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Biomedical subjects

D Allen

Publications and source records attributed to D Allen.

At least 199 records · Page 11Linked to original sources

In vitro reactivity of digital arteries and veins to vasoconstrictive mediators in healthy horses and in horses with early laminitis.

The in vitro reactivity of vasoconstrictive mediators that are implicated in acute laminitis was determined in palmar and plantar digital arteries and veins obtained from healthy horses and in palmar digital vessels of horses with early laminitis (Obel grade I). To obtain baseline reactivity data, 3 experiments were conducted, using healthy horses: (1) the reactivity of palmar and plantar digital arteries and veins to angiotensin II, norepinephrine, and 5-hydroxytryptamine (serotonin) were compared; (2) the direct effects of bacterial endotoxin on vascular reactivity were assessed; and (3) the reactivity of palmar digital arteries and veins to angiotensin II, norepinephrine, prostaglandin F2 alpha (PGF2 alpha), serotonin, and a thromboxane-endoperoxide analog (U46619) were determined. The vascular reactivity of these same 5 vasoconstrictors then was determined in horses with early laminitis and was compared with data from healthy (control) horses. Obel grade-I laminitis was experimentally induced in horses, using carbohydrate overload. Dose responses were conducted for each agent at concentrations between 10(-8)M and 10(-4)M. The potency of a drug was defined as the mean effective concentration necessary to induce 50% of maximal contraction (EC50). There were no differences in EC50 concentrations and in maximal contractions between forelimb and hind limb arteries and veins for angiotensin II, norepinephrine, and serotonin. Incubation with endotoxin had no effect on the reactivity of arteries and veins to angiotensin II, norepinephrine, and serotonin.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

Clinical studies of a vegetarian food diet mixture.

A vegetarian food mixture when incorporated into a commercially prepared diet can be used as a supplement or in a vegetarian protein-sparing modified fast. A modification of this diet was given to protein-energy deficient malnourished children in Ethiopia, and it reversed their biochemical defects. The soluble or gel-forming fiber in the mixture also gives the product a favorable glycemic index and reduces glycemic excursion as well as fasting blood glucose and insulin levels. This accounts for the improvements seen in glucose tolerance in type II diabetic patients. These results, however, were preceded by a study of the effects of the mixture in improving glucose tolerance in diabetic rats. A clinical study among New Orleans police officers also suggests that this mixture helps people, without much self-motivation, to lose weight.

Adult↗

Interactions of alcohol with amitriptyline, fluoxetine and placebo in normal subjects.

Amitriptyline (up to 75 mg/day), fluoxetine (up to 40 mg/day) and placebo were administered to 12 normal, healthy subjects for a period of 7 days. Subjects received each drug in random order and a minimum of 28 days was left between drug treatments. A battery of physiological, psychomotor and subjective tests was administered before drugs (day 1) and on days 4 and 8. On day 8 a measured dose of alcohol was given and the tests repeated at 1 and 3 h after alcohol. Tests before alcohol showed little effect on physiological or psychomotor activity either between drugs or between drugs and placebo. Subjective ratings did show some differences between drugs and in general amitriptyline was tolerated less well than fluoxetine. There were few differences between drugs after alcohol but with some measures the interaction with amitriptyline was subjective rather than additive or potentiating. This reflected the already substantial effects of amitriptyline alone.

Amitriptyline↗

Ileal impaction in the horse: 75 cases.

Records of 75 horses with ileal impactions were examined retrospectively. There was a sex predilection towards mares. Arabians were over-represented compared to the hospital population. The average age was 8.3 years. Abdominal pain was observed in 96% of horses. Nasogastric reflux was present in 56% of horses, small intestinal distention was found on rectal palpation in 96% and an ileal impaction in 25%. Exploratory celiotomy was performed in 69 horses, the mass was reduced by extramural massage in 67 horses, and ingesta was removed via enterotomy in 2. Jejunocecostomies were performed in 47 horses. Twenty-five horses developed postoperative ileus, and 11 developed laminitis. Twenty-seven horses survived. Significant differences (p less than 0.05) between survivors and non-survivors were found for rectal temperature (37.7 and 38.2 degrees C, respectively), plasma protein concentration (7.8 and 8.9 g/dl, respectively) and anion gap (15 and 21.3 mEq/l, respectively). Survival decreased with increasing duration of clinical signs. Enterotomy, enterectomy, and/or jejunocecostomy performed during surgery had a deleterious effect on survival.

Animals↗

Treatment of patent urachus associated with a congenital imperforate urethra in a calf.

