Late diagnosis of primary hyperoxaluria after failed kidney transplantation

Primary hyperoxaluria type 1 (PH1) is a rare autosomal recessive inborn error of the glyoxylate metabolism that is based on absence, deficiency or mislocalization of the liver-specific peroxisomal enzyme alanine:glyoxylate aminotransferase. Hyperoxaluria leads to recurrent formation of calculi and/or nephrocalcinosis and often early end-stage renal disease (ESRD) accompanied by systemic calcium oxalate crystal deposition. In this report, we describe an adult female patient with only one stone passage before development of ESRD. With unknown diagnosis of PH, the patient received an isolated kidney graft and developed an early onset of graft failure. Although initially presumed as an acute rejection, the biopsy revealed calcium oxalate crystals, which then raised a suspicion of primary hyperoxaluria. The diagnosis was later confirmed by hyperoxaluria, elevated plasma oxalate levels and mutation of the AGXT gene, showing the patient to be compound heterozygous for the c.33_34InsC and c.508G > A mutations. Plasma oxalate levels did not decrease after high-dose pyridoxine treatment. Based on this case report, we would recommend in all patients even with a minor history of nephrolithiasis but progression to chronic renal failure to exclude primary hyperoxaluria before isolated kidney transplantation is considered.     

Nateglinide or gliclazide in combination with metformin for treatment of patients with type 2 diabetes mellitus inadequately controlled on maximum doses of metformin alone: 1-year trial results

AIM: To compare long-term efficacy and safety of nateglinide plus metformin with those of gliclazide plus metformin in patients with type 2 diabetes not adequately controlled with metformin monotherapy. METHODS: Double-blind, double-dummy, multicentre study extended to a total of 52 weeks. Patients with inadequate glucose control on maximal doses of metformin were randomized to nateglinide (N = 133) or gliclazide (N = 129) add-on treatment. After the initial 6-month study, the majority of patients in the nateglinide group [n = 112 (93.3%)] and in the gliclazide group [n = 101 (92.7%)] entered a 6-month, double-blind, extension study. RESULTS: There was no significant difference between treatment regimens in haemoglobin Alc (HbA1c) change from baseline to 52 weeks (-0.14% for nateglinide vs. -0.27% for gliclazide; p = 0.396). Proportions of patients achieving an endpoint HbA1c of <7% were similar (40 vs. 47.4%) for nateglinide and gliclazide groups. There was no significant between-treatment difference in fasting plasma glucose change from baseline to 52 weeks (nateglinide: -0.2 mmol/l and gliclazide: -0.7 mmol/l; p = 0.096). The decreases in prandial plasma glucose area under the curve(0-4 h) from baseline were -3.26 and -1.86 h x mmol/l in the nateglinide and the gliclazide groups respectively, and the change was statistically significant in the nateglinide group only (p = 0.006). Initial insulin response to a meal was augmented with nateglinide treatment only, without between-treatment difference in 2-h insulin response. The overall rate of hypoglycaemic events was similar with nateglinide and gliclazide combinations with metformin. Nateglinide plus metformin treatment was not associated with weight gain. CONCLUSIONS: No significant difference was seen between nateglinide plus metformin and gliclazide plus metformin in terms of HbA1c. Treatment with nateglinide plus metformin for up to 12 months was not associated with weight gain.     

Recombinase-activating gene 1 immunodeficiency: different immunological phenotypes in three siblings

We report different immunological phenotypes in three siblings from consanguineous family with recombinase-activating gene 1 ( RAG1 ) gene mutations. Null mutations of RAG genes result in severe combined immunodeficiency (SCID) with absent T and B cells. Hypomorphic mutations with retained activity of RAG genes may lead to a 'leaky' SCID with some features of Omenn syndrome (OS) or typical OS. In our three patients, homozygous, hypomorphic RAG1 gene mutation (g.368–369delAA) was detected. Two patients presented with T−B−SCID phenotype while the youngest patient developed T+B+NK+SCID phenotype with expansion of autologous T-cell receptor (TCR) γδ-positive T cells, increased immunoglobulin levels and retained ability for antibody production. Similar to originally reported patients with this newly recognized immune phenotype, our patient developed disseminated cytomegalovirus (CMV) infection and autoimmune cytopenia.
Conclusion: In infants with disseminated cytomegalovirus infection and autoimmune cytopenia, even if basic immunologic investigation appears normal, RAG1 immunodeficiency should be considered.     

Effect of aminophylline on aspirin penetration into the central nervous system in rats

This study investigated with the effect of aminophylline on the penetration of aspirin through the blood-brain barrier (BBB) into the central nervous system (CNS) in rats. Acetylsalycylic was injected into the right axillary artery, to avoid the drug affecting the peripheral organs before it reached the CNS. The test animals received subcutaneously (s.c.) aminophylline 30 min before aspirin injection, while the control animals received an equimolar dose of physiological solution s.c. At time intervals of 30, 60, 90, 120, and 240 s after aspirin injection, the animals were decapitated and blood samples from the left jugular vein, as well as samples from the brainstem, cerebellum and left and right cerebral hemispheres, were taken to determine aspirin concentrations in all of them by a standard method. It was found that aspirin concentrations in the CNS were even 30 times lower than in the blood, with the concentrations being higher in the brainstem and cerebellum than in the left and right hemispheres. The presence of aminophylline did not alter aspirin concentrations either in the blood or the brain, and therefore did not affect significantly the aspirin penetration through the BBB into the CNS.     

