Biomedical subjects
E T Zawada
Publications and source records attributed to E T Zawada.
Post-obstruction diuresis: influence of renal prostaglandins.
The possible role of altered renal prostaglandin metabolism in the generation of post-obstruction diuresis (POD) was examined in 16 adult male Sprague-Dawley rats. Inhibition of cyclooxygenase by the administration of a combination of two nonsteroidal anti-inflammatory drugs (NSAID), meclofenamate and indomethacin in 8 of these rats exaggerated, rather than lowered the degree of natriuresis and diuresis that followed the release 24 h after bilateral ureteral ligation. Urine osmolarity was similar in the two groups of rats treated with the NSAID and vehicle. The results suggest an enhanced synthesis of renal vasoconstrictor and antidiuretic prostaglandins (thromboxane A2 or PGF2 alpha) during bilateral ureteral ligation. NSAIDs such as aspirin, indomethacin, meclofenamate and others may promote POD by blocking this prostaglandin pathway while promoting the cytochrome P450 monooxygenase pathway which may produce vasodilator, diuretic and natriuretic paracrine hormones. Additionally, inhibition of prostaglandin synthesis may have enhanced post-obstruction diuresis in the present studies by allowing a greater volume expansion during obstruction, as indicated by a reduced hematocrit in the rats that were pretreated with NSAID.
Isoniazid overdose. Successful treatment with pyridoxine and hemodialysis.
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Influence of calcium infusion on plasma atrial natriuretic peptide in conscious dogs: intervention with calcium antagonist, verapamil.
In studies in conscious dogs, 1 liter 0.3% calcium chloride infusion resulted in a 163% increase in serum ionized calcium (iCa2+), 166% increase in plasma immunoreactive atrial natriuretic peptide (irANP) and 33% increase in mean blood pressure with significant positive correlation between serum iCa2+ and plasma irANP levels. Pretreatment with verapamil reversed the effects of calcium infusion. These studies have demonstrated that calcium ions play an important role in ANP secretion with reversal by calcium antagonist, verapamil. Hyponatremia seen with calcium infusion could reflect calcium-enhanced sodium excretion. Hypercalcemia was accompanied by non-significant changes in plasma renin activity and significantly elevated serum aldosterone not reversed by verapamil.
Metabolic considerations in the approach to diabetic hypertensive patients.
The effects of antihypertensive drugs on glucose metabolism are an important consideration in the selection of pharmacologic therapy for diabetic patients. Diuretics can elevate blood glucose levels, aggravate glucose intolerance, and predispose diabetic patients to hyperosmolar non-ketotic coma. Beta-blocking drugs often exacerbate and prolong insulin-induced hypoglycemia in diabetics. Beta-blockers may also cause hyperglycemia. Central agonists, alpha-blockers, and vasodilators apparently have neutral effects on carbohydrate metabolism in normal subjects or in hypertensive diabetics. Calcium channel blockers may disturb carbohydrate metabolism in diabetic patients. Angiotensin-converting enzyme inhibitors have little effect on glucose metabolism. Because diabetic patients are prone to fluid, electrolyte, hormone, and lipid disturbances, it is important to consider the effects of antihypertensive drugs on these aspects of metabolism when selecting pharmacologic therapy. The effects of various antihypertensive drugs on sodium, calcium, magnesium, and acid/base balance are reviewed. The effects of these drugs on serum uric acid and potassium, as well as on hormone and lipid levels, are also considered.
Toxic epidermal necrolysis: a medical student's perspective.
As a third year medical student, I was hospitalized for approximately one month with Toxic Epidermal Necrolysis (TEN). Consequently, I have developed an insight into the role of patient as well as that of medical care giver. My experience prompted an intense interest in this particular adverse drug reaction and research into treatment recommendations. Treatment has changed in recent years and this resulted in significantly improved survival. Steroids, once commonly used, are now considered contraindicated. Because of the wide variety of medications which may be associated with this adverse reaction, it is essential to be familiar with the clinical presentation of TEN, as well as the initial steps in treatment.
Plasma dilution during transdermal clonidine antihypertensive monotherapy.