Patent urachus is a common condition in calves which is frequently associated with omphalitis. A membranous urethral diaphragm prevented closure of the urachus in a female calf. The patent urachus was complicated by an ascending infection of the intraabdominal umbilical remnants. Following surgical removal of the urachus and umbilical vessels along with transection of the membranous diaphragm the calf experienced an uncomplicated recovery. This case stresses the importance of assuring urethral patency when managing a case of patent urachus.

Abnormalities, Multiple↗

Lymphocytic enteritis in a filly.

A yearling Hanoverian filly had intermittent colic for 6 weeks, chylous peritoneal effusion, and a firm mass palpable per rectum. Exploratory laparotomy revealed mesenteric lymphadenopathy, adhesion of the mesenteric root to the duodenum and jejunum, distention of the mesenteric veins and lymphatic vessels, and increased jejunal venous pressure. Lesions in the duodenum, jejunum, and colon included infiltration of lymphocytes and plasma cells in the lamina propria.

Animals↗

Modulation of antibody binding affinity by somatic mutation.

The affinity of hapten binding of monoclonal antibodies (MAbs) specific for 4-hydroxy-3-nitrophenylacetyl (NP) has been investigated at the molecular level by both site-specific mutagenesis and recombinant antibody construction, followed by expression in myeloma cells. We have shown that a single point mutation (trp----leu at codon 33) in the variable region of the heavy chain (VH) is sufficient to endow a primary-response, germline-encoded antibody with an affinity for antigen typical of a secondary-response antibody carrying the same mutation. We have also demonstrated that mutations additional to the trp----leu exchange in the heavy chain and further mutations in the light chain are irrelevant to the high-affinity phenotype of secondary-response antibodies. Since some of these are "parallel" mutations common to clonally unrelated antibodies, this suggests that the mutation rate is not constant across the entire immunoglobulin variable region. Although antibodies with a trp----leu exchange at position 33 are positively selected because of improved hapten binding affinity, we have found that, under rare circumstances, other patterns of mutations may be selected through particular D-JH combinations; we have demonstrated one case where this has generated an antibody with very efficient hapten binding ability.

Animals↗

Antibody engineering for the analysis of affinity maturation of an anti-hapten response.

The influence of structural variation, previously observed in a panel of V186.2 VH/V lambda 1-expressing anti-NP antibodies from the secondary response, on the affinity of these antibodies was examined by site-specific mutagenesis and recombinant antibody construction. A tryptophan----leucine exchange at position 33 in the VH segment of all but one of the high-affinity antibodies is the most frequently observed somatic mutation and by itself leads to a 10-fold higher affinity; all other somatic exchanges are irrelevant for affinity selection. In the single case of a high-affinity antibody without this common exchange, high affinity is mediated by a combination of mutations (including a one-codon deletion) in VH and the particular D-JH rearrangement carried by this antibody. The data indicate that the pattern of somatic diversification through hypermutation is shaped by affinity selection, but that only a single point mutation is available in the VH and the VL gene of lambda 1 chain-bearing anti-NP antibodies which by itself leads to an increase of hapten-binding affinity. Based on the analysis of two secondary response antibodies from which somatic mutations in VH and VL have been eliminated, it is also concluded that the recruitment of B cell clones into the pathway of hypermutation involves a mechanism which is not based upon affinity differences towards the antigen.

Amino Acid Sequence↗

A comparative study of the interactions of alcohol with amitriptyline, fluoxetine and placebo in normal subjects.

1. Twelve normal volunteer subjects were given amitriptyline, fluoxetine and placebo in clinically relevant doses, each for a period of 7 days. A minimum of 28 days intervened between each drug treatment. 2. A battery of physiological, psychomotor and subjective tests was administered before drugs and on days 4 and 8. 3. On day 8 a measured dose of alcohol was given and the tests repeated 1 hour and 3 hours later. 4. Before alcohol, little effect was shown on physiological or psychomotor activity. Subjective ratings indicated that amitriptyline was less-well tolerated than fluoxetine. 5. Significant differences were found for many measures after alcohol but there were few differences with respect to the drugs.

Alcohol Drinking↗

A comparative study of the interaction of alcohol with alpidem, lorazepam and placebo in normal subjects.

