Isolated Donor Specific Alloantibody-Mediated Rejection after ABO Compatible Liver Transplantation

Antibody-mediated rejection (AMR) after liver transplantation is recognized in ABO incompatible and xeno-transplantation, but its role after ABO compatible liver transplantation is controversial. We report a case of ABO compatible liver transplantation that demonstrated clinical, serological and histological signs of AMR without evidence of concurrent acute cellular rejection. AMR with persistently high titers of circulating donor specific antibodies resulted in graft injury with initial centrilobular hepatocyte necrosis, fibroedematous portal expansion mimicking biliary tract outflow obstruction, ultimately resulting in extensive bridging fibrosis. Immunofluorescence microscopy demonstrated persistent, diffuse linear C4d deposits along sinusoids and central veins. Despite intense therapeutic intervention including plasmapheresis, IVIG and rituximab, AMR led to graft failure. We present evidence that an antibody-mediated alloresponse to an ABO compatible liver graft can cause significant graft injury independent of acute cellular rejection. AMR shows distinct histologic changes including a characteristic staining profile for C4d.     

Central serous chorioretinopathy and risk for obstructive sleep apnea

Patients with obstructive sleep apnea (OSA), in comparison to controls, have increased levels of circulating epinephrine and norepinephrine, both of which are risk factors for the development of central serous chorioretinopathy (CSCR). The aim of this pilot study was to investigate the frequency of symptoms that suggest OSA in CSCR patients and normal controls. The Berlin Questionnaire, a validated research tool to assess risk for OSA, was administered to 29 patients who met the criteria for active, acute, non-steroid-induced CSCR and 29 controls matched for age and sex. In this retrospective case-controlled study, the main outcome measure was increased risk for OSA. The mean age of the patients was 47.8 years (range 29–72) and the mean age of controls was 47.3 years (range 25–70). Seventy-six percent (22) of both groups were men. Survey scores showed 58.6% (17) of patients with CSCR to be at an increased risk for OSA compared to 31.0% (nine) of controls. A conditional logistic regression analysis showed that the CSCR group had a higher proportion with an increased risk for OSA compared to the control group (odds ratio=3.67; 95% CI: 1.02, 13.14; P = 0.046). Patients with CSCR may be more likely than other adults to have OSA, and screening for this sleep disorder should be considered in this population. Further research is warranted to determine whether sleep apnea may contribute to the development of CSCR, and to assess whether treatment of sleep apnea might offer a new therapeutic option for some patients with CSCR.     

Health-related quality of life and pressure ulceration assessment in patients treated in the community

Little is known of the impact of pressure ulceration on adult patients' health-related quality of life. The purpose of this study was to determine the impact pressure ulceration has on pressure ulcer patients cared for in the community. A case control study design was used by drawing a random sample from patients receiving community nursing care, stratified by the presence of pressure ulceration. In all, 75 patients with pressure ulcers were compared with 100 controls without ulcers using the four-point ulcer grading scale described by United Kingdom consensus guidelines. Patients were interviewed using the Short Form-36 (SF-36) questionnaire and activities of daily living assessed using the modified Barthel scale. Patients with pressure ulcers had significantly poorer physical function (mean difference (d) = 37.6, 95% CI 28.6-46.6, p < 0.001) and social functioning (d = 33.9, 95 % CI 24.0-43.9, p < 0.001) than published age- and sex-matched normative data from the United Kingdom. The difference between cases and controls was much smaller in these domains, with neither approaching statistical significance. After adjustment for age and gender, scores for bodily pain were poorer in patients with no ulceration (d = -10.5, 95% CI - 20.6 to - 0.4, p = 0.042) indicating greater pain in these patients compared with the cases with ulceration. Activities of daily living determined by the modified Barthel scale showed reduced self-care (d = -7.6, 95% CI -12.5 to - 2.7, p = 0.010) and mobility (d = -9.2, 95% CI -14.6 to - 3.8, p = 0.001) in patients with pressure ulceration. The overall ability to perform these activities was also significantly poorer in this group (d = -16.3, 95% CI -27.3 to -5.3, p = 0.004). While patients with pressure ulceration experience some deficits in their health-related quality of life compared with a normal population, these differences are similar to those experienced by other patients receiving community nursing care.     

