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1.
Chest ; 118(5): 1397-404, 2000 Nov.
Article in English | MEDLINE | ID: mdl-11083692

ABSTRACT

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(1) [PC(20)], 1.77 mg/mL). Responders (PC(20), < 8 mg/mL) had significantly lower values for forced expiratory flow between 25% and 75% of the outflow curve (FEF(25-75)), FEF(25-75) percent predicted, and FEF(25-75)/FVC ratio. Among all 32 subjects, the natural logarithmic transformation performed on PC(20) values (lnPC(20)) correlated with FEF(25-75) percent predicted, FEV(1) percent predicted, and FEF(25-75)/FVC ratio but not with FVC percent predicted. Responders with PC(20) values < 2 mg/mL (n = 13) had significantly reduced values for FVC, FVC percent predicted, FEV(1), and FEV(1) percent predicted compared to those with PC(20) values between 2 mg/mL and 8 mg/mL. In addition, among responders, there was a significant correlation between lnPC(20) and FVC percent predicted. A significant relationship was found between maximal inspiratory pressure (PImax) and both FEV(1) percent predicted and FEF(25-75) percent predicted, but not between lnPC(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(20) are associated with parallel reductions in surrogate spirometric indexes of airway size (FEV(1) percent predicted and FEF(25-75) percent predicted) and airway size relative to lung size (FEF(25-75)/FVC ratio). The absence of an association between lnPC(20) and FVC percent predicted for the entire group or between lnPC(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.


Subject(s)
Bronchial Hyperreactivity/physiopathology , Lung/pathology , Quadriplegia/physiopathology , Adult , Aerosols , Aged , Bronchial Provocation Tests , Bronchoconstrictor Agents/administration & dosage , Dose-Response Relationship, Drug , Forced Expiratory Volume/physiology , Histamine/administration & dosage , Humans , Inhalation/physiology , Linear Models , Lung/innervation , Lung/physiopathology , Maximal Expiratory Flow Rate/physiology , Maximal Midexpiratory Flow Rate/physiology , Middle Aged , Muscle, Smooth/physiopathology , Pressure , Pulmonary Ventilation/physiology , Respiratory Muscles/physiopathology , Spirometry , Vital Capacity/physiology
2.
Chest ; 115(6): 1533-8, 1999 Jun.
Article in English | MEDLINE | ID: mdl-10378545

ABSTRACT

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.


Subject(s)
Adrenergic beta-Agonists/therapeutic use , Bronchial Hyperreactivity/physiopathology , Metaproterenol/therapeutic use , Spinal Cord Injuries/physiopathology , Administration, Inhalation , Adrenergic beta-Agonists/administration & dosage , Adult , Aged , Bronchial Hyperreactivity/diagnosis , Bronchial Hyperreactivity/drug therapy , Bronchial Provocation Tests , Bronchoconstriction/drug effects , Chronic Disease , Follow-Up Studies , Forced Expiratory Volume , Histamine , Humans , Metaproterenol/administration & dosage , Methacholine Chloride , Middle Aged , Nebulizers and Vaporizers , Neck , Respiratory Function Tests , Spinal Cord Injuries/drug therapy , Treatment Outcome
3.
Spinal Cord ; 37(4): 279-83, 1999 Apr.
Article in English | MEDLINE | ID: mdl-10338349

ABSTRACT

OBJECTIVE: 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 > or =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.


Subject(s)
Bronchial Hyperreactivity/drug therapy , Cholinergic Antagonists/therapeutic use , Mandelic Acids/therapeutic use , Spinal Cord Injuries/complications , Adult , Aerosols , Bronchial Hyperreactivity/etiology , Bronchial Hyperreactivity/prevention & control , Bronchodilator Agents/administration & dosage , Histamine/administration & dosage , Humans , Male , Methacholine Chloride/administration & dosage , Middle Aged , Spirometry
4.
J Appl Physiol (1985) ; 86(4): 1165-9, 1999 Apr.
Article in English | MEDLINE | ID: mdl-10194198

