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Antireroviral therapy is still very much a guessing game, but clear guidance is emerging on two other fronts: heading off opportunistic infections and preventing perinatal transmission. [ABSTRACT FROM AUTHOR]

Objectives: We investigated potential risk factors for active injection drug use (IDU) in an inner-city cohort of patients infected with hepatitis C virus (HCV)., Methods: We used log-binomial regression to identify factors independently associated with active IDU during the first 3 years of follow-up for the 289 participants who reported ever having injected drugs at baseline., Results: Overall, 142 (49.1%) of the 289 participants reported active IDU at some point during the follow-up period. In a multivariate model, being unemployed (prevalence ratio [PR] = 1.93; 95% confidence interval [CI] = 1.24, 3.03) and hazardous alcohol drinking (PR = 1.67; 95% CI = 1.34, 2.08) were associated with active IDU. Smoking was associated with IDU but this association was not statistically significant. Patients with all 3 of those factors were 3 times as likely to report IDU during follow-up as those with 0 or 1 factor (PR = 3.3; 95% CI = 2.2, 4.9). Neither HIV coinfection nor history of psychiatric disease was independently associated with active IDU., Conclusions: Optimal treatment of persons with HCV infection will require attention to unemployment, alcohol use, and smoking in conjunction with IDU treatment and prevention.

Background: Cervical cancer is a leading cause of cancer death for women in Latin America, and vaccinating against human papillomavirus (HPV) has the potential to limit this disease. We sought to determine Honduran women's awareness of HPV vaccination and interest in vaccinating their daughters against HPV., Methods: We interviewed mothers aged ≥17 at primary care clinics in Honduras. First, we collected demographic information and assessed knowledge related to cervical cancer prevention and awareness of HPV and HPV vaccination. Because most participants were not familiar with HPV, education about the relationships among HPV, sexual activity, and cervical cancer was provided before we asked participants if they would accept HPV vaccination for a 9-year-old daughter. We used multivariable logistic regression to determine predictors of vaccine acceptance., Results: We interviewed 632 mothers. Only 13% had heard of HPV vaccination before the interview. After education, 91% would accept HPV vaccination for a 9-year-old daughter. Mothers who intended to vaccinate knew more at baseline about cervical cancer prevention than did those who did not endorse vaccination. Demographic characteristics did not predict vaccine acceptance., Conclusions: Few Honduran mothers were aware of HPV or HPV vaccination. However, most Honduran mothers would accept HPV vaccination for their daughters after receiving education about the relationship between HPV infection and cervical cancer. Baseline cervical cancer knowledge was associated with vaccine acceptance.

Background: Standard practice in obstructive sleep apnea (OSA) management requires that a positive diagnostic, overnight polysomnography (PSG) test be obtained before initiating treatment. However, long waiting times due to lack of access to PSG testing facilities may delay the initiation of definitive treatment for OSA., Objectives: To evaluate the response of patients who had a high clinical suspicion for OSA and who were waiting for a PSG test to an empirical continuous positive airway pressure (CPAP) trial., Methods: A retrospective study of all patients who had been offered empirical CPAP therapy for suspected OSA was conducted. After outpatient assessment, 183 patients with a high pretest probability of having OSA began empirical CPAP testing using an arbitrary CPAP pressure. The presence of OSA, the accuracy of empirical CPAP pressure prescription, the adherence to empirical CPAP and the improvement in daytime somnolence were evaluated at the time of PSG., Results: Of 183 patients on a CPAP trial, 91% had OSA, which was at least moderate (more than 15 apneas and hypopneas per hour of sleep) in 75% of the patients. Eighty per cent of the patients had significant daytime somnolence (Epworth Sleepiness Scale [ESS] greater than 10, mean +/- SD ESS 14+/-5), which improved with CPAP (ESS 9.0+/-5, P<0.01). In 40% of the patients, the arbitrary CPAP pressure was lower than that determined by manual titration. Adherence to a trial of CPAP (longer than 2 h/night) predicted OSA with a sensitivity of 82% and a specificity of 41%; the positive and negative predictive values were 92% and 22%, respectively., Conclusions: At the time of PSG testing, OSA was present in 91% of the patients who had received empirical CPAP. An empirical CPAP provided satisfactory interim treatment for excessive somnolence, despite the fact that the CPAP pressure was suboptimal in 40% of the patients.

