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Biomedical subjects

T Morgan

Publications and source records attributed to T Morgan.

At least 19 recordsLinked to original sources
PubMed1992

Local recurrence after cystectomy alone for bladder carcinoma.

Although the role of preoperative irradiation in the treatment of bladder carcinoma is questioned, patterns of failure after cystectomy alone are not well documented. Local failure patterns were analyzed retrospectively in 83 patients (67 men and 16 women) treated with cystectomy without adjuvant therapy at three institutions. The follow-up period ranged from 0 to 167 months. Disease was assessed preoperatively by clinical stage and postoperatively by pathologic stage. Thirteen patients had pelvic recurrences, a 5-year actuarial failure rate of 18%. Pathologic stage was the only significant predictor of local recurrence, which ranged from 6% in patients with pT2 tumors to 51% in patients with pT3b tumors. The median time to local recurrence was 9 months (range, 3 to 62 months). Clearer documentation of failure patterns will provide a basis for evaluating survival with combined treatment methods, including preoperative radiation therapy, surgery, and chemotherapy.

Aged↗
PubMed1992

The effect of presentation and mode of delivery on neonatal outcome in the second twin.

OBJECTIVE: The purpose of this study was to determine if cesarean delivery of the nonvertex second twin improved neonatal outcome. STUDY DESIGN: We examined the maternal and neonatal records from 457 sets of twins delivered from 1985 to 1990. We compared 1- and 5-minute Apgar scores, umbilical artery and vein blood pH values, duration of neonatal hospitalization, the incidence and length of ventilation, intraventricular hemorrhage, birth trauma, and mortality rate between vertex and nonvertex second twins delivered either vaginally or by cesarean section. RESULTS: The presentation and mode of delivery of the second twin was not associated with a significant difference in any of the outcome variables except for the 1-minute Apgar score, which was lower in the nonvertex group delivered vaginally. CONCLUSION: Our data do not support routine cesarean delivery for twins of any birth weight when the second twin is nonvertex.

Apgar Score↗
PubMed1992

The role of the renal nerves in renin synthesis.

1. Renin synthesis and secretion were studied in Balb/c mice with a denervated left kidney. 2. Denervation inhibited renin secretion. 3. Denervation reduced the renal renin content. 4. Denervation reduced renal renin mRNA. 5. Renal denervation inhibits renin secretion by blocking the synthetic system prior to mRNA formation.

Animals↗
PubMed1992

Clinical efficacy of perindopril in hypertension.

1. Perindopril's effectiveness in mild to moderate hypertension was evaluated in three studies. 2. Perindopril was more effective than sodium restriction in reducing blood pressure, and the effects were additive. 3. Perindopril was as effective as atenolol in reducing blood pressure, and was well tolerated. 4. Perindopril lowered blood pressure to the same extent as enalapril at peak drug levels but had a greater effect at the trough level of the drugs. 5. Perindopril is an effective antihypertensive agent with an acceptable side-effect profile in people with hypertension.

Aged↗
PubMed1991

A phase I trial of alpha-interferon in combination with pentostatin in hematologic malignancies.

Pentostatin, a novel inhibitor of adenosine deaminase, has shown activity in various lymphoid malignancies of both the T and B cell lineage. This agent has unique side effects and in general myelosuppression has been mild. Interferon has both antiviral and antineoplastic properties. This agent has shown activity in hairy cell leukemia, chronic granulocytic leukemia, low grade lymphoma, and myeloma. Side effects from interferon are in general dissimilar to those that have been seen with pentostatin and in particular myelosuppression has not been a major toxicity with low doses of interferon. This current trial explored the combination of pentostatin and interferon in hematologic malignancies. Fifteen patients were enrolled in this phase I trial at a fixed dose of pentostatin of 4 mg/m2 biweekly and interferon at doses of 0.5, 1, 2, or 4 million units/m2 of interferon. At the first three dose levels of interferon nausea and vomiting were the predominant toxicity and appeared to worsen with time on study. Fatigue also was seen at the lowest level of interferon and was severe enough to cause two individuals to discontinue the study medications. At higher dose levels of interferon, myelosuppression, nausea and vomiting, and fatigue were the predominant toxicities. One patient with hairy cell leukemia had a complete response and a second patient with T cell cutaneous lymphoma had a partial response which lasted for 6 to 7 weeks. The maximum tolerated dose of interferon with pentostatin in this patient population was four million units/m2.

Adult↗
PubMed1991

The role of the macula densa in renin synthesis.

1. The role of the macula densa in renin synthesis was studied using mice with one hydronephrotic kidney. 2. Renin synthesis was assessed by measurement of renal renin, renal mRNA for renin and plasma renin. 3. Sodium depletion stimulated mRNA and renal renin to a similar extent in the hydronephrotic and contralateral kidney. 4. Enalapril stimulated mRNA concentration in both kidneys but renal renin did not rise in the hydronephrotic kidney. 5. Propranolol did not alter the response to sodium depletion in either kidney. 6. The macula densa is not crucial for the stimulation of renin synthesis following sodium depletion. However, it may regulate renin production after mRNA synthesis, possibly by controlling the conversion of prorenin to renin.

