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Biomedical subjects

N M Graham

Publications and source records attributed to N M Graham.

At least 91 records · Page 5Linked to original sources
PubMed1992

Prevalence of tuberculin positivity and skin test anergy in HIV-1-seropositive and -seronegative intravenous drug users.

OBJECTIVES: --To identify differences in purified protein derivative (PPD) tuberculin positivity and skin test anergy rates by human immunodeficiency virus (HIV) serostatus, CD4+ lymphocyte count, and other risk factors in intravenous drug users (IVDUs); and to evaluate the appropriateness of the Centers for Disease Control (CDC)--recommended definition for a positive PPD tuberculin skin test result in HIV-1-seropositive patients. DESIGN: --Nested case-control and cross-sectional analyses. SETTING: --Community-based cohort of IVDUs. PATIENTS: --Two hundred sixty HIV-1-seropositive and -seronegative IVDUs, drawn from an unselected cohort, were skin-tested for sensitivity to PPD tuberculin, mumps, and Candida antigens using the Mantoux method. OUTCOME MEASURES: --Positivity to PPD tuberculin, skin test anergy. RESULTS: --Even using the CDC definition of an induration 5 mm or greater in diameter in HIV-1 seropositives, this group was substantially less likely to be PPD tuberculin positive than HIV-1 seronegatives (13.8% vs 25.2%; P = .02). In the HIV-1 seropositives the relative odds of being PPD positive varied depending on whether 10 mm or greater (odds ratio [OR], 0.3; 95% confidence interval [CI], 0.2 to 0.7), 5 mm or greater (OR, 0.5; 95% CI, 0.2 to 0.9), or 2 mm or greater (OR, 0.7; 95% CI, 0.4 to 1.3) was used to define a positive test result. The mean diameter induration in the HIV-1-seropositive group was 2.6 mm vs 5.4 mm in the seronegative group (P = .005). Skin test anergy (to mumps and Candida) appeared to explain the differential. Anergy was substantially higher in the HIV-1 seropositive group and increased as the CD4+ lymphocyte count fell (chi 2 for linear trend, 24.5; P less than .0001). An inverse linear trend for PPD positivity and CD4+ lymphocyte count was also observed (chi 2 for trend, 6.1; P = .01). In multivariate analyses, being 35 years of age or older and being HIV-1 seronegative were significantly associated with PPD positivity, while history of previous police arrest was of borderline significance. Only HIV-1 seropositivity was significantly associated with anergy. CONCLUSIONS: --These findings show that CDC-recommended definition of an induration 5 mm or greater in diameter for PPD tuberculin positivity in HIV-1 seropositives significantly underestimates the "true" infection rate (using the PPD positivity rate in HIV-1 seronegatives as the criterion standard). A definition of 2 mm or greater would appear to be a better cutoff for reducing misclassification in HIV-1 seropositives. This study also confirms that delayed-type hypersensitivity is seriously depressed in HIV-1 seropositive IVDUs and that anergy testing is mandatory to properly assess a negative PPD test result.

Adolescent↗
PubMed1992

Effect of CD4+ cell count measurement variability on staging HIV-1 infection.

A single CD4+ cell count (CD4) measurement is often used to stage HIV-1 infection, decide when to initiate prophylactic therapy and inform patients, and may soon even define AIDS onset. Documentation of the reliability and validity of employing CD4 for the above purposes in a population-based setting is needed. We utilized data from 4,954 homosexual/bisexual men followed over 6 years, with CD4 testing at 6 month intervals, to study the timing of CD4-based staging of HIV-1 disease and quantify and evaluate the potential impact of CD4 measurement error. The median time from seroconversion to first CD4 test below 500 x 10(6)/L or clinical AIDS was 1.70 years, and the first CD4 test below 200 x 10(6)/L or clinical AIDs was 5.29 years. The time from first testing less than 500 x 10(6)/L to clinical AIDS in untreated men was 5.55 years. With confirmatory retesting, these times were significantly lengthened. The 95% confidence ranges for the true CD4 state in individuals with measured CD4 of 500 and 200 x 10(6)/L are at least (297 x 10(6), 841 x 10(6)/L) and (118 x 10(6), 337 x 10(6)/L), respectively. Without confirmatory retesting, individuals with true CD4 remaining at 700 x 10(6) and 280 x 10(6)/L have at least a 40% chance for one of five CD4 measurements to fall below guideline limits of 500 x 10(6) and 200 x 10(6)/L, respectively. Confirmatory retesting can reduce these probabilities to as low as 4%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Antibody responses to Haemophilus influenzae type B vaccines in men with human immunodeficiency virus infection.