In eight hypertensive patients treated with transdermal clonidine for one year, there was plasma dilution, as shown by a reduction in serum sodium, hemoglobin, and serum protein levels. Free water clearance did not change significantly. Plasma dilution was likely sustained by increased water intake due to "dry mouth", as frequently seen with central acting drugs such as clonidine.
Hemodialysis for acute renal failure in a patient with life-long myalgias after exercise.
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Canine renal and systemic hemodynamic measurements after 4 weeks of a magnesium deficient diet.
To probe renal hemodynamic measurements in relation to simultaneous systemic hemodynamic measurements in normal, adult, conscious dogs on a magnesium-deficient diet, 6 experimental animals were given 4 weeks of a magnesium-deficient diet compared to 9 animals whose dietary magnesium was normal. Systemic hemodynamics were estimated using a thermodilution catheter, and renal hemodynamics were estimated by standard renal clearance techniques. Electrolytes and hormones were also surveyed in these same animals at the time of hemodynamic measurements. Heart rate was significantly higher in magnesium-deficient dogs, but there were no other systemic hemodynamic differences between the two groups of dogs. Renal blood flow, effective renal plasma flow, and urinary osmolality were significantly higher in the magnesium-deficient animals. Whole-blood ionized calcium and potassium, serum magnesium, and fractional excretion of magnesium were lower in the magnesium-deficient dogs. We conclude that the renal circulation is more sensitive than the systemic circulation to disturbances in magnesium balance. Disturbances of other electrolytes accompanying magnesium deficiency were also confirmed.
Salt sensitivity in blacks. Salt intake and natriuretic substances.
Accumulating evidence suggests that hypertension in blacks is manifested in part by impaired renal excretion of salt. Consequently, this study was performed to determine if hypertensive and normotensive black subjects differ in their ability to generate known natriuretic substances. Fourteen normotensive and 11 hypertensive blacks were maintained on constant metabolic diets containing either 40 or 180 mmol of salt per day for 14 days each. During the last 4 days of each salt intake period, urine was collected for measurement of sodium, dopamine, and norepinephrine. On the last day of each 14-day dietary period, blood pressures were measured, blood was collected for measurement of plasma atrial natriuretic factor (ANF) and aldosterone, and urine was collected over 2 hours for measurement of prostaglandin E2 (PGE2). Both the normotensive and the hypertensive groups manifested salt sensitivity; their mean arterial pressure rose by 7 +/- 0.2 and 6 +/- 0.2%, respectively, when salt intake was increased from 40 to 180 mmol/day. The hypertensive group exhibited decreased (p less than 0.05) dopamine excretion as compared with the normotensive group for both dietary salt intakes. Plasma ANF levels increased (p less than 0.05) in the hypertensive group, but not in the normotensive group, with increasing dietary salt. Plasma aldosterone and urinary norepinephrine and PGE2 were comparable in the two groups for both dietary salt intakes. These data suggest that salt sensitivity is not unique to hypertensive blacks but occurs in normotensive blacks as well. Decreased renal production of dopamine may be a pathogenic factor in the development and maintenance of hypertension in blacks.
Efficacy and safety of two-year therapy with transdermal clonidine for essential hypertension.
We evaluated the safety and efficacy of transdermal clonidine (TC) in 23 patients with essential hypertension over a two-year period. Fourteen patients achieved control of blood pressure using TC alone. Six patients achieved control with a combination of TC and the diuretic chlorthalidone (CH). Three patients had control with CH alone or did not achieve control with either TC alone or TC plus CH and were dropped from the study. Of the 20 patients remaining in the study, six patients remained on TC or TC plus CH for the two-year study. Ten of the 20 patients quit the study because of skin reactions and four because of other side effects. No clinically significant changes were noted in serum or urinary laboratory parameters. Finally, TC was effective as long-term monotherapy for essential hypertension in only four of our patients. The major limitation is skin-related side effects.
Antihypertensive effectiveness of the nifedipine gastrointestinal therapeutic system.
