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Biomedical subjects

J E Williams

Publications and source records attributed to J E Williams.

At least 19 recordsLinked to original sources

Real time measurement of stimulated dopamine release in the conscious rat using fast cyclic voltammetry: dopamine release is not observed during intracranial self stimulation.

Fast cyclic voltammetry (FCV) was used to measure real time release of electrically stimulated endogenous dopamine in the nucleus accumbens (NAc) of conscious freely moving rats for up to 17 days. The method of electrode construction, implantation, electrical stimulation and recording of changes of extracellular dopamine concentration in the conscious rat are described. Rats trained on a continuous reinforcement schedule to perform intracranial self stimulation (ICSS) were implanted with electrodes for FCV. During ICSS, no faradaic signal was observed at an electrode implanted in the NAc. Decreasing the intensity of the stimulating current abolished ICSS, increasing the stimulating current disrupted ICSS. Operator delivered electrical stimulations using currents greater than those needed for ICSS yielded dopamine signals. It is concluded that during ICSS, sufficient dopamine does not reach the extracellular fluid space to yield a faradaic signal detectable by FCV.

Animals

Comparing analgesic efficacy of non-steroidal anti-inflammatory drugs given by different routes in acute and chronic pain: a qualitative systematic review.

AIM: To test the evidence for a difference in analgesic efficacy and adverse effects of non-steroidal anti-inflammatory drugs (NSAIDs) given by different routes. METHODS: Systematic review of published randomised controlled trials. Relevant trials were comparisons of the same drug given by different routes. Presence of internal sensitivity was sought as a validity criterion. Analgesic and adverse effect outcomes were summarised, and synthesised qualitatively. RESULTS: In 26 trials (2225 analysed patients), 8 different NSAIDs were tested in 58 comparisons. Fifteen trials (58%) compared the same drug by different routes. Drugs were given by intravenous, intramuscular, intrawound, rectal and oral routes in postoperative pain (14 trials), renal colic (4), acute musculoskeletal pain (1), dysmenorrhoea (1), and rheumatoid arthritis (6). Five of the 15 direct comparisons were invalid because they reported no difference between routes but without evidence of internal sensitivity. In all 3 direct comparisons in renal colic, intravenous NSAID had a faster onset of action than intramuscular or rectal. In 1 direct comparison in dysmenorrhoea, oral NSAID was better than rectal. In the 5 direct comparisons in postoperative pain, results were inconsistent. In 1 direct comparison in rheumatoid arthritis, intramuscular NSAID was better than oral. Injected and rectal administration had some specific adverse effects. CONCLUSION: In renal colic there is evidence that NSAIDs act quickest when given intravenously. This may be clinically relevant. In all other pain conditions there is a lack of evidence of any difference between routes. In pain conditions other than renal colic, there is, therefore, a strong argument to give oral NSAIDs when patients can swallow.

Acute Disease

Supplemental protein plus ruminally protected methionine and lysine for primiparous beef cattle consuming annual rye hay.

Primiparous beef cows (n = 35 Bos taurus, average initial BW of 498 kg) were allotted to treatments in a split-plot designed experiment to determine the effects of supplemental ruminally protected amino acids on cow and calf productivity and metabolic changes in the cows. Cows were fed chopped annual rye hay at 1.5% of BW. The following treatments were used: 1) .8 kg soybean hulls, 1.4 kg ground corn, .6 kg soybean meal (CON); 2) 1.4 kg ground corn, 1.4 kg soybean meal (PRO); 3) PRO plus ruminally protected methionine and lysine (supplied 5 and 10 g, respectively; PRO1); and 4) PRO with twice the level of ruminally protected amino acids in PRO1 (PRO2). Cow weight gain was not different (P > .26) among treatments and averaged 1.2 kg/d for the 45 + 6 d before parturition. After parturition, cow weight gain did not differ (P > .47) between CON and PRO treatments, but it decreased quadratically (P < .01) with increasing level of ruminally protected amino acids. Total milk yield, protein, and fat (4 h) were greater (P < .05) for cows consuming PRO supplements than for CON, whereas CON cattle tended (P = .11) to lose less body condition. Total milk protein showed a quadratic increase (P < .05) in response to level of ruminally protected amino acids that was the inverse of the quadratic response noted for cow weight gain. Serum urea N concentration was greater (P = .07) for cattle consuming additional protein. Metabolic hormones were not affected (P > .18) by dietary treatment, but they responded (P < .05) to changes in physiological state. Supplements with additional protein supported greater (P = .0001) milk urea N concentration and output. Milk urea N concentration increased (P < .05) and milk IGF-I decreased (P < .05) as the lactation period progressed. The measurement of CON and PRO diets revealed that supplements with additional soybean meal had greater (P < .05) DM and N degradation; the extent of forage DM and NDF degradation was similar (P > .05) among treatments. Production shifted away from body weight gain to increased milk protein production when daily supplementation of ruminally protected methionine and lysine increased from 5 and 10 to 10 and 20 g, respectively. This shift in production was not reflective of changes in the metabolic regulators measured.