ABSTRACT

The majority of otherwise healthy subjects with chronic cervical spinal cord injury (SCI) demonstrate airway hyperresponsiveness to aerosolized methacholine or histamine. The present study was performed to determine whether ultrasonically nebulized distilled water (UNDW) induces airway hyperresponsiveness and to further elucidate potential mechanisms in this population. Fifteen subjects with SCI, nine with tetraplegia (C4-7) and six with paraplegia (T9-L1), were initially exposed to UNDW for 30 s; spirometry was performed immediately and again 2 min after exposure. The challenge continued by progressively increasing exposure time until the forced expiratory volume in 1 s decreased 20% or more from baseline (PD20) or the maximal exposure time was reached. Five subjects responding to UNDW returned for a second challenge 30 min after inhalation of aerosolized ipratropium bromide (2.5 ml of a 0.6% solution). Eight of nine subjects with tetraplegia had significant bronchoconstrictor responses to UNDW (geometric mean PD20 = 7.76 +/- 7.67 ml), whereas none with paraplegia demonstrated a response (geometric mean PD20 = 24 ml). Five of the subjects with tetraplegia who initially responded to distilled water (geometric mean PD20 = 5.99 +/- 4.47 ml) were not responsive after pretreatment with ipratropium bromide (geometric mean PD20 = 24 ml). Findings that subjects with tetraplegia are hyperreactive to UNDW, a physicochemical agent, combined with previous observations of hyperreactivity to methacholine and histamine, suggest that overall airway hyperresponsiveness in these individuals is a nonspecific phenomenon similar to that observed in patients with asthma. The ability of ipratropium bromide to completely block UNDW-induced bronchoconstriction suggests that, in part, airway hyperresponsiveness in subjects with tetraplegia represents unopposed parasympathetic activity.


Subject(s)
Paraplegia/physiopathology , Quadriplegia/physiopathology , Respiratory Mechanics/physiology , Spinal Cord Injuries/physiopathology , Water/pharmacology , Adult , Aerosols , Bronchoconstriction/drug effects , Bronchoconstriction/physiology , Bronchodilator Agents/administration & dosage , Bronchodilator Agents/pharmacology , Humans , Ipratropium/administration & dosage , Ipratropium/pharmacology , Male , Nebulizers and Vaporizers , Paraplegia/etiology , Quadriplegia/etiology , Smoking , Spirometry , Ultrasonics , Water/administration & dosage
5.
J Chromatogr B Biomed Sci Appl ; 712(1-2): 1-10, 1998 Aug 07.
Article in English | MEDLINE | ID: mdl-9698223

ABSTRACT

We developed a mass spectral method to verify the detection of free tuberculostearic acid (TSA) by frequency-pulsed electron-capture gas chromatography (FPEC-GC) in cerebrospinal fluid (CSF), serum, pericardial fluid, ascites fluid and pleural fluid of patients infected with Mycobacterium tuberculosis. To obtain satisfactory sensitivity and specificity for comparison of the test using mass spectrometry (MS) in the single ion monitor (SIM) mode to the FPEC-GC test, we developed a specific, sensitive, quantitative chemical ionization mass spectrometry capillary gas chromatography (QCIGC-MS) test. The procedure maximized the molecular ion (i.e., made it the base peak) for increased specificity and sensitivity, and instrument parameters for increased sensitivity. The procedure uses a computerized approach, requiring an internal standard (nonadecanoic acid) for precise measurement of the retention time and quantitation of the molecular ion of TSA. Data from this study suggest that QCIGC-MS analysis could be a valuable tool to confirm FPEC-GC identification of TSA in CSF, serum, and in pleural, ascites, and pericardial fluids.


Subject(s)
Body Fluids/chemistry , Stearic Acids/analysis , Ascitic Fluid/chemistry , Gas Chromatography-Mass Spectrometry/methods , Humans , Male , Mycobacterium tuberculosis/isolation & purification , Pericardial Effusion/chemistry , Pleural Effusion/chemistry , Stearic Acids/blood , Stearic Acids/cerebrospinal fluid , Tuberculosis/metabolism , Tuberculosis/microbiology , Tuberculosis, Meningeal/metabolism , Tuberculosis, Meningeal/microbiology , Tuberculosis, Pulmonary/metabolism , Tuberculosis, Pulmonary/microbiology
6.
Clin Auton Res ; 8(2): 111-8, 1998 Apr.
Article in English | MEDLINE | ID: mdl-9613801