The results of a multicenter trial conducted in order to determine the therapeutic efficacy of the gastrointestinal therapeutic system (GITS) formulation of nifedipine in comparison with hydrochlorothiazide and placebo in the management of mild to moderate essential hypertension are presented. During a one-week wash-out phase, antihypertensive therapy was discontinued in all patients. After a three-week single-blind placebo period, eligible patients were randomly assigned in a double-blind fashion to one of three treatment groups for a one-week titration period and a nine-week efficacy period. Patients received either nifedipine GITS, 30 or 60 mg daily; hydrochlorothiazide, 25 or 50 mg daily; or placebo. Sitting and standing blood pressures decreased by an average 11.6/10.4 and 10.8/10.8 mm Hg, respectively, with nifedipine GITS therapy, and 14.8/10.8 and 14.3/8.2 mm Hg, respectively, with hydrochlorothiazide therapy. Compared with placebo, these changes were highly significant for both sitting (p less than or equal to 0.005) and standing (p less than or equal to 0.02) measurements. Heart rate remained essentially unchanged in all three groups. It was therefore concluded that monotherapy with nifedipine GITS, at doses of 30 or 60 mg given once daily, effectively reduces blood pressure in patients with hypertension to a degree comparable with that seen in hydrochlorothiazide therapy.
Comparison of hydrochlorothiazide and sustained-release diltiazem for mild-to-moderate systemic hypertension.
The safety and efficacy of sustained-release diltiazem, 120 to 180 mg twice daily, was compared with those of hydrochlorothiazide, 25 to 50 mg twice daily, in 207 patients with mild-to-moderate hypertension (supine diastolic blood pressure [BP] 95 to 114 mm Hg) using a baseline, placebo, parallel-design study protocol. All patients received placebo for 2 to 4 weeks, followed by either study drug during the double-blind phase, titrated over 8 weeks to achieve a goal of supine diastolic BP reduction of at least 10 mm Hg and/or a diastolic BP of less than 90 mm Hg. Patients not achieving the treatment goal with either drug alone received the other drug in combination. Both drugs produced significant decreases in supine and upright BP throughout the 26-week study. The magnitude of decrease in mean supine diastolic BP was similar for both drugs as monotherapy at week 14 (-11.4 and -12.1 mm Hg, respectively). Hydrochlorothiazide produced significantly greater reductions at week 14 in mean supine systolic BP than sustained-release diltiazem (-19.5 and -12.7 mm Hg, respectively). The difference in mean supine diastolic BP reduction with the 2 drugs diminished when hydrochlorothiazide (50 mg/day) was compared with sustained-release diltiazem. The BP effects were sustained for 6 months with both drugs. The 2 drugs appeared to lower BP more in patients older than 60 years and more in black than in white patients. The combination of the 2 drugs decreased supine diastolic BP to goal levels in about 56% of the patients not achieving goal with either drug alone. Adverse effects were minimal with either drug alone and in combination, except for hypokalemia, which increased with thiazide alone and in combination.
Systemic and renal hemodynamic consequences of manipulation of serum calcium and/or parathyroid hormone in the intact conscious mongrel dog.
Studies were undertaken in conscious mongrel dogs to separate the systemic and renal hemodynamic effects of alterations in serum calcium (Ca) from those of parathyroid hormone (PTH) in an intact conscious animal. Blood pressure was measured intra-arterially, cardiac output was determined by dye-dilution or thermodilution, total peripheral resistance (TPR) was calculated from standard formulae, and renal hemodynamics were estimated by the clearance of inulin and para-aminohippurate. Measurements were made before and after a 2 hour calcium chloride (CaCl2) infusion in 10 dogs (group 1). These animals had previously received a dose of PTH to prevent suppression of PTH during the CaCl2 infusion. Ionized calcium (Ca++) and TPR increased significantly. Blood pressure increased but not significantly. Administration of EDTA did not significantly change any systemic hemodynamic variable in eight thyroparathyroidectomized dogs (group 2). Chelation in seven dogs with intact parathyroid glands (group 3) reduced mean arterial blood pressure and total peripheral resistance. Renal hemodynamic measurements were not affected. Isolated acute elevation of serum Ca++, independent of suppression of PTH, increased total peripheral resistance. Decreased serum Ca++ required normal activity of parathyroids to reduce total peripheral resistance. The renal circulation was resistant to acute manipulation of ionized serum calcium and PTH. CaCl2 infusion to intact dogs (group 1) decreased serum magnesium significantly, increased urine flow rate, and decreased urinary PGE2 excretion. Comparisons between group 2 and group 3 revealed a greater decline in serum Mg and urinary prostaglandin E2 excretion in group 2 vs group 3. Elevation of peripheral resistance due to acute Ca elevations was accompanied by decreased serum Mg and decreased renal prostaglandin excretion.(ABSTRACT TRUNCATED AT 250 WORDS)
Preliminary report: natriuretic effect of calcium supplementation in hypertensive women over forty.
