Hydrogen ion secretion by the rat distal nephron: adaptation to chronic alkali and acid ingestion

Isolated rat kidneys perfused at a low bicarbonate concentration were subjected to increased rates of buffer excretion, provided as creatinine, in order to examine the maximal hydrogen ion secretory capacity of the distal nephron. Preliminary experiments with kidneys from normal rats indicated that the quantity of hydrogen ion that titrated creatinine from urine pH to a pH of 6.0, designated TA-pH 6.0, provided an index of net hydrogen ion secretion by a functional segment of the distal nephron. With this technique the response of distal nephron hydrogen ion transport to ingestion of both acid and alkali loads was examined. Perfused kidneys from rats with chronic metabolic acidosis, produced by drinking 1.5% NH4Cl for 3-5 days, excreted urine with a lower pH and higher total titratable acid and TA-pH 6.0 than appropriate controls. Perfused kidneys from rats that ingested NaHCO3 for 7 days exhibited a higher urine pH and lower rates of total titratable acid and TA-pH 6.0 than controls. By contrast, kidneys from rats acutely tube-fed NaHCO3 3 h prior to study showed no change in urinary acidification parameters. Thus, chronic ingestion of an acid load stimulates, and chronic ingestion of an alkali load inhibits, the intrinsic hydrogen ion secretory capacity of the rat kidney at a distal nephron site. This intrinsic adaptation of the hydrogen ion transport mechanism is not secondary to changes in aldosterone because rats that ingested NaHCO3 chronically had higher plasma aldosterone levels than controls.     

Squamous cell carcinoma of the perineum: management with Mohs' surgical excision and gluteal thigh flap

Two patients with squamous cell carcinoma of the perineum are presented. The carcinomas were treated by wide local excision using Mohs' fresh-tissue technique for control of the surgical margins. The wounds were closed using a gluteal thigh flap. In 1 patient the flap was extended across the midline for coverage of a contralateral perineal site. Healing was complete in each case. The combination of Mohs' fresh-tissue methods and the posterior thigh flap provided accurate identification and removal of the perineal tumor with stable wound coverage.     

The scintigraphic localization of mineralocorticoid-producing adrenocortical carcinoma

I-131-6 beta-iodomethylnorcholesterol (NP-59) was used to localize mineralocorticoid-secreting adrenocortical carcinomas in two patients and functioning metastases in a third patient studied after the removal of the primary tumor. The presence of sufficient NP-59 activity within these lesions for discernable imaging is unusual and would not have been expected based on previous experience with other functioning and nonfunctioning carcinomas of the adrenal cortex. These cases serve to illustrate the variable spectrum of iodocholesterol uptake into adrenocortical malignancies and suggest that scintigraphic studies, preoperatively for localization and postoperatively to confirm the presence of recurrence or metastases, might be useful to identify and characterize these rare neoplasms.     

Endocrine hypertension

Many endocrine abnormalities may lead to hypertension. An awareness of these disorders is important for clinicians caring for hypertensive patients, as direct therapy of the endocrine abnormality is frequently successful in reversing the hypertension. All patients with hypertension should be screened for hypokalemia and hypercalcemia, but other screening tests should be performed only under specific circumstances. Biochemical diagnosis of the endocrine abnormality must be established before localization or visualization procedures are undertaken. Therapy of endocrine hypertension is disorder specific, and frequently rests upon surgical correction of the underlying disorder. Despite this, antihypertensive medications are effective in controlling hypertension in many instances.     

Efficacy of a 2–mm spot size lens for the treatment of superficial vascular lesions with a flashlamp-pumped dye laser

Background The flashlamp-pumped dye laser, using either a 3 or 5 mm spot size, is an excellent instrument for the treatment of port-wine stains and other superficial cutaneous vascular lesions. Problems exist with patient acceptance due to prominent and prolonged blue-black discoloration and the pain associated with the treatment. Objective To assess the effectiveness of a flashlamp-pumped dye laser equipped with a 2 mm spot size lens in the treatment of superficial vascular lesions. Methods Twenty-one patients with telangiectasias, cherry angiomas, and angiokeratomas were treated at a variety of fluences. Results Three of 21 patients had complete clearing of their superficial vascular lesions. An improvement of greater than 75% was noted by 11 patients, and six patients noted a 50%–75% improvement. One patient had less than 50% improvement. Less post-treatment discoloration and less pain were noted with the 2 mm spot size lens. Conclusions The 2 mm spot size lens, used with the flashlamp-pumped dye laser is an effective instrument for the treatment of superficial cutaneous vascular lesions.     