BACKGROUND: Persons with human immunodeficiency virus (HIV) infection are at increased risk for serious infections caused by Haemophilus influenzae, yet there are few data on their antibody responses to the H. influenzae type b vaccines. METHODS: We evaluated antibody responses in 248 men who were randomly assigned to receive a single dose of either the H. influenzae type b polysaccharide (PRP) vaccine or the polysaccharide-mutant diphtheria toxoid conjugate vaccine (PRP-CRM). The subjects were stratified into four groups: seronegative men (67 subjects), men with asymptomatic HIV infection (79), men with symptomatic HIV infection (47), and men with the acquired immunodeficiency syndrome (AIDS) (55). RESULTS: Before immunization, the subjects with AIDS had the lowest PRP-antibody titers; 40 percent had titers below the putative protective level (less than 0.15 micrograms per milliliter). In the seronegative subjects, those with asymptomatic HIV infection, and those with symptomatic HIV infection, the PRP-CRM vaccine led to a threefold greater increase in geometric mean antibody titers than did the PRP vaccine (P less than 0.01). However, the subjects with AIDS had a greater antibody response to the PRP vaccine. The antibody response of HIV-seropositive men to the PRP-CRM vaccine correlated significantly with the number of CD4 lymphocytes (r = 0.47, P less than 0.0001, as compared with r = -0.01 for the PRP vaccine). In these HIV-infected men, both vaccines elicited the dominant anti-PRP idiotype described previously in populations not infected with HIV. CONCLUSIONS: Immunization with the PRP-CRM conjugate vaccine early in the course of HIV infection is likely to confer protection against disease caused by H. influenzae type b.

AIDS Vaccines↗
PubMed1991

Effect of zidovudine and Pneumocystis carinii pneumonia prophylaxis on progression of HIV-1 infection to AIDS. The Multicenter AIDS Cohort Study.

Although used widely, the effectiveness of zidovudine therapy and primary prophylaxis for Pneumocystis carinii pneumonia (PCP) in HIV-1-infected individuals, has not been assessed in a large cohort. We have done an observational study between October, 1986, and October, 1990, of a cohort of 2145 HIV-1-seropositive men and 371 who seroconverted during the study. A Markov chain transitional analysis was used to examine the effect of zidovudine and PCP prophylaxis on the probability of progression of HIV-1 infection to AIDS (after 6, 12, 18, and 24 months) after follow-up visits categorised into one of six disease states. The six starting states were based on CD4+ lymphocyte counts and the presence of HIV-related symptoms. Use of pre-AIDS zidovudine and PCP prophylaxis was associated with significant reductions in rates of progression to AIDS at 6, 12, 18, and 24 months for participants starting with less than 350 CD4+ lymphocytes/microliter. For those starting with 350 or more CD4+ lymphocytes/microliter, non-significant protective trends were seen during 12, 18, and 24 month intervals. In multivariate log-linear models virtually all the treatment effect was due to zidovudine. However, after adjusting for the effects of zidovudine, PCP prophylaxis reduced significantly the probability of progression to a first episode of PCP during 6, 12, 18, and 24 month intervals. This study suggests that early primary PCP prophylaxis is effective in preventing first episodes of PCP, and that the efficacy of zidovudine demonstrated in clinical trials can be translated to the population level.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Acute respiratory illness in Adelaide children--the influence of child care.

