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Objectives: We administered aerosolized histamine to 32 subjects with tetraplegia to determine whether there were differences in spirometric and/or lung volume parameters between responders and nonresponders. Results: Baseline pulmonary function parameters revealed mild to moderate restrictive dysfunction. We found that 25 subjects (78%) were hyperreactive to histamine (mean provocative concentration of a substance causing a 20% fall in FEV[sub 1] [PC[sub 20]], 1.77 mg/mL). Responders (PC[sub 20], <8 mg/mL) had significantly lower values for forced expiratory flow between 25% and 75% of the outflow curve (FEF[sub 25-75]), FEF[sub 25-75] percent predicted, and FEF[sub 25-75]/FVC ratio. Among all 32 subjects, the natural logarithmic transformation performed on PC[sub 20] values (lnPC[sub 20]) correlated with FEF[sub 25-75] percent predicted, FEV[sub 1] percent predicted, and FEF[sub 25-75]/FVC ratio but not with FVC percent predicted. Responders with PC[sub 20] values <2 mg/mL (n = 13) had significantly reduced values for FVC, FVC percent predicted, FEV[sub 1], and FEV[sub 1] percent predicted compared to those with PC[sub 20] values between 2 mg/mL and 8 mg/mL. In addition, among responders, there was a significant correlation between lnPC[sub 20] and FVC percent predicted. A significant relationship was found between maximal inspiratory pressure (PImax) and both FEV[sub 1] percent predicted and FEF[sub 25-75] percent predicted, but not between lnPC[sub 20] and either PImax or maximal expiratory pressure (PEmax). Conclusions: These findings demonstrate that subjects with tetraplegia who exhibit airway hyperreactivity (AHR) have reduced baseline airway caliber and that lower values for lnPC[sub 20] are associated with parallel reductions in surrogate spirometric indexes of airway size (FEV[sub 1] percent predicted and FEF[sub 25-75] percent predicted) and airway size relative to lung size (FEF[sub 25-75]/FVC ratio). The absence of an association between lnPC[sub 20] and FVC percent predicted for the entire group or between lnPC[sub 20] and either PImax or PEmax indicates that reduced lung volumes secondary to respiratory muscle weakness cannot explain the mechanism(s) underlying AHR. Among responders, however, a possible role for reduction in lung volume, as it pertains to increasing AHR, cannot be excluded. Proposed mechanisms for reduced baseline airway caliber relative to lung size in subjects with tetraplegia include unopposed parasympathetic activity secondary to the loss of sympathetic innervation to the lungs and/or the inability to stretch airway smooth muscle with deep inhalation. [ABSTRACT FROM AUTHOR]

OBJECTIVE:&EMSP;:To further investigate mechanisms of airway hyperreactivity among subjects with chronic cervical spinal cord injury (SCI), we assessed airway responsiveness to aerosolized methacholine and histamine in subjects receiving chronic oxybutynin chloride therapy, and compared the findings with those not receiving the agent. Methods: Twenty-five male subjects with cervical SCI participated in this study; 12 were maintained on oral oxybutynin chloride and 13 served as age-matched controls. Six of the 12 subjects receiving oxybutynin were challenged with aerosolized methacholine, and six with histamine; seven of the 13 control subjects were challenged with aerosolized methacholine and the remaining six with histamine. Results: All 13 control subjects and all six oxybutynin/histamine subjects exhibited a significant bronchoconstrictor response (PC20<8 mg/ml), whereas mean PC20 values for the oxybutynin/methacholine group were 25 mg/ml. Conclusion: Our finding that the bronchoconstrictor effects of methacholine were blocked by oxybutynin chloride while those of histamine were not suggests that oxybutynin acts primarily through anticholinergic pathways rather than by causing generalized airway smooth muscle relaxation. [ABSTRACT FROM AUTHOR]

Study Objective: Aerosolized ipratropium bromide or orally administered baclofen or oxybutynin chloride (Ditropan) block methacholine-associated airway hyperreactivity in subjects with chronic cervical spinal cord injury (SCI), whereas these agents do not inhibit airway hyperreactivity associated with the inhalation of histamine. The present study was performed to determine whether pretreatment with a beta2-agonist attenuates airway hyperresponsiveness in these subjects., Participants: Subjects with chronic cervical SCI previously demonstrating airway hyperreactivity were challenged with methacholine (n = 9) or histamine (n = 16) alone and, on a separate day, 25 min following inhalation of nebulized metaproterenol sulfate., Results: Inhalation of the beta2-agonist was associated with an increase in provocative concentration causing a 20% decrease in FEV1 (PC20) values (geometric mean) from 1.01+/-2.76 to 20.54+/-6.24 mg/mL for methacholine and from 2.29+/-2.26 to 19.82+/-5.93 mg/mL for histamine. No correlation was found between specific PC20 values for individual subjects and percentage improvement in FEV1 (liter) following inhalation of metaproterenol sulfate and between PC20 values and baseline FEV1 percent., Conclusion: These data, combined with findings that patients with chronic high cervical SCI experience increased breathlessness following exposure to exogenous agents, suggest that long-term prophylactic beta2-agonist therapy may reduce respiratory symptoms associated with airway hyperreactivity in these patients.

