Lack of association between KIR and HLA-C type and susceptibility to idiopathic bronchiectasis.

INTRODUCTION: Idiopathic bronchiectasis is a poorly defined disease characterised by persistent inflammation, infection and progressive lung damage. Natural killer (NK) cells provide a major defense against infection, through the interaction of their surface receptors, including the activating and inhibitory killer immunoglobulin-like receptors (KIR), and human leukocyte antigens (HLA) class I molecules. Homozygosity for HLA-C has been shown in a single study to confer increased genetic susceptibility to idiopathic bronchiectasis. We aimed to assess whether the KIR and HLA repertoire, alone or in combination, may influence the risk of developing idiopathic bronchiectasis, in an independent replication study. METHODS: In this prospective, observational, case-control association study, 79 idiopathic bronchiectasis patients diagnosed following extensive aetiological investigation were compared with 98 anonymous, healthy, age, sex and ethnically-matched controls attending blood donor sessions in the same geographical location. DNA extraction was performed according to standardised techniques. Determination of presence or absence of KIR genes was performed by a sequence specific oligonucleotide probe method. Allele frequencies for the proposed KIR, HLA-B and HLA-C risk alleles both individually and in combinations were compared. RESULTS: We found no significant differences in allele frequency between the idiopathic bronchiectasis and control samples, whether considering HLA-C group homozygosity alone or in combination with the KIR type. DISCUSSION: Our results do not show an association between HLA-C and KIR and therefore do not confirm previous positive findings. This may be explained by the lower frequency of HLA-C1 group homozygosity in the control population of the previous study (27.2%), compared to 42.3% in our study, which is consistent with the genetic profiling of control groups across the UK. The previous positive association study may therefore have been driven by an anomalous control group. Further larger prospective multicentre replication studies are needed to determine if an association exists.

Phenotyping adults with non-cystic fibrosis bronchiectasis: a prospective observational cohort study.

BACKGROUND: Bronchiectasis is the outcome of a number of different airway insults. Very few studies have characterised the aetiology and utility of a dedicated screening proforma in adult patients attending a general bronchiectasis clinic. METHODS: A prospective observational study of 189 bronchiectasis patients attending two centres in the North East of England over a two-year period was performed. RESULTS: The aetiology of bronchiectasis was identified in 107/189(57%) patients. Idiopathic bronchiectasis (IB) represented the largest subgroup (43%). Post-infection bronchiectasis (PIB) constituted the largest proportion (24%) of known causes. Mean age (SD) at diagnosis was 54(20) years with a mean age at symptom onset of 37(24) years, accounting for a diagnostic delay of 17 years. Age of symptom onset was significantly younger in patients with PIB compared to IB (p < 0.0001) and in Pseudomonas sputum positive patients (p = 0.007). Screening for APBA and total immunoglobulin deficiency identified 9 (5%) patients who then had tailored treatment. Routine screening for other aetiologies was deemed unnecessary. CONCLUSION: IB and PIB accounted for two thirds of cases of bronchiectasis in a general population. We recommend routine screening for ABPA and total immunoglobulin deficiency but not for other rarer aetiologies.

Angiotensin-(1-7) via the mas receptor alleviates the diabetes-induced decrease in GFAP and GAP-43 immunoreactivity with concomitant reduction in the COX-2 in hippocampal formation: an immunohistochemical study.

