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[Mortality in workers of a primary aluminum foundry in Portovesme in Sardinia].

The standard mortality rates (SMRs) were calculated for 1148 workers of a primary aluminium plant in Portovesme, Sardinia, hired between 1971, when production started, and 1980. Status (living or decreased) was ascertained as at 31 December 1990 and the relationship between observed and expected deaths with respective 95% confidence limits were calculated on the basis of age-specific regional rates for each calendar year of the follow-up. The SMR for all causes was 81 with confidence limits between 61 and 108 based on a total of 48 deaths. Mortality due to malignant neoplasms did not differ from the expected rate. The observed deaths due to lung cancer were decidedly less than the expected number (3 observed versus 4.7 expected). A significant excess of cancer of the pancreas was observed with special reference to anode production, based, however, on only 3 observed cases against 0.8 expected. In the absence of a more precise definition of the causes of death, of the environmental exposure levels and of the non-occupational confounding factors, and considering the young age of the cohort under study, it is at present doubtful whether the excess of cancer of the pancreas can be associated with work in the primary aluminium industry. The results should therefore be taken as preliminary, indicating that further studies are required.

Aluminum↗

Monitoring nitric oxide: a comparison of three monitors in a paediatric ventilator circuit.

Simultaneous measurements of nitric oxide (NO) (0-80 ppm) using a chemiluminescence monitor and two electrochemical monitors were performed during simulated paediatric mechanical ventilation. The mean difference (bias) between the chemiluminescence (Model 42H Thermo Environmental Instruments Inc) and an electrochemical monitor (Pulmonox Research and Development Corp) was 0.52 +/- 6.52 ppm (SD). The 95% confidence limits of the mean difference were 3.00 to -1.96 ppm and the limits of agreement between the two techniques were 13.56 to -12.52 ppm. The mean difference between the chemiluminescence monitor and another electrochemical monitor (NOxBox, Bedfont Scientific Inc) was -7.27 +/- 4.29 ppm. The 95% confidence limits of the mean difference were -9.02 to -5.56 ppm and limits of agreement of the two techniques were -16.13 to 1.55 ppm. These results suggest that electrochemical monitors may be used to guard against potentially toxic concentrations of NO (greater than 20 ppm). However they do not suggest that either of the electrochemical monitors may be used with confidence in lieu of the chemiluminescence monitor to regulate NO at low clinical NO levels (1-5 ppm).

Child↗

Cervical dystonia severity scale reliability study.

Cervical dystonia (CD) is characterized by sustained contractions of the neck musculature, resulting in abnormal head postures. The Cervical Dystonia Severity Scale (CDSS) was developed to provide a reliable measure of treatment response in patients with CD. The CDSS uses a protractor and wall chart to rate the severity of the head's deviation from neutral in each of three planes of motion (rotation, laterocollis, anterocollis/retrocollis), which is then scored in 5 degree intervals (1 degree to 5 degrees deviation = 1; 86 degree to 90 degrees deviation = 18). To test the reliability of the CDSS, four centers, each with two independent examiners, evaluated 42 patients with CD. At each site, each of the two examiners used the CDSS to evaluate the head position of each patient twice, on the same day, for a total of four evaluations. The kappa value for intra-examiner agreement was 0.94 (95% confidence limit of 0.900-0.972), indicating excellent intra-examiner reliability. The kappa value for interexaminer reliability was 0.79 for the first evaluation and 0.86 for the second evaluation (95% confidence limits of 0.668-0.920 and 0.790-0.920) indicating excellent interexaminer reliability. Thus, the CDSS was highly reliable in both intra-examiner and interexaminer scoring comparisons.

Adult↗

The relative bioavailability and in vivo-in vitro correlations for four marketed carbamazepine tablets.

