Exhaled nitric oxide levels correlate with measures of disease control in asthma.

BACKGROUND: Asthma guidelines emphasize maintaining disease control. However, objective measures of asthma disease control are lacking. OBJECTIVE: We sought to examine the relationship between exhaled nitric oxide (NO) levels and measures of asthma disease control versus asthma disease severity. METHODS: We performed a cross-sectional study of 100 patients (age range, 7-80 years) with asthma. We administered a questionnaire to identify characteristics of asthma, performed spirometric testing before and after administration of a bronchodilator, and measured exhaled NO levels in all participants. RESULTS: Exhaled NO was significantly correlated with the following markers of asthma disease control: asthma symptoms within the past 2 weeks (P =.02), dyspnea score (P =. 02), daily use of rescue medications (P =.01), and reversibility of airflow obstruction (P =.02). Exhaled NO levels were not correlated with the following markers of asthma disease severity: history of respiratory failure (P =.20), health care use (P =.08), fixed airflow obstruction (P =.91), or a validated asthma severity score (P =.19). Markers with relevance to both disease control and severity showed either a weak correlation (FEV(1) and FEV(1) percent predicted) or no correlation (controller drug use) with exhaled NO. CONCLUSION: We conclude that exhaled NO levels are correlated predominantly with markers of asthma control rather than asthma severity. Monitoring of exhaled NO may be useful in outpatient asthma management.

Pneumoperitoneum: a review of nonsurgical causes.

OBJECTIVE: To review causes of nonsurgical pneumoperitoneum (NSP), identify nonsurgical etiologies, and guide conservative management where appropriate. DATA SOURCE: We conducted a computerized MEDLINE database search from 1970 to 1999 by using key words pneumoperitoneum and benign, nonsurgical, spontaneous, iatrogenic, barotrauma, pneumatosis, diaphragmatic defects, free air, mechanical ventilation, gynecologic, and pelvic. We identified 482 articles by using these keywords and reviewed all articles. Additional articles were identified and selectively reviewed by using key words laparotomy, laparoscopy, and complications. STUDY SELECTION: We reviewed all case reports and reviews of NSP, defined as pneumoperitoneum that was successfully managed by observation and supportive care alone or that required a nondiagnostic laparotomy. DATA SYNTHESIS: Each unique cause of nonsurgical pneumoperitoneum was recorded. When available, data on nondiagnostic exploratory laparotomies were noted. Case reports were organized by route of introduction of air into the abdominal cavity: abdominal, thoracic, gynecologic, and idiopathic. CONCLUSIONS: Most cases of NSP occurred as a procedural complication or as a complication of medical intervention. The most common abdominal etiology of NSP was retained postoperative air (prevalence 25% to 60%). NSP occurred frequently after peritoneal dialysis catheter placement (prevalence 10% to 34%) and after gastrointestinal endoscopic procedures (prevalence 0.3% to 25%, varying by procedure). The most common thoracic causes included mechanical ventilation, cardiopulmonary resuscitation, and pneumothorax. One hundred ninety-six case reports of NSP were recorded, of which 45 involved surgical exploration without evidence of perforated viscus. The clinician should maintain a high index of suspicion for nonsurgical causes of pneumoperitoneum and should recognize that conservative management may be indicated in many cases.

Increased exhaled nitric oxide in chronic bronchitis: comparison with asthma and COPD.