Background: The incidence and severity of herpes zoster and postherpetic neuralgia increase with age in association with a progressive decline in cell-mediated immunity to varicella-zoster virus (VZV). We tested the hypothesis that vaccination against VZV would decrease the incidence, severity, or both of herpes zoster and postherpetic neuralgia among older adults., Methods: We enrolled 38,546 adults 60 years of age or older in a randomized, double-blind, placebo-controlled trial of an investigational live attenuated Oka/Merck VZV vaccine ("zoster vaccine"). Herpes zoster was diagnosed according to clinical and laboratory criteria. The pain and discomfort associated with herpes zoster were measured repeatedly for six months. The primary end point was the burden of illness due to herpes zoster, a measure affected by the incidence, severity, and duration of the associated pain and discomfort. The secondary end point was the incidence of postherpetic neuralgia., Results: More than 95 percent of the subjects continued in the study to its completion, with a median of 3.12 years of surveillance for herpes zoster. A total of 957 confirmed cases of herpes zoster (315 among vaccine recipients and 642 among placebo recipients) and 107 cases of postherpetic neuralgia (27 among vaccine recipients and 80 among placebo recipients) were included in the efficacy analysis. The use of the zoster vaccine reduced the burden of illness due to herpes zoster by 61.1 percent (P<0.001), reduced the incidence of postherpetic neuralgia by 66.5 percent (P<0.001), and reduced the incidence of herpes zoster by 51.3 percent (P<0.001). Reactions at the injection site were more frequent among vaccine recipients but were generally mild., Conclusions: The zoster vaccine markedly reduced morbidity from herpes zoster and postherpetic neuralgia among older adults., (Copyright 2005 Massachusetts Medical Society.)

Although carboxyhemoglobin (COHb) is often increased in smokers, American Thoracic Society recommendations for adjusting the single breath carbon monoxide (CO) diffusing capacity (DL(CO)(SB)) for COHb remain optional. Using a previously described 3-equation technique, we measured DL(CO)(SB) and an index of diffusion inhomogeneity (DI) in 10 healthy, nonsmoking subjects who performed DL(CO)(SB) maneuvers both before and after increasing COHb. CO backpressure (FA(CO)) was measured from the exhaled gas of a standardized deep breath of room air that immediately preceded each DL(CO)(SB) and was validated by measurement of FA(CO) from an identical "sham" maneuver without inhaling CO. Without adjustments for FA(CO) or COHb, DL(CO)(SB) decreased with increasing COHb. This effect persisted when DL(CO)(SB) was adjusted only for FA(CO), but it was eliminated with further adjustment for the anemia effect of increasing COHb. The anemia adjustment was proportional to the fractional COHb. DI, adjusted for FA(CO), was unaffected by increasing COHb. We conclude that DL(CO)(SB) must be adjusted for both the buildup of CO backpressure and the anemia effect of increasing COHb. Adequate corrections of DL(CO)(SB) can be implemented using FA(CO) measured during a standardized deep breath immediately preceding the DL(CO)(SB) maneuver. Current American Thoracic Society recommendations for DL(CO)(SB) standardization do not adequately compensate for COHb.

Study Objectives: Validation of test-shortening procedures for the 2-min tidal breathing methacholine challenge method., Design: Retrospective chart review., Setting: Tertiary-care university clinical pulmonary function laboratory., Patients: One thousand subjects aged 10 to 85 years (mean +/- SD, 44.5 +/- 16.0 years), 44.5% male, referred for methacholine challenge., Intervention: Two-minute tidal breathing methacholine challenge was performed, with both physician and technician access to published test-shortening procedures., Measurements and Results: There were 315 positive test results (provocative concentration of methacholine causing a 20% fall in FEV(1) [PC(20)] < or = 8 mg/mL) and 685 negative test results. The subjects with positive test results were less likely to be male (39.1 vs 47.5%; p < 0.02) and had lower FEV(1) (91.8 +/- 14.9% predicted vs 97.2 +/- 13.9% predicted; p < 0.001). The average starting PC(20) was between 0.5 mg/mL and 1.0 mg/mL; the most common PC(20) was 1 mg/mL (67%). There were 431 skipped concentrations in 380 subjects. The mean number of methacholine inhalations was 3.7 +/- 1.1 (3.9 +/- 0.1 for negative test results vs 3.3 +/- 1.2 for positive test results; p < 0.001). Eighteen subjects had a > or = 20% FEV(1) fall on the first inhalation, and 11 subjects had a > or = 20% FEV(1) fall after a skipped concentration. In only one case (0.1%) an FEV(1) fall > or = 40% on the first concentration was reported, compared with no cases after a skipped concentration and seven cases with a > or = 40% FEV(1) fall after a routine doubling dose step-up., Conclusions: The 2-min tidal breathing methacholine test in clinical practice can be safely shortened to an average of less than four inhalations using starting concentrations based on FEV(1), asthma medication, and clinical features, and by occasionally omitting concentrations.

