[Ochronosis: A case report]. / Ochronose : une observation.

INTRODUCTION: Ochronosis, also known as alkaptonuria, is a rare autosomal recessive disease. It is caused by a lack of homogentisic acid oxidase, which causes homogentisic acid deposition in the tissues. CASE REPORT: We report a 69-year-old patient who presented with chronic mechanical low back and radicular pain. The clinical examination revealed lumbar lordosis loss, lumbar spinal stiffness, and knee joint limitations of range of motion. On an extra-articular level, the pavilions of the ears and the internal angles of the eyes had a bluish color. Extensive lumbar disc calcifications, vacuum discal phenomenon and osteophytic bridges were demonstrated on standard radiographs of the spine. Clinical and radiographic criteria were used to make the diagnosis of ochronosis. CONCLUSION: Alkaptonuria is a degenerative arthropathy that leads to reduction of functional ability. The use of molecular analysis and genetic research is useful.

Effect of thermosonication process on physicochemical properties and microbial load of goat's milk.

In this study, thermosonication was used as a combined treatment of raw goat milk (RGM) using pasteurization (72 °C for 15 s) and ultrasound treatments (20 kHz at the power variance of 150 W, 200 W, 300 W and 400 W for 10 min). Investigation on the impact of the microbial load, protein content, protein aggregation, the particle size of fat and casein micelles, pH, viscosity, turbidity, color, and soluble calcium and phosphorus contents were carried out, whiles RGM and PGM served as the control. Our results revealed that at 400 W, that thermosonication resulted in a significant reduction (α = 0.05) in the microbial load of the samples to less than 2.3 log cfu/mL in comparison to those of RGM and pasteurized goat milk (PGM) at 5.94 log cfu/mL and 4.76 log cfu/mL respectively. In RGM, the fat size (3.5 µm) decreased to 0.4 µm at 300 W; while those of casein micelles also decreased from 406 to 256.4 nm at 400 W. However, no significant effect was observed in the color and soluble calcium and phosphorus contents of all samples. The effect on the microbial load and fat homogenization would promote thermosonication process in the dairy industry.

[Expression of EphA2 in Metastatic and Non-Metastatic Primary Uveal Melanoma]. / Expression von EphA2 in metastasierten und nicht metastasierten primären uvealen Melanomen.

BACKGROUND: Little is known about how the expression of Ephrin type-A receptor 2 (EphA2) influences cell-cell adhesion, migration, angiogenesis, and the formation of vasculogenic mimicry (VM) channels in uveal melanomas or how this may be related to the rate of metastasis. MATERIAL AND METHODS: Paraffin embedded sections of 50 histopathologically well characterised primary uveal melanomas (mean largest tumour diameter: 16.3 mm) were evaluated with respect to the expression of EphA2. Systemic metastasis was detected in 29 patients. The remaining 21 patients were followed for a mean of 10 years. Tumour angiogensis was analysed by endoglin expression (CD105), the activity of the mature vascular system (von Willebrand factor) and the presence of VM (CD31/PAS staining). RESULTS: All uveal melanomas expressed EphA2, with a mean of 95.93 % positive cells ± SD: 6.3 %. There was no significant association between EphA2 and the rate of metastases (p = 0.196), endoglin expression (p = 0.652), VM (p = 0.267) or with any other clinical or histopathological factors (p < 0.05). However, there was significant up-regulation of EphA2 in the nucleus of the metastatic uveal melanoma subgroup, while cytoplasmatic localisation in the subgroup was associated with better prognosis (p = 0.006). There were low levels of EphA2 expression in the specific retinal layers, the ciliary and corneal epithelium, and the choroidal and corneal endothelium. CONCLUSION: Nuclear expression of EphA2 in this series of large tumours was significantly associated with an increased rate of metastasis. On the other hand, cytoplasmic localisation was associated with a better prognosis. As there was no correlation between EphA2 expression and angiogenesis, the mature vasculature or VM, EphA2 appears to become less important in the advanced stages of the disease.

