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Biomedical subjects

D J Cotton

Publications and source records attributed to D J Cotton.

At least 19 recordsLinked to original sources
PubMed1992

Computer-based interview for screening blood donors for risk of HIV transmission.

OBJECTIVE: To test the ability of a computer-based interview to detect factors related to the risk of the human immunodeficiency virus (HIV) among potential blood donors and to determine donor reactions to the use of the interview. DESIGN: A comparison of the rate of detection of HIV-related factors elicited by a computer interview with that obtained by standard American Red Cross procedures for assessment of donor suitability, including a randomized crossover trial in which the order of the two methods was reversed. Information obtained by the computer was not available to influence the use of blood components for transfusion. SETTING: The computer interview was administered to donors at an American Red Cross blood donor center and at a mobile blood drive at a hospital. SUBJECTS: Consecutive sample of 294 male and female blood donors 18 to 75 years of age. MAIN OUTCOME MEASURES: Subjects' responses to the computer-based interview as well as responses to the standard Red Cross written questionnaires and face-to-face interviews were used for donor assessment. RESULTS: The interview took an average of 8 minutes to complete. From among 272 donors who provided complete data, the computer identified 12 donors who reported either behaviors associated with a risk of HIV acquisition or symptoms compatible with the acquired immunodeficiency syndrome; none of these donors had been so identified either by routine written questionnaires or by face-to-face interviews used to screen potential blood donors. Only one of the 12 identified donors used the confidential unit exclusion procedure to prevent use of his donated unit. The rate of elicitation of HIV-related factors by the computer interview was 12 (4.4%) of 272 (95% confidence interval [CI], 2.3% to 7.6%), compared with two (0.13%) of 1536 (95% confidence upper bound, 0.28%) using the standard Red Cross procedure (P less than .0001). Tests for antibodies to HIV were negative in blood samples from all of the 272 subjects studied. The subjects enjoyed the computer interview and judged it to be more private than the standard donor assessment method. They also predicted that donors would be more honest with the computer interview than with a human interviewer. CONCLUSIONS: Computer-based screening elicits more HIV-related factors in the health histories of blood donors than do the standard questionnaire and interviewing methods currently in use. Computer-based screening is also acceptable to blood donors.

Adolescent↗
PubMed1992

Quality-of-life evaluation in a clinical trial of zidovudine therapy in patients with mildly symptomatic HIV infection. The AIDS Clinical Trials Group.

OBJECTIVE: To evaluate the effects of zidovudine therapy in patients with mildly symptomatic HIV infection using Q-TWiST (quality-adjusted: Time Without Symptoms and Toxicity). DESIGN: Analysis of a previously reported multicenter, randomized, placebo-controlled clinical trial. SETTING: Thirty-two AIDS Clinical Trial units. PATIENTS: A total of 351 patients with mildly symptomatic HIV infection were assigned to placebo, and 360 patients were assigned to zidovudine, 1200 mg/d. MEASUREMENTS: A modified Q-TWiST method for comparing treatments based on time spent without severe symptomatic adverse events and without disease progression. Zidovudine and placebo were compared in a threshold utility analysis considering reduction in quality of life associated with adverse events and disease progression. Adverse events defined by laboratory findings were distinguished from findings representing symptomatic events. RESULTS: The incidence of severe symptomatic adverse events was 22.8% for the zidovudine group and 15.1% for the placebo group (P = 0.01), but, as previously reported, zidovudine improved progression-free survival relative to placebo (at 18 months, 91% compared with 81%; P = 0.001). In an 18-month period, patients receiving zidovudine went an average of 14.5 months without disease progression or a severe symptomatic adverse event compared with 14.7 months for placebo. The zidovudine group gained 0.9 months without disease progression but lost 1.1 months due to adverse events. Within the 18-month observation period, treatment provided more Q-TWiST than placebo if the quality of life after HIV disease progression was assumed to be 10% to 20% worse than the quality of life after a severe symptomatic adverse event. CONCLUSIONS: The Q-TWiST analysis projects that quality-of-life reductions due to severe symptomatic adverse events might be balanced by the quality-of-life benefits of delayed HIV disease progression for patients who received zidovudine for mildly symptomatic HIV infection. At currently recommended doses (500 to 600 mg/d, half the dose used in this study) zidovudine therapy is likely to yield a more favorable result.

Double-Blind Method↗
PubMed1992

Effect of volume history on changes in DLcoSB-3EQ with lung volume in normal subjects.