Twelve healthy volunteers took part in a double-blind, cross-over comparison of the effects of lorazepam and alpidem on a battery of physiological, psychomotor and subjective tests before and after alcohol. Each subject received each treatment for 8 days and alcohol was given on day 8. Tests were carried out on days 1 and 4 and on day 8 before and after alcohol. Before alcohol the effects of alpidem on most tests were generally similar, but considerably less marked than those seen with lorazepam. There were some interesting differences between the two drugs in the effects on EEG and memory. In line with the effects seen with other anxiolytic drugs, lorazepam decreased the amplitude of auditory evoked potential. In contrast, alpidem was associated with an increase or a significantly smaller decrease. This suggests that there is no attenuation of input or central processing of the auditory stimuli. Both lorazepam and the higher dose of alpidem (50 mg) reduced the number of words recalled but the lower dose of alpidem (25 mg) had significantly less effect on both immediate and delayed recall. These differences persisted after alcohol. On most of the tests the depressant effects of the drug before alcohol were enhanced after alcohol. However, the depressant effects of alcohol combined with active drug were in general no greater than those with alcohol with placebo, suggesting some degree of cross-tolerance.

Affect↗

Multivariate diallel analysis of ethanol withdrawal symptoms in mice.

Mice from five highly inbred strains were crossed in a complete diallel design. Five hundred and fifty-five offspring were given a liquid diet containing ethanol as their sole food source for 9 days in an attempt to induce dependence. At 6 hr postwithdrawal on day 10, the mice were given a battery of physiological and behavioral measures designed to assess the symptoms of withdrawal. Littermate data were aggregated separately by sex and the aggregate litter mean data was employed in a multivariate extension of Hayman's diallel analysis. Hypothesis sums of squares and cross-products were tested against pooled-within-cell sums of squares and cross-products using Wilk's lambda as a criterion. For each sex, a highly significant additive effect was found, with some evidence for dominance effects as well, suggesting the raw materials are present for successful genetic selection. There was some evidence for dominance effects as well, but no evidence for maternal and other reciprocal effects was found for the set of seven measures. Composites derived from the additive and general dominance hypotheses correlation matrices and error correlation matrix were compared with a composite index currently being used in a multivariate selection study of ethanol dependence. Total ethanol consumption during the exposure period was positively correlated with low dependence between strains, and negatively correlated with measures of low dependence within cells.

Alcohol Drinking↗

Sex hormone-binding globulin and the natural history of breast cancer.

Low concentrations of SHBG in the blood appear to be related to rapid tumour growth rates whereas normal values are associated with slower rates. The inferences drawn from these and other experimental results are as follows: 1. It is no longer necessary to postulate that an abnormal endocrine environment is related to the risk of breast cancer. 2. Variation within the normal range of endocrine function may be sufficient to account for marked differences in the growth rates of transformed cells. 3. It is suggested that women whose tumours arise in an environment characterised by SHBG concentrations at the lower end of the normal range (and, hence, non-SHBG-bound oestradiol levels at the top end of the range) will tend to have an earlier age at diagnosis, a lower frequency of oestrogen-receptor positive tumours and a lower proportion of hormone responsive tumours than women with SHBG levels at the top of the range. 4. Case/control studies in which growth rates are not taken into account may be difficult to interpret.

Adult↗

Use of stapling instruments to aid in the removal of ovarian tumours in mares.

Ovarian granulosa theca cell tumours were removed surgically in 10 mares. Stapling instruments were used to facilitate haemostasis of the ovarian pedicle in five out of 10 cases and as a sole method of haemostasis in the remaining five cases. Postoperative haemorrhage from the ovarian pedicle was suspected in only one case. All cases survived long term follow-up from six months to four years. Results from this series of cases indicate that stapling instruments provide a rapid, easy and efficient means of ligating ovarian pedicles when performing ovariectomy in the mare.

Animals↗

Curettage of subchondral bone cysts in medial femoral condyles of the horse.

Fifty-one horses and unilateral or bilateral femorotibial arthrotomy with medial condyle bone cyst curettage. A total of 60 cyst were treated. Treated horses responded to the surgery three to 12 months postoperatively. In 42 horses lameness was reduced or eliminated, enabling them to return to an remain in their intended function. Of these 42 horses 35 are sound, four of which have not started training, and seven showed partial improvement, two of which had no long term follow up. Of the remaining nine horses, two showed no reduction in lameness and seven were not followed up. Arthrotomy was successful in reducing or eliminating lameness in 82 per cent of all horses and 95 per cent of those where follow-up was possible (42 of 44). Arthrotomy with subchondral bone cyst enucleation and curettage was determined to be a satisfactory treatment in anticipation of a variety of athletic activities.

Animals↗