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Biomedical subjects

H Smith

Publications and source records attributed to H Smith.

At least 307 records · Page 17Linked to original sources

The effects of drugs on Sephadex-induced eosinophilia and lung hyper-responsiveness in the rat.

1. Rats given an intravenous injection of Sephadex particles (0.5 mg of G200 in 1 ml of saline) on days 0, 2 and 5 had a blood eosinophilia which was maximal on day 7. 2. On day 7, broncho-alveolar lavage (BAL) fluids taken from the rats contained an increased number of eosinophils and fewer mononuclear cells but there was no change in the small number of neutrophils. In addition the rats were hyper-sensitive to the increase in resistance to artificial respiration produced by 5-hydroxytryptamine (5-HT), given intravenously, with a shift to the left of the log dose-response curve. Lung parenchymal strips, taken from the rats on days 6, 7 and 8, were hyper-reactive to 5-HT with an increase in slope of the log dose-response curve. 3. Compounds with a wide variety of activities were evaluated for their effects on the blood eosinophilia on day 7 when given before each injection of Sephadex. The eosinophilia was reduced by glucocorticosteroids, beta-adrenoceptor agonists, aminophylline, dapsone and phenidone. 4. Dexamethasone, isoprenaline, dapsone and phenidone at doses that reduced the blood eosinophilia also reduced the changes in number of leucocytes in the BAL fluids and the hyper-responsiveness to 5-HT in vivo and in vitro, except that the effects of dapsone on the hyper-sensitivity to 5-HT in vivo did not reach significance. Aminophylline was the least effective of the drugs at reducing the blood eosinophilia and its effects on the other changes did not reach significance. Sodium cromoglycate reduced the BAL eosinophilia but had no effect on the other changes produced by Sephadex. 5. The correlation coefficients between blood eosinophil numbers and reactivity to 5-HT in vitro and sensitivity in vivo were r = 0.76, (n = 88; P < 0.001) and r = 0.53, (n = 61; P < 0.001) respectively. 6. Doses of dexamethasone, isoprenaline, dapsone and phenidone that reduced the blood eosinophilia when given before each injection of Sephadex were inactive when given up to 8 h after the Sephadex. 7. These data show an association between blood eosinophilia and hyper-responsiveness of the lung. The blood eosinophilia in the rats was triggered within the first few hours of injecting the Sephadex and drugs have been identified which inhibit this trigger.

Animals↗

Non-traumatic chest pain in young adults: a medical audit.

Four hundred consecutive young patients who attended an accident and emergency department with non-traumatic chest pain as their primary complaint were reviewed. They represented 0.7% of total new attendances. Most were self-referrals, but ambulance transport was requested for over 25%. The majority of investigations (mainly chest radiography and electrocardiography) performed in this group of patients were normal; however, almost one in six investigations was judged to be abnormal. Although this group of patients is at low risk for serious cardiorespiratory disease, a small but significant number of underlying (mainly non-cardiac) disorders was found and 22.5% (90) required in-patient admission. In contrast, almost one-fifth of patients received no specific diagnosis, while almost 40% were deemed to require no follow-up.

Adolescent↗

Effects of induced anemia in normal and autoimmune mice.

Normal and autoimmune mice were studied with regard to signals eliciting differentiation and division of bone marrow stem cells. The erythropoiesis induced by anemia following serial bleedings was analyzed in young autoimmune New Zealand Black (NZB) mice and non-autoimmune strains. No difference in the response to the stimulus created by anemia was noted between the strains. After serial bleedings as a stimulus to stem cell proliferation, a five-fold increase in numbers of proliferating spleen cells occurred in both NZB and DBA/2 strains; the increased proliferating spleen cells in both strains were non-lymphoid. The bled animals had decreased percentages of B cells. The production of autoantibodies was not significantly altered by the experimentally induced anemia. In contrast, anti-immunoglobulin activation of resting B cells was increased in response to anemia. Young mice which had experimentally induced anemia had several characteristics in common with old autoimmune NZB mice. Both old NZB mice and young anemic animals had splenomegaly, increased numbers of proliferating spleen cells, decrease in splenic Ly 5+ cells and an increase in splenic colony forming units (CFUs). The anemic normal strains of animals lacked other characteristics of old NZB mice such as hyperimmunoglobulinemia or autoantibody production or elevated CD5+B cell numbers. This work supports the concept that the increase in spleen cell number, proliferating spleen cells, CFUs and the increased percentages of non-Ly-5 cells (which include erythroid precursors) found in the spleens of old NZB mice may in part result from their autoimmune hemolytic anemia.

