A clinical and microbiological study of approximal carious lesions. Part 1: the relationship between cavitation, radiographic lesion depth, the site-specific gingival index and the level of infection of the dentine

A clinical study was carried out to assess relationship between the presence of approximal cavitation, the radiographic depth of the lesion, the site-specific gingival index and the level of infection of the dentine. Adult patients assessed as needing operative treatment and presenting with approximal lesions visible in the outer third of dentine on bite-wing radiographs were included in the study. Direct lesion depth measurements were recorded from the radiographs and the site-specific gingival index adjacent to the lesion was noted. The presence or absence of a cavity was recorded on an impression following tooth separation. During operative treatment samples of dentine were taken on entry to the lesions to ascertain the level of infection of the dentine. Visual evaluation of 54 successfully recorded impressions revealed that 85% were cavitated. Cavitated lesions were found to have higher site-specific gingival index scores compared to non-cavitated lesions (p = 0.03). The probability of cavitation was greater for lesions >0.5 mm from the enamel-dentine junction on bite-wing radiographs (p<0.01). The level of infection of the dentine was significantly higher for cavitated lesions than for non-cavitated lesions (p = 0.02). However, the non-cavitated lesions were still infected.     

An epidemiological study of the relations between exposure to organophosphate pesticides and indices of chronic peripheral neuropathy and neuropsychological abnormalities in sheep farmers and dippers

OBJECTIVES—To investigate the hypothesis that chronic low level exposure to organophosphates (OPs) in sheep dips is related to clinically detectable measures of polyneuropathy.
METHODS—The design was a cross sectional exposure-response study of sheep dippers and other non-exposed groups. The study group consisted of 612 sheep dipping farmers, 53 farmers with no sheep dipping experience, and 107 ceramics workers. Retrospective exposure information was obtained by questionnaire based on stable and easily identifiable features of sheep dipping found during the first phase of the study; in particular, estimates of handling concentrate and splashing with dilute dip. Neurological assessments were based on a standard neuropathy symptoms questionnaire, and thermal and vibration quantitative sensory tests.
RESULTS—Adjusted for confounders there was a weak positive association between cumulative exposure to OPs and neurological symptoms, the significance of which was dependent on the inclusion of a few individual workers with extremely high exposure. There was no evidence of an association between cumulative exposure and the thermal or vibration sensory thresholds. However, separating the effects of exposure intensity and duration showed a higher prevalence of symptoms, primarily of a sensory type, among sheep dippers who handled the OP concentrate. There was also evidence that sensory and vibration thresholds were higher among concentrate handlers, the highest exposed group of dippers.
CONCLUSIONS—The findings showed a strong association between exposure to OP concentrate and neurological symptoms, but a less consistent association with sensory thresholds. There was only weak evidence of a chronic effect of low dose cumulative exposure to OPs. It is suggested that long term health effects may occur in at least some sheep dippers exposed to OPs over a working life, although the mechanisms are unclear.


Keywords: organophosphates; sheep dippers; neuropathy     

Protection against 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine cytotoxicity and DNA adduct formation in human prostate by glutathione S-transferase P1

The prostate has been identified as a target for 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced carcinogenesis. Humans are exposed to PhIP through ingestion of well-done cooked meats, and there is evidence from epidemiological studies that implicates red meat consumption in prostate carcinogenesis. The alpha and pi class isoforms of glutathione S-transferases (GSTs) have been shown to inhibit adduction of activated PhIP metabolites to DNA in cell-free systems. In humans, silencing of GST pi(GSTP1) through CpG island hypermethylation is found in nearly all prostate carcinomas and is believed to be an early event in prostate carcinogenesis. We hypothesized that suppressed GSTP1 expression in prostate cells would increase their vulnerability to cytotoxicity and DNA adduct formation mediated by activated PhIP metabolites. To test this hypothesis, the human prostate adenocarcinoma cell line, LNCaP, which contains a silenced GSTP1 gene, was genetically modified to constitutively express high levels of GSTP1. Both LNCaP and LNCaP-GSTP1 cells exposed to N-OH-PhIP, but not parent PhIP, for 24 h showed a dose-dependent decrease in cell viability. GSTP1-overexpressing cells had LC50s 30-40% higher than cells transfected with the vector alone. PhIP-DNA adducts isolated from LNCaP-derived cells and primary human prostate tissue cultures exposed to N-OH-PhIP were analyzed by liquid chromatography/electrospray ionization mass spectrometry. Primary cultures of human prostate tissue and LNCaP-GSTP1 cells had approximately 50% lower adduct levels than parental LNCaP and vector control cells. Bioactivation assays using LNCaP cytosols showed that enzymatic activation of N-OH-PhIP to a DNA binding species was dependent on ATP and could be inhibited by recombinant human GSTP1 in the presence of glutathione. This evidence confirms that N-OH-PhIP can be bioactivated to a DNA binding species in human prostate and human prostate-derived cells. These observations provide the basis for using LNCaP and LNCaP-GSTP1 cells as a model system for studying the role of this enzyme in protection against N-OH-PhIP induced DNA damage in prostate carcinogenesis. Loss of GSTP1 expression in human prostate may, therefore, enhance its susceptibility to carcinogenic insult by compounds such as N-OH-PhIP. Conversely, induction of GSTs in early-stage prostate carcinogenesis may be a useful protective strategy.     

