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Biomedical subjects

H J Smith

Publications and source records attributed to H J Smith.

At least 127 records · Page 7Linked to original sources
PubMed1989

Novel inhibitors of enkephalin-degrading enzymes. II: N5'-substituted-4-thioxohydantoic acids as aminopeptidase inhibitors.

Some 2-substituted-(2'-aminophenyl)-4-thioxohydantoic acids (o-amino PTC-amino acids) have antinociceptive activity when administered (icv) alone (IC50 = 0.04-0.87 microM/animal) and show a striking prolongation of the antinociceptive action of (D-Ala-2 D-Leu5)-enkephalin (DADL) in combination. The effects are thought to be mediated via opioid receptors since they are naloxone-reversible. Although inhibitors of the enkephalin degrading puromycin-insensitive, bestatin-sensitive aminopeptidase (possibly aminopeptidase M) their action is weak (IC50 = 32 microM leucine, 536 microM, glycine) and they might be considered to have a direct antinociceptive effect on opioid receptors. The titled compounds constitute novel 'lead' compounds for the development of potent aminopeptidase M inhibitors.

Aminopeptidases↗
PubMed1989

Comparative pharmacokinetics of enalapril and lisinopril, alone and with hydralazine.

A single-dose, single-blind, crossover study of vasodilator/angiotensin-converting enzyme (ACE) inhibitor interactions was carried out in 16 volunteers. Enalapril 20 mg and lisinopril 20 mg were administered either alone or in combination with hydralazine 25 mg. Co-administration of hydralazine significantly increased the area under the plasma concentration time curve (AUC) of lisinopril (AUC0-48 h 766.8 +/- 66.3 ng.h/ml (lisinopril) vs 1022.3 +/- 115.3 ng.h/ml (lisinopril + hydralazine)). This did not occur with enalaprilat (AUC 710.1 +/- 51.2 ng.h/ml (enalapril) vs 681.9 +/- 44.9 ng.h/ml (enalapril + hydralazine); mean +/- SEM). Urinary recovery of lisinopril showed a similar trend, but group differences did not achieve statistical significance despite comparable confidence intervals. Although hydralazine had no effect on the bioavailability of enalapril, significantly increased bioavailability was observed with lisinopril. This type of drug interaction is rare. The underlying mechanism is unclear, but may relate to increased absorption of lisinopril.

Adult↗
PubMed1989

Survival of Salmonella typhimurium and Staphylococcus aureus in Genoa salami of varying salt concentration.

Genoa salami prepared using three different salt concentrations (2.0, 2.75 and 3.3%) were inoculated with 2.0 x 10(3) and 1.1 x 10(3) bacteria/g of Salmonella typhimurium and Staphylococcus aureus respectively. Over a period of 74 days samples were taken and analyzed for water activity and pH, counts of S. aureus and presence of Salmonella. After 11 days of dry-curing Salmonella could no longer be detected by preenrichment followed by selective enrichment procedures. Viable S. aureus were still found after 74 days of dry-curing. The results of this study would suggest that water activity and pH measurements are useful in evaluating the safety of dry-cured products.

Animals↗
PubMed1989

Comparative assessment of a double antibody enzyme immunoassay test kit and a triple antibody enzyme immunoassay for the diagnosis of Trichinella spiralis spiralis and Trichinella spiralis nativa infections in swine.

Enzyme immunoassays using the triple antibody enzyme linked immunosorbent assay (ELISA) with both Trichinella spiralis spiralis and T. spiralis nativa excretory-secretory (ES) antigens and a commercial Trichinella spiralis enzyme immunoassay test kit were carried out on sera from pigs that were infected with light, moderate and high doses of infective T. spiralis spiralis and T. spiralis nativa respectively. Seroconversion occurred in all pigs given infective Trichinella larvae although no trichinae were recovered from pigs given T. spiralis nativa larvae and examined between days 92 and 99 postinfection by pepsin digestion. Anti-Trichinella antibodies were detected in pigs infected with T. spiralis spiralis and T. spiralis nativa by ELISA using either the homologous or heterologous ES antigen. The commercial Trichinella spiralis enzyme immunoassay test kit also detected anti-Trichinella antibodies in both the T. spiralis spiralis and T. spiralis nativa infected pigs. The commercial test kit did not appear to be as sensitive as the triple antibody ELISA since it usually took two to three days longer for seroconversion to be detected by the former procedure. Finally seroconversion occurred more rapidly in swine infected with T. spiralis spiralis than with pigs receiving comparable doses of T. spiralis nativa.

