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Biomedical subjects

A J Lewis

Publications and source records attributed to A J Lewis.

At least 19 recordsLinked to original sources
PubMed1992

Strategies for the development of new antiarthritic agents.

Therapeutic advances in rheumatoid arthritis (RA) have largely focused on the development of non-steroidal antiinflammatory drugs (NSAIDs) with improved characteristics compared with aspirin [Brooks & Day, New Engl. J. Med., 324, 1716-1725 (1991)]. For example, greater potency, safety, improved tolerance in the elderly and reduced frequency of dosing have been achieved. However, these agents are generally considered to be palliative treating of the symptoms of the disease. The development of disease modifying drugs (DMD), also known as second line drugs, for RA has not been very successful. Most of the agents that are currently used in this category were originally used to treat other diseases such as malignancy (cyclophosphamide, methotrexate), Wilson's disease (d-penicillamine) and tuberculosis (gold salts) [Pullar, Br. J. clin. Pharmac., 30, 501-510 (1990)]. Unfortunately, none of the agents is ideal and each has potentially serious side-effects. There have been several attempts to develop agents with new mechanisms of action that hopefully will greatly improve these current therapies.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1992

Bioavailability of threonine in soybean meal for rats and chicks.

The bioavailability of threonine in soybean meal and the effects of the excess amino acids in soybean meal on the estimate were measured using rats and chicks in slope-ratio assays. In Exp. 1, a corn-based diet containing .23% threonine was supplemented with 0 to 45% L-threonine in .05% increments. The growth rate of weanling rats fed these diets increased quadratically (P less than .001) with L-threonine addition, the increase being essentially linear up to the .10% addition. In Exp. 2, the basal diet was supplemented with 0, .025, .050, .075, or 100% threonine from L-threonine, simulated soybean meal (a mixture of crystalline amino acids with a pattern designed to simulate soybean meal), or soybean meal. Regressions of partitioned weight gain and body N gain of rats vs supplemental threonine intake were calculated for each source using multiple regression. Slope ratios (soybean meal:L-threonine) were .91 for weight gain and .92 for body N gain. The additional amino acids in simulated soybean meal did not affect the estimate. For Exp. 3, a corn-soybean meal-based diet containing .48% threonine was supplemented with 0 to 60% L-threonine in .10% increments. The growth rate of broiler chicks fed the diets increased quadratically (P less than .001) with L-threonine addition. The increase was essentially linear up to the .10% addition. In Exp. 4, the basal diet was supplemented as in Exp. 2. Regressions of partitioned weight gain of chicks vs supplemental threonine intake were calculated for each source. The slope ratio for soybean meal:L-threonine was 1.03; however, the model exhibited fundamental invalidity and therefore the estimate should be interpreted with caution. The additional amino acids in the simulated soybean meal did not affect the value.

Animal Feed↗
PubMed1992

Plasma amino acid response to graded levels of escape protein.

A trial was conducted to examine the potential of using plasma amino acid responses to graded levels of escape protein to determine limiting amino acids in cattle. Growing calves (n = 120; mean BW = 220 +/- 21 kg) were fed a basal diet of corncob:sorghum silage (61:39) and were individually supplemented with distillers' dried grains (DDG), heat-damaged DDG (H-DDG), feather meal (FTH), or urea. The urea supplement was mixed with DDG and H-DDG to allow 0, 20, 35, 50, 65, or 80% of the supplemental CP to come from distillers' protein and maintain an 11.5% CP diet. Urea supplement was mixed with FTH to allow 0, 22, 39, 56, 73, or 90% of the supplemental CP to come from FTH. Dietary CP ranged from 11.5% at the 0% level to 17.3% at the 90% level. Plasma concentration of most essential plasma amino acids responded (P less than .10) linearly and(or) quadratically to increased escape protein. The broken-line response of plasma methionine at low DDG intake suggested that methionine was limiting at low levels of escape protein. An initial decrease followed by a plateau fit by a broken line indicated that histidine became limiting in FTH diets, and lysine eventually became limiting for DDG, H-DDG, and FTH diets before maximum BW gain was reached. Results indicate that plasma amino acid responses may identify amino acids that become limiting with increasing escape protein.

Amino Acids↗
PubMed1991

Hilger facial nerve stimulator: a 25-year update.

