Donald C. Zavala

Elevated bronchoalveolar lavage fluid histamine levels in allergic asthmatics are associated with methacholine bronchial hyperresponsiveness.

Using a sensitive single isotope enzymatic assay we measured bronchoalveolar lavage (BAL) fluid histamine in asymptomatic normal (nonallergic), allergic rhinitic, and allergic asthmatic subjects. Normal subjects were found to have little or no detectable amounts of histamine in BAL fluid (11 +/- 11 pg/ml), and few BAL fluid mast cells. In comparison, the allergic rhinitics and allergic asthmatics had much higher amounts of BAL fluid histamine (113 +/- 53 and 188 +/- 42 pg/ml, respectively), and a significantly greater number of BAL fluid mast cells. Furthermore, despite having equivalent baseline pulmonary function values, allergic asthmatics with BAL fluid histamine levels greater than 100 pg/ml required only 7 +/- 2 breath units of methacholine to induce a 20% drop in forced expiratory volume in 1 s (FEV1) (PD20FEV1) while asthmatics with BAL fluid histamine levels less than 100 pg/ml required 49 +/- 19 breath units (P less than 0.05). These data suggest that allergic asthmatics have ongoing lung mast cell degranulation that might contribute to the etiology of airway hyperresponsiveness.

Recombinant Human Erythropoietin Treatment in Pre-Dialysis Patients: A Double-Blind Placebo-Controlled Trial

STUDY OBJECTIVE To determine the efficacy and safety of recombinant human erythropoietin (r-HuEPO) in predialysis renal patients. DESIGN Randomized, double-blind, placebo-controlled trial for 8 weeks. SETTING Inpatient and outpatient facility in the Clinical Research Center of a university-based hospital. PATIENTS Fourteen adult subjects with renal insufficiency (mean serum creatinine, 473 mumol/L +/- 61 [6.2 +/- 0.8 mg/dL]) and anemia (mean hematocrit, 0.27 +/- 0.01). INTERVENTIONS Recombinant human erythropoietin, 50, 100, or 150 IU/kg body weight or placebo given intravenously three times per week. MEASUREMENTS AND MAIN RESULTS Subjects who received active r-HuEPO showed a dose-dependent rise in hematocrit; mean hematocrit increased 41% from 0.27 +/- 0.01 to 0.38 +/- 0.01. At the same time, erythrocyte mass rose 43% from 13.7 +/- 0.6 mL/kg in the baseline state to 19.6 +/- 1.0 mL/kg after treatment. Maximal oxygen consumption during exercise increased 9% from 16.0 mL/min.kg +/- 1.8 to 17.5 mL/min.kg +/- 1.9. CONCLUSIONS Recombinant human erythropoietin is effective and safe in ameliorating the anemia of pre-dialysis patients.

Direct evidence of a role for mast cells in the pathogenesis of antigen-induced bronchoconstriction.

We measured bronchoalveolar lavage (BAL) fluid histamine levels in allergic asthmatics and nonallergic normal subjects after local airway antigen and cold 22 degrees C normal saline challenges. Immediately after instillation of antigen through a bronchoscope wedged into a subsegmental airway, all 17 allergic asthmatics but none of the nine normal subjects had visible airway constriction. The asthmatics had a concomitant mean increase in BAL histamine of 23% (P = 0.005), whereas the normals had no change in BAL histamine. Among the allergic asthmatics, the change in BAL histamine content in response to antigen directly correlated with the control (baseline) BAL histamine content (r = 0.66, P = 0.003). Moreover, asthmatics with large antigen-induced changes in BAL histamine had greater airway methacholine sensitivity than did asthmatics without measurable increases in BAL histamine (8 +/- 2 vs. 41 +/- 31 breath units). Neither asthmatics nor normal subjects had airway constriction or changes in BAL histamine levels in response to nonspecific challenge with cold saline. Our data suggest that when allergic asthmatics are exposed to relevant antigens they have in vivo lung mast cell degranulation which results in airway constriction and contributes to nonspecific airway hyperresponsiveness.

Respiratory symptoms and lung function among workers in swine confinement buildings: a cross-sectional epidemiological study

To study possible chronic respiratory problems of people working in swine confinement buildings, a cross-sectional epidemiological study was initiated. A cohort of swine confinement workers was matched for age, sex, and smoking history with nonconfinement swine producers. Pulmonary function studies and a survey questionnaire for chronic respiratory disease symptoms (the American Thoracic Society, Epidemiologic Standardization Project Questionnaire) were performed on both groups. Compared to controls, the confinement workers experienced significantly higher prevalence of chronic bronchitis and wheezing, (odds ratio 7 and 4, respectively). There were, however, no significant differences in baseline pulmonary functions. Based on the high prevalence of chronic respiratory disease symptoms, this study emphasizes an emerging occupational concern in agriculture to the estimated 500,000 persons working in swine confinement operations and the estimated 500,000 additional persons who work in poultry, veal, beef, or dairy confinement operations. It is important to study a representative population of these workers prospectively to determine if a progressive loss in lung function is evident.