PURPOSE: To determine if three marketed generic carbamazepine tablets were bioequivalent to the innovator formulation, as well as to each other. In addition, to examine in vivo-in vitro relationships among the four formulations. METHODS: Each formulation was given as a single dose to 18 healthy male and female subjects using a crossover design. Blood samples were collected for 169 hr. Carbamazepine was assayed by HPLC with UV detection. RESULTS: In vivo fraction absorbed plots indicated that the three generic formulations were absorbed more rapidly than the innovator product, and the mean time of maximum plasma concentration was 6-7 hr sooner for the generic formulations. The mean maximum plasma concentration ranged from 17-19 percent higher for the generic products compared to the innovator, and the 90% confidence limits for Cmax data ranged from 11 1% to 126%. The mean AUC(0-infinity) for the generic products ranged from 101-104% compared to the innovator, and the confidence limits for AUC ranged from 97-108%. CONCLUSIONS: The generic products were all more rapidly absorbed than the innovator, but simulations of steady-state concentrations indicated that it would be unlikely that these differences would have any significant clinical effect. An excellent association was seen between the Cmax and the percent of drug dissolved in vitro. The correlation was used to accurately predict the Cmax of four other 200 mg tablets evaluated in an earlier study.

Adult↗

Family history and risk of breast cancer.

The risk of breast cancer in first degree relatives of patients with breast cancer can be derived from family history and is dependent upon the age at diagnosis in the index patient. For the relatives of index patients older than 55, the relative risk is 1.57, if less than 55 the relative risk is 2.29, and 3.85 if less than 45 (95% confidence limits 0.83 to 2.68, 1.18 to 4.01, and 1.67 to 3.85, respectively). First degree relatives of patients with bilateral breast cancer have a 6.43-fold increase in risk (95% confidence limits 1.32 to 18.77). The genetic contribution to overall lifetime liability to breast cancer in the relatives declines rapidly with increasing age of onset of breast cancer in the index patient from 37% at 20 years to 8% by 45 years. This information can be used in clinical practice for counselling and the establishment of screening programmes.

Adult↗

Biological dosimetry in a group of radiologists by the analysis of dicentrics and translocations.

The results of a cytogenetic study carried out in a group of nine radiologists are presented. Chromosome aberrations were detected by fluorescence plus Giemsa staining and fluorescence in situ hybridization. Dose estimates were obtained by extrapolating the yield of dicentrics and translocations to their respective dose-effect curves. In seven individuals, the 95% confidence limits of the doses estimated by dicentrics did not include 0 Gy. The 99 dicentrics observed in 17,626 cells gave a collective estimated dose of 115 mGy (95% confidence limits 73-171). For translocations, five individuals had estimated doses that were clearly higher than the total accumulated recorded dose. The 82 total apparently simple translocations observed in 9722 cells gave a collective estimated dose of 275 mGy (132-496). The mean genomic frequencies (x100 +/- SE) of complete and total apparently simple translocations observed in the group of radiologists (1.91 +/- 0.30 and 2.67 +/- 0.34, respectively) were significantly higher than those observed in a matched control group (0.53 +/- 0.10 and 0.87 +/- 0.13, P < 0.01 in both cases) and in another occupationally exposed matched group (0.79 +/- 0.12 and 1.14 +/-0.14, P < 0.03 and P < 0.01, respectively). The discrepancies observed between the physically recorded doses and the biologically estimated doses indicate that the radiologists did not always wear their dosimeters or that the dosimeters were not always in the radiation field.

Adult↗

Ingrowth of blood vessels in disc degeneration. Angiographic and histological studies of cadaveric spines.

Angiograms were made of twenty-two cadaveric lumbar spines to determine the presence of any new blood vessels between adjacent lumbar vertebrae and corresponding discs. The annulus and adjacent longitudinal ligaments were also analyzed histologically. A total of 105 intervertebral spaces were studied. It was found that the normal anastomosing arteries in the posterior longitudinal ligament were significantly obliterated with advancing degeneration of the disc (p < 0.001), whereas several tiny tortuous arteries--often running between the osteophytic spurs--were seen in the anterolateral aspects of the intervertebral spaces connecting the adjacent vertebrae. Histological examination of the anterolateral part of the annulus showed that the vascularity of the annulus increased significantly with degeneration of the disc (p < 0.001), and most of the arteries had a vertical orientation. Regression analysis showed that vascular changes occurred before degeneration of the disc at every lumbar level, suggesting that disturbances in the nutritional supply may precede degeneration. The correlation coefficient was 0.77 (95 per cent confidence limit, 0.52 to 0.90) for the increase in annular vascularity with an increase in the age of the individual at the time of death and 0.86 (95 per cent confidence limit, 0.69 to 0.94) for the increase in degeneration of the disc with an increase in age.