ABSTRACT

Due to the increased prevalence of ischemic heart disease and hypertension reported in individuals with chronic spinal cord injury (SCI), we investigated whether subjects with low level SCI (paraplegia), without apparent evidence of coronary artery disease, exhibit normal baroreceptor and autonomic function. Eighteen males participated in this study: seven normotensive with paraplegia, five hypertensive with paraplegia and six normotensive non-SCI controls. The Valsalva maneuver was performed by maintaining a pressure of 40 mmHg over 15 s and R-R intervals (RRI) and arterial blood pressure were measured continuously. Phase IV of the Valsalva maneuver was determined by linear regression analysis between RRI and systolic pressure, with a final slope calculated. The power spectra for RRI and blood pressure variability parameters were also analyzed, in addition to the index alpha, a frequency domain estimate of the overall gain in baroreceptor control of the RRI-arterial blood pressure. The normotensive subjects with paraplegia were found to have an impaired baroreceptor response when compared with age-matched, non-SCI controls. In addition, the levels of both the low frequency and high frequency spectral components of RRI and the index alpha were reduced in these individuals at rest. These cumulative findings strongly suggest that the integrity of the sinoaortic baroreceptors, as well as efferent parasympathetic function, may be compromised in otherwise apparently healthy individuals with chronic paraplegia.


Subject(s)
Pressoreceptors/physiopathology , Spinal Cord Injuries/physiopathology , Valsalva Maneuver , Adult , Humans , Hypertension/complications , Hypertension/physiopathology , Male , Middle Aged , Paraplegia/complications , Paraplegia/physiopathology , Reference Values , Sinus of Valsalva/physiopathology , Spinal Cord Injuries/complications
7.
Arch Phys Med Rehabil ; 79(3): 293-7, 1998 Mar.
Article in English | MEDLINE | ID: mdl-9523781

ABSTRACT

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.


Subject(s)
Breathing Exercises , Dyspnea/rehabilitation , Respiratory Muscles/physiopathology , Spinal Cord Injuries/physiopathology , Adult , Aged , Chronic Disease , Dyspnea/etiology , Dyspnea/physiopathology , Exercise Therapy , Humans , Male , Respiratory Function Tests , Spinal Cord Injuries/complications , Treatment Outcome
8.
J Asthma ; 35(1): 49-55, 1998.
Article in English | MEDLINE | ID: mdl-9513582

ABSTRACT

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.


Subject(s)
Bronchial Hyperreactivity/physiopathology , Bronchoconstriction/drug effects , Ipratropium/pharmacology , Muscarinic Antagonists/pharmacology , Spinal Cord Injuries/physiopathology , Adult , Bronchial Provocation Tests , Bronchoconstriction/physiology , Histamine , Humans , Male , Middle Aged , Spirometry
9.
Spinal Cord ; 35(10): 652-7, 1997 Oct.
Article in English | MEDLINE | ID: mdl-9347593

ABSTRACT

To determine the prevalence of respiratory symptoms in subjects with chronic spinal cord injury (SCI), 180 subjects completed a standard respiratory questionnaire modified for subjects with limited mobility. Subjects were categorized as high tetraplegia (HT:C5 and above not requiring mechanical ventilation), low tetraplegia (LT: C6-8), high paraplegia (HP: T1-7), or low paraplegia (LP: T8-L3). Overall, 68% of subjects reported one or more respiratory symptom. Breathlessness, the most prevalent complaint, was associated with level of lesion: HT = 73%, LT = 58%, HP = 43% and LP = 29%, whereas complaints of cough, phlegm, cough and phlegm, and wheeze did not differ significantly among subjects in the four groups. Breathlessness occurred significantly more often in the group with HT during rest or following exposure to hot air or passive smoke. Awareness of phlegm or wheeze was reported with increased prevalence among subjects with tetraplegia who had complete injuries. Among subjects with tetraplegia, respiratory complaints did not differ significantly in current smokers, former smokers, and non-smokers, whereas among subjects with paraplegia, phlegm and wheeze were reported more frequently, among current smokers.


