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C Horton

Publications and source records attributed to C Horton.

86 records · Page 5Linked to original sources
PubMed1985

Nitrendipine-induced stimulation of renin release by the isolated perfused rat kidney.

The direct effects of the organic calcium antagonist nitrendipine upon renin release were assessed using the isolated rat kidney perfused at constant pressure. This model circumvents the indirect actions of vasodilating agents by artificially maintaining perfusion pressure constant, thereby avoiding the hypotensive effects associated with the systemic administration of such agents. Renin release as assessed by radioimmunoassay was stimulated 2.6-fold upon the administration of 10(-6) M nitrendipine. Since this stimulation of renin release occurred in the absence of any alteration in perfusion pressure, we conclude that it represents a direct action of nitrendipine. This finding is in support of the current hypothesis concerning the inverse relationship between cytosolic Ca2+ and renin secretory rate, and suggests that Ca entry into the juxtaglomerular cells of the juxtaglomerular apparatus is sensitive to blockade by organic calcium antagonists such as nitrendipine.

Angiotensin I↗
PubMed1985

Reversal by the calcium antagonist nisoldipine of norepinephrine-induced reduction of GFR: evidence for preferential antagonism of preglomerular vasoconstriction.

We have demonstrated previously that the organic Ca++ antagonist diltiazem augments the glomerular filtration rate (GFR) of the isolated perfused rat kidney during norepinephrine (NE) - induced vasoconstriction. These earlier studies, however, did not elucidate the precise mechanism or site of action responsible for this effect. Nisoldipine (NIS) interacts with the same Ca+2 channels as diltiazem but differs in its physicochemical properties, binding characteristics and tissue specificity. We examined, therefore, the effects of NIS using an identical model. Renal perfusate flow and GRF were assessed in the isolated perfused rat kidney under conditions of constant renal perfusion pressure (100 mm Hg). NIS (10(-7) M) completely reversed the NE-induced reduction in GFR but was significantly less effective in augmenting renal perfusate flow. In additional series of experiments, filtration pressure was estimated during these manipulations by monitoring ureteral pressure during ureteral occlusion (stop-flow pressure). The NE-induced decrease in GFR was accompanied by a reduction in stop-flow pressure, which was abolished by the subsequent administration of NIS. Thus, nisoldipine preferentially attenuated NE-induced constriction of preglomerular resistance vessels but was less effective in reversing the effects of NE on postglomerular arterioles. These findings indicate that separate postreceptor mechanisms mediate the activation of pre- and postglomerular vessels by NE.

Animals↗
PubMed1983

Four-drug combination chemotherapy (methotrexate, cyclophosphamide, hexamethylmelamine, and CCNU) for non-small cell bronchogenic carcinoma: a Cancer and Leukemia Group B study.

Ninety-eight evaluable patients with nonresectable regional or metastatic non-small cell bronchogenic carcinoma were treated with a four-drug combination chemotherapy program of methotrexate, cyclophosphamide, hexamethylmelamine, and CCNU (MCHC). Fifteen partial or complete responses (15%) were obtained, all but one of which occurred in good performance status (0-1) patients. While "responders lived longer than non-responders", this was due more to initial performance status among responding patients than to achievement of partial (greater than 50%) or complete disease regression. Evaluation of those patients with good performance status (PS 0-1), indicated no statistically significant differences in median survival time for complete response and partial response patients compared to patients with "improved" or "stable" disease status in this group. This combination of modestly active single agents produced disappointing results in our lung cancer population. A search for more active single agents in lung cancer is necessary.

Altretamine↗
PubMed1981

Functional adaptation to reduction in renal mass: renal handling of amino acids by isolated perfused remnant rat kidneys.