Animal Feed

Intravascular contrast media: can we justify the continued use of ionic contrast agents?

Cost has been the major factor preventing the universal conversion to non-ionic contrast agents. We assessed the costs and potential benefits of making this change in our department. During a 10-month-period the use of all intravascular contrast agents and reaction rates were audited prospectively. One thousand three hundred and ninety-four examinations were included. A local protocol for the use of ionic and non-ionic contrast media was already in place, based on the Royal College of Radiologists Guidelines. For each patient the contrast agent used, risk factors, and presence or absence of a contrast reaction were recorded. Non-ionic contrast agent usage exceeded ionic by a factor of 10. Patients receiving ionic agents intravenously had a reaction rate of 16.8% compared with 2.7% for non-ionic contrast media. The use of ionic contrast media was subsequently suspended and the effect of this on overall costs assessed by retrospectively and prospectively analysing hospital expenditure on contrast agents. No increase in costs was found. The reasons for this are two-fold. Firstly in our institution the protocol in place and the nature of the workload resulted in relatively small volumes of ionic contrast media being used compared with non-ionic agents. Secondly, since our department is a bulk purchaser of non-ionic agents, substantial discounts could be negotiated. The benefits of non-ionic contrast media are well recognized and our experience suggests that cost may no longer be a barrier to conversion to these lower risk agents.

Contrast Media

Blastic natural killer cell leukemia/lymphoma: a clinicopathologic study.

The classification of natural killer (NK)-cell and NK-like T-cell malignancies has undergone significant evolution in recent years. Although examples of NK-cell tumors resembling acute leukemia have been described anecdotally as blastic, blastoid, or monomorphic NK-cell leukemia/lymphoma (NKL/L), the clinical and pathologic features of these tumors have not been systematically defined. We report four patients with blastic NKL/L and describe the clinical, pathologic, and immunophenotypic findings in these cases. All patients were elderly (58-82 years) and presented with cutaneous plaques. Two patients also had adenopathy, and three patients had marrow involvement at presentation. Biopsy of cutaneous lesions showed atypical superficial and deep dermal lymphoid infiltrates. Involved lymph nodes were architecturally effaced by an interfollicular infiltrate with blastic cytologic features. In Wright-Giemsa-stained blood or marrow smears, tumor cells had finely distributed nuclear chromatin, many with nucleoli, and variable amounts of cytoplasm. In contrast to many NK and NK-like T-cell disorders, azurophilic cytoplasmic granules were absent or inconspicuous. The tumor cells were immunophenotypically distinctive. They expressed intermediate density CD45, as is characteristic of blasts; in addition, the cells were positive for HLA-DR, CD2, CD4, and the NK-associated antigen CD56. Surface CD3, cytoplasmic CD3, and CD5 were negative in all cases tested, whereas CD7 was expressed in two cases. In formalin-fixed tissue, tumor cells marked with antibodies to CD43, but not with other T- or B-lineage-related antibodies. All three cases studied for Epstein-Barr viral RNA by in situ hybridization were negative. Although treatments varied, all three patients with clinical follow-up died within months of the diagnosis. The clinical course in two patients culminated in an overtly leukemic phase. These findings suggest that blastic NKL/L represents a distinct clinicopathologic entity, characterized by cutaneous, nodal, and marrow involvement by blastic cells with immunophenotypic characteristics of true NK cells. The disease afflicts elderly patients, pursues an aggressive course, and may culminate in overt leukemia.

Aged

Influence of postpartum weight and body condition change on duration of anestrus by undernourished suckled beef heifers.

