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Biomedical subjects

B Allen

Publications and source records attributed to B Allen.

At least 109 records · Page 6Linked to original sources

Occluded peripheral arteries: clinical utility of argon laser recanalization.

Optically diverged direct argon laser light energy was used prior to conventional balloon angioplasty to recanalize 30 occluded peripheral arteries in 26 patients. Three of five (60%) iliac and 22 of 25 (88%) femoropopliteal lesions ranging in length from 1 to 47 cm (mean, 17.3 cm) were successfully treated, for an overall technical success rate of 83%. In the femoropopliteal system, 13 of 14 (93%) procedures in lesions less than 20 cm and nine of 11 (82%) procedures in lesions greater than 20 cm were treated successfully. No statistically significant differences in success rate based on lesion site, lesion length, degree of lesion calcification, or severity of peripheral vascular disease were found. Major complications were a laser perforation resulting in treatment failure in one case (3%) and a successfully treated distal embolus in another (3%). No reocclusions occurred in the immediate postoperative period. While long-term follow-up will be required to assess continued patency, this system can potentially increase the number of patients amenable to conventional balloon angioplasty and is currently advocated as an alternative to amputation in patients in whom surgical bypass grafting is contraindicated or unfeasible.

Aged↗

A safety profile of controlled release naproxen tablets.

This randomised single blind controlled study examines adverse reactions to standard Naprosyn (naproxen) 750 mg daily with controlled release naproxen, Naprosyn CR, 750 mg daily, in a total of 520 patients. Overall there were no major differences between the two preparations. The reporting rate of any adverse clinical event was greater in the group taking the controlled release preparation but withdrawals from medication were similar in the two groups, for whatever reason. The main finding of the study was that patients in each decile age group, mainly between 40 and 80 years, were more likely to continue on this preparation for the full 10 weeks of the trial: 57% of patients on controlled release and 46% on plain Naprosyn completed the study. Patients over 60 years, particularly females, tended to complete the study, indicating that the simpler treatment regimen without any increase in major adverse effects is useful in the elderly who are thought to be at special risk of adverse reactions from NSAIDs. In addition, a review of spontaneous reports of adverse reactions to naproxen reported nationally to the Medicines Adverse Reactions Committee shows that the pattern has not changed over the last two years during which the controlled release formulation has been available. This experience supports the acceptability of controlled release naproxen.

Aged↗

Evaluation of uncertainty in input parameters to pharmacokinetic models and the resulting uncertainty in output.

Physiologically-based pharmacokinetic (PBPK) models may be used to predict the concentrations of parent chemical or metabolites in tissues, resulting from specified chemical exposures. An important application of PBPK modeling is in assessment of carcinogenic risks to humans, based on animal data. The parameters of a PBPK model may include metabolic parameters, blood/air and tissue/blood partition coefficients, and physiological parameters, such as organ weights and blood flow rates. Uncertainty in estimates of these parameters results in uncertainty regarding tissue concentrations and resulting risks. Data are reviewed relevant to the quantification of these uncertainties, for a PBPK model-based risk assessment for tetrachloroethylene. Probability distributions are developed to express uncertainty in model parameters, and uncertainties are propagated by a sequence of operations that simulates processes recognized as contributing to estimates of human risk. Distributions of PBPK model output and human risk estimates are used to characterize uncertainty resulting from uncertainty in model parameters.

Animals↗

Choice of dose measure for extrapolating carcinogenic risk from animals to humans: an empirical investigation of 23 chemicals.

When estimating carcinogenic risk in humans from animal data, animal to human extrapolation is often accomplished by assuming that humans and animals are equally sensitive when dose is measured appropriately in common units in both species. This paper reports on an empirical investigation of several dose units, based on data from 23 chemicals for which both animal and human data were available. The dose units were evaluated using a measure called "bias," which represents roughly the factor by which the TD25 calculated from animal data must be multiplied to correspond, on average, to the TD25 calculated from human data. (A TD25 is the average human dose rate per unit of body weight in mg kg-1 d-1, administered between ages 20 and 65, that would cause an extra lifetime cancer risk of 25%.) Biases of greater than one mean that estimates of human risk from animal data exceeded estimates made from human data. Five dose measures are evaluated in this paper; they are based on several risk assessment methods. The resulting ranges of biases are: dose rate per surface area in mg m-2 d-1, 2.1 to 12; dose rate per unit of body weight in mg kg-1 d-1, 0.36 to 1.6; parts per million in diet, 1.1 to 6.2; cumulative dose per unit of body weight in mg kg-1 per lifetime, 13 to 84; parts per million in air, 1.1 to 4.5. These findings suggest that all of these measures of dose except dose rate per unit of body weight tend to result in overestimation of human risk.