STUDY OBJECTIVES: To test the hypothesis that exhaled nitric oxide (NO) is increased in patients with chronic bronchitis, and to compare the results with exhaled NO in patients with asthma and COPD. STUDY DESIGN: Cross-sectional survey. SETTING AND PATIENTS: Veterans Administration pulmonary function laboratory. Patients (n = 179) were recruited from 234 consecutive patients. Two nonsmoking control groups of similar age, with normal spirometry measurements and no lung disease, were used (18 patient control subjects and 20 volunteers). MEASUREMENTS: Participants completed questionnaires and spirometry testing. Exhaled NO was measured by chemiluminescence using a single-breath exhalation technique. RESULTS: Current smoking status was associated with reduced levels of exhaled NO (smokers, 9. 2 +/- 0.9 parts per billion [ppb]; never and ex-smokers, 14.3 +/- 0. 6 ppb; p < 0.0001). Current smokers (n = 57) were excluded from further analysis. Among nonsmokers, the levels of exhaled NO were significantly higher in patients with chronic bronchitis (17.0 +/- 1. 1 ppb; p = 0.035) and asthma (16.4 +/- 1.3 ppb; p = 0.05) but not in those with COPD (14.7 +/- 1.0 ppb; p = 0.17) when compared with either control group (patient control subjects, 11.1 +/- 1.6 ppb; outside control subjects, 11.5 +/- 1.5 ppb). The highest mean exhaled NO concentration occurred in patients with both chronic bronchitis and asthma (20.2 +/- 1.6 ppb; p = 0.005 vs control subjects). CONCLUSIONS: Exhaled NO is increased in patients with chronic bronchitis. The increase of exhaled NO in patients with chronic bronchitis was similar to that seen in patients with asthma. The highest mean exhaled NO occurred in patients with both chronic bronchitis and asthma. Exhaled NO was not increased in patients with COPD. Although chronic bronchitis and asthma have distinct histopathologic features, increased exhaled NO in patients with both diseases suggests common features of inflammation.

Smoking cessation in primary care clinics.

OBJECTIVES: To document smoking cessation rates achieved by applying the 1996 Agency for Health Care Policy and Research (AHCPR) smoking cessation guidelines for primary care clinics, compare these quit rates with historical results, and determine if quit rates improve with an additional motivational intervention that includes education as well as spirometry and carbon monoxide measurements. DESIGN: Randomized clinical trial. SETTING: Two university-affiliated community primary care clinics. PATIENTS: Two hundred five smokers with routinely scheduled appointments. INTERVENTION: All smokers were given advice and support according to AHCPR guidelines. Half of the subjects received additional education with spirometry and carbon monoxide measurements. MEASUREMENTS AND MAIN RESULTS: Quit rate was evaluated at 9-month follow-up. Eleven percent of smokers were sustained quitters at follow-up. Sustained quit rate was no different for intervention and control groups (9% vs 14%; [OR] 0.6; 95% [CI] 0.2, 1.4). Nicotine replacement therapy was strongly associated with sustained cessation (OR 6.7; 95% CI 2.3, 19.6). Subjects without insurance were the least likely to use nicotine replacement therapy ( p =.05). Historical data from previously published studies showed that 2% of smokers quit following physician advice, and additional support similar to AHCPR guidelines increased the quit rate to 5%. CONCLUSIONS: The sustained smoking cessation rate achieved by following AHCPR guidelines was 11% at 9 months, which compares favorably with historical results. Additional education with spirometry did not improve the quit rate. Nicotine replacement therapy was the strongest predictor of cessation, yet was used infrequently owing to cost. These findings support the use of AHCPR guidelines in primary care clinics, but do not support routine spirometry for motivating patients similar to those studied here.

Nasal administration of the nitric oxide synthase inhibitor L-NAME induces daytime somnolence.

In preliminary studies, human subjects complained of drowsiness after aerosolization of NG-nitro-L-arginine methyl ester (L-NAME) into the nasal passages. We compared the effects of a nasal aerosol of L-NAME (0.5 M, 4 ml) to those of saline on sleep onset latency and exhaled nasal nitric oxide (NO). L-NAME decreased sleep onset latency and exhaled nasal NO. Vasoconstriction and local effects of L-NAME on NO synthesis are unlikely to explain this effect since oxymetazoline, a vasoconstrictor, decreased exhaled NO but had no effect on sleep onset latency. We conclude that aerosolization of L-NAME to the nasal passages induces daytime sleepiness.

Associations of smoking with hospital-based care and quality of life in patients with obstructive airway disease.