Percutaneous nerve excitability testing using the Hilger facial nerve stimulator was introduced about 25 years ago. The test is reliable, easy to use, and inexpensive; it continues to be the most frequently used method for predicting prognosis of facial nerve disorders. Between 1966 and 1974, we recorded 10,243 nerve excitability tests on 865 patients with a mean of 3.29 tests for each peripheral branch and 3.43 for the trunk. Using a multiple regression model, we determined the effect on nerve stimulation values of age, sex, race, diabetes, hypertension, partial or complete clinical paralysis, diagnosis of herpes zoster, year of testing, and eventual facial paralysis recovery profile. We discuss statistical reliability, provide a table of interpretive results, and offer "tips and traps" invaluable to the practitioner. A prospective study of 25 patients with residual facial paralysis was evaluated by two separate otolaryngologists to determine intertester reliability.

Adult↗
PubMed1991

Effects of supplemental biotin during gestation and lactation on reproductive performance of sows: a cooperative study.

A cooperative experiment to evaluate biotin addition to sow diets was conducted at three research stations using 303 litters. Primiparous and multiparous sows (overall average parity 2.8) were fed a 14% CP corn-soybean meal diet (140 micrograms/kg biotin), with or without supplemental biotin (330 micrograms added biotin per kg feed), throughout gestation and lactation. As many sows as possible were fed their respective diets through three successive parities. During gestation, sows were given from 1.82 to 2.27 kg of feed per day, depending on environmental conditions; during lactation sows had ad libitum access to feed. Supplemental biotin had no effect (P greater than .35) on sow weights at breeding, at d 109 of gestation, at farrowing or at weaning. No differences were found in litter size at birth (P greater than .18), but at d 21 of lactation, sows fed the diet containing supplemental biotin had larger litters than sows fed the unsupplemented diet (9.4 vs 8.7 pigs, respectively; P = .01). Pig weights at birth and d 21 of lactation were not affected (P greater than .20) by dietary treatment. Biotin supplementation did not affect (P greater than .28) the length of the interval from weaning to estrus. No evidence was found that feet cracks or bruises were reduced by biotin supplementation. The results indicate that biotin supplementation of a corn-soybean meal diet during gestation and lactation increased the number of pigs at d 21 of lactation, but it did not decrease the incidence of foot lesions.

Animal Feed↗
PubMed1991

Feeding value of grain sorghum for the lactating sow.

Two experiments were conducted to investigate the effects of a corn-soybean meal (C-SBM) and a sorghum-soybean meal (S-SBM) diet on reproductive performance and nutrient utilization by sows. In Exp. 1, 75 sows (39 gilts; 36 primiparous) were fed either a C-SBM or a S-SBM gestation diet from breeding to d 109. On d 110, sows were assigned to lactation diets; half of the sows from each dietary treatment were assigned to a lactation diet based on the opposite grain. Sow weight change from d 54 to farrowing was greater (P less than .06) for sows fed S-SBM than for sows fed C-SBM. There was no difference (P greater than .50) in weight change of sows during lactation. Feed consumption during lactation was greater (P less than .01) for sows fed C-SBM than for sows fed S-SBM. Litter size at birth and d 21 did not differ between treatments (P greater than .13). Litter weights at birth were similar, but litters of sows fed C-SBM gained more weight (P less than .05) during the 21-d lactation than those fed S-SBM. There were no differences (P greater than .30) in the number of days from weaning to estrus. In Exp. 2, the energy and N metabolism of the two diets was compared in 12 lactating, primiparous sows from d 15 to 20 of lactation. Dry matter digestibility, DE and ME percentages were not affected by grain source (P greater than .46).(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Feed↗
PubMed1991

Amino acid and energy interrelationships in pigs weighing 20 to 50 kilograms: I. Rate and efficiency of weight gain.

The relationships between dietary amino acids and DE for pigs weighing 20 to 50 kg were investigated in two experiments. In Exp. 1, there were three dietary lysine levels that were either adjusted (1.50, 2.35 and 3.20 g/Mcal DE) for five DE levels (3.00 to 4.00 Mcal/kg) or unadjusted (.45, .71 and .96% of the diet) for three DE levels (3.50 to 4.00 Mcal/kg). In Exp. 2, the effects of six lysine:DE ratios (1.90 to 3.90 g/Mcal) at two DE levels (3.25 and 3.75 Mcal/kg) were investigated. In both experiments, diets were formulated using a constant ratio of corn and soybean meal. Pigs (equal numbers of barrows and gilts) were housed and fed individually and had ad libitum access to feed and water. Digestible energy intake was not affected by energy content of the diets. In Exp. 1, lysine intake did not differ with DE in the adjusted diets but decreased (P less than .001) as DE increased in the unadjusted diets. Weight gain was relatively consistent and gain:DE intake increased (P less than .001) as DE increased in the adjusted diets, but both decreased (P less than .005) with increasing DE in the unadjusted diets. Both criteria increased (P less than .001) in response to higher lysine:DE in the adjusted and lysine in the unadjusted diets. In Exp. 2, weight gain increased (P less than .005), but there was no effect (P greater than .05) on gain:DE intake as DE increased. Both weight gain and gain:DE intake increased (P less than .001) and backfat decreased (P less than .01) as lysine:DE ratios increased. The results demonstrate the need to increase dietary amino acid levels in concert with increases in energy contents. Regression analyses indicated that weight gain and gain:DE intake for 20- to 50-kg pigs were maximized at approximately 3.0 g lysine/Mcal DE (or 49 g of balanced protein/Mcal DE).