Animals↗
PubMed1989

An assessment of residual ovine nematodes on pasture under maritime conditions.

Residual ovine nematode pasture infections were assessed by grazing groups of ewes and their lambs on permanent sheep and cattle pastures and by the use of tracer lambs. Ostertagia spp., Cooperia oncophora, Nematodirus spp., Chabertia ovina and Trichuris spp. eggs and/or larvae survived on pastures overwinter. Second generation Ostertagia larvae were present in greatest numbers on pasture during the latter part of August and early September. The failure of a significant build-up of Cooperia oncophora was attributed to negligible worm egg output of this species in sheep. A build-up of Nematodirus spp. on pasture was not detected in this study.

Animal Feed↗
PubMed1989

[To what extent are oscillometric data of a simple resistor-volume model physically recordable?].

To obtain data on the volume-dependence of the oscillatory parameters of the Siregnost FD 5, we investigated the course of iso-volume and iso-resistance lines in a simple mechanical resistor-volume model in the different coordinate systems, initially in the absence of additional superimposed stationary flow. While the P-psi diagram reveals no uniform course, and no preferential relationship of changes in resistance to P or Ros, or of changes in volume to psi, such a relationship develops on transformation to the Rre-phi and the Rre-X diagram. Rre proves to contain not only the purely resistor component, but also a reactance-proportional or inversely volume-proportional component, which is apparently due to internal friction resulting from volume compression. On the other hand, reactance is almost totally derivable from volume compression. With reference to the theoretical Franken model and others (1981), we discussed the influence of various physical factors on the impedance of a tube segment, and the different volume-dependence of impedance of closed- and open-ended cylindrical tubes. Further work on the theoretical consideration of the forced oscillation technique will examine the influence of additional superimposed stationary flow, which has a considerable effect on the resistor-volume model. Furthermore, the critical value of Reynold's number may be expected to be exceed in the FD 5 reference tube already at low respiratory flow.

Airway Resistance↗
PubMed1989

[Optimizing monofrequent oscillometry].

Against the background of the working hypothesis of the 1-parametric Siregnost FD 5 forced oscillation technique-phase angle psi may be invariant in a clinical reference population-the hypothetical straight Ros-P line is in good agreement with the crowd of extremely nonlinear Rre-P-lines only within narrow limits. Neglecting phase angle measurements it might be useful to insert a known linear resistor into the airway to determine the pertaining Rre-P relation. In spite of selective tuning to the oscillation frequency of 10 Hz there is full sensitivity to stationary flow; alinear stationary flow characteristics of resistors can be readily determined by forced oscillation. There is a marked improvement in the P-psi/Rre-phi-evaluating system with respect both to the symmetry of phase angle and unequivocality of pressure when the reference phase angle alpha is shifted from 81 degrees to 0 degrees. Using digital data acquisition and processing, a flexible evaluation technique with monitor-oriented test management, automatical calculation of secondary values and multidimensional presentation of results on a graphical display is provided, which has proved its worth in experimental and clinical-physiological studies.

Airway Resistance↗
PubMed1989

[Oscillometric differentiation of lung fibrosis and lung emphysema].

In three groups of healthy subjects and patients with pulmonary fibrosis or pulmonary emphysema, the secondary periodical oscillatory phenomena observed under conditions of normal breathing and a slow VC manoeuvre on the Siregnost FD 5 were broken down into a volume- and a flow-synchronous component, as also a third component with no correlation with either volume or flow, and which can be observed in the primary parameters Ros and psi, as also the secondary parameters Rre and phi. While both fibrotic patients and healthy subjects revealed a volume-inverse phase behaviour, patients with pulmonary emphysema revealed a volume-proportional phase behaviour. This difference in volume dependence is explained by the difference in elastic recoil in patients with fibrosis as compared with those suffering from emphysema, and the associated different influence on the filling of the lungs with air and blood.