The mechanical efficiency of treadmill running against a horizontal impeding force

1. A method for determining the apparent mechanical efficiency of running against a horizontal impeding force is described. The results of studies on three well trained athletes have been summarized.2. A linear relation was found between metabolic rate and external work rate. The apparent mechanical efficiency was calculated as the inverse of the slope of the linear regression line of metabolic rate on external work rate x 10(2) (percentage).3. The over-all mean for apparent load-running efficiency (LRE) was 36.1%. The differences in LRE between subjects were not statistically significant. No measurable change in LRE occurred with habituation.4. Values are given for E(k), the net energy cost of unloaded horizontal treadmill running per kilogram of bodyweight and per kilometre of distance covered. The over-all mean for E(k) was 0.83 kcal. kg(-1). km(-1).5. The efficiency values obtained are discussed and compared with other values of running efficiency obtained by different methods, and with studies on isolated muscle.     

Three novel PROC gene lesions causing protein C deficiency

Hallam PJ, Mannucci P, Tripodi A, Bevan D, Laursen B, Tengborn L, Wacey A, Cooper DN. Three novel PROC gene lesions causing protein C deficiency. Clin Genet 1998: 54: 231–233. 0 Munksgaard, 1998
Missense mutations. three of them novel (Am210→Val, Asn248→ Ile, Ah355→Val), were found in the protein c ( PROC ) genes of 7 patients with inherited protein C deficiency associated with venous thrombosis. Comparison with the phenotypic effects of mutations in the analogous residues of factor IX causing hdernophilia B and the use of molecular modelling has provided explanations as to how these lesions might alter either the structure, function or secretion of the protein C molecules encoded.     

The contribution of genotypes at the MEFV and SAA1 loci to amyloidosis and disease severity in patients with familial Mediterranean fever

OBJECTIVE: The clinical profile in familial Mediterranean fever (FMF), including its major manifestation, amyloidosis, is influenced by MEFV allelic heterogeneity and other genetic and/or environmental factors. In this study, we analyzed the contribution of genotypes at the MEFV and SAA1 loci to disease severity and to the development of amyloidosis, and further defined the factors affecting the clinical profile of FMF. METHODS: We investigated a sample of 277 FMF patients (154 men and 123 women), including 62 patients with nephropathic amyloidosis, in whom both FMF alleles had been identified. A detailed chart review, interview, and physical examination were undertaken to determine the patients' demographic characteristics, medical history, clinical manifestations, and treatment. The disease severity score was calculated from the Tel-Hashomer key. Genotypes at the SAA1 locus (isoforms alpha, beta, and gamma) were determined in all patients. The SAA1 13C/T polymorphism of the SAA1 promotor was analyzed in a subset of cases. RESULTS: The male:female ratio (154:123, or 1.3) was higher among patients with amyloidosis (40:22, or 1.8) compared with patients without amyloidosis (114:101, or 1.1). Logistic regression analysis showed that homozygosity for the M694V allele (odds ratio [OR] 4.27, 95% confidence interval [95% CI] 2.01-9.07), the presence of the SAAalpha/alpha genotype (OR 2.99, 95% CI 1.47-6.09), the occurrence of arthritis attacks (OR 2.43, 95% CI 1.17-5.06), and male sex (OR 1.73, 95% CI 0.90-3.33) were significantly and independently associated with renal amyloidosis. Disease severity was mainly influenced by MEFV mutations and was not associated with genotypes at the SAA1 locus. The SAA1 13T allele was rare, being associated mainly with the SAA gamma isoform, and not related to renal amyloidosis. CONCLUSION: Overall, disease severity and the development of amyloidosis in FMF are differentially affected by genetic variations within and outside the MEFV gene.