We have previously shown that chronic treatment with angiotensin-(1-7) [Ang-(1-7)] can prevent diabetes-induced cardiovascular dysfunction. However, effect of Ang-(1-7) treatment on diabetes-induced alterations in the CNS is unknown. The aim of this study was to test the hypothesis that treatment with Ang-(1-7) can produce protection against diabetes-induced CNS changes. We examined the effect of Ang-(1-7) on the number of cyclooxygenase-2 (COX-2) immunoreactive neurons and the glial fibrillary acidic protein (GFAP)-immunoreactive astrocytes and assessed the changes in the neuronal growth-associated protein-43 (GAP-43) of the hippocampal formation in streptozotocin-induced diabetes in rats. Animals were sacrificed 30 days after induction of diabetes and/or treatment with Ang-(1-7). Ang-(1-7) treatment significantly prevented diabetes-induced decrease in the number of GFAP immunoreactive astrocytes and GAP-43 positive neurons in all hippocampal regions. Co-administration of A779, a selective Ang-(1-7) receptor antagonist, inhibited Ang-(1-7)-mediated protective effects indicating that Ang-(1-7) produces its effects through activation of receptor Mas. Further, Ang-(1-7) treatment through activation of Mas significantly prevented diabetes-induced increase in the number of the COX-2 immunolabeled neurons in all sub-regions of the hippocampus examined. These results show that Ang-(1-7) has a protective role against diabetes-induced changes in the CNS.

Seroepidemiological study of Rift Valley fever (RVF) in animals in Saudi Arabia.

Serological prevalence of IgG antibodies against Rift Valley fever (RVFV) virus was investigated in 22 major localities in five different regions of Saudi Arabia where vaccination against RVF virus (RVFV) is not practiced. The study excludes the southwestern region where a major outbreak of RVF occurred in 2000 and where annual vaccination of ruminants is practiced. Sheep and goat IgG-sandwich ELISA were used to test serum samples from sheep and goats, and bovine IgG-sandwich ELISA was used to test cattle sera. A nonspecies-specific, nonantibody isotype-specific ELISA was used to test camel sera. A total of 3,480 sheep, goats, cattle and camels with no previous history of vaccination against RVFV were randomly tested. All tested animals were negative for IgG class antibodies against the virus except four out of 1,508 sheep and three out of 913 goats, which tested positive. All animals were clinically normal and no evidence was found of virus activity in the studied areas. It is, therefore, most likely that those rare positive cases, which constituted 0.002% of the total animals tested, were either false positives or vaccinates smuggled from the outbreak zone. The need for regular monitoring of animals both within the outbreak zone of 2000 and other parts of the kingdom is strongly emphasized.

Radiofrequency ablation combined with percutaneous ethanol injection in patients with hepatocellular carcinoma.

BACKGROUND AND STUDY AIMS: Hepatocellular carcinoma (HCC) is a major burden on health-care systems worldwide. Although radiofrequency ablation (RFA) is currently considered the best technique for coagulative necrosis, the superiority of concomitant use of RFA and percutaneous ethanol injection (PEI) needs to be determined. The study was designed to compare efficacy, safety and rate of survival of patients with HCC assigned to receive combined PEI-RFA versus RFA alone and versus PEI alone. PATIENTS AND METHODS: This 3-year study enrolled 90 cirrhotic patients with HCC (Child's class A or B, but not class C). They were randomly assigned for either PEI-RFA (group I), RFA alone (group II) or PEI alone (group III). The primary end point was ablation of the tumour. The secondary end point was rate of survival and recurrence. RESULTS: After the first session, complete ablation was significantly higher in the combination group (87.9%) compared with the RFA group (54.54%). After the second session, complete ablation was achieved in 97.0% of the combination group and in 84.8% of the RFA group. Regarding the PEI group, 75% had complete ablation, whereas 25% had partial ablation after multiple sessions. The survival rate, 1.5 years later, was significantly higher in group I (86.7%) compared with group III (63.3%). The overall incidence of serious adverse events was nil. CONCLUSION: Combined treatment is superior to RFA alone and to PEI alone, in safety and efficacy in patients with HCC.

Anti-HCV prevalence among diabetic and non-diabetic Egyptian children.

