK cells) and RT-PCR. Virological surveillance was carried out by the ISS, in collaboration with a network of peripheral laboratories. RESULTS: In Apulia, vaccination coverage progressively increased to 68.6% during the 2002-2003 season. The analysis of ILI cases showed higher incidence rates during the 1999-2000 and 2002-2003 seasons. ARI rates appeared to have a more constant trend. ILI and ARI incidence rates were higher in the 0-14 year age group. CONCLUSION: The increase in vaccination coverage rates and implementation of the network of clinical, and epidemiological and virological surveillance are fundamental for the control and prevention of influenza.     

The role of the anterior commissure in callosal agenesis

Two individuals with callosal agenesis (J.P. and M.M.) and 10 neurologically normal participants were tested on tasks requiring interhemispheric visual integration. M.M., whose anterior commissure was within normal limits, was much worse at matching colors and letters between visual fields than within visual fields, whereas J.P., whose anterior commissure was greatly enlarged, showed no evidence of interhemispheric disconnection. This suggests that in some cases of callosal agenesis, probably a minority, an enlarged anterior commissure may compensate for the lack of the corpus callosum. Neither acallosal participant showed interhemispheric disconnection on tasks requiring integration of location and orientation, however, suggesting that the anterior commissure plays no role in such tasks. These tasks may depend on subcortical commissures, such as the intertectal commissure.     

Surface electromyographic analysis of exercises for the trapezius and serratus anterior muscles

STUDY DESIGN: This study used a prospective, single-group repeated-measures design to analyze differences between the electromyographic (EMG) amplitudes produced by exercises for the trapezius and serratus anterior muscles. OBJECTIVE: To identify high-intensity exercises that elicit the greatest level of EMG activity in the trapezius and serratus anterior muscles. BACKGROUND: The trapezius and serratus anterior muscles are considered to be the only upward rotators of the scapula and are important for normal shoulder function. Electromyographic studies have been performed for these muscles during active and low-intensity exercises, but they have not been analyzed during high intensity exercises. METHODS AND MEASURES: Surface electrodes recorded EMG activity of the upper, middle, and lower trapezius and serratus anterior muscles during 10 exercises in 30 healthy subjects. RESULTS: The unilateral shoulder shrug exercise was found to produce the greatest EMG activity in the upper trapezius. For the middle trapezius, the greatest EMG amplitudes were generated with 2 exercises: shoulder horizontal extension with external rotation and the overhead arm raise in line with the lower trapezius muscle in the prone position. The arm raise overhead exercise in the prone position produced the maximum EMG activity in the lower trapezius. The serratus anterior was activated maximally with exercises requiring a great amount of upward rotation of the scapula. The exercises were shoulder abduction in the plane of the scapula above 120 degrees and a diagonal exercise with a combination of shoulder flexion, horizontal flexion, and external rotation. CONCLUSION: This study identified exercises that maximally activate the trapezius and serratus anterior muscles. This information may be helpful for clinicians in developing exercise programs for these muscles.     

O6-alkylguanine-DNA alkyltransferases repair O6-methylguanine in DNA with Michaelis-Menten-like kinetics

O(6)-Alkylguanine-DNA alkyltransferase (AGT) repairs O(6)-methylguanine (O(6)mG) by transferring the methyl group from the DNA to a cysteine residue on the protein. The kinetics of this reaction was examined by reacting an excess of AGT (0-300 nM) with [5'-(32)P]-labeled oligodeoxynucleotides (0.5 nM) of the sequence 5'-CGT GGC GCT YZA GGC GTG AGC-3' in which Y or Z was G or O(6)mG, annealed to its complementary strand. The reactions, conducted at 25 degrees C, were quenched by the addition of 0.1 N NaOH at various times, and the extents of reaction were monitored by ion exchange HPLC with radiochemical detection. The time courses followed first-order kinetics. The first-order rate constants were plotted against the initial concentration of AGT and fitted to the hyperbolic equation k(obs) = k(inact)[AGT](0)/(K(S) + [AGT](0)). The K(S) values for hAGT of 81-91 nM are 10-fold lower than the dissociation constants of hAGT (C145S) to unmodified and O(6)mG-containing DNA obtained by EMSA and indicate that AGT has a preference for binding to O(6)mG in DNA. The proteins reacted with DNA in which Y = O(6)mG and Z = G faster than Y = G and Z = O(6)mG due to an approximately 10-fold increase in k(inact). These results suggest that the sequence specificity in the repair of O(6)mG is manifested in the methyl transfer not in the O(6)mG recognition step.     

Palliative treatment for malignant jaundice: endoscopic vs surgical approach

In this retrospective, comparative study a total of 107 patients, presenting with malignant inoperable strictures of common bile duct, due to a pancreatico-biliary malignancy, underwent palliative treatments. In a group, consisting of 82 patients (76.64%), endoscopic stenting procedures were performed; polyethylene stents or self-expanding metal stents were applied in 37 and 45 patients, respectively. The prerequisites for a successful endoscopic stenting were a) accuracy of diagnosis and b) exclusion of patients presenting with tumors potentially treatable by a curative resection. In the other group, consisting of 25 patients (23.36%), biliary-enteric bypass procedures were performed. Endoscopic treatment was successful in 97.5% of the cases (80/82); complication rate was 7.3% (6 patients on 82), and mortality rate was 3.6% (3 patients on 82). Median hospital stay was 13.4 and 7.3 days in patients treated with plastic stents and metallic stents, respectively. Bypass surgery was successful in 99% of the cases (24/25); complication rate was 24% (6 patients on 25), and mortality rate was 16% (4 patients on 25). Median hospital stay was 26 days. For the patients in whom a curative resection could not be performed, both the above mentioned methods resulted in a high rate of immediate technical and therapeutic success. However, the surgical approach showed a significantly higher rate in procedure-related mortality and morbidity; in addition, the hospital stay lasted longer in surgically treated patients. The patients who are definitely unsuitable for curative resection are better managed by positioning a stent. The use of metal stents should be preferred in those less serious patients who may supposedly survive longer.     

High-risk pulmonary surgery in potential candidates for a heart transplant

Severe ventricular dysfunction and concomitant infection are considered absolute contraindications for major thoracic operations and immunosuppressive therapy, respectively. However, cardiac transplantation represents the first-choice treatment in advanced heart failure. We report the case of a patient with dilated cardiomyopathy and severe left ventricular dysfunction (ejection fraction = 25%), initially not considered as a potential heart transplant candidate due to the presence of a lung abscess. The patient subsequently underwent atypical pulmonary resection with intraoperative and perioperative intraaortic balloon counter-pulsation for circulatory support and was then listed for cardiac transplant. Pitfalls and intra/postoperative strategy, all of which are potentially important aspects in minimizing operative risk, are discussed.