Nitric oxide modulation of human leukemia cell differentiation and gene expression.

Nitric oxide (NO) functions as an intercellular messenger molecule in such varied contexts as neurotransmission, immune regulation, and the control of vascular tone. We report that NO, delivered as purified gas or released from the pharmacologic NO donors sodium nitroprusside or 6-morpholino-sydnonimine, caused monocytic differentiation of cells of the human myeloid leukemia cell line HL-60 and altered gene expression. The treated cells stopped proliferating, became spread and vacuolated, had increased expression of nonspecific esterase and the monocyte marker CD14, and displayed increased capacity to produce hydrogen peroxide. Furthermore, these treated cells had increased steady-state expression of messenger RNA (mRNA) for tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta), but decreased expression of mRNA for the proto-oncogenes c-myc and c-myb. The increase in TNF-alpha and IL-1 beta mRNA levels was due (at least in part) to a new transcription of these specific mRNAs. NO elaborated in the bone marrow microenvironment may have a role in normal and malignant hematopoietic cell growth and differentiation.

The clinical manifestations of Degos' syndrome.

Pathologic mechanisms underlying Degos' syndrome are poorly characterized. Thrombosis, either as a consequence of a postulated vasculitis or as a primary defect, is often a clinical complication of this syndrome. We have studied multiple coagulation parameters, including potential defects in fibrin assembly and other adhesive proteins, in a patient with Degos' syndrome and found no specific abnormality to explain the pathologic features of this syndrome. An extensive literature review as well as detailed biochemical and biophysical coagulation studies are presented. The alternative possibility of Degos' syndrome as a mucinosis is discussed.

Longitudinal evaluation of glomerular filtration rate during long-term lithium therapy.

Lithium produces many renal effects, but the important question of whether or not it causes chronic interstitial nephritis with consequent reduced glomerular filtration rate (GFR) remains unanswered. The several studies carried out in this area have been cross-sectional and, therefore, have not contained prospective information regarding creatinine clearance. The present study provides data from seven patients in whom creatinine clearances were obtained bracketing an average span of 7.5 years of continuous lithium therapy. Over this time, there was no significant change either in mean serum creatinine concentration or in average creatinine clearance (first determination: 1.1 +/- 0.1 [SE] mg/dL, 99 +/- 8 mL/min/1.73 m2; second determination 1.0 +/- 0.1, 105 +/- 4, respectively). The data, thus, support preservation of GFR during long-term lithium therapy.

Residents' leadership styles and effectiveness as perceived by nurses.

Although physicians are required to act as leaders in a variety of situations, leadership ability and leadership training have been largely ignored by medical educators. The leadership styles and leadership effectiveness of 17 residents in a community hospital were studied as part of a leadership training seminar. Self-ratings and ratings of the residents by nurses who had worked with them were used to assess the residents' leadership style and the nurses' perceptions of the effectiveness of those styles. Styles that emphasized relationships with co-workers (encouraging and coaching styles) predominated over low relationship-oriented styles (delegating and structuring). The nurses perceived individual residents who exhibited encouraging and coaching leadership styles as being distinctly more effective leaders than the residents who exhibited structuring and delegating styles. The residents, however, rated all four styles as similarly effective. Leadership training programs and studies of the type reported here may provide an opportunity for faculty members to help residents learn more appropriate and productive styles of leadership.

Urinary carbon dioxide tension in lithium carbonate-treated patients.

Renal acidification was studied in 12 lithium carbonate-treated psychiatric patients. The urinary Pco2 response to oral sodium bicarbonate loading, a qualitative index of distal hydrogen ion secretion, was evaluated in all patients and the results were compared with those obtained in 10 control subjects. The average maximal urine to arterial blood Pco2 difference (U-A Pco2) in the psychiatric patients [26 +/- 3 (S.E.) mm Hg] was significantly lower (P less than .001) than that of control subjects (51 +/- 3 mm Hg) and only three patients had values greater than 31 mm Hg (2 S.D. below the mean control value). Eight of these patients were also evaluated with NH4CL acid loading. Seven of eight patients had a minimal urine pH less than 5.30 after NH4CL administration; only one of the seven had a normal U-APco2 after bicarbonate loading. Three patients were evaluated prior to treatment and after 2 weeks of lithium administration. Pretreatment U-APco2 values were normal. After therapy the values were lower in all three patients becoming definitely abnormal in two. The present investigation, in concert with previous animal studies, demonstrates that chronic lithium carbonate therapy in man may result in decreased U-A Pco2.

Effect of long-term lithium administration on renal phosphorus handling.

Renal phosphorus handling was evaluated in 12 lithium carbonate-treated psychiatric patients. Serum phosphorus was normal and serum lithium values were within the therapeutic range in all subjects. Serum calcium concentrations measured in 6 of the patients were found to be within the normal range; in the same patients serum parathyroid hormone levels were normal in 4 and slightly elevated in 2. Phosphorus clearance (14 +/- 3 [se] ml/min) and tubular reabsorption of phosphorus (88 +/- 2%) during oral sodium bicarbonate loading were not significantly different from those in 10 healthy control subjects. In a subgroup of 5 patients and 5 control subjects, phosphorus excretion did not increase after bicarbonate loading. In these subjects, phosphorus excretion rates after bicarbonate loading were not different. Although experimental studies suggest that lithium inhibits renal cortical adenylate cyclase stimulation by parathyroid hormone, our data did not indicate any striking effect of long-term lithium administration on serum calcium and serum phosphorus or on renal phosphorus handling.