Arsenic and porphyrins

BACKGROUND: To evaluate the possible effect of inorganic arsenic (iAs) and of its species on the urinary excretion of porphyrin homologues. METHODS: Total porphyrins and their homologues (copro, penta, hexa, hepta, uroporphyrins) and arsenic species (trivalent and pentavalent As; monomethyl arsonic acid; dimethyl arsenic acid; arsenobetaine) were measured respectively by HPLC and HPLC-ICP MS in urine from 86 art glass workers exposed to iAs and from 54 controls. RESULTS: A significant increase in the excretion of penta and uroporphyrins was demonstrated for workers exposed to As; As3 was the species best correlated with urinary porphyrin excretion. CONCLUSIONS: The increase of urinary excretion for some porphyrin homologues appears to be consistent with the inhibition by As of URO-decarboxylase in the heme biosynthesis pathway. The determination of urinary porphyrin homologues could be useful to assess, on a group basis, some early effects of arsenic and to demonstrate possible individual susceptibility to the element.     

Evaluation of downstaging in the detection of cervical neoplasia in Kolkata,India

Unaided visual inspection or "downstaging" has been suggested as a potential alternative method for cervical cancer screening in developing countries. Our study was designed to evaluate the accuracy of downstaging to detect cervical neoplasia in a low-resource setting. A total of 6,399 women aged 30-64 years were screened with downstaging by trained nonmedical health workers. Two thresholds were used to define positive downstaging: "low threshold" when any visible abnormality on the cervix was considered positive and "high threshold" when selected abnormalities such as bleeding on touch, bleeding erosion, hypertrophied oedematous cervix, congested stippled cervix and growth or ulcer constituted the positive test. All women underwent a colposcopy examination. Biopsies were directed when colposcopy revealed abnormal lesions. True disease status was defined as histologically proven moderate dysplasia and worse lesions. Since all the participants received a diagnostic (reference) investigation (biopsy and/or colposcopy), sensitivity, specificity and predictive values were estimated directly. Low- and high-threshold downstaging were positive in 1,585 (24.8%) and 460 (7.2%) women, respectively. The sensitivities of low- and high-threshold downstaging to detect high-grade precursors and invasive cancers were 48.9% and 31.9%, respectively. The specificities were 75.8% and 93.3%, respectively. These results indicate that downstaging is not suitable as an independent primary screening modality for cervical neoplasia.     

Impact of videotaped information on frequency and confidence of breast self-examination

Background Videotaped education materials to teach breast self-examination (BSE) are used worldwide. However, evaluation of videotaped BSE instructions is lacking. Methods Premenopausal women (mean age 33.4±11.2 years) without history of breast cancer were approached to participate in this experimental study and randomly assigned to a video intervention group (VG; n=130; length of the video=15 min) or non-video comparison group (NVG; n=121). All participants answered a questionnaire on BSE behavior and health beliefs. No additional training was given. The total duration of the session including completion of the questionnaire was 15min for the NVG and 30min for the VG. Three months later, changes in BSE behavior were compared in the two groups. The influence of health beliefs on actual BSE behavior was investigated as well. Results Women of both the VG and NVG performed BSE significantly more frequently at follow-up than at baseline. Analysis of covariance, using the baseline BSE-frequency as co-variate and the follow-up BSE frequency as the dependent variable, revealed that women in the VG (adjusted mean=7.9 times per year, 95%CI=6.5–9.4) performed BSE more frequently than women of the NVG (adjusted mean=6.1 times per year, 95%CI=4.6–7.5) (F=4.2, df=2, p=0.02). Among motivational predictors, having an example of a role model (modeling) was shown by regression analysis to explain the greatest amount of variance (13%) in BSE frequency. Conclusion Use of an educational videotape increased the frequency of BSE among premenopausal women.     

Association of early life factors and acute lymphoblastic leukaemia in childhood: historical cohort study

In a historical cohort study of all singleton live births in Northern Ireland from 1971-86 (n=434,933) associations between early life factors and childhood acute lymphoblastic leukaemia were investigated. Multivariable analyses showed a positive association between high paternal age (> or =35 years) and acute lymphoblastic leukaemia (relative risk=1.49; 95% confidence interval (CI)=0.96--2.31) but no association with maternal age. High birth weight (> or =3500 g) was positively associated with acute lymphoblastic leukaemia (relative risk=1.66; 95% CI=1.18--2.33). Children of mothers with a previous miscarriage or increased gestation (> or =40 weeks) had reduced risks of ALL (respective relative risks=0.49; 95% CI=0.29--0.80, and 0.67; 95% CI=0.48--0.94). Children born into more crowded households (> or =1 person per room) had substantially lower risks than children born into less crowded homes with also some evidence of a lower risk for children born into homes with three adults (relative risks=0.56; 95% CI=0.35-0.91 and 0.58; 95% CI=0.21-1.61 respectively). These findings indicate that several early life factors, including living conditions in childhood and maternal miscarriage history, influence risk of acute lymphoblastic leukaemia in childhood.     