STUDY OBJECTIVES: To investigate the relationship between direct or environmental tobacco smoke (ETS) exposure and both hospital-based care (HBC) and quality of life (QOL) among subjects with asthma. STUDY DESIGN: We report baseline cross-sectional data on 619 subjects with asthma, including direct or ETS exposure and QOL, and prospective longitudinal data on HBC using administrative databases for 30 months following baseline evaluation. SETTING AND PATIENTS: Participants were health maintenance organization members with physician-diagnosed asthma involved in a longitudinal study of risk factors for hospital-based asthma care. MEASUREMENTS: Demographic characteristics and QOL were assessed with administered questionnaires, including the Marks Asthma Quality-of-Life (AQLQ) and SF-36 questionnaires. HBC was defined as episodes per person-year of hospital-based asthma care, which included emergency department and urgency care visits, and hospitalizations for asthma. RESULTS: Current smokers reported significantly worse QOL than never-smokers in two of five domains of the AQLQ (p < 0.05). Subjects with ETS exposure also reported significantly worse QOL than those without ETS exposure in two domains (p < 0.05). On the SF-36, current smokers reported significantly worse QOL than never-smokers in five of nine domains (p < 0.05). Subjects with ETS exposure reported significantly worse QOL than those without ETS exposure in three domains (p < 0.05). Current smokers used significantly more hospital-based asthma care than never-smokers (adjusted relative risk [RR], 1.40; 95% confidence interval [CI], 1.01 to 1.95) while ex-smokers did not exhibit increased risk compared with nonsmokers (adjusted RR, 0.94; 95% CI, 0.7 to 1.3). Also, subjects with ETS exposure used significantly more hospital-based asthma care than those without ETS exposure (RR, 2.34; 95% CI, 1.80 to 3.05). CONCLUSIONS: Direct or environmental tobacco exposure prospectively predicted increased health-care utilization for asthma and reduced QOL in patients with asthma. These findings add to our existing knowledge of the detrimental effects of tobacco smoke and are of relevance specifically to patients with asthma.

Abnormal oxygen uptake kinetic responses in women with type II diabetes mellitus.

Persons with type II diabetes mellitus (DM), even without cardiovascular complications have a decreased maximal oxygen consumption (VO2 max) and submaximal oxygen consumption (VO2) during graded exercise compared with healthy controls. We evaluated the hypothesis that change in the rate of VO2 in response to the onset of constant-load exercise (measured by VO2-uptake kinetics) was slowed in persons with type II DM. Ten premenopausal women with uncomplicated type II DM, 10 overweight, nondiabetic women, and 10 lean, nondiabetic women had a VO2 max test. On two separate occasions, subjects performed 7-min bouts of constant-load bicycle exercise at workloads below and above the lactate threshold to enable measurements of VO2 kinetics and heart rate kinetics (measuring rate of heart rate rise). VO2 max was reduced in subjects with type II DM compared with both lean and overweight controls (P < 0.05). Subjects with type II DM had slower VO2 and heart rate kinetics than did controls at constant workloads below the lactate threshold. The data suggest a notable abnormality in the cardiopulmonary response at the onset of exercise in people with type II DM. The findings may reflect impaired cardiac responses to exercise, although an additional defect in skeletal muscle oxygen diffusion or mitochondrial oxygen utilization is also possible.

Extralobar pulmonary sequestration presenting as a mediastinal malignancy.

Pulmonary sequestration is an uncommon congenital anomaly usually diagnosed in childhood. It frequently presents as a lower lobe mass with symptoms from vascular shunting, anatomic impingements, or associated anatomic defects. This case report describes an adult with asymptomatic extralobar sequestration involving the mediastinum and left upper lobe. The unusual location and radiographic appearance, suggestive of malignancy, led to prompt surgical exploration. We review the literature on this topic, focusing on anatomic variability and difficulties with preoperative diagnosis.

Effect of keyhole limpet hemocyanin (KLH) and bacillus Calmette-Guérin (BCG) instillation on carcinoma in situ of the urinary bladder.

Patients with histologically verified carcinoma in situ (CIS) of the urinary bladder (13 primary and 8 secondary CIS) were treated with intravesical instillations of Keyhole Limpet Hemocyanin (KLH) (20 mg KLH weekly for 6 weeks, then monthly for 1 year or bimonthly for 2 subsequent years. Patients, non-responding to 2 courses of KLH were then treated with regular Bacillus Calmette-Guerin instillations (120 mg BCG-Connaught strain). The follow-up period ranged from 10 to 54 months (mean 23.5 months). 7 patients (33%) were free of tumor after the first therapeutical KLH course and 4 patients (19%) presented a complete-remission after the second KLH course (total primary response: 52%). 5 patients (24%) remained free of tumor during the established follow-up period (mean 31.7 months) and no evidence of further tumor progression occurred in patients after two courses of KLH treatment. However, 2 patients (9.5%) had to be cystectomized after KLH instillations because of progressive disease or tumor recurrence. 8 patients (38%) had to be radically cystectomized because of CIS persistence or progression after KLH and subsequent BCG treatment. Altogether 9 patients (42.8%) presented long-term remissions, with a mean duration of 31.3 months. Instillations of KLH did not induce major side effects; however, instillations of BCG caused severe dysuria in 60% and fever in 40% of patients.