Our aim was to determine the prevalence of the HCV infection among children with type 1 DM as compared to a group of non-diabetic children attending the general outpatient clinics of the same hospital and investigate the possible risk factors. The study was carried out on 692 children with type 1 DM attending the Pediatric Diabetes Unit at Cairo University Pediatric Hospital, Egypt, and 1042 non-diabetic children attending the general outpatient clinics of the same hospital. They were screened for HCV antibodies using third generation ELISA. Anti-HCV antibody prevalence in diabetic children below 9 years of age was comparable to that of non diabetic children (2.5% vs. 1.4%; p=0.25). Diabetic children had higher exposure to medical care (p=0.04); all diabetics were exposed to daily insulin injections and daily blood glucose monitoring. Non-diabetics had higher exposure to razors used by others (p=0.05) and higher rate of traditional hair cutting (p=0.05). To conclude, the prevalence of anti-HCV in diabetic children below 9 years of age was comparable to non diabetic children of the same age group. Application of standard precautions for infection control could successfully limit spread of HCV infection in our Pediatric Diabetes Unit, in a country with high HCV load as Egypt.

Thioredoxin and thioredoxin reductase expression in thyroid cancer depends on tumour aggressiveness.

Thyroid cancer is the second most common malignancy following breast cancer in Arab females. Thioredoxin (TRX) is a small multi-functional redox protein with both intracellular and extracellular functions. The protein exists in either a reduced form (thioredoxin-SH2) or an oxidized form (thioredoxin-S2). TRX acts as an enhancement for growth factors and stimulates the growth of cancer cells. In this study of thyroid neoplasms, involving 121 female and 62 male patients, expression of TRX and TRX-R was studied using purified mouse anti-human TRX monoclonal antibody and anti-human TRX-R antiserum from rabbits, respectively. In order to delineate tumour cell growth, proliferating cell nuclear antigen (PCNA) polyclonal antibody was used. Compared to normal thyroid tissue, expression of TRX and TRX-R was increased in the cytoplasm and nuclei of thyroid cancer cells. Furthermore, TRX expression correlated with that of TRX-R. Of the 183 thyroid neoplasms investigated, overexpression of TRX-R was found in different types of neoplasms. The majority of carcinomas showed a correlation between strongly positive TRX and TRX-R expression and neoplastic cellular proliferation, as measured by PCNA. This indicates that increased TRX and TRX-R expression may be associated with tumourigenesis by acting as an autocrine growth stimulus. This study suggests that TRX immunoreactivity in thyroid tumours is a function of malignancy and cancer progression. In addition, secreted TRX can also act as an extracellular growth factor for both normal and tumour cells and enhance the sensitivity of the cells. Furthermore, this study emphasizes the potential benefits of anti-TRX/TRX-R agents in cancer therapeutics in the treatment of thyroid cancer.

Effects of long-term low-dose azithromycin in patients with non-CF bronchiectasis.

UNLABELLED: We describe our institutional efficacy experience of azithromycin 250 mg thrice weekly in adult non-cystic fibrosis bronchiectasis. METHODS: Eligibility criteria for prophylactic azithromycin included 3 exacerbations requiring rescue antibiotics over the previous 6 months. The clinical records of 56 bronchiectasis patients on azithromycin were retrospectively reviewed. Exacerbation frequency, sputum microbiology, self-reported change in sputum volume, and spirometry results were recorded. RESULTS: Mean length of treatment was 9.1 months (7.5) and 50 patients had treatment > or = 3 months. Spirometry, pre- and post-azithromycin in 29 patients, who had 3 or more months of treatment, showed a mean increase in FEV(1) of 83 ml (0.14) (P=0.005) from 1.560 to 1.643l. There was a decrease in the exacerbation frequency from 0.81/month (SD) (0.32) pre-azithromycin to 0.41/month (0.45) (P<0.001) post-azithromycin. Clinically significant suppression of previous sputum microbial isolates was also observed. CONCLUSION: Azithromycin improves exacerbation frequency, spirometry, and sputum microbiology in bronchiectasis.

Optimal age of sexual maturation in Egyptian children.

To establish the optimal age of sexual maturation in Egyptian children, Tanner's maturity stages were determined for a sample of children and adolescents (1550 girls, 1563 boys) ranging from 6.5 to 18.5 years. The mean age for attainment of pubic hair (stage PH2) was 10.46 (SD 1.36) years for girls and 11.86 (SD 1.45) years for boys. For axillary hair (stage A2), mean age was 11.65 (SD 1.62) years for girls and 13.55 (SD 1.52) years for boys. The mean age at menarche in girls was 12.44 years and for breast development (stage B2) was 10.71 (SD 1.30) years. Testicular volume by palpation showed that the mean age of genital stage G2 for boys was 10.56 (SD 1.40) years. The study results can aid in the assessment of sexual maturation and pubertal disorders in Egyptian adolescents.

