Non-HLA immunogenetic polymorphisms and the risk of complications after allogeneic hemopoietic stem-cell transplantation

BACKGROUND: Existing data indicate that non-human leukocyte antigen (HLA) immunogenetic polymorphisms influence the risk of complications after allogeneic hemopoietic stem-cell transplantation. However, prior studies have been limited by small sample size and limited genotyping. METHODS: We examined 22 polymorphisms in 11 immunoregulatory genes including cytokines, mediators of apoptosis, and host-defense molecules by polymerase chain reaction using sequence-specific primers in 160 related myeloablative transplants. Associations were confirmed in two independent cohorts. RESULTS: An intronic polymorphism in the tumor necrosis factor gene (TNF 488A) was associated with the risk of acute graft-versus-host disease (GVHD) (odds ratio [OR] 16.9), grades II to IV acute GVHD (OR 3.3), chronic GVHD (OR 12.5), and early death posttransplant (OR 3.4). Recipient Fas -670G and donor interleukin (IL)-6 -174G were independent risk factors for acute GVHD. Recipient IL-10 ATA and Fas -670 genotype were independent risk factors for chronic GVHD. Recipient IL-1beta +3953T was associated with hepatic acute GVHD, and Fas -670G was associated with major infection. CONCLUSIONS: These results highlight the potential importance of cytokine and apoptosis gene polymorphisms in stem-cell transplantation, and indicate that non-HLA genotyping may be useful to identify individuals at the highest risk of complications and new targets for therapeutic intervention.     

POCOman: new system for quantifying posterior capsule opacification

PURPOSE: To describe a new method of measuring posterior capsule opacification (PCO) and intraocular lens (IOL) rotation and report the validation of the method. SETTING: Ophthalmology Department, St. Thomas' Hospital, and Medical Imaging, Department of Physics, King's College, London, United Kingdom. METHOD: A new interactive software program, POCOman, was developed for the semiobjective assessment of PCO. Digital images of the posterior capsule, which can be acquired by any technique, are analyzed by the observer to determine the percentage area of PCO and assign a severity score. The system was validated by comparing it to clinical slitlamp evaluation of PCO and automated POCO system analysis using a library of 100 images taken from archives. The software also measures sequential IOL rotation for the evaluation of toric IOLs. RESULTS: An image could be analyzed in approximately 2 minutes. The results of the POCOman system correlated well with the results of the automated POCO system and clinical evaluation. CONCLUSIONS: The POCOman is an effective, user-friendly system for quantifying PCO. It can be obtained for free and has advantages over other methods.     

Hepatic artery infusion chemotherapy for metastatic colorectal cancer to the liver at the lahey clinic: comparison between two methods of treatment, surgical versus percutaneous catheter placement

This study updates our experience with hepatic artery infusion chemotherapy for colorectal liver metastases at the Lahey Clinic. It compares surgical versus percutaneous catheter methods, employing an external pump. The surgical series (SS) consisted of 58 patients (1970-1995) treated with floxuridine (FUDR), 20 mg/d for 4 to 5 weeks (modified in 1985; 2-week cycles). Percutaneous series (PS) consisted of 42 patients (1976-1995) treated with fluorouracil (5-FU), 20 mg/d for 10 days followed by a floxuridine (FUDR) schedule as with SS. Analysis consisted of tumor response, survival, and toxicity data between the two methods. Response rates showed no significant difference, SS (34%) and PS (48%) (P = 0.22). There were no significant differences in survival from treatment until death in SS (n = 58) of 13 months versus PS (n = 42) of 10.6 months (P = 0.39), from diagnosis until death, SS being 28.4 months versus PS of 26.4 months (P = 0.71) and from metastases until death, SS being 17.4 months versus PS of 22.2 months (P = 0.35). Hepatic toxicity was similar, but there was increased bone marrow toxicity, mucositis, and diarrhea for the PS. Response rates are similar for both our SS and PS and to that reported in recently randomized surgical trials. Hepatic artery infusion chemotherapy with FUDR by percutaneous catheter placement may be as effective as surgical catheter placement for colorectal liver metastases, but further study is needed.     

Steroid prophylaxis in eyes with uveitis undergoing phacoemulsification

AIM: To compare the efficacy of two preoperative steroid regimens for cataract surgery in patients with uveitis. METHODS: 40 uveitis patients with cataract underwent phacoemulsification and intraocular lens (IOL) implantation. Preoperatively they were randomised into two groups: group 1 (20 patients) received a single dose of intravenous methylprednisolone (15 mg/kg) half an hour before surgery, and group 2 (20 patients) received a 2 week course of oral prednisolone (0.5 mg/kg) which was tapered postoperatively. Preoperatively patients had aqueous flare and cells measured with the Kowa laser flare meter. On days 1, 7, 28, and 90 aqueous flare and cells were measured, and on days 7 and 90 fluorescein angiography was performed to determine the incidence of cystoid macular oedema (CMO). RESULTS: At all postoperative visits the mean increase in flare was greater for group 1 (intravenous steroid). Patients with posterior synechiae had greater blood-aqueous barrier damage (BAB) postoperatively. There were no statistically significant differences in logMAR visual acuity and incidences of CMO between the two groups at 7 and 90 days. CONCLUSION: A 2 week course of oral prednisolone, tapered postoperatively, produced a better recovery of the BAB than a single dose of intravenous methylprednisolone and is thus the recommended preoperative regimen.     

