Living-Related Versus Deceased Donor Pediatric Liver Transplantation: A Multivariate Analysis of Technical and Immunological Complications in 235 Recipients

Timely access to a living donor (LD) reduced pretransplant mortality in pediatric liver transplantation (LT). We hypothesized that this strategy may provide better posttransplant outcome. Between July 1993 and April 2002, 235 children received a primary LT from a LD (n = 100) or a deceased donor (DD) (n = 135). Demographic, surgical and immunological variables were compared, and respective impact on posttransplant complications was studied using a multivariate analysis. Five-year patient survival rates were 92% and 85% for groups LD and DD, respectively (p = 0.181), the corresponding graft survival rates being 89% and 77% (p = 0.033). At multivariate analysis: (1) type of donor (DD) was correlated with higher rate of artery thrombosis (p < 0.012); (2) biliary complication rate at 5 years was 29% and 23% for groups LD and DD, respectively (p = 0.451); (3) lower acute rejection incidence could be correlated with type of donor (DD) (p = 0.001), and immunosuppressive therapy (tacrolimus) (p < 0.001). We conclude that (1) according to the multivariate analysis, LT with LD provided similar patient and graft outcome, when compared to DD; (2) a higher rate of artery thrombosis and a lower rate of rejection were observed in group DD; (3) this study confirms the efficacy of tacrolimus for immunoprophylaxis, whatever the type of organ donor is.     

P-31 MR spectroscopy of skeletal and cardiac muscle metabolism in patients with systemic sclerosis: A multiple case study

Three-dimensionally localized proton-decoupled phosphorus-31 magnetic resonance (MR) spectroscopy of skeletal and cardiac muscle was performed in six patients with systemic sclerosis. Cardiac (n = 9) and skeletal (n = 6) spectra were also obtained in healthy volunteers. Metabolite ratios and intracellular pH were determined from the spectra of skeletal and cardiac muscle. The phosphocreatine-to-adenosine triphosphate ratio was normal for both skeletal and cardiac muscle in patients with systemic sclerosis. The pH values of skeletal muscle were similar in patients and control subjects (7.13 ± 0.02 vs 7.12 ± 0.01, respectively). In skeletal muscle, the inorganic phosphate-to-phosphocreatine ratio in patients was increased relative to that of control subjects (0.106 ± 0.014 vs 0.086 ± 0.006, respectively; P =.02). P-31 MR spectroscopy showed no abnormalities in the myocardium of patients with systemic sclerosis. Assessment of the inorganic phosphate-to-phosphocreatine ratio in peripheral skeletal muscle may be helpful for assessing disease activity.     

Acute arteriolar vasoconstriction following furosemide in conscious spontaneously hypertensive rats

In a previous study in conscious spontaneously hypertensive rats (SHR), we observed an immediate decrease in the cardiac index (CI) and an increase in the total peripheral resistance index (TPRI) following the administration of furosemide. The present study was designed to evaluate the regional hemodynamic effects and the involvement of sinoaortic baroreceptors in the increase in TPRI. In SHR instrumented for the measurement of central hemodynamics, 8 mg.kg-1 furosemide decreased CI from 31.0 +/- 2.5 ml.min-1.100 g bw-1 by 9.5 +/- 1.3 ml.min-1.100 g bw-1 (n = 7). TPRI increased maximally from 5.7 +/- 0.8 by 2.7 +/- 0.5 mm Hg.min.100 g bw.ml-1. The effect on TPRI was not affected by sinoaortic denervation (SAD) to abolish arterial baroreflexes. However, furosemide induced a significantly greater decrease in CI (-12.6 +/- 1.2 ml.min-1.100 g bw-1; n = 7) after SAD. Furosemide effectively reduced the mean arterial pressure in SAD SHR (-21 +/- 9 mm Hg) but not in sham-denervated SHR. Furosemide (8 mg.kg-1) reduced renal, mesenteric and hindquarter blood flow to a comparable extent (approximately 20%) in intact SHR. The reduction in renal flow at 3.5 min after injection (-17.9 +/- 4.1%; n = 8) was significantly greater than the reduction in mesenteric (-7.1 +/- 4.7%) and hindquarter blood flow (-4.2 +/- 3.7%), suggesting that the renal bed responds faster. Thereafter, the flow reductions in the three beds were not different. The results show that furosemide causes a general vasoconstriction in conscious SHR.(ABSTRACT TRUNCATED AT 250 WORDS)     

Kupffer cell depletion in vivo results in clearance of large-sized IgA aggregates in rats by liver endothelial cells.

We investigated the clearance kinetics and tissue distribution of different sized IgA in normal and macrophage-depleted rats. Rats were injected iv with liposomes containing dichloromethylene diphosphonate (DMDP). DMDP treatment resulted in complete depletion of liver macrophages 24-48 h after administration. Normal and macrophage depleted rats were injected intravenously with monomeric, dimeric, polymeric or aggregated polymeric IgA (AIgA) and assessed for blood clearance and tissue distribution. In normal rats, clearance of IgA was size dependent, i.e. a faster clearance with increasing size. No differences in clearance kinetics were observed of the different sized IgA between normal and DMDP-treated rats. TCA non-precipitable radioactivity, a measure for degradation of IgA, was found in the circulation of normal and DMDP-treated rats after AIgA administration. The liver was the main organ responsible for the clearance of IgA in normal and DMDP-treated rats. Immunofluorescence studies on liver biopsies indicated that AIgA was associated with Kupffer cells in normal rats. Electron microscopical studies revealed that the AIgA was internalized and located in vesicles in Kupffer cells. In DMDP-treated rats the AIgA was associated with endothelial cells and electron microscopy studies showed that this AIgA was taken up by endothelial cells. These data show that rat liver endothelial cells are able to bind, internalize and degrade AIgA in situations where Kupffer cells are absent, and that these cells may play an important role in the handling of AIgA and IgA-immune complexes.     

