Gastrointestinal amyloidosis in Australian indigenous patients.

This study documents the symptoms, racial distribution, pathological findings and outcomes of patients diagnosed with gastrointestinal amyloidosis in Alice Springs Hospital. In a 4 year retrospective survey. 9 patients, all indigenous, 7F/2M, had biopsy proven gastrointestinal amyloidosis. Four out of four patients tested were found to have AA amyloidosis. Presenting symptoms included diarrhoea, bloody in some, vomiting and abdominal pain. All but one had diabetes mellitus, type 2. Multiple infections were common and most patients had low serum albumin and transferrin concentrations but high serum ferritin concentrations. Five of the patients died, and the gastrointestinal symptoms of the remaining 4 remitted. Gastrointestinal amyloidosis should be included in the differential diagnosis of indigenous patients presenting with chronic diarrhoea, vomiting or abdominal pain. It carries a grave prognosis, is probably secondary to chronic infections but is potentially reversible.

Association of TLR2 and TLR4 gene single nucleotide polymorphisms with Fungal Keratitis in Chinese Han population.

PURPOSE: Toll-like receptor 2 (TLR2) and Toll-like receptor 4 (TLR4) play a crucial role in the primary defense against fungal pathogens, and since genetic variation in genes may regulate the response. This study aimed to test whether variants in the TLR4 gene are associated with fungal keratitis (FK) of Chinese Han population. MATERIALS AND METHODS: Two-hundred sixty-nine subjects (109 cases and 160 matched controls) in a Han Chinese population were genotyped. Seven single nucleotide polymorphisms (SNPs) which located, respectively, in the TLR2 and TLR4 genes were selected and their associations with FK risk factors were assessed. RESULTS: Allele A of TLR4 rs10983755 was found significantly higher in the group of FK patients, being detected in 32.11% of the FK patients alleles and in 22.19% of the healthy control alleles (p = 0.01).Those AA/AG genotypes carrying the allele A of rs10983755 had a risk effect on the etiology of FK, and the odds ratio for the FK patients versus controls was 2.075 (OR = 2.075, 95%CI = 1.264-3.407). The Ht3 haplotype, which carried the A allele of TLR4 rs10983755, was associated with the significantly increased risk of FK (OR = 1.786, 95%CI = 1.207-2.642). While, the Ht2 haplotype, which carried the wild G allele of TLR4 rs10983755, was a protective haplotype (OR = 0.488, 95%CI = 0.333-0.715). The genotype and allele frequency of TLR2 showed no differences between the two groups (p > 0.05). CONCLUSIONS: The rs10983755, located in the 5'-untranslated region (UTR) of TLR4, was most strongly associated with FK of Chinese Han population (p < 0.05). The analysis of TLR2 gene polymorphisms showed no significant association upon FK susceptibilities of Chinese Han population.

Evaluation of the autoimmune regulator (AIRE) gene mutations in a cohort of Italian patients with autoimmune-polyendocrinopathy-candidiasis-ectodermal-dystrophy (APECED) and in their relatives.

OBJECTIVE: Autoimmune-polyendocrinopathy-candidiasis-ectodermal-dystrophy (APECED) is a rare syndrome characterized by chronic candidiasis, chronic hypoparathyroidism and Addison's disease. APECED has been associated with mutations in autoimmune regulator (AIRE) gene. Our aim is to perform a genetic analysis of the AIRE gene in Italian APECED patients and in their relatives. Design AIRE mutations were determined by DNA sequencing in all subjects. Patients were tested for clinical autoimmune or non-autoimmune diseases, or for organ and non-organ specific autoantibodies. PATIENTS: A total of 24 Italian patients with APECED (15 from the Venetian region, 2 from Southern-Tyrol, 4 from Apulia, 3 from Sicily), 25 relatives and 116 controls were studied. RESULTS: Ten out of the 15 Venetian patients (66%) were homozygous for R257X or compound heterozygous with 1094-1106del13. One patient was homozygous for 1094-1106del13 and another for R139X. A novel mutation (1032-1033delGT) in combination with 1094-1106del13 was identified in one patient. No mutations were found in two cases. Two patients from Southern Tyrol were homozygous for R257X and for 1094-1106del13bp. All patients from Apulia were homozygous or heterozygous for W78R combined with Q358X. The patients from Sicily were homozygous for R203X or compound heterozygous with R257X. The analysis of the genotype-phenotype revealed that patients carrying 1094-1106del13 at the onset of Addison's disease were significantly older than those carrying other mutations. The genetic study of 25 relatives identified 20 heterozygous subjects. They suffered from various autoimmune and non-autoimmune diseases but no major disease of APECED was found. CONCLUSION: These data demonstrate the great genetic heterogeneity for the AIRE mutations in Italian APECED patients, and that the heterozygosity for AIRE mutations do not produce APECED.