Recurrent falls are associated with increased length of stay in elderly psychiatric inpatients

OBJECTIVES: To identify factors which may contribute to prolonged length of stay in an elderly psychiatric inpatient setting. DESIGN: Retrospective case note study. METHODS: A list of all patients over the age of 65 discharged from a private psychiatric hospital over a three-year period excluding those with a length of stay of over 365 days was obtained (n = 1147). A random sample of 150 patients was selected from the study population. A case note study was then performed looking at a number of variables which have been postulated to affect length of stay. The resulting data was analysed using multivariate statistics. RESULTS: There was no statistically significant association found between baseline factors (including age, gender, cognitive impairment, marital status, order of admission and preadmission living arrangement) and length of stay. Having recurrent falls whilst an inpatient was associated with prolonged hospital stay (p = 0.0006). CONCLUSION: Experiencing recurrent falls whilst an inpatient is associated with prolonged length of stay. Recurrent falls in the elderly may be associated with both physical illness and the use of psychotropic medications. A prospective study examining factors contributing to falls would be important in decreasing fall risk and reducing length of stay.     

Rarity of colon cancer in Africans is associated with low animal product consumption, not fiber

OBJECTIVE: To investigate whether the rarity of colon cancer in black Africans (prevalence, < 1:100,000) can be accounted for by dietary factors considered to reduce risk, and by differences in colonic bacterial fermentation. METHODS: Samples of the adult black South African population were drawn from several rural and urban regions. Food consumption was assessed by home visits, food frequency questionnaires, computerized analysis of 72-h dietary recall, and blood sampling. Colonic fermentation was measured by breath H2 and CH4 response to a traditional meal, and to 10-g of lactulose. Cancer risk was estimated by measurement of epithelial proliferation indices (Ki-67 and BrdU) in rectal mucosal biopsies. Results were evaluated by comparison to measurements in high-risk white South Africans (prevalence, 17:100,000). RESULTS: Epithelial proliferation was significantly lower in rural and urban blacks than whites. The diets of all the black subgroups were characterized by a low animal product and high boiled maize-meal content, whereas whites consumed more fresh animal products, cheese, and wheat products. Blacks consumed below RDA quantities of fiber (43% of RDA), vitamin A (78%), C (62%), folic acid (80%) and calcium (67%), whereas whites consumed more animal protein (177% of RDA) and fat (153%). Fasting and food-induced breath methane production was two to three times higher in blacks. CONCLUSIONS: The low prevalence of colon cancer in black Africans cannot be explained by dietary "protective" factors, such as, fiber, calcium, vitamins A, C and folic acid, but may be influenced by the absence of "aggressive" factors, such as excess animal protein and fat, and by differences in colonic bacterial fermentation.     

Spontaneous ambulatory activity as a quantifiable outcome measure for rheumatoid arthritis

OBJECTIVE: To validate the objective monitoring of ambulatory activity as an outcome measure for rheumatoid arthritis (RA). METHODS: We have compared ambulatory activity to a range of currently favoured outcome measures, ranging from subjective opinions to X-ray damage, in a population of 93 RA sufferers. RESULTS: Correlations were stronger with measures of joint damage and disability, and less strong with measures of disease activity. Sensitivity to change was good. Three different interventions were compared for the quantity of the response, and the results agree with clinical experience, with steroid injection of the knee and use of non-steroidal anti-inflammatory drugs (NSAIDs) having a similar response and the provision of surgical shoes producing a more modest increase in ambulation. CONCLUSION: The measurement of ambulatory activity has validity for RA assessment. It provides different but related data to the currently used measures. It is objective, relevant, quantifiable and of unlimited scale. It could be used to quantify interventions aimed at increasing ambulation, in carefully constructed studies.     

Assay of topically administered ibuprofen using a model of post-injury hypersensitivity

Objective: To develop a reliable assay for quantifying the analgesic efficacy of non-steroidal anti-inflammatory drugs (NSAIDs) using a model that is accepted as a paradigm of clinical pain. Subjects: Fifteen normal subjects, all of whom were volunteers from medical school staff, took part in the study. Methods: Capsaicin (20 μl) in solution (0.03 mg/ml) was applied to the volar surface of the forearm, and the skin was maintained at a constant temperature using a thermal stimulator. The magnitude of the surrounding area of mechanical allodynia to a brush stimulus (i.e. a clinical correlate of tenderness to touch) was assessed. Under double-blind, placebo-controlled conditions, the test was repeated using skin previously treated with ibuprofen gel or placebo. Results: A close linear relationship was observed between skin temperature over a range of 30 °C to 40 °C and the area of capsaicin-induced allodynia. Ibuprofen gel significantly reduced (P < 0.004) the area of touch-evoked allodynia at a constant skin temperature of 40 °C. Conclusions: The thermal-facilitated adaptation of the capsaicin model described in this study represents an inexpensive and reliable assay for the effects of topical formulations of NSAID upon mechanical sensitivity. As such, it is a potential alternative to many clinical studies in which inherent confounding and bias can preclude a meaningful conclusion. Received: 13 September 1999 / Accepted in revised form: 14 March 2000