The purpose of this study was to determine the relationship between the three-equation diffusing capacity for carbon monoxide (DLcoSB-3EQ) and lung volume and to determine how this relationship was altered when maneuvers were immediately preceded by a deep breath. DLcoSB-3EQ maneuvers were performed in nine healthy subjects either immediately after a deep breath or after tidal breathing for 10 min. The maneuvers consisted of slow inhalation of test gas from functional residual capacity to 25, 50, 75, or 100% of the inspiratory capacity and, without breath holding, slow exhalation to residual volume. After either a deep breath or tidal breathing, we found that DLcoSB-3EQ decreased nonlinearly with decreasing lung volume. At all lung volumes, DLcoSB-3EQ was significantly greater when measured after a deep breath than after tidal breathing. This effect increased as lung volume decreased, so that the greatest difference between DLcoSB-3EQ after a deep breath and that after tidal breathing occurred at the lowest lung volume. We conclude that a deep breath or spontaneous sigh has a role in reestablishing the pathway for gas exchange during tidal breathing.

Adult↗
PubMed1992

Effects of ventilation inhomogeneity on DLcoSB-3EQ in normal subjects.

In patients with airflow obstruction, we found that ventilation inhomogeneity during vital capacity single-breath maneuvers was associated with decreases in the three-equation single-breath CO diffusing capacity of the lung (DLcoSB-3EQ) when breath-hold time (tBH) decreased. We postulated that this was due to a significant resistance to diffusive gas mixing within the gas phase of the lung. In this study, we hypothesized that this phenomenon might also occur in normal subjects if the breathing cycle were altered from traditional vital capacity maneuvers to those that increase ventilation inhomogeneity. In 10 normal subjects, we examined the tBH dependence of both DLcoSB-3EQ and the distribution of ventilation, measured by the mixing efficiency and the normalized phase III slope for helium. Preinspiratory lung volume (V0) was increased by keeping the maximum end-inspiratory lung volume (Vmax) constant or by increasing V0 and Vmax. When V0 increased while Vmax was kept constant, we found that the tBH-independent and the tBH-dependent components of ventilation inhomogeneity increased, but DLcoSB-3EQ was independent of V0 and tBH. Increasing V0 and Vmax did not change ventilation inhomogeneity at a tBH of 0 s, but the tBH-dependent component decreased. DLcoSB-3EQ, although independent of tBH, increased slightly with increases in Vmax. We conclude that in normal subjects increases in ventilation inhomogeneity with increases in V0 do not result in DLcoSB-3EQ becoming tBH dependent.

Adult↗
PubMed1992

Miliary Mycobacterium bovis induced by intravesical bacille Calmette-Guérin immunotherapy.

Intravesical instillation of bacille Calmette-Guérin (BCG), an attenuated strain of Mycobacterium bovis, is the treatment of choice for many patients with bladder cancer. In a small percentage, this therapy is associated with systemic side effects including pneumonitis. It is uncertain whether these systemic manifestations are due to dissemination of infection or due to hypersensitivity, an etiologic distinction that has important therapeutic implications. We report the first case in which miliary M. bovis was proven to be the responsible mechanism, by culture of M. bovis biovar BCG from a transbronchial lung biopsy and complete resolution on anti-tuberculous chemotherapy.

Administration, Intravesical↗
PubMed1991

Primary prophylaxis for Pneumocystis carinii pneumonia in HIV-infected people with CD4 counts below 200/mm3: a cost-effectiveness analysis.

We developed a decision-analytic model to assess the effectiveness and costs of dapsone, trimethoprim-sulfamethoxazole, or aerosolized pentamidine as initial prophylaxis for Pneumocystis carinii pneumonia in human immunodeficiency virus-infected people without prior symptoms AIDS and with CD4 counts less than 200/mm3. Each strategy increased life expectancy by about 18% compared with no prophylaxis; annual per-person costs were $440, $700, and $1,680 for dapsone, trimethoprim-sulfamethoxazole, and aerosolized pentamidine, respectively. These cost differences make a strategy beginning with dapsone most cost effective, with an incremental cost-effectiveness ratio of $13,400 per life year saved compared with no prophylaxis. Aerosolized pentamidine was substantially less cost effective, but the incremental cost effectiveness ratios were highly dependent on estimates for quality of life, efficacy, toxicity, and compliance. We conclude that, based on currently available data, initial prophylaxis with either dapsone or trimethoprim-sulfamethoxazole is most cost effective. For every 100,000 people treated, starting prophylaxis with trimethoprim-sulfamethoxazole or dapsone--with crossover to aerosolized pentamidine if oral therapy is not tolerated--may save between $98 million and $124 million per year.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Effect of a deep breath on gas mixing and diffusion in the lung.