X-ray imaging performance of structured cesium iodide scintillators

Columnar structured cesium iodide (CsI) scintillators doped with Thallium (Tl) have been used extensively for indirect x-ray imaging detectors. The purpose of this paper is to develop a methodology for systematic investigation of the inherent imaging performance of CsI as a function of thickness and design type. The results will facilitate the optimization of CsI layer design for different x-ray imaging applications, and allow validation of physical models developed for the light channeling process in columnar CsI layers. CsI samples of different types and thicknesses were obtained from the same manufacturer. They were optimized either for light output (HL) or image resolution (HR), and the thickness ranged between 150 and 600 microns. During experimental measurements, the CsI samples were placed in direct contact with a high resolution CMOS optical sensor with a pixel pitch of 48 microns. The modulation transfer function (MTF), noise power spectrum (NPS), and detective quantum efficiency (DQE) of the detector with different CsI configurations were measured experimentally. The aperture function of the CMOS sensor was determined separately in order to estimate the MTF of CsI alone. We also measured the pulse height distribution of the light output from both the HL and HR CsI at different x-ray energies, from which the x-ray quantum efficiency, Swank factor and x-ray conversion gain were determined. Our results showed that the MTF at 5 cycles/mm for the HR type was 50% higher than for the HL. However, the HR layer produces approximately 36% less light output. The Swank factor below K-edge was 0.91 and 0.93 for the HR and HL types, respectively, thus their DQE(0) were essentially identical. The presampling MTF decreased as a function of thickness L. The universal MTF, i.e., MTF plotted as a function of the product of spatial frequency f and CsI thickness L, increased as a function of L. This indicates that the light channeling process in CsI improved the MTF of thicker layers more significantly than for the thinner ones.     

Learning deficits in rats with early neurotoxic lesions to the globus pallidus, substantia nigra, median raphe or pontine reticular formation

Previous studies have shown that weanling rats with electrolytic lesions of the globus pallidus (GP), substantia nigra (SN), median raphe (MR) or pontine reticular formation (PRF) are deficient in learning a wide variety of laboratory tasks. The current study was designed to investigate whether this nonspecific learning deficiency is due to destruction of cells intrinsic to these subcortical regions or to fibers passing through these regions. Accordingly, neurotoxic lesions of the GP, SN, MR or PRF were made in weanling rats using ibotenic acid. Rats were subsequently required to learn a visual discrimination, a 3-cul maze and a nonvisual (incline plane) discrimination. While those groups with GP, SN or MR lesions showed significant deficits on all three problems, only the animals with GP lesions exhibited deficits comparable in magnitude to those associated with corresponding electrolytic lesions. Animals with lesions to the PRF were impaired only on the nonvisual discrimination. These results suggest that while destruction of neurons alone within the GP, SN or MR can produce a nonspecific learning impairment, the combined destruction of neurons and fibers of passage within the SN, MR or PRF produces a more profound learning deficit.     

Onychatrophy in a female patient with lichen planus

A case of female patient with onychatrophy, as a single clinical manifestation of lichen planus is reported. Nail histopathologic and direct immunofluorescent findings confirmed the diagnosis.     

Conversion of azathioprine to mycophenolate mofetil and chronic graft failure progression

The purpose of the study was to evaluate the impact of conversion from azathioprine (AZA) to mycophenolate mofetil (MMF) on graft function in 35 renal transplant recipients with chronic allograft nephropathy (CAN). The immunosuppressive regimen originally consisted of AZA, cyclosporine (CsA), and prednisone (Pr). At the onset of the study (mean period = 39 posttransplant months), a graft biopsy was performed on all patients who were randomly divided into group 1 (n = 17) in whom MMF was introduced instead of AZA. The remaining 18 subjects (group 2) were maintained on the previous regimen. Two periods were analyzed: period I: 12 months before, and period II: 12 months after biopsy and therapy conversion. Graft function was assessed monthly by measurements of the 24-hour creatinine clearance (CCr). Analysis of variance (ANOVA) was used to compare the differences in CCr and proteinuria between the two groups. No difference was observed in the baseline characteristics, in the incidence of delayed graft function and acute rejection, or in the mean CsA dose. Pathohistological analysis revealed advanced CAN in the majority of patients in both groups. The morphological changes negatively correlated with graft function. The graft function showed parallel deterioration in the two groups; no significant difference was observed in the mean CCr values in the periods studied. Proteinuria was similar for both groups throughout the study. Conversion of AZA to MMF in recipients with CAN, albeit safe, was without significant benefit on the progression of chronic graft failure over the period of a year.