How to Include the Trauma History in the Diagnosis and Treatment of Psychiatric Inpatients

Although the high prevalence of significant psychological trauma among populations of patients with serious and persistent mental illness is well-known, and is duly recorded in initial psychiatric histories, such trauma rarely is reflected in the primary (or secondary) diagnosis, and thus, rarely becomes the focus of treatment. There are many complex reasons why the traumatic etiology of many presenting symptoms goes unrecognized. Failure to recognize it leads to prolonged hospitalization and to exclusion from participation in PTSD treatments in community settings, where they are more readily available. The author suggests some practical, general systems changes which might lead to more effective treatment and earlier recovery for patients with trauma-related symptoms.     

Assessing change in early intervention programs for children with autism

Assessing the efficacy of any intervention can be a difficult task. In the case of children with autism who require comprehensive and long-lasting interventions, the task becomes even more difficult. In this paper, intervention studies based on comprehensive interventions for young children with autism are reviewed and examined in reference to elements that are essential to a well-designed treatment study, e.g., randomization/matching procedures, and outcome measures. Given the complexity of these comprehensive intervention programs, and the few data available on interventions with clear empirical validation, a plea is made for studies to consider the active ingredients or component parts of an intervention, e.g., number of hours, type of setting, and teaching approach. Suggestions are further made for improving future studies, including more rigorous designs, and measuring change.     

Chronic symptoms are common in patients with neuroborreliosis -- a questionnaire follow-up study

OBJECTIVES: The existence of chronic neuroborreliosis is controversial. The aim of our study was to investigate the existence and kind of persistent symptoms in patients previously treated because of neurological symptoms as a result of neuroborreliosis. MATERIALS AND METHODS: A total of 106 patients with neuroborreliosis, according to established criteria, and a control group of 123 patients with Borrelia induced erythema migrans diagnosed in a general practitioner office were studied. A questionnaire was sent to patients and controls concerning their health situation. Time from onset of neurological symptoms to the questionnaire send out was 32 months (mean) for the patients with neuroborreliosis and 33 months (mean) for the controls. RESULTS: Fifty per cent of the individuals in the patient group compared with 16% of the individuals in the control group showed persistent complaints after their Borrelia infection (P < 0.0001). The most significant differences between the groups were the presence of neuropsychiatric symptoms such as headache, attention problems, memory difficulties and depression. Paresthesia, pain and persistent facial palsy was also significantly more common in patients treated because of neuroborreliosis. CONCLUSION: Our study shows that persisting neurological symptoms are common after a neuroborreliosis infection. The pathological mechanisms that lay behind the development of chronic symptoms, however, are still uncertain.     

Survey of epidural analgesia management in general intensive care units in England

BACKGROUND: The management of epidural analgesia is controversial. Many intensive care unit (ICU) patients may benefit from this form of analgesia but have one or more contraindications to its use. Sepsis, coagulopathy, insertion in a sedated, ventilated patient, and lack of consent are common problems in ICU patients. Little has been published to help guide practice in this area. I wished to establish the current practice of the management of epidural analgesia in general ICUs in England when relative or absolute contraindications occur, in order to determine the current standard of care for placement and use of epidural analgesia in ICU patients. METHODS: A postal questionnaire survey of the management of epidural analgesia in critically ill patients was sent to the named clinical director of all (216) general ICUs in England. RESULTS: Responses were received from 159 (75%) units: 89% of responding units use epidural analgesia but only 51(32%) have a written policy covering its use. Anesthetists or intensivists with an anesthetic background sited all epidural catheters; 68% of units would not site an epidural in a patient with positive blood cultures; but only 52% considered culture negative sepsis (systemic signs of sepsis with no organism isolated) to be a contraindication. Neither lack of consent nor the need for anticoagulation after the catheter had been sited were considered contraindications to inserting an epidural catheter by the majority of respondents. Although 71% of the units would remove an epidural catheter if a patient developed positive blood cultures after it had been sited, the majority of the ICUs did not consider culture negative sepsis and the need for anticoagulation contraindications to maintain a previously sited epidural. CONCLUSIONS: Practice varied considerably with little consensus. Although all the respondents use epidural analgesia in critically ill patients, the indications and contraindications to epidural analgesia remain controversial, and further research is required to help define the role of epidural analgesia in this high-risk group.     

Immediate early genes and p21 regulation in liver of rats with acute hepatic failure

It has been observed that liver regeneration in acute hepatic failure (AHF) is suppressed [Eguchi et al. Hepatology 1996;24(6):1452-9]. The molecular mechanism regulating this inhibition is not known. We previously reported that in AHF rats, hepatocyte proliferation was significantly impaired with elevation in serum IL-6, TGF-beta1, and HGF [Kamohara et al. Biochem Biophys Res Commun 2000;273(1):129-35]. Following either 70% partial hepatectomy (PH) or liver injury, quiescent mature hepatocytes are "primed" to re-enter the cell cycle. The process of "priming" appears to be triggered by extracellular cytokines (IL-6 and TNF-alpha) and is characterized by expression of immediate early genes. Under the stimulation of growth factors such as HGF, "primed" hepatocytes exit the G1 phase of the cell cycle. G1-associated cyclins and their inhibitors play a pivotal role in G1/S cell cycle transition. Here, we demonstrate that immediate early gene (i.e. c-myc, c-fos) expression and AP-1 activity are preserved in AHF rat livers despite absence of hepatocyte proliferation. In contrast, p21 mRNA and protein are both over-expressed in AHF livers compared to livers from rats undergoing PH; this elevation leads to inhibition in Cdk2 activity, resulting in G1 cell cycle arrest and inhibition of regeneration.