We examined the effect of a previous deep breath on both inert gas mixing and the single breath diffusing capacity (DLCOSB) during submaximal single breath maneuvers in normal subjects. Single breath washouts were performed either immediately after a deep breath or after breathing tidally for 10 min. Maneuvers consisted of inhaling test gas from functional residual capacity to 50% inspiratory capacity and, after either 0 or 6 s of breath holding, exhaling slowly back to residual volume. We measured the Fowler dead space, the Phase III slope of the alveolar plateau of the He washout (delta He/L), the amplitude of the cardiogenic oscillations (Oc), closing capacity, mixing efficiency (Emix) and DLCOSB using the three equation method. For maneuvers immediately after a deep breath we found that delta He/L was steeper and the Oc were larger for washouts with 6 s but not 0 s of breath holding, while Emix was significantly lower and DLCOSB significantly higher for both the 0 s and the 6 s breath holding maneuvers. We conclude that a deep breath increases DLCOSB but simultaneously also increases convective-dependent inhomogeneity in the lung.

Adult↗
PubMed1990

Pulmonary diffusing capacity in adult cystic fibrosis: reduced positional changes are partially reversed by hyperoxia.

In seated adult cystic fibrosis (CF) patients, vascular recruitment of the relatively normal regions of the pulmonary circulation could occur in response to vascular destruction or hypoxia elsewhere in the pulmonary vasculature, thus limiting overall reductions in the single breath CO diffusing capacity (DLcoSB) with advancing disease. The purpose of this study was to determine the extent to which pulmonary capillary recruitment limits reductions in DLcoSB in seated adult cystic fibrosis patients, to define the role of hypoxia, and to develop strategies to improve detection of diffusion abnormalities in this disease. In normal subjects and adult CF patients breathing room air, and in a subgroup, after breathing both 40% and 100% O2 for 20 min, we measured changes (compared to sitting) in the three equation DLcoSB by changing transvascular pressure either with 15 degrees head down position (15 degrees HD), or with high negative inspiratory pressure (HNIP). In CF patients breathing room air, the changes in DLcoSB with both 15 degrees HD and HNIP were significantly smaller (p less than 0.01) than in controls and the positional changes correlated with the degree of airway obstruction. Although CF patients had no significant positional changes in diffusional resistance (1/DLcoSB) breathing room air, the positional changes in 1/DLcoSB after breathing 100% O2 for 20 min were similar in magnitude to the positional changes in normal subjects. We conclude that compensatory pulmonary capillary recruitment occurs in the relatively normal regions of the pulmonary vasculature breathing room air in the resting seated position in CF patients, thus minimizing reductions in DLcoSB in the seated position. This accounts for reduced responses of DLcoSB to both position and HNIP. The improved positional changes in 1/DLcoSB breathing hyperoxic gas mixtures in CF patients suggests that the vascular recruitment breathing room air is partly due to hypoxic vasoconstriction rather than due solely to fixed pathological changes in the pulmonary vasculature.

Adolescent↗
PubMed1989

Effect of lung volume on ventilation distribution.

To examine the effect of preinspiratory lung volume (PILV) on ventilation distribution, we performed multiple-breath N2 washouts (MBNW) in seven normal subjects breathing 1-liter tidal volumes over a wide range of PILV above closing capacity. We measured the following two independent indexes of ventilation distribution from the MBNW: 1) the normalized phase III slope of the final breaths of the washout (Snf) and 2) the alveolar mixing efficiency during that portion of the washout where 80-90% of the lung N2 had been cleared. Three of the subjects also performed single-breath N2 washouts (SBNW) by inspiring 1-liter breaths and expiring to residual volume at PILV = functional residual capacity (FRC), FRC + 1.0, and FRC - 0.5, respectively. From the SBNW we measured the phase III slope over the expired volume ranges of 0.75-1.0, 1.0-1.6, and 1.6-2.2 liters (S0.75, S1.0, and S1.6, respectively). Between a PILV of 0.92 +/- 0.09 (SE) liter above FRC and a PILV of 1.17 +/- 0.43 liter below FRC, Snf decreased by 61% (P less than 0.001) and alveolar mixing efficiency increased from 80 to 85% (P = 0.05). In addition, Snf and alveolar mixing efficiency were negatively correlated (r = 0.74). In contrast, over a similar volume range, S1.0 and S1.6 were greater at lower PILV. We conclude that, during tidal breathing in normal subjects, ventilation distribution becomes progressively more inhomogeneous at higher lung volumes over a range of volumes above closing capacity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Effect of airway closure on ventilation distribution.

