Environmental exposure to arsenic and chromium in children is associated with kidney injury molecule-1.

Environmental hazards from natural or anthropological sources are widespread, especially in the north-central region of Mexico. Children represent a susceptible population due to their unique routes of exposure and special vulnerabilities. In this study we evaluated the association of exposure to environmental kidney toxicants with kidney injury biomarkers in children living in San Luis Potosi (SLP), Mexico. A cross-sectional study was conducted with 83 children (5-12 years of age) residents of Villa de Reyes, SLP. Exposure to arsenic, cadmium, chromium, fluoride and lead was assessed in urine, blood and drinking water samples. Almost all tap and well water samples had levels of arsenic (81.5%) and fluoride (100%) above the permissible levels recommended by the World Health Organization. Mean urine arsenic (45.6ppb) and chromium (61.7ppb) were higher than the biological exposure index, a reference value in occupational settings. Using multivariate adjusted models, we found a dose-dependent association between kidney injury molecule-1 (KIM-1) across chromium exposure tertiles [(T1: reference, T2: 467pg/mL; T3: 615pg/mL) (p-trend=0.001)]. Chromium upper tertile was also associated with higher urinary miR-200c (500 copies/µl) and miR-423 (189 copies/µL). Arsenic upper tertile was also associated with higher urinary KIM-1 (372pg/mL). Other kidney injury/functional biomarkers such as serum creatinine, glomerular filtration rate, albuminuria, neutrophil gelatinase-associated lipocalin and miR-21 did not show any association with arsenic, chromium or any of the other toxicants evaluated. We conclude that KIM-1 might serve as a sensitive biomarker to screen children for kidney damage induced by environmental toxic agents.

Single nucleotide polymorphisms of the inflamatory cytokine genes: interleukin-1B, tumor necrosis factors-A and tumor necrosis factor-B in adult patients with immune thrombocytopenia.

Immune thrombocytopenia (ITP) is an autoimmune disease characterized by thrombocytopenia due to platelet autoantibodies, causing an accelerated clearance of opsonized platelets by phagocytes. The etiology of ITP remains unclear, both genetic and environmental factors may have a role in the disease development. The aim of our study was to investigate a possible association of three single nucleotide polymorphisms (SNP) in the genes for interleukin beta (IL1B-511C/T), tumor necrosis factor beta (TNF+252G/A) and tumor necrosis factor alpha (TNFA-308G/A) with ITP. We have analyzed 125 adult patients with ITP and 120 healthy matched controls. Genotyping was performed by using PCR- RFLP methods. Our results demonstrated significantly different genotype distributions and allele frequencies for TNFB+252G/A in patients with ITP, p = 0.005 and p = 0.009 with Yates correction. We did not find any significant differences in the genotype distribution or allele frequencies for the other two genes. We have found significantly different genotype distribution and allele frequencies for TNFA-308G/A between patients with unresponsive and responsive ITP patients, p = 0.016 and p = 0.009. There were no significant differences in genotype distribution and allele frequencies for ILB-511C/T and TNFB+252G/A polymorphisms between those two groups of patients. We did not find any significant differences in genotype distribution and allele frequencies for all three polymorphisms between splenectomized and unsplenectomized ITP patients. The obtained data indicate that the A allele of TNFB+252G/A is more frequent in these patients than in the controls and that this polymorphism may play a significant role in disease susceptibility. The A allele of TNFA-308G/A was more frequent in patients with unresponsive ITP, indicating that this gene polymorphisms may contribute to therapy resistance.

Immune thrombocytopenic purpura in adults in the last 10 years: single-centre experience.

BACKGROUND: Immune thrombocytopenic purpura (ITP) is a benign disease with low morbidity and mortality and frequent remissions that occur spontaneously or in response to first-line treatment with steroids or splenectomy. AIM: The purpose of this study is to describe the clinical outcomes of 170 patients with ITP diagnosed and/or treated in our hospital between 2000 and 2010. METHODS AND RESULTS: The median age at diagnosis was 47 years. Forty three (25%) were asymptomatic, 65% had minor skin or mucosal bleeding and 10% had significant bleeding from the gastrointestinal or genitourinary system. The median platelet count at diagnosis was 13x10(9)/L (range: 0-98x10(9)/L). Median follow-up of all patients was 13 months. Ninety-five patients had a follow-up longer than 12 months, with median 44 months (range 14-384). Corticosteroids were the initial treatment for 161/170 (95%) patients, 38 (22%) were splenectomized, 25 (14.7%) were treated with intravenous gamma globulins, while 9 did not received any specific treatment. A complete response to initial treatment (prednisone±splenectomy) was achieved in 55/161 (34.2%), a partial response in 90 (55.9%) and no response in 16 (9.9%) patients. In the group of patients with follow-up longer than 1 year; 28 (29%) patients had refractory or unresponsive ITP with a median follow-up of 66 months. All patients with refractory ITP were treated with steroids, 11 were splenctomized, significantly more patients with refractory ITP 12 (43%) were treated with IVIG compared with other ITP patients (16%), p=0.005. The median age of 38 splenectomized patients was 28 years and it is significantly different from the other patients (p<0.001). There were no significant differences in other characteristics between splenctomized or refractory ITP and other patients at diagnosis. CONCLUSION: Our results were similar to results already reported in other similar studies.

