Association of Early Kidney Allograft Failure with Preformed IgA Antibodies to β2-Glycoprotein I

In the current immunosuppressive therapy era, vessel thrombosis is the most common cause of early graft loss after renal transplantation. The prevalence of IgA anti–β₂-glycoprotein I antibodies (IgA-aB2GPI-ab) in patients on dialysis is elevated (>30%), and these antibodies correlate with mortality and cardiovascular morbidity. To evaluate the effect of IgA-aB2GPI-ab in patients with transplants, we followed all patients transplanted from 2000 to 2002 in the Hospital 12 de Octubre prospectively for 10 years. Presence of IgA-aB2GPI-ab in pretransplant serum was examined retrospectively. Of 269 patients, 89 patients were positive for IgA-aB2GPI-ab (33%; group 1), and the remaining patients were negative (67%; group 2). Graft loss at 6 months post-transplant was significantly higher in group 1 (10 of 89 versus 3 of 180 patients in group 2; P=0.002). The most frequent cause of graft loss was thrombosis of the vessels, which was observed only in group 1 (8 of 10 versus 0 of 3 patients in group 2; P=0.04). Multivariate analysis showed that the presence of IgA-aB2GPI-ab was an independent risk factor for early graft loss (P=0.04) and delayed graft function (P=0.04). There were no significant differences regarding patient survival between the two groups. Graft survival was similar in both groups after 6 months. In conclusion, patients with pretransplant IgA-aB2GPI-ab have a high risk of early graft loss caused by thrombosis and a high risk of delayed graft function. Therefore, pretransplant IgA-aB2GPI-ab may have a detrimental effect on early clinical outcomes after renal transplantation.     

Adrenergically mediated variations in the energy required to defibrillate the heart: observations in closed-chest, nonanesthetized dogs

The day-to-day variations in epicardial defibrillation threshold (DFT) were examined in closed-chest, unanesthetized dogs. In 11 animals, DFT decreased from 15.8 +/- 2.1 J (mean +/- SE) at the beginning of the study (day 1), to 7.4 +/- 1.7 J on day 2 (p less than .0001). DFT measured daily for 5 consecutive days in seven dogs decreased from 22.1 +/- 3.1 J on day 1 to 9.3 +/- 2.3 J on day 2 (p less than .01) and remained stable from day 2 to day 5. Transcardiac impedance, measured in six dogs, decreased from 112 +/- 6 omega on day 1 to 100 +/- 6 omega on day 2 (p = NS). Propranolol given on day 2 in 14 dogs increased DFT from 12.0 +/- 2.2 to 18.0 +/- 3.1 J (p less than .05). The effects on DFT of sequential administration of isoproterenol and propranolol were examined in 10 dogs. Isoproterenol decreased DFT from 10.0 +/- 1.9 to 5.5 +/- 1.5 J when given before propranolol (p less than .001, n = 10), and from 11.7 +/- 3.0 to 9.7 +/- 3.1 J when given after propranolol (p less than .05, n = 9). Propranolol increased DFT from 10.6 +/- 3.0 to 14.6 +/- 3.9 J when given before isoproterenol (p less than .02, n = 9), and from 10.7 +/- 1.4 to 14.4 +/- 1.5 J when given after isoproterenol (p less than .01, n = 10). These experiments demonstrate a sustained cardiac effect of epicardial defibrillation reflected by a decrease in DFT that is partially reversible by propranolol.(ABSTRACT TRUNCATED AT 250 WORDS)     

Beneficial effect of verapamil added to chronic ACE inhibitor treatment on renal function in hypertensive elderly patients

This study analysed the effect of low doses ofverapamil added to chronic treatment withangiotensin-converting enzyme (ACE) inhibitors onblood pressure and serum creatinine levels in eightelderly hypertensive patients who had a steadyincrease of serum creatinine while on ACE inhibitors.The study was performed in eight elderly hypertensivesubjects, five men and three women (mean age 70 ±2 years; systolic blood pressure 173 ± 4 mmHg; diastolic blood pressure 99 ± 1 mm Hg) andserum creatinine of 1.60 ± 0.27 mg/dl beforetreatment. During an average of 25 weeks, ACEinhibitors significantly reduced both systolic anddiastolic blood pressures, but serum creatinine levelswere increased over basal levels (0,68 ± 0,20 mg/dl, p < 0.05). During an average of 10 weeks,the addition of verapamil did not decrease bloodpressure further, but serum creatinine levels werereduced to baseline. Our study suggests that theaddition of verapamil to ACE inhibitors can reverseACE-induced increase in creatinine levels in elderlyhypertensive patients in whom this side effect isobserved. This revised version was published online in August 2006 with corrections to the Cover Date.     