We examined the effect of airway closure on ventilation distribution during tidal breathing in six normal subjects. Each subject performed multiple-breath N2 washouts (MBNW) at tidal volumes of 1 liter over a range of preinspiratory lung volumes (PILV) from functional residual capacity (FRC) to just above residual volume. All subjects performed washouts at PILV below their measured closing capacity. In addition five of the subjects performed MBNW at PILV below closing capacity with end-inspiratory breath holds of 2 or 5 s. We measured the following two independent indexes of ventilation maldistribution: 1) the normalized phase III slope of the final breaths of the washout (Snf) and 2) the alveolar mixing efficiency of those breaths of the washout where 80-90% of the initial N2 had been cleared. Between a mean PILV of 0.28 liter above closing capacity and that 0.31 liter below closing capacity, mean Snf increased by 132% (P less than 0.005). Over the same volume range, mean alveolar mixing efficiency decreased by 3.3% (P less than 0.05). Breath holding at PILV below closing capacity resulted in marked and consistent decreases in Snf and increases in alveolar mixing efficiency. Whereas inhomogeneity of ventilation decreases with lung volume when all airways are patent (J. Appl. Physiol. 66: 2502-2510, 1989), airway closure increases ventilation inequality, and this is substantially reduced by short end-inspiratory breath holds. These findings suggest that the predominant determinant of ventilation distribution below closing capacity is the inhomogeneous closure of airways subtending regions in the lung periphery that are close together.

Adult↗
PubMed1988

Volume acceleration as an index of neuromuscular output.

At the transition from expiration to inspiration, when flow and volume changes are small, changes in the respiratory system driving pressure could determine the degree of volume acceleration (AI), which, in turn, could reflect the degree of respiratory center output. To test this hypothesis, we calculated AI occurring in each respiratory cycle at the transition from expiration to inspiration during CO2 rebreathing in 4 healthy supine subjects. To minimize the flow and volume change over the measurement interval, we measured AI just prior to inspiration within the limits of an expiratory flow of 0.2 L . sec -1 to zero flow using digital differentiation. We also measured mouth pressure 100 msec after the onset of inspiration (P0.1) during intermittent transient inspiratory airway occlusions. During CO2 rebreathing AI increased significantly with both increasing PCO2 and P0.1. We also compared pairs of rebreathing studies, performed without and with an alinear (16 cm H2O . L -1 . sec -1) inspiratory resistor (IR), repeated twice in the 4 subjects. IR markedly decreased delta VE/delta PCO2 and the slope of the increase in mean inspiratory flow rate with PCO2 (delta VT/TI/delta PCO2) but did not significantly alter either delta AI/delta PCO2 or the increase in P0.1 with PCO2 (delta P0.1/delta PCO2). However, the effects of IR on AI and P0.1 differed between the early and late phases of each rebreathing run; early in the rebreathing runs (PCO2 = 55 Torr) IR increased both AI and P0.1 by a similar amount, but near the end of rebreathing (PCO2 = 60 Torr) IR increased P0.1 but not AI. Our results are consistent with the possibility that AI reflects neuromuscular output under the conditions of the study. Hence this approach justifies further evaluation to determine its general applicability.

Adult↗
PubMed1987

Clinical features and therapeutic interventions in 17 cases of Bacillus bacteremia in an immunosuppressed patient population.

We retrospectively examined episodes of Bacillus bacteremia at a hospital with a large proportion of immunosuppressed patients. Seventeen episodes in 9.5 years met our case definition: two of two bottles of one blood culture or one of two bottles of two or more separately obtained blood cultures drawn on the same date. During the same period, there were 59 additional episodes in which a single blood culture had only one of two bottles positive for Bacillus species. Only 2 of 59 such episodes resulted in recurrent bacteremia (3%), as compared with 5 of 17 episodes meeting our case definition (29%) (P = 0.004). In four of five episodes complicated by recurrent bacteremia and in which appropriate antibiotics were used, a Hickman-Broviac catheter was in place and was not removed. We suggest that our case definition permits the differentiation of infection from contamination based on outcome and that patients with Bacillus bacteremia have chronic venous catheters removed as well as receive antibiotic treatment.

