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Biomedical subjects

L H Smith

Publications and source records attributed to L H Smith.

At least 91 records · Page 5Linked to original sources

Transport of citrate across renal brush border membrane: effects of dietary acid and alkali loading.

Dietary acid or alkali loading was given to rats by providing 150 mM NH4Cl or 150 mM NaHCO3 in place of drinking water for 6 days; control animals received 150 mM NaCl. After 6 days, the citrate clearance was 0.04 +/- 0.01 ml/min (mean +/- SE) in the acid-loaded group, 0.9 +/- 0.1 ml/min in the control group, and 2.5 +/- 0.2 ml/min in the alkali-loaded group. At the end of the experiment, the rats were killed, and the Na+ gradient-dependent (Nao+ greater than Nai+) citrate uptake (pmol/mg protein) was measured in brush border membrane (BBM) vesicles prepared from each group. At 0.3 min, the [14C]citrate uptake was 198 +/- 8 pmol/mg protein (mean +/- SE) in the acid-loaded group, 94 +/- 16 pmol/mg protein in the control group, and 94 +/- 13 pmol/mg protein in the alkali-loaded group. The rate of Na+-independent (NaCl in medium replaced by KCl) [14C]-citrate uptake by BBM vesicles was the same for acid-loaded, control, and alkali-loaded animals. Thus, the increased capacity of the proximal tubular BBM to transport citrate from the tubular lumen into the cell interior may be an important factor that contributes to decreased urinary citrate in the presence of metabolic acidosis induced by chronic dietary acid loading.

Acid-Base Equilibrium↗

Urinary citrate excretion in normal persons and patients with idiopathic calcium urolithiasis.

The 24-hour urinary excretion of citrate was measured in 83 normal persons and in 132 consecutive patients with idiopathic calcium urolithiasis, uninfected urine, and normal renal function. The urinary excretion of citrate in normal men was not significantly different from that in normal women (P greater than 0.05). There was a significant (P less than 0.001) increase of urinary citrate excretion with increasing age in normal persons. No increase of urinary citrate excretion with age was demonstrated in stone formers. There was no statistically significant difference between active and inactive stone formers in regard to regression of the citrate/calcium ratio or the citrate/uric acid ratio, and there was no difference in these ratios between men and women considered separately or in subgroups by hypercalciuria or hyperuricuria or by individual age. Hypocitraturia was found in 29.2% of patients with idiopathic calcium urolithiasis. No relationship could be demonstrated between the 24-hour urinary excretion of citrate and severity of stone disease before presentation at our clinic or the frequency of stone growth or new stone formation at follow-up. Twenty-two of 35 patients with hypocitraturia had multiple urinary citrate measurements. In 15 of these 22 patients, at least one normal urinary citrate measurement was obtained. Further prospective study is required to establish the value of urinary citrate determinations in patients consuming an uncontrolled diet in an outpatient setting.

Adult↗

Pentosan polysulfate as an inhibitor of calcium oxalate crystal growth.

Pentosan polysulfate was studied as a calcium oxalate crystal growth inhibitor. The inhibition from pentosan polysulfate at concentrations ranging from 3.5 to 110 mg./l. was measured in simple inorganic calcium oxalate solutions at pH 5, 6 and 7. Pentosan polysulfate also was mixed with urine at concentrations from 10 to 350 mg./l. and inhibition determined. Measurement of calcium oxalate crystal growth inhibition was performed in a seeded crystal growth system. One inhibitory unit (concentration of pentosan polysulfate necessary to give a 50 per cent reduction in the rate of crystal growth) was 5.7 +/- 2 mg./l. at pH 5, 7.2 +/- 1.1 mg./l. at pH 6 and 6.0 +/- 2.1 mg./l. at pH 7. Urine-pentosan polysulfate mixtures showed more inhibitory activity than the predicted inhibition present. Addition of pentosan polysulfate to urine at a concentration of 10 mg./l. increased the inhibitory activity from 45 +/- 3 to 59 +/- 3 IU/l. Pentosan polysulfate is a potent calcium oxalate crystal growth inhibitor in urine at physiologic pH levels. If the urinary concentration of pentosan polysulfate after oral administration reaches 10 mg./l., the increase in inhibitory activity in urine that may occur might be important in the treatment of patients who form calcium oxalate calculi within the urinary tract.

Calcium Oxalate↗

Calcium oxalate dihydrate formation in urine.

Factors that promote the formation of calcium oxalate dihydrate (COD) in urine were investigated. Crystals resulting from the incubation of 25-ml aliquots of the solution to be tested and 1 ml of 0.05 M ammonium oxalate were examined by infrared spectrophotometry. With reference spectra of known mixtures, the fractional content of COD could be estimated. At pH 6.5, only COD formed in human urine. In a supersaturated inorganic solution of calcium oxalate, the percentage of COD was 7.5 +/- 1.4. Pyrophosphate (1 to 8 X 10(-5) M), citrate (10(-4) to 2 X 10(-3) M), RNA from yeast (5 X 10(-9) to 0.5 X 10(-7) M), or heparin (2 X 10(-9) to 2 X 10(-7) M) added to a supersaturated solution of calcium oxalate increased the percentage of COD proportional to the concentration of the additives. Chondroitin sulfate and magnesium had no effect. An increase in pH increased the formation of COD in inorganic solutions containing citrate, pyrophosphate, and heparin and in undiluted urine. RNA-citrates and citrate-pyrophosphate mixtures showed additivity. Urine showed an effect that was inversely proportional to its dilution. Substances that promote COD formation in this system had their phase-stabilizing effects at concentrations normally found in urine. Further, these same substances are known inhibitors of calcium oxalate crystal formation. With both inhibition and phase stabilization, there is additivity of effects, and changes in pH alter the response.

