Serologial screening of human T cell lymphotropic virus I and II (HTLV I/II) in blood banks by immunoblotting and enzyme-immuno assays: to demand or to defeat?

Human T cell lymphotropic virus I and II (HTLV I/II) has been recommended to be screened for blood donors since 1988, and it become a mandatory test to get college of american Pathologists (CAP) accreditation. The present study aimed at investigating the prevalence rate of HTLV I/II among Arab blood donors, to revise whether is its screening mandatory? Thirty-thousand (30,000) Arab donors along two years attending two central hospital blood banks in Jeddah. Antibodies to HTLV I/II have been screened using enzyme immunoassay (E.I.A) and immunoblotting assay (Western blot). Results revealed zero prevalence rate. Based upon this finding, no potential risk of HTLV I/II transmission among blood donors population exist. As screening for HTLV I/II is still mandatory, it could be done on pools of sera rather than on individual serum samples, after standardization of a pooling protocol, to fulfill coast-effectiveness and reduce the coasts by 90-95%.     

Developmental changes in proximal tubule tight junction proteins

We demonstrated previously that neonatal proximal tubules have a lower passive paracellular permeability to chloride ions and higher resistance than that of adult proximal tubules. In addition, administration of thyroid hormone to neonates, before the normal maturational increase in serum thyroid hormone levels, prematurely accelerates the developmental increase in chloride permeability to adult levels. To test the hypothesis that there is a maturational change in tight junction proteins and that thyroid hormone mediates these changes, we examined the two known tight junction proteins present in proximal tubules, occludin and claudin 2. Using immunoblot and immunohistochemistry, we demonstrated that claudin 2 has a 4-fold greater abundance in neonatal proximal tubules than in adult tubules. Occludin, however, has a 4-fold greater expression in adult tubules than in neonatal tubules. Administration of thyroid hormone to neonates did not affect claudin 2 expression, occludin expression, or the transepithelial resistance in rat proximal tubule cells in vitro. In conclusion, there are postnatal maturational changes in tight junction proteins. The factors that cause these maturational changes are unknown but unlikely to be due solely to the maturational increase in thyroid hormone.     

Lichen sclerosus mistaken for child sexual abuse

A 3-year-old girl presented to the primary care clinic at King Abdulaziz Medical City (KAMC) with asymptomatic white discoloration of the vulva of 3 months’ duration. Dysuria, genital itching, and vaginal discharge followed 2 months later. The discharge was yellowish-greenish in color and occasionally associated with blood-tinged staining of the underwear. The mother had noted that the genital skin changes had worsened in the last 2 weeks and that the genital itching and dysuria had become more frequent. There was no history of trauma, behavioral problems, abnormal sexual behaviour, encopresis, or any underlying disease. On questioning the mother, the possibility of sexual abuse could not be ruled out as she reported that the father was drug and alcohol dependent and behaved inappropriately when under the influence of these factors. Because of this possibility, the girl and her parents were referred to the suspected child abuse and neglect (SCAN) team at KAMC for further evaluation. The physician, social worker, and child psychiatrist interviewed the girl, her three older brothers, and the parents separately. The girl and her siblings denied any abnormal touching by an adult. The mother reported that she and the father had been separated for 1 year; however, the couple had been reunited for the last month and were currently living together. The mother linked the appearance of the genital changes to the time the father returned; however, no definite history of sexual abuse was obtained. The father denied any sexual or other abnormal encounter with the child. On examination, the child was well developed and well nourished, cooperative, and showed no abnormal fear of genital or anal examination. Genital examination revealed sharply demarcated, hypopigmented, atrophic plaques symmetrically surrounding the labia majora ( Fig. 1 ). Three sharply demarcated, 0.5 cm, nonpalpable, reddish purpuric macules on the medial aspect of both the labia majora and the base of the clitoris were noted ( Fig. 2 ). Two sharply defined healing erosions were noted on the left side distal to the introitus. The hymenal ring could not be seen, but the hymenal orifice was not dilated. The introitus and the anus appeared normal. Because of the genital findings and the mother's concerns, the possibility of sexual abuse was contemplated. Extensive laboratory testing for sexually transmitted diseases, including syphilis, chlamydia, human immunodeficiency virus, and gonorrhea, were negative. Urine analysis and culture were negative. Routine vaginal culture grew group B β-hemolytic streptococcus, and the patient was treated with amoxicillin-clavulanate orally for 10 days. Due to a lack of evidence of sexual abuse, the SCAN team decided to follow up the child and to investigate further before reporting to the protective agency.