Adolescent↗
PubMed1986

Pulmonary function in Pi M and MZ grainworkers.

Twenty-eight men with the Pi MZ phenotype who have been employed in the Saskatchewan country grain elevators and thus regularly exposed to high levels of grain dust, were case matched for age, years of employment, employment status, smoking status, and smoking history with grainworkers of type Pi M. Individuals answered a questionnaire, had a chest roentgenogram, skin tests, and performed a battery of pulmonary function tests. There were no differences between the two groups in prevalence of symptoms or atopy. Although not statistically significant, the MZ group had three times as many individuals with abnormal roentgenograms suggestive of COPD as the M group. The Pi MZ grainworkers had consistently poorer mean results for the pulmonary function tests with significantly lower mean values for FEV1, FEV1/FVC, MMFR, and Vmax50, leading us to suggest that Pi MZ individuals may be at higher risk of COPD than Pi M individuals, but only in the presence of other risk factors such as grain dust exposure.

Adult↗
PubMed1985

Effect of breath-hold time on DLCO(SB) in patients with airway obstruction.

The single-breath diffusing capacity of the lung for CO [DLCO(SB)] is considered a measure of the conductance of CO across the alveolar-capillary membrane and its binding with hemoglobin. Although incomplete mixing of inspired gas with alveolar gas could theoretically influence overall diffusion, conventional calculations of DLCO(SB) spuriously overestimate DLCO(SB) during short breath-holding periods when incomplete mixing of gas within the lung might have the greatest effect. Using the three-equation method to calculate DLCO(SB) which analytically accounts for changes in breath-hold time, we found that DLCO(SB) did not change with breath-hold time in control subjects but increased with increasing breath-hold time in both patients with asthma and patients with emphysema. The increase in DLCO(SB) with increasing breath-hold time correlated with the phase III slope of the single-breath N2 washout curve. We suggest that in patients with ventilation maldistribution, DLCO(SB) may be decreased for the shorter breath-hold maneuvers because overall diffusion is limited by the reduced transport of CO from the inspired gas through the alveolar gas prior to alveolar-capillary gas exchange.

Adult↗
PubMed1985

Reduction of the single breath CO diffusing capacity in cystic fibrosis.

The single breath diffusing capacity of the lung for carbon monoxide (Dsb) was measured using three equations to describe CO uptake separately during inhalation, breath holding, and exhalation in 24 patients with cystic fibrosis and 30 control subjects with similar age and height distributions. Using the control group, we developed two prediction equations for Dsb: one based on height, age, and sex; and another based on alveolar lung volume (VA) to the 2/3 power. We also developed a prediction for Dsb/VA (Kco) based on height. The Dsb as percent predicted (% pred) using either prediction equation decreased with increasing age and height as well as with decreasing % pred maximal midexpiratory flow rate (FEF25-75) in cystic fibrosis patients but not in controls. The Kco (% pred) also decreased in cystic fibrosis with increasing age and decreasing percent pred FEF25-75. We conclude that in patients with cystic fibrosis, Dsb decreases with variables that relate to increasing disease severity (age, height, and increasing airflow obstruction).

Adolescent↗
PubMed1983

Selective defect in human neutrophil superoxide anion generation elicited by the chemoattractant N-formylmethionylleucylphenylalanine in pregnancy.

Pregnancy has been associated with alterations of polymorphonuclear neutrophil (PMN) function. Superoxide anion production was studied in pregnant women paired with nonpregnant women of childbearing age. There was a significant decrease in the amount of cytochrome c reduced in response to 1 microM N-formylmethionylleucylphenylalanine (fMet-Leu-Phe) but not to phorbol myristate acetate, 4 or 20 ng/ml. Chemotaxis was also depressed. Binding of tritiated fMet-Leu-Phe to PMNs from pregnant women was not defective. Incubation of normal cells in up to 10(-6) M estradiol or progesterone did not mimic the defect, but 10(-7) M progesterone caused a decrease in chemotaxis. Serum pooled from women with the defect had no effect on superoxide anion production by normal PMNs. PMN rosetting with IgG-sensitized human erythrocytes was normal. Defective production of superoxide anion may contribute to the amelioration of connective tissue disease and increased susceptibility to infection often seen during pregnancy.

Chemotaxis, Leukocyte↗