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Biomedical subjects

C M Smith

Publications and source records attributed to C M Smith.

At least 181 records · Page 10Linked to original sources
PubMed1990

Medication compliance and substance abuse among schizophrenic patients.

The relationship between use of alcohol and street drugs and compliance with prescribed medication before admission to an acute psychiatric inpatient setting was studied in 42 schizophrenic patients, more than half of whom had a history of alcohol abuse or dependence. Most patients, even those without a history of alcohol abuse, admitted to drinking alcohol in the month before admission. Alcohol abusers drank significantly more often and drank significantly greater quantities than nonabusers. The majority of patients were noncompliant with prescribed medication before admission, and most of these patients specifically reported being noncompliant when drinking alcoholic beverages.

Adult↗
PubMed1990

Effects of ibuprofen on doxorubicin toxicity.

The cardiotoxicity of doxorubicin (Adriamycin) restricts the usefulness of this potent antineoplastic agent. Since the cardiotoxic mechanism (generation of oxygen radicals) is distinct from the primary chemotherapeutic mechanism (intercalation of DNA) efforts to decrease the cardiotoxic potential are warranted. Three nonsteroidal anti-inflammatory drugs, aspirin, ibuprofen and sulindac were tested for effects upon survival in the chronic mouse model of doxorubicin cardiotoxicity. The original premise in these studies was that nonsteroidal anti-inflammatory drugs, through inhibition of cyclooxygenase activity, would suppress the attending generation of superoxide anions and reduce a synergism with oxygen radicals produced by redox cycling of doxorubicin. Acetaminophen was included in the studies as an example of an analgesic agent which lacks anti-inflammatory efficacy. Doxorubicin (4 mg/kg) was injected intraperitoneally at 3-week intervals in Swiss-Webster mice. The interventions were administered in equianalgesic doses in the drinking water for 2 days before and 3 days after the doxorubicin injections. Ibuprofen (1 mg/ml) increased survival from 16.0%, for doxorubicin alone, to 63.6% (p less than 10(-6); none of the other interventions demonstrated protection. Ibuprofen-treated mice also lost less weight during the treatment period than all other doxorubicin injected animals (p less than 10(-6]. Since the three antiinflammatory drugs tested are all cyclooxygenase inhibitors, but only ibuprofen inhibits neutrophil infiltration, the latter mechanism is proposed as the primary basis for the observed protection.

Acetaminophen↗
PubMed1990

Inhalational challenge using hypertonic saline in asthmatic subjects: a comparison with responses to hyperpnoea, methacholine and water.

Non-isotonic aerosols are being used increasingly for bronchial provocation testing in patients with asthma. We investigated changes in forced expiratory volume in one second (FEV1) in response to inhaling ultrasonically nebulized 4.5% saline in 10 normal subjects and 68 subjects with asthma. A comparison of the sensitivity to this challenge was made with sensitivity to challenge with methacholine, water, exercise and eucapnic voluntary hyperventilation (EVH). In normal subjects the FEV1 was reduced by 6 +/- 2% (mean +/- SD) after inhalation of 33 ml of aerosol. Eighty four percent of the asthmatic subjects exhibited a fall in FEV1 of greater than 20% after inhaling 4.5% saline. The provoking dose (geometric mean +/- 95% confidence limits) of saline to induce a 20% fall (PD20) was 2.05 ml (1.34-4.48). The sensitivity to inhaled 4.5% saline was significantly related (p less than 0.001) with responsiveness to methacholine, exercise and EVH, but not to water. Those patients recording a PD20 to 4.5% saline had a PD20 to methacholine less than 2 mumol which is a response consistent with moderate to severe bronchial hyperresponsiveness.

Adult↗
PubMed1990

High frequency of elongated platelet forms in guinea pig blood: ultrastructure and resistance to micropipette aspiration.

