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Biomedical subjects

H Smith

Publications and source records attributed to H Smith.

At least 379 records · Page 21Linked to original sources
PubMed1986

Dementia in idiopathic Parkinson's disease. Variables associated with its occurrence in 203 patients.

A series of 203 patients with primary Parkinson's disease treated with L-DOPA, with adequate neurological documentation of mental status at serial intervals during their illness, constitutes the study population. Based on the results of the latest neurological examination, slightly less than one-third (29%) had mental impairment assessed as neurologically significant. Of the eleven clinical variables analysed (Cox regression analysis) for potential influence on the occurrence of an organic mental syndrome, four had a statistically significant effect: (1) the stage of disease at initial neurological examination; (2) the occurrence of acute confusional states; (3) the years of Parkinson's prior to L-DOPA; and (4) the total duration of L-DOPA therapy. The pathogenesis of dementia in this subgroup of Parkinson's disease is discussed.

Age Factors↗
PubMed1986

The effects of drugs on leucocyte changes following the injection of antigen into the peritoneal cavities of actively sensitised rats.

The injection of antigen into the peritoneal cavities of actively sensitised rats produced an immediate reaction characterised by an increase in concentrations in the peritoneal fluids, collected 5 min later, of extravasated dye labelled plasma proteins, histamine and slow reacting substance of anaphylaxis (SRS-A). Changes were also produced in the numbers of leucocytes in the blood and peritoneal cavity. 5 min after antigen challenge there was a reduction in the number of cells that could be washed from the peritoneal cavity. 4 h after antigen there was an increase in numbers of neutrophils both in the blood and peritoneal washings and these fell to the levels in control rats at 24 h. 24 h after antigen, and continuing for 72 h, there was an increase in numbers of eosinophils and mononuclear cells in the peritoneal washings. The rats were injected intravenously with sephadex particles to produce a blood eosinophilia at the time of antigen challenge, this increased the numbers of eosinophils migrating into the peritoneal cavity but had no effect on antibody levels, the numbers of other leucocytes or on the immediate reaction. An inhibitor of lipoxygenase and cyclo-oxygenase metabolism of arachidonic acid, phenidone, at 100 mg/kg p.o., inhibited SRS-A release to control levels, in the immediate reaction, but had no effect on the leucocyte changes. The glucocorticosteroid, dexamethasone, at doses of 0.1 and 1 mg/kg p.o., produced little inhibition of SRS-A release but significantly inhibited neutrophil, eosinophil and mononuclear cell infiltration into the peritoneal cavity.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminophylline↗
PubMed1986

Molecular studies of the differential replication at pyrexial temperatures of two influenza viruses differing in virulence for ferrets.

Replication of a virulent clone (7a) of the reassortant influenza virus A/Puerto Rico/8/34-A/England/939/69 (H3N2) in ferret nasal turbinate tissue is less affected than that of an attenuated clone (64d) by temperatures which occur during pyrexia in ferrets. This is a factor which contributes to the difference in virulence of the two clones. The differential replication of the two clones at pyrexial temperatures has been reproduced in allantois-on-shell (egg-bit) cultures, and the synthesis of viral polypeptides and RNA species examined. This virus-host system was chosen because it was more convenient to use than organ cultures but, like the latter, might provide information relevant to the in vivo situation. With this system it was not possible to achieve single cycle replication: the observed effects are cumulative over several (2 to 3) cycles of replication (24 h) and therefore conclusions from them may not be as definitive as those from single cycle conditions. However, in cells infected with clone 64d both A(+) cRNA and polypeptide synthesis were little affected at 40 degrees C but levels were decreased by about 70-80% at 41 degrees C; A(+) cRNA and polypeptide levels were unaffected even at 41 degrees C with clone 7a. These reductions seem insufficient to account for the 10-fold reduction in infectious yields of clone 64d at 40 degrees C or the 100-fold and 10-fold reductions in yields of clones 64d and 7a respectively at 41 degrees C. There was no evidence of increased production of non-infectious virus at elevated temperatures by either clone. Levels of vRNA were considerably reduced at 40 and 41 degrees C for both clones, but the levels were considerably greater at all temperatures in clone 7a-infected cells than in those infected with clone 64d; vRNA levels were higher for clone 7a at 41 degrees C than for clone 64d at 37 degrees C. The different levels of vRNA do not reflect differences in the availability of template A(-) cRNAs since levels of these were similar for both clones at 37 and 40 degrees C and only reduced for clone 64d at 41 degrees C. Although the interpretation of these data is complicated by multiple cycles of replication it appears that limited availability of vRNA could be an important constraint on the ability of clone 64d to replicate at pyrexial temperatures.

