Improved recognition of cor pulmonale in patients with severe chronic obstructive pulmonary disease.

To compare sensitivity of clinical methods (physical examination, electrocardiogram, and chest radiograph) to echocardiography in the detection of cor pulmonale, and to determine the role of nocturnal oxygen desaturation in its development, 33 non-hypoxemic patients who had severe chronic obstructive pulmonary disease (COPD) were evaluated by clinical methods, echocardiography, and overnight ear oximetry. Compared to 25 age-matched control subjects, COPD patients had higher peak pulmonary systolic pressures by contrast-enhanced Doppler (40 +/- 13 versus 22 +/- 5 mm Hg, or 5.3 +/- 1.7 versus 2.9 +/- 0.7 kPa) and ratios of right to left ventricular volume (1.1 +/- 0.6 versus 0.6 +/- 0.1, both p less than 0.05). Defining cor pulmonale as pulmonary hypertension, right ventricular enlargement, or right ventricular hypertrophy, 25 COPD patients (75 percent) had cor pulmonale by echocardiography and 13 (39 percent) by clinical methods (p less than 0.05). Nocturnal desaturation was present in only 21 percent of patients. Echocardiographic measurements were similar between patients with emphysema and patients with bronchitis, and between patients with and without sleep desaturation. In patients who have severe COPD without waking hypoxemia, cor pulmonale is detected nearly twice as often by echocardiography as by clinical methods, but is usually not associated with sleep desaturation.

Biochemical and histomorphometric characterization of a rat model for humoral hypercalcemia of malignancy.

Humoral hypercalcemia of malignancy is a common but incompletely understood syndrome in humans. In an effort to define an animal model of this syndrome, we studied the transplantable Rice-500 Leydig cell tumor in male Fisher rats. Animals were studied 4-9, 10-12, and 13-14 days after tumor transplantation. By days 13-14, tumor-bearing animals were significantly hypercalcemic, hypercalciuric, and hyperphosphaturic compared to control animals. Fractional phosphorus excretion was elevated 4-fold in the tumor-bearing group despite hypophosphatemia. Mean nephrogenous cAMP in the tumor-bearing animals was 5 times the value in controls at days 13-14, while simultaneous immunoreactive PTH levels were undetectable. Plasma 1,25-dihydroxyvitamin D was significantly elevated in the tumor-bearing animals on day 14. Quantitative bone histomorphometry showed uncoupling of bone cell function in the tumor group, with marked suppression of bone formation, while indices of bone resorption were more than 2-fold elevated. Conditioned medium from tumor cells grown in culture consistently showed activity in a fetal bone-resorbing assay. This activity was heat stable and had an estimated mol wt of 30,000-50,000 daltons. Incubation of cells with indomethacin had no effect on bone-resorbing activity. These data indicate that the mediator in the model shares some of the actions of PTH, but is clearly distinct from native PTH. The findings exactly parallel those in human humoral hypercalcemia of malignancy, with the elevated 1,25-dihydroxyvitamin D values being the sole exception. The demonstration of in vitro bone-resorbing activity will aid in further characterization of the mediator.

Evidence for bidirectional net movement of creatinine in the rat kidney.

Although the clearance of endogenous creatinine is used in many physiologic and metabolic studies in the rat as an index of glomerular filtration rate, there is no evidence that creatinine is a reliable test substance. Studies were therefore performed in anesthetized and conscious rats to determine the creatinine-to-inulin clearance ratio (CCr/CIn). In anesthetized animals the CCr/CIn ratio was 0.5 and in conscious rats it was 0.7 at normal basal plasma creatinine levels. After an increase in plasma creatinine to 1.9 mg/dl induced by the intravenous infusion of creatinine, the CCr/CIn ratio was 1.2. Accordingly, these data indicate that net creatinine transport across the renal tubule is bidirectional and that transport is influenced by the plasma creatinine level. At normal plasma levels creatinine is extensively reabsorbed along the nephron, whereas net secretion is associated with elevated plasma creatinine. The results demonstrate that creatinine is not a reliable marker of glomerular filtration rate in the rat.