OBJECTIVE: To test the hypothesis that children attending child care centres are more likely to be prone to acute respiratory illness. DESIGN: A case-control study. SETTING: A community-based study in the Adelaide metropolitan area. PARTICIPANTS: A randomly selected sample of Adelaide children whose births were registered in 1983. MAIN OUTCOME MEASURE: A respiratory illness score was calculated for each child, based on parents' reports of acute respiratory illness in the previous 12 months. RESULTS: Information was obtained by postal survey for 2618 children (mean age at time of study, 26 months). Eight hundred and nineteen of these children (31%) were reported to be regular or occasional attenders of child care centres or crèches. Home interviews were carried out with parents of children whose respiratory illness scores fell in the top 20% of the range and those whose score was in the bottom 20%. Children prone to respiratory illness were more likely to be users of child care centres or crèches than the children who were not prone (odds ratio = 2.28; 95% confidence interval, 1.53-3.40). The risk of being prone to respiratory illness increased with the frequency of use of child care, and tended to be greater the younger children were when they first attended child care centres. Adjustment in multivariate analysis for confounding factors made little difference to the strength of the association of proneness to respiratory illness with the use of child care (adjusted odds ratio = 2.23; 95% confidence interval 1.38-3.61). CONCLUSION: Use of child care centres is an important cause of acute respiratory illness among Australian children.

Case-Control Studies↗
PubMed1991

Epidemiologic patterns of upper respiratory illness and Pneumocystis carinii pneumonia in homosexual men.

The relationship between self-reported upper respiratory illness symptoms (URI) and human immunodeficiency virus Type 1 (HIV-1) was examined in homosexual men using semiannual visits from 1984 to 1988. Temporal and geographic patterns of Pneumocystis carinii pneumonia (PCP) diagnosis in these men during the same time period are also described. URI, including acute sinusitis, was reported more often by 916 HIV-1-seropositive participants than by 2,161 seronegative participants (32.21 versus 28.86% p less than 0.001). For 387 seropositive subjects who progressed to acquired immunodeficiency syndrome (AIDS), the proportion reporting URI peaked one visit pre-AIDS at a level significantly higher than matched control subjects (0.45 versus 0.28, p less than or equal to 0.001). The peak was higher for those with PCP as an initial diagnosis. Reported URI peaked in winter and troughed in summer, and PCP diagnosis rates peaked and troughed 4 months later, respectively. Cities with the highest reported rates of URI also had the highest proportions of AIDS cases with PCP as an initial diagnosis. No temporal or geographic patterns were observed for other HIV-1-related symptoms or non-PCP AIDS diagnoses. These patterns suggest the possibility of a person-to-person transmission of P. carinii similar to that of other respiratory pathogens, which would imply a need to consider stricter methods to prevent nosocomial transmission of this pathogen in inpatient and outpatient settings. Further investigation of these issues is needed.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Zidovudine use in AIDS-free HIV-1-seropositive homosexual men in the Multicenter AIDS Cohort Study (MACS), 1987-1989.

Zidovudine use data were examined in the Multicenter AIDS Cohort Study to determine (i) if the proportion of pre-AIDS participants (i.e., CD4+ cells less than 200/mm3 or AIDS-related complex) taking zidovudine is high enough to explain a slower than expected rise in AIDS incidence in U.S. homosexual men since mid-1987; (ii) which factors are associated with starting zidovudine and clinical trials of zidovudine; and (iii) if pre-AIDS patients, as a group, are being undertreated. Data on zidovudine use, clinical trial participation, and sociodemographic, clinical, and hematologic variables were collected every 6 months from 1,195 AIDS-free HIV-1-seropositive homosexual men from April 1987 to September 1989. Overall prevalence of zidovudine use rose from 3.6% in mid-1987 (visit 7) to 23% in mid-1989 (visit 11). Of those with less than 200 CD4+ lymphocytes/mm3, the prevalence of zidovudine use rose from 23% (24% if those taking zidovudine or placebo as part of a clinical trial are included) at visit 7 to 58% (69%) at visit 11. Of those with ARC, 20% (23%) were using zidovudine at visit 7 and 55% (65%) at visit 11. Although numbers were small, the advanced ARC participants (CD4+ cells less than 200/mm3 and two or more symptoms) reported the highest treatment rates (50, 78, 80, 60, and 74% at visits 7-11, respectively). By September 1989, 42% (31%) of those with CD4+ lymphocyte levels less than 200/mm3 were still not receiving zidovudine, suggesting that many high-risk, pre-AIDS individuals are being undertreated. To explore this finding further, we examined a range of sociodemographic, hematologic, and clinical variables to determine which factors best predicted initiation of zidovudine therapy outside of clinical trials. In multivariate analyses, CD4+ lymphocyte number was the most consistent predictor of initiation of therapy over all four study visits. For each 100 cells/mm3 deficit, the odds ratios were 2.3 (95% C.I. of 1.7-3.1) at visit 7 and 1.7% (95% C.I. of 1.4-2.0) at visit 11. Symptom status and education level were also associated with starting zidovudine, but not at all visits. The relatively low predictive power of the clinical variables raises and the possibility that nonclinical factors not measured in the MACS (drug cost, third-party insurance restrictions, and individual preferences) may play an important role in predicting zidovudine use. Finally, comparisons were made between seropositive participants starting clinical trials of zidovudine and the rest of the study population. No important differences were found in demographic or major clinical variables between clinical trial participants and zidovudine nonusers in this study.