Animals↗
PubMed1986

Loss of patients in clinical trials that measure long-term survival following myocardial infarction.

Loss of patients from clinical trials can nullify adequate randomization if the loss is unequally distributed among treatment groups. This study was designed to assess the magnitude of the problem in randomized control trials evaluating long-term therapy for survivors of myocardial infarction (MI). Only 19 of 52 trials reported having an explicit policy on withdrawals in the design stage; only 2 reported blinding the decision for withdrawal and only 7 reported accounting for withdrawals in sizing. In addition, only 16 gave the reader enough information to calculate the effect of withdrawals on trial results. In 2 of these 16 trials a p less than 0.05 result obtained by including withdrawals (intention to treat method) was reduced to p less than 0.05 when withdrawals were excluded. It is evident that many long-term trials do not contain adequate data on withdrawals. Readers of published trials are seldom able to judge whether or not withdrawals might affect the final results.

Clinical Trials as Topic↗
PubMed1986

Studies on 1,2,3-triazoles. 13. (Piperazinylalkoxy) [1]benzopyrano[2,3-d]-1,2,3-triazol-9(1H)-ones with combined H1-antihistamine and mast cell stabilizing properties.

Several N-benzylpiperazino derivatives of [1]benzopyrano[2,3-d]-1,2,3-triazol-9(1H)-one and its 5-methyl homologue have been prepared and evaluated for H1-antihistamine activity on guinea pig ileum. The most potent compounds were also evaluated for their ability to stabilize mast cells in the rat passive peritoneal anaphylaxis (PPA) system and were shown to inhibit histamine release at concentrations below those required to inhibit extravasation, suggesting that this might be relevant to their antianaphylactic activity in this system. The compound tested with the most potent H1-antihistamine activity was 6-[3-[4-(4-chlorobenzyl)-1-piperazinyl]propoxy][1]benzopyrano[2,3- d]-1,2,3-triazol-9(1H)-one, 28, which had a pA2 of 9.1 against histamine on guinea pig ileum, comparable to that of mepyramine, and inhibited histamine release in the rat PPA system with an IC50 value of 5.4 X 10(-6) M.

Anaphylaxis↗
PubMed1986

Erythrocytic sedimentation rate as a measure of clinical activity in inflammatory bowel disease.

To assess the reliability of the erythrocytic sedimentation rate (ESR) as a measure of clinical activity in inflammatory bowel disease, we analyzed the correlations of ESR with a global assessment of clinical activity in 77 patients with varying extents of Crohn's disease and ulcerative colitis. Analysis of all 141 ESR determinations in all 77 patients showed a highly significant correlation between mean ESR and clinical activity score (r = 0.54, p less than 0.001). Analysis of 133 ESR determinations in these 77 patients when their disease activity was either mild, moderate, or severe showed some significant differences among certain disease categories. The highest mean ESRs were in patients with the most extensive colon involvement (Crohn's colitis 40.7 +/- 3.3, universal ulcerative colitis 31.0 +/- 3.9), whereas the lowest mean ESRs were in patients with the most limited disease (ulcerative proctitis and proctosigmoiditis 19.2 +/- 2.1). The rate of increase in ESR with progressively increasing clinical activity from mild to moderate was the same in all disease categories, with the exception of Crohn's disease limited to the small bowel (ileitis or jejunoileitis), in which the ESR was relatively unchanged in a small sample of patients. By the time clinical activity became severe, however, patients in all disease categories manifested similarly high ESRs, with the exception of ulcerative proctitis in which the ESR remained low in the single patient tested.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Sedimentation↗
PubMed1986

Severity of fever in influenza: differential pyrogenicity in ferrets exhibited by H1N1 and H3N2 strains of differing virulence.