Background: Methacholine-induced bronchoconstriction is associated with significant hypoxemia, which can be assessed noninvasively by transcutaneous oxygen tension and pulse oximetry., Objectives: To assess the value of the monitoring of finger pulse oximetry during routine methacholine challenges in a clinical pulmonary function laboratory with regard to both safety and the possibility that a significant fall in oxygen saturation as measured by pulse oximetry (SpO(2)) might be a useful surrogate for determining the response to methacholine., Methods: Two hundred consecutive patients undergoing diagnostic methacholine challenges in the pulmonary function laboratory of a tertiary-care, university-based referral hospital were studied. Methacholine challenges were performed by the standardized 2-min tidal breathing technique, and the DeltaFEV(1) was calculated from the lowest postsaline solution inhalation to the lowest postmethacholine inhalation value. SpO(2) was measured immediately prior to each spirogram, and the DeltaSpO(2) was measured from the lowest postsaline solution inhalation value to the lowest postmethacholine inhalation value. We examined the data for safety (ie, any SpO(2) value < 90). Based on previous reports, we used a DeltaSpO(2) of > or = 3 as significant and looked at the sensitivity, specificity, and positive and negative predictive values for DeltaSpO(2) > or = 3 vis-à-vis a fall in FEV(1) of > or = 15%., Results: There were 119 nonresponders (DeltaFEV(1), < 15%) and 81 responders. The baseline FEV(1) percent predicted was slightly but significantly lower in the responders (responders [+/- SD], 91.6 +/- 15%; nonresponders, 96.4 +/- 14%; p < 0.05). DeltaSpO(2) was 3.1 +/- 1.6 in the responders and 1.6 +/- 1.8 in the nonresponders (p < 0. 001). There was a single recording in one patient of SpO(2) < 90 (88). A DeltaSpO(2) > or = 3 had a sensitivity of 68%, a specificity of 73%, a positive predictive value of 63%, and negative predictive value of 77% for a fall in FEV(1) > or = 15%., Conclusions: Pulse oximetry is not routinely useful for safety monitoring during methacholine challenge. DeltaSpO(2) is not helpful in predicting a positive spirometric response to methacholine. However, the negative predictive value is adequate to allow the DeltaSpO(2) to be used as an adjunct in assessing a negative result of a methacholine test in patients who have difficulty performing spirometry.

Objective: To prospectively examine differences in baseline characteristics and study outcomes between HIV-infected women and men during a clinical trial of nucleoside analogue therapy., Methods: ACTG 175 randomized HIV-infected patients with CD4+ counts between 200 and 500 cells/mm3 to one of four nucleoside analogue regimens: zidovudine (ZDV), didanosine (ddI), ZDV + ddI, or ZDV + zalcitabine (ddC). Differences in time to first dose modification, voluntary withdrawal, development of toxicity and symptomatology, and AIDS progression were compared by gender., Results: The study included 438 women and 2029 men. Baseline values of HIV RNA plasma concentrations were significantly lower for women (0.3 log10) than men in a subset of patients in whom assays were taken and this difference persisted after adjustment for CD4+ count. Women reported reducing dosage and discontinue ddI-containing regimens more frequently than men did; adjustment for weight did not completely explain this difference. Women were at lower risk than men for progression to a study endpoint (19% of women versus 24% of men; p <.0001). Among those antiretroviral-naive study subjects receiving ZDV, men were four times more likely to progress to a study endpoint than women., Conclusions: Differences in pretreatment characteristics and on study experiences were demonstrated between women and men enrolled in this clinical trial. The suggestion of a gender difference in response to ZDV monotherapy by antiretroviral-naive study subjects and the lower baseline values for HIV RNA in women compared with those in men provides evidence for gender differences in the relationship between virus replication, CD4+ decline, and responses to nucleoside analogue therapy.