Adult↗

Puerperal endometritis after abdominal twin delivery.

The infectious complications of 122 consecutive abdominal twin deliveries over the period 1984-1989 were analyzed in a prospective clinical study, comparing them with 761 singleton abdominal deliveries over the period 1984-1986. The incidence of endometritis was nearly three-fold after twin deliveries and the incidence of abdominal wound infections nearly two-fold compared with singleton abdominal pregnancies (13.1/4.7% and 5.6/3.0%). The risk of amnionitis was increased ten-fold, 6 hours after rupture of the membranes in abdominal twin delivery, but no connection was found between amnionitis and endometritis, as in singleton abdominal deliveries. Multiple regression analysis indicated only two risk factors as regards puerperal endometritis after abdominal twin delivery: age under 25 years (odds ratio 6.9, 95% confidence limits 1.9-24.8), an association also seen in singleton abdominal deliveries, and a period of more than 6 hours from rupture of membranes to delivery (odds ratio 7.8, 95% confidence limits 2.1-28.5). Multiple pregnancy appears to be associated with an increased risk of endometritis. The etiological factors remain unknown, but a large placental bed and/or immunological factors may be implicated.

Cesarean Section↗

Placebo-controlled trial of active immunization with third party leukocytes in recurrent miscarriage.

OBJECTIVE: To investigate whether active immunization with third party leukocytes improves pregnancy outcome in women with unexplained recurrent miscarriages. DESIGN: A double-blind prospective placebo-randomized trial. PATIENTS: Sixty-six patients with unexplained recurrent miscarriages achieved pregnancy after having received active immunization or placebo. INTERVENTIONS: Among the patients who achieved pregnancy, 43 were immunized with third party leukocytes and 23 received autologous leukocytes. MAIN OUTCOME MEASURES: Frequency of new miscarriages in actively immunized women compared with placebo. RESULTS: In the total group of patients, 71% of the actively immunized patients had a successful pregnancy compared with 48% of the placebo treated patients (not significant, RR = 0.6; 95% confidence limits = 0.3-1.1). In a subgroup of patients with primary recurrent miscarriages the success rate was 76% compared with 38% in the placebo group (p < 0.02, RR = 0.4; 95% confidence limits = 0.2-0.9). In this subset of patients, median birthweight was also significantly higher in actively immunized patients than in placebo treated patients (3445 g versus 3000 g; p < 0.05). CONCLUSIONS: Active immunization did not provide any benefit in the overall group of women with recurrent miscarriages. However, among women with primary recurrent miscarriages it may improve outcome with respect to the number of livebirths and birthweight.

Abortion, Habitual↗

Inhibition by nociceptin on excitatory non-adrenergic non-cholinergic response in guinea pig airways.

AIM: To study the effect of nociceptin (NC), a newly discovered heptadecapeptide, and U-50488H, a kappa-opioid receptor agonist, on excitatory non-adrenergic non-cholinergic (eNANC) constriction responses in guinea pig isolated bronchus. METHODS: An eNANC response was induced by electric field stimulation (EFS) in the preparation via activation of the sensory nerve terminals. The effect of NC and U-50488H was analyzed on the response. RESULTS: Nociceptin 0.001 - 0.1 micromol/L inhibited the eNANC constriction which was induced by EFS but not by capsaicin in guinea pig bronchus. The constriction inhibited by NC 0.01 micromol/L was (43 +/- 31) % compared with the control. After pretreatment with naloxone 0.1 micromol/L, the constriction was inhibited by (46 +/- 28) %, without marked change compared with the above figure. IC50 (95 % of confidence limits) was 6.12 (3.8 - 9.9) nmol/L. U-50488H also inhibited the EFS-evoked eNANC constriction and the effect was abolished after pretreatment with naloxone. IC50 (95 % of confidence limits) was 1.08 (0.5 - 2.2) micromol/L. Capsaicin 0.01 - 1 micromol/L caused a cumulative constriction response in the preparation. Moreover, the effect of capsaicin was not affected by pretreatment with NC 0.01 micromol/L or U-50488H 0.1 micromol/L. The constriction induced by exogenous neurokinin A, were also unaffected by treatment with NC 0.01 micromol/L or U-50488H 0.1 micromol/L in isolated bronchus. CONCLUSION: Nociceptin inhibits EFS-induced eNANC constriction, which is not reversed by naloxone, while U-50488H inhibits EFS-induced eNANC response via activation of opioid receptor in guinea pig airways.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

