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Papers by David Juan

Gastroenterology, 1976

Previous studies have shown that synthetic salmon calcitonin (SCT) infused intravenously causes s... more Previous studies have shown that synthetic salmon calcitonin (SCT) infused intravenously causes secretion of water and electrolytes in the jejunum of normal human subjects. The present experiments were carried out to learn more about the nature ofthis intestinal secretory process. During SCT-or synthetic human calcitonin (HCTHnduced intestinal secretion, the following observations were made: (1) There was no change in potential difference; (2) CI was secreted against an electrochemical gradient; (3) unidirectional Na flux out of the lumen was decreased while the opposite flux was normal; (4) luminal pCO, fell; (5) addition of glucose to the jejunal contents stimulated Na absorption, and this in tum counteracted the secretory effect of calcitonin. These findings suggest that calcitonin induces active CI secretion and inhibits active Na absorption, and that HCO, absorption is reduced by virtue of OH secretion; furthermore, jejunal glucose absorption and glucose-stimulated Na absorption are intact during calcitonin-induced secretion. Intravenous infusion of HCT caused intestinal secretion only when blood levels were much higher than occur physiologically; therefore, calcitonin is probably not a mediator of spontaneous variations of intestinal transport in normal people. However, because calcitonin induces secretion in the ileum as well as in the jejunum, hypercalcitonemia (within the range commonly found in patients with medullary carcinoma of the thyroid) could be a cause of severe secretory diarrhea. The intravenous infusion of synthetic salmon calcitonin (SCT), at a rate that does not reduce serum Ca concentration, causes secretion of fluid and electrolytes by the human jejunum. 1 This suggests that the effect of intravenous calcitonin infusion on small bowel function might provide insight into the mechanisms of intestinal secretion and secretory diarrhea, and in this report we describe the results of an additional series of such studies. The three major purposes of the experiments reported in this paper were: (1) to learn more about the possible physiological and pathophysiological role of calcitonin as a regulatory hormone for intestinal water and electrolyte transport; (2) to see whether glucose in the intestine modifies calcitonin-induced secretion; and (3) to gain insight into the mechanism of intestinal secretion stimulated by calcitonin. Methods Absorption in a 30-cm segment of jejunum or ileum was studied by the triple lumen perfusion method that has previously been described in detail. I. , This involves the infusion of

The Journal of Clinical Endocrinology & Metabolism, 1976

The jejunal absorption of inorganic phosphate (P) was studied under basal conditions and during t... more The jejunal absorption of inorganic phosphate (P) was studied under basal conditions and during the intravenous infusion of synthetic salmon calcitonin (SCT) in normal subjects. Net P absorption increased as the intraluminal P concentration was raised. At intraluminal P concentrations equal to or above the plasma P level P absorption manifested first order kinetics. At intraluminal P concentrations below the plasma P level, net P absorption was non-linear presumably due to the movement of P from plasma to the lumen down a chemical gradient. A net secretion of water and electrolytes occurred in six normal subjects given SCT (250 ng/kg/hr) while saline infusion instead of SCT had no effect on jejunal absorption. Along with the secretory effect SCT reduced calcium and P absorption by 58% and 62% respectively, without any significant fall in the serum levels of calcium or P. The jejunal response to SCT was reproduced twice in a hypoparathyroid subject showing that endogenous parathyroid hormone was not involved in this effect. Calcium and P absorption were positively correlated with water movement suggesting that the observed changes in calcium and P absorption are due primarily to SCT-induced secretion of water. It is concluded that SCT induces a net secretion of water and ions while simultaneously reducing calcium and P absorption.

Postgraduate Medicine, 1980

Vitamin D3 must undergo two hydroxylation steps before it becomes fully active: 25-hydroxylation ... more Vitamin D3 must undergo two hydroxylation steps before it becomes fully active: 25-hydroxylation in the liver and 1- or 24-hydroxylation in the kidney. Parathyroid hormone, serum phosphate, and serum calcium are important in regulation of renal production of 1,25-dihydroxy vitamin D3 (1,25-[OH]2D3) and 24,25-dihydroxy vitamin D3. An enzyme involved in renal hydroxylation is deficient or defective in patients with chronic renal failure, the Fanconi syndrome, vitamin D-dependent rickets, hypoparathyroidism, and pseudohypoparathyroidism. Altered vitamin D metabolism also occurs in various hepatic diseases, postmenopausal osteoporosis, and anticonvulsant osteomalacia. Recently, 1,25-(OH)2D3 was approved for treatment of renal osteodystrophy. In physiologic doses, it predictably corrects many of the clinical and biochemical abnormalities associated with this disorder.