CAL remains an important cause of morbidity and mortality. The diffusing capacity has ranked high in the assessment of CAL because it represents the best pulmonary function test to assess the integrity of the pulmonary capillary bed. Unfortunately, numerous physiologic, pathologic, and technical factors affect the test, thus limiting its sensitivity and specificity. HRCT techniques offer the potential to assess the extent of emphysema more accurately, but the technique requires greater standardization and is more expensive and less noninvasive than DLcoSB testing. Although the CIBA symposium considered DLcoSB "essential" in the investigation of the CAL patient, 16 the use of conventional DLcoSB testing in the seated position at rest is not currently advised as a routine screening procedure. The test must be performed in a center with high degree of quality control, and the results can be of value only by integrating the result into a comprehensive clinical assessment. Within this context, conventional DLcoSB testing may provide limited information about the extent of emphysema because reductions in DLcoSB correlate with the extent of emphysema by HRCT. When DLcoSB is normal, it may point in the direction of considering asthma as the cause of the airflow limitation. It may also provide information about disease severity and prognosis in O2-dependent CAL patients. The test should be a part of the investigation of the patient with unexplained dyspnea. It remains controversial how emphysema correlates with the degree of impairment in CAL, and further work needs to be done to clarify this relationship. This requires a reexamination of current CT methods 110 and the relationship between DLcoSB, structural changes in the lung, and HRCT evidence of emphysema. Refinements in DLcoSB testing methods, such as the measurement of DLcoSB-3EQ are linked to rapidly responding CO analyzers and computer-driven software, which will potentially improve the accuracy and reproducibility of the test, particularly in the presence of airway obstruction and nonuniform distribution of ventilation. Such refinements, which offer the possibility that tests of diffusion could become more useful markers of disease, include measuring DLcoSB when the pulmonary capillary recruitment is near maximal (head-down position, exercise), enhancing the sensitivity of the test to alterations in the lung periphery, standardizing previous volume history, developing more precise corrections for Hb and COHb, and developing an index of diffusion nonuniformity.

Computers are steadily being incorporated in clinical practice. We conducted a nonrandomised, controlled, prospective trial of electronic messages designed to enhance adherence to clinical practice guidelines. We studied 126 physicians and nurse practitioners who used electronic medical records when caring for 349 patients with HIV infection in a primary care practice. We analysed the response times of clinicians to the situations that triggered alerts and reminders, the number of ambulatory visits, and hospitalisation. The median response times to 303 alerts in the intervention group and 388 alerts in the control group were 11 and 52 days (p < 0.0001), respectively. The median response time to 432 reminders in the intervention group was 114 days and that for 360 reminders in the control group was over 500 days (p < 0.0001). There was no effect on visits to the primary care practice. There was, however, a significant increase in the rate of visits outside the primary care practice (p = 0.02), which is explained by the increased frequency of visits to ophthalmologists. There were no differences in admission rates (p = 0.47), in admissions for pneumocystosis (p = 0.09), in visits to the emergency ward (p = 0.24), or in survival (p = 0.19). We conclude that the electronic medical record was effective in helping clinicians adhere to practice guidelines.