Adult↗

Oxalate absorption and postprandial urine supersaturation in an experimental human model of absorptive hypercalciuria.

The effect of 1.25-dihydroxyvitamin D [1,25-(OH)2D] on dietary oxalate absorption and postprandial urine supersaturation with calcium oxalate was determined in 11 normal subjects. 1,25-(OH)2D increased the urinary excretion of orally administered [14C]oxalate in the 8 h period after a liquid meal containing 1.875 mmol of calcium and 0.83 mmol of oxalate (P less than 0.01), and during a 48 h period when the subjects ingested a diet containing 25 mmol of calcium and 3.3 mmol of oxalate/day (P less than 0.01); however, 1,25-(OH)2D administration had no effect on [14C]oxalate excretion when calcium was removed from the liquid meal. 1.25-(OH)2D increased 24 h urinary oxalate excretion from 28.7 +/- 2.1 mmol/mol of creatinine to 36.8 +/- 2.6 mmol/mol of creatinine (P less than 0.05) on the 10 mmol/day calcium diet and from 26.4 +/- 2.9 to 33.2 +/- 2.2 mmol/mol of creatinine (P less than 0.1) on the 25 mmol/day calcium diet. A linear correlation (r = 0.72) was found between plasma 1,25-(OH)2D levels and urinary [14C]oxalate excretion after the liquid meal. 1,25-(OH)2D administration produced postprandial supersaturation of urine with calcium oxalate and calcium oxalate crystalluria. These studies suggest that 1,25-(OH)2D increases oxalate absorption (and urinary excretion) by increasing calcium absorption, which results in less binding of calcium to oxalate in the intestine; therefore more oxalate is available for absorption. The combined effect of increased calcium and oxalate absorption results in postprandial supersaturation of urine with calcium oxalate, with resultant crystalluria.

Adult↗

Detection of malignant ovarian neoplasms: a review of the literature. III. Immunological detection and ovarian cancer-associated antigens.

In summarizing the data on characterization of the immune system in the ovarian cancer patient, it is possible to conclude that both cellular and humoral immune responses occur in the presence of ovarian cancer. However, the specificity of such reactions is less certain. Although most of the tests outlined above are of doubtful utility in cancer immunodetection, data obtained from some studies support the assumption that there exist epithelial ovarian cancer-associated antigens which are expressed in tumors arising in different individuals, and that these antigens are the target of an immune response in many patients. It is unclear, however, how widely distributed such antigens are among normal tissues and other neoplasms. Direct characterization of ovarian cancer-associated antigens may provide more well-defined test antigens with which to assay individuals for a specific immune response. An immune response to specific cancer-associated antigens could precede the appearance of detectable levels of such antigens in the circulation.

Antibodies, Neoplasm↗

Detection of malignant ovarian neoplasms: a review of the literature. I. Detection of the patient at risk; clinical, radiological and cytological detection.

Risk factors for epithelial ovarian cancer are summarized in Table 1. Calculation of ovulation-years appears to be a potentially useful and practical method for identification of the high-risk individual. Risk factors for nonepithelial ovarian cancer are largely unknown, and consequently clinical diagnosis is stressed in the early detection of these tumors. Patients with Peutz-Jeghers syndrome or ovarian dysgenesis are significantly at risk and require at least regular pelvic examination. Of course, individuals with sexual precocity are at high risk for sex cord/stromal or germ cell malignancies. Individuals with a family history of Sertoli-Leydig cell tumors and benign thyroid disease also deserve close observation. Early clinical detection requires a sensitivity to presenting symptomatology (e.g., diffuse abdominopelvic complaints) as well as the skill and knowledge needed to recognize and appropriately manage adnexal masses. Harbingers of ovarian malignancy in the elderly woman, including unexplained hypercalcemia, new onset dermatomyositis, and cerebellar degeneration, should motivate thorough gynecologic evaluation. While radionuclide ovarian imaging for detection of early epithelial cancers of the ovary may become more generally available in the future, ultrasound imaging of the postmenopausal ovary, and peritoneal cytology may be of immediate value in screening high-risk women.

Age Factors↗

Percutaneous lithotripsy.

We have performed percutaneous extractions of renal pelvic stones in 194 patients via the Wolf percutaneous universal nephroscope. At 1 session, with the patient under general anesthesia, a percutaneous tract is dilated to 24F and the stone is removed immediately. We have removed 185 stones successfully by ultrasonic lithotripsy, basket retrieval and/or use of forceps. Average operating time was 54 minutes and mean hospitalization was 5 days. The advantages of this technique are that a skin incision of only 1 cm. is required to remove the stone, hospital days are fewer than with open procedures and postoperative morbidity is minimal. In selected situations this method represents a significant advance over standard open surgical procedures for removal of renal pelvic stones.