Anemia↗

Mumps.

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Child, Preschool↗

Angioplasty of persistent "stump" of internal carotid artery.

An unusual sequela of internal carotid artery occlusion is the development of cerebral ischemia caused by emboli in a residual stump of the internal carotid artery. Five patients with transient ischemic attacks due to this condition are presented. Stump angioplasty was employed successfully in each case.

Aged↗

Neonatal thymectomy results in a repertoire enriched in T cells deleted in adult thymus.

In B6AF1 mice, T lymphocytes that use the V beta 11-positive (and not V beta 6-positive or V beta 8-positive) segment in their receptor for antigen are greatly reduced in the thymus and peripheral lymphoid tissues, most likely as a result of clonal deletion. The relative number of V beta 11-positive cells in adult lymph nodes was ten times as high in B6AF1 mice thymectomized 1 to 4 days after birth as in normal mice. Moreover, for the first 10 days of life of B6AF1 mice, mature V beta 11-positive T cells were readily detected in the thymus and spleen. Thus neonatal thymectomy results in the maintenance of the receptor repertoire of early postnatal life, and this correlates with the subsequent development of organ-specific autoimmune diseases.

Animals↗

Public without profit.

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Community Mental Health Services↗

Failure to predict intraoperative myocardial ischaemia in patients with coronary artery disease.

Patients with severe coronary artery disease were studied to determine if the preoperative assessment or intraoperative haemodynamic monitoring could predict the occurrence of myocardial ischaemia. Thirty-eight patients undergoing coronary artery surgery who had normal electrocardiograms before induction of anaesthesia were included. Leads II and CS5 were recorded on a Holter monitor and radial arterial and pulmonary artery catheters were used to measure haemodynamic variables. Eight patients developed ST-segment changes greater than or equal to 0.1 mV before sternotomy. Preoperative factors could not be used to predict which patients would develop ST-segment changes. In all 38 patients haemodynamic determinants of myocardial oxygen supply and demand remained within an optimal range despite evidence of ischaemia in eight. This syndrome of ECG changes in the absence of tachycardia and hypertension resembles the syndrome of silent ischaemia documented in awake patients. Our findings suggest that myocardial ischaemia may be caused by decreases in coronary blood flow not associated with changes in haemodynamic variables.

Adult↗

Routine excretory urography in follow-up of superficial transitional cell carcinoma of bladder.

To determine cost-effective guidelines for the follow-up of patients with superficial transitional cell carcinoma of the bladder (STCCAB), we reviewed clinical histories, pathology reports, and intravenous pyelography results in 84 patients with Stage Ta or T1 disease. In 4 patients (4.8%) subsequent upper tract tumors developed with an average interval from initial presentation to the development of upper tract disease of 5.4 years. Three of these patients were treated successfully. We recommend upper tract surveillance in this group of patients with intravenous pyelography at diagnosis and every twenty-four months thereafter, or selection of those patients who are at high risk for development of upper tract disease (i.e., ureteral-vesical reflux) with voiding cystourethrography one month following each resection of tumors near a ureteral orifice. Refluxing patients should then either undergo surgical repair of their reflux or yearly pyelography.

Carcinoma, Transitional Cell↗

Sialylation of lipopolysaccharide and loss of absorption of bactericidal antibody during conversion of gonococci to serum resistance by cytidine 5'-monophospho-N-acetyl neuraminic acid.

