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91.
JT Green GA Thomas J Rhodes BK Evans MA Russell C Feyerabend GS Fuller RG Newcombe WJ Sandborn 《Canadian Metallurgical Quarterly》1997,61(3):340-348
BACKGROUND: Ulcerative colitis is largely a disease of nonsmokers, and transdermal nicotine is of therapeutic value in the active disease. Because side effects are common, we developed a topical enema formulation of nicotine. OBJECTIVE: To study the pharmacokinetics of nicotine complexed with a polyacrylic carbomer and administered by enema to eight healthy volunteers and to eight patients with active ulcerative colitis, verified sigmoidoscopically. PATIENTS AND METHODS: All 16 subjects were nonsmokers. The mean age for normal subjects was 33 years; the mean for patients with ulcerative colitis was 60 years. Median stool frequency for patients with ulcerative colitis was four daily. Patients were taking 5-amino salicylic acid compounds and five were taking oral prednisolone (median dose, 12 mg daily). Nicotine, 6 mg, complexed with carbomer 974P, 400 mg, was administered in a 100 ml enema after an overnight fast, with serial blood measurements taken over 8 hours. Serum nicotine and cotinine were measured by gas liquid chromatography. Area under the concentration-time curves were calculated by the trapezoidal method, and the terminal elimination half-life was derived by extrapolation of the log-linear terminal phase. RESULTS: With the exception of nicotine time to reach peak concentration, which was longer in patients (median of 60 minutes compared with 45 minutes; p < 0.005), other comparisons between normal subjects and patients showed no statistically significant difference, although there was considerable inter-subject variation. Maximum concentration of nicotine, 8.1 +/- 3.5 ng/ml, in the 16 subjects occurred after a median of 60 minutes (range, 30 to 180 minutes); maximum cotinine concentrations of 60.4 +/- 11.5 ng/ml occurred after 4 hours. Side effects in five subjects were mild (four subjects) or moderate (one subject) and included lightheadedness, nausea, and headache; these five subjects were female lifelong nonsmokers of low body weight. CONCLUSION: Because most of the active ingredient of nicotine is converted to continine on the first pass through the liver, substantial concentrations can be achieved at the site of disease with only modest rises in serum nicotine, which are responsible for side effects; cotinine has low pharmacologic activity. Topical administration of nicotine may be useful treatment for distal ulcerative colitis. 相似文献
92.
JP Gibbs G Murray L Risler JY Chien R Dev JT Slattery 《Canadian Metallurgical Quarterly》1997,57(24):5509-5516
Busulfan, a bifunctional alkylating agent, is a mainstay of myeloablative preparative regimens before hematopoietic stem cell transplantation. The apparent oral clearance of busulfan expressed relative to body surface area is 2-3-fold higher in children 1-4 years old than it is in adults. The first step in busulfan elimination is the formation of a tetrahydrothiophenium ion (THT+) in a glutathione S-transferase-catalyzed reaction. We present computer simulations that demonstrate that the ratio of the AUC of THT+ to that of busulfan over 6 h [(AUC(THT+)/AUC(BU))(0-->6)] is highly correlated (r2 = 0.805) with the determinants of THT+ formation and is virtually independent of the determinants of its elimination (r2 = 0.0201). We compared (AUC(THT+)/AUC(BU))(0-->6) determined in 14 children (0.5-4 years) to that of 11 adults (12-54 years) and found a 1.5-fold elevation in the area ratio (P = 0.0098) and a similarly significant increase in busulfan apparent oral clearance expressed relative to body surface area (P = 0.042). The only common explanation for the elevated busulfan apparent oral clearance and (AUC(THT+)/AUC(BU))(0-->6) is an enhanced ability of children to metabolize busulfan through glutathione conjugation. 相似文献
93.