High-fat diet elevates blood pressure and cerebrovascular muscle Ca(2+) current

Dietary fat contributes to the elevation of blood pressure and increases the risk of stroke and coronary artery disease. Previous observations have shown that voltage-gated Ca(2+) current density is significantly increased in hypertension and can be affected by free fatty acids (FAs). We hypothesized that a diet of elevated fat level would lead to an increase in blood pressure, an elevation of L-type Ca(2+) current, and an increase in saturated FA content in vascular smooth muscle cell membranes. Male Osborne-Mendel rats were fed normal rat chow or a high-fat diet (Ob/HT group) for 8 weeks. Blood pressures in the Ob/HT group increased moderately from 122.5+/-0.7 to 134.4+/-0.8 mm Hg (P<0.05, n=26). Voltage-clamp examination of cerebral arterial cells revealed significantly elevated L-type Ca(2+) current density in the Ob/HT group. Voltage-dependent inactivation of the Ob/HT L-type channels was significantly delayed. Total serum FA contents were significantly elevated in the Ob/HT group, and HPLC analyses of fractional pools of FAs from segments of abdominal aorta revealed that arachidonic acid levels were elevated in the phospholipid fraction in Ob/HT. No differences in vascular membrane cholesterol contents were noted. Plasma cholesterol was significantly elevated in portal venous and cardiac blood samples from Ob/HT rats. These findings suggest that an elevation of plasma FAs may contribute to the development of hypertension via a process involving the elevation of Ca(2+) current density and an alteration of channel kinetics in the vascular smooth muscle membrane.     

Effect of vasopressors on atrial natriuretic factor and hemodynamic function in humans

To assess the effects of vasopressors on plasma levels of immunoreactive atrial natriuretic factor (ANF), 13 normal men were studied on two occasions. On the experimental day, subjects received sequential 15-minute intravenous infusions of angiotensin II in doses of 4, 8, and 16 pmol/kg/min. Following a 30-minute recovery period, subjects received sequential 15-minute infusions of phenylephrine in doses of 0.4 and 0.8 micrograms/kg/min. Right atrial pressure, mean pulmonary capillary wedge pressure, pulmonary artery pressure, mean systemic arterial pressure, and plasma levels of renin activity, aldosterone, angiotensin II, and immunoreactive ANF were obtained sequentially throughout the protocol. During the control day, vehicle was infused and plasma samples were obtained for hormone measurements. Infusion of angiotensin II and phenylephrine increased mean systemic arterial pressure in a stepwise fashion. Both right atrial pressure and pulmonary capillary wedge pressure increased significantly during both doses of phenylephrine, but only the highest dose of angiotensin II significantly increased atrial pressures. Plasma levels of immunoreactive ANF increased parallel with the changes in right atrial pressure and pulmonary capillary wedge pressure, with significant increases occurring only at the highest dose of both pressors. Angiotensin II and aldosterone levels increased and renin activity decreased during infusion of angiotensin II. There were no significant changes in plasma levels of immunoreactive ANF during the control day. These studies demonstrate that infusion of vasopressors increases plasma levels of ANF, but only when the vasopressor effect is associated with significant increases in right atrial and pulmonary capillary wedge pressures. Atrial stretch is the most likely mediator of the increase in plasma levels of immunoreactive ANF during vasoconstriction.     

Acromegaly due to ectopic growth hormone (GH)-releasing hormone (GHRH) production: dynamic studies of GH and ectopic GHRH secretion

Dynamic studies of GH and GH-releasing hormone (GHRH) secretion were performed in a man with a GHRH-producing carcinoid tumor and acromegaly. Insulin hypoglycemia stimulated and metoclopramide inhibited both GH and GHRH acutely. Bromocriptine suppressed GH both acutely and chronically without altering circulating GHRH levels and also blunted the GH response to exogenous GHRH. TRH acutely stimulated GH, but not GHRH, secretion, and iv bolus doses of synthetic GHRH-(1-40) stimulated GH release acutely. Somatostatin infusion decreased both GH and GHRH concentrations and blunted the GH responses to TRH and GHRH-(1-40). We conclude that prolonged exposure of the pituitary gland to high concentrations of GHRH is associated with chronic GH hypersecretion and may be accompanied by a preserved acute GH response to exogenous GHRH; a paradoxical response of GH to TRH may be mediated at the pituitary level, consequent to prolonged pituitary exposure to GHRH; bromocriptine suppression of GH in acromegaly is due to a direct pituitary effect of the drug; and somatostatin inhibits both ectopic GHRH secretion as well as GH responsiveness to GHRH in vivo. Since GH secretory responses in patients with somatotroph adenomas are similar to those in this patient, augmented GHRH secretion may play a role in development of the "classic" form of acromegaly.