Elongated cylindric and beaded platelet forms are infrequently observed in the circulation, and have been termed "proplatelets," as presumed precursors to discoid platelets. Some 15% of the blood platelets obtained from the guinea pig by cardiac puncture were elongated forms (1/5 beaded and 4/5 cylindric) under conditions of steady state thrombopoiesis, thus providing an opportunity to contrast the structure and deformability of platelets of potential graded maturation. Ultrastructural studies were consistent with graded maturation. Longitudinal bundles of microtubules in cylindric platelets gave way to the appearance of basket-weave arrays in the nodal thickenings of beaded forms, and, finally, to circumferential coils in a portion of the discoid platelets. Individual platelets were aspirated into micropipettes of 0.8 microns internal diameter by application of incremental pressure up to a maximum pressure of 10 cm water. None of the guinea pig platelets fragmented into smaller forms even when aspiration was performed under physiologic environmental conditions. All the guinea pig platelets passed through the micropipette in aspiration studies performed under conditions minimizing platelet activation and adhesion. Elongated platelets aspirated at the very ends of the cells passed through the pipette at lower pressure than discoid forms, whereas elongated platelets aspirated along the length of the cell were more resistant to deformation and cell passage than were discoid platelets. Beaded forms were similar in deformability to cylindric platelets at low aspiration pressure but were more resistant to deformation at high pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Micropipette aspiration of guinea pig megakaryocytes: absence of fragmentation and dependence on maturation stage.

Platelet release has been alternatively viewed as a fragmentation of platelet territories demarcated within the cytoplasm of mature megakaryocytes or as a later event involving segmentation of proplatelet pseudopodia extended from the cell. The mechanical constraints on platelet release were evaluated by measuring the resistance of guinea pig megakaryocytes to aspiration into micropipettes of similar diameter to the width of naturally forming proplatelet projections. Application of increasing negative pressure to the surface of the cells resulted in progressively longer extensions being drawn into the pipette until maximal extension lengths were reached. None of the passively aspirated cytoplasmic extensions fragmented off the cells even at the highest aspiration pressure under physiologic study conditions. The longest extensions were aspirated from megakaryocytes of the most advanced maturation stage, and a proportion of the mature cells yielded very long extensions over 50 mu and up to 150 mu in length. Surprisingly, the ease of aspiration did not correlate to cell size during any stage of maturation. The mechanical behavior of guinea pig megakaryocytes indicates a large availability of surface for extension in mature cells ideal for active proplatelet projection. The lack of mechanical fragility suggests that platelet release is a very late maturational event not yet initiated in the "mature" megakaryocytes available for study from marrow harvests.

Animals↗
PubMed1989

Evaluation of the yield stress of normal blood as a function of fibrinogen concentration and hematocrit.

The yield stress is a sensitive index of blood fluidity at low shear. Seven healthy adults were studied at hematocrits varying between 40 and 80% and fibrinogen concentrations from 0.0 to 0.935 g/dl. Multivariable analysis was used to determine the functional dependence of yield stress on hematocrit and fibrinogen level. The major findings from this analysis include a decreasing effect of fibrinogen at high concentrations (saturation effect), a relative insensitivity of yield stress to fibrinogen at low concentration (threshold effect), and a strong interaction between the effects of hematocrit and fibrinogen concentration on yield stress. Our results give the normal range of yield stress for a given value of fibrinogen and hematocrit and can be used to predict the effect of reductions in hematocrit or fibrinogen on the yield stress of normal blood.

Adult↗
PubMed1989

Inhalation provocation tests using nonisotonic aerosols.

