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Biomedical subjects

D E Midthun

Publications and source records attributed to D E Midthun.

26 records · Page 2Linked to original sources

Evolving strategies in lung transplantation for emphysema.

Evolving strategies of pulmonary preservation, bronchial revascularization, immunosuppression, and infectious disease management were used in 15 initial consecutive patients undergoing lung transplantation for emphysema. There were 10 women and 5 men with a mean age of 49 years (range, 36 to 60 years). All patients required supplemental oxygen therapy. One bilateral, 9 left, and 5 right transplantations were performed. Mean preoperative forced expiratory volume in 1 second and total lung capacity were 16% and 146%, respectively, of predicted. Quadruple drug immunosuppression was used. Actuarial 1-year survival in this initial series is 93.3% +/- 6.4% (Kaplan-Meier) with one early cardiac death at day 71. Mean forced expiratory volume in 1 second and diffusing capacity for carbon monoxide at discharge were 43% and 62%, respectively, of predicted. Rehabilitation has been excellent, and all survivors are active and free of supplemental oxygen. During the study, the following treatment strategies have evolved: (1) University of Wisconsin solution has replaced Euro-Collins' solution for pulmonary preservation; (2) direct bronchial revascularization with the internal thoracic artery now is used; (3) an algorithm-based variable dose OKT3 induction regimen has resulted in a major reduction in dosage; and (4) infectious disease management focuses on the prophylaxis of cytomegalovirus and fungal infection using prolonged ganciclovir and early itraconazole therapy as well as the avoidance of Epstein-Barr virus mismatches. Single-lung transplantation for emphysema has excellent early results with continuing evolving management strategies.

Adenosine↗

Approach to the solitary pulmonary nodule.

Because many malignant and benign processes may manifest as a solitary pulmonary nodule on a chest roentgenogram, this finding presents a diagnostic challenge. The major concern is whether the lesion is malignant. The likelihood of a malignant tumor correlates with the age of the patient, the size of the nodule, a history of a prior malignant lesion, and a history of smoking. Recent advances in radiologic techniques, such as the detection of calcium or the inference of the presence of calcium by high attenuation values on computed tomography, provide assistance in identifying benign lesions. The history, physical examination, and radiographic information can help determine an appropriate course of action. The goals are to remove malignant nodules promptly and to avoid surgical intervention in patients whose nodules are benign.

Biopsy, Needle↗

Outpatient care of COPD patients.

Chronic obstructive pulmonary disease (COPD) is a disorder of airflow limitation that is often progressive. Interventions aimed at slowing this progression include smoking cessation, avoidance of exacerbating factors, and prevention or early treatment of infection. Reversible symptoms can be controlled pharmacologically, with supplemental oxygen prescribed when needed. Finally, quality of life can be improved through education and pulmonary rehabilitation.

Environment↗

Clinical strategies for solitary pulmonary nodule.

The solitary pulmonary nodule frequently presents a diagnostic dilemma to the physician and the patient. Is it malignant or benign? Should it be observed, biopsied, or removed? Much has been learned through surgical, biopsy, and radiographic studies to help answer these questions. We review what is known about the solitary nodule and discuss the clinical approach to its evaluation.

Biopsy↗

Transmembrane signaling during natural killer cell-mediated cytotoxicity. Regulation by protein kinase C activation.

NK cells can mediate either FcR-dependent cytotoxicity against antibody-coated target cells or direct cytotoxicity against a variety of tumor cells. We used homogeneous, cloned populations of CD16+/CD3- human NK cells to characterize and compare the transmembrane signaling mechanisms used during these alternative forms of cytotoxicity. Cross-linkage of NK cell FcR with anti-FcR (anti-CD16) mAb or direct binding to NK-sensitive tumor targets resulted in a rapid release of inositol phosphates and increases in [Ca2+]i. The receptor-dependent [Ca2+]i increase (as monitored in indo-1 loaded NK cells by flow cytometry) consisted of an initial release of calcium from intracellular stores, followed by a sustained influx of calcium across the plasma membrane. To assess the potential regulatory feedback role of protein kinase C (PKC) activation in these proximal signaling events, NK cells were pretreated with either PKC-activating phorbol esters, nonactivating phorbol ester homologs, or synthetic diacylglycerols. Brief pretreatment with activating phorbol esters rapidly inhibited, in a concentration-dependent manner, both phosphoinositide hydrolysis and increases in [Ca2+]i induced by FcR ligation, whereas pretreatment with an inactive phorbol ester had no effect. This acute inhibitory effect was not explained by FcR down-regulation, which occurred with more prolonged exposure to phorbol esters. In contrast, the phosphoinositide turnover and [Ca2+]i increase in NK cells stimulated with NK-sensitive tumor targets were not affected by prior exposure to PKC-activating phorbol esters. This differential regulatory effect of phorbol ester on proximal signaling was paralleled by a corresponding effect on cytotoxicity, i.e., phorbol ester-induced activation of PKC inhibited FcR-dependent cytotoxicity, but did not alter direct cytotoxicity against NK-sensitive tumor cells. These results indicate that PKC activation can differentially regulate alternative forms of NK cell-mediated cytotoxicity by rapidly and specifically desensitizing the FcR.

Antigens, Differentiation↗

Reduced work of breathing after single lung transplantation for emphysema.

BACKGROUND: Pulmonary emphysema, with or without chronic bronchitis, has emerged as the most common indication for successful single lung transplantation. Although gas exchange can be expected to improve after successful transplantation, such changes do not adequately explain the improvement in dyspnea experienced by these patients and resulting in improved quality of life. METHODS: We prospectively studied the respiratory mechanics of 14 single lung transplantation recipients with pulmonary emphysema, of whom 10 have been followed up beyond 1 year. The mean age of the group was 48.8 years (range, 42 to 60 years) for the seven men and seven women. Average donor-predicted total lung capacity was 0.6 L (+0.2 [standard error]) greater than recipient-predicted total lung capacity. Comparison of pulmonary resistance, dynamic lung compliance, and static lung compliance were taken to examine the possible role of reduced airways resistance and of improved elastic recoil in the reduced work of breathing. Results were analyzed by means of a one-tailed paired Student t test and linear regression analysis (both stepwise and multivariate); results are tabulated by mean (+/- 1 [standard error]). RESULTS: Between preoperative measurements and 12 months postoperatively, maximum lung elastic recoil increased from 8.1 (+/- 0.7) to 11.3 (+/- 1.0) cm H2O, p < 0.01; pulmonary resistance fell from 8.3 (+/- 0.8) to 5.4 (+/- 0.7) cm H2O sec/L, p < 0.01. Dynamic lung compliance fell from 0.23 (+/- 0.04) to 0.12 (+/- 0.02) L/cm H2O, p < 0.02, and static lung compliance fell from 0.66 (+/- 0.13) to 0.22 (+/- 0.05) L/cm H2O, p < 0.001. CONCLUSIONS: The decline in lung compliance after single lung transplantation reflects the importance of improvement in elastic recoil and reduced chest wall distention, improving the work of breathing. The 67% decline in static lung compliance (300% increase in elastic recoil) is probably the single most important mechanical factor leading to reduced dyspnea after single lung transplantation for emphysema.

Airway Resistance↗