Association of APC gene mutations and histological characteristics of colorectal adenomas.

Fifty-nine colonic adenomas and 6 hyperplastic colonic polyps were analyzed by single-strand conformation polymorphism analysis for mutations in the adenomatous polyposis coli gene (APC). Frameshifts and premature stop codons in at least one copy of APC were detected in 25 of these adenomas. Five adenomas carried 2 APC mutations. No mutations in APC were found in any of the 6 hyperplastic polyps. The detection of APC mutations increased with size and degree of dysplasia and in rectal as compared to colonic adenomas, although the association was not statistically significant. The frequency of detectable APC mutations was higher in tubulovillous and villous adenomas (10 of 13) than in tubular adenomas (15 of 45) (odds ratio, 6.67; 95% confidence limits, 1.39-41.83; P = 0.005). The significance of the association between the detection of APC mutations and a villous architecture was confirmed in multivariate analysis (relative risk, 6.67; 95% confidence limits, 1.54-28.8; P = 0.005). In conclusion, APC mutation plays a role in adenoma progression; its frequency is significantly higher in lesions with a more villous morphology.

Adenoma, Villous↗

Early increase precedes a depletion of VIP and PGP-9.5 in the skin of insulin-dependent diabetics--correlation between quantitative immunohistochemistry and clinical assessment of peripheral neuropathy.

Diabetic neuropathy affects both sensory and autonomic peripheral nerve fibres. Vasoactive intestinal polypeptide (VIP) is present in autonomic fibres which modulate sweat secretion, while calcitonin gene-related peptide (CGRP) is localized to cutaneous sensory fibres. In this study, immunohistochemistry and image analysis were used to assess changes of VIP and CGRP, and of the pan-neuronal marker protein gene-product (PGP)-9.5, in skin biopsies of 18 patients affected by type 1 diabetes (age range 18-46 years) and from seven aged-matched controls. Patients were divided into three groups: group 1 (n = 6), with diabetes for 6 months to 3 years; group 2 (n = 5), with the disease for 5-10 years; and group 3 (n = 7), with diabetes for more than 10 years. VIP immunoreactivity (IR) and PGP-9.5-IR were significantly reduced around sweat glands (P < 0.005) in groups 2 and 3. Epidermal CGRP-IR and PGP-9.5-IR were significantly reduced in group 3 (P < 0.05). Twenty-eight per cent (5/18) of all patients showed high VIP-IR around sweat glands (> 95 per cent confidence limits of controls) and all of these patients had diabetes for less than 3 years. Conversely, 55 per cent (10/18) of patients had low VIP-IR (< 5 per cent confidence limit of controls). The latter, compared with the former, showed a significantly longer duration of diabetes (Fisher exact test P = 0.002), presence of clinical autonomic neuropathy (Fisher exact test P = 0.04), and a reduced sural nerve conduction velocity (Fisher exact test P = 0.04). These results suggest that quantitative immunohistochemical analysis of peptide-containing cutaneous nerves allows an objective evaluation of nerve fibre alterations at early stages of diabetes than is currently possible with neurophysiological functional tests.

Adolescent↗

A rapid radiochemical bacterial bioassay to evaluate copper toxicity in freshwaters.