Figure 1 Open in figure viewer PowerPoint Photograph of the vulva showing atrophic, hypopigmented, sharply defined plaques     

A randomized trial of letrozole versus clomiphene citrate in women undergoing superovulation

OBJECTIVE: To compare the effects of the aromatase inhibitor letrozole (7.5 mg) and clomiphene citrate (CC; 100 mg) in women undergoing superovulation and IUI. DESIGN: Prospective randomized trial. SETTING: University teaching hospital. PATIENT(S): We studied a total of 238 cycles of superovulation and IUI in women with idiopathic infertility. INTERVENTIONS: Patients were randomized into treatment with 7.5 mg of letrozole daily (74 patients, 115 cycles) or 100 mg of CC daily (80 patients, 123 cycles). MAIN OUTCOME MEASURE(S): Number of follicles, endometrial thickness, pregnancy rate, and miscarriage rate. RESULT(S): The mean age, parity, and duration of infertility in both groups of patients were similar. There was no significant difference between the total number of developing follicles in the letrozole (5.7 +/- 3.7) and in the CC groups (4.8 +/- 2.5). The number of follicles of > or =14 mm and of >18 mm were 2.1 +/- 1.2 and 1.4 +/- 0.7 in the letrozole group, and 1.7 +/- 0.9 and 1.1 +/- 0.5 in the CC group, respectively. No difference was found in the endometrial thickness between the two groups (7.1 +/- 0.2 mm in the letrozole group, 8.2 +/- 5.9 mm in the CC group). The pregnancy rate per cycle was 11.5% in the letrozole group and 8.9% in the CC group. Four of the 11 pregnancies in the CC group resulted in a miscarriage (36.6%). CONCLUSION(S): Superovulation and IUI with letrozole and CC are associated with similar pregnancy rates, but the miscarriage rate is higher with CC. The ideal dose of letrozole remains unknown and further study is needed.     

Matrix metalloproteinase-2, squamous cell carcinoma antigen, and tissue polypeptide-specific antigen expression in Egyptian patients with cervical carcinoma: Relationship with prognosis

Matrix metalloproteinases (MMPs), a family of proteolytic enzymes produced by both stromal and tumor cells, appear to have a key role in the events leading to local invasion and metastasis by malignant neoplasms. In the present study, we evaluated the role of MMP-2, squamous cell carcinoma antigen (SCCA), and tissue polypeptide - specific antigen (TPS) in cervical neoplasia. Using Western blotting and enzyme immunoassay (EIA), we analyzed 50 patients with cervical carcinoma (CC) and 25 normal controls for expression of MMP-2 in tissue cell lysates. We also quantified SCCA and TPS with microparticle immunoassay and EIA, respectively. The results were correlated with human papilloma virus (HPV) infection, clinicopathological findings, and disease outcome. The cutoff point for each marker was estimated from receiver operating characteristic curves. Logistic regression analysis was performed to estimate the odds ratio (OR) and 95% confidence interval (CI) for each marker. MMP-2, SCCA, and TPS protein expression were significantly higher in patients with CC than in normal controls. While TPS was the best marker for discriminating between patients and controls, MMP-2 was associated with an advanced tumor stage (OR, 13.9 [95% CI, 1.4-133.9]) and poor histological grade (OR, 10.2 [95% CI, 1.7-60.5]). Moreover, independent of the effect of an advanced CC stage and grade, the patients' age, and the presence of HPV infection, MMP-2 was considered a strong predictor for CC recurrence (OR, 8.1 [95% CI, 1.3- 49.1]). Tissue markers may be used to select high-risk patients for early detection of and adjuvant therapy for recurrence. Our MMP-2 findings are particularly relevant to the development of protease inhibitors as a new cancer therapy approach.     

Influenza a common viral infection among Hajj pilgrims: time for routine surveillance and vaccination

BACKGROUND: The annual Hajj pilgrimage to Mecca, Saudi Arabia brings over two million people to a small confined area. Respiratory tract infection is the most common disease transmitted during this period. For most of the etiologic agents of upper respiratory tract infections, no vaccine or prophylaxis is available, except for influenza. Yearly influenza vaccination of high-risk groups is recommended, but no special recommendations are available for those performing the Hajj or other similar large congregational activities. Viral surveillance studies are being carried out through more than 100 centers around the world to identify newly emerging viruses. Saudi Arabia is not one of those centers and no routine surveillance takes place. METHODS: Five hundred Hajj pilgrims presenting with upper respiratory tract symptoms from different parts of the world were screened by way of a throat swab for viral culture, including influenza A and B, parainfluenza, respiratory syncytial virus (RSV), adenovirus, herpes simplex virus (HSV), and enteroviruses. Information was collected on age, sex, nationality, smoking habits and upper respiratory tract symptoms. Vaccination status for influenza and meningococcus was obtained by self-declaration, since most pilgrims did not have their vaccination cards with them. Only those with symptoms including at least fever, reported by the patient to be >38.3 degrees C, and/or sore throat were included. Pilgrims with any other symptoms, especially myalgia and fatigue alone, were excluded, since many of the physical chores during the pilgrimage may contribute to such symptoms. RESULTS: Fifty-four patients (10.8%) had positive viral throat cultures. Of these, 27 (50%) were influenza B, 13 (24.1%) were HSV, 7 (12.9%) were RSV, 4 (7.4%) were parainfluenza, and 3 (5.6%) were influenza A. No enteroviruses or adenoviruses were detected, and no multiple infections were detected. Only 22 (4.7%) pilgrims received the influenza vaccine. When the results are applied to the total number of pilgrims in 2003, an estimate of 24,000 cases of influenza is obtained. CONCLUSION: The findings from this study suggest a high incidence of influenza as a cause of upper respiratory tract infection among pilgrims, estimated to be 24,000 cases per Hajj season, excluding those becoming ill from contact with Hajj pilgrims returning home. They also indicate a very low vaccination rate for the influenza vaccine; as well as poor knowledge of its existence. Continued surveillance during the Hajj pilgrimage is necessary. The influenza vaccine should be a priority for those attending the Hajj pilgrimage, and should also be considered for antiviral prophylaxis.     