To date, the renal handling of amino acids by remnant kidneys remains undefined. We have determined the renal handling of eight amino acids using the isolated perfused rat kidney. 6 normal and 22 partially infarcted rat kidneys (16 stage III [contralateral kidney removed], and 6 stage II [contralateral kidney left intact] were evaluated at perfusate amino acid concentrations approximately ten times normal plasma levels. Despite the reduction in glomerular filtration rate, the urinary excretion of most amino acids in remnant kidneys tended to exceed that of controls. Fractional amino acid excretion by both stage II and III kidneys tended to be or was higher than that of controls. The findings indicate that the fractional reabsorption of amino acids by residual nephrons of remnant kidneys is decreased. Our observations suggest that the changes are unrelated to a functional adaptation to the uremic environment.

Adaptation, Physiological↗
PubMed1980

Uptake and release of amino acids by normal and remnant kidneys: studies in the isolated perfused rat kidney.

In order to evaluate the capacity of normal and remnant kidneys to take up and release amino acids when plasma concentrations are increased above normal levels, we have determined the simultaneous net uptake or release of eight representative amino acids using the isolated perfused rat kidney model. Eight normal and five partially infarcted kidneys from Sprague-Dawley rats were perfused with Krebs-Ringer's bicarbonate buffer containing glucose 8 g/100 ml albumin and amino acids at concentrations approximately 10 times above normal plasma levels. Urine was collected every 15 min for 75 min, and perfusate samples were obtained at the midpoint of each urine collection. Amino acids were measured by gas-liquid chromatography. During perfusion, there was substantial net utilization of asparate, proline, alanine, and glycine by normal kidneys. In remnant kidneys the net uptake of amino acids tended to be lower than that of the normal kidneys. The fractional excretion of most amino acids by remnant kidneys was significantly higher than that of controls. These studies demonstrate the substantial capacity of the kidney to take up or release amino acids when presented with an increased load. The findings suggest that the fractional reabsorption of amino acids by residual nephrons of remnant kidneys is decreased.

Amino Acids↗
PubMed1980

Procarbazine, vincristine, CCNU, and cyclophosphamide (POCC) in the treatment of metastatic malignant melanoma.

Twelve previously untreated patients with histologically documented, metastatic, malignant melanoma were treated with the combination of procarbazine, vincristine, CCNU, and cyclophosphamide, with an objective response rate of 33%. The median survival time was 10 months for responders versus 5 months for nonresponders. Bone marrow suppression was the major toxic effect. Further clinical trials are needed to better assess the utility of this combination in advanced melanoma.

Adult↗
PubMedDate not supplied

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Community Health Nursing↗
PubMedDate not supplied

Long-term efficacy of Al3+ for prevention of bioprosthetic heart valve calcification.

AI3+ preincubation has been shown in 21 and 60 day implants to inhibit calcification of glutaraldehyde preserved bovine pericardium (GPBP) in the rat subdermal model. This study was designed to assess the long-term anticalcification efficacy of GPBP AI3+ preincubation. Rat (50-60 gm, male, CD Sprague-Dawley) subdermal implants of GPBP, pretreated with 0.01 M or 0.1 M AICI3, were carried out for 21, 60, 90, and 120 days. Each explanted GPBP was analyzed for Ca2+ by atomic absorption spectroscopy and for AI3+ by atomic absorption spectroscopy or neutron activation irradiation. Results showed profound long-term (implant duration 120 days) inhibition of calcification after GPBP preincubation in 0.1 M AICI3 (Ca2+ = 21.8 +/- 12.6 micrograms/mg), compared to control (Ca2+ = 329.0 +/- 20.3 micrograms/mg). After preincubation in 0.1 M AICI3 and 21 day rat subdermal implantation, GPBP AI3+ levels declined from 9033 +/- 680 micrograms/g (control = 6.3 +/- 3.7 micrograms/g) to 2700 +/- 156 micrograms/g; however, there was no further significant decline in GPBP AI3+ levels after long-term implantation of 120 days (2618.4 +/- 349 micrograms/g). The authors conclude that GPBP preincubation in 0.1 M AICI3 markedly inhibited pathologic calcification to 7% of control values in the rat model after long-term (120 day) subdermal implantation.

Aluminum↗