Optimal age of sexual maturation in Egyptian children

To establish the optimal age of sexual maturation in Egyptian children, Tanner's maturity stages were determined for a sample of children and adolescents [1550 girls, 1563 boys] ranging from 6.5 to 18.5 years. The mean age for attainment of pubic hair [stage PH2] was 10.46 [SD 1.36] years for girls and 11.86 [SD 1.45] years for boys. For axillary hair [stage A2], mean age was 11.65 [SD 1.62] years for girls and 13.55 [SD 1.52] years for boys. The mean age at menarche in girls was 12.44 years and for breast development [stage B2] was 10.71 [SD 1.30] years. Testicular volume by palpation showed that the mean age of genital stage G2 for boys was 10.56 [SD 1.40] years. The study results can aid in the assessment of sexual maturation and pubertal disorders in Egyptian adolescents

Spontaneous dislocation of posterior polar cataract.

We report an unusual case of unilateral spontaneous lens dislocation in a 52-year-old woman with a posterior polar cataract. We postulate that the increasing lens size secondary to nuclear sclerosis may have exerted pressure on a thinned posterior capsule, causing the capsule to rupture spontaneously. The unusual weak posterior capsule in posterior polar cataract is a well-recognized risk factor in phacoemulsification surgery. We believe this is the first report case of spontaneous lens dislocation secondary to posterior capsule rupture in posterior polar cataract.

Polycyclic aromatic hydrocarbon in rain and street runoff in Amman, Jordan.

Concentrations of polycyclic aromatic hydrocarbons (PAHs) were determined in the rain and street runoff samples from two sites in the vicinity of Amman City during the pluvial period 1999-2000. The results showed that elevated levels of PAHs were detected in the city center (site 1) than the residential area (site 2) and that the levels were higher in street runoff than rain samples of the same sites. The highest concentration of PAHs in both street runoff and rain samples were observed in the first rainy month (November 1999) which indicated a wash out effect of PAHs originating from vehicular emission accumulated during the long dry summer season before sampling. Within the investigated cold winter seasons, fluctuations in PAHs concentration were observed. The variation was attributed to the fossil combustion for heating purposes and to intervals between rainfalls: as the longer the intervals between rains were, the higher the PAH concentration were. Removal of PAHs from the atmosphere through precipitation over the investigated period varied with time and places depending on the amount of rainfall where higher rainfall removed higher amount of PAHs from the atmosphere. The amount of PAHs washed out through precipitation was estimated to be around 14.8 mg/m2 and 21.1 mg/m2 for sites 1 and 2 respectively.

Correlation of plasma levels of tumor necrosis factor, interleukin-6 and nitric oxide with the severity of human malaria.

Thirty two patients of malaria (15, 11 & 6) having P. vivax, uncomplicated and complicated P. falciparum malaria respectively, and 10 healthy controls were subjected to full clinical and laboratory examinations as well as estimation of plasma levels of tumor necrosis factor (TNF), interleukin-6 (IL-6) and nitric oxide (NO). The main clinical presentations were fever, pallor, jaundice, splenomegaly and anaemia which were more pronounced in patients with complicated falciparum malaria. Light coma (50%), convulsions (33.3%), severe anaemia (66.6%). severe hypoglycemia (66.6%) and increased blood lactate levels (50%) were detected in patients with complicated falciparum malaria. The results showed significant elevation of plasma levels of TNF, IL-6 and NO in all malaria patients as compared to the controls. The levels were significantly higher in patients with complicated falciparum malaria than in the other patient groups. The TNF, IL-6 and NO had an effective role in pathogenesis of malaria and their levels in can be a useful diagnostic markers for malaria and severity.