Subject(s)
Respiratory Tract Diseases/epidemiology , Smoking/adverse effects , Spinal Cord Injuries/complications , Adult , Analysis of Variance , Chi-Square Distribution , Follow-Up Studies , Humans , Male , Middle Aged , Paraplegia/complications , Prevalence , Quadriplegia/complications , Respiratory Tract Diseases/etiology , Risk Factors , Surveys and Questionnaires
10.
Am J Physiol ; 272(2 Pt 2): H835-42, 1997 Feb.
Article in English | MEDLINE | ID: mdl-9124446

ABSTRACT

This study investigated the effect of abnormal autonomic cardiovascular function on heart rate variability (HRV) in individuals classified into four groups: complete quadriplegia, incomplete quadriplegia, low paraplegia, and non-spinal cord injury (SCI) controls. Measurements were collected at baseline and during provocative maneuvers. Spectral analysis using a fast-Fourier transform algorithm revealed two spectral components of HRV, termed low frequency (LF) and high frequency (HF); the LF-to-HF ratio (estimate of sympathovagal balance) was also calculated. Each group of subjects with quadriplegia exhibited significantly lower spectral components for both baseline and composite provocative measures compared with the non-SCI controls (P < 0.05). In addition, the group with paraplegia demonstrated significantly lower HF baseline and LF composite levels than controls (P < 0.05). No differences were observed among all groups for the LF-to-HF ratio. This consistency in the LF-to-HF ratio suggests that the two autonomic divisions that regulate the cardiovascular system maintain homeostasis even when one component is severely compromised. This is supported by the additional findings of decreased parasympathetic activity in the two groups with quadriplegia and the absence of significant differences among any of the four groups at rest in either heart rate or blood pressure.


Subject(s)
Heart Conduction System/physiopathology , Heart/physiopathology , Spinal Cord Injuries/physiopathology , Sympathetic Nervous System/physiopathology , Vagus Nerve/physiopathology , Adult , Blood Pressure , Heart Rate , Humans , Male , Middle Aged , Paraplegia/physiopathology , Quadriplegia/physiopathology , Reference Values
11.
Lung ; 175(5): 333-41, 1997.
Article in English | MEDLINE | ID: mdl-9270990

ABSTRACT

Bronchial provocation studies performed in our research center have consistently demonstrated airway hyperresponsiveness to both inhaled methacholine and histamine in subjects with chronic cervical spinal cord injury (SCI). More recently, we reported that the airways of such subjects maintained on chronic baclofen (gamma-aminobutyric acid) therapy were not hyperreactive to inhaled methacholine. In this study we determined whether baclofen also blocks the effects of the bronchoprovocative agent histamine in subjects with cervical SCI. Twenty-four male subjects with cervical SCI participated in this study; 14 were maintained on oral baclofen, and 10 served as age-matched controls. The subjects were challenged with increasing concentrations of aerosolized histamine until either a 20% fall in forced expiratory volume in 1 s (FEV1) from baseline (defined as PC20) was observed, or a maximum of 25 mg/ml histamine was administered. We found that 11 of the 14 baclofen subjects (78.5%) and 8 of the 10 control subjects (80%) responded (PC20 < 8 mg/ml) to the histamine challenge. Mean PC20 values among responders in the baclofen (PC20 = 2.91 +/- 2.3) and control (PC20 = 2.18 +/- 1.9) groups did not differ significantly. Because histamine acts directly on histamine receptors and indirectly on cholinergic pathways, our findings that baclofen blocks bronchoconstriction due to inhaled methacholine, but not that due to histamine, suggests that hyperresponsiveness in subjects with cervical SCI may be secondary to nonspecific airway hyperreactivity.