To meet the needs of primary care physicians caring for patients with HIV infection, we developed a knowledge-based medical record to allow the on-line patient record to play an active role in the care process. These programs integrate the on-line patient record, rule-based decision support, and full-text information retrieval into a clinical workstation for the practicing clinician. To determine whether use of a knowledge-based medical record was associated with more rapid and complete adherence to practice guidelines and improved quality of care, we performed a controlled clinical trial among physicians and nurse practitioners caring for 349 patients infected with the human immuno-deficiency virus (HIV); 191 patients were treated by 65 physicians and nurse practitioners assigned to the intervention group, and 158 patients were treated by 61 physicians and nurse practitioners assigned to the control group. During the 18-month study period, the computer generated 303 alerts in the intervention group and 388 in the control group. The median response time of clinicians to these alerts was 11 days in the intervention group and 52 days in the control group (PJJ0.0001, log-rank test). During the study, the computer generated 432 primary care reminders for the intervention group and 360 reminders for the control group. The median response time of clinicians to these alerts was 114 days in the intervention group and more than 500 days in the control group (PJJ0.0001, log-rank test). Of the 191 patients in the intervention group, 67 (35%) had one or more hospitalizations, compared with 70 (44%) of the 158 patients in the control group (PJ=J0.04, Wilcoxon test stratified for initial CD4 count). There was no difference in survival between the intervention and control groups (P = 0.18, log-rank test). We conclude that our clinical workstation significantly changed physicians' behavior in terms of their response to alerts regarding primary care interventions and that these interventions have led to fewer patients with HIV infection being admitted to the hospital.

Data on the prevalence and patterns of use of concomitant medications among participants in three large phase III clinical trials of zidovudine (ZDV) in human immunodeficiency virus type 1 (HIV-1) infection were analyzed. Overall, 2,801 patients reported 43,331 uses of concomitant medications. Over 85% of clinical trial participants used one or more concomitant medications at some point during the study. Patients with acquired immune deficiency syndrome (AIDS) used an average of 7.1 drugs per month. Patients with AIDS-related complex (ARC) or who were asymptomatic used relatively fewer drugs: 3.1 and 2.7 per month, respectively. Fourteen percent of patients with AIDS used more than 10 concomitant medications per month. The three most commonly utilized classes of drugs were antiinfectives (57%), analgesics or antipyretics (55%), and vitamins (47%). A total of 17% of patients overall and 30% of AIDS patients used acyclovir while on trial. Consumption of prescription drugs was greater, and "over-the-counter" drugs less, among AIDS patients. Reported use of agents not approved by the Food and Drug Administration or approved drugs used for off-label indications was infrequent. Overall use of concomitant medications did not differ across demographic subgroups when corrected for disease stage at the time of enrollment. White, non-Hispanic, homosexual and bisexual men consumed significantly more antivirals and vitamins than other trial participants. Women in all three protocols took more analgesics or antipyretics than did men.(ABSTRACT TRUNCATED AT 250 WORDS)

The dynamic changes in CO concentration [CO] during a single breath could be influenced by topographic inhomogeneity in the lung or by peripheral inhomogeneity due to a gas mixing resistance in the gas phase of the lung or to serial gradients in gas diffusion. Ten healthy subjects performed single-breath maneuvers by slowly inhaling test gas from functional residual capacity to one-half inspiratory capacity and slowly exhaling to residual volume with target breath-hold times of 0, 1.5, 3, 6, and 9 s. We calculated the three-equation single-breath diffusing capacity of the lung for CO (DLSBCO-3EQ) from the mean [CO] in both the entire alveolar gas sample and in four successive equal alveolar gas samples. DLSBCO-3EQ from the entire alveolar gas sample was independent of breath-hold time. However, with 0 s of breath holding, from early alveolar gas samples DLSBCO-3EQ was reduced and from late alveolar gas samples it was increased. With increasing breath-hold time, DLSBCO-3EQ from the earliest alveolar gas sample rapidly increased, whereas from the last alveolar gas sample it rapidly decreased such that all values from the small alveolar gas samples approached DLSBCO-3EQ from the entire alveolar sample. These changes correlated with ventilation inhomogeneity, as measured by the phase III He concentration slope and the mixing efficiency, and were larger for maneuvers with inspired volumes to one-half inspiratory capacity vs. total lung capacity.(ABSTRACT TRUNCATED AT 250 WORDS)

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 computer, we compared the rate of detection of HIV-related factors elicited by the computer interview with the rate elicited by standard American Red Cross procedures (written questionnaires and face-to-face interviews) for assessment of donor suitability. The study was performed at a Red Cross blood donor center and a hospital. A consecutive sample of 294 male and female blood donors 18 to 75 years of age participated in a randomized crossover trial in which the order of the two methods was reversed. Among 272 prospective donors who provided complete data, the computer identified 12 who reported either behavior associated with a risk of acquiring HIV or symptoms compatible with AIDS. None of these 12 was so identified by face-to-face interviews or written questionnaires. Only one used the confidential unit exclusion procedure to prevent use of his donated blood. Tests for antibody to HIV were negative in blood from all 272 subjects. The subjects enjoyed the computer interview and judged it to be more private than the standard method for donor assessment.

