Fibrin glue: an alternative technique for nerve coaptation--Part II. Nerve regeneration and histomorphometric assessment

The results of nerve repair with fibrin glue and microsuture were evaluated in rat nerve transection models. Ninety Wistar-Furth rat median nerves were exposed, transected, and repaired in an end-to-end fashion with one of four substances/techniques: 1) human fibrin sealant (Quixil); 2) autologous graft and human fibrin sealant (Quixil); 3) bovine fibrin sealant (Tissucol); and 4) nylon microsuture, epineurial technique. Histologic analyses were performed at 3-, 6-, and 9-month postoperative intervals, and factors evaluated included: presence of inflammatory cells (i.e., macrophages and T cells); number of Schwann cells at the repair site; number of blood vessels; fibrosis; axonal regeneration; and fiber alignment. An additional group underwent histologic analysis at 3 weeks following repair with Quixil. Surgical time of repair was also measured. Nerve repairs performed with fibrin sealants produced less inflammatory response and fibrosis, and better axonal regeneration and fiber alignment than nerve repairs performed with microsuture. In addition, the fibrin sealant techniques were quicker and easier to use. The authors conclude that fibrin sealant represents a good alternative technique to microsuture for peripheral-nerve repair.     

De novo gastrointestinal tumours after renal transplantation: role of CMV and EBV viruses

The development of new and more effective immunosuppressive agents has provided long-term survival for transplant recipients, thereby increasing the risk of de novo malignancy in chronic immunocompromised hosts. While de novo post-transplant lymphoproliferative diseases and skin cancer has been shown to have an increased incidence in long-term surviving solid organ transplant recipients, the association with gastrointestinal (GI) cancer is controversial. Over 12 yr, 20 patients (5%) out of 395 renal transplant recipients developed 23 de novo tumours; 11 skin cancer and 12 non-skin cancer. Four patients (1%) developed de novo tumours of the GI tract (three colon, and one gastric cancer). Immediately after tumour's diagnosis, immunosuppressive therapy was reduced; all patients were shifted from cyclosporine to Rapamicine within 30 d. The tumour was surgically resected with curative intent in three cases, while one patient had only palliative surgery because of metastatic disease. The post-operative courses was uneventful. All patients maintained normal graft function. However, three out of four patients (75%) died of progression of the neoplasm, within a median time from the diagnosis of 12 months. Further, we investigated a possible correlations between de novo GI cancer and HCV, HBV status, infections, cytomegalovirus (CMV) and Epstein-Barr virus (EBV) reactivation, episodes of rejection, and blood transfusions. All cases with GI de novo cancers reported in this paper developed CMV and EBV reactivation within three months after transplantation. Thereafter we suggest a closer follow-up for de novo GI cancer in renal transplants with early CMV and EBV reactivation in order to avoid delayed diagnosis.     

Open-label olanzapine treatment in bipolar I disorder: clinical and work functional outcomes

OBJECTIVES: The objective of this study was to describe clinical and work functional outcomes associated with 6-month open-label olanzapine treatment for bipolar I disorder. METHODS: The study consisted of 249 patients entering a 6-month open label phase after 12 weeks of acute double-blind haloperidol or olanzapine treatment. Baseline for analysis was defined as the beginning of open-label treatment. The clinical outcomes were symptomatic remission defined by a Y-MRS total score < or = 12 and a HAM-D total score < or = 8 at the end of 6 months of treatment. The work functional outcomes included work functional scores, the proportion of patients who reported to 'work' as employee, volunteers, students, or house workers and the proportion of patients who specifically reported to 'work for pay'. RESULTS: A total of 240 patients reported work functional outcomes post open-label baseline. Among them, 15.4% patients moved into a 'work group' from a 'no-work group' at baseline, while 7.1% did the opposite (p = 0.0065) and 13.3% reported an improvement to 'work for pay' status from a 'not working for pay' status at baseline, while there was 4.2% of worsening in employment status (p = 0.0007). Overall, improvement in the work functional score was found at all post-baseline time points, beginning at month two (p = 0.003).Limitations: Results of this study need to be confirmed by double-blind randomized controlled studies. There was a lack of detailed information on work functioning from the questionnaire. CONCLUSIONS: Open-label olanzapine treatment for 6 months was associated with improvements in work functional outcomes in patients with bipolar disorder.     