Twenty-four hypertensive women over 40 years of age were given calcium carbonate 1 g/d for 12 weeks after a 4-week period of observation. Blood pressures were measured every 2 weeks. Plasma ionized calcium (Ca++), sodium (Na), and potassium (K) were measured twice in the control period and twice in the Ca-supplementation period. Urine measurements included Ca, Magnesium (Mg), Na, K, prostaglandin E2, and osmolality. Blood pressures were averaged to get group means, and these were compared using the paired t-test. For the group, seated systolic blood pressure fell from 141.5 +/- 13.2 to 136.3 +/- 11.4 mm Hg (p less than 0.025) at the end of 12 weeks of supplementation, and diastolic blood pressure fell from 84.5 +/- 7.5 to 81.1 +/- 7.1 mm Hg (p less than 0.025). There was no correlation between serum Ca++ and blood pressure. The urinary Na excretion was markedly elevated during the Ca supplementation period: 25.8 +/- 14.2 vs. 18.4 +/- 7.9 mmol/4 hr (p less than 0.005). These results suggest an indirect (natriuretic) effect as the means by which Ca supplementation lowers blood pressure.
Nephrotic syndrome and renal failure in an elderly man.
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Magnesium prevents acute hypercalcemic hypertension.
Systolic and mean blood pressures were shown to increase from means of 159 +/- 7 and 111 +/- 7 mm Hg to 174 +/- 8 and 122 +/- 6 mm Hg, respectively (p less than 0.05 in each case), after a 2-hour intravenous infusion of CaCl2 during which serum magnesium levels were found to decrease from 1.8 +/- 0.06 to 1.4 +/- 0.05 mg/dl (p less than 0.0005). A significant increase in blood pressure was not seen when MgSO4 was given intravenously concomitantly with the CaCl2 so that serum magnesium levels did not decline. We conclude that hypercalcemic hypertension is due in part to altered serum magnesium and is prevented if serum magnesium is sustained.
Renal tubular effect of nisoldipine, a calcium channel blocker, in rats.
The renal tubular effect of nisoldipine (10 micrograms/kg/h) was evaluated using clearance and micropuncture techniques in spontaneously hypertensive rats made diuretic by i.v. infusion of 2.5% NaCl. In one group of 11 rats the renal innervation was intact, whereas in a second group of 10 rats the left kidney was denervated. The drug reduced mean blood pressure in both groups of rats without a significant change in heart rate or glomerular filtration rate. Nisoldipine increased urine flow from 22.3 +/- 2.1 to 26.8 +/- 2.5 microliter/min/100 g BW and from 23.8 +/- 1.3 to 31.5 +/- 1.4 microliter/min/100 g BW in the innervated and denervated rats, respectively (p less than 0.05 for both). Fractional excretion of sodium and total solute were significantly higher under nisoldipine action in both groups of rats, indicating reduced reabsorption of water as well as solute by the nephron. Potassium excretion was unaltered in the innervated rats while in the denervated group it was significantly reduced by the drug. Fractional water excretion was enhanced from 3.3 +/- 0.3% to 4.1 +/- 0.4% of the filtrate in the innervated rats and from 3.4 +/- 0.2% to 4.6 +/- 0.3% in the denervated rats. Tubular fluid to plasma inulin concentration ratios at late distal puncture sites were lowered by nisoldipine in both the innervated kidneys (from 10.5 +/- 1.6 to 8.3 +/- 0.8, with p less than 0.05) and denervated kidneys (from 8.8 +/- 0.5 to 6.7 +/- 0.5, with p less than 0.05). The mean percentage of filtrate reabsorbed between late proximal and late distal tubular fluid collection sites was lowered in both groups of rats.(ABSTRACT TRUNCATED AT 250 WORDS)