Helen Moriarty

Organophosphate-based pesticides and genetic damage implicated in bladder cancer

Organophosphate-based pesticides have been associated with pathology and chromosomal damage in humans. There are also epidemiologic links with cancer. The few screening tests for low-level occupational exposure are of doubtful sensitivity; this investigation evaluated four methods. Blood samples were studied from 10 farmers before and after occupational exposure to organophosphate-based pesticides and five unexposed controls. The standard cholinesterase test was insensitive to the exposure (P=0.815). However, a significant increase in Howell-Jolly bodies within erythrocytes was observed (P=0.001). Cytogenetic studies on routine and aphidicolin-induced blood cultures revealed that following organophosphate exposure the total number of gaps and breaks on human chromosomes was significantly increased (P=0.004 and P=0.0006, respectively). We concluded that Howell-Jolly body and fragile site analysis were sensitive indicators of nuclear damage resulting from low-level occupational exposure to organophosphate. Such nuclear damage could be implicated in carcinogenesis. The development of bladder cancer is one such example.

Randomized, Controlled Trial of Individualized Heparin and Protamine Management in Infants Undergoing Cardiac Surgery With Cardiopulmonary Bypass

OBJECTIVES We sought to determine whether infants (younger than 1 year old) had similar clinical benefits with individualized anticoagulation management as older children and adult undergoing cardiopulmonary bypass (CPB). BACKGROUND Individualized heparin and protamine management in older children and adults undergoing CPB has been associated with improved clinical outcomes. METHODS Ninety infants younger than 1 year of age undergoing CPB were enrolled in a randomized, controlled trial comparing weight-based anticoagulation management using activated clotting time (ACT) to individualized management with Hemostasis Management System Plus. Manufacturers guidelines were followed for the first 33 patients. A modified protocol was used for the last 57 patients with adjustments for coagulation system immaturity and hemodilution on CPB. RESULTS The hemostasis management system (HMS) device consistently underestimated plasma anti-Xa levels, leading to an overestimated required heparin dose. After a blinded interim analysis revealed poor outcomes in the experimental HMS group using manufacturer guidelines, the safety committee suspended the study pending protocol modifications. The use of the HMS device following the modified protocol resulted in more stable anti-Xa levels during CPB with improved post-operative outcomes including reduced need for transfusions (71 ml/kg vs. 80 ml/kg; p = 0.003), ventilation time (33 h vs. 49 h; p = 0.04), intensive care (88 h vs. 99 h; p = 0.003), and hospital length of stay (192 h vs. 216 h; p < 0.001), compared with the weight-based protocol. CONCLUSIONS This study supports the use of the HMS device, with a modified protocol for infants younger than 1 year of age, for anticoagulation management during CPB. Clinical guidelines for the use of the HMS device should be modified for infants younger than 1 year of age.

Comparison of thromboplastins using the ISI and INR system.

&NA; Twelve thromboplastins were tested against a secondary reference thromboplastin (human brain CRM BCR No. 147) or a tertiary house standard (human brain thromboplastin) with plasmas from normal healthy individuals and patients on oral anticoagulant therapy. The relationship between the prothrombin ratios of the thromboplastins tested versus the reference reagent was either a straight or curved line. The International Sensitivity Index (ISI) was estimated for each of the test thromboplastins and these ranged from 0.98 to 2.24. Some ISIs stated by manufacturers were different from our results. Thromboplastins with a high ISI showed a loss of sensitivity in assessing the level of anticoagulation at the upper end of the therapeutic range. In addition, the 95% Confidence Interval (CI) of the ISI estimations were widest for thromboplastins with the highest ISIs. Conversion of the prothrombin ratio to International Normalized Ratio (INR) was most accurate with the Australasian Reference Thromboplastin (ART) and least accurate with reagents having an ISI of 2.00 and over. Thromboplastins with an ISI between 1.10 and 1.50 may be adequate for the control of oral anticoagulant therapy, but were less accurate than a thromboplastin with an ISI approximating 1.00. Factors other than ISI should be considered in the choice of a thromboplastin, in particular a measurement of the accuracy of the ISI estimation such as the 95% confidence interval estimation used here.