Association of polymorphisms in human platelet antigens with idiopathic thrombocytopenic purpura in Macedonians.

Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disease characterized by thrombocytopenia due to the presence of platelet autoantibodies specific for platelet membrane glycoproteins, such as GPIIb/IIIa, GPIb/IX and GPIa/IIa. These autoantibodies cause an accelerated clearance of opsonized platelets by phagocytes and inhibition of platelet production. Human platelet antigen (HPA) systems HPA-1, HPA-2, HPA-3 and HPA-5 are components of platelet GP complexes GPIIb/IIIa, GPIb/IX and GPIa/IIa. The HPA system consists of more than 12 bi-allelic antigen polymorphisms in which a base-pair substitution leads to change in an amino acid sequence of a membrane glycoprotein expressed on the platelet surface. The aim of this study was to examine the association of HPA-1, HPA-2, HPA-3 and HPA-5 polymorphisms with idiopathic thrombocytopenic purpura. We performed genotyping of HPA-1, HPA-2, HPA-3, and HPA-5 systems in 60 patients with ITP and 120 healthy participants. Genotyping of HPA-1, -2, -3, and -5 alleles were performed by PCR and RFLP methods by using specific primers and restriction enzymes. Allele and genotype frequencies of HPA-1, HPA-3, and HPA-5 were not significantly different between patients and healthy participants. After Bonferroni adjustment a significant association in ITP patients with HPA-2 alleles (P=0.015, OR=1.923, CI=1.126-3.284) was found. Allele frequencies for HPA-2a were 0.852 in healthy participants and 0.750 in patients, and for HPA-2b 0.148 and 0.250 respectively. These results suggests that HPA-2b allele was more frequent in patients with ITP and may be involved in the formation of a specific autoepitope.

Immunosupressive treatment with cyclosporin-A for a patient with hypoplastic myelodisplastic syndrome: a case report.

BACKGRAOUND: Imunosupressive therapy with antithymocyte globulin (ATG), cyclosporine (CsA) or both has been shown to induce haematological responses in a subset of patients with myelodysplastic syndromes (MDS), in particular in the hypocellular form of MDS. CASE REPORT: We report our first case with hypocellular MDS treated with CsA. A 54-year-old female referred to our Department due to weakness and severe pancytopenia. Hypocellular form of MDS was diagnosed after bone marrow biopsy. Treatment with CsA was started one year after diagnosis. Treatment with CsA resulted in clinical improvement, a very good partial haematological response, resolution of transfusion requirement and an increase in bone marrow cellularity. CONCLUSIONS: In our experience, immunosuppressive treatment with CsA and/or ATG could be an alternative for patients with hypoplastic MDS for whom there is no possibility of allogenic bone marrow transplantation as only curative therapy.

Osteonecrosis of the jaw in patients with multiple myeloma treated with bisphosphanates.

Bisphosphonates are pyrophosphate analogues which inhibit osteoclastic activity. Long term use of bisphosphonates has recently been associated with osteonecrosis of the jaw (ONJ) defined as a three month non-healing defect in the jaw. ONJ is commonly precipitated by a tooth extraction or other stomatological procedure in patients treated with long-term, potent, high dose intravenous bisphosphonates for the management of myeloma, breast or prostate cancer. The aim of this study was to evaluate the incidence of ONJ in patients with MM treated with bisphosphonates during the last 8 years in our institution and to pre-sent the first two cases. We have analysed 247 myeloma patients diagnosed in our institution in the period 2002-09. Only 190/247 patients (76.9%) were treated with bisphosphonates. The incidence of ONJ in our group of patients treated with bisphosphonates was 2/190 (1%). The most commonly used bisphosponate was i.v. pamidronate (17.8%) and 46.6% were treated with two or more types of bisphosphonates. Sixty-five patients (34.2%) received oral forms of bisphosphonates; 42.1% patients were treated with i.v. forms of pamidronate, ibondronate or clodronate, and 45 patients (23.7%) received a combination of oral and i.v. forms of bisphosphonates. The mean duration of bisphosphonates therapy was 24.7±17.7 months. The low incidence of ONJ in our institution could be explained by the rare use of zolendronate, which is the most commonly referred bisphosphonate causing ONJ, and by a relatively shorter duration of bisphosphonates treatment in patients with MM. Despite the fact that ONJ is a rare complication in our institution, preventive measures must be considered.