AIDS-Related Complex↗
PubMed1991

Relationship of serum copper and zinc levels to HIV-1 seropositivity and progression to AIDS.

Dietary, serum, and tissue levels of copper and zinc were determined at baseline in a cohort of homosexual men to investigate the relationship of these factors to human immunodeficiency virus type 1 (HIV-1) seropositivity and subsequent progression to AIDS. Using a nested case control design, 54 asymptomatic HIV-1 seropositives who later progressed to AIDS were compared with 54 HIV-1 seropositives who did not progress and 54 seronegatives (mean follow-up time 2.5 years). Serum levels of copper and zinc were estimated from frozen serum samples, tissue levels from stored toenail samples, and dietary intakes from a semiquantitative food frequency questionnaire administered at baseline. Neither dietary copper and zinc nor their levels in toenails were associated with HIV-1 seropositivity or progression to AIDS. However, serum copper levels were higher (p = 0.002) in HIV-1-seropositive progressors (mean = 115.6 micrograms/dl; SD = 17.1) than the seropositive nonprogressors (mean = 109.0 micrograms/dl; SD = 15.8) and the seronegatives (mean = 101.9 micrograms/dl; SD = 16.7). Conversely, serum zinc levels were lower (p = 0.016) in the seropositive progressors (mean = 85.2 micrograms/dl; SD = 11.5) than the seropositive nonprogressors (mean = 90.7 micrograms/dl; SD = 12.0) and the seronegatives (mean = 92.0 micrograms/dl; SD = 14.7). Furthermore, in a logistic regression, higher serum copper (odds ratio per 20-micrograms/dl increase = 2.23; 95% confidence interval = 1.02-4.87) and lower serum zinc (odds ratio per 20-micrograms/dl increase = 0.30; 95% confidence interval = 0.14-0.66) predicted progression to AIDS independently of baseline CD4+ lymphocyte level, age, and calorie-adjusted dietary intakes of both nutrients.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1990

"Sick of Smoking": evaluation of a targeted minimal smoking cessation intervention in general practice.

Several smoking intervention studies have been conducted overseas which use a minimal amount of general practitioners' time and are conducted within the constraints of a normal consultation. However, there are no published reports of minimal interventions in Australian general practice. This study reports on 1238 South Australian smokers who were assigned to a non-intervention control group or a group which received firm general practitioner advice to quit smoking plus literature. At one-year follow-up, 7.5% of smokers in the minimal advice group who had quit for six or more months remained non-smokers compared with 3.2% in the control group. If similar analytical procedures had been used in this study as were used in the benchmark study in England in 1979, the quit rate for this study would have been 11.3% in the intervention group, and 4.8% in the control group--a net gain of 6.5%. These results are discussed with regard to widespread implementation in Australian general practice.

Adolescent↗
PubMed1990

Acute respiratory illness in Adelaide children. II: The relationship of maternal stress, social supports and family functioning.