A rapid, highly sensitive bacterial bioassay to determine copper toxicity in freshwaters was developed based on the inhibition of cellular assimilation of radiolabeled glucose. The test used a copper-sensitive bacterium isolated from a freshwater stream. Employing sensitive radiochemical techniques enabled environmentally relevant concentrations of the test bacterium (10(5) cells mL(-1)) and a short incubation period (4 hours) to be used, which minimized the potential for changes in copper speciation during the test. The 4-hour median effective concentration (EC(50)) for inorganic copper at pH 7.5 in synthetic freshwater was 0.6 microg L(-1) (95% confidence limits 0.4 to 1.0 microg L(-1)). This compared well with chronic growth inhibition of this bacterium in minimal medium (48-hour EC(50) of 0.9 microg L(-1) [95% confidence limits 0.7 to 1.0 microg L(-1)]). MINEQL + software (Environmental Research Software) was used to calculate copper (II) ion concentrations in synthetic freshwater at pH 7.5, giving an EC(50) value of pCu(2+) 8.8. However, using nitrilotriacetic acid metal-ion buffers (Cu-NTA), 50% inhibition occurred at a pCu(2+) of 9.7, suggesting this bacterium was markedly more inhibited by copper in these Cu(2+)-buffered solutions. This may indicate that the Cu-NTA species was contributing to toxicity. The radiochemical bioassay was evaluated further using freshwater samples from both copper-impacted and pristine environments. Measured EC(50) values ranged from 3.4 to 34.0 microg L(-1)inorganic copper and were strongly correlated with dissolved organic carbon (DOC) concentrations (r = 0.88, p < 0.05).

Australia↗

Fractionation sensitivity of a functional endpoint: impaired shoulder movement after post-mastectomy radiotherapy.

A clinical radiobiological study of the fractionation sensitivity of impaired shoulder movement after postmastectomy radiotherapy is presented. From 1978 to 1980, 163 breast cancer patients received postmastectomy irradiation delivered in 12 fractions, 2 fractions per week, over a period of 37 to 46 days. The total dose was specified either as a maximum absorbed dose of 51.36 Gy, or as a minimum target dose of 36.6 Gy specified at the level of midaxilla. From 1981 to 1982, 66 patients received a minimum target dose of 40.92 Gy in 22 fractions with 5 fractions per week over a period of 29 to 35 days. The treatment technique remained essentially unchanged during the whole period of 1978 to 1982. Maximal flexion and abduction of the arm were measured with unfixed scapula. A relative score, indicating the grade of impaired shoulder movement on a nominal scale from 0-3, was established by comparison with the mobility of the contralateral arm. In addition, working ability and pain at movement and at rest were evaluated. These performance parameters significantly correlated with the grade of impaired shoulder movement. The occurrence of moderately or severely impaired shoulder movement was analyzed using a mixture model incorporating dose-fractionation, latency, and predisposing clinical factors. The risk of shoulder problems was significantly higher among patients above 60 years of age. The analysis pointed to subcutaneous fibrosis as a disposing factor and indicates that postoperative physical exercise programs are beneficial. Arm edema had no statistically significant influence on shoulder performance. The alpha/beta ratio was estimated at 3.5 Gy with 95% confidence limits (c.l.) [0.7, 6.2] Gy. The length of time to expression of 90% of the ultimate frequency of moderate and severe shoulder impairment was estimated at 3.9 years with 95% confidence limits [3.1, 4.6] years. The nominal standard dose (NSD) formalism failed to produce isoeffective total doses with respect to impaired shoulder movement in the two fractionation schedules. Although the deleterious effects of larger-than-conventional dose fractions have been documented in a number of clinical series, this study represents the first quantitation of the fractionation sensitivity of a functional clinical endpoint.

Adult↗

Coffee consumption and mortality in the Chicago Western Electric Company Study.

