Effect of cyclical therapy with phosphorus and etidronate on axial bone mineral density in postmenopausal osteoporotic women.

Forty seven women with postmenopausal osteoporosis and at least one but no more than four vertebral compression fractures received sequential and cyclical therapy with phosphorus and etidronate (p/etid). During the same 2-year period of observation, three other groups of patients received either sodium fluoride (n = 12), estrogen replacement therapy (n = 12), or vitamin D and calcium (Ca++) alone (n = 15). Axial bone mineral density (BMD) was measured by means of dual-photon absorptiometry. Lateral thoracic and lumbar spine radiographs were taken to assess fractures. Bone mineral density increased from baseline during p/etid therapy: Mean 15.7 +/- 1.6% (SD) (P less than 0.001). During the same time, the patients in the sodium fluoride group showed a comparable increase in their BMD from baseline: mean 15.7 +/- 1.1% (P less than 0.001). During the first year of therapy, patients in the estrogen replacement group had an increase in their BMD from baseline: mean: 4.6% +/- 1.1% (P less than 0.05). No change in BMD was seen in the control group that received vitamin D and Ca++ alone. No patient who received p/etid, sodium fluoride, or estrogen replacement therapy had any new vertebral compression fractures or height loss, whereas in the control group that received vitamin D and Ca++ alone 6 out of 15 had height loss and at least one new vertebral fracture (P less than 0.01). p/etid therapy increases BMD in women with postmenopausal osteoporosis comparable to sodium fluoride but without side effects or toxicity and stabilizes vertebral compression fractures.

Effects of lithium on cAMP generation in cultured rat inner medullary collecting tubule cells.

The effects of lithium (Li) on the cAMP system in rat inner medullary collecting tubule cells were studied. While acute exposure to 5 mM Li was without effect, 10 mM, 25 mM and 50 mM Li significantly decreased AVP-stimulated cAMP formation. In contrast, cells grown in 5 mM Li for 72 hours which caused no morphologic changes enhanced cAMP formation (fmol/microgram protein) in response to both 10 nM AVP (114.5 +/- 9.2 vs. 71.6 +/- 7.4, P less than 0.005) and 100 nM AVP (182 +/- 14 vs. 120 +/- 8.3, P less than 0.001), N = 16. A similar enhancement was observed when cAMP formation was stimulated by a post-receptor agonist, cholera toxin. The role of eicosanoids was examined with 5 microM meclofenamate which reversed Li-enhanced cAMP formation in response to both AVP and cholera toxin. To define the eicosanoid responsible, cyclooxygenase products were measured. Prostaglandin E2 and thromboxane B2 synthesis were unchanged by Li, but the production of prostacyclin was significantly (P less than 0.02) increased. Prostacyclin (3 microM) mimicked the effect of Li to enhance the response to 10 nM AVP as cAMP levels increased from 100 +/- 11 to 173 +/- 13, P less than 0.05. The experiments suggest that acute exposure of Li at concentrations of 10 mM or greater inhibit cAMP formation but prolonged Li exposure enhances cAMP formation by increasing the formation of prostacyclin.

Eosinophiluria--a new method of detection and definition of the clinical spectrum.

Eosinophiluria is considered a useful marker of drug-induced acute interstitial nephritis. However, recognition of eosinophiluria by Wright's staining is technically difficult, and the spectrum of disorders causing eosinophiluria is not completely defined. We have adapted Hansel's stain for the examination of urinary sediment. Whereas there was a variable uptake of Wright's stain by eosinophils in the urine, such eosinophils were readily recognized with Hansel's stain by the presence of bright red granules. The prevalence of eosinophiluria in acute interstitial nephritis was 10 of 11 patients, in acute tubular necrosis none of 30, in acute pyelonephritis none of 10, in acute cystitis 1 of 15, in postinfectious glomerulonephritis 1 of 6, in rapidly progressive glomerulonephritis 4 of 10, and in acute prostatitis 6 of 10. Eosinophiluria in acute interstitial nephritis was demonstrated by Hansel's stain in 10 of 11 patients but by Wright's stain in only 2 of 11 patients. We conclude that Hansel's stain substantially improves the recognition of eosinophiluria as compared with Wright's stain. Eosinophiluria is useful in distinguishing acute interstitial nephritis from acute tubular necrosis. The clinical spectrum of eosinophiluria also includes rapidly progressive glomerulonephritis, acute prostatitis, and occasionally, acute cystitis or postinfectious glomerulonephritis.

Vasopressin and the concentrating mechanism.

The role of vasopressin in the kidney has classically been considered to result from its ability to increase water permeability in the collecting duct. Recent data, however, suggest that the hormone may also promote urinary concentration by increasing interstitial tonicity. The mechanisms whereby vasopressin could enhance interstitial tonicity include increasing urea permeability in the inner medullary collecting tubule, stimulation of solute reabsorption in the thick ascending limb of the loop of Henle, increasing the glomerular filtration rate of juxtamedullary nephrons, and decreasing vasa recta blood flow. We review experiments directed at assessing the role of vasopressin in these four processes. The multitude of effects of vasopressin appears to be well integrated and contributes to the tightly regulated urinary concentration mechanisms.