A comparison of the sensitivity of APTT reagents to the effects of enoxaparin, a low-molecular weight heparin

Summary Low‐molecular weight heparin (LMWH) is the product of enzymatic or chemical degradation of unfractionated heparin (UFH). It has been found to have better bio‐availibility, more predictable dose response and can be used as an alternative to UFH for prophylaxis and treatment of thrombotic disorders. It is claimed that no laboratory monitoring is necessary for LMWH therapy; however, for the aged, renal impaired, obese or grossly underweight, monitoring of dose effect with anti‐Xa assay is recommended. The activated partial thromboplastin time (APTT), which is the test of choice for UFH monitoring, is believed to be insensitive to the effect of LMWH. The sensitivity of the APTT to heparin lies in the APTT reagent used. In this study, eight different APTT reagents were used to compare the APTT with anti‐Xa activity in ex vivo plasma from patients who were on enoxaparin (LMWH, Clexane) therapy. It was found that, as with UFH, APTT reagents show variable sensitivity to LMWH. The APTTs from all eight reagents were found to have a linear relationship to anti‐Xa activity. The APTT results using three of the reagents gave an indication of the use of LMWH therapy. It was also found that patients who were lupus anticoagulant (LA)‐positive had much more prolonged APTTs when on LMWH therapy; however, a linear correlation between APTT and anti‐Xa was not present in these patients.

Fragile sites and bladder cancer

Continued reports of associations between environmentally induced chromosomal fragile sites and cancer prompted us to undertake a review of current literature to examine whether there might be a relationship between fragile sites and chromosomal alterations reported for bladder cancer. It was found that more than half (56%; odds ratio [OR] = 4.70) of chromosomal rearrangements reported for bladder cancer were located at 77 (65%) of the 118 recognized fragile sites (OR = 6.88). Furthermore, 55% of the fragile sites implicated coincided with one or more genes that have been associated with human cancer (such as oncogenes, tumor suppressor, relonc, transloc, disorder, apoptotic, and angiogenic genes). The most common fragile sites involved were FRA1D, FRA1F, FRA8C, FRA9D, FRA9E, and FRA11C. This correlation suggests that there may be profiles of genetic damage via fragile site expression that lead to the development of at least a proportion of bladder cancers.

Cytogenetic investigations of chronic lymphocytic leukemia

This study aimed to determine which culture method would yield the highest culture success rate, mitotic index, banding resolution, and abnormality rate in investigation of patients with chronic lymphocytic leukemia (CLL). A range of culture techniques for conventional cytogenetic (CC) analyses was compared: 24-hour unstimulated, 72 hours incubation with additional fetal calf serum, 72 hours stimulation with interleukin 4, 72 hours stimulation with lipopolysaccharide (LPS), 72 hours stimulation with TPA (12-O-tetradecanoylphorbol 13-acetate), and 72 hours stimulation with CpG-oligonucleotide DSP30 + Interleukin-2 (IL-2). CC abnormality rates were also compared to fluorescence in situ hybridization (FISH) results using probes for CLL (LSI D13S319/13q34/CEP 12: LSI ATM/p53). Forty-five samples from 24 patients (consisting of 11 newly diagnosed and 13 previously diagnosed patients) were included. For CC, a 100.0% culture success rate was achieved (n = 45) by means of an EDTA (ethylenediaminetetraacetic acid) peripheral blood sample with an associated 62.5% CC abnormality rate (n = 24). FISH detected an abnormality rate of 75.0% (n = 24). The combined CC and FISH abnormality rate was 87.5% (n = 24). This study demonstrates that CC that uses TPA and DSP30 + IL-2 on EDTA peripheral blood is effective in the investigation of CLL and may be used as a supplement to FISH studies.