Angiography↗

The stone clinic effect in patients with idiopathic calcium urolithiasis.

The "stone clinic effect" refers to the effect of encouraging a high intake of fluid and avoiding dietary excesses on stone formation and growth in patients with urolithiasis. To determine the extent of this effect we reviewed the clinical courses of 108 patients with idiopathic calcium urolithiasis and indeterminant metabolic activity. There was no evidence of stone growth or new stone formation (metabolic inactivity) after a mean followup of 62.6 months in 63 of the 108 patients (58.3 per cent), including 12 of 17 (70.6 per cent) with hypercalciuria and 7 of 15 (46.7 per cent) with hyperuricosuria. Comparison of initial and followup 24-hour urine volumes demonstrated a significant increase in patients who were metabolically inactive at followup (p less than 0.0005), while no increase was detected in patients who were metabolically active at followup. We recommend that specific drug therapy should not be given to patients with idiopathic calcium urolithiasis until the stone clinic effect has been evaluated.

Adolescent↗

beta-Adrenergic blocking agents. 23. 1-[Substituted-amido)phenoxy]-3-[[(substituted-amido)alkyl]amino] propan-2-ols.

The synthesis of a series of 1-phenoxy-3-[(amidoalkyl)amino]propan-2-ols, in which the phenoxy ring is variously substituted with ortho and para amidic moieties, is described. Several of the compounds have beta-blocking potency comparable to that of propranolol and cardioselectivity similar to that of practolol, when given intravenously to anesthetized cats. In contrast to previous findings with cardioselective beta blockers, both ortho and para substitution give variable degrees of cardioselectivity. Potency, however, is favored by ortho substitution.

Adrenergic beta-Antagonists↗

Sulphate conjugation of p-hydroxytriamterene by platelet phenol sulphotransferase: assay conditions and correlation with metabolism in man.

1 Sulphate conjugation catalyzed by phenol sulphotransferase (PST) is an important pathway in the metabolism of many drugs including triamterene. Variations in PST activity in an easily obtained tissue such as the platelet might reflect individual differences in the sulphate conjugation in other organs and tissues. Human platelets contain at least two forms of PST, a thermolabile (TL) form for which dopamine is a substrate and a thermostable (TS) form for which low concentrations of p-nitrophenol serve as a substrate. 2 p-OH-triamterene, the major metabolite of triamterene, is conjugated with sulphate in vivo. p-OH-triamterene was a substrate for platelet PST with an apparent Michaelis-Menten value of 26 microM. Thermal stability studies indicated that p-OH-triamterene was a substrate for only the TS form of platelet PST. 3 When platelet homogenates from 29 individual subjects were tested, there was a significant correlation between PST activities measured with 4 microM p-nitrophenol and with p-OH-triamterene (r = 0.985, P less than 0.0001) but not between activities measured with dopamine and with p-OH-triamterene (r = 0.023, P greater than 0.2). These results confirmed that p-OH-triamterene was a substrate for only the TS form of human platelet PST. 4 The same 29 subjects were treated with 1 mg/kg of triamterene orally. 24-h urinary excretions of triamterene, p-OH-triamterene and p-OH-triamterene sulphate averaged 15.3%, 6.3% and 78.4%, respectively, of the total of triamterene plus measured metabolites excreted. The excretion of triamterene plus the two metabolites averaged 43.1 +/- 2.6% (mean +/- s.e. mean) of the ingested dose. There was not a significant correlation between the proportion of p-OH-triamterene excreted as sulphate conjugate and the activities of either the TS or TL forms of platelet PST activity.

Adult↗

Potentiation of butylated hydroxytoluene-induced acute lung damage by oxygen. Cell kinetics and collagen metabolism.

Changes in cell proliferation and in collagen synthesis were studied in young adult male BALB/c mice injected intraperitoneally with 400 mg/kg of butylated hydroxytoluene (BHT) in corn oil or corn oil alone and immediately exposed to 70% oxygen or air for 6 days. Mice received [3H]thymidine either as a single injection 90 min before being killed or as a continual infusion via an osmotic minipump. Autoradiography was done 2 to 14 days after BHT injection, and cell kinetic studies were performed. In a similar experiment, mice were injected intraperitoneally with [3H]proline 3 h before being killed, and type l/type III collagen ratio in newly synthesized lung collagen was determined. We found that exposure to 70% oxygen immediately after the administration of BHT initially delayed the epithelial cell proliferation and the decrease in the percentage of newly synthesized type III collagen that occurred after BHT alone. Once the animals were removed from oxygen there was a compensatory burst of cell proliferation and a precipitous drop in the percentage of newly synthesized type III collagen. The proliferating cell population after removal from oxygen was primarily interstitial and not epithelial. When exposure to oxygen was delayed, cell proliferation was similar to that seen after BHT injection alone.

Animals↗