Objective: To determine whether pulmonary function, respiratory muscle strength, and dyspnea can be improved in individuals with chronic cervical spinal cord injury (SCI)., Study Design: Ten subjects participated in an 8-week resistive inspiratory muscle training (IMT) program for 15 minutes twice daily. Spirometry, lung volumes, maximum inspiratory pressure (MIP), maximum expiratory pressure (MEP), and dyspnea were measured at baseline, week 4, and week 8. Six months after the study, spirometry, MIP, and MEP were re-measured in a subgroup of the original participants., Results: We found that regular IMT in subjects with cervical SCI significantly improved forced vital capacity (means +/- SE) (11% +/- 2.82% increase), forced inspiratory vital capacity (21% +/- 6.91%), vital capacity (8% +/- 4.36%), total lung capacity (12% +/- 3.23%), functional residual capacity (15% +/- 5.96%), and MIP (24% +/- 6.98%) (p < .05). Furthermore, although no statistical differences were observed for the dyspnea scale, the fact that subjects reported decreased levels (43% +/- 21.30% reduction) of perceived difficulty breathing may be of greater importance. No significant differences from baseline values were found in the seven subjects whose spirometry and respiratory muscle strength were measured 6 months after the study., Conclusions: Our findings suggest that in individuals with cervical SCI regular resistive IMT may result in decreased restrictive ventilatory impairment and reported dyspnea and, thus, reduced incidence of chronic respiratory complaints, respiratory infection, and other pulmonary complications.

Previously, we reported that a majority of subjects with chronic cervical spinal cord injury (SCI) demonstrated airway hyperreactivity in response to inhaled methacholine. To further investigate mechanisms of airway hyperreactivity, 15 male subjects with cervical SCI were challenged with aerosolized histamine, and on a separate day responders were rechallenged 30 min after the inhalation of 72 micrograms of ipratropium bromide. Twelve of 15 subjects demonstrated airway hyperresponsiveness to histamine (geometric mean PC20 of 1.27 mg/ml), which was not blocked by pretreatment with ipratropium bromide (geometric mean PC20 1.50 mg/ml). Baseline forced vital capacity and forced expiratory volume in 1 sec were not significantly different between responders and nonresponders (2.8 +/- 0.6 vs. 3.0 +/- 0.4 L and 2.3 +/- 0.6 vs. 2.4 +/- 0.2 L, respectively). Findings that subjects with cervical SCI are hyperresponsive to methacholine and histamine, chemical agents with direct action through distinct receptor systems, suggest that bronchial hyperreactivity in these subjects represents a nonspecific process similar to that observed in patients with asthma.

Male veterans with spinal cord injury (SCI) were surveyed regarding their smoking history. Subjects (n = 250) were placed in one of two categories: never smokers (smoked < or = 100 cigarettes in lifetime), or ever smokers (divided into former smokers, quit smoking for > 1 year, or current smokers). Never smokers constituted 23.2%, and ever smokers constituted 76.8% of the sample. Among the ever smokers, 59.4% had quit, compared with 49.1% in the general population (p < 0.05). In the former smokers, 23% had quit before injury, 24% quit within 1 year of injury, and the remaining 53% quit > 1 year after injury. In this sample veteran SCI population, the number of current smokers is comparable to that found in the general population. The lower number of never smokers with SCI (23.2%) compared with the general population (49.9%) most likely reflects the smoking habits of a veteran population.

Airway hyperresponsiveness was recently described in patients with chronic cervical spinal cord injury (tetraplegia). The response was attributed to unopposed cholinergic broncho-constrictor activity due to loss of sympathetic innervation of the airway. To determine if the administration of a cholinergic antagonist alters resting airway tone in these patients, ipratropium bromide (72 micrograms) was administered by aerosol to 25 tetraplegic patients. We found that 12 of 25 patients (48%) had significant improvement (defined as > or = 12%) in forced expired volume in 1 s (FEV1) and/or forced vital capacity (FVC). A significant correlation between airway responsiveness and complaints of dyspnea at rest, completeness of injury (sensory), or smoking history was not found. These findings of improved airflow after the use of an anticholinergic bronchodilator agent provides further evidence that transection of the cervical cord results in unopposed parasympathetic activity and a resultant increase in resting airway tone.