Added value of trabecular bone score over bone mineral density for identification of vertebral fractures in patients with areal bone mineral density in the non-osteoporotic range.

UNLABELLED: Detection of patients with vertebral fracture is similar for areal bone mineral density (aBMD) and trabecular bone score (TBS) in patients with non-vertebral fracture. In non-osteoporotic patients, TBS adds information to lumbar spine aBMD and is related to an index of spine deterioration. INTRODUCTION: Vertebral fractures (VFs) are more predictive of future fracture than aBMD. The number and severity of VFs are related to microarchitecture deterioration. TBS has been shown to be related to microarchitecture. The study aimed at evaluating TBS in the prediction of the presence and severity of VFs. METHODS: Patients were selected from a Fracture Liaison Service (FLS): aBMD and vertebral fracture assessment (VFA) were assessed after the fracture, using dual-energy X-ray-absorptiometry (DXA). VFs were classified using Genant's semiquantitative method and severity, using the spinal deformity index (SDI). TBS was obtained after analysis of DXA scans. Performance of TBS and aBMD was assessed using areas under the curves (AUCs). RESULTS: A total of 362 patients (77.3% women; mean age 74.3 ± 11.7 years) were analysed. Prevalence of VFs was 36.7%, and 189 patients (52.2%) were osteoporotic. Performance of TBS was similar to lumbar spine (LS) aBMD and hip aBMD for the identification of patients with VFs. In the population with aBMD in the non-osteoporotic range (n = 173), AUC of TBS for the discrimination of VFs was higher than the AUC of LS aBMD (0.670 vs 0.541, p = 0.035) but not of hip aBMD; there was a negative correlation between TBS and SDI (r = -0.31; p < 0.0001). CONCLUSION: Detection of patients with vertebral fracture is similar for aBMD and TBS in patients with non-vertebral fracture. In patients with aBMD in the non-osteoporotic range, TBS adds information to lumbar spine aBMD alone and is related to an index of spine deterioration.

[Intra-articular use of sodium hyaluronate (2,2,-2,7 MDa) in the treatment of Moroccan patients with knee osteoarthritis: randomized controlled trial]. / Intérêt de la viscosupplémentation a l'hyaluronate de sodium (2,2-2,7 MDa) dans le traitement de la gonarthrose chez des patients marocains: etude randomisée contrôlée.

OBJECTIVE: To assess the efficacy of intra-articular sodium hyaluronate, administred once weekly for 3 weeks (3 injections) in Moroccan patients with knee osteoarthritis over 6-month period. MATERIAL AND METHODS: We prospectively studied the outcome of 75 patients with painful knee osteoarthritis in grade 1, 2 and 3 on ACR radiological criteria in our rheumatology clinic in Morocco. Group 1: 45 patients were treated with 3-weekly injections of intra-articular sodium hyaluronate (1%; 2,2-2,7 MDa). Group 2 : 30 patients treated with symptomatic slow-acting drugs for osteoarthritis (SYSADOA). The efficacy parameters were Visual Analogue Scale (VAS) and Lequesne index. RESULTS: In group 1: 35/45 were female, a mean age of patients was 57.2 (± 8.2) years, and a mean Body Mass Index (BMI) was 28 (± 1.4) kg/m2. In group 2: 23/30 were female, a mean age of patients was 58.6 (± 2.8) years, and a mean of BMI was 27.8 (± 1.4) kg/m2. Before treatment in group 1, the mean of VAS was 6.5 cm (± 1), and of Lequesne index 10.5 (± 2.1). At 3 and 6 months after the third injection of sodium hyaluronate, there was a significant improvement from baseline of Lequesne index and VAS (P = 0.001). In group 2 before treatment, the mean of VAS was 7 cm (± 0,7), and of Lequesne index 8 (+ 1.1), but the improvement from baseline at 3 and 6 months of treatment was lower than group 1. CONCLUSION: The results of this prospective study, showed the efficacy of 3-weekly injections of sodium hyaluronate in the treatment of knee osteoarthritis in Moroccan patients over a 6-month period.