Subject(s)
Baclofen/pharmacology , Bronchial Hyperreactivity/physiopathology , GABA Agonists/pharmacology , Histamine , Spinal Cord Injuries/physiopathology , Adult , Aerosols , Baclofen/therapeutic use , Bronchial Provocation Tests , Bronchoconstriction/drug effects , Bronchoconstriction/physiology , Case-Control Studies , GABA Agonists/therapeutic use , Humans , Male
12.
Chest ; 110(4): 911-5, 1996 Oct.
Article in English | MEDLINE | ID: mdl-8874244

ABSTRACT

Previously, we found that never-smokers with quadriplegia were hyperresponsive to aerosolized methacholine. To further explore the phenomenon, we compared responsiveness to methacholine in never-smokers with that of smokers and ex-smokers. We also evaluated responsiveness in subjects with high paraplegia (lesions at T-1 to T-6) or low paraplegia (lesions at T-7 and below). We found that smokers and ex-smokers with quadriplegia were hyperresponsive to methacholine (provocative concentration causing a 20% fall in FEV1 = 1.9 mg/mL), and that the response was comparable to that found in never-smokers, revealing that hyperresponsiveness among never-smokers cannot be attributed to preinjury airway hyperreactivity that precluded cigarette use. In contrast, subjects with low paraplegia were not hyperresponsive to methacholine. Among subjects with high paraplegia, the three subjects demonstrating airway hyperresponsiveness had significantly lower FEV1 (percent predicted). The findings support the hypothesis that airway hyperresponsiveness in subjects with quadriplegia represents loss of sympathetic innervation of the lung, thereby leaving intact unopposed bronchoconstrictor cholinergic activity. However, reduced lung volumes in these subjects also suggest the possibility that airway hyperresponsiveness is due to loss of ability to stretch airway smooth muscle by deep breathing.


Subject(s)
Bronchi/drug effects , Bronchial Hyperreactivity , Bronchoconstrictor Agents/pharmacology , Methacholine Chloride/pharmacology , Spinal Cord Injuries/physiopathology , Adult , Bronchial Provocation Tests , Bronchoconstriction/physiology , Humans , Middle Aged , Muscle, Smooth/physiopathology , Quadriplegia/physiopathology , Smoking/physiopathology
13.
Chest ; 110(4): 965-71, 1996 Oct.
Article in English | MEDLINE | ID: mdl-8874253

ABSTRACT

STUDY OBJECTIVE: To compare therapeutic outcome and perform a cost-benefit analysis of inpatients with community-acquired pneumonia (CAP) treated with a shortened course of i.v. antibiotic therapy. DESIGN: A prospective, randomized, parallel group study with a follow-up period of 28 days. SETTING: Bronx Veterans Affairs Medical Center (VAMC) and the Castle Point VAMC; university-affiliated VAMC general medical wards from September 1993 to March 1995. PATIENTS: Seventy-two male veterans and 1 female veteran with 75 episodes of CAP defined by a new infiltrate on chest radiograph and either history or physical findings consistent with pneumonia. Study population was 42%(31) black, 33%(24) white, and 25%(18) Hispanic. INTERVENTIONS: Patients were randomized (1:1:1) to 1 of 3 treatment groups: group 1 received 2 days of i.v. and 8 days of oral therapy; group 2 received 5 days of i.v. and 5 days of oral therapy; and group 3 received 10 days of i.v. therapy. Antibiotics consisted of cefuroxime, 750 mg every 8 h for the i.v. course, and cefuroxime axetil, 500 mg every 12 h for the oral therapy. MEASUREMENTS AND RESULTS: No differences were found in the clinical course, cure rates, or resolution of chest radiograph abnormalities among the three groups. A significant difference was found in the length of stay (LOS) among the three groups. The mean +/- SD LOS was 6 +/- 3 days in group 1, 8 +/- 2 days in group 2, and 11 +/- 1 days in group 3. The shortened LOS could potentially save $95.5 million for the Department of Veterans Affairs and $2.9 billion for the US private sector. CONCLUSIONS: Adult patients hospitalized for CAP who are not severely ill can be successfully treated with an abbreviated (2-day) course of i.v. antibiotics and then switched to oral therapy. A longer course of i.v. therapy prolongs hospital stay and cost, without improving the therapeutic cure rate.