DM Kriegsman DJ Deeg JT van Eijk BW Penninx AJ Boeke 《Canadian Metallurgical Quarterly》1997,51(6):676-685
STUDY OBJECTIVES: To determine whether disease specific characteristics, reflecting clinical disease severity, add to the explanation of mobility limitations in patients with specific chronic diseases. DESIGN AND SETTING: Cross sectional study of survey data from community dwelling elderly people, aged 55-85 years, in the Netherlands. PARTICIPANTS AND METHODS: The additional explanation of mobility limitations by disease specific characteristics was examined by logistic regression analyses on data from 2830 community dwelling elderly people. MAIN RESULTS: In the total sample, chronic non-specific lung disease, cardiac disease, peripheral atherosclerosis, diabetes mellitus, stroke, arthritis and cancer (the index diseases), were all independently associated with mobility limitations. Adjusted for age, sex, comorbidity, and medical treatment disease specific characteristics that explain the association between disease and mobility mostly reflect decreased endurance capacity (shortness of breath and disturbed night rest in chronic non-specific lung disease, angina pectoris and congestive heart failure in cardiac disease), or are directly related to mobility function (stiffness and lower body complaints in arthritis). For atherosclerosis and diabetes mellitus, disease specific characteristics did not add to the explanation of mobility limitations. CONCLUSIONS: The results provide evidence that, to obtain more detailed information about the differential impact of chronic diseases on mobility, disease specific characteristics are important to take into account. 相似文献
94.
Fluoride's role in decreasing dental caries has been recognized for decades. The professional fluoride treatment has recently been augmented with home-use fluoride products. The introduction of many attractive products makes it difficult for dental professionals to know which are effective. Both professional and home-use products are described, as are proven techniques for their use. Recognition of fluoride toxicity, and its prevention and treatment, are also discussed. 相似文献
95.
MM Couttenye PC D'Haese JT Deng VO Van Hoof GA Verpooten ME De Broe 《Canadian Metallurgical Quarterly》1997,12(10):2144-2150
BACKGROUND: Adynamic bone disease (ABD) has been described in the current dialysis population to have an unexpectedly high prevalence. Moreover, it is clearly more prevalent in CAPD patients, compared to haemodialysis patients. Recently we demonstrated that both a low (< or = 27 U/1) level of bone alkaline phosphatase (BAP) as determined by an optimized agarose gel electrophoretic technique and a low (< or = 150 pg/ml ) level of iPTH are good markers of ABD with sensitivities of 78.1% and 80.6% and specificities of 86.4% and 76.2% respectively. METHODS: In this study (n = 212), the prevalence of ABD in the European CAPD population was evaluated by means of these biochemical markers. Clinical data on the patients included were recorded at the moment of blood sampling. In patients under CAPD treatment for longer than 9 months, we calculated an index of calcium exposure through PD fluid. RESULTS: In this population with a low exposure to aluminium, the prevalence of ABD as indicated by either a low level of BAP or PTH was 43%. The following risk factors could be identified: advanced age, shorter time on renal replacement therapy, male gender, and high calcium content of PD fluid. The index of calcium exposure was significantly higher in the patients with low BAP and low iPTH levels compared to those with either BAP > or = 27 U/1 or iPTH > 150 pg/ml. The latter finding gives further support to the hypothesis that a high calcium load administered to renal failure patients may lead to 'oversuppressed' parathyroids in ABD. In a subgroup of patients with a high level of BAP associated with a low iPTH level a profile previously shown to be associated in the presence of aluminium overload, significantly higher serum aluminium levels were noted. suggesting that even in patients with low exposure to aluminium, this element still can affect bone metabolism. CONCLUSION: A high prevalence of ABD--as diagnosed by biochemical markers--was observed in the European CAPD population. A number of risk factors could be put forward. The aetiology and pathogenesis of this type of renal osteodystrophy remain to be elucidated, but appear, however, to be multifactorial. 相似文献
96.
97.
PURPOSE: In a recent study we found an increased resistive index immediately after extracorporeal shock wave lithotripsy (ESWL) in patients older than 60 years, which suggests renovascular disturbance. The present 26-month followup study was undertaken to investigate the relevance of elevated resistive index levels and the incidence of new onset hypertension. MATERIALS AND METHODS: Of the initial 76 patients 57, including 20 of the 23 at risk patients 60 or greater years, group 3), were followed for more than 26 +/- 6 months after ESWL. Followup included 2 resistive index measurements by Doppler ultrasound of the treated and the contralateral kidney, at least 2 blood pressure measurements 1 week apart and excretory urography as well as determination of plasma renin activity in 9 patients. RESULTS: With 1 exception, elevated resistive index levels and hypertension were observed exclusively in patients older than 60 years. In these patients the resistive index ranged between 0.65 and 0.86 (mean plus or minus standard deviation 0.74 +/- 0.05, normal less than 0.7). This increase in resistive index was statistically significant (p < 0.0001). Compared to the levels obtained immediately after ESWL, the resistive index continued to increase in all 9 patients older than 60 years who had hypertension (45%), whereas in the normotensive patients the resistive index was either stable or decreased. There was a strong positive correlation (0.903) between pathological resistive index levels and blood pressure. CONCLUSIONS: Patients older than 60 years are at risk for disturbances of renal perfusion as assessed by the resistive index, and 45% of these patients have new onset hypertension within 26 months of treatment. 相似文献
98.