The measurement of bronchial hyperresponsiveness with inhaled aerosols is now accepted as an objective measurement of the severity of asthma. The most commonly used agents administered as aerosols are methacholine and histamine, which are believed to cause airways to narrow by contracting bronchial smooth muscle via specific receptors. Patients with asthma may also have an attack provoked by inhaling aerosols that increase or decrease the osmolarity of the fluid lining the airways. There is evidence to suggest that a change in the osmolarity of the airways causes the release of mediators from inflammatory cells in the airways. Thus, inhalational challenge with nonisotonic aerosols, such as water and hyperosmolar saline, may be useful to assess bronchial hyperresponsiveness to endogenously released mediators. Described in this article are some of the techniques used to challenge with nonisotonic aerosols, and airway responses are discussed in relation to responses obtained with other bronchial provocation tests. The mechanisms whereby these aerosols cause airways to narrow are considered, and the clinical implications of identifying responsiveness to these aerosols are discussed. Specific recommendations are made with respect to equipment, technique, and choice of aerosol.

Aerosols↗
PubMed1989

Non-isotopic DNA probes for the identification of subgingival microorganisms.

The purpose of the present investigation was to examine the potential of non-isotopic DNA probes to identify pure cultures in predominant cultivable microbiota studies. Non-isotopic DNA probes to 7 subgingival species were prepared by 2 methods. In the first, biotin-labelled probes were prepared by nick translation. In the second, single-stranded DNA was covalently linked to horseradish peroxidase via polyethyleneimine. The relative sensitivities and specificities of these probes were tested against pure cultures of a range of subgingival species. Aliquots of broth cultures were standardized by optical densities, placed on nitrocellulose or Whatman 541 filters and then treated to lyse the cells, denature and fix DNA to the filter. Using a streptavidin-alkaline phosphatase detection system, 10(4)-10(5) cells were detected by homologous biotin-labelled probes. Horseradish peroxidase-labelled probes were approximately one order of magnitude less sensitive. Non-specific reactions with unrelated species, displayed by both biotin- and horseradish peroxidase-labelled probes, were eliminated by treatment of filters with proteinase K and organic solvents. Cross-reactions between closely related species could be discriminated by comparing reaction intensities of the test strains with probes to the each of the cross-reacting species involved. Thus, nonisotopic DNA probes could be used for the rapid identification of subgingival isolates. The technique could also be used for the recognition and grouping of strains of unknown species. A probe made to the strain of an unknown species may be used to rapidly screen hundred of unknown isolates for related strains.

Biotin↗
PubMed1989

Rapid method for the purification of DNA from subgingival microorganisms.

A method is described which facilitates the rapid purification of high molecular weight chromosomal DNA from gram positive and gram negative bacteria grown on solid media. A total of 32 reference strains and fresh isolates were examined in this study. The purification procedure involved lysis of cells with SDS in the presence of proteinase K, followed by removal of cellular polysaccharides and proteins with hexadecyltrimethyl ammonium bromide (CTAB) and phenol:chloroform:isoamyl alcohol. Preparations were incubated with RNase and, after removal of the enzyme, DNA was precipitated with ethanol. Several hundred micrograms of DNA could be prepared within 5 h from cells grown on 1-2 agar plates. None of the final preparations contained RNA; protein was detected in 12/32 preparations. The resultant DNA proved suitable for restriction enzyme digestion and biotin-labelling by a random primer technique. DNA probes constructed from these preparations were capable of detecting 100 pg of homologous target DNA fixed to nitrocellulose. Cross reactions between closely related species displayed weaker signal intensities than, and, thus, were easily distinguished from, true positive reactions between homologous species. DNA obtained by this procedure may also be suitable for DNA-DNA homology studies, recombinant DNA experiments and molecular fingerprinting.

Bacteria↗
PubMed1989

Identification of a umuDC locus in Salmonella typhimurium LT2.

The umuDC operon of Escherichia coli is required for efficient mutagenesis by UV light and many other DNA-damaging agents. The existence of a umuDC analog in Salmonella typhimurium has been questioned. With DNA probes to the E. coli umuD and umuC genes, we detected, by Southern blot hybridization, sequences similar to both of these genes in S. typhimurium LT2. We also confirmed that the presence of cloned E. coli umuD enhances the UV mutability and resistance of S. typhimurium. Our data strongly suggest that S. typhimurium contains a functional umuDC operon.

