Changes in the proliferative activity of human hematopoietic stem cells in NOD/SCID mice and enhancement of their transplantability after in vivo treatment with cell cycle inhibitors.

Human hematopoietic tissue contains rare stem cells with multilineage reconstituting ability demonstrable in receptive xenogeneic hosts. We now show that within 3 wk nonobese diabetic severe combined immunodeficiency (NOD/SCID) mice transplanted with human fetal liver cells regenerate near maximum levels of daughter human hematopoietic stem cells (HSCs) able to repopulate secondary NOD/SCID mice. At this time, most of the human HSCs (and other primitive progenitors) are actively proliferating as shown by their sensitivity to treatments that kill cycling cells selectively (e.g., exposure to high specific-activity [(3)H]thymidine in vitro or 5-fluorouracil in vivo). Interestingly, the proliferating human HSCs were rapidly forced into quiescence by in vivo administration of stromal-derived factor-1 (SDF-1) and this was accompanied by a marked increase in the numbers of human HSCs detectable. A similar result was obtained when transforming growth factor-beta was injected, consistent with a reversible change in HSCs engrafting potential linked to changes in their cell cycle status. By 12 wk after transplant, most of the human HSCs had already entered G(o) and treatment with SDF-1 had no effect on their engrafting activity. These findings point to the existence of novel mechanisms by which inhibitors of HSC cycling can regulate the engrafting ability of human HSCs executing self-renewal divisions in vivo.

Airway coccidioidomycosis--report of cases and review.

Infection due to Coccidioides immitis usually begins in the lungs. Despite the initial pulmonary portal of entry, endotracheal and endobronchial coccidioidomycosis has rarely been described. Since the introduction of fiberoptic bronchoscopy and the AIDS epidemic, more C. immitis lesions of the large airways have been noted. We present data on 38 cases of coccidioidomycosis of the airways, including 6 cases detailed from our own experience and 32 from the literature. Direct infection of the airways (28 cases) is a more common mechanism of airways disease than is erosion into the airways from a lymph node (5 cases). Bronchoscopic findings vary and may show mucosal involvement or intrinsic obstruction. Endotracheal and endobronchial disease is not a self-limited disease and requires antifungal therapy. Disseminated disease in these patients is common. Coccidioidomycosis must be considered in the differential diagnosis of airway pathology.

Lung volumes in 4,774 patients with obstructive lung disease.

STUDY OBJECTIVES: To determine the correlates of static lung volumes in patients with airways obstruction, and to determine if static lung volumes differ between asthma and COPD. PATIENTS AND METHODS: We examined the data from all of the adult patients (mean age of 69) who were referred to a pulmonary function laboratory from January 1990 through July 1994 with an FEV1/FVC ratio of < 0.70 and tested using a body plethysmograph. Correlates were determined using regression analysis. MEASUREMENTS AND RESULTS: Of the 4,774 patients observed with evidence of airways obstruction, 61% were men. Self-reported diagnoses included asthma, 19%; emphysema or COPD, 23%; chronic bronchitis, 1.5%; and alpha1-antiprotease deficiency, 0.6%. Fifty-six percent of the patients did not report a respiratory disease. The degree of hyperinflation, as determined by the residual volume (RV)/total lung capacity (TLC) ratio, or the RV % predicted (but not the TLC % predicted), was strongly associated with the degree of airways obstruction (the FEV1 % predicted). Patients with moderate to severe airways obstruction and high RV and TLC levels were more likely to have COPD than asthma. Of the 1,872 patients with a reduced vital capacity determined by spirometry testing, 87% had hyperinflation as defined by the RV/TLC, and 9.5% had a low TLC (with less severe airways obstruction). CONCLUSION: In patients found to have airways obstruction by spirometry, the additional measurement of static lung volumes added little to the clinical interpretation.

Management of rectal injuries. Dogma versus practice.

The current treatment of civilian rectal injuries stems from military practice. Five principles have evolved: 1) complete fecal diversion, 2) debridement and closure, 3) rectal stump irrigation, 4) presacral drainage, and 5) broad spectrum antibiotics. To assess our practice results, the records of 52 consecutive patients with rectal injury seen at Detroit Receiving Hospital from 1980-88 were reviewed. Etiologies were gunshot (40), shotgun (9), anal assault (2), and stab (1). There were no blunt injuries and no deaths. Treatment consisted of celiotomy (52), diverting colostomy (51), presacral drains (35), rectal stump irrigation (26), and primary closure (1). Broad spectrum antibiotics were administered in all patients. Despite lack of universal application of the "standard" principles, only five patients had postoperative complications and none were related to the rectal injury. Our results demonstrate that a single approach may not be justified, as excellent outcome was achieved with low morbidity and no mortality despite selective management. The universal application of colostomy, repair, irrigation, drainage, and antibiotics cannot be supported.