A pilot prospective study of the vascular repair response following red cell transfusion in critically ill patients.

BACKGROUND: Red blood cell transfusion has been associated with adverse outcomes including infection, delayed recovery and increased mortality in some patient populations. Circulating cells that yield endothelial-like vascular progenitor cell (VPC) clusters are correlated with vascular repair and recovery after ischaemic injury. The impact of red cell transfusion on VPC clusters and vascular repair remains uncertain. STUDY DESIGN: We prospectively enrolled patients admitted to intensive care requiring red cell transfusion and subjects at low likelihood of requiring red cell transfusion. Levels of VPC clusters and plasma levels of angiogenic cytokines were compared. A total of 17 patients were recruited and had blood samples collected at time of enrolment and at 24-48 h, 48-72 h and 1 week following transfusion. RESULTS: We could not discern differences in the number of VPC clusters between transfused patients (n = 6) and non-transfused subjects (n = 11) at baseline or throughout the study period. VPC cluster levels demonstrated wide variance and were highest at 24-h post-enrolment in the entire cohort. Furthermore, levels of all 16 cytokines analysed were not significantly different between transfused and non-transfused patients and we did not observe a correlation between cytokine concentrations and levels of circulating VPC-cluster forming cells in the overall study population. CONCLUSIONS: Our data suggest that assessment of vascular repair responses after red blood cell transfusion in critically ill patients is challenging. Although our study did not allow us to discern an influence of red cell transfusion on VPC cluster levels or angiogenic cytokines, new methods evaluating vascular repair mechanisms may be required.

(90)Y-ibritumomab tiuxetan followed by reduced-intensity conditioning and allo-SCT in patients with advanced follicular lymphoma.

Reduced-intensity conditioning (RIC) hematopoietic SCT (HSCT) is a potentially curative therapeutic option for patients with advanced follicular lymphoma (FL), but disease relapse remains the most common cause of failure. Radioimmunoconjugates administered before RIC allo-HSCT may enhance cytoreduction and allow more time for GVL effect to develop without the associated toxicity of a myeloablative HSCT. We performed a retrospective study to describe the outcomes of patients with relapsed, refractory or transformed FL who received yttrium-90 ((90)Y)-ibritumomab tiuxetan followed by fludarabine and low-dose BU RIC allogeneic HSCT at the Dana-Farber Cancer Institute between 2006 and 2009, inclusively. Twelve patients were identified with a median age of 55 (40-66) years and a median number of lines of therapy of 5 (2-10). Two patients (17%) had transformed to a more aggressive histology and five (42%) had chemorefractory FL. Cumulative incidences of grade II-IV acute GVHD at 100 days were 17% (±11%) and chronic GVHD at 12 months were 63% (±19%). Two-year non-relapse mortality was 18% (±12%). Two-year OS and PFS were 83% (±11%) and 74% (±13%), respectively. This treatment is associated with favorable outcomes including acceptable rates of GVHD and relapse in advanced FL patients, and warrants prospective studies.

Analysis of the D1S80 (pMCT118) VNTR locus polymorphism in a native Kuwaiti population by the polymerase chain reaction.

We have determined the allele and genotype frequencies at the hypervariable locus D1S80 in a native Kuwaiti population using the polymerase chain reaction technique and subsequent high resolution gel electrophoresis. In a sample of 200 individuals, 21 alleles and 57 genotypes were detected. The alleles with 18 and 24 repeat units were most common with frequencies of 0.188 and 0.408 respectively. The distribution of the observed genotypes was in agreement with the Hardy-Weinberg equilibrium prediction. The observed heterozygosity for the population sample was 0.80 with the allelic diversity of 0.781 +/- 0.029 and the power of discrimination was 0.94. The data obtained in this study are potentially useful for individual identification in forensic casework.

Sporadic occurrence of nondeletion Prader-Willi syndrome in two cases: a female with maternal uniparental disomy and a male with complex chromosomal rearrangement.

