The role of prostaglandins in Na retention of porta-cava shunted rats.

The importance of prostaglandins (PG) in Na and water retention of liver cirrhosis was studied in rats with porta-cava shunt (PCS) compared to control, non-shunted animals. Balance studies were performed in metabolic cages with diets of high, normal and low Na. An experimental phase, during which the animals received either 5 mg X kg-1 of indomethacin daily or placebo, was preceded by a control period and followed by a post-indomethacin period identical to the control phase. In each diet, indomethacin, but non placebo, caused a positive Na balance, correlated with Na intake, which in overall pooled data amounted to -1453 +/- 255 muEq in PCS rats, significantly larger than that measured in controls, of -295 +/- 320 muEq (P less than 0.01). This was attended by a reverse change in K balance of -35.6 +/- 349 muEq versus -1566 +/- 582 muEq (P less than 0.01); glomerular filtration rate (GRF) was unchanged. These data demonstrate that PGs contribute to the control of Na homeostasis in the presence of PCS.

Studies on the nephron segment with reduced sodium reabsorption during starvation natriuresis.

The segment of the nephron where carbohydrate deprivation depresses Na transport leading to natriuresis was sought by a new clearance technique designed to measure segmental reabsorption in each portion of the human renal tubule. Experiments were performed during maximal water diuresis before and 4 days after carbohydrate withdrawal. Proximal reabsorption had fallen from 70 +/- 4 to 60 +/- 5 ml X min-1, p less than 0.05, by the 4th day of sugar deprivation, accounting for the natriuresis and the associated weight loss of 1.8 kg. By the 4th day of fasting, when Na excretion had returned to control levels, GFR had fallen nonsignificantly from 99 +/- 6 to 95 +/- 5 ml X min-1, while Na reabsorption along distal segments had risen. In fact, Na transport, expressed by the equivalent volumes of solute free-water generated, rose from 17.4 +/- 3.4 to 23.6 +/- 2.1 along the ascending limb of Henle's loop, and from 8.1 +/- 0.8 to 9.2 +/- 1.3 ml X min-1 X GFR-1 X 100 along the distal tubule. Thus, analysis of segmental Na transport by this method discloses that starvation natriuresis is a proximal tubular event, progressively counterbalanced by enhanced Na reclamation in more distal sites. Volume contraction and the attendant fall in GFR concur to curb delivery out of the proximal tubule which is matched by enhanced distal Na reabsorption till a new steady-state excretion is attained.

IgA pseudo-linear deposits in glomerular basement membranes in dermatitis herpetiformis.

An 18-year-old-woman, with dermatitis herpetiformis, acute glomerulonephritis, malabsorption and villous atrophy due to massive infiltration of IgA producing plasma cells was studied. By light microscopy, her renal biopsy specimen showed heavy immunofluorescence for IgA, a mixed proliferative and membranous lesion with occasional crescents and focal sclerosis. Electron microscopic examination revealed three main lesions: (1) swelling and bleb formation in endothelial cells, (2) extensive fusion of foot processes of podocytes, and (3) a dense quasi-linear, continuous deposition of immune complexes, encompassing several loops; they were characteristically located within the basement membrane at the boundary between the lamina densa and the lamina rara interna. At occasional points where the immune complexes had reached the outer aspects of the basement membrane, there was damage to the podocyte cytoplasm. This electron microscopic aspect supports the interpretation that these immune complexes, although non-complement fixing, exhibit a high damaging potential, leading to relentless disease progression.

Experimental dissociation of the effects of prostaglandins on renal sodium and water reabsorption by cyclo-oxygenase inhibitors in the rat.

1 The relative importance of the effect of prostaglandins on renal sodium and water reabsorption was assessed in rats. 2 Clearance experiments were performed on 24 anaesthetized rats divided into 3 groups. Each group was infused throughout either with Ringer solution at 9 ml/h (Protocol I), or at 3 ml/h (Protocol II) or with hypotonic fluid at 5 ml/h (Protocol III). Clearance periods were performed before and after intravenous injection of indomethacin (5 mg/kg) and then of aspirin (20 mg/kg). The natriuretic response to different degrees of volume expansion was not modified during the action of the inhibitors. 3 When baseline urine osmolality (Uosm) was high (Protocol II) no further increase occurred in the presence of prostaglandin inhibition. Conversely, Uosm rose from 771 +/- 134 to 1356 +/- 414 and from 575 +/- 245 to 841 +/- 407 mosm/kg (P less than 0.05) in Protocol I and Protocol III respectively, when antidiuretic hormone secretion was inhibited by the higher degree of volume expansion. 4 There was a significant correlation between the change in urine flow rate induced by cyclooxygenase inhibitors and the attendant variations in Na excretion, r = 0.42, n = 41, P less than 0.01. 5 Thus, prostaglandins affect Na loss during saline load as a side effect of their action on water permeability. They could play an important role in volume depletion by counterbalancing the large secretion rate of renal vasoconstrictors.