American Journal of Physiology-Endocrinology and Metabolism, 1984

The objective of this investigation was to determine whether physiological levels of vitamin D an... more The objective of this investigation was to determine whether physiological levels of vitamin D and its metabolites have part of their mechanisms of action through stimulation of guanylate cyclase (EC 4.6.1.2). These sterols enhanced both soluble and particulate guanylate cyclase activities as well as cGMP levels two- to threefold in human and rat tissues. At a concentration of 1 nM, 1,25(OH)2D3 greater than 25(OH)D3 greater than vitamin D3 greater than 24,25(OH)2D3 = 25,26(OH)2D3 = vitamin D2. Dose-response curves revealed that maximal stimulation of guanylate cyclase by these sterols was at 1 nM and that there was no augmented guanylate cyclase activity at 0.01 nM. The precursors of vitamin D, cholesterol and 7-dehydrocholesterol, had no effect on guanylate cyclase activity. The activation of guanylate cyclase activity by the vitamin D sterols required the presence of manganese ion. Calcium was not as efficient as manganese in optimizing basal or hormone-stimulated guanylate cyclas...

Clinical Pharmacology and Therapeutics, 1986

The effects of low- and high-protein diets on theophylline kinetics and the time course of change... more The effects of low- and high-protein diets on theophylline kinetics and the time course of changes in 13C-labeled caffeine and aminopyrine CO2 breath tests were examined in six young men. With a low-protein diet, mean theophylline clearance fell 21% (P less than 0.04) and the t1/2 rose from 8.0 to 10.6 hours (P less than 0.02). With a high-protein diet, mean theophylline clearance rose 26% (P less than 0.004) and the t1/2 shortened to 7.4 hours (P less than 0.03). Theophylline volume of distribution and protein binding did not change. Renal clearance of theophylline was lowered during the low-protein diet. Theophylline clearance correlated with caffeine breath test values during the low- (r = 0.73) and high- (r = 0.70) protein diets. Theophylline clearance correlated less well with the aminopyrine breath test values during the low- (r = 0.47) and high- (r = 0.55) protein diets. Thus dietary protein significantly influenced theophylline clearance, but the caffeine and aminopyrine breath tests showed a differential response to this important environmental factor.

Clinical Pharmacology and Therapeutics, 1989

Pharmacokinetics of N-acetylprocainamide in patients profiled with a stable isotope method N-Acet... more Pharmacokinetics of N-acetylprocainamide in patients profiled with a stable isotope method N-Acetylprocainamide (NAPA) absorption and disposition were profiled in five patients with ventricular arrhythmias by the simultaneous intravenous administration of NAPA-"C and oral administration of a 500 mg NAPA hydrochloride tablet. NAPA distribution was modeled with a three compartment mammillary system. The central compartment volume of 14.1 ± 2.6 L (mean ± SD) was similar to expected intravascular space, corrected for NAPA partitioning between erythrocytes and plasma. Other compartment volumes, intercompartmental and nonrenal clearances, and the steady-state distribution volume of 1.45 ± 0.09 L/ kg were similar to normal subject values. The least-squares estimate of 1.67 for the NAPA renal dearance/creatinine clearance ratio was similar to the value of 1.68 previously reported for functionally anephric patients and showed the expected age-associated decrease. The oral NAPA dose was 78.0% ± 11.7% absorbed and interindividual variation in NAPA absorption was correlated with fast intercompartmental clearance (r = 0.89, p = 0.045). Because fast intercompartmental clearance partly reflects splanchnic blood flow, hemodynamic changes may affect NAPA bioavailability, as has been found for procainamide. (CLIN PHARMACOL THER 1989;46:182-9.