Subject(s)
Cefuroxime/analogs & derivatives , Cefuroxime/therapeutic use , Cephalosporins/therapeutic use , Pneumonia/drug therapy , Adult , Aged , Cefuroxime/administration & dosage , Cephalosporins/administration & dosage , Community-Acquired Infections , Cost-Benefit Analysis , Female , Humans , Length of Stay , Male , Middle Aged , Pneumonia/economics , Prospective Studies , Time Factors
14.
Thorax ; 51(5): 530-3, 1996 May.
Article in English | MEDLINE | ID: mdl-8711683

ABSTRACT

BACKGROUND: Acid fast cell wall deficient forms (CWDF) of bacteria have been grown from blood, bronchial washings, and ocular anterior chamber fluid from patients with sarcoidosis. A monoclonal antibody raised against Mycobacterium tuberculosis whole cell antigen (H37RV) was used to characterise further CWDF grown from the blood of patients with sarcoidosis. METHODS: Blood from 20 patients with active sarcoidosis and from 20 controls was cultured using methods favourable for the growth of CWDF. Isolates were further characterised by indirect fluorescent antibody analysis using a monoclonal antibody highly reactive with M tuberculosis. RESULTS: CWDF were grown from the blood of 19 of 20 subjects with sarcoidosis. All isolates stained positively with the monoclonal antibody and with a modified Kinyoun stain. No organisms were grown from the blood of controls. CONCLUSIONS: These data demonstrate that CWDF can be grown from the blood of nearly all patients with active sarcoidosis. The results confirm that the organisms are mycobacterial in origin and are similar, if not identical, to M tuberculosis. Their role in the pathogenesis of sarcoidosis is unknown.


Subject(s)
L Forms/isolation & purification , Mycobacterium tuberculosis/isolation & purification , Sarcoidosis/microbiology , Fluorescent Antibody Technique, Indirect , Humans , L Forms/growth & development , Mycobacterium tuberculosis/growth & development , Sarcoidosis/blood
15.
Peptides ; 17(1): 13-6, 1996.
Article in English | MEDLINE | ID: mdl-8822504

ABSTRACT

Endopeptidase 24.11 (EP 24.11), a membrane-bound cell surface enzyme, modulates chemotactic responsiveness of neutrophils to f-Met-Leu-Phe. It is unknown if the enzyme degrades potent formylmethionyl tetrapeptides or if an enzyme with similar activities, endopeptidase 24.15 (EP 24.15), degrades formylated chemotactic peptides. In a study of five formylmethionyl tetrapeptides and f-Met-Leu-Phe, we found that EP 24.11 had high affinity for all peptides evaluated, although it did not effectively degrade f-Met-Ile-Leu-Phe. EP 24.15 had high affinity for three of the tetrapeptides, and for f-Met-Leu-Phe, although, for unclear reasons, it did not degrade f-Met-Ile-Leu-Phe or f-Met-Leu-Phe, the apparent natural products of Staphylococcus aureus and Escherichia coli, respectively.


Subject(s)
Chemotactic Factors/metabolism , Metalloendopeptidases/metabolism , N-Formylmethionine/metabolism , Neprilysin/metabolism , Oligopeptides/metabolism , Amino Acid Sequence , Animals , Binding Sites , Chemotactic Factors/chemistry , Chemotactic Factors/genetics , Hydrolysis , In Vitro Techniques , Kinetics , Male , Metalloendopeptidases/antagonists & inhibitors , Molecular Sequence Data , N-Formylmethionine/chemistry , Neprilysin/antagonists & inhibitors , Oligopeptides/chemistry , Oligopeptides/genetics , Rabbits , Rats
16.
Lung ; 174(6): 349-58, 1996.
Article in English | MEDLINE | ID: mdl-8887930

ABSTRACT

To explore further the possible etiologic role of mycobacteria in the development of sarcoidosis, we measured free, nonbound tuberculostearic acid (TSA, 10-methyloctadecanoic), a component of mycobacteria, in the sera of subjects with sarcoidosis or active untreated pulmonary tuberculosis and in healthy controls by use of frequency-pulsed electron capture gas-liquid chromatography (FPEC-GLC). The selective analytic system is capable of measuring as little as 15-fmol quantities of free, nonbound TSA in serum and cerebral spinal fluid. We found that TSA was present in the sera of all subjects with Mycobacterium tuberculosis (n = 10) but was undetectable in subjects with sarcoidosis (n = 15) and in healthy controls (n = 15), thereby suggesting that if sarcoidosis is caused by a mycobacterial organism, TSA is not produced or does not gain access to the systemic circulation in quantities sufficient for measurement. However, in the course of the studies we found that a peak, designated p11, was elevated in the sera of all subjects with acute sarcoidosis (n = 4). Also, a peak designated p3 was reduced significantly in all subjects with acute and chronic sarcoidosis and absent in subjects with M. tuberculosis compared with healthy controls. Both peaks were later shown by chemical analysis and mass spectral studies to be carboxylic acids not previously associated with specific disease entities. Follow-up detailed studies will be needed to determine if quantitation of these unique carboxylic acids will be useful in differentiating sarcoidosis from other disorders.