To determine factors influencing the enrollment of women in a large multicenter human immunodeficiency virus (HIV) clinical trials program in the United States, we analyzed enrollment and demographic data of the AIDS Clinical Trials Group (ACTG) during the period 1987-90. Women comprised 6.7% of 11,909 ACTG participants enrolled in 1987-90. Women entering ACTG trials were significantly more likely to be white (48.5%) and less likely to have ever used i.v. drugs (22.6%) than U.S. women reported to have AIDS (26.5% were white; 51.0% had ever used i.v. drugs, p < 0.0001). In a multiple logistic regression model, specific attributes of individual trials did not influence enrollment of women with the exception that trials that targeted asymptomatic persons had greater enrollment of women. There was wide variation among research units in the percentage of women enrolled (1.0-37.5%), and evidence of significant regional variation in the ability of units to recruit available women. Units with female principal or coprincipal investigators had more than twice the percentage of female enrollment as units headed by men (10.8 vs. 5.3%, p < 0.001). Enrollment of women in a large HIV clinical trials program was low and appeared to be influenced more by demographic and geographic factors that attributes of specific trials. An apparent positive influence of female leadership on the enrollment of women warrants further study.

In normal seated subjects we increased single-breath ventilation inhomogeneity by changing both the preinspiratory lung volume and breath-hold time and examined the ensuing effects on two different techniques of measuring the diffusing capacity of the lung for carbon monoxide (DLCO). We measured the mean single-breath DLCO using the three-equation method (DLCOSB-3EQ) and also measured DLCO over discrete intervals during exhalation by the "intrabreath" method (DLCOexhaled). We assessed the distribution of ventilation using the normalized phase III slope for helium (SN). DLCOSB-3EQ was unaffected by preinspiratory lung volume and breath-hold time. DLCOexhaled increased with increasing preinspiratory lung volume and decreased with increasing breath-hold time. These changes correlated with the simultaneously observed changes in ventilation inhomogeneity as measured by SN (P < 0.01). We conclude that measurements of DLCOexhaled do not accurately reflect the mean DLCO. Intrabreath methods of measuring DLCO are based on the slope of the exhaled CO concentration curve, which is affected by both ventilation and diffusion inhomogeneities. Although DLCOexhaled may theoretically provide information about the distribution of CO uptake, the concomitant effects of ventilation nonuniformity on DLCOexhaled may mimic or mask the effects of diffusion nonuniformity.

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.

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.

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.

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.

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.

Objective: To determine the effectiveness and costs of alternative management strategies for patients infected with the human immunodeficiency virus (HIV) who present with pulmonary symptoms., Design: Decision analysis comparing initial testing (arterial blood gas analysis, induced sputum analysis, or bronchoscopy with bronchoalveolar lavage) with empiric antibiotics (trimethoprim-sulfamethoxazole or erythromycin). Subsequent steps in management are detailed based on the results of initial management. Patients were stratified by initial CD4 lymphocyte count (less than 200/mm3, 200-500/mm3, or greater than 500/mm3) and results of chest radiography., Setting: Hypothetical., Measurements and Main Results: The estimated levels of effectiveness among strategies were relatively similar, but costs varied markedly. If potentially reasonable strategies are defined as those that have incremental cost-effectiveness ratios below $50,000 per quality-adjusted life year (QALY), the recommended strategies would be: for patients at highest risk for Pneumocystis carinii pneumonia (PCP), with a probability of PCP above 30% (CD4 less than 200/mm3 and abnormal chest radiograph or prior history of PCP), begin with induced sputum analysis ($34,174/QALY); for intermediate-risk patients, with a probability of PCP between 6% and 30% (CD4 less than 200/mm3, regardless of chest radiograph; or CD4 200-500/mm3, regardless of chest radiograph findings), begin with arterial blood gas analysis ($4,593 to $8,310/QALY); for low-risk patients, with a probability of PCP below 6% (CD4 greater than 500/mm3, regardless of chest radiograph findings), begin with one week of erythromycin, followed by induced sputum examination if symptoms persist ($675 to $3,306/QALY). For highest-risk patients, if empiric trimethoprim-sulfamethoxazole was considered entirely to be outpatient therapy, it was preferred management if the probability of PCP was above 38%., Conclusions: The authors conclude that preferred management strategies are determined more by differences in costs than by differences in levels of effectiveness, and that they vary depending on the probability of PCP in definable patient subgroups.

