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Biomedical subjects

S M Albelda

Publications and source records attributed to S M Albelda.

141 records · Page 8Linked to original sources

Effects of increased ventilation on lung lymph flow in unanesthetized sheep.

To determine the effect of an increase in spontaneous minute ventilation on lung fluid balance, we added external dead space to the breathing circuit of six tracheostomized, unanesthetized, spontaneously breathing sheep in which lung lymph fistulas had been created surgically. The addition of 120-180 ml of dead space caused minute ventilation to increase by 50-100% (secondary to increases in both tidal volume and frequency), without changing pulmonary arterial pressure, pulmonary capillary wedge pressure, cardiac output, or arterial blood gas tensions. The increase in spontaneous ventilation was associated with an average increase of 27% in lung lymph flow (P less than 0.05) and an average reduction of 11% in the lymph-to-plasma concentration ratio (L/P) for total protein (P less than 0.05). Lymph flow and L/P for total protein approached stable values after 2-3 h of hyperpnea, and the increase in lymph flow persisted for at least 18 h of dead-space breathing. Removal of dead space was associated with a rapid return (within 45 min) of lymph flow to base-line levels. These results suggest that hyperpnea increases the pulmonary transvascular filtration rate. Since no changes in vascular pressures or cardiac output were observed, this increase in transvascular filtration is most likely due to a fall in interstitial fluid pressure.

Animals↗

Diffuse pulmonary hemorrhage: a review and classification.

Diffuse pulmonary hemorrhage is an uncommon condition that is difficult to differentiate radiographically from diffuse pneumonia or pulmonary edema. The diagnosis should be suspected when a patient has even mild hemoptysis or has one of the diseases known to be associated with diffuse pulmonary hemorrhage. This paper reviews the clinical and radiographic features of diffuse pulmonary hemorrhage and presents a classification scheme depicted as a Venn diagram formed by four overlapping circles representing pulmonary hemorrhage, renal disease, immune complex disease, and antiglomerular basement membrane (anti-GBM) disease. This scheme results in six categories of pulmonary hemorrhage: associated with glomerulonephritis and anti-GBM antibody; associated with renal disease without demonstrable immunologic abnormalities; associated with glomerulonephritis and immune complex disease; associated with immune complex disease without renal disease; associated with anti-GBM antibodies without renal disease; without associated immunologic or renal abnormality. Examples of these disorders are illustrated. Improved clinical-radiographic correlation may lead to earlier diagnosis and treatment of diffuse pulmonary hemorrhage and its causes.

Anemia↗

Expanding spectrum of pulmonary disease caused by nontuberculous mycobacteria.

The clinical and radiographic features of 35 patients with nontuberculous mycobacterial (NTMB) pulmonary infections were reviewed. Radiographs of half the patients showed the pattern of cavitary upper-lobe infiltrates typical of reactivation tuberculosis; those of the other half had a radiographic pattern characterized by patchy, nodular infiltrates without an upper-lobe prevalence. Approximately half of the latter group showed multiple small cavities resembling those seen in bronchiectasis. These results suggest that studies in which the diagnosis of NTMB infection has been made primarily from sputum cultures may have been biased toward detecting cavitary disease. The spectrum of pulmonary disease caused by NTMB appears to be larger than previously appreciated. An enhanced awareness of alternate presentations of NTMB infections may result in earlier diagnosis.

Adult↗

Invasive pulmonary aspergillosis and acute leukemia. Limitations in the diagnostic utility of the air crescent sign.

The air crescent sign is regarded as an important diagnostic finding in invasive pulmonary aspergillosis (IPA). This study examined the incidence, clinical importance, and natural history of air crescents in 25 patients with acute leukemia and IPA. Twelve (50%) of the patients had cavities (ten with an air crescent) that appeared an average of 15 days after the initial infiltrate. The diagnostic utility of the air crescent sign was relatively minor; cavities developed after the diagnosis was established in 50% of cases and after therapy was started in 75% of cases. In each case, the pneumonia improved at the time of cavitation. In six patients (50%), the cavities resolved over 2-8 months. Three patients (25%), however, experienced massive hemoptysis. Air crescent formation, previously shown to be dependent on granulocyte recovery, was associated with improved survival (67%) compared with the group without cavitation (8%). In the latter group, the pneumonia in ten (77%) of 13 patients progressed to diffuse disease. In patients with leukemia, the diagnostic value of the air crescent sign is limited by cavities that develop relatively late, as the infection improves after white blood cell recovery; cavities that do not occur in patients who remain neutropenic; and associated hemorrhage, at times life-threatening, that obscures the air crescent. The diagnosis of IPA should not await observation of air crescents in these patients.