Subject(s)
Chromatography, Gas , Sarcoidosis, Pulmonary/diagnosis , Stearic Acids/analysis , Tuberculosis, Pulmonary/diagnosis , Carboxylic Acids/analysis , Diagnosis, Differential , Follow-Up Studies , Gas Chromatography-Mass Spectrometry , Humans , Mycobacterium tuberculosis/chemistry , Mycobacterium tuberculosis/pathogenicity , Sarcoidosis, Pulmonary/microbiology , Tuberculosis, Pulmonary/microbiology
17.
Mil Med ; 160(6): 308-11, 1995 Jun.
Article in English | MEDLINE | ID: mdl-7659231

ABSTRACT

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.


Subject(s)
Smoking/epidemiology , Spinal Cord Injuries , Veterans , Adult , Aged , Aged, 80 and over , Confidence Intervals , Humans , Male , Middle Aged , Prevalence
18.
Paraplegia ; 33(5): 274-7, 1995 May.
Article in English | MEDLINE | ID: mdl-7630654

ABSTRACT

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.


Subject(s)
Bronchodilator Agents/therapeutic use , Dyspnea/drug therapy , Ipratropium/therapeutic use , Quadriplegia/complications , Adult , Dyspnea/etiology , Forced Expiratory Volume/drug effects , Humans , Male , Respiratory Function Tests , Smoking/physiopathology , Spinal Cord Injuries/physiopathology , Spirometry , Vital Capacity/drug effects
20.
Lung ; 173(5): 297-306, 1995.
Article in English | MEDLINE | ID: mdl-7564488

ABSTRACT

Spirometry was performed on 165 subjects with spinal cord injury (84 with quadriplegia and 81 with paraplegia). Subjects were characterized by level of lesion as: high quadriplegia (HQ, C4 and above not requiring mechanical ventilation), low quadriplegia (LQ, C5-8), high paraplegia (HP, T1-7), and low paraplegia (LP, T8-L3). Thirty-nine subjects had complete motor lesions, and 126 had incomplete motor lesions. Nonsmokers (54 with quadriplegia and 53 with paraplegia) were defined as those who had never smoked or those who had stopped smoking for 1 year. Current smokers (28 with quadriplegia and 28 with paraplegia) were defined as those who currently smoked cigarettes, cigars, and/or pipe or those who had quit for < or = 1 year. We found by linear regression analysis that forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), peak expiratory flow (PEF), and maximal voluntary ventilation (MVV) were inversely correlated with the level of injury (i.e., the higher the level of injury, the lower the parameter). In the HQ group, those with complete injury had significantly lower pulmonary function parameters than those with incomplete lesions. In contrast, there were no significant differences in pulmonary function parameters between complete and incomplete lesions in subjects in the LQ, HP, and LP groups. In the LQ, HP, and LP groups, the FEV1 and PEF were significantly lower in smokers than in nonsmokers. Thus, this study demonstrates the effects of completeness of injury and smoking on pulmonary function in a large group of subjects with spinal cord injury.


Subject(s)
Respiratory Paralysis/physiopathology , Smoking/adverse effects , Spinal Cord Injuries/physiopathology , Spirometry , Adolescent , Adult , Aged , Airway Resistance/physiology , Follow-Up Studies , Humans , Lung/innervation , Lung Volume Measurements , Male , Middle Aged , Motor Neurons/physiology , Paraplegia/physiopathology , Pulmonary Gas Exchange/physiology , Quadriplegia/physiopathology , Smoking/physiopathology , Spinal Cord/physiopathology , Sympathetic Nervous System/physiopathology
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