Long-term effect of laser treatment for dry age-related macular degeneration on choroidal hemodynamics

PURPOSE: To determine whether laser treatment applied according to the complications of age-related macular degeneration prevention trial (CAPT) has an effect on the choroidal circulation. DESIGN: Randomized controlled trial. METHODS: This study included 30 CAPT patients with bilateral drusen. Laser Doppler flowmetry was used to measure relative choroidal blood flow (Ch(flow)) in the fovea. Measurements were obtained through dilated pupils in both eyes of each patient before photocoagulation was applied in one eye. Measurements were repeated at three months (30 patients) and 28 months (23 patients). RESULTS: Average Ch(flow) at baseline, three months, and 28 months was 7.2 +/- 2.1 (+/-1 SD), 7.3 +/- 2.5, and 6.8 +/- 2.7 arbitrary units (AU) in the control eyes and 6.6 +/- 1.6, 7.0 +/- 2.3, and 7.8 +/- 3.0 AU in the treated eyes. In comparison to control eyes, there was no significant change in Ch(flow) in the treated eyes at three months after treatment. At 28 months, however, there was a 5.6% drop in Ch(flow) in control eyes and an 18.2% increase in Ch(flow) in treated eyes from baseline. The average difference of 23.8% between the percentage changes in Ch(flow) observed in the control and treated eyes was statistically significant (paired two-tailed Student t test; P = .05). CONCLUSIONS: Our results suggest an increase in choroidal blood flow 28 months after laser treatment according to the CAPT protocol. This increase may play a role in the mechanism leading to the disappearance of drusen after photocoagulation. Whether removal of drusen after photocoagulation is beneficial to the patients is not known at this time.     

A controlled clinical trial comparing the safety and immunogenicity of a new adjuvanted hepatitis B vaccine with a standard hepatitis B vaccine

A randomised trial was conducted in 285 adults not immune to hepatitis B (HB) to compare the safety and immunogenicity of a commercial aluminium-adjuvanted HB vaccine with and without an additional new adjuvant (AgB/RC-210-04 or AgB study groups, respectively). The additional adjuvant RC-529 is a fully synthetic monosaccharide mimetic of monophosphoryl lipid A. Subjects in the AgB/RC-210-04 (n=136) and AgB (n=149) groups were vaccinated intramuscularly on days 0, 30, and 180, according to the standard vaccination schedule for hepatitis B vaccines. Serum levels of anti-HBs were measured on days 30, 60, 90, 180, and 210. Standard safety assessments were made throughout the study period. The rates of seroprotection (anti-HBs > or =10.0 mIU/ml) were significantly greater for the AgB/RC-210-04 group at all time points: at day 90, the seroprotection rate, the primary endpoint of the trial, was 99% for AgB/RC-210-04 compared with 84% for AgB (p<0.0001). Similarly, geometric mean anti-HBs titres were significantly higher at all time points for the AgB/RC-210-04 group. There were more local reactions in the AgB/RC-210-04 group, however they were transient and this double-adjuvanted formulation was well tolerated. We conclude that the addition of a synthetic adjuvant to the AgB vaccine significantly enhanced the immunogenicity of the commercial vaccine AgB. The results indicate furthermore that a two-dose regime of the double-adjuvanted vaccine (schedule: 0-1 month) may be sufficient to achieve seroprotection in nearly 100% of individuals.     