Objectives: Esophageal variceal ligation is a new approach to the treatment of esophageal varices that does not result in transmural tissue injury and inflammation, and therefore might produce fewer sequelae and symptoms than sclerotherapy. We conducted a prospective, randomized comparison of sclerotherapy with ligation to study the relative short-term risks of these two procedures with respect to bacteremia, pulmonary and coagulation function, esophageal motility, and gastroesophageal reflux., Methods: Patients with previously documented high grade esophageal varices were randomized to receive sclerotherapy or ligation. Blood was drawn for culture and coagulation profiles, and patients underwent pulmonary function tests, esophageal manometry, and intraesophageal pH monitoring before and after treatment., Results: Six patients with Childs class B cirrhosis and one patient with pre-sinusoidal portal hypertension underwent 20 courses of therapy. Neither sclerotherapy nor ligation produced significant clinical changes in pulmonary or coagulation parameters, or bacteremia requiring treatment. The majority of ligation treatments were without worsening of motility or reflux scores, and none were associated with symptoms. Sclerotherapy was followed by significantly greater esophageal dysmotility and worsening reflux patterns., Conclusions: Patient acceptance of ligation was much greater than that for sclerotherapy. Our data define the advantages of ligation over sclerotherapy.

A reliable test that detects malignancy and indicates response to therapy is needed. Frequency-pulsed electron-capture gas-liquid chromatography (FPEC-GLC), a selective analytical technique that is sensitive to 15 fmol quantities of metabolites, was used to analyse derivatised acidic chloroform extracts of sera from patients with biopsy-proven cancer, non-malignant infectious and non-infectious disease, and healthy controls. Two peaks designated P1 and P10, not found in serum from healthy controls (n = 7) or patients with non-malignant disease (n = 85), were detected in biopsy-proven samples (n = 52) from cancer patients. P1 and P10 were later shown by chemical and mass spectral studies to be carboxylic acids. When one or both of these peaks were detected in the sera of non-treated patients they were always associated with malignancy. In patients responding to therapy, a reduction or disappearance of these peaks was observed. Further, it was noted that P10 persisted or increased in sera of patients with progressive cancer not responding to therapy. We conclude that this test has potential in diagnosis and for following the response of the disease to therapy.

The objective of the study was to determine if bradykinin-induced airway microvascular leakage in rats was altered by pretreatment of animals with enalaprilat, an inhibitor of angiotensin-converting enzyme (ACE), or phosphoramidon, an inhibitor of endopeptidase 24.11 (EP 24.11). We found that the intravascular infusion of bradykinin induced microvascular leakage of Evans blue dye in tracheal tissue (0.088 +/- 0.035 micrograms/mg tissue) that was significantly amplified by pretreatment with 3.27 mM enalaprilat (0.458 +/- 0.226 micrograms/mg tissue), but not by pretreatment with 10 mM phosphoramidon (0.082 +/- 0.0453 micrograms/mg tissue). Leakage in carinal tissue was also amplified by pretreatment with 3.27 mM enalaprilat (0.205 +/- 0.050 vs. 0.036 +/- 0.006 micrograms/mg tissue for bradykinin alone), whereas no amplification was observed in parenchymal tissue by pretreatment with either inhibitor. These findings indicate that in the rat, ACE, but not EP 24.11, modulates bradykinin-induced airway microvascular leakage following intravascular infusion of these agents.

In subjects with spinal cord injury (SCI) a restrictive ventilatory impairment has been well described. Despite numerous studies of pulmonary function in patients with SCI, evidence of an obstructive component of respiratory dysfunction as a result of paralysis has not been observed in this population. We performed spirometry in 34 patients with cervical SCI before and after administration of an inhaled bronchodilator. Significant improvement in flow rate was demonstrated in 14 (41%) subjects. Our results suggest that transection of the cervical spine may result in obstruction to air flow, possibly due to interruption of the sympathetic innervation of the lung with resultant unopposed parasympathetic tone producing bronchoconstriction.

Patients with cancer are at increased risk for disease caused by mycobacteria when there is immunosuppression resulting from the underlying disease or its treatment. Pulmonary disease is usual with Mycobacterium tuberculosis or with mycobacteria other than M tuberculosis (MOTT) and atypical presentations with extrapulmonary dissemination occur frequently. No clinical features reliably distinguish between disease caused by M tuberculosis or MOTT. The incidence of M tuberculosis infection depends on a history of prior exposure in patients and on patterns of disease within hospitals and the surrounding community. Infection with different species of MOTT reflects their environmental prevalence. Diagnosis of mycobacterial infection can be clinically challenging and must be pursued aggressively. Despite recent improvements in clinical and laboratory methods, diagnosis of mycobacterial infection may take weeks. Recent increases in the incidence of M tuberculosis infection and the emergence of drug-resistant strains require heightened alertness to its diagnosis and careful epidemiological control measures to prevent continued spread of this contagion. M tuberculosis with routine antimicrobial susceptibility responds well to conventional therapy when initiated early. Prophylaxis of tuberculin positive patients is effective and should be started before immunosuppressive therapy. Guidelines for therapy of MOTT depend on the species isolated but remains poorly defined in most cases. There are several new compounds that may be useful for treatment of drug-resistant species of MOTT. New methods for the rapid diagnosis, speciation, and epidemiological investigation of mycobacterial infection are being developed, and some are available for clinical application. Nonetheless, the timely diagnosis of mycobacterial disease in patients with cancer remains a challenge of increasing clinical importance.