Effects of non-insulin-dependent diabetes on oxygen consumption during treadmill exercise.

Persons with non-insulin-dependent diabetes mellitus (NIDDM), in the absence of complications, have a decreased exercise performance compared with nondiabetic subjects. However, degree of impairment and factors associated with reduced exercise performance have not been fully characterized. Maximal exercise performance using a graded treadmill protocol was assessed in 10 sedentary persons with uncomplicated NIDDM (aged 51 +/- 7) and 10 healthy age- and activity-matched controls. Potential correlates of exercise performance measured included fasting and post-exercise glucose concentrations and fasting insulin concentration, hemoglobin A1C, hematocrit, and whole blood viscosity. At maximal exercise, diabetic persons had a 24% lower maximal walking time and 20% lower maximal VO2 than controls (both P < 0.05), while hemodynamic measures did not differ between groups. During graded exercise, at work loads below the maximal one, the relationship between VO2 and work load was significantly lower in persons with NIDDM than controls by an average of 16%. No correlations were found between peak exercise performance and any of the potential correlates of exercise performance measured. We conclude that persons with NIDDM have an impaired peak exercise performance not associated with degree of glycemic control. The reduced rate of increase in oxygen consumption during increasing submaximal work loads in NIDDM suggests that limitations in oxygen delivery may impair exercise performance in otherwise healthy persons with diabetes.

Effects of non-insulin-dependent diabetes on oxygen consumption during treadmill exercise.

Persons with non-insulin-dependent diabetes mellitus (NIDDM), in the absence of complications, have a decreased exercise performance compared with nondiabetic subjects. However, degree of impairment and factors associated with reduced exercise performance have not been fully characterized. Maximal exercise performance using a graded treadmill protocol was assessed in 10 sedentary persons with uncomplicated NIDDM (aged 51 +/- 7) and 10 healthy age- and activity-matched controls. Potential correlates of exercise performance measured included fasting and post-exercise glucose concentrations and fasting insulin concentration, hemoglobin A1C, hematocrit, and whole blood viscosity. At maximal exercise, diabetic persons had a 24% lower maximal walking time and 20% lower maximal VO2 than controls (both P < 0.05), while hemodynamic measures did not differ between groups. During graded exercise, at work loads below the maximal one, the relationship between VO2 and work load was significantly lower in persons with NIDDM than controls by an average of 16%. No correlations were found between peak exercise performance and any of the potential correlates of exercise performance measured. We conclude that persons with NIDDM have an impaired peak exercise performance not associated with degree of glycemic control. The reduced rate of increase in oxygen consumption during increasing submaximal work loads in NIDDM suggests that limitations in oxygen delivery may impair exercise performance in otherwise healthy persons with diabetes.

Urinary interleukin-1 alpha levels are increased by intravesical instillation with keyhole limpet hemocyanin in patients with superficial transitional cell carcinoma of the bladder.

