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.     

Pregnancy outcome in spontaneous twins versus twins who were conceived through in vitro fertilization

OBJECTIVE: The purpose of this study was to compare maternal and neonatal complications in spontaneous versus in vitro fertilization twins. STUDY DESIGN: Twin gestations that were delivered from 1995 to 2000 were reviewed. Cases consisted of 56 in vitro fertilization twins, each of which was matched to two control mothers by age and parity. They were compared regarding various maternal and neonatal complications. RESULTS: In vitro fertilization twins were more likely to have preterm labor compared with control twins, with no difference in the incidences of pregnancy-induced hypertension, gestational diabetes mellitus, placenta previa, or preterm premature rupture of membranes between the two groups. The cesarean delivery rate was significantly higher in cases of twins who were conceived by in vitro fertilization (76.8% vs 58.0%, P=.026), despite a similar rate of elective cesarean delivery and the incidence of nonvertex twin A in both groups. The preterm delivery rate was significantly higher (67.9% vs 41.1%, P=.002) and the gestational age was significantly lower (35+/-3 weeks vs 36+/-3 weeks, P=.043) in cases compared with control subjects. Both twins were, on the average, 230 g lighter in the in vitro fertilization group compared with the control group. However, intrauterine growth restriction was more frequent in the control group (36.6% vs 25%, P=.044). There was a significantly higher incidence of admission to the neonatal intensive care unit, respiratory distress syndrome, a need for mechanical ventilation, and pneumothorax in cases compared with control subjects. CONCLUSION: When compared with spontaneous twins, in vitro fertilization twins are more likely to be delivered by cesarean delivery and to have a higher incidence of preterm birth and prematurity-related respiratory complications with a longer nursery stay.     

Providing written information for patients with head and neck cancer

Nurses in one Northern Ireland hospital asked patients, their relatives and members of the multidisciplinary care team for their input in compiling an information booklet for patients undergoing major surgery for head and neck cancer, with the aim of creating an information source which would be attractive to a range of patients with head and neck cancer.     

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.     

Localised Ewing sarcoma/PNET of bone--prognostic factors and international data comparison

BACKGROUND: To determine if the distribution of prognostic factors accounted for the differences when the outcome for localised Ewing Sarcoma/PNET bone in Saudi Arabia was compared with results from countries with well developed health care systems. PROCEDURE: Retrospective analysis was undertaken of 163 consecutive patients of all ages, treated with radical intent at KFSHRC from 1975 to 1998. Standard chemotherapy was commenced in all patients. The local treatment modality was resection +/- radiation in 30% and radiation treatment alone in 67%. Size data were available for 51 patients treated from 1994 to 1998, inclusive. One third of these patients had tumors with volume >500 ml. RESULTS: Three year survival significantly increased with the year of diagnosis, 1975-1988 45%; 1989-1993 55%; and 1993-1998 63% (P = 0.006). Favorable prognostic factors were age < or =14 (P = 0.07); site, distal extremity, and skull (P = 0.08); and volume < or = 200 ml (P = 0.06). Secondary prognostic factors were response to induction chemotherapy, both histological, 100% necrosis, (P = 0.04) and clinical CR+PR, (P = 0.02). From 1994 to 1998, 3 year survival for tumors in the distal extremity and skull was 80% and for small tumors, < 200 ml, at any site was 82%. In comparison, the 3 year survival for patients with tumors at any other sites was 60%, and for tumors >200 ml, 55%. CONCLUSIONS: Overall survival progressively improved. From 1994 to 1998 the survival of patients with small tumors and/or favorable sites was similar to the best reported results. It was not possible to compare results by tumor size for large tumors, > 500 ml, due to the absence of data from elsewhere. A better staging system is required for the international comparison of results.     