Changes in lipopolysaccharide (LPS) which occur when serum susceptible gonococci are converted to resistance by incubation with cytidine 5'-monophospho-N-acetyl neuraminic acid (CMP-NANA) have been investigated. Transfer of radioactivity to bacterial LPS from CMP-NANA labelled with 14C in the NANA moiety was detected by fluorography following lysis, proteinase K digestion and SDS-PAGE. Incorporation of radioactivity was inhibited by cytidine 5'-monophosphate (CMP). Both the radioactivity of the LPS and the resistance of gonococci to fresh human serum were largely lost after incubation with neuraminidase. No evidence was obtained to suggest that CMP-NANA is an inducer of new protein synthesis as well as a substrate for the sialylation of LPS. Little radioactivity was incorporated into components other than LPS. Sialylated, serum resistant gonococci were less able than serum susceptible gonococci to absorb the bactericidal activity of fresh human serum. Hence, we conclude that serum resistance conferred on gonococci by CMP-NANA is due to transfer of sialyl groups to surface LPS sites and this inhibits their reaction with bactericidal antibody in human serum.

Antibodies, Bacterial↗

Eosinophils and the granulomatous reaction in rats injected with Sephadex particles.

Treatment of rats with a single intravenous injection of 0.5 mg Sephadex G200 caused a blood and lung eosinophilia first detected on day 2, peaking on day 7 and declining to control levels by days 28 and 84 respectively. The increase in eosinophil numbers was accompanied by the development of pulmonary granulomas reaching their maximum size 2-7 days after Sephadex treatment and persisting for 84 days. This reaction was characterised by an early infiltration with polymorphonuclear leucocytes followed by increased numbers of mononuclear cells. Few eosinophils were associated with the Sephadex particles but large numbers were found in the adventitial layers of the lung. There was an increase in the size of the granulomas in rats given Sephadex on days 0, 2 and 5 compared with the response in rats given a single injection of Sephadex. The inflammation was more intense and more eosinophils were detected in the blood, alveolar tissues and adventitia. The effects of drugs given before each injection of Sephadex were evaluated. Dexamethasone, dapsone and isoprenaline reduced the blood and tissue eosinophilia but had no effect on the number of granulomas. Dexamethasone and dapsone, but not isoprenaline caused a slight reduction in the size of the inflammatory reaction around the Sephadex particles. Indomethacin had no effect on the granuloma formation, nor did it reduce the eosinophilia. Isoprenaline and indomethacin increased the proportion of eosinophils associated with the granuloma, although in neither instance did this reach significance.

Animals↗

Psychiatric profile of the noncompliant geriatric patient in the community.

A pharmacist collected data in an active geriatric outpatient program on 140 patients admitted consecutively over a 1-year period. Compliance was monitored by patient statement, pill counting, and daily written record-keeping of all medications with the help of a pocket diary provided in the program. Weekly pharmacist counseling sessions were then initiated for all patients. After four compliance sessions, two subgroups of patients were identified: 120 compliant patients and 20 patients showing persistent 50% noncompliance. Patients were interviewed by a psychiatrist to develop a profile of the noncompliant patient. This profile may be useful in identifying other noncompliant geriatric patients. Early recognition of this special group of patients in need of directed counseling may help reduce medical misjudgment in prescribing for the frail elderly population.

Aged↗

Mechanism of immunity to influenza: maternal and passive neonatal protection following immunization of adult ferrets with a live vaccinia-influenza virus haemagglutinin recombinant but not with recombinants containing other influenza virus proteins.

Neonatal ferrets are protected against infection with influenza virus by milk-derived anti-influenza virus IgG after suckling on an immune mother. Live vaccines protect better than killed vaccines despite their stimulation of lower maternal haemagglutination-inhibiting antibody levels. This suggests that antibody to virus proteins other than the haemagglutinin may also be involved. To investigate this, adult ferrets were immunized intradermally with live vaccinia-influenza virus recombinants each expressing one of the 10 influenza virus polypeptides. Adult ferrets immunized with a recombinant expressing the H3 haemagglutinin were completely protected, and also passively protected their offspring, against a live challenge with clone 7a of the reassortant influenza virus A/Puerto Rico/8/34-A/England/939/69 (H3N2), immunity being mediated by IgG antibody. However, ferrets immunized similarly with recombinants expressing the H1 haemagglutinin, neuraminidase (N1 or N2), polymerases (PB1, PB2 or PAC), matrix protein (M1 or M2), nucleoprotein (NP) or non-structural proteins (NS1 or NS2) were completely susceptible to the influenza virus.

Animals↗