Intracardial inoculation of large quantities (200 micrograms viral protein/kg body weight) of infectious or u.v.-inactivated purified influenza viruses into ferrets resulted in a rapid febrile response which was significantly lower for two recently isolated H1N1 viruses, A/USSR/90/77 and A/Fiji/15899/83, than for two virulent clones, 7a and 64c, of the A/Puerto Rico/8/34-A/England/939/69 (H3N2) reassortant virus system. These results, which are in accord with the severity of fever produced by these strains in intranasally infected ferrets, show that influenza virus strains can differ in their capacity to induce fever (probably reflecting a differential capacity to induce endogenous pyrogen from phagocytes) and indicate, since u.v.-inactivated strains are pyrogenic, that this may be due to differences between strains in the nature or amount of certain virion components.

Animals↗
PubMed1986

A determinant of resistance of Neisseria gonorrhoeae to killing by human phagocytes: an outer membrane lipoprotein of about 20 kDa with a high content of glutamic acid.

A protein of about 20 kDa was extracted by sodium cholate (1%, w/v) from outer membranes of a strain of Neisseria gonorrhoeae, BS4 (agar), which is resistant to killing by human phagocytes. When the protein was purified by repeated fractionation on Sephadex G75, contamination with other outer-membrane proteins and lipopolysaccharide was negligible. The protein contained a full complement of amino acids, with high levels of glutamic acid. Carbohydrate, detected by the anthrone method and by sugar and hexosamine analysis, was present, but at very low levels. There was a significant content of fatty acids (about 5.7% of the protein), indicating a lipoprotein. The 20 kDa lipoprotein: (1) neutralized the ability of antiserum against whole organisms of BS4 (agar) to reduce the resistance of this strain to phagocyte killing; (2) evoked in mice an antiserum which reduced this resistance and immunoblotted only with 20 kDa lipoprotein in the cholate extract of outer membranes; and (3) promoted resistance to intracellular killing of an otherwise phagocyte susceptible gonococcal strain (BSSH). This is strong evidence that it is a determinant of gonococcal resistance to phagocyte killing.

Bacterial Outer Membrane Proteins↗
PubMed1986

Lipopolysaccharide alteration is associated with induced resistance of Neisseria gonorrhoeae to killing by human serum.

On SDS-PAGE, solubilized and proteinase K treated preparations of Neisseria gonorrhoeae strain BS4 (agar) showed differences in silver stained lipopolysaccharide (LPS) patterns, before and after induction to resistance to serum killing by incubation for 3 h at 37 degrees C with low Mr fractions from lysates of guinea pig red blood cells. Preparations from the original serum susceptible gonococci and LPS purified from such bacteria showed two components, but the preparations from the serum resistant gonococci were deficient in the higher Mr component. Furthermore, on immunoblotting with fresh human serum (FHS), the two LPS components of the susceptible gonococci reacted strongly with IgM. With preparations from the serum resistant gonococci there was no reaction in the area corresponding to the higher Mr component and a weaker reaction with the component of low Mr. Purified LPS from the susceptible gonococci neutralized the bactericidal activity of FHS against N. gonorrhoeae strain BS4 (agar) probably by reacting with the relevant antibody, since heated FHS was no longer bactericidal when mixed with a source of complement (human placental serum) after prior reaction with the LPS. These neutralization tests coupled with the results of immunoblotting strongly suggest that increased serum resistance is due to the lack of the high Mr LPS moiety.

Blood Bactericidal Activity↗
PubMed1986

A new projective test: the Caine-Marteau-Dympna Test (CMD).

The Caine-Marteau-Dympna (CMD) Test, a new thematic apperception projective test, has acceptable inter-rater reliability. Validity was demonstrated by its ability to differentiate psychiatric in-patients from out-patients and non-patients, and by the relationships found between ratings derived from the test protocols and various questionnaires. These latter provide measures associated with either an inner or outer orientation towards the world. This has implications for many different areas of life, including occupational preference and adjustment, psychiatric symptom formation, psychological treatment expectancies and therapeutic outcome. Thus, the inner oriented individual, who is likely to be responsive to interpretative psychotherapy, tends to produce CMD responses displaying individualistic, abstract themes; a concern with intrapsychic conflict, deficiencies in social interaction and lack of structure; and internal control.