In a community-based study we investigated the relationships between maternal stress, maternal social supports, family functioning and proneness to acute respiratory illness (AR1) in childhood. 'Prone' and 'not prone' children were identified from the responses to a mail questionnaire sent to the addresses of a randomly selected group of Adelaide children who had been born in 1983. 'Prone' children (n = 255) were defined by a respiratory score (based on frequency and severity of reported symptoms in the preceding 12 months) in the top quintile of the distribution, while 'not prone' children (n = 227) were defined by a score in the bottom 20% of the range. Further information was obtained from a questionnaire administered at a home visit. Maternal stress levels were determined from a combination of major life events, minor life events and psychological distress. Maternal stress was significantly associated with respiratory proneness in a stepwise multiple logistic regression (adjusted odds ratio/high versus low = 3.8; 95% confidence interval 2.0-7.2; p = 0.000), while controlling for the effects of maternal smoking, group child care, early chest illness, number of siblings, breastfeeding, occupation, sex, age, home heating, birthweight and parental history of respiratory illness. Family dysfunction was associated with respiratory proneness in bivariate analyses but not after adjustment for the effects of other psychosocial factors in multivariate analyses. Lack of maternal social support was not associated with having a child who was prone to respiratory illness. These findings raise a number of questions about the nature and direction of the relationship between parental psychological status and child health.

Acute Disease↗
PubMed1990

Adverse effects of aspirin, acetaminophen, and ibuprofen on immune function, viral shedding, and clinical status in rhinovirus-infected volunteers.

A double-blind, placebo-controlled trial was conducted to study the effects of over-the-counter analgesic/antipyretic medications on virus shedding, immune response, and clinical status in the common cold. Sixty healthy volunteers were challenged intranasally with rhinovirus type 2 and randomized to one of four treatment arms: aspirin, acetaminophen, ibuprofen, or placebo. Fifty-six volunteers were successfully infected and shed virus on at least 4 days after challenge. Virus shedding, antibody levels, clinical symptoms and signs, and blood leukocyte levels were carefully monitored. Use of aspirin and acetaminophen was associated with suppression of serum neutralizing antibody response (P less than .05 vs. placebo) and increased nasal symptoms and signs (P less than .05 vs. placebo). A concomitant rise in circulating monocytes suggested that the suppression of antibody response may be mediated through drug effects on monocytes and/or mononuclear phagocytes. There were no significant differences in viral shedding among the four groups, but a trend toward longer duration of virus shedding was observed in the aspirin and acetaminophen groups.

Acetaminophen↗
PubMed1990

The epidemiology of acute respiratory infections in children and adults: a global perspective.

While a number of advances have been made in our understanding of the epidemiology of acute respiratory infections in the past two decades, a number of serious questions still require urgent answers. The associations of factors such as chronic disease in adults, direct smoking, passive smoking, crowding, and breast feeding to acute respiratory infections are now well documented. Appropriate changes in public health policy need not be predicated on results from still further studies. However, in virtually all of the other areas cited in this review, further data are required. In developing countries, studies being currently conducted on vitamin A supplementation, malnutrition, and indoor air pollution will help address the most pressing issues. More studies are also needed on the relations between HIV infection and acute respiratory infections, as well as low birth weight and respiratory infection. The National Research Council studies have provided important additional data on etiologic agents in children in developing countries, but data on adult pneumonia remain sparse. In developed countries the issues that may be of greatest interest are the relation between maternal antibody levels and passive immunity in infants, the reasons for the increase in pneumonia mortality in older age groups, and the relation between air pollution and acute respiratory infections (as opposed to morbidity from bronchial reactivity). From a methodological viewpoint, the relation between previous respiratory infection (particularly in the first year of life) and subsequent acute respiratory infection morbidity has been inadequately explored. Adjustment for autocorrelation in multivariate models may be necessary if this relation is strong. Greater standardization of data collection methods in developed and developing countries also needs to be more seriously addressed. Given that some advances have been made in this area, the time may be right for development of acute symptom questionnaires, akin to the American Thoracic Society chronic respiratory questionnaire, for use in both developed and developing countries. Standardization of diaries, although somewhat more difficult, would also be extremely useful in many instances.