We report here two cases of nondeletion Prader-Willi syndrome (PWS). Case 1 is a 9-yr-old female patient with classical features of the syndrome and cytogenetically normal chromosome 15. DNA analysis using polymorphic probes for Prader-Willi Critical Region (PWCR) showed absence of paternal alleles while maternal uniparental isodisomy (UPisoD) was confirmed. This is the first report of nondeletion PWS with uniparental disomy (UPD) in the population of Kuwait. The second case with Prader-Willi syndrome-like features had normal chromosome 15 but showed familial complex chromosomal rearrangement (CCR) involving chromosomes 13, 19, and 20 inherited from his mother. No paternal deletion or UPD disomy was observed after DNA molecular analysis. This is a case of "atypical" PWS with no cytogenetic or molecular abnormality for PWCR. The two cases represent two different mechanisms associated with nondeletion PWS.

HLA-DQ alpha allele and genotype frequencies in a native Kuwaiti population.

We report the allele and genotype frequencies in a sample of an unrelated native Kuwaiti population determined by the use of polymerase chain reaction (PCR) and reverse dot-blot analysis. This technique, involving the use of commercially available AmpliType HLA-DQ alpha forensic DNA amplification and typing kit, has permitted the definition of six alleles and 21 genotypes in a sample of 220 people. The allelic frequencies are in the range 5.7-27.5%. This locus demonstrated a heterozygosity of 0.80 with an allelic diversity of 0.81 and the power of discrimination (PD) was 0.93. The distribution of observed genotypes conformed to Hardy-Weinberg equilibrium thus indicating genetic equilibrium of the different variants. This population data should permit the use of HLA-DQ alpha marker for individual identification in forensic casework.

Chemical modification of rat liver cytosolic NADP(+)-linked isocitrate dehydrogenase by N-ethylmaleimide. Evidence for essential sulphydryl groups.

Incubation of rat liver cytosolic isocitrate dehydrogenase with N-ethylmaleimide (NEM) resulted in the inactivation of the enzyme following pseudo-first order kinetics. Isocitrate affords considerable protection against inactivation whereas NADP+ enhances modification of the enzyme, suggesting localization of the modified group at the active site. Correlation of loss of activity with incorporation of [14C]NEM indicated that two sulphydryl residues/sub-unit are modified of which only one is shown to be involved in catalysis. pH dependence of the inactivation process implicates a reactive group of pKa 8.1 in catalysis. We conclude that a unique cysteine residue is essential for maximal catalytic activity of isocitrate dehydrogenase.

Purification and partial characterisation of NADP(+)-linked isocitrate dehydrogenase from rat liver cytosol.

NADP(+)-linked isocitrate dehydrogenase from rat liver cytosol was purified (approximately 135-fold) to apparent homogeneity in 27% yield. The purified enzyme has specific activity of 73 units.mg-1. The native enzyme showed an apparent M(r) of 94,000 by gel filtration and was composed of two identical subunits of M(r) 45,000 as judged by SDS/PAGE. In isoelectric focusing, a pI value of 5.7 was estimated for the enzyme.

Heredity of asthma in Saudi population.

In a cross-sectional study, the prevalence of asthma, hay fever and eczema was studied in 1150 schoolchildren attending school in Jeddah Western region of Saudi Arabia. The family histories of asthma, hay fever and eczema were examined in first degree relatives. The age range of children studied was 7-12 years, with a mean of 9.3 years (47% boys and 53% girls). A self-administered questionnaire was completed by the parents of the child to collect information concerning bronchial asthma, hay fever, and eczema in the target child and family history of respiratory allergy. A detailed family history and personal histories of asthma were available for 1035 Saudi children aged 7-12 years old. The rate of asthma and hay fever were significantly higher among siblings and offspring (cases) compared to their parents (p < 0.001). The results showed a high positive correlation between the relatives of affected children with respect to asthma and hay fever. These findings support the hypothesis that asthma and hay fever may be inherited in the Saudi population, but the mode of inheritance has yet to be determined.