Adipose Tissue↗
PubMed1991

Amino acid and energy interrelationships in pigs weighing 20 to 50 kilograms: II. Rate and efficiency of protein and fat deposition.

Two experiments were conducted to investigate the relationships between amino acids and DE for pigs weighing 20 to 50 kg. In Exp. 1, there were three dietary lysine levels that were either adjusted (1.50, 2.35 and 3.20 g/Mcal DE) for five DE levels (3.00 to 4.00 Mcal/kg) or unadjusted (.45, .71 and .96% of the diet) for three DE levels (3.50 to 4.00 Mcal/kg). In Exp. 2, diets containing six lysine:DE ratios (1.90 to 3.90 g/Mcal) at two DE levels (3.25 and 3.75 Mcal/kg) were fed. Pigs were housed individually, and could eat and drink ad libitum. When pigs weighed 50 kg, their empty body composition was determined by the urea dilution technique in Exp. 1 and by prediction equations based on backfat in Exp. 2. For the adjusted diets in Exp. 1, protein deposition and protein deposition:DE intake increased (P less than .01) slightly as DE levels increased. These criteria decreased linearly (P less than .001), and fat deposition increased (P = .11) as DE increased when lysine:DE ratios were not maintained. As lysine levels increased, protein deposition and protein deposition: DE intake increased (P less than .001) in both the adjusted and unadjusted diets. In Exp. 2, there was no effect of DE on either the rate or efficiency of protein deposition. Both protein deposition and protein deposition:DE intake increased (P less than .001) and fat deposition decreased as lysine:DE ratios increased up to 3.00 g lysine/Mcal DE. Protein deposition: lysine intake decreased (P less than .01) progressively as the lysine:DE ratio increased. Regression analyses indicated the protein deposition increased up to 3.00 g lysine/Mcal DE. The results demonstrate the need to adjust lysine according to energy levels and indicate that the optimum ratio for protein deposition was approximately 3.00 g lysine/Mcal DE (or 49 g of balanced protein/Mcal DE).

Adipose Tissue↗
PubMed1991

WY-50, 295 tromethamine: an orally active 5-lipoxygenase inhibitor with anti-allergic activity.

WY-50,295 tromethamine inhibited antigen-induced peptidoleukotriene (pLT) release from fragmented sensitized guinea pig lung (IC50 = 0.63 microM), antagonized LTD4-induced contractions of isolated guinea pig trachea (pA2 = 6.06), and suppressed antigen-induced contraction of sensitized guinea pig trachea over the 0.1-10 microM concentration range. In vivo, WY-50,295 tromethamine inhibited LTD4-induced bronchoconstriction (ED50 = 1.3 mg/kg i.v. and 6.6 mg/kg p.o.) and antigen-induced bronchoconstriction (ED50 = 2.5 mg/kg i.v. and 7.3 mg/kg p.o.) in anesthetized guinea pigs. Peak activity vs antigen was noted at 4-6 h after oral dosing and remained significant through 18 h. These studies demonstrate that WY-50,295 tromethamine possesses the complimentary actions of 5-LO inhibition and LTD4 receptor antagonism.

Administration, Oral↗
PubMed1990

Clinical significance of carotid plaque hemorrhage.

We correlated the clinical and pathologic findings in 77 consecutive carotid plaques removed at endarterectomy to determine the clinical role of intraplaque hemorrhage. Intraplaque hemorrhages of various severity were seen in 86% of plaques. They were, for the most part, deeply located (63%) and infrequently connected with the lumen. They related closely to the severity of carotid stenosis, but bore no relationship to the timing of symptoms. Luminal thrombus was infrequently seen, and was always microscopic. Hemorrhage into carotid plaque appears to represent an index of the severity of the stenosis and plaque instability rather than to play a direct role in the pathogenesis of transient ischemic attacks or stroke.