Base Sequence↗
PubMed1989

Characterization of the major DNA repair methyltransferase activity in unadapted Escherichia coli and identification of a similar activity in Salmonella typhimurium.

Escherichia coli has two DNA repair methyltransferases (MTases): the 39-kilodalton (kDa) Ada protein, which can undergo proteolysis to an active 19-kDa fragment, and the 19-kDa DNA MTase II. We characterized DNA MTase II in cell extracts of an ada deletion mutant and compared it with the purified 19-kDa Ada fragment. Like Ada, DNA MTase II repaired O6-methylguanine (O6MeG) lesions via transfer of the methyl group from DNA to a cysteine residue in the MTase. Substrate competition experiments indicated that DNA MTase II repaired O4-methylthymine lesions by transfer of the methyl group to the same active site within the DNA MTase II molecule. The repair kinetics of DNA MTase II were similar to those of Ada; both repaired O6MeG in double-stranded DNA much more efficiently than O6MeG in single-stranded DNA. Chronic pretreatment of ada deletion mutants with sublethal (adapting) levels of two alkylating agents resulted in the depletion of DNA MTase II. Thus, unlike Ada, DNA MTase II did not appear to be induced in response to chronic DNA alkylation at least in this ada deletion strain. DNA MTase II was much more heat labile than Ada. Heat lability studies indicated that more than 95% of the MTase in unadapted E. coli was DNA MTase II. We discuss the possible implications of these results for the mechanism of induction of the adaptive response. A similarly active 19-kDa O6MeG-O4-methylthymine DNA MTase was identified in Salmonella typhimurium.

Cysteine↗
PubMed1989

An investigation of the effects of heat and water exchange in the recovery period after exercise in children with asthma.

It has been reported that asthma provoked by breathing subfreezing air during exercise is enhanced when air at BTPS is inhaled in the recovery period (1). It was concluded that the rate of airway rewarming is an important event in asthma provoked by exercise. It is also possible, however, that the enhanced response was due to hypo-osmolarity caused by condensation of water from inspired air at BTPS on the cooled mucosa. We examined, in a group of boys with asthma, the response to rapid rewarming of the airways after exercise, with and without the potential for condensation. On two test days, two exercise tests were performed 4 h apart on a cycle ergometer. On Day 1 (n = 17), the inspired air during exercise was -5 degrees C, dry. During recovery, the air was either -5 degrees C, dry or 50 degrees C, 23 mg H2O/L. On Day 2 (n = 11), the inspired air during exercise was -15 degrees C, dry, and during recovery was either -15 degrees C, dry or at BTPS. We did not find enhancement of the response with either condition designed to cause rapid airway rewarming. On Day 1 the mean (+/- 1 SD) percent fall in FEV1 was 23 +/- 22 (-5 degrees C, dry) and 24 +/- 21 (50 degrees C, 23 mg H2O/L) (r = 0.92), and on Day 2 it was 19 +/- 17 (-15 degrees C, dry) and 18 +/- 17 (BTPS) (r = 0.96).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

Mental hospital depopulation in Canada: patient perspectives.

This paper reviews briefly the history of mental health depopulation in Canada over the past 30 years. The term "deinstitutionalization" is often used but is unsatisfactory. Using an exploratory, qualitative, methodological approach, data were collected on the problems encountered by a disproportionate, stratified random sample of 139 formerly institutionalized patients living in various geographical locales in Eastern Canada. Adopting a symbolic interactionist theoretical approach, this study, in an effort to fill a neglect in the literature, attempted to discover what the everyday world(s) of Canadian ex-mental patients was really like. Problems encountered related to stigma, poor housing, lack of back living skills, poverty, unemployment and aftercare. Quotations from patients are provided to illustrate such themes. The findings are discussed.

Activities of Daily Living↗
PubMed1989

Management for interstitial lung disease. State of the art.