Evaluation of Gateshead carbon fibre rod as an implant material for repair of osteochondral defects: a morphological and mechanical study in the rabbit knee

Use of the Gateshead carbon fibre rod system remains controversial. Although it has been shown to enhance the repair of lesions in load bearing areas of convex articular surfaces, there is a lack of evidence to support the claim that it provides an inert scaffold for ingrowth of organised fibrous tissue. and thereby increasing the rate and quality of articular surface regeneration. This study examined osteochondral repair following implantation of a Gateshead rod in the femoral condyles of 25 rabbits for up to 32 weeks. using radiology, histology, scanning electron microscopy and mechanical testing. The repaired fibrocartilaginous surface layer was found to be persistently softer than the normal control and some repaired surfaces were worn, exposing the rod at 32 weeks. Whilst fibrous tissue grew into the outer braided sheath of the rod, the core remained impervious. The rod appeared to act as a space occupier, initially providing better subsurface support than found in natural healing. In the long term, however, it prevented subchondral bone restoration and re-establishment of the normal osteochondral junction, resulting in a quality of repair which did not differ from that found in naturally healing defects.     

The smoking cessation efficacy of varying doses of nicotine patch delivery systems 4 to 5 years post-quit day

BACKGROUND: This study was undertaken to evaluate the long-term smoking cessation efficacy of varying doses of transdermal nicotine delivery systems 4 to 5 years post-quit day. METHODS: A follow-up study was conducted 48 to 62 months after quit day among patients who were enrolled in the Transdermal Nicotine Study Group investigation. The latter study included group smoking cessation counseling and randomized assignment to 21, 14, or 7 mg nicotine patches or placebo patches. Seven of nine smoking cessation research centers participated in the long term follow-up investigation. RESULTS: The self-reported continuous quit rate among patients originally assigned 21 mg (20.2%) was significantly higher than rates for patients assigned 14 mg (10.4%), 7 mg (11.8%), or placebo patches (7.4%). Log rank survival analysis found no difference in relapse rates after 1 year postcessation. Smokers under age 30 years were significantly less likely to be abstinent at long term follow-up compared to smokers > or = 30 years of age (3 vs 13%, respectively). Mean weight gain in confirmed continuous quitters was 10.1 kg in men and 8.0 kg in women. Of the 63 continuous abstainers surveyed, 30 respondents (48%) reported that they no longer craved cigarettes, and no individual reported daily craving for cigarettes. CONCLUSIONS: Nicotine patch therapy with 21 mg/day patches resulted in a significantly higher long-term continuous abstinence rate compared to lower dose patches and placebo. Relapse rates among the various treatment conditions were similar after 1 year postcessation.     

Mannose-binding lectin deficiency does not increase the prevalence of Helicobacter pylori seropositivity

BACKGROUND: Mannose-binding lectin is an immune molecule that can bind to pathogens and initiate the complement cascade. In certain clinical situations, often characterized by immune compromise, mannose-binding lectin deficiency can increase the risk of infectious complications. Helicobacter pylori is one of the most common human infections and can bind mannose-binding lectin. Therefore, we examined whether mannose-binding lectin status influences the prevalence of H. pylori infection. METHODS: Two distinct populations were targeted. The first consisted of 166 volunteer blood donors, the second included 108 peripheral blood stem cell donors. All were tested for serological evidence of H. pylori infection, and had their mannose-binding lectin status characterized by genotyping, and quantification of mannose-binding lectin mannan-binding level and C4-deposition function in plasma. RESULTS: H. pylori positive blood donors had higher blood mannose-binding lectin levels, as measured by C4 deposition (median 0.67 vs. 0.40, P=0.009, hazard ratio 2.82, 95% confidence interval 1.29-6.19) and mannan-binding assays (median 1.83 vs. 1.26, P=0.02, hazard ratio 1.28, 95% confidence interval 1.03-1.59). A trend was also found between the presence of an MBL2 coding mutation and a reduced prevalence of H. pylori. No significant associations were found in the second population. CONCLUSIONS: Mannose-binding lectin deficiency does not increase the risk of H. pylori infection. The finding in one population that greater mannose-binding lectin activity might predispose to infection, suggests that this study should be repeated in other large cohorts of normal subjects.