Candida albicans GRX2, encoding a putative glutaredoxin, is required for virulence in a murine model

Resistance of Candida albicans to reactive oxygen species is thought to enhance its virulence in mammalian hosts. Genes such as SOD1, which encodes the anti-oxidant, superoxide dismutase, are known virulence factors. We disrupted the gene GRX2, which encodes a putative glutathione reductase (glutaredoxin) in C. albicans, and we compared the mutant with an sod1 Delta mutant. In vitro, the grx2 Delta strain, but not the sod1 Delta strain, was defective in hypha formation. The grx2 Delta strain, but not sod1 Delta, was significantly more susceptible to killing by neutrophils. When exposed to two compounds that generate reactive oxygen species, both mutants were susceptible to 1 mM menadione, but grx2 Delta null alone was resistant to diamide. Both mutants were attenuated in a murine intravenous challenge model, and a GRX2 reintegrant regained partial virulence. Emphasis on the putative function of products of genes such as SOD1 and GRX2 in resistance to oxidative stress may oversimplify their functions in the virulence process, since the grx2 Delta strain also gave defective hypha formation. Both mutants were sensitive to menadione and were slow to form germ tubes, though growth rates matched controls once the lag phase was passed.

Ethnicity and other possible risk factors for candidemia at 3 tertiary care university hospitals in Hawaii.

A total of 108 cases of candidemia detected in 3 tertiary care university hospitals in Hawaii between January 2001 and December 2002 were retrospectively reviewed. Candida albicans, Candida glabrata, and Candida tropicalis accounted for 28% of the cases. Mortality among Filipino patients was significantly higher than that among other ethnic groups (71% vs 48%; P<.05).

Candida and squamous (pre)neoplasia of immigrants and Dutch women as established in population-based cervical screening.

The objective of this study was to establish the relationship between Candida vaginalis and (pre)neoplasia and the prevalence of Candida and (pre)neoplasia related to age and ethnicity. Data were collected from 445,671 asymptomatic women invited for mass screening between 1995 and 2002 and coded according to the Dutch cervical smear coding system (KOPAC) with six grades for (pre)neoplastic changes. Prevalence and relative risks (RRs) were established for Candida and squamous abnormalities in Dutch women and four groups of immigrants. The prevalence of Candida is significantly higher in the cohort of 30-year-old women and lower in the cohorts of 45-, 50-, 55-, and 60-year-old women. The RR of having Candida was higher for Surinamese women (1.24; CI 1.08-1.42). Furthermore, the RR of having mild dysplasia was higher for Surinamese women (1.47; CI 1.14-1.89) and for women born in other countries than in The Netherlands, Turkey, and Morocco (1.36; CI 1.13-1.62). No statistically significant relationship between (pre)neoplasia and Candida was observed. C. vaginalis is more frequent among Surinamese women. Presence of Candida is not associated with an increased risk for squamous abnormalities; therefore, women carrying Candida are not at an increased risk of developing cervical cancer.

Race, Candida sepsis, and retinopathy of prematurity.

The objective of this observational cohort study at Georgetown University Hospital from January 1, 1994 through December 31, 1997 was to investigate race, Candida sepsis, and duration of oxygen exposure in infants with retinopathy of prematurity (ROP) with birth weight < or = 1,000 g. The incidence of ROP was 70.8% (114/161). The incidence of stage III or greater ROP in the Caucasian infants was significantly higher at 46.7% (14/30) than in the African-American infants at 23.8% (20/84) with p < 0.02. In addition, the incidence of threshold disease was higher in Caucasian infants 33.3% (10/30) when compared to African-American infants 9.5% (8/84) with p < 0.002. Using multiple logistic regression, African-American race was found to be an independent protective factor against developing severe ROP [adjusted odds ratio 0.39; 95% confidence interval (UCI) 0.16-0.97]. Extremely-low-birth-weight African-American infants with comparable severity of illness (including birth weight, gestational age, duration of supplemental oxygen exposure, and Candida sepsis) are less likely to develop severe ROP than Caucasian infants.

Case report: familial chronic mucocutaneous candidiasis complicated by deep candida infection.

Chronic mucocutaneous candidiasis (CMC) is usually characterized by onset in childhood and is almost never complicated by deep fungal infection. The authors report two cases of fatal candida meningitis in patients who suffered from mild, adult-onset CMC. The pedigrees suggest an autosomal recessive disorder. In the index cases and in a symptomatic sibling, the immunologic work-up showed a specific cellular deficit as opposed to Candida albicans, as is typical of other forms of CMC. Both families were of French Canadian descent and originated from eastern Quebec. Three other cases of primary candida meningitis in patients of the same ethnic origin are also reported and reviewed. It is suggested that these cases may represent a variant of familial adult-onset CMC, in which there is a striking predisposition to deep infection.