The relations between coffee consumption and 19-year mortality from all causes, coronary heart disease, and non-coronary causes were assessed in 1,910 white males aged 40-56 years in 1957-1958 from the Chicago Western Electric Company Study. Mortality rates, adjusted for age, serum cholesterol, diastolic blood pressure, and smoking status, were compared for those consuming 0-1, 2-3, 4-5, and 6+ cups of coffee per day; coffee intake, measured at the first anniversary examination, included both caffeinated and decaffeinated intake. Mortality from all causes was greatest in the highest and lowest intake groups. The increased mortality in the 6+ cups per day group was due to coronary heart disease, while the increased mortality in the lowest intake group was due to noncoronary causes. The adjusted relative risk of coronary heart disease death for those drinking 6+ cups of coffee per day compared with those drinking less was 1.71 (95 per cent confidence limits 1.27, 2.30). This increased risk of coronary heart disease death was present in both smokers and nonsmokers, with adjusted relative risks of 1.62 and 2.21, respectively (95 per cent confidence limits 1.17, 2.24 and 1.06, 4.62). The increased mortality from non-coronary causes in the lowest intake group was due primarily to increased mortality from cancer and cardiovascular diseases other than coronary heart disease. The results of this study support the hypothesis that those who drink 6+ cups of coffee per day may be at an increased risk of death from coronary heart disease.

Adult↗

Refractive error changes in cortical, nuclear, and posterior subcapsular cataracts.

AIMS: To determine the effect of the three main morphological types of cataract on refractive error. METHODS: Data were prospectively collected from 77 subjects (age 67 (SD 8) years) with one morphological type of cataract. 34 had cortical, 21 had nuclear, and 21 had posterior subcapsular cataract. 22 subjects with clear lenses (60 (7) years) were recruited as controls. The spherical equivalent and astigmatic vector change between spectacle correction and optimal refraction were calculated. RESULTS: The cortical cataract group showed a significant astigmatic change of 0.71 (0.67) D (mean (1 SD)) compared to the control group (0.24 (0.20) D), with 24% outside the 95% confidence limit (0.63 D). The nuclear cataract group showed a significant myopic shift of -0.38 (0.60) D compared to the control group (+0.02 (0.21) D), with 52% beyond the minus 95% confidence limit (-0.39 D). CONCLUSION: A quarter of subjects with cortical cataract showed larger changes in astigmatism than subjects with clear lenses. This is probably because of the localised refractive index changes along cortical spoke opacities within the pupillary area. The well known myopic shift of nuclear cataract was also demonstrated.

Aged↗

Cantonese-style salted fish as a cause of nasopharyngeal carcinoma: report of a case-control study in Hong Kong.

Two hundred fifty incident cases of nasopharyngeal carcinoma under age 35 years in Hong Kong Chinese and an equal number of age- and sex-matched friend controls were interviewed. Mothers of cases and controls were interviewed also, if available, to obtain information on childhood events concerning the study subjects. Consumption of Cantonese-style salted fish during all time periods was significantly associated with nasopharyngeal carcinoma; the association was especially strong during childhood. The relative risk for having Cantonese-style salted fish as one of the first solid foods during weaning was 7.5 (95% confidence limits, 3.9, 14.8), and the relative risk for consuming the food at least once a week compared to less than once a month at age 10 years was 37.7 (95% confidence limits, 14.1, 100.4). It is estimated that over 90% of young nasopharyngeal carcinoma cases in Hong Kong Chinese can be attributed to consumption of this food during childhood.

Adult↗

[Free radical scavenging and antifatigue activities of Saussurea involucrata polysaccharides].

The polysaccharides of Saussurea involucrata Kar et Kir was first isolated and identified by us. The polysaccharides scavenged superoxide anions by nitroblue tetraazolium colorimetric method with a median scavenging concentration of 22 micrograms.ml-1 and 95% confidence limit was 19.9-24.1 micrograms.ml-1. The polysaccharides inhibited the formation of thiobarbituric acid reaction substance in mouse liver homogenate and its IC50 was 2.3 mg/g fresh liver and 95% confidence limit was 2.05-2.55 mg/g fresh liver. By ip 25 mg.kg-1.d-1 x d in mice, the polysaccharides decreased oxygen consumption by 34.4% and ip same dosage x 6 d, the polysaccharide prolonged swimming time by 1.69-fold.

Animals↗