Two experiments were conducted to determine the relationship between change in weight and body condition on postpartum interval of thin first-calf beef heifers. Twenty-nine (Exp. I) and 36 (Exp. II) Angus and Angus-sired crossbred heifers were limit-fed to reduce their condition score (BCS) to 4 (scale of 1 to 9) at calving. After calving, heifers were assigned to one of four daily ME intakes (range of 198 to 305 kcal ME/kg BW.75) designed to create a range of BCS changes. Each unit change in BCS was associated (R2 = .72; P < .0001) with a 33-kg weight change. Mean postpartum interval (PPI) from calving to initiation of luteal activity was 121 +/- 6.0 d. As dietary energy density increased, PPI decreased (P < .01). Condition score at calving (CCS) accounted for a greater proportion of the variation (R2 = .37) associated with PPI than did condition score change from calving to d 90 postpartum (CSCH90; R2 = .27) or weight change from calving to d 90 postpartum (WTCH90; R2 = .17). The "best fit" equation (R2 = .56) for predicting PPI included CCS and CSCH90: PPI = 244.5 - 28.28(CCS) - 23.07(CSCH90) + 6.36(CSCH90(2)). Maximum reduction in PPI occurred when heifers gained 1.8 units of BCS during the first 90 d of lactation. Gaining BCS at a faster rate was of no additional benefit.

Aging

[Myositis caused by Pleistophora in a patient with AIDS].

The third case in the literature is reported of an infection produced by Pleistophora. The clinical detail of the three cases are discussed. Two of the patients-including the reported one-were infected by HIV. All patients suffered from myositis with fever, resting and at palpation myalgia, and progressive weakness. Blood tests showed anaemia and high levels of muscle enzymes. Necrotic muscle fibrosis induced disabling contractures. Diagnosis was obtained by detecting the protozoon in a muscle biopsy. The spores may be detectable by means of different staining methods at light microscopy although electron microscopy remains the most reliable technique. Since this is such a rare condition there is no known treatment. Whether the albendazole could be as useful as occurs in patients infected by other genera of microsporidia in still uncertain.

Acquired Immunodeficiency Syndrome

The differentiation of snoring mechanisms using sound analysis.

Ten subjects known to suffer from heavy snoring but not obstructive sleep apnoea were studied using the technique of sleep nasendoscopy. The mechanism of snoring was noted for each and sound recordings of the snoring noise were made. Six subjects were observed to snore using their soft palate only, three snored using only their tongue base and one snored using a combination of palate and tongue base. The sound recordings were subjected to computer analysis of waveform and frequency. Palatal flutter snoring and tongue base snoring appear to have distinct waveform and frequency patterns which allows them to be differentiated from each other.

Confounding Factors, Epidemiologic

The effect of postruminal amino acid flow on muscle cell proliferation and protein turnover.

An experiment was conducted to characterize the effects of postruminal administration of casein, glutamine, cornstarch, and water on protein turnover and in vitro muscle cell proliferation. Four MARC III steers (205 kg) were fed a protein-restricted bromegrass hay-based diet (2.86 Mcal of DE/kg and 13.6 g of N/kg). Using a 4 x 5 Latin square arrangement balanced for residual effects, casein and glutamine, equal to 50% of basal dietary nitrogen intake, cornstarch, isocaloric with casein infusion, or an equal volume of water was continuously infused into the abomasum of steers. Blood samples, collected every 2 h for 24 h after 7 d of infusion, were tested for the effect on cell cycle kinetics and myotube protein turnover. Urine and feces were also collected for 4 d after blood sampling for nitrogen balance and fractional skeletal muscle degradation. The mitogenic activity and ability of serum to influence rate of myoblast proliferation in a dose-dependent manner was influenced (P < .05) by infusate: casein > cornstarch > glutamine = water. Abomasal infusion of casein and cornstarch increased (P < .05) in vitro muscle protein synthesis and decreased (P < .05) in vitro muscle protein degradation, whereas abomasal glutamine infusion only increased (P < .05) in vitro muscle protein synthesis. Abomasal glutamine infusion decreased (P < .05) fractional skeletal muscle protein degradation and synthesis; however, fractional muscle protein accretion tended to increase due to a greater decline in fractional muscle protein degradation. In contrast, abomasal casein infusion increased (P < .05) fractional skeletal muscle protein synthesis, breakdown, and accretion. These results suggest that muscle hypertrophy may be regulated by serum constituents whose activity is affected by postruminal amino acid flow.

Amino Acids

Parametric analysis of the effects of cocaine and cocaine pretreatment on dopamine release in the nucleus accumbens measured by fast cyclic voltammetry.