Regulation of microtubule, apoptosis, and cell cycle-related genes by taxotere in prostate cancer cells analyzed by microarray

Taxotere showed antitumor activity against solid tumors including prostate cancer. However, the molecular mechanism(s) of action of Taxotere has not been fully elucidated. In order to establish such molecular mechanism(s) in both hormone-insensitive (PC3) and hormone-sensitive (LNCaP) prostate cancer cells, comprehensive gene expression profiles were obtained by Affymetrix Human Genome U133A Array. The RNA from the cells treated with 2 nM Taxotere was subjected to microarray analysis. We found that a total of 166, 365, and 1785 genes showed greater than two-fold change in PC3 cells after 6, 36, and 72 hours of treatment, respectively compared to 57, 823, and 964 genes in LNCaP cells. The expression of tubulin was decreased, whereas the expression of microtubule-associated proteins was increased in Taxotere-treated prostate cancer cells, confirming the microtubule-targeting effect of Taxotere. Clustering analysis showed downregulation of some genes for cell proliferation and cell cycle. In contrast, Taxotere upregulated some genes that are related to induction of apoptosis and cell cycle arrest. From these results, we conclude that Taxotere caused alterations of a large number of genes, many of which may contribute to the molecular mechanism(s) by which Taxotere affects prostate cancer cells. Further molecular studies are needed in order to determine the cause and effect relationships between these genes altered by Taxotere. Nevertheless, our results could be further exploited for devising strategies to optimize therapeutic effects of Taxotere for the treatment of prostate cancer.     

Assessment of carcinogenicity, using PAH-DNA adducts, in workers exposed to polycyclic aromatic hydrocarbons

Introduction

Polycyclic aromatic hydrocarbons (PAH) are environmental contaminants that have been of interest in cancer research for a considerable length of time. DNA adduct formation is considered a marker and indicator for exposure to PAH. The aim of this study was to determine PAH-DNA adduct levels in peripheral blood lymphocytes and urine obtained from workers exposed to PAH, and to evaluate tobacco use, GSTM1 and GSTT1 as possible contributory risk factors.

Material and methods

Our study included a random sample of 66 workers exposed to PAH and 49 non-exposed workers.

Results

PAH-DNA adduct levels of exposed workers were lower than that of the non-exposed group (p<0.05). However, current smoking, GSTM1-negatives, and current smoking with GSTM1-negatives were more frequent in the non-exposed group. In addition, non-exposed workers reported exposure to PAH in their current jobs, as compared with the exposed group (p<0.001). Linear regression analysis identified the levels of benzo-[b]-fluoranthene in the working area as the only significant DNA adduct-forming risk factor (p=0.025).

Conclusion

Further research, with an appropriately large sample size, is highly recommended in measuring PAH-DNA adduct levels and evaluating their relationship with the different types of PAH.     

Epidemiology and outcome of “Early-onset” vs “Late-onset” necrotizing enterocolitis

Objective: We hypothesized that among neonates with necrotizing entercolitis (NEC), important epidemiologic and outcome differences exist between those with early-onset vs. those with late-onset NEC.Methods : We reviewed all records of neonates cared for in the King Fahad University Hospital during the past ten years who had the diagnosis of NEC. We separated cases into two groups depending on age at diagnosis. Specifically, we termed “early-onset” those cases diagnosed during the first seven days of life, and “late-onset” those diagnosed thereafter. We compared, in the two groups, gestational age, clinical signs at onset, laboratory data, surgical findings, complications, and mortality.Results: From 1989 to 1999, 37 cases of stage lla (or higher) NEC were diagnosed; 25 “early-onset “ and 12 “late-onset”. Neonates with “earlyonset” NEC were more mature (35.4 ±2.5 weeks gestation) than those with “late-onset” (27.7 ±2.8 weeks, P = 0.0001), were more likely to have feedings begun in the first 48 hours of life (P = 0.0002), and more likely to have feeding increments of >25 ml/kg/day (P=0.03). Neonates with “late-onset” NEC were more likely to present with vomiting (P=0.003) and apnea (P=0.001), and were more likely to have ileal rather than colonic necrotic lesions, short bowel syndrome, and mortality (P = 0.03).Conclusion: During the past 10 years at the King Fahad University Hospital, cases of early and late-onset NEC have had distinct epidemiologic and outcome features. Recognizing these differences may be useful in prognostication and counseling