Southern Medical Journal, 1982

Urology, 1981

Pheochromocytoma accounts for about 0.1 per cent of patients with diastolic hyperstension. It mim... more Pheochromocytoma accounts for about 0.1 per cent of patients with diastolic hyperstension. It mimics many diseases varying from anxiety psychoneurosis to intracranial tumors. Cardinal symptoms include sevre headache (72 to 92 per cent), sweating (60 tp 70 per cent), palpitations (51 to 73 per cent), and hypertension (&amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 90 per cent) of which 50 per cent is sustained, 50 per cent paroxysmal. Many drugs (phenothiazines, Saralasin, antiemetics, steroids, etc.) have been reported as precipitating factors. Patients who should be screened for pheochromocytoma include: (1) all symptomatic patients with sustained or paroxysmal hyperstension; (2) asymptomatic hypertension; (3) all patients with MEA 2a,b (hyperparathyroidism, medullary carcinoma of the thyroid, neurocutaneous lesions) and their first degree relatives, even if the latter are asymptomatic and normotensive; (4) hypertension plus diabetes mellitis or hypermetabolism; (5) hypertensive episode during induction of anesthesia or radiologic procedure; and (6) hypertensive response during histamine administration, i.e., gastric analysis. Urinary metanephrine is the single best screening test. Plasma catecholamine determination is particularly helpful when collected before and immediately after an attack. Provacative agents (histamine, glucagon, tyramine) are needed rarely. Preoperative localization of the tumor can be done with nephrotomography IVP, computerized axial tomography, ultrasound, 131-I-19-iodocholesterol scan, arteriography, venography.

Urology, 1984

A family of idiopathic hypercalciuria (IH), 3 symptomatic and 2 asymptomatic, plus 3 normal subje... more A family of idiopathic hypercalciuria (IH), 3 symptomatic and 2 asymptomatic, plus 3 normal subjects were given the 1 Gm oral calcium challenge. Biochemical parameters measured included: serum and urinary calcium and phosphate, urinary cyclic AMP, and serum intact and carboxyl-terminal parathyroid hormone. Major differences between the normal control and the family with IH include: (1) higher calcemic response in the family with IH (0.9 vs 0.4 mg/dl); (2) a fall in carboxyl-terminal PTH and urinary cyclic AMP in the IH family in contrast to control subjects in whom there were no changes; (3) a rise in serum phosphorus in the IH family (0.8 vs 0.2 162 UROLOGY / AUGUST 1984 / VOLUME XXIV, NUMBER

Urology, 1985

The effects of a 2 Gm oral phosphorus load in a family with idiopathic hypercalciuria (IH) consis... more The effects of a 2 Gm oral phosphorus load in a family with idiopathic hypercalciuria (IH) consisting of 3 symptomatic (DT, CS, DS) and 2 asymptomatic (MS, PD) members were compared with 12 normal control subjects. Biochemical parameters measured included: total and ionized calcium, phosphorus, intact and carboxyl-terminal parathyroid hormone, urinary calcium, phosphorus, and sodium. Water loading had no effect on these parameters. After the phosphorus load, serum phosphorus rose 1.60 mg/dl in the control subjects but only 1.34 mg/dl in the IH family at the end of one hour. Basal tubular reabsorption of phosphate (TRP) were comparable in the control subjects and the IH family. After the phosphorus load, the TRP in the control subjects fell (average 9.2 %) accompanied by a significant (P < 0.02) rise in the carboxyl-terminal parathyroid hormone. Except for DT who had been taking hydrochlorothiaxide, the TRP fell dramatically in the rest of the IH family (DS 25 % , CS 12 % , PD 26 % , MS 50 %) in the absence of any perturbations in either the intact or carboxyl-terminal parathyroid hormone. A hypocalciuric effect was observed in the IH family but not in the control subjects after phosphorus loading. The oral phosphorus challenge unmasked a parathyroid hormone independent renal phosphate leak in both symptomatic and asymptomatic members in a family with idiopathic hypercalciuria.