Fast cyclic voltammetry was used to measure dopamine (DA) release in the nucleus accumbens of anaesthetized rats, in response to electrical sine-wave stimulation of the ventral tegmental area. Voltammetric signals followed increases in either frequency (50-100 Hz), intensity (50-100 microA) or duration (0.5-5.0 s) of the stimulus. Cocaine administration (10 mg/kg) preferentially increased DA release by weak electrical stimuli. Cocaine pretreatment (3 x 10 mg/kg, two weeks earlier) preferentially increased DA release by stronger stimuli, and the effects of acute cocaine were potentiated in these animals. The effects of increasing stimulus duration conformed to first order kinetics. Cocaine pretreatment selectively increased the kinetic parameter representing maximal release, while acute cocaine administration preferentially decreased the parameter representing the stimulus duration eliciting half maximal release. The lack of statistical interaction between these two effects suggests that sensitization of the response to acute cocaine by cocaine pretreatment may simply reflect an increase in the size of the releasable pool of DA.

Animals

Biomechanics of snoring.

A large proportion of the population either snores or suffers the snoring of others. Recent advances with the use of fibre-optic endoscopes have enabled surgeons to observe the inside of the pharynx while a patient is asleep and snoring. In this article we look at the underlying structure of the upper airway and explain, with the use of simple mechanical models, the aerodynamic events occurring inside the upper airway during snoring.

Adult

Oxygen transport and cardiovascular effects of resuscitation from severe hemorrhagic shock using hemoglobin solutions.

OBJECTIVE: To test the short-term efficacy of three hemoglobin solutions in restoring cardiac output, intravascular pressures, oxygen transport (DO2), and oxygen consumption (VO2) after resuscitation from severe hemorrhagic shock. DESIGN: Prospective study. SETTING: Research laboratory. SUBJECTS: Beagle dogs. INTERVENTIONS: After anesthesia and instrumentation, hemorrhagic shock was induced for 2 hrs by blood withdrawal to maintain systolic blood pressure at 50 mm Hg. Resuscitation then occurred with one of four different resuscitation fluids. One group of dogs was not resuscitated. Survival rate was monitored for 8 days. MEASUREMENTS AND MAIN RESULTS: In 33 beagle dogs, cardiovascular variables (DO2 and VO2) were compared after resuscitation with 8% stroma-free hemoglobin, 4% or 8% pyridoxalated-hemoglobin-polyoxyethylene conjugate (PHP44 and PHP88, respectively), or autologous whole blood. The dogs were anesthetized, paralyzed, mechanically ventilated (FIO2 of 0.21), and instrumented with arterial and pulmonary artery catheters. An average of 63% of estimated blood volume was removed to maintain systolic blood pressure at 50 mm Hg for 2 hrs. The dogs then were either not resuscitated (n = 4) or resuscitated with 8% stroma-free hemoglobin (n = 7), PHP44 (n = 6), PHP88 (n = 8), or whole blood (n = 8), with a volume equivalent to the withdrawn blood. Cardiovascular variables, DO2, VO2, oxygen extraction ratios, and blood concentrations of lactic acid and catecholamines were determined before, and for < or = 6 hrs after, resuscitation from hemorrhagic shock. Blood smears were microscopically examined. In addition, the survival rate was monitored for 8 days after resuscitation. By 2 hrs of hemorrhagic shock, there was a large decrease in DO2 (p < .05) and an increase in oxygen extraction ratio from 0.27 to 0.70 (p < .05). There was a 3.5-fold increase in lactate concentrations and a 25-fold increase in catecholamine concentrations as compared with preshock values. All dogs not resuscitated died within 1.75 hrs after 2 hrs of shock. After resuscitation with whole blood, all cardiovascular and oxygen transport variables returned to approximately prehemorrhage values and remained so throughout the measurement period. After resuscitation with any hemoglobin solution, DO2 returned transiently to control values. However, recovery of DO2 was short-lived in all hemoglobin solution groups, and, by 4 hrs postresuscitation in all groups, DO2 was less than the DO2 of the dogs receiving whole blood (p < .05). These changes were associated with decreases in total hemoglobin concentrations compared with the values immediately before resuscitation (p < .05). In addition, with resuscitation using the PHP solutions, blood smears demonstrated aggregation of red blood cells and platelets. On day 8 after hemorrhagic shock, the survival rate was 100% for whole blood and PHP44, 86% for 8% stroma-free hemoglobin, and 33% for PHP88. CONCLUSIONS: Resuscitation from severe hemorrhagic shock with 8% stroma-free hemoglobin, PHP44, or PHP88 is equally effective in restoring cardiac index and vascular pressures as using whole blood. However, resuscitation with the three hemoglobin solutions only transiently restored DO2 after hemorrhagic shock. The subsequent reduction of DO2 compared with the DO2 value using whole blood was due mostly to hemodilution. With the two PHP solutions, formation of red blood cell aggregates probably resulted in sequestration of red cell mass and additional loss of oxygen carrying capacity.