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.

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.

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.

In 10 nonasthmatic subjects and 11 patients with asthma, we measured pulmonary resistance (RL), functional residual capacity (FRC), and specific conductance (sGaw) before, during, and after submaximal treadmill exercise. Nonasthmatic subjects did not change RL, FRC, or sGaw from base-line resting values during or after exercise. In patients with asthma, RL decreased significantly during exercise, both when exercise was begun from the control resting state and from conditions of elevated RL after a preceding period of exercise. When asthmatic patients inhaled a standardized dose of aerosolized histamine, the increase in RL during exercise was significantly less than the increase in RL when they breathed histamine at rest. When patients hyperventilated at rest with tidal volumes, breathing frequencies, and end-tidal CO2 tensions similar to those during exercise conditions, bronchodilatation also occurred, and the increase in RL following inhaled histamine during isocapnic hyperventilation was also less than at rest. Since bronchodilatation and inhibition of histamine-induced bronchoconstriction occur during both exercise and isocapnic hyperventilation, we suggest that the mechanism of bronchodilatation during exercise may not necessarily be related to metabolic factors associated with exercise.

We measured nonspecific bronchial reactivity to inhaled histamine in 26 lifetime nonsmoking grain handlers and 29 lifetime nonsmoking unexposed control subjects matched for age, sex and specific conductance. Routine lung function tests revealed a total lung capacity that was higher in control subjects than in workers (P less than 0.05) with no difference in other subdivisions of lung volume, or expiratory flow rates between the two groups. An index of allergy was significantly greater in the control subjects than in the grain workers (P less than 0.01). None of the grain handlers was sensitive to grain dust by history or by skin tests. Respiratory symptoms (cough, sputum, dyspnea, or wheezing) were more prevalent in the grain workers than in controls (P less than 0.05). The mean concentration of histamine required to reduce the specific conductance by 35 percent was 4.5 +/- 2.0 mg/ml in grain workers and 5.9 +/- 3.0 mg/ml in controls (P less than 0.05). Chronic exposure to grain dust in nonallergic individuals appears to be associated with both increased prevalence of respiratory symptoms and increased nonspecific bronchial reactivity when compared to nonexposed control subjects.

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.

Two cases of facial erysipelas in immunologically altered hosts are reported herein. The unusual presentation with absence of erythema in the skin lesion is emphasized. Atypical fever patterns were also noted. In one patient, the facial lesion followed the onset of fever by 48 hours, and, in the other, the facial swelling preceded the fever. Various aspects of the patient's altered host status are discussed in light of the atypical clinical presentation. Recognition of facial erysipelas as a potential source of group A beta-hemolytic streptococcemia in immune-altered hosts is important to ensure rapid and appropriate therapeutic intervention.

A 55-year-old nonatopic man presented with a 2-year history of progressively severe conjunctivitis, rhinitis, and asthma related to exposure to freshly cut red cedar. Chest roentgenogram, lung volumes, diffusing capacity for carbon monoxide, and expiratory flow rates were normal. A histamine inhalation test demonstrated mild, nonspecific bronchial hyperreactivity. After a 35-min cumulative exposure to Western Red Cedar sawdust in the laboratory, the patient developed a late asthmatic response. Bronchial reactivity to inhaled histamine increased significantly after exposure to red cedar in the laboraotry and again after natural exposure to red cedar at work. However, on both occasions forced expiraotry volume in one sec was decreased when compared to control values. Exposure to red cedar sawdust for 15 min was repeated in the laboratory, and histamine inhalation tests were performed the day before, for 4 consecutive days after, and 11 days after exposure. Before each test, one-sec forced expiratory volume, lung volumes, specific conductance, maximal expiratory flow rates at 25 and 50 per cent of vital capacity, closing capacity, and the slope of phase III from the single-breath O2 test were measured. Six hours after exposure to cedar, all measurements documented significant airway obstruction that persisted until the second day. Bronchial responsiveness to inhaled histamine also increased on the first 2 days after exposure to cedar, but this increase persisted on the third and fourth day when all other pulmonary function tests had returned to control values. Eleven days later, the bronchial hyperreactivity to inhaled histamine had also returned to control values. In a sensitized subject, exposure to Western Red Cedar induced a transient increase in nonspecific bronchial reactivity that was present in the absence of airflow obstruction. Factors other than decreased airway caliber are probably important in this phenomenon.

