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     

Human brucellosis: do we need to revise our therapeutic policy?

OBJECTIVE: To identify risk factors of relapse among patients with osteoarticular brucellosis. METHODS: In a prospective cohort study, we investigated 90 patients with diagnosis of brucellosis, as established by clinical picture and at least 4-fold rise in antibody titer. Osteoarticular involvement was defined by inflammatory signs and radiographic changes. Thirty-five patients received combination therapy of 2 drugs (rifampicin + cotrimoxazole or doxycycline), while 55 patients received a combination of 3 drugs (streptomycin + rifampicin + doxycycline). Monthly followup comprised clinical and laboratory examinations (seroagglutination, IgG, IgM antibody titers). Recovery of patients was based on clinical improvement and seroagglutination antibody titer < or = 1:80, as well as negative results for IgG and IgM antibody titers. Incidence of relapse was recorded during the 2 year period of followup after finishing the course of treatment. RESULTS: All patients continued treatment beyond the usual 6 week period previously recommended. Relapse occurred in 59.3% in patients who received treatment for 5 months or less, while relapse occurred in 7.9% among those who received treatment for more than 5 months (p < 0.001). Sixty percent of patients who received combination therapy of 2 drugs had relapse, while there was no relapse in patients who received 3 drugs in combination (p < 0.001). Logistic regression analysis identified duration of treatment < 5 months and IgG level (above 50 U/ml) as independent predictors for relapse; the predictivity of the model was 85.6%. CONCLUSION: Extending treatment for longer than previously recommended (6 weeks) resulted in an incidence of relapse significantly lower than for shorter courses of treatment. IgG antibody in addition to seroagglutinating antibody titers are useful for serological followup of patients with brucellosis.     

Vulvovaginitis caused by Candida spp. and Trichomonas vaginalis in sexually active women

Vulvovaginitis accounts for 20 to 30% of gynecological diseases and it is observed in women from 20 to 30 years of age. It has a higher frequency in women using oral contraceptives and during the third trimester of pregnancy. The aim of this research was to assess the prevalence of Candida spp and Trichomonas vaginalis in patients with the diagnosis of vulvovaginitis from the Gynecology Service in Hospital Universitario "Ruiz y Páez" in Ciudad Bolívar and Hospital "Raúl Leoni" in San Félix (Bolívar State, Venezuela). Two hundred women with symptoms of vulvovaginitis were examined, and samples were taken from the uterocervical cul-de-sac. Each patient was asked to fill a questionnaire. The following studies were made in each sample: a) fresh wet mount examination, b) orange acridine and Giemsa stains for Trichomonas and c) culture for the identification of yeasts. The latter were identified by means of the germinal tube assay, resistance to actidione and the presence of clamidospores in rice-cream agar and sugar utilization test, using the commercial kit ID32C (BioMérieux). Only in 57 women of 200 patients with vulvovaginitis the causative agent was demonstrated; Candida spp was present in 84.2% (n = 48) and Trichomonas vaginalis in 14% (n = 8). A single case of Zygosaccharomyces spp (1.8%) was detected. The age group mainly affected was that of 25-35 years old, the 38.6% of the studied population. Candida species detected were: C. albicans in 87% of cases (n = 42), C. glabrata, in 10.42% (n = 5), and C. guillermondii, in 2.08 (n = 1). Vaginal flux, vulvar pruritus and leucorrhoea were observed in significant number of patients with vulvovaginal candidiasis. The use of antibiotics was considered predisposing factor for Trichomonas vaginalis infection. The relationship between age and the etiological agent was not statistically significant. Due to the low specificity of clinical manifestations of infections caused by Candida spp and Trichomonas vaginalis, we conclude that performing the etiologic diagnosis of vulvovaginitis is necessary in order to take the appropriate therapeutic and preventive measures, specially in those patients with a recurrent disease.     

Cerebellar hypoplasia, hypergonadotrophic hypogonadism, retinitis pigmentosa, alopecia, microcephaly, psychomotor retardation, and short stature: "D-CHRAMPS syndrome"

We here report a rather novel syndrome of dysmorphic features, short stature, microcephaly, alopecia, psychomotor retardation, retinitis pigmentosa and secondary amenorrhoea. This may present a new complex multisystem disorder distinct from those reported in the literature and we propose the acronym D-CHRAMPS for this novel disorder.