A survey of 109 pulmonary physicians representing both private practice and academic medicine was conducted to learn their practice of management and treatment of interstitial lung disease. Of the 109, 25 (23 percent) responded. Twenty-two of 23 routinely obtain tissue diagnosis. The routine method was transbronchial biopsy by 15 physicians vs open lung biopsy by seven. Few (n = 5) use BAL cell analysis. The majority of clinicians used two to four criteria to initiate therapy. Physiology laboratory data were the predominant criteria used by the majority of physicians and also were most commonly used to monitor a patient's course over time. Prednisone was the drug of choice for therapy. Immunosuppressive therapy was not used until failure of steroid therapy was observed. There was little consistency in the diagnostic procedures applied, criteria for the decision to treat, the drugs used to treat, or methods for monitoring.

Azathioprine↗
PubMed1989

A comparison between the airway response to isocapnic hyperventilation and hypertonic saline in subjects with asthma.

We compared the response to isocapnic hyperventilation (ISH), where both cooling and drying of the mucosa occur, with the response to inhaling aerosols of hypertonic saline (HS), where airway osmolarity increases without airway cooling. We studied nine subjects on two days. For ISH, subjects ventilated at 70% of their estimated maximum voluntary ventilation (MVV). For HS, they inhaled aerosols of 2.7, 3.6, or 4.5% saline. The concentration that was used depended on the rate of ventilation during ISH. For both challenges the stimulus was given for one minute. Forced expiratory volume in one second (FEV1) was measured once between each minute, and the challenge ceased when the FEV1 did not change for two successive minutes. A plateau in FEV1 occurred after 8.1 +/- 2.4 (mean +/- 1 SD) min of ISH, and 8.3 +/- 2.4 min of HS. The lowest FEV1 (% predicted) after ISH was 45 +/- 16% and after HS was 51 +/- 18% (r = 0.93). However, the maximum responses occurred after the final challenge and were not the same as the plateau. For HS, the plateau represented 89 +/- 11% of the maximum response which developed within one minute of the final challenge. For ISH, the plateau was only 56 +/- 26% of the maximum response, which developed within 5.2 +/- 2.9 min after challenge. The similarities in the response to these challenges are consistent with the hypothesis that ISH induces asthma via hyperosmolarity. The delayed response to ISH suggests that cooling may delay the response to hyperosmolarity.

Adolescent↗
PubMed1989

Viscoelastic properties of the oxygenated sickle erythrocyte membrane.

Although most apparent in permanently misshapen irreversibly sickled erythrocytes (ISC), biochemical and structural alterations are present in the majority of sickle cell membranes. The relationship of membrane rigidity to cell shape and its dependence upon the internal hemoglobin cytosol are not clarified. We therefore examined the frequency dependent viscoelasticity of oxygenated, packed sickle red cell and ghost suspensions and hemoglobin solutions prepared from density gradient separated ISC and reversibly sickled cell (RSC) fractions. Low amplitude, oscillatory shear was applied in a Weissenberg cone and plate viscometer and the resultant viscoelastic signals provided a dynamic viscosity (eta') and elastic storage modulus (G') which varied with frequency of deformation. The viscoelastic response of the cell and ghost suspensions reflected the material properties of the membrane over most of the frequency range tested. Sickle erythrocyte, red ghost, and white ghost suspensions demonstrated greater viscocoelasticity than comparable normal suspensions. The viscoelastic magnitude of ISC was several-fold greater than normal, with little variation of viscoelasticity with frequency. RSC samples which were characterized by normal shape, size, and internal hemoglobin concentration were also significantly harder than normal, although similar in frequency dependence. Red ghosts prepared from ISC manifested 80% of the viscoelasticity of intact ISC despite diminution of the internal hemoglobin concentration by 90%. Under conditions of low amplitude shear, the behavior of the RSC membrane is compatible with a cytoskeleton possessing an increased number of molecular associations. The mechanical stability of the ISC membrane is related to a substantial, intrinsic reorganization of the cytoskeleton.

Adult↗