Combined hypophyseal function test in children with homozygous beta-thalassemia]

Nowadays, endocrine problems like retarded sexual maturation and growth deficiency, lead to substantial suffering in patients with beta-thalassemia major. The aim of the present study is the differentiation between a possible insufficiency of the pituitary gland and dependent target organs, respectively. 12 patients (age 1.9-18.10 years) were examined by means of a combined pituitary function test. The corticotropic axis turned out to be normal as shown by a regular stimulation of cortisol in all patients tested. The thyrotropic function was unaffected in all children: elevated levels of TSH pointed to primary hypothyroidism. Pubertal values of LH and FSH were found in only 3 out of 7 patients at pubertal age. In 10 out of 12 children, stimulation led to a rise in STH levels above 10 ng/ml. On the whole, there was no evidence for pituitary insufficiency in beta-thalassemia major.     

Elevated body mass index and mortality risk in the elderly

The purpose of this report was to perform a systematic review and meta-analysis of the studies examining the impact of an elevated body mass index (BMI) on mortality risk in elderly (> or =65 years) men and women. A variance-based method of meta-analysis was used to summarize the relationships from available studies. The summary relative risk of all-cause mortality from the 26 analyses that included a risk estimate for a BMI within the overweight range was 1.00 (95% confidence intervals, 0.97-1.03). The summary relative risk of all-cause mortality for the 28 analyses that included a risk estimate for a BMI within the obese range was 1.10 (1.06-1.13). These calculations indicate that a BMI in the overweight range is not associated with a significantly increased risk of mortality in the elderly, while a BMI in the moderately obese range is only associated with a modest increase in mortality risk.     

Gouty tenosynovitis and compression neuropathy of the median nerve

Two cases of gouty tenosynovitis were associated with carpal tunnel syndrome. Both patients had carpal tunnel release with good relief of symptoms. In one patient, gout was not suspected before operation; this patient developed wound dehiscence with tophaceous urate crystal drainage that eventually disappeared. Proper preoperative antigout therapy may have prevented this complication. Carpal tunnel syndrome associated with gout is rare. Preoperative investigations for gout may be indicated in patients with carpal tunnel syndrome.     

Early onset of autoimmunity in MRL/++ mice following immunization with beta 2 glycoprotein I.

Antiphospholipid antibodies (aPL) are associated with thrombosis, thrombocytopenia and recurrent fetal loss in humans and in some animal models. Immunization with beta 2 glycoprotein I (beta 2GPI) induced aPL production in normal rabbits and mice. However, the association of these antibodies with disease manifestations remains controversial. To determine whether induction of aPL by beta 2GPI immunization in an autoimmune strain of mice (MRL/++) would result in acceleration of clinical and serological autoimmune disease manifestations, three groups of 8-week-old female mice were studied. One group was immunized with beta 2GPI, and one with ovalbumin (OVA); the third was not immunized. After two booster injections, sera were analysed for the presence of anticardiolipin (aCL) and anti-DNA by ELISA and anti-nuclear antibody (ANA) by immunofluorescence. Mice were studied for thrombocytopenia, proteinuria, fecundity rates, litter sizes and the development of central nervous system dysfunction. Elevated levels of aCL, anti-DNA and ANA were detected in all beta 2GPI-immunized, in three OVA-immunized, and in none of the unimmunized mice. The anti-DNA antibodies were inhibited by CL micelles, suggesting cross-reactivity between aCL and anti-DNA. Platelet counts, fecundity rates and litter size were reduced in beta 2GPI-immunized but not in OVA-immunized or unimmunized mice. None of the mice developed neurological dysfunction or significant proteinuria over a 10-week period post-immunization. These findings suggest that beta 2GPI immunization induces aPL in MRL/++ mice associated with accelerated autoimmune manifestations resembling the antiphospholipid syndrome.     

Spontaneous remission in a patient with therapy-related myelodysplastic syndrome (t-MDS) with monosomy 7

We describe a case of spontaneously reversible refractory anaemia, a subtype of myelodysplastic syndrome (MDS), with monosomy 7 secondary to chronic treatment with azathioprine (AZA) in a young renal transplant recipient. AZA was stopped after that conventional cytogenetics and fluorescence in situ hybridization (FISH) had demonstrated the existence of a monosomy 7 clone. 4 months later, haematological values had considerably improved and the karyotypic examination as well as the FISH analysis were normal. The spontaneous remission of this MDS with monosomy 7, which is usually associated with a particularly poor prognosis, could be due to the recovery of a better immunosurveillance following the withdrawal of AZA.     

Recombinant human interferon-alpha induced cytoreduction in chronic myelogenous leukemia

Summary Fourteen patients with Ph'-chromosome positive chronic myelogenous leukemia (CML) in first chronic phase were treated with recombinant interferon-_2c. Interferon-_2c 5 to 10×10⁶ units s.c. was given for 12 weeks as an induction therapy. Maintenance treatment consisted of interferon-_2c 5 × 10⁶ units twice weekly s.c.. Two patients (14%) attained a complete clinical remission and 6 (43%) a partial remission, 3 of whom developed progressive disease during maintenance therapy. A complete disappearance of Ph'-chromosome was achieved in 1 patient. All patients had a more than 45% initial decline of the leukocyte count. Four out of ten patients with an initially enlarged spleen demonstrated reduction in spleen size. Influenza-like symptoms, anorexia, nausea, weight loss and fatigue were common side effects. Interferon-alpha is active in CML but additional clinical investigations are warranted to assess more precisely the therapeutic value of the interferons in this disease.