Adult↗
PubMed1986

Effect of drugs on the increase in cell numbers in the peritoneal cavity of the actively sensitised mouse after intraperitoneal challenge with antigen.

The injection of antigen into the peritoneal cavity of actively sensitised mice produced an increase in the number of neutrophils in peritoneal washings collected 4 h later but after 1 day the numbers had returned to control levels. The increase in numbers of mononuclear cells and eosinophils in the peritoneal washings peaked at 2 days and persisted for at least 5 days. Dosing the mice with phenidone, a dual inhibitor of the cyclo-oxygenase and lipoxygenase pathways of arachidonic acid metabolism, potentiated the neutrophil infiltration at 4 h but had no significant effect upon the subsequent mononuclear cell and eosinophil infiltration. In contrast, treatment with the corticosteroid, dexamethasone, reduced the infiltration by all three types of cells, providing further evidence that the corticosteroids can inhibit immune-induced cellular infiltrations by mechanisms other than the inhibition of arachidonic acid metabolism. Isoprenaline, given to the mice before antigen challenge, had no effect on the subsequent neutrophil infiltration, but repeated doses did inhibit the mononuclear cell and eosinophil infiltration measured 4 days later. Aminophylline, disodium cromoglycate and cyproheptadine had no effect upon the cellular changes.

Animals↗
PubMed1986

Airway hyper-reactivity and blood, lung and airway eosinophilia in rats treated with Sephadex particles.

The intravenous injection of Sephadex particles (G200) into rats produced a specific increase in numbers of blood eosinophils peaking 7 days later. A second injection, given on day 14 when the numbers of blood eosinophils had fallen to control levels, produced a dose-dependent increase in numbers, greater than the first, and peaking 5 days later. At this time there was a dose-dependent increase in numbers of eosinophils, but not of other leucocytes, in broncho-alveolar lavage fluids and lung tissue, together with an increase in sensitivity of the rats to the respiratory effect produced by the intravenous injection of 5-hydroxytryptamine.

Animals↗
PubMed1986

Measurement of regional wall motion from biplane contrast ventriculograms: a comparison of the 30 degree right anterior oblique and 60 degree left anterior oblique projections in patients with acute myocardial infarction.

The value of performing biplane vs single plane analysis of regional wall motion from contrast ventriculograms was determined in 102 patients who received thrombolytic therapy and who underwent biplane ventriculography during acute myocardial infarction (n = 67), at follow-up more than 2 weeks later (n = 80), or both (n = 45). Hypokinesis in the infarct region and hyperkinesis in the noninfarct region were measured by the centerline method in the respective artery territories, which were defined from the data of 62 patients with single-vessel disease and were expressed in units of standard deviations from the mean of 32 normal subjects. Hypokinesis was more severe and extended over a longer segment of the left ventricular contour when measured in the right anterior oblique (RAO) projection in thrombosis of the left anterior descending coronary artery (LAD) but more severe and extensive in the left anterior oblique (LAO) projection in circumflex stenosis. Hyperkinesis opposite the LAD or the circumflex was greater in the LAO projection. In patients with thrombosis of the right coronary artery, wall motion abnormalities were similar in the two projections. Thus the evaluation of hypokinesis caused by acute coronary thrombosis and of the effect of therapeutic interventions in salvaging function can be adequately evaluated from single-plane 30 degree RAO ventriculograms, except in the small minority of patients with circumflex thrombosis.

Cineradiography↗
PubMed1986

Altered chromatin in childhood leukaemic lymphoblasts: association with virus-like particles.