Acute Disease↗
PubMed1990

Acute respiratory illness in Adelaide children: breast feeding modifies the effect of passive smoking.

STUDY OBJECTIVE: The aim was to investigate the relation between passive smoking and childhood acute respiratory illness. DESIGN: The study involved an initial postal survey on a random sample of children followed by a case-control study based on the survey. A respiratory illness score was calculated from maternal reports of episodes of illness in the previous 12 months. SETTING: The study was a population survey based on Adelaide metropolitan area in South Australia. PARTICIPANTS: The reference population (n = 13,996) was all live born children registered in South Australia in 1983 whose parents lived in Adelaide metropolitan area. Of these, 4985 families were contacted by post and from 2125 respondents, 1218 (58%) gave consent for home interview. "Cases" were children with respiratory illness scores in the top 20%, controlling for age and time of year (n = 258); "controls" were taken in the bottom 20% (n = 231). MEASUREMENTS AND MAIN RESULTS: Maternal smoking in the first year of life was associated with a doubling in relative odds of respiratory proneness in the child (odds ratio = 2.06, 95% CI 1.25-3.39) after adjustment for confounding by parental history of respiratory illness, other smokers in the home, use of group child care, parent's occupation, and levels of maternal stress and social support. There was no evidence that this association was attributable to differences in the way smoking and non-smoking parents perceived or managed childhood acute respiratory illness. Maternal smoking in the first year, without smoking in pregnancy, was also associated with increased risk of respiratory proneness (odds ratio 1.75, 95% CI 1.03-3.0), showing an effect of passive smoking independent of any in utero effect. There was a strong negative effect modification by breast feeding: relative odds of respiratory proneness with maternal smoking were seven times higher among children who were never breast fed than among those who were breast fed. CONCLUSIONS: The results suggest a relatively small but real effect of passive smoking on childhood acute respiratory illness. Effect modification by breast feeding may be due to a combination of behavioural and biological mechanisms.

Acute Disease↗
PubMed1990

Relationship between milk intake and mucus production in adult volunteers challenged with rhinovirus-2.

In the first of three studies investigating the widely held belief that "milk produces mucus," 60 volunteers were challenged with rhinovirus-2, and daily respiratory symptoms and milk and dairy product intake records were kept over a 10-day period. Nasal secretion weights were obtained by weighing tissues collected and sealed immediately after use. Information was obtained on 51 subjects, yielding 510 person-days of observation. Subjects consumed zero to 11 glasses of milk per day (mean, 2.7; SE, 0.08), and secretion weights ranged from zero to 30.4 g/day (mean, 1.1; SE, 0.1). In response to an initial questionnaire, 27.5% reported the practice of reducing intake of milk or dairy products with a cold or named milk or dairy products as bad for colds. Of the latter group, 80% stated the reason as "producing more mucus/phlegm." Milk and dairy product intake was not associated with an increase in upper or lower respiratory tract symptoms of congestion or nasal secretion weight. A trend was observed for cough, when present, to be loose with increasing milk and dairy product intake; however, this effect was not statistically significant at the 5% level. Those who believe "milk makes mucus" or reduce milk intake with colds reported significantly more cough and congestion symptoms, but they did not produce higher levels of nasal secretions. We conclude that no statistically significant overall association can be detected between milk and dairy product intake and symptoms of mucus production in healthy adults, either asymptomatic or symptomatic, with rhinovirus infection.

Adolescent↗
PubMed1988

Does anxiety reduce the secretion rate of secretory IgA in saliva?

The effects of anxiety, depression and psychological stress on the secretion rate of salivary immunoglobulin (Ig)A were examined in a cross-sectional study of 114 registered nurses. A single, timed (five minutes) sample of whole unstimulated saliva was collected from each nurse; at the time of collection, psychosocial data for each nurse were collected by questionnaire. Nurses who reported more frequent episodes of anxiety had significantly lower mean secretion rates of salivary IgA than did nurses who reported only occasional episodes of anxiety. The concentration of secretory IgA in saliva decreased as the salivary volume increased. It was not possible to demonstrate whether anxiety influenced IgA secretion in saliva independently of its effects on salivary flow.

Adult↗