Intravesical instillation of keyhole limpet hemocyanin (KLH) is a possible treatment for decreasing tumor recurrence after transurethral resection (TUR) in patients with superficial transitional cell carcinoma of the bladder (stages pTa-pT1, grades 1-3). Our study confirms the theory that instillation of KLH stimulates production of cytokines, resulting in their secretion in urine. Interleukin-1 (IL-1) stimulates the immune cascade through a domino effect and is produced mainly by activated macrophages. The instillation program was started 5-7 days after TUR of primary superficial cell carcinoma. 20 mg KLH in 20 ml of 0.9% NaCl was instilled into the bladder each week for 6 consecutive weeks and then monthly for 1 year. When KLH is instilled into the bladder, IL-1 alpha is secreted in the urine. A specific enzyme-linked immunosorbent assay (ELISA) was used for analysis. The ELISA for IL-1 alpha was established in our laboratory and showed a detection limit of 5 pg/ml. This IL-1 alpha ELISA deviation amounts to 3-7% within a series of measurements, and 5-15% from series to series. In the therapy group the IL-1 alpha secretion ranged from 0 to 30,905 pg/24 h and in the control group from 0 (collection period) to 2,472 pg/4 h. IL-1 alpha production increased significantly after KLH instillation in bladder cancer patients; however, the level varied considerably from patient to patient. Maximum production was achieved within a period of 4-8 h, decreasing within 24 h. There was a striking difference between the amount of IL-1 alpha produced over the 24-hour period in the control group and that of the KLH group. 8 of 14 patients (57%) who responded to KLH therapy had higher urine IL-1 alpha levels after 6 weeks of KLH treatment than those who failed to respond within 12 months, but the levels were not of statistical significance. The secretion of IL-1 alpha in urine is the biological response of the bladder to the antigen stimulus of KLH. No IL-2 was detected in the urine samples. It remains to be determined whether no IL-2 cytokine was present, or whether the amount was smaller than the minimal detection limit required for the ELISA.

Meningitis and encephalitis at the Abbassia Fever Hospital, Cairo, Egypt, from 1966 to 1989.

A total of 7,809 patients with meningitis or encephalitis were admitted to the Abbassia Fever Hospital in Cairo, Egypt from November 1, 1966 to April 30, 1989. The etiology was Neisseria meningitidis (mostly group A) in 27.3% of the patients, Mycobacterium tuberculosis in 19.7%, Streptococcus pneumoniae in 7.3%, and Haemophilus influenzae in 4.1%. Almost 27% of the cases had purulent meningitis but without detectable etiology; however, the epidemiologic data suggest that most of these had meningococcal meningitis. Encephalitis was suspected in 12.5% of the patients. Most of the meningococcal, pneumococcal, and Haemophilus cases occurred during the winter months. The number of meningococcal and culture-negative purulent cases per year reached a maximum three times during the 22.5 years of this study. There were more males than females in all etiologic groups, with the ratio for the total patient population being 1.6:1. The average age ranged between 11.7 and 16.5 years for all groups except for Haemophilus patients, who had a mean age of 2.5 years. The mortality rate was almost 55% for tuberculous patients and was approximately 40% for both pneumococcal and Haemophilus patients; it was 8.5% in patients with meningococcal disease.

Detection of IgM antibodies to Neisseria meningitidis group A polysaccharide in meningitis patients by direct and antibody capture enzyme-linked immunosorbent assays.

Serum specimens obtained from culture-positive group A meningococcal meningitis patients in Cairo, Egypt were tested for immunoglobulin M (IgM) antibodies to Neisseria meningitidis group A polysaccharide by direct and IgM capture enzyme-linked immunosorbent assays (ELISAs). Sera from patients with meningitis caused by other bacteria were used as negative control specimens. The IgM antibodies to this antigen were detected by direct ELISA in 93% of 58 specimens obtained from patients with group A meningococcal disease three or more days after hospital admission, and by IgM capture ELISA in 83% of 60 such specimens. Sixteen percent of 25 specimens obtained three or more days after admission from negative control patients were positive by direct ELISA, and 4% were positive by IgM capture ELISA. The correlation coefficient of the results with the two assays was 0.85.

A review of the treatment of bacterial meningitis.

This is review of our experience in the treatment of meningitis carried out at the Naval Medical Research Unit No. 3 (NAMRU-3), Cairo, Egypt since 1967. We have demonstrated that the serum and cerebrospinal fluid concentrations of ampicillin and its efficacy when used in the treatment of meningitis are comparable whether they are administered intravenously or intramuscularly. The third generation cephalosporin ceftriaxone was found to be very safe and effective when administered intramuscularly once a day in the treatment of the different types of acute bacterial meningitis. Aztreonam given intramuscularly was successful in the treatment of Gram-negative meningitis caused by multi-resistant organisms. The fatality rates and morbidity were significantly reduced in patients with meningitis when dexamethasone was given in conjunction with antibacterial chemotherapy.