Acute Disease↗

Pulmonary cavitation and massive hemoptysis in invasive pulmonary aspergillosis. Influence of bone marrow recovery in patients with acute leukemia.

The influence of bone marrow recovery on the clinical and radiographic course of invasive pulmonary aspergillosis in patients with acute leukemia has not been well characterized. We studied 26 patients with acute leukemia and invasive pulmonary aspergillosis, comparing those who recovered from chemotherapy-induced granulocytopenia (Group 1, 15 patients) with those who did not (Group 2, 11 patients). Radiographic evidence of pulmonary cavitation was not seen in any Group 2 patient, but developed in 11 of 15 (73%) Group 1 patients (p less than 0.005). In these patients, cavitation always occurred after marrow recovery, an average of 2.0 days (range: 0 to 6 days) after the granulocyte count exceeded 500/mm3. Eight patients in Group 1 and 2 in Group 2 experienced a total of 38 episodes of hemoptysis. Four of the 26 patients, all in Group 1, developed massive hemoptysis (greater than 150 ml of blood per episode), leading to 1 death. In 3 of these 4 patients, cavitation preceded the episode of massive hemoptysis. At the time of massive bleeding, the granulocyte count was greater than 500/mm3, the platelet count greater than 38,000/mm3, and the other coagulation parameters were normal in all 4 patients. Our findings demonstrate that in patients with acute leukemia undergoing chemotherapy, bone marrow recovery markedly influences the clinical and radiographic course of invasive pulmonary aspergillosis. Development of a granulocyte count greater than 500/mm3 is associated with pulmonary cavitation, and on occasion with massive hemoptysis.

Acute Disease↗

Diagnostic utility of pleural fluid eosinophilia.

It has been stated that pleural fluid eosinophilia (defined as greater than 10 percent eosinophils in the pleural white cell differential count) is not helpful in the diagnosis of exudative effusions. By review of the recent literature, it was found that pleural fluid eosinophilia was associated most often with idiopathic effusions or with air previously introduced into the pleural space. Also, a high proportion of "idiopathic" and benign asbestos effusions were characterized by pleural fluid eosinophilia, a previously unrecognized phenomenon. The diagnostic utility of finding eosinophils in the pleural space was assessed from its impact on prior probabilities of disease. Estimates of pretest likelihoods of malignant versus nonmalignant pleural effusions and the prevalence of eosinophilia in effusions of known cause were obtained from extensive literature review. These were modified by using Bayes' rule to estimate the revised probability of disease in the presence of an eosinophilic effusion. The presence of pleural fluid eosinophilia considerably reduced the probability of malignancy or tuberculosis and increased the likelihood of an underlying benign disorder. Pleural fluid eosinophilia is a useful finding that can aid in the diagnosis of an exudative pleural effusion.

Eosinophilia↗

Role of fiberoptic bronchoscopy in the diagnosis of invasive pulmonary aspergillosis in patients with acute leukemia.

The utility and safety of fiberoptic bronchoscopy in the diagnosis of invasive pulmonary aspergillosis in patients with acute leukemia have not been examined. The results of 21 bronchoscopic procedures in 19 patients with invasive pulmonary aspergillosis and acute leukemia were reviewed. Analysis was confined to the 16 patients who had histopathologically documented infection on biopsy or at autopsy. Fiberoptic bronchoscopy established or suggested the diagnosis of invasive pulmonary aspergillosis in eight of 16 (50 percent) patients. Transbronchial or bronchial biopsy added only one diagnosis to those obtained by bronchial washing and brushing. Although fiberoptic bronchoscopy was a safe and well-tolerated procedure in our patients with invasive pulmonary aspergillosis and acute leukemia, its success rate was only 50 percent overall, and it appeared to be even less successful when performed early in the course of the disease. Fiberoptic bronchoscopy is a useful first procedure for the evaluation of patients with acute leukemia and possible invasive pulmonary aspergillosis, but a negative result does not exclude aspergillosis. Further diagnostic procedures, including repeated bronchoscopy, or institution of empiric antifungal therapy may be warranted if the clinical suspicion of invasive pulmonary aspergillosis is high.

Acute Disease↗

Ventilator-induced subpleural air cysts: clinical, radiographic, and pathologic significance.

Alveolar rupture from the high airway pressures used in the treatment of adult respiratory distress syndrome may cause interstitial dissection of gas peripherally and the formation of "subpleural air cysts." These thin-walled, rounded air collections are easily detectable radiographically, and their recognition can provide an important early sign of pulmonary barotrauma. This report summarizes the clinical, radiographic, and pathologic features of this lesion in 5 adult patients. We found that tension pneumothorax rapidly occurs after the appearance of these cysts if airway pressures are not reduced or chest tubes are not in place. Secondary infection of the cysts was also common and added significant morbidity to this already compromised group of patients.