Aged↗
PubMed1990

Detection and typing of papillomavirus DNA in formaldehyde-fixed paraffin-embedded tissue.

Clinical specimens from nine patients with papillomatosis of the vocal cords and three patients with vocal cord polyps were evaluated for the presence of human papillomavirus (HPV) DNA using two complementary molecular hybridization techniques. In one method, involving polymerase chain reaction (PCR) amplification, HPV DNA sequences were replicated in vitro from tissue DNA extracted from paraffin sections prior to hybridization. Polymerase chain reaction amplification was compared with the standard method of Southern blot hybridization. Results of the two techniques for all nine laryngeal papillomas agreed completely: five patients harbored HPV type 6 and four HPV type 11. Both PCR amplification and Southern blot hybridization found two of the three polyps to be free of HPV infection, while PCR detected HPV type 18 in one polyp specimen that was reported negative by Southern blot hybridization, suggesting a greater sensitivity of PCR. Our results demonstrate that PCR amplification is as reliable and at least as sensitive as Southern blot hybridization. Moreover the PCR technique opens the way to the undertaking of a whole variety of retrospective studies using formaldehyde-fixed paraffin-embedded tissues.

Blotting, Southern↗
PubMed1990

Diffuse Lewy body disease with dementia and oculomotor dysfunction.

The case is presented of an elderly patient who had dementia, axial rigidity, and bradykinesia with limitation of horizontal and vertical gaze. Pathological examination disclosed Lewy and Lewy-like bodies in the substantia nigra, locus ceruleus, and neocortex, leading to a final diagnosis of diffuse Lewy body disease. Similar inclusions were found in areas of the pons and midbrain believed to be associated with gaze control. Moderate numbers of neuritic plaques, but no neurofibrillary tangles, were present in limbic cortex and neocortex. Review of the literature has not shown previous association of diffuse Lewy body disease with both horizontal and vertical gaze anomalies.

Aged↗
PubMed1990

Effects of ethanol extraction and duration of heat treatment of soybean flakes on the utilization of soybean protein by growing rats and pigs.

Three experiments were conducted to determine the effects of ethanol extraction and duration of heat treatment of soybean flakes on the utilization of soybean protein by growing rats and pigs. In the first experiment, the treatments were no extraction or extraction with a 55% ethanol-water mixture (v/v), and heat treatments of 0, 5, 10, 20 and 40 min in an autoclave. Ethanol extraction improved rate (P less than .002) and efficiency of gain (P less than .001) of rats. As heat treatment was increased from 0 to 20 min, rate of gain increased, but it decreased again as heating time was increased from 20 to 40 min (P less than .03). In Exp. 2 and 3, 45 pigs were used in a growth assay and 54 were used in a N balance experiment to determine the effects of ethanol extraction on under-, intermediate- and over-processed soybean flakes (i.e., 5, 20 and 60 min of autoclaving). The heat treatments were applied either without, before or after extraction with ethanol. Responses in rate and efficiency of gain to ethanol extraction were greater for soybean flakes heated for either 5 or 60 min than for the soybean flakes heated for 20 min. When pooled across heat treatment, pigs fed the soybean flakes heated before or after extraction with ethanol gained faster (P less than .001), had greater gain:feed (P less than .001) and lower plasma urea concentrations (P less than .002) than pigs fed soybean flakes heated without extraction. Feeding soybean flakes heated and extracted with ethanol also resulted in greater apparent N retention (P less than .003), apparent N digestibility (P less than .001) and apparent biological value (P less than .03) than soybean flakes that were heated without extraction. Ethanol extraction improved the protein quality of soybean flakes, especially when the flakes were under- or overprocessed with heat.

Animals↗
PubMed1990

Effects of ethanol extraction and heat treatment of soybean flakes on function and morphology of pig intestine.

Digesta and tissue samples were collected from the intestinal tracts of 27 pigs to determine the relationship between intestinal morphology and the utilization of nutrients from soybean flakes. Soybean flake treatments were under-, intermediate- and over-processed (i.e., 5, 20 and 60 min of autoclaving) either without extraction or with heating before or after extraction with a 55% ethanol-water mixture. Final BW was greatest (P less than .001) for pigs fed soybean flakes given 20 min of heat treatment. There was a trend (P less than .09) for plasma lysine concentrations to be reduced when the unextracted soybean flakes were over-processed (60 min of heat). Differences in the flow rate of DM and N through the ileum and colon reflected differences in DM and N intake, rather than differences in intestinal function. The soybean flake treatments had no effect (P greater than .08) on pH of the contents of the stomach, duodenum, ileum or colon. The ethanol extraction process increased (P less than .001) N digestibility of the soybean flakes, especially when the soybean flakes were underprocessed (interaction, P less than .02). Villus size (area, height and perimeter length) tended to be greater in pigs fed the soybean flakes heated after extraction and(or) exposed to the intermediate level of heat treatment. Indicators of villus shape (villus area/villus height) and proliferative activity (crypt depth and villus height/crypt depth) were not affected by soybean flake treatment (P greater than .08). Ethanol extraction and heat treatment affected the utilization of nutrients from soybean flakes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

The effects of porcine somatotropin and dietary lysine on growth performance and carcass characteristics of finishing swine.