A novel mutation in the chloride channel gene,CLCNKB, as a cause of Gitelman and Bartter syndromes

BACKGROUND: Gitelman syndrome (GS) and Bartter syndrome (BS) are hereditary hypokalemic tubulopathies with distinct phenotypic features. GS has been considered a genetically homogeneous disorder caused by mutation in the gene encoding the NaCl cotransporter (TSC) of the distal convoluted tubule. In contrast, BS is caused by mutations in the genes encoding either the Na-K-2Cl cotransporter (NKCC2), the K+ channel (ROMK) or the Cl- channel (ClC-Kb) of the thick ascending limb. The purpose of this study was to examine the clinical, biochemical and genetic characteristics of a very large inbred Bedouin kindred in Northern Israel with hereditary hypokalemic tubulopathy. METHODS: Twelve family members affected with hypokalemic tubulopathy, as well as 26 close relatives were clinically and biochemically evaluated. All study participants underwent genetic linkage analysis. Mutation analysis was performed in affected individuals. RESULTS: Evaluation of affected family members (age range 3 to 36 years) revealed phenotypic features of both GS and classic Bartter syndrome (CBS). Features typical of GS included late age of presentation (>15 years) in 7 patients (58%), normal growth in 9 (75%), hypomagnesemia (SMg <0.7mmol/L) in 5 (42%), hypermagnesiuria (FEMg>5%) in 6 (50%) and hypocalciuria (urinary calcium/creatinine mmol/mmol <0.15) in 5 (42%). Features typical of CBS included early age of presentation (<1 year) in 3 (25%), polyuria/dehydration in 4 (33%), growth retardation in 3 (25%), hypercalciuria (urinary calcium/creatinine mmol/mmoverline>0.55) in 4 (33%) and nephrolithiasis in 1 (8%). Linkage analysis in affected patients excluded the TSC gene, SLC12A3, as the mutated gene, but demonstrated linkage to the Cl- channel gene, CLCNKB, on chromosome 1p36. Mutation analysis by direct sequencing revealed a novel homozygous missense mutation, arginine 438 to histidine (R438H), in exon 13 of CLCNKB in all patients. A restriction fragment length polymorphism (RFLP) analysis has been developed to aid in genotyping of family members. CONCLUSIONS: Our findings demonstrate intrafamilial heterogeneity, namely the presence of GS and CBS phenotypes, in a kindred with the CLCNKB R438H mutation. We conclude that GS can be caused by a mutation in a gene other than SLC12A3. The exact role of the CLCNKB R438H mutation in the pathogenesis of the electrolyte and mineral abnormalities in GS and CBS remains to be established.     

Surgically staged focal liver lesions: accuracy and reproducibility of dual-phase helical CT for detection and characterization

PURPOSE: To assess the accuracy and reproducibility of dual-phase helical computed tomography (CT) in enabling preoperative detection and characterization of surgically staged focal liver lesions. MATERIALS AND METHODS: Surgically and histopathologically proven liver lesions were evaluated by three experienced CT readers. These lesions were present in 77 patients who underwent dual-phase helical CT. Images were interpreted separately by the three blinded reviewers. Each lesion was graded on a nine-point scale of confidence, with 1 being definitely benign, 9 being definitely malignant, and 5 being indeterminate. The chi2 test was used to determine if the distribution of lesion classifications was different between readers. RESULTS: There was a total of 237 lesions: 73 were benign and 164 were malignant. Sensitivity for lesion detection was 69%, 70%, and 71% for the three reviewers, respectively. Specificity was 91%, 86%, and 90%, and the area under the curve for the alternative-free response receiver operating characteristic curve was 0.84, 0.83, and 0.85, respectively. The difference in the distributions of lesion classification between the three reviewers was not statistically significant (P =.67) as determined by chi2 analysis. CONCLUSION: Dual-phase CT has sensitivity of 69%-71% and high specificity (86%-91%) in enabling the detection and characterization of focal liver lesions. Interpretation is highly reproducible, as there is minimal variation between experienced reviewers.     

Carcinosarcoma of the urinary bladder: dynamic contrast-enhanced MR imaging with clinical and pathologic correlation

OBJECTIVE: This article describes the MR imaging features of carcinosarcoma of the urinary bladder with clinical presentation and pathologic correlation in three adults. CONCLUSION: Carcinosarcoma of the urinary bladder is a rare and aggressive tumor that has a clinical presentation similar to that of transitional cell carcinoma of the bladder. Dynamic gadolinium-enhanced MR imaging features are discussed.