Adult↗

Bronchopleural fistula complicating invasive pulmonary aspergillosis.

Pleural involvement has been notably absent in reviews of invasive pulmonary aspergillosis. This report describes the development of a bronchopleural fistula complicating invasive aspergillosis in a patient receiving chemotherapy for leukemia. The fungal hydropneumothorax occurred despite early diagnosis of the pulmonary infection and prompt treatment with amphotericin B. Closed pleural drainage and continued antifungal medication resulted in ultimate cure of the infection. The presumed pathophysiologic aspects of this event are discussed and the literature on pleural aspergillosis is reviewed.

Adult↗

Pleural thickening: its significance and relationship to asbestos dust exposure.

The admission chest radiographs of 824 were screened for the presence of bilateral pleural thickening. Those patients with pleural thickening were scored according to the ILO classification of radiographs of the pneumoconioses. The prevalence of bilateral pleural thickening was high (6.2%) in these patients, of whom 67% had an environmental or occupational history suggestive of asbestos exposure. The predictive value of bilateral pleural thickening alone as an indicator of previous asbestos exposure was 67%. If one excludes known medical or surgical etiologies of pleural thickening then the predictive value increased to 81%. The radiographic detection of bilateral pleural thickening has a strong association with prior asbestos exposure.

Adult↗

Ventricular tachycardia terminated by carotid sinus massage.

Carotid sinus massage affects supraventricular arrhythmias primarily through vagotonic effects on the sinus and AV nodes, but vagal innervation of the ventricle also exists and has been shown to have functional significance. The case presented here illustrates an unusual example of a ventricular tachycardia that was repeatedly converted to normal sinus rhythm by carotid sinus massage following administration of digoxin. The clinician should be aware that a wide QRS-complex tachycardia that responds to carotid sinus massage is not necessarily supraventricular in origin.

Carotid Sinus↗

The evaluation of adenoviral p53-mediated bystander effect in gene therapy of cancer.

Because many tumors have mutated p53, one potential strategy proposed for cancer gene therapy is the introduction of the wild-type p53 gene into tumor cells. One puzzling aspect of this approach is that currently available gene transfer protocols result in a small percentage of tumor cells being transduced in vivo, thus implicating a "bystander effect" to achieve therapeutic efficacy. Because bystander effects in the context of p53-mediated gene therapy have not been well characterized, we evaluated the role of in vitro and in vivo bystander effects of adenovirally delivered p53 (AdWTp53). Using human tumor cell lines that did not express p53 protein but were infectible with adenovirus and showed sensitivity to p53-mediated apoptosis, we were unable to demonstrate an AdWTp53-mediated in vitro bystander effect, despite seeing strong bystander effects when cells were infected with an adenovirus containing the suicide gene herpes simplex virus thymidine kinase and treated with ganciclovir. In contrast, in vivo flank mixing studies using one of these cell lines showed a weak but significant p53-mediated bystander effect (a 40% inhibition of tumor growth). This bystander effect translated into a small survival advantage in an established intraperitoneal tumor model when tumor burden was low at the time of viral instillation. The survival advantage was lost, however, when tumor burden was increased. This study indicates that treatment of human tumors using AdWTp53 may be possible; however, because of the weak bystander effect in vivo, effective treatment will likely require a large percentage of tumor cells to be transduced.

Adenoviridae↗

The effect of promoter strength in adenoviral vectors containing herpes simplex virus thymidine kinase on cancer gene therapy in vitro and in vivo.

The use of adenoviral vectors to deliver the herpes simplex virus thymidine kinase (HSVtk) gene followed by treatment with the prodrug ganciclovir (GCV) has promise for a variety of applications where excess cell proliferation is detrimental such as treatment of tumors and vascular restenosis. Optimizing this system is thus an important goal. The purpose of this study was to determine if the induction of higher levels of HSVtk expression would augment the sensitivity to GCV. This was accomplished by generating adenoviral vectors that expressed HSVtk from promoters of different efficiencies (the CMV versus RSV promoters). Despite higher levels of HSVtk expression per cell with the CMV promoter, there was no significant enhancement of antitumor effects between RSV- and CMV-driven adenovirus vectors in in vitro and in vivo studies indicating that simply increasing HSVtk enzyme levels per cell above a minimal threshold level will not be effective in augmenting the HSVtk/GCV system. These results suggest that other strategies, e.g., the use of higher doses of GCV, augmentation of the "bystander effect," the generation of mutant HSVtk genes with higher substrate affinities, the discovery of improved vectors with increased transduction efficiencies, or the development of new prodrugs with higher affinities for HSVtk will therefore be needed to enhance therapeutic responses.

Adenoviridae↗