Verhandlungen Ärztlicher Gesellschaften

Ohne Zusammenfassung     

Intrarater and Inter-rater Reliability of Maximal Voluntary Neck Muscle Strength Assessment Using a Handheld Dynamometer in Women With Headache and Healthy Women

Objective

This study aimed to determine the inter-rater and intrarater reliability, agreement, and minimal detectable change (MDC) of the neck muscle strength test using a handheld dynamometer in healthy women and women with headaches.

Combination of a long-acting delivery system for luteinizing hormone-releasing hormone agonist with Novantrone chemotherapy: increased efficacy in the rat prostate cancer model.

The combination of hormonal treatment based on a long-acting delivery system for the agonist [6-D-tryptophan]luteinizing hormone-releasing hormone ([D-Trp6]-LH-RH) with the chemotherapeutic agent Novantrone (mitoxantrone dihydrochloride) was studied in the Dunning R3327H rat prostate cancer model. Microcapsules of [D-Trp6]-LH-RH formulated from poly(DL-lactide-co-glycolide) and calculated to release a controlled dose of 25 micrograms/day were injected intramuscularly once a month. Novantrone (0.25 mg/kg) was injected intravenously once every 3 weeks. Three separate experiments were carried out. When the therapy was started 45 days after transplantation and continued for 70 days, tumor volume in the presence of the microcapsules (966 +/- 219 mm3) or Novantrone (3606 +/- 785 mm3) given alone was significantly decreased compared to controls (14,476 +/- 3045 mm3). However, the combination of microcapsules and Novantrone caused a greater inhibition of tumor growth (189 +/- 31 mm3) than the single agents. Similar effects were seen when the percent increase in tumor volume was examined. Tumor volume increased 10,527 +/- 1803% for the control group. The inhibition of growth caused by the [D-Trp6]LH-RH microcapsules alone (672 +/- 153% increase in volume) was again greater than that caused by Novantrone alone (2722 +/- 421% increase). The combination of the two agents was again the most effective, resulting in an increase in tumor volume of only 105 +/- 29%. Control tumors weighed 30.0 +/- 6.5 g. Tumor weights were much less in the groups treated with either microcapsules (3.28 +/- 0.69 g) or Novantrone (19.53 +/- 3.3 g) alone. The lowest tumor weights after 70 days of treatment were obtained in the group that received the combination of [D-Trp6]LH-RH microcapsules and Novantrone (1.02 +/- 0.2 g). Testes and ventral prostate weights were significantly diminished by the administration of microcapsules of [D-Trp6]LH-RH alone or in combination with Novantrone. In both of these groups, luteinizing hormone and prolactin levels were reduced and serum testosterone was suppressed to undetectable levels. Similar results were obtained in two other experiments in which the duration of treatment was 60 or 105 days. These results suggest that the overall response could reflect the inhibition of proliferation of hormone-independent cancer cells by Novantrone in addition to the suppressive effect of [D-Trp6]LH-RH on the growth of androgen-dependent tumor cells. The administration of Novantrone in combination with microcapsules of [D-Trp6]LH-RH might produce a better clinical response than LH-RH analog alone in patients with advanced prostate carcinoma.     

Do Implant Length and Width Matter for Short Dental Implants (<10 mm)? A Meta‐Analysis of Prospective Studies

Background: This meta‐analysis of prospective clinical trials was conducted to determine the effects of dental implant length and width on implant survival rate of short (<10 mm) implants. Methods: An electronic search of the PubMed database for relevant studies published in English from November 1998 to March 2012 was performed. Selected studies were randomized clinical trials, human clinical trials, or prospective trials with a clear aim of investigating the success or survival rate of short (<10 mm) implants. Results: Eight studies fulfilled the inclusion criteria and were subsequently analyzed. A total of 525 short (<10 mm) dental implants were analyzed, of which 253 were 3.5 mm in diameter (48.19%), 151 were 4.0 mm (28.76%), 90 were 4.1 mm (17.14%), 21 were 4.8 mm (4%), and 10 were 5.1 mm (1.9%). All implants included in this meta‐analysis had a follow‐up period of 12 to 72 months. The included studies reported on the survival rate and diameter of the implants. Six of the studies used “short implants” (7 to 9 mm), and the remaining were classified as “extra‐short implants” (≤6 mm). Five‐year estimated failure rates were 1.61% and 2.92%, respectively, for extra‐short and short implants (z = ?3.49, P <0.001, 95% confidence interval = 0.51% to 4.10%). Furthermore, it was found that the wider the implant, the higher the failure rate (estimated failure rate = 2.36%, 95% confidence interval = 1.07% to 5.23%). Conclusions: Neither implant length nor width seemed to significantly affect the survival rate of short implants (<10 mm). Nonetheless, further well‐designed randomized clinical trials are needed to confirm these findings.