Seventy-two finishing pigs (initial weight = 57.6 kg) were utilized to determine the effects of porcine somatotropin (pST) and dietary lysine level on growth performance and carcass characteristics. Pigs were injected daily with 4 mg pST in the extensor muscle of the neck and fed either a pelleted corn-sesame meal diet (.6% lysine, 17.8% CP) or diets containing .8, 1.0, 1.2 or 1.4% lysine provided by additions of L-lysine.HCl. All diets were formulated to contain at least twice the required amounts of other amino acids. Control pigs received a placebo injection and the .6%-lysine diet. Increasing levels of dietary lysine resulted in increased ADG and improved feed conversion (quadratic, P less than .01) for pST-treated pigs. The calculated daily lysine intake was 16.6, 13.6, 19.6, 25.1, 29.6 and 33.6 g for the control and pST-treated pigs fed .6, .8, 1.0, 1.2 and 1.4% lysine, respectively, over the entire experiment. Breakpoint analysis indicated that cumulative ADG and feed conversion were optimized at 1.19 and 1.22% lysine, respectively. Longissimus muscle area and trimmed ham and loin weights increased as dietary lysine was increased among pST-treated pigs (quadratic, P less than .01). Breakpoint analysis indicated that 1.11% lysine maximized longissimus muscle area, whereas trimmed ham and loin weights were maximized at .91 and .98% lysine, respectively. Adjusted backfat thickness was not affected by dietary lysine, but pST-treated pigs had less backfat (P less than .05) than control pigs did. Percentage moisture of the longissimus muscle increased (linear, P less than .05), as did percentage CP (quadratic, P less than .05), whereas fat content decreased (linear, P less than .05) as lysine level increased. Similar trends in composition were observed for muscles of the ham (semimembranosus, semitendinosus, and biceps femoris). Shear-force values from the longissimus and semimembranosus were lowest for control pigs, but they increased as dietary lysine level increased among pST-treated pigs. Sensory panel evaluations indicated that juiciness and tenderness decreased (linear, P less than .05) as dietary lysine level increased. Plasma urea concentrations decreased linearly (P less than .01) on d 28 as lysine level increased, whereas plasma lysine and insulin were increased (quadratic, P less than .01). Plasma glucose and free fatty acid concentrations on d 28 tended to increase (quadratic, P less than .10) with increasing dietary lysine level.(ABSTRACT TRUNCATED AT 400 WORDS)

Adipose Tissue↗
PubMed1990

Efficacy of the urea dilution technique in estimating empty body composition of pigs weighing 50 kilograms.

The efficacy of the urea dilution technique in estimating the empty body composition of pigs weighing 50 kg was evaluated in three trials using 17 contemporary (Large White X Landrace X Hampshire X Duroc) and 8 Nebraska Gene Pool X contemporary pigs. Blood samples were collected via ear catheter before infusion (-60, -30 and 0 min) and at various times (3 to 90 min) after urea infusion (2.16 mmol/kg live BW), and analyzed for plasma urea. Backfat thickness of live pigs from the contemporary line was measured ultrasonically. Pigs then were killed by euthanasic injection, and total bodies (with gastrointestinal contents removed) were analyzed for water, protein and fat. In Trials 1 and 2, there were linear relationships (P less than .001) between chemically determined body water and fat and between body water and protein. Urea space was related (P less than .05) to empty body components with few exceptions, but regression coefficients for urea space in Trial 3 were different from those of Trials 1 and 2. Inclusion of additional independent variables with urea space improved estimation of empty body components. Although backfat alone did not estimate empty body components (except fat) as well as urea space alone, the addition of other common independent variables resulted in better estimates using backfat than urea space. The results of this experiment indicate that the urea dilution technique can be used to estimate the body composition of growing pigs. However, the accuracy obtained depended on the population of pigs being investigated and was no greater than the accuracy with appropriate equations based on backfat.

Animal Feed↗