Sister chromatid exchange analysis in monitoring chlorambucil therapy in primary nephrotic syndrome of childhood.

Sister chromatid exchange (SCE) analysis is the most sensitive method for assessing chromosome damage induced by chemical mutagens. We report the SCE of peripheral blood lymphocytes in children with primary nephrotic syndrome (NS) treated with chlorambucil. Group I consisted of 20 normal children, group 2 of 14 children with primary NS who had never received a cytotoxic drug and group III of 7 children with primary NS who had received chlorambucil, which was discontinued 6-36 months prior to the study. Group IV consisted of 4 nephrotic children who were receiving chlorambucil therapy during the study. There was no significant increase in SCE in group III compared with group I or group II (P much greater than 0.05). A significant rise in SCE (P less than 0.05) was seen in all patients in group IV.

Epidemiology of multiple sclerosis in Arabs in Kuwait: a comparative study between Kuwaitis and Palestinians.

On December 31, 1988 there were 201 registered multiple sclerosis patients in Kuwait, an overall prevalence rate (PR) of 10.2 per 100,000; among them were 186 Arabs, of whom 72 were Palestinians and 51 Kuwaitis. Comparison of these two subgroups, who had a similar age distribution revealed that the disease was 2 1/2 times more frequent among Palestinians (PR 23.8/100,000) than among Kuwaitis (PR 9.5/100,000). Palestinians also showed significant differences from Kuwaitis in eye color, blood group distribution and HLA-DR and HLA-DQW epitopes frequency. This suggests that genetic rather than environmental factors might be the underlying cause for the high susceptibility to develop MS among Arabs originating from the Eastern Mediterranean basin.

Autosomal recessive ataxia, slow eye movements, dementia and extrapyramidal disturbances.

An Arab family with an autosomal recessive form of spinocerebellar degeneration with slow eye movements is reported. Hitherto all the reported cases were either sporadic or of autosomal dominant inheritance. Associated are progressive intellectual impairment and extrapyramidal dysfunction as well as peripheral neuropathy and skeletal abnormalities. Muscle biopsy revealed non-specific mitochondrial abnormalities. The spectrum of eye movement abnormalities is discussed and the literature is reviewed. It is concluded that the hallmark of this syndrome (slow or even absent saccades) is one of a group of oculomotor abnormalities, all being characterized by delayed initiation and slow velocity. The syndrome seems to be related to the olivopontocerebellar degenerations, but differs in that there is in addition selective degeneration of certain tracts and nuclei in the mesencephalon and probably more rostral structures.

Late onset cerebello-pontomesencephalic degeneration.

Two siblings are presented with late onset, rapidly progressive truncal ataxia, paralysis of down-gaze and loss of up-gaze saccades in association with other oculomotor dysfunctions as well as dementia. Electron microscopic muscle studies revealed abnormal distribution and form of the mitochondria, probably being the ultrastructural basis of the pathologic changes. A neurological syndrome as that described here has not been reported before.

Autosomally inherited recessive spastic ataxia, macular corneal dystrophy, congenital cataracts, myopia and vertically oval temporally tilted discs. Report of a Bedouin family--a new syndrome.

A Bedouin family is described with an unusual form of spinocerebellar degeneration. Spastic ataxia was found to be associated with congenital cataracts, macular corneal dystrophy and non-axial myopia, in the absence of retardation of somatic or mental maturation. Immunological abnormalities were common. Genetic analysis revealed that the pedigree is expressing the transmission and segregation of a single mutant autosomal recessive gene.

The genetic structure of the Kuwaiti population. I. Distribution of 17 markers with genetic distance analysis.

Frequency estimates were determined on seventeen blood group, serum protein, and red-cell enzyme markers on random samples of 193 individuals from two Bedouin tribes in addition to the general population in Kuwait. Genetic heterogeneity between the three communities is evident from the significant differences in allelic distribution of the polymorphic markers. Genetic distance measurements were used to compare the results with the oral history of descent of the two tribal communities. Results were in agreement with tribal history.