G Wu PK Davis NE Flynn DA Knabe JT Davidson 《Canadian Metallurgical Quarterly》1997,127(12):2342-2349
This study was conducted to determine whether endogenous synthesis of arginine plays a role in regulating arginine homeostasis in postweaning pigs. Pigs were fed a sorghum-based diet containing 0. 98% arginine and were used for studies at 75 d of age (28.4 kg body weight). Mitochondria were prepared from the jejunum and other major tissues for measuring the activities of Delta1-pyrroline-5-carboxylate (P5C) synthase and proline oxidase (enzymes catalyzing P5C synthesis from glutamate and proline, respectively) and of ornithine aminotransferase (OAT) (the enzyme catalyzing the interconversion of P5C into ornithine). For metabolic studies, jejunal enterocytes were incubated at 37 degrees C for 30 min in Krebs-Henseleit bicarbonate buffer containing 2 mmol/L L-glutamine, 2 mmol/L L-[U-14C]proline, and 0-200 micromol/L gabaculine (an inhibitor of OAT). The activities of P5C synthase, proline oxidase and OAT were greatest in enterocytes among all of the tissues studied. Incubation of enterocytes with gabaculine resulted in decreases (P < 0.05) in the synthesis of ornithine and citrulline from glutamine and proline. When gabaculine was orally administered to pigs (0.83 mg/kg body weight) to inhibit intestinal synthesis of citrulline from glutamine and proline, plasma concentrations of citrulline (-26%) and arginine (-22%) decreased (P < 0.05), whereas those of alanine (+21%), ornithine (+17%), proline (+107%), taurine (+56%) and branched-chain amino acids (+21-40%) increased (P < 0.05). On the basis of dietary arginine intake and estimated arginine utilization, the endogenous synthesis of arginine in the 28-kg pig provided >/=50.2% of total daily arginine requirement. Taken together, our results suggest an important role for endogenous synthesis of arginine in regulating arginine homeostasis in postweaning growing pigs, as previously shown in neonatal pigs. 相似文献
99.
A task-based approach to assessing lead exposure among iron workers engaged in bridge rehabilitation
The assessment of worker exposures to airborne contaminants in the dynamic environment present at most construction sites poses considerable challenges to the industrial hygienist. In this study, we applied a task-based approach to the assessment of lead exposure among structural steel iron workers engaged in a large, complex bridge rehabilitation project. We evaluated the usefulness of task-based exposure data for the development of worker protection programs. Task-specific and multitask samples were collected, and operation-specific and 8-hr time-weighted averages were calculated. The task-specific data showed significant differences in exposure levels among different tasks. Arithmetic mean exposures varied from 1,357 micrograms/m3 lead for torch cutting and 989 micrograms/m3 for scaling to 31 micrograms/m3 for reaming and 4 micrograms/m3 for drilling. Our task-specific data were compared with the task-based exposure levels presented by OSHA in its Lead Exposure in Construction-Interim Final Rule (29 CFR 1926). There was good general agreement between our results and OSHA's reported data. Task-based data were very useful in exposure assessment and much more precise than full-shift and operation-based measurements in guiding strategies for worker protection. These findings suggest that task-based data should routinely be collected in evaluating exposure to lead and perhaps other toxic substances in construction work. 相似文献
100.
Yeow Meng Chee Son Hoang Dau Ling A.C.H. San Ling 《IEEE transactions on information theory / Professional Technical Group on Information Theory》2010,56(1):140-151
An optimal constant-composition or constant-weight code of weight w has linear size if and only if its distance d is at least 2w-1. When d ? 2w, the determination of the exact size of such a constant-composition or constant-weight code is trivial, but the case of d=2w-1 has been solved previously only for binary and ternary constant-composition and constant-weight codes, and for some sporadic instances. This paper provides a construction for quasicyclic optimal constant-composition and constant-weight codes of weight w and distance 2w-1 based on a new generalization of difference triangle sets. As a result, the sizes of optimal constant-composition codes and optimal constant-weight codes of weight w and distance 2w-1 are determined for all such codes of sufficiently large lengths. This solves an open problem of Etzion. The sizes of optimal constant-composition codes of weight w and distance 2w-1 are also determined for all w ? 6, except in two cases. 相似文献