Journal of the American College of Nutrition, 1989

The effect of a low calorie (1100 kcal), low protein (35 g) intake for 9 days on nutritional and ... more The effect of a low calorie (1100 kcal), low protein (35 g) intake for 9 days on nutritional and laboratory parameters was studied in six young and six elderly healthy subjects. All subjects lost weight on the test diet (an average of 2.0 kg in the young and 2.1 kg in the elderly). Basal serum albumin, serum transferrin, creatinine height index, and creatinine clearance in the elderly subjects were lower than in the young (p less than 0.05). Serum albumin remained unchanged at the end of diet in both groups. There was, however, a significant decrease in the transferrin level in the younger subjects (p less than 0.01). The decrease in creatinine height index was not significant in either group. Baseline nitrogen balance of the elderly was -1.1 g/day compared to +0.5 g/day (p less than 0.01) in the young subjects. The test diet caused a negative nitrogen balance of about -5 g/day in both groups (p less than 0.005). Blood urea nitrogen was significantly lower at the end of the test diet and was related to the intake of protein in both groups. At the end of the diet the serum potassium and GGT were significantly lower in the young (p less than 0.01); serum creatinine was unchanged but creatinine clearance was significantly lower in both groups. From this study it appears that significant changes occur in nutritional and laboratory parameters within 9 days on a diet deficient in calories and protein in normal healthy subjects. These changes need to be recognized as having nutritional basis and should not be attributed to illness or drug therapy.

The Journal of Clinical Pharmacology, 1990

The purpose of this study was to determine the effect of oral estazolam at two and three times th... more The purpose of this study was to determine the effect of oral estazolam at two and three times the usually recommended dosage (2 mg) on ventilation and respiratory drive during wakefulness. Sixty healthy subjects were randomized to receive a single oral dose of either: 1) estazolam 4 mg; 2) estazolam 6 mg; 3) placebo; or 4) morphine 0.15 mg/kg. Predrug and postdrug measurements were obtained for ventilation, respiratory cycle timing, metabolic rate, temperature, and ventilatory and mouth occlusion pressure (P0.1) responses to exogenous CO2. No difference between placebo and the study drugs was noted during eupneic breathing. During administration of exogenous CO2, morphine caused a decrease in the slope of the ventilatory (-0.4 +/- 0.1 L/min/mm Hg, P = .008) and P0.1 (-0.22 +/- 0.06 cm H2O/mm Hg, P = .015) responses. Estazolam (4 and 6 mg) had no effect on the ventilatory response to exogenous CO2. However, estazolam (6 mg) caused the P0.1 at a PCO2 of 57 mm Hg to decrease (-0.67 +/- 0.30 cm H2O, P = .005). The preservation of ventilation with the highest dose of estazolam, despite the decrease in P0.1, indicates that a compensatory strategy independent of respiratory center drive may have been activated. Sedation was a common side effect of estazolam reported in 13% and 53% of subjects at the 4 mg and 6 mg doses, respectively. We conclude that a single, high dose of estazolam does not cause ventilatory depression during wakefulness in healthy subjects.

The Journal of Clinical Pharmacology, 1992

The efficacy and safety of once-daily 2.5- or 5.0-mg methyclothiazide (MCTZ) added to once-daily ... more The efficacy and safety of once-daily 2.5- or 5.0-mg methyclothiazide (MCTZ) added to once-daily 5.0-mg terazosin (TRZ) versus 5.0-mg TRZ alone was evaluated in this double-blind, multicenter study. All patients received TRZ during a 6-week titration period. Hypertensive patients (222) (mean blood pressure of 159/104 mm Hg) were randomized to one of three treatment groups: TRZ alone (N = 76); TRZ+MCTZ-2.5 mg (N = 74); and TRZ+MCTZ-5.0 mg (N = 72) for the 8-week double-blind period. Changes in the supine and standing SBP/DBP from preTRZ period were: TRZ alone (-4.8/-8.1 and -2.6/-6.1 mm Hg); TRZ+MCTZ-2.5 mg (-17.3/-12.4 and -16.0/-11.2 mm Hg); and TRZ+MCTZ-5.0 mg (-20.6/-14.4 and -23.3/-14.6 mm Hg). Blood pressure changes in the combination groups were significantly greater than those in the TRZ alone group. However, there were no statistically significant differences between the TRZ+MCTZ-2.5-mg and TRZ+MCTZ-5.0-mg groups. The combination of TRZ and MCTZ tends to mitigate the adverse effects on serum glucose, uric, potassium and lipids usually associated with thiazide diuretics. Thus, combination treatment that begins with TRZ and adds MCTZ is effective in lowering blood pressure without any significant adverse metabolic effects.