Adult↗
PubMed1989

Delayed resumption of development of inhibited Cooperia oncophora in a yearling calf.

During a study of larval inhibition, resumption of development of Cooperia oncophora was observed in one calf to occur over a prolonged period of time. This animal had grazed for 14 weeks, was treated with thiabendazole and stabled for eight weeks prior to grazing the same pasture for ten days in late fall. A marked increase in Cooperia egg output started about six months after restabling. Worm egg outputs persisted for about 14 months with counts of up to 1000 eggs per gram during the first eight months of this period followed by a period with low counts of 50 to 150 eggs per gram.

Animals↗
PubMed1989

Experimental trichinosis in sheep.

Trichinella spiralis spiralis infections were established in sheep by administering infective larvae via gavage or feeding infected musculature. Trichinella spiralis nativa infective larvae had a low infectivity for sheep although light infections may be established in some animals with large infective doses. For the most part, sheep were averse to ingesting musculature mixed in a grain ration unless it was camouflaged with molasses. The heaviest infections usually occurred in the masseter muscle. The fact that sheep are averse to ingesting muscle tissue may reduce the likelihood of trichinosis. Anti-Trichinella antibodies to both T: spiralis spiralis and T. spiralis nativa were produced as demonstrated by the enzyme-linked immunosorbent assay. Seroconversion occurred in several sheep challenged with T. spiralis nativa even though larvae were not recovered from the musculature by pepsin-digestion.

Animals↗
PubMed1989

Destruction of Trichinella spiralis spiralis during the preparation of the "dry cured" pork products proscuitto, proscuittini and Genoa salami.

Genoa salami, proscuittini and proscuitto were prepared from pork carcasses that were heavily infected experimentally with Trichinella spiralis spiralis. Genoa salami was prepared with salt concentrations of 2.0%, 2.75% and 3.3%. Proscuitto was prepared by two procedures approved by Agriculture Canada. At various times postpreparation, samples of the various cured products were taken and examined by pepsin digestion and rat bioassay for the presence of viable trichinae. Water activity and pH of the cured meat were also determined. Curing of the various products was shown to destroy the Trichinella larvae. Pepsin digestion revealed that larvae progressively became loosely coiled, uncoiled and more subject to digestion (ghost larvae) during the curing process. Rat bioassay revealed the presence of viable trichinae in the proscuitto prepared using a sodium chloride salt mixture at day 34 but not at day 48 postpreparation. All other bioassays carried out on Genoa salami between 13 and 42 days postpreparation, on proscuittini between days 27 and 69 and on proscuitto between days 34 and 69 were negative for viable trichinae. Under the conditions of this study, preparing Genoa salami with salt concentrations as low as 2% did not appear to affect the destruction of Trichinella larvae.

Animals↗
PubMed1988

Patent foramen ovale in young stroke patients.

The prevalence of patent foramen ovale in patients presenting with non-haemorrhagic stroke or transient ischaemic attacks under the age of 40 years was determined by contrast echocardiography. Studies were performed at rest and with a Valsalva manoeuvre in 40 stroke patients and in an age and sex matched control group. Right-to-left shunting was found in 20 (50%) of the stroke patients and 6 (15%) of the controls (p less than 0.001). Paradoxical embolism through a patent foramen ovale may be an under-recognised cause of stroke in young adults.

Acute Disease↗
PubMed1988

Amelioration of naloxone-precipitated opioid withdrawal symptoms by peripheral administration of the enkephalinase inhibitor acetorphan.