An electron microscopic examination was made of masses identified as altered heterochromatin in the cytoplasm of childhood leukaemic lymphoblasts, and their relation to 'virus-like' particles (VLP). The masses were found to occur more frequently in leukaemic lymphoblasts than in normal lymphocytes, but abnormally frequent occurrence was a feature of non T rather than T or B lymphoblasts. Although these masses may be derived by phagocytosis of dead cells or cellular material, a more likely origin is by detachment of altered portions of the containing cell's own nucleus. Such in situ alterations in nuclei were seen in leukaemic lymphoblasts but not in normal lymphocytes. A close relation demonstrated between altered chromatin and VLP might suggest that VLP are a response to the presence of damaged chromatin. However, the occurrence in some VLP of solid cores and budding might make it more likely that VLP are viral, with chromatin damage as a morphologically recognizable cytopathic effect of their activity.

B-Lymphocytes↗
PubMed1986

Acute respiratory distress related to chemotherapy of advanced pulmonary tuberculosis: a study of two cases and review of the literature.

Two patients with non-miliary pulmonary tuberculosis developed a syndrome resembling adult respiratory distress following initiation of drug treatment. They were studied clinically and with a representative range of in vitro and in vivo tests of immune function. Both were alcoholic, malnourished and presented with radiologically widespread, smear-positive disease and lymphocytopenia. One had cutaneous anergy in vivo and profound reduction on mononuclear cell proliferative and interferon responses to tuberculoprotein (PPD) in vitro; the other patient, who died two weeks after starting treatment, had relatively normal values for these measures of cell-mediated immunity. In both cases there was a progressive increase during treatment, in peripheral blood lymphocyte counts, skin reactions and in vitro cellular responses to PPD, and a sudden rise in ESR at the time of their deterioration. We propose that the reactions may represent local manifestations of heightened delayed hypersensitivity, mounted by increasing numbers of 'resuscitated' lymphocytes against immunogenic cell wall substances released from dying tubercle bacilli in patients whose level of cellular immunity is being enhanced as a result of chemotherapy. The likelihood of an acute respiratory reaction during treatment may therefore depend on the bacillary load, the extent of lung disease present, and its severity may be related to the pre-treatment immune status of the patient.

Adult↗
PubMed1985

Extraintestinal cancers in inflammatory bowel disease.

The case histories of 1961 patients with inflammatory bowel disease (IBD), 1227 with Crohn's disease (CD) and 734 with ulcerative colitis (UC), have been studied for the incidence of extraintestinal malignant neoplasms. There were 54 extraintestinal cancers in 51 patients: 28 patients with CD and 23 with UC; 25 men and 26 women. There were 9 breast, 7 skin, 15 reticuloendothelial, 11 genitourinary, 3 lung, 3 perianal, 2 pancreatic islet cell, and several miscellaneous cancers. The number of patient-years from the onset of disease to the last date of follow-up was calculated for men and women with each form of IBD. The observed number (O) of neoplasms was recorded. The expected number (E) of neoplasms was derived from the Department of Health, Education, and Welfare (DHEW) incidence figures for the same neoplasms that occurred in a standard age- and sex-matched population. The O/E ratio was then calculated for each type of cancer as well as for the entire series. There were no statistically significant increases in overall O/E ratios of extraintestinal cancers for either CD (0.76) or UC (1.32). On the other hand, several specific types of cancer did appear to occur with a frequency that was significantly greater than expected. These cancers were classified into two groups. The first group included reticuloendothelial neoplasms. There was an excess of leukemias in UC (P less than 0.005) and an excess of lymphomas in both UC and CD (P less than 0.005). The second group included three squamous cell cancers of the perianal region, an incidence 30 times greater than expected, and two squamous cell cancers of the vagina, also in excess of the expected number. Lymphoma, leukemia, and squamous cell cancers have been reported to occur in excess in immunosuppressed or irradiated patients. It may therefore be speculated that the apparently increased incidence of these neoplasms in the patients with ileitis and colitis might be related to immunologic deficiencies associated with IBD, to the long-term administration of steroids or other immunosuppressive medications that were given to most of the patients or, possibly, to increased exposure to ionizing radiation. The apparently increased incidence of perianal and vaginal cancers of the squamous variety might be a consequence of the combined effects of chronic inflammatory disease involving these areas and primary immune suppression.

Adult↗