Archives of Internal Medicine, 1979

There is much individual variability in the clinical manifestations of hypocalcemia. The rapidly ... more There is much individual variability in the clinical manifestations of hypocalcemia. The rapidly of the development of hypocalcemia will determine whether or not symptoms will be present. Signs and symptoms of hypocalcemia consisted of tetany (Chvostek&amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s and Trousseau&amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s signs), seizures, diminshed to absent deep tendon reflexes, papilledema, mental changes (weakness, fatigue, irritability, memory loss, confusion, delusion, hallucination), and skin changes. Etiologic factors for hypocalcemia in man include (1) decreased calcium absorption or increased loss from the gastrointestinal tract; (2) parathyroid hormone deficiency; (3) skeletal resistance to parathyroid hormone; (4) ineffective parathyroid hormone; (5) decreased production or increased degradation of 25-hydroxycholecalciferol or 1,25-dihydroxycholecalciferol; (6) increased complex formation with calcium; (7) increased skeletal uptake of calcium; (8) hypomagnesemic state; and (9) direct inhibition of bone resorption. Measurement of total and ionic calcium, magnesium, parathyroid hormone, vitamin D metabolites (25-hydroxycholecalciferol, 1,25-dihydroxycholecalciferol), and nephrogenous cyclic adenosine monophosphate are especially helpful in the laboratory evaluation of the hypocalcemic patient.

The American Journal of Medicine, 1984

The increasing biologic uniqueness of older persons requires an individualized approach to their ... more The increasing biologic uniqueness of older persons requires an individualized approach to their medical care. The physician must be aware of his or her own attitudes and beliefs regarding aging and death and how these views influence the physician-patient relationship. The physician must understand how older persons behave when they are ill and know how to interpret a changing constellation of multiple disease possibilities and interrelationships. The physician requires knowledge skills and the willingness to carefully evaluate each individual situation and to formulate a specifically tailored care plan. Because of the magnitude and complexity of medical, psychological, and social problems in older persons, the physician must cooperate with other members of the health care team. The accumulation and constant refinement of these skills defines the maturity and scientific grounding of the physician.

Journal of the American Dietetic Association

A prospective study was done in 21 hospitalized medical patients to determine the effects of age ... more A prospective study was done in 21 hospitalized medical patients to determine the effects of age and gender on food intake. From precise weighing of food served and uneaten, macronutrients and micronutrients ingested during the hospital stay were determined. Even though the hospital diet served was adequate in energy and protein, 38% of the patients ingested less than 65% of their nutritional requirements, with a higher percentage of those with inadequate intake among the elderly than among the young (28% vs. 10%). Patients over 65 years of age ingested less energy and protein than those under 65 years of age (1,167 vs. 1,967 kcal, p less than .01; 47 vs. 78 gm, p less than .05). The gender of the patients had no influence on food intake. More than 60% of the medical patients, especially the elderly, had an inadequate intake of micronutrients: folate, 100% of the elderly vs. 93% of the young; zinc, 90% vs. 64%; magnesium, 90% vs. 36%; and vitamin B-6, 90% vs. 64%. Multiple stepwise regression analysis showed that age and body weight on admission were of predictive value in terms of subsequent nutrient intakes during the hospitalization. Patients who were over 65 years old and weighted less than 80% of their ideal body weight consumed significantly less energy and fewer macronutrients and micronutrients.

Postgraduate Medicine

Malignant disease and primary hyperparathyroidism are the most common causes of hypercalcemia, bu... more Malignant disease and primary hyperparathyroidism are the most common causes of hypercalcemia, but there are many minor causes. Mechanical or humoral factors, or both, may underlie the increase in bone resorption. Parathyroid hormone (PTH) is a major mediator of bone resorption, but many other humoral agents have the same effect, eg, prostaglandin, osteoclast-activating factor, and thyroid hormone. Serial determination of total calcium concentration is the most important laboratory test in hypercalcemia. Other useful tests include the determination of serum and urinary phosphorus concentration, chloride/phosphate ratio, urinary cyclic adenosine 3',5'-monophosphate (cAMP) level; carboxyl-terminal PTH assay; corticosteroid challenge; and appropriate radiologic studies. Nephrogenous cAMP and urinary prostaglandin determinations are research tools that hold great promise in the future. Differentiation between PTH- and non-PTH-mediated hypercalcemia determines subsequent steps in diagnosis and treatment.

Surgery, gynecology & obstetrics, 1981