Blunting of furosemide diuresis by aspirin in man.

Experiments were performed on humans to study the blunting on the diuretic action of furosemide by prostaglandin synthetase inhibitors. Maximal water diuresis was instituted. At the peak of urine flow, clearance periods were performed during baseline conditions and repeated after the injection of aspirin and, subsequently, of furosemide. Control subjects did not receive aspirin. Urine flow rate (V), Cosm, and Na excretion (UNa) . V were significantly lower when the administration of the diuretic had been preceded by that of aspirin. In the absence of furosemide, however, aspirin did not influence renal hemodynamics nor Na and water reabsorption. Therefore, the same experimental protocol was repeated in paired experiments where each normal subject served as his own control, being studied twice, in the presence and absence of aspirin, respectively. The average changes in water and Na excretion induced by furosemide were not different when the patients were pretreated with aspirin as compared with those measured in the absence of prostaglandin inhibition. Changes occurring in individual experiments were significantly correlated (r = 0.95, P less than 0.01) with those in calculated furosemide clearance. Since aspirin, indomethacin, and meclophenamate are secreted by the organic acid transport system of the proximal tubule, competition for a common secretory mechanism, rather than prostaglandin inhibition, could mediate the blunting of furosemide diuresis.

Multicentric giant lymph node hyperplasia. A hyperimmune syndrome with a rapidly progressive course.

A patient who had diffuse lymph node enlargement, fever, skin rashes, anemia and polyclonal hypergammaglobulinemia is described. Histologic examination of lymph nodes taken from different sites (cervical, axillary and inguinal) revealed the presence of giant lymph node hyperplasia. The liver and bone marrow showed a moderate lymphocytic and plasma cell infiltration. The clinical presentation of a multicentric variety of giant lymph node hyperplasia in the reported case is similar to the clinical features usually associated with angio-immunoblastic lymphadenopathy with dysproteinemia, indicating that these two disorders may be related and may affect the same organs and systems. Alternatively, this histologic reactive giant lymph node hyperplasia progressing with a rapid declivitous course can be considered distinctive of a separate entity.

Oxdralazine, a new peripheral vasodilator, combined with propranolol and hydrochlorothiazide: a rational approach to antihypertensive treatment.

Forty-three patients suffering from hypertension of different origin (chronic renal failure, gout, or idiopathic) were treated with propranolol (121 +/- 12 mg q.d.) plus hydrochlorothiazide (50 mg q.d.) for 75 +/- 9 days. Blood pressure did not return to normal limits in 15 patients, who were continued on the same protocol plus 10 to 50 mg oxdralazine q.d. After an average of 68 +/- 35 days blood pressure fell from 180/110 mm Hg to 145/90 mm Hg without orthostatism, significant side effects, or changes in GFR. This combination seems particularly successful since propranolol will prevent the undesired rise in cardiac output due to oxdralazine as well as the activation of the renin-angiotensin axis due to diuretics. Thus, the antihypertensive properties of each agent will be enhanced by a reduction in side effects by the associated drug, resulting in optimal blood pressure control.

Acute agnogenic myeloid metaplasia with chromosomal abnormalities.

A case of a 37-year-old woman presenting with acute agnogenic myeloid metaplasia (AAMM) is described. The disease had a stormy course and was characterized by moderate splenomegaly, persistently depressed WBC counts, extramedullary hemopoiesis and presence of a high percentage of atypical myeloblasts in the peripheral smear. Platelets were persistently low, reticulocytes significantly below normal, notwithstanding anemia. Hot tended to fall progressively to intolerably low values in the absence of transfusion. The chromosomal mapping of peripheral blood revealed the presence of a trisomy of chromosome No. 8. This abnormality already demonstrated in two previous cases of acute myelofibrosis and the clinical course of the disease suggest that acute myelofibrosis and AAMM could be the same disease while chronic myelofibrosis should be considered a separate entity. Also, it is possible that AAMM with trisomy of chromosome No. 8 and stormy clinical course may be a different entity from the acute myeloproliferative disorders associated with other chromosomal abnormalities.