Evaluation of telomerase activity in patients with chronic B lymphocytic leukemia versus age matched controls. Correlation between telomerase activity and bone marrow infiltration.

Telomerase is a ribonucleoproteic enzyme associated with cellular immortality and malignancy. This enzyme, besides the catalytic subunit bearing reverse transctiptase activity, contains an RNA template complementary to TTAGGG telomeric repeats, thus permitting de novo synthesis of telomeric DNA onto chromosomal telomeric ends. Increased telomerase activity has been reported in Chronic Lymphocytic Leukemia (CLL) by many authors. In order to investigate the telomerase activity in patients with CLL and its correlation to commonly used morphologic prognostic markers, 38 frozen blood lymphocyte samples from patients with CLL and 47 age-matched controls were investigated for telomerase activity using the Telomerase PCR ELISA-plus kit from Roche. Trepanobiopsies from the same patients were analysed for the type of bone marrow infiltration as well. Analysis showed highly variable Relative Telomerase Activity (RTA) in B-CLL patients, ranging from comparable or even lower than the mean RTA of controls (in Binet A stage patients) to manifold increase in the majority of patients with advanced stage disease. The sex and age of the patients showed no influence on RTA in CLL patients, in contrast to the control group, where the age influenced telomerase activity. We found a positive correlation between the RTA and disease stages (Binet), as well as between RTA and the type of BM infiltration.

Gene frequencies of human platelet antigens in the Macedonian population.

Human platelet antigen (HPA) systems consist of more than 12 bi-allelic antigen polymorphisms. Due to these polymorphisms, platelet-membrane glycoproteins can be recognized as alloantigens or autoantigens and can cause conditions such as fetomaternal alloimmune thrombocytopenia, post-transfusion refractoriness to platelets, and post-transfusion throbocytopenic purpura. The purpose of this study was to investigate the distribution of HPA-1, -2, -3, and -5 in Macedonian population by using the polymerase chain reaction and restriction fragment length polymorphism. The allele frequencies were 0.865 for HPA-1a, 0.135 for HPA-1b, 0.852 for HPA-2a, 0.148 for HPA-2b, 0.578 for HPA-3a, 0.422 for HPA-3b, 0.909 for HPA-5a, and 0.091 for HPA-5b. Results of our study were not significantly different from those reported in the other European studies. Our population displayed the highest frequency for HPA-2b allele (0.148) reported among European population.

Tubular urachal remnants in adult bladders.

We studied the structure and histologic appearance of intramural tubular urachal remnants in bladders from an unselected series of 122 autopsies, in which the patient age at death was 38 to 91 years. The bladders were fixed with formaldehyde introduced 10 minutes to 5 hours post mortem. Of the bladders 32 per cent showed tubular urachal remnants. The remnants were classified into 3 types on the basis of the epithelial extent and structure. Of the remnants 68.4 per cent had lumen covered with transitional epithelium, while the remainder had columnar epithelium. Bud-like epithelial proliferations were found in 43.6 per cent and mild dysplasia of the epithelium was found in 7.7 per cent of the urachal remnants, while mild inflammation in the loose peritubular tissue was demonstrated in 23.1 per cent.

[Metaplastic and proliferative processes of the bladder mucosa in elderly patients (author's transl)]. / Metaplastiche und proliferative Prozesse der Blasenschleimhaut im höheren Lebensalter.

The frequency of 20 morphological findings in bladders fixed shortly after death obtained at post mortem examination from an unselected nonurological series of 70 patients with a median age of 74 years, we studied by evaluation of 12 600 histological data. Squamous metaplasia was found in 27.8% of male and 82.2% of female subjects predominantly at the bladder neck and floor. Squamous metaplasia with different structures at the posterior and lateral wall showed a preponderance in the male subjects. Brunn's nests were observed in 88.9% of male and 88.2% of female patients, sometimes as "Brunn's nests in situ". Focal urothelial hyperplasia was seen in 41.7% of male and 38.2% of female, "labile epithelium" in 13.9% of male and 29.4+ female, micropapillomas in 13.9% male and 11.8% female patients. One male subject (72 years old) had an urothelial carcinoma measuring 1.2 cm (G-2-pT1) which was not recognised clinically.