The effects of 60 min pretreatment with the enkephalinase inhibitor acetorphan were assessed on naloxone-precipitated (2.5 mg/kg IP) abstinence in chronically morphinized rats. In addition, the antinociceptive activity of the compound was investigated in mice. Intraperitoneal injection (50 mg/kg) in rats attenuated some aspects of the opioid withdrawal syndrome such as burrowing, wet dog shakes, squeal on touch hostility, tachypnoea, ptosis and rough hair, whereas jumping and escape behaviour were significantly increased in acetorphan-treated animals. No effect was observed on withdrawal hypothermia or acute weight loss. Similarly, chronic dosing with acetorphan after withdrawal produced no significant effect on body weight. Acetorphan (50 mg/kg IP) failed to produce any antinociceptive activity in the mouse tail immersion test, but potentiated the antinociceptive effect of D-Ala2-D-Leu5-enkephalin. These results are discussed in terms of acetorphan crossing the blood-brain barrier before being hydrolysed to thiorphan, thus yielding opioid withdrawal relieving effects.

Amino Acids, Sulfur↗
PubMed1988

Gastric emptying of an indigestible solid in patients with end-stage renal disease on continuous ambulatory peritoneal dialysis.

Using radiopaque markers, we evaluated gastric emptying in 10 male patients with end-stage renal disease on continuous ambulatory peritoneal dialysis and in 15 normal men. Dialysis patients were studied twice, once without peritoneal dialysate in the abdomen (drained) and once with 2 L of dialysate in the abdomen (full). Each normal man and 9 of 10 dialysis patients, when drained, emptied all 10 markers by 6 h after a test meal. In contrast, 5 of the 10 dialysis patients, when full, had delayed emptying of radiopaque markers. Thus, continuous ambulatory dialysis may delay gastric emptying of indigestible solids.

Adult↗
PubMed1988

Aminoglutethimide and ketoconazole: historical perspectives and future prospects.

Aminoglutethimide and ketoconazole, although originally developed as an anticonvulsant and antifungal agent respectively, have both been used to suppress steroid biosynthesis in patients with hormone-sensitive cancer. Aminoglutethimide inhibits several enzymes involved in the synthesis of corticosteroids as well as the aromatase enzyme which converts androgens to oestrogens. About one third of patients with breast cancer show objective improvement with aminoglutethimide, and it may also be of use in the treatment of adrenal carcinoma. However, its toxicity, and the need for concomitant cortisol replacement, severely limit its usefulness. Ketoconazole also inhibits several steroidogenic enzymes, notably C17,20-lyase, and has been used to treat carcinoma of the prostate. Again however, its toxicity and limited efficacy limit its value, although it may be useful in the treatment of certain endocrine conditions such as precocious puberty. Several aromatase inhibitors similar in structure to aminoglutethimide have been developed in an attempt to create more selective and efficient inhibitors. Some of these compounds have been tested in animals but none have as yet been subjected to clinical trials. Attempts to produce imidazole inhibitors of steroidogenesis are less advanced, although one compound (CGS 16949A) has been reported to be a more selective and potent aromatase inhibitor than aminoglutethimide. Selective and effective compounds could be of great value in the treatment of hormone-sensitive carcinoma.

Adrenal Gland Neoplasms↗
PubMed1988

What happens to patients after upper and lower gastrointestinal tract barium studies?

We investigated the occurrence of new constipation, diarrhea, nausea, vomiting, visible blood in stool, abdominal pain, black stools, belching, and flatus in 324 outpatients following upper or lower gastrointestinal tract barium procedures. We also evaluated the roles of age, sex, patient mobility, and types of barium enema (single- or double-contrast). At least one new symptom was reported after 51% of all examinations. Constipation was the most frequently reported single symptom after barium meal or small bowel examinations. Fifty percent of all constipation occurred following upper gastrointestinal examinations. Abdominal pain was common in patients of the seventh decade, especially following barium enema. Nausea typically followed barium swallow or upper gastrointestinal series. Belching and passage of flatus were the most frequently reported symptoms after barium enema, both single- and double-contrast. No significant relationship between the frequency of symptoms and patient age, sex, or the type of barium enema was established.

Adult↗