It has been shown that measurements of the diffusing capacity of the lung for CO made during a slow exhalation [DLCO(exhaled)] yield information about the distribution of the diffusing capacity in the lung that is not available from the commonly measured single-breath diffusing capacity [DLCO(SB)]. Current techniques of measuring DLCO(exhaled) require the use of a rapid-responding (less than 240 ms, 10-90%) CO meter to measure the CO concentration in the exhaled gas continuously during exhalation. DLCO(exhaled) is then calculated using two sample points in the CO signal. Because DLCO(exhaled) calculations are highly affected by small amounts of noise in the CO signal, filtering techniques have been used to reduce noise. However, these techniques reduce the response time of the system and may introduce other errors into the signal. We have developed an alternate technique in which DLCO(exhaled) can be calculated using the concentration of CO in large discrete samples of the exhaled gas, thus eliminating the requirement of a rapid response time in the CO analyzer. We show theoretically that this method is as accurate as other DLCO(exhaled) methods but is less affected by noise. These findings are verified in comparisons of the discrete-sample method of calculating DLCO(exhaled) to point-sample methods in normal subjects, patients with emphysema, and patients with asthma.

In this study we have examined the relationship between the bronchial response to inhaled histamine and the bronchial response to breathing cold air at rest in nine control subjects and nine patients with asthma. Dried warm air (mean temp: +/- 1SD: 25.4 +/- 1.6 degrees C) and cold air (-19.7 +/- 2.6 degrees C) were breathed for 10 minutes each during quiet breathing at rest prior to as well as during both measurements of forced expired spirograms and the phase 3 slope of the single-breath oxygen test (delta N2/L). Subjects were also challenged with inhaled aerosolized histamine to determine the concentration required to reduce the forced expired volume in one second (FEV1) by 20 percent (PC20). Both asthmatic and control subjects had significantly greater respiratory heat exchange breathing cold as compared to warm air (p less than 0.01 in both cases). Control subjects did not change FEV1 or delta N2/L breathing cold air. Asthmatic patients increased delta N2/L from a mean warm air value of 2.41 +/- 1.31% N2/L to a mean cold air value of 5.39 +/- 4.55% N2/L (p less than 0.05). There was a significant linear correlation between the percent increase in delta N2/L from warm to cold air and 1/log10PC20 (r = -0.97, p less than 0.001) and also the percent decrease in FEV1 and log PC20 (r = -0.76, p less than 0.03) in the asthmatic patients. We conclude that cold air-induced alterations in ventilation/distribution and expired flow rates in asthmatic patients are related to pre-existing nonspecific airways reactivity.

Recent studies have shown that diffusing capacities measured at multiple intervals during a single exhalation [DLCO(exhaled)] remained constant with lung volume in normal subjects, but decreased with decreasing lung volume in patients who may have had diffusion nonuniformity. We have examined the theoretical basis of these results by determining what factors affected DLCO(exhaled) in a computerized lung model in which diffusion in each compartment remained constant with lung volume. DLCO(exhaled) decreased with decreasing lung volume when a small lung region lacked diffusion. However, the change in DLCO(exhaled) with lung volume was also affected by nonuniform ventilation and these effects could not be eliminated by correcting the carbon monoxide decay and the simultaneous decay of helium. DLCO(exhaled) values were also influenced by the exhaled flow rate in the presence of nonuniform ventilation and/or nonuniform diffusion. However, prolonging the period of breath holding prior to exhalation reduced DLCO(exhaled) values at all lung volumes when non-uniform diffusion was simulated, but did not affect DLCO(exhaled) when only nonuniform ventilation was simulated.