Evaluation of iodine levels in the Riverina population.

OBJECTIVE To assess the iodine status in a random group of adults in a rural region. DESIGN A cross-sectional study; urinary iodine concentrations (UIC) were correlated with results of a questionnaire that collected demographic information. SETTING Primary care. PARTICIPANTS A total of 173 adults from the Riverina region provided a morning midstream urine sample and completed a questionnaire. There were no exclusion criteria. MAIN OUTCOME MEASURES Iodine status was based upon mean UIC (MUIC) values and categorised according to World Health Organisation criterion. Subgroups were classified according to sex, age, town, salt usage, vitamin/supplement usage, pregnant or breast-feeding status and diet. RESULTS The MUIC for the study population was 79 microg L(-1); 29% were iodine-replete, 52% had mild deficiency and 18.5% were moderately to severely deficient. Use of iodised salt produced a non-clinically significant increase in MUIC of 81 microg L(-1)compared with 71 microg L(-1)(P = 0.1907). Daily vitamin supplementation led to iodine sufficiency with a MUIC of 111 microg L(-1)(P = 0.0011). Participants aged 50-59 years had a significantly lower MUIC than participants aged 18-39 years (67 versus 89 microg L(-1), respectively, P = 0.0106). Further, the MUIC decreased with age from 18 to 59 years (P = 0.0208). CONCLUSIONS A mild iodine deficiency was found in this sample of the Riverina population, consistent with other Australian studies. Salt iodisation might not be an effective strategy to correct iodine deficiencies within Australia.

The detection of Chlamydia pneumoniae in atherosclerotic plaques of Australian subjects.

Aim: To determine whether the common respiratory pathogen, Chlamydia pneumoniae, was associated with atherosclerotic plaques in Australian subjects. Methods: A total of 29 coronary atherosclerotic lesions and 18 normal coronary arterial samples were tested for the presence of C. pneumoniae by PCR and immunofluorescence methods. Results: Chlamydia pneumoniae was detected in 15 of the atheromatous lesions as well as in three of the normal tissues; the immunofluorescence assay was more sensitive ( P = 0.028) than PCR ( P = 0.26). Conclusions: These findings contradict previous Australian studies which did not detect C. pneumoniae in atherosclerotic plaques, thereby discounting the speculation that its absence was likely due to geographical variation. The detection of the bacterium in some of the normal tissues suggests that C. pneumoniae infection might be an initial trigger of atherosclerotic development.

Prevalence of iodine deficiency in infants and young children in Western Sydney, Australia: a cross-sectional analysis.

Iodine is an essential element required for the production of triiodothyronine and thyroxine. The absence of these hormones can cause numerous developmental defects, including irreversible mental retardation in infants and a loss of up to 13 intelligence quotient points in children. It has been reported that iodine deficiency has reemerged in Australians. In this study, random urinary iodine levels were measured in 106 infants and children of up to 5 years of age. The median urinary iodine concentration was 102 µg/L, but 47.2% of the population was below the World Health Organization—recommended level of 100 µg/L, ranging from mild (25.5%) to severe deficiency (6.6%). Of particular interest was the finding that children older than 2 years had significantly lower urinary iodine values (P = .02) than those in the 0- to 2-year age group. These results suggest inadequate dietary iodine intake in youth and point to the emergence of iodine deficiency as likely occurring from 2 years of age. They also support ot...

CAPILLARY PROTHROMBIN TIME TEST FOR ORAL ANTICOAGULANT CONTROL

The capillary prothrombin time test is an ideal alternative to the plasma prothrombin time test in the therapeutic control of oral anticoagulation. Capillary blood collection has distinct advantages over venous collection. Large numbers of outpatients can be tested in a relatively short time. The capillary prothrombin time can be undertaken minutes before the patient sees the physician, who would check out any evidence of bleeding or thromboembolic symptoms. Having the International Normalised Ratio (INR) of the patient, he could determine the dose of oral Pathology (1989), 21, January