Epidemiology, prevalence and clinical diagnosis of meningitis at Abbassia Fever Hospital, Cairo, 1966-1989.

The United States Naval Medical Research Unit No. 3 and the Abbassia Fever Hospital in Cairo, Egypt have together diagnosed and treated 7809 patients admitted to a meningitis ward since 1966. Aetiological diagnosis was based on clinical evaluation and laboratory studies. Marked increases in annual admissions in 1970-1972, 1980-1982 and 1987-1988 were related to increases in admissions due to meningococcal disease, while in 1977-1981 the increase was due to encephalitis related to Rift Valley fever. Better, rapid diagnostic procedures are needed to enable effective treatment to be given earlier and to reduce mortality rates.

Laboratory diagnosis of bacterial meningitis.

This overview summarizes studies conducted since 1970 on the laboratory diagnosis of bacterial meningitis at the Naval Medical Research Unit No. 3. These investigations demonstrated that counterimmunoelectrophoresis (CIE), agglutination of sensitized staphylococcal cells or latex particles, and enzyme-linked immunosorbent assay (ELISA) effectively detect and identify specific antigens in the cerebrospinal fluid of patients with meningococcal, pneumococcal, and Haemophilus meningitis. ELISA was the most sensitive of these methods and CIE the least sensitive. ELISA was also used to measure antibodies to meningococcal outer membrane protein antigens in patients. Finally, high rates of group A meningococcal nasopharyngeal carriage were found in group A meningococcal meningitis patients and populations associated with group A patients, but not in populations that were not associated with group A disease.

Indirect immunoglobulin G (IgG) and IgM enzyme-linked immunosorbent assays (ELISAs) and IgM capture ELISA for detection of antibodies to lipopolysaccharide in adult typhoid fever patients in Pakistan.

Sera from 339 adult febrile patients in Pakistan were tested for antibodies to Salmonella typhi lipopolysaccharide by indirect immunoglobulin G (IgG) and IgM enzyme-linked immunosorbent assay (ELISA) and IgM capture ELISA. A total of 55 patients had S. typhi cultured from their blood, 20 had S. typhi cultured from their stool, 24 were blood or stool culture positive for S. paratyphi A, 41 were culture negative but clinically diagnosed as having enteric fever, 41 had gastrointestinal or urinary tract infections, 41 were clinically diagnosed as having malaria, 20 were smear-positive patients with malaria, 58 had respiratory infections, and the remaining 39 individuals were placed in a miscellaneous group who did not have Salmonella infection. The sensitivities of the indirect IgG ELISA, indirect IgM ELISA, and IgM capture ELISA determined with specimens obtained from the blood culture-positive patients with typhoid fever (positive controls) were 80, 64, and 62%, respectively. The specificities of the assays determined with sera from the patients with respiratory infections (negative controls) were 95, 95, and 97%, respectively. The percentage of smear-positive patients with malaria who were positive by these assays was lower than that in the negative control group. The percentages of individuals in the other patient categories who were positive by these tests were between those obtained with the positive and negative controls. Of the positive controls, 26 were positive by both IgM assays, 9 were IgM positive only by indirect ELISA, and 8 were IgM positive only by IgM capture ELISA. A total of 70% of the positive control patients who were tested for O agglutinins by the Widal tube agglutination assay were positive; however, 29% of the negative control patients were also positive. The indirect IgG ELISA was the single most effective test for the serodiagnosis of typhoid fever in this population.

Evaluation of performance parameters of a membrane-based dot immunoassay for meningococcal polysaccharide.

Increasingly, membrane-based enzyme immunoassays are being developed as the preferred solid-phase enzyme immunoassay format. We describe the rate kinetics of a polyvinylidene difluoride membrane-based dot immunoassay for meningococcal group A polysaccharide. Antigen detection sensitivity decreased logarithmically with linear decreases in incubation time. The sensitivity of a 30-min assay (5-min incubation steps) was increased to nearly the level of the standard assay (1-h incubation steps) by increasing the concentration of assay reagents fourfold. These results support the idea that existing microtiter plate assays can be transferred to rapid dot immunoassay formats with little or no loss of sensitivity.