Foreign body removal: a new role for the fiberoptic bronchoscope.

Artificial and animal lung models initially were used to investigate the removal of foreign bodies from the tracheobronchial tree with the flexible fiberoptic bronchoscope. Different extraction instruments (claw, basket, forceps, and balloon catheter) were passed separately through the channel of the bronchofiberscope, and tested for usefulness prior to human application. The Fogarty balloon catheter served as a valuable aid in dislodging impacted objects so that the operator could then grasp them with the claw, basket or forceps. The wire claw recovered many of the metallic and organic objects, the wire basket was successful in retrieving only the bulky objects and the forceps (ACMI) was effective in capturing all of the metallic foreign bodies. These techniques, developed in our laboratory, are now being used to augment rigid bronchoscopy in the removal of foreign bodies from adults and older children. At the present time fiberoptic foreign body removal is not recommended for pediatric cases because of the small diameter of the trachea and glottis in infants and young children.

A Combined Surgical Approach to Non-Oat-Cell Pulmonary Carcinoma with Single Cerebral Metastasis

Eighty consecutive patients with pulmonary non-oat-cell carcinoma and a single cerebral metastasis were followed for at least 5 years after therapy. Forty were treated by surgical excision at both sites of disease plus whole-brain irradiation in most cases (group 1). The remaining 40 patients, an observational cohort, were treated either by surgery at only one site of disease (usually craniotomy), whole-brain irradiation, chemotherapy, or some combination of these modalities (group 2). The 1-year survival in group 2 was 15%, and all were dead at 2 years. In group 1, hospital mortality was 1.5%, the 1-year survival rate 35%, the 2-year survival rate 25%, and the 5-year survival rate 12.5%. All the five year survivors were patients with N0 disease. In this subgroup of group 1, the five year survival was 20%. All patients surviving for more than 2 years were in group 1 and had a Karnofsky rating greater than 50 and N0 disease after staging. These data indicate that a combined surgical approach can be accomplished with low morbidity, low mortality, and increased survival rates, especially for patients with N0 disease who are vigorous enough to undergo the combined treatment.

Endobronchial foreign body removal using the bronchofiberscope.

In certain situations the flexible fiberoptic bronchoscope can augment rigid bronchoscopy in foreign body removal. A case of a successful fiberoptic removal of an endobronchial foreign body (dental bridge) is presented. A wire basket, inserted through the channel of the bronchofiberscope, was used to capture the object.

THE RECOGNITION AND TREATMENT OF HEPATIC AMEBIASIS

Excerpt Hepatic amebiasis is a serious disorder and often it is not diagnosed. The variability and multiplicity of complaints frequently focus the clinicians attention on other disease entities. T...

Selective bronchial catheterization for the study of experimental lung damage in the rabbit.

Summary A nonsurgical rabbit model is described for study of selected lung segments. The technique is easily learned and does not require unusual dexterity. The method utilizes intrabronchial catheterization through a plastic endotracheal tube. The remainder of the lung may serve then as a control.

Light and immunofluorescent study of the Arthus reaction in the rabbit lung

A localized Arthus reaction was produced in the lung of sensitized rabbits by delivery of antigen into a lower lobe bronchus using a method of selective bronchial catheterization under fluoroscopy. The rabbits were sensitized with bovine immunoglobulin G (B-IgG) in incomplete Freunds adjuvant (IFA) to produce precipitating antibody without classic delayed hypersensitivity. Pulmonary histopathology was studied at intervals following antigen challenge, using light and immunofluorescent microscopy. Gross lesions peripheral to the lower lobe bronchus receiving antigen were found within 12 hr. Subsequent necrosis resulted in a dense scar by 6 wk. Microscopically, early lesions were typified by localized bronchitis, bronchiolitis, alveolitis, and vasculitis with exuberant exudates containing predominantly polymorphonuclear leukocytes. Extensive focal necrosis was present by 72 hr. Immunofluorescent studies revealed the presence of B-IgG, rabbit IgG, and complement (C3) in and around bronchi, bronchioles, alveoli, and vessels. No granulomatous lesions were found, and proliferation of alveolar lining cells was not detected in these studies. Thus, the lung can participate in an acute Arthus reaction following local antigen challenge in systemically sensitized animals. The pathology more closely resembles a necrotizing bacterial pneumonia than an interstitial or hypersensitivity pneumonitis under the conditions of this experimental system. Implications for human disease are speculative.