Administration, Inhalation↗

Effect of secondary substrate binding in penicillopepsin: contributions of subsites S3 and S2' to kcat.

The kinetic parameters kcat, KM, and kcat/KM were determined at 25 degrees C and pH 4.5, 5.5, and 6.0 for the series of penicillopepsin substrates Ac-Alam-Lys-(NO2)Phe-Alan-amide, where (NO2)Phe is p-nitrophenylalanine and m and n equal 0-3. KM values at pH 6.0 were the same for all 12 peptides and averaged 0.088 +/- 0.02 mM but increased to different degrees at lower pH. In contrast, kcat values increased with increasing chain length. At pH 6 and at the pH optimum of kcat, the largest increases (about 37-fold on average) were obtained when alanine residues were added in positions P2' and P3. Only 1-2-fold increases were observed for positions P2, P3', P4, and P4'. These results show that occupation of subsites S2' and S3 is largely responsible for the rate enhancements caused by secondary substrate interactions with this series of peptides. Additional support for an important role of subsite S3 comes from the observation that the two peptides where m = 1 and n = 1 or 2, respectively, are cleaved not only between lysine and p-nitrophenylalanine but also between the latter and alanine, suggesting that occupation of subsite S3 by the N-terminal alanine overcomes the unfavorable interaction of alanine in subsite P1'. Subsite S3 is also important in the binding of pepstatin analogues and in transpeptidation reactions. It is proposed that the roles of subsites S3 and S2' are to facilitate the conversion of the first enzyme-substrate complex into a productive complex and to assist in the distortion of the scissile bond.(ABSTRACT TRUNCATED AT 250 WORDS)

Aspartic Acid Endopeptidases↗

Computed tomography of strangulated gastric hernia complicated by perforation and pneumothorax.

A case of traumatic rupture of the diaphragm with partial gastric herniation is reported. The initial radiographic presentation was left lower lobe pneumonia. Subsequent strangulation and perforation of the stomach caused pneumothorax. Serial chest radiographs, computed tomography of the chest and abdomen with oral contrast, and a high index of suspicion were instrumental to the diagnosis. Pneumothorax, though rare, must be recognized as a morbid, obstructive phase complication of traumatic diaphragmatic hernia requiring immediate surgical intervention.

Adult↗

Fracture analysis of retrieved orthopedic wires.

Ten retrieved samples of 316L stainless steel wires, implanted for times from 11 months to 11 years, were examined fractographically and metallurgically to evaluate the effects of a physiological environment on their fracture. Seven samples were from L-rod instrumentation, and three samples were from trochanter reattachment. Of 16 breaks in the 10 samples, 94% were caused primarily by cyclic loading (fatigue), and 6% were caused by tensile forces. Two factors were found to influence the effective life of an implanted wire. First, the surface condition (deformation) appeared to be most important, and second, corrosion pits present on most wire surfaces could possibly be an influence in initiating a crack. Biomechanical forces on wires enveloping L-rods tended to promote metal deformation and faceting, which decreased time to fracture. This decrease in wire life was evident from a substantial hardness increase in faceted areas.

Bone Wires↗

Transport of fluid and biliary lipids in the canine gallbladder in experimental cholecystitis.

In acute cholecystitis the cystic duct is usually obstructed by a gallstone and the gallbladder is often tensely distended with clear fluid. Because these findings suggest that fluid absorption in the gallbladder may be reversed in cholecystitis, we examined the effect of inflammation on the gallbladder mucosal function in dogs. In 20 dogs cholecystitis was induced by ligating the cystic duct and allowing inflammation to develop from bile stasis and the presence of a chronic indwelling cannula in the gallbladder. Every morning an aliquot of normal hepatic bile was infused into the gallbladder through a cannula in the gallbladder fundus. After either 4 or 24 hr the gallbladder contents were aspirated, the volume was measured, and the concentrations of bile acids, cholesterol, phospholipids, and protein were determined. Changes in volume were checked using [14C]PEG as a nonabsorbable tracer. A net absorption of fluid, bile acids, cholesterol, and phospholipids occurred during the first 24 to 48 hr after ligation of the cystic duct. Thereafter, fluid, cholesterol, and protein were secreted into the lumen, but absorption of bile acids continued. The lithogenic index of bile placed in the inflamed gallbladder was always greater when the bile was removed 24 hr later. The rate of fluid secretion into the lumen of the inflamed gallbladder increased after a meal and decreased after indomethacin. These findings demonstrate that inflammation can stimulate the gallbladder mucosa to secrete fluid, a process that may be important in the pathophysiology of acute cholecystitis in man. Since inflammation also resulted in an increased cholesterol saturation of gallbladder bile, cholecystitis per se may contribute to the formation of cholesterol gallstones.

Animals↗