Chapter 27: Research needs following initial licensure of virus-like particle HPV vaccines

Human papillomavirus virus-like particle (HPV VLP) HPV vaccines currently evaluated for licensing are likely to be available soon. Licensure will be based on evidence that the vaccine is well tolerated and provides near complete type-specific protection against HPV infections and their resulting lesions in the first few years after vaccination. Several important questions will remain to be answered after licensure to guide vaccine implementation and to permit the rational evaluation of vaccination in cancer prevention programs. These include the long-term safety and efficacy of vaccination, the optimal ages for vaccination, efficacy against HPV types not included in the vaccine and against existing infections, and efficacy in males. Modulators of vaccine efficacy (e.g., HIV infection) and immune mechanisms of long-term protection also remain to be defined. The real-world effectiveness of vaccination programs will need to be assessed. Issues related to the implementation of a vaccine that targets pre-adolescents and early adolescents and to the acceptability of a cancer vaccine targeted against a sexually transmitted infection will need to be understood before vaccination programs can be successful. It is hoped that continued improvements to the current HPV vaccines will lead to the introduction in future years of second generation vaccines that simplify delivery and/or expand its coverage. Finally, the natural history of HPV types not covered in the candidate vaccines will need to be carefully studied following vaccination. Public health authorities in various countries will play a pivotal role in determining if these questions are answered in a timely manner.     

Edge-to-edge mitral valve repair: the Columbia Presbyterian experience

Background

The edge-to-edge mitral valve repair, first described by Alfieri in 1995 treats mitral regurgitation when standard reparative techniques are difficult, unlikely to succeed, or have failed. This study examines one institution's medium-term experience with this procedure.

Methods

This study involved patients undergoing edge-to-edge mitral valve repair at a single institution from 1997 to 2003. Preoperative and postoperative echocardiograms were compared. Postoperative morbidity was examined including need for reoperation and long-term medical management. Thirty-day survival and long-term actuarial survival were also determined.

Results

Seventy-one patients comprised this study. Mitral regurgitation on echocardiogram went from 3.43 ± 0.86 to 0.39 ± 0.61 (p < 0.001) following repair. Thirty-day mortality was 3 of 71 (4.2%) patients. Actuarial survivals at 24 and 60 months were 84.5% and 58.3%, respectively; adjusted excluding noncardiac death they were 89.5% and 82.3%, respectively. Forty (56.3%) patients had concomitant ring placement and experienced similar survival to those repaired with the bow-tie stitch alone. Home telephone follow-up was conducted, and current medical therapy was determined on 51 patients; 59% were on a β-blocker, 31% were on an angiotensin-converting enzyme (ACE) inhibitor, 27% were on a diuretic, and 22% were on digoxin. All were New York Heart Association (NYHA) class I or II. Three patients (4.2%) underwent mitral valve reoperation after a mean of 299 ± 429 days. In no case did the bow-tie suture rupture.

Conclusions

Edge-to-edge mitral valve repair is a valuable tool in the armamentarium available to treat complex cases of mitral insufficiency or as an adjunct to standard repair techniques that fail to achieve an acceptable result.     

Infant mortality and air pollution: modifying effect by social class

Studies link air pollution with increased mortality; however, information on infants is scarce and inconclusive. OBJECTIVE: We studied short-term PM10 exposure, relating to increased respiratory-related infant mortality, and estimated for poor living conditions. METHODS: A case-crossover approach modeled the relationship between infant mortality (1 month-1 year of age), and ambient PM10 levels on days before death in Ciudad Juarez, Mexico (1997-2001). Socioeconomic level (SES) of the deceased was defined by residence location. RESULTS: Overall air pollutants did not affect infant mortality (odds ratio [OR] = 1.02, 95% confidence interval [CI] = 0.94-1.11 for PM10, lag1) but low SES increased risk. Each 20 microg/m3 in PM10 (24-hour average, lag1, cumulative over 2 previous days) increased respiratory-related mortality (OR = 1.61, 95% CI = 0.97-2.66; OR = 2.56; 95% CI = 1.06-6.17, respectively). Ozone levels did not affect infant mortality for any SES. CONCLUSIONS: Worse living conditions among lower SES concurred with increased mortality.