The pharmacodynamics and pharmacokinetics of beta-lactam antibiotics in patients with cystic fibrosis are discussed. A hypothetical dosing regimen based on these principles is considered. The usual dosing regimens may be suboptimal. New dosage regimens should be studied using prospective, controlled, randomized and blinded clinical trials.

The chest x-ray film a 22-year-old man showed a large right-sided pleural effusion that was grossly hemorrhagic when aspirated. A computerized tomographic scan showed a complex mass with cystic components contiguous with the diaphragm. On thoracotomy the mass was found to be arising from the diaphragm and had the consistency of an organizing hematoma. Pathologic studies showed the mass to be an epithelioid hemangioendothelioma. This rare tumor has never been reported previously as arising from the diaphragm. It has a variable prognosis, but surgery remains the treatment of choice. In this report, we review the clinical and pathologic characteristics of this unusual tumor, as well as the distinctive roentgenographic findings with which it presented.

There is now incontrovertible evidence that there is a progressive and strikingly increased mortality from bronchial asthma in the US. The increase is more dramatic in the older age groups, but younger age groups are not spared. The exact cause or causes of this increased mortality are not known, and it is even possible (although not likely) that the increase is artifactual. This increased death rate is in sharp contrast to the general medical perception that major advances in the management of bronchial asthma have occurred. Perhaps they have, but if so, more patients are dying during this period of advances than were dying before. The most prudent course would be to assume that the excess deaths are iatrogenic in origin and to act accordingly. Even if this assumption is flawed, acting on it would improve the management of patients with bronchial asthma. If it is true that the major purpose of risk-benefit analysis is to improve patient outcome rather than merely analyze risk-benefit balance, then a series of proposals can be generated to grapple with this problem in bronchial asthma.

The possible contribution of computed tomography (CT) in the management of patients with solitary pulmonary nodules (SPNs) or masses was reviewed retrospectively in 65 patients undergoing fiberoptic bronchoscopy (FOB). Nodules were evaluated by size, location, surface contour, and the presence in cross-section of a bronchus leading to or contained within the nodule or mass, a "positive bronchus sign." Thirty-five lesions were associated with a positive bronchus sign; 21 of 35 (60 percent) were diagnosed endoscopically, (p = .027); of 30 cases with a negative bronchus sign, only ten (30 percent) had a diagnosis made by FOB (p = .034). It is concluded that CT may be of use in the routine evaluation of pulmonary nodules, prior to bronchoscopy, especially in cases for which histologic evaluation is essential, especially to determine the presence or absence of a CT bronchus sign.

To evaluate available clinical methods (self ratings and questionnaire) for rating dyspnea, we (1) compared scores from the recently developed baseline dyspnea index (BDI) with the Medical Research Council (MRC) scale and the oxygen-cost diagram (OCD) in 153 patients with various respiratory diseases who sought medical care for shortness of breath; and (2) evaluated the relationships between dyspnea scores and standard measures of physiologic lung function in the same patients. The dyspnea scores were all significantly correlated (r = 0.48 to 0.70; p less than 0.001). Agreement between two observers or with repeated use was satisfactory with all three clinical rating methods. The BDI showed the highest correlations with physiologic measurements. Dyspnea scores were most highly related to spirometric values (r = 0.78; p less than 0.001) for patients with asthma, maximal respiratory pressures (r = 0.34 and 0.35; p less than 0.001) for patients with chronic obstructive pulmonary disease, and PImax (r = 0.51; p = 0.01) and FVC (r = 0.44; p = 0.03) for those with interstitial lung disease. These results show that: (1) the BDI, MRC scale, and OCD provide significantly related measures of dyspnea; (2) the clinical ratings of dyspnea correlate significantly with physiologic parameters of lung function; and (3) breathlessness may be related to the pathophysiology of the specific respiratory disease. The clinical rating of dyspnea may provide quantitative information complementary to measurements of lung function.

An intravenous drug abuser presented with bilateral pyopneumothoraces and bacteremia which is a previously unreported complication of jugular vein self-injection. The patient sustained direct pleural trauma and resultant infection by injecting herself with contaminated needles.

This study analyzed the relationship between total respiratory resistance (Rrs) measured by forced oscillation technique and FEV1 during histamine provocation test in 31 children between seven and 17 years of age. Rrs was measured at frequencies between 6 (R6) and 26 Hz (R26). (R6-R26)/R26 was used as an index of frequency dependency of Rrs. A positive histamine test was defined as PC20 less than 8 mg/ml. Seventeen subjects had a positive test, and all of these had increases from baseline of R6 greater than 50 percent and (R6-R26)/R26 greater than 0.45. Of the 14 subjects whose PC20 was greater than 8 mg/ml, only two had changes in R6 and (R6-R26)/R26 of this magnitude. These two subjects had changes in FEV1 of 16 and 18 percent. There was a strong linear relationship between the changes in FEV1 and both R6 and (R6-R26)/R26 from baseline to the final value at the end of the test (r = 0.87 and 0.91 respectively). In conclusion, this study demonstrated that the evaluation of airway reactivity by histamine challenge may be done by forced oscillation technique. It is easy to administer and may allow testing of children unable to perform spirometry.

Theophylline has been utilized widely as a bronchodilator. However, recent studies have shown the potential for administering this drug to enhance cardiovascular performance in patients with chronic obstructive pulmonary disease (COPD). Administered to COPD patients orally as a sustained-action preparation or intravenously as aminophylline, theophylline enhances both right and left heart systolic pump function and lowers both pulmonary artery pressure and pulmonary vascular resistance. These favorable cardiovascular actions suggest an additional use for theophylline in COPD beyond its effects as a bronchodilator.

Dyspnea is influenced by both physiologic and psychologic factors. Breathlessness is common in patients with chronic obstructive pulmonary disease (COPD) and often is the reason that the individual patient seeks medical attention. In order to evaluate the different clinical studies involving the use of theophylline in COPD patients, it is important to consider the three distinct approaches for measuring dyspnea--psychophysical testing, clinical methods, and ratings during exercise. Four randomized, double-blind, placebo-theophylline trials from one to four weeks in duration have evaluated the impact of theophylline on lung function and breathlessness. In these studies, the overall improvement in forced expiratory volume in one second was quite consistent for theophylline compared with placebo therapy. When appropriate clinical methods for measuring dyspnea were used, theophylline showed a positive reduction in breathlessness. These reports suggest that theophylline provides modest objective and subjective improvement in patients with symptomatic chronic air flow obstruction.

Hypergammaglobulinemia, chronic endobronchial infection with Pseudomonas aeruginosa (PA), and the resulting systemic humoral immune response to PA are each associated with worsened clinical status and prognosis in patients with cystic fibrosis (CF). Major serum immunoglobulin isotype levels (IgG, IgA, IgM, and IgG1-4 subclasses) were measured in 31 CF patients and ten control subjects. Immunoglobulin levels were related to airway infection with PA and the resulting IgG antibody response against PA lipopolysaccharide (LPS). Hyperimmunoglobulinemia G was present with elevated IgG1 and IgG2 in 48 percent, IgG3 in 52 percent, and IgG4 in 42 percent of CF patients. The PA infection was associated with striking increases in IgG2. IgG2 levels correlated well with IgG2 antibodies to PA LPS (r = +0.70, p less than 0.001). However, even CF patients who were not infected with PA had an increased prevalence of high IgG3 (p less than 0.05) and IgG4 (p less than 0.01). The PA infection thus appears to be a major, but not the only factor causing hypergammaglobulinemia in CF.