Animals

Health behavior segmentation and campaign planning to reduce cardiovascular disease risk among Hispanics.

Using the social marketing principle of audience segmentation, a Hispanic audience was disaggregated to examine heterogeneous behaviors and lifestyles that could guide planning for public information campaigns designed to reduce cardiovascular disease (CVD) risk. Signal detection analysis resulted in six mutually exclusive subgroups, based on self-reported behavioral changes to improve health. Subgroups differed significantly in communication, behavioral, psychological, and demographic dimensions, indicating they may require unique campaign planning strategies. To determine whether subgroups were meaningful relative to external health-related criteria, they were compared as to health knowledge and status on cardiovascular disease risk factors. The results showed significant differences among audience subgroups in plasma high-density lipoprotein levels and hypertensive status. Results are discussed in terms of their implications for campaign planning and the need for public health campaigns to diversify strategies when targeting Hispanic audiences.

Adolescent

Effects of feeding wash-water solids on health and performance of ewes and lambs.

Diets containing 0, 10, or 20% dried wash-water solids (WWS) from a milk processing plant were fed to 48 Hampshire crossbred wews (average weight 58.1 kg) for 3 yr. Data were obtained on BW gains, hematology, tissue elements, and survival for ewes and BW gains, tissue elements and survival for their lambs. Ewes fed 20% WWS gained less (P < .05 ) BW during gestation and lactation in yr 1 and had lower BW (P < .05) in yr 2 and 3 than those fed 0 or 10% WWS. Lambs from ewes fed 20% WWS gained less (P < .05) BW in yr 2 and 3. Hematology variables of ewes, survival of ewes and survival of lambs were not effected by diet. Although WWS-containing diets contained high concentrations of Ca, P, Mn, and Fe and moderate concentrations of Mo, Mg, and Zn, diets had few effects on tissue elements in ewes and lambs. Concentrations of some tissue elements were less (P < .05) in lambs in yr 2 and 3 than in yr 1. Wash-water solids can be incorporated into ruminant diets, providing a disposal alternative that recycles and conserves nutrients. Long-term feeding posed only minor or negligible health of safety problems. Because fo low energy and N availability and high ash content, WWS probably should be limited to 10% or less of conventional diets.

Animal Feed

Clozapine attenuates the discriminative stimulus properties of (-)-nicotine.

Rats were trained to discriminate 1.9 mumol/kg (-)-nicotine (0.3 mg/kg) from saline in a standard two-bar operant conditioning paradigm with food reinforcement. The effect of neuronal nicotinic acetylcholine receptor (nAChR) agonists and antagonists were verified, and the participation of dopaminergic receptors subtypes in the expression of the (-)-nicotine cue was investigated with cis-flupentixol (D1-D2 antagonist), haloperidol (D2 antagonist) and clozapine (D4 antagonist). The stereoselectivity of the behavioral response was indicated by the 10-fold less sensitivity to (+)-nicotine in (-)-nicotine-trained rats. (+/-)-Anabasine and (-)-cytisine exhibited partial agonist profiles at the 1.9 mumol/kg dose while (-)-lobeline was devoid of any effect in doses up to 19 mumol/kg. (-)-Lobeline did not show antagonist properties in this paradigm. The nicotinic channel blockers mecamylamine, chlorisondamine and hexamethonium were inactive on their own but mecamylamine and chlorisondamine were able to block the effect of (-)-nicotine. Clozapine attenuated the (-)-nicotine cue while cis-flupentixol and haloperidol were ineffective. Similar doses of cis-flupentixol significantly blocked the locomotor stimulant effect of (-)-nicotine in rats indicating that blockade of dopaminergic receptors was achieved at the doses used in the drug discrimination studies. These data suggest that the discriminative stimulus properties of (-)-nicotine are mediated through neuronal nAChRs and involves the activation of dopaminergic receptors of the D4 subtype.

Alkaloids