Animals↗
PubMed1991

Carotid stenosis in lacunar stroke.

The prevalence of extracranial carotid stenosis in patients with a clinical syndrome of lacunar stroke has not been extensively studied using noninvasive methods. We performed carotid duplex sonography on 168 patients referred to the neurosonology laboratory with a diagnosis of ischemic stroke. Strokes were independently classified as lacunar or nonlacunar hemispheric infarction without knowledge of the ultrasound results. We excluded patients with infarcts that were clearly vertebrobasilar, presumed to be cardioembolic, or had occurred greater than 1 year earlier, and patients for whom classification of the nature and location of the event was not possible. Fifty-five patients had lacunar and 54 had nonlacunar stroke. No differences in age, sex, distribution, or prevalence of hypertension, diabetes, prior ischemia, or Hispanic surname existed between the two groups. Tobacco use was more frequent in the nonlacunar group (p less than 0.01). The prevalence of important extracranial carotid stenosis (greater than or equal to 50% diameter reduction) in the lacunar stroke group was 13% (seven of 55) in the ipsilateral and 4% (two of 55) in the contralateral carotid artery. Of the 54 patients with nonlacunar hemispheric stroke, 41% (22) had ipsilateral (p less than 0.01) and 26% (14) had contralateral (p less than 0.01) carotid stenosis. This study suggests that important carotid stenosis is infrequent among patients presenting with a clinical syndrome of lacunar stroke. These data impact on decisions regarding cerebrovascular work-up in such patients.

Adult↗
PubMed1990

Effect of portal hypertension on in vivo bile acid-mediated small intestinal mucosal injury in the rat.

This study's purpose was to determine whether portal hypertension adversely affects small intestinal mucosal injury. Portal hypertension was produced in male Sprague-Dawley rats by two-stage ligation of the portal vein. Sham-operated rats were used as controls. Two weeks later, intestinal injury was produced by in vivo perfusion with 5 mM chenodeoxycholic acid for 30 min. Intestinal injury was assessed by quantitative morphometry and by measuring intestinal water and mannitol absorption. Portal hypertension resulted in more injury in the distal perfused intestine as manifested by increased villus tip denudation [portal hypertensive 52.5 +/- 9.6 (SEM) vs controls 28.1 +/- 5.7 microns, P = 0.05). Additionally there was a significant decrease in the unperfused duodenal villus height in portal hypertensive rats (portal hypertensive 755 +/- 22 vs controls 848 +/- 28 microns, P less than 0.02). Portal hypertension had no significant effect on the increase in mannitol absorption or water secretion caused by chenodeoxycholic acid perfusion. This study suggests that portal hypertension alters small intestinal mucosa and increases susceptibility to injury.

Absorption↗
PubMed1990

Simvastatin in the treatment of hypercholesterolaemia in patients with essential hypertension.

Mortality from coronary artery disease is a common problem in treated hypertensive patients, and these people have a high prevalence of elevated cholesterol levels. A study was undertaken to determine whether cholesterol could be lowered effectively without major side effects in patients with treated hypertension. Forty-nine patients (mean age 67.6 years) with cholesterol greater than 5.5 mmol/l were placed on a reduced-fat (less than 30% of calories from fat with a ratio of polyunsaturated to saturated fats of less than 1) diet for 3 months. If the cholesterol was between 5.5 and 7.5 mmol/l and total cholesterol divided by high-density lipoprotein cholesterol was greater than 4.5, the patients were randomly allocated either to the simvastatin (24 patients) or the placebo group (25 patients). Diet and placebo caused minor and insignificant falls in cholesterol and no change in triglycerides or lipids. Treatment with simvastatin reduced cholesterol levels from 6.85 to 4.75 mmol/l (P less than 0.001), triglycerides from 2.7 to 2.1 mmol/l (P less than 0.01), low-density lipoproteins from 4.6 to 2.6 mmol/l (P less than 0.001) and high-density lipoproteins rose from 1.09 to 1.18 mmol/l (P less than 0.01). Total cholesterol divided by high-density lipoprotein cholesterol fell from 6.3 to 4.0 (P less than 0.001). The drug was well tolerated and the side-effect profile did not differ from the placebo in clinical or biochemical events. The active drug was stopped in one patient (abdominal pain, dizziness, headache, tiredness) and in two patients taking the placebo (elevated creatine phosphokinase, cardiovascular collapse). Simvastatin effectively lowered total cholesterol and improved the lipoprotein profile. The dose required in most patients was 40 mg/day. Simvastatin may be an acceptable drug to improve the lipoprotein profile in order to determine whether this improves the prognosis in patients treated for hypertension.

Adult↗
PubMed1990

Interaction of enalapril with sodium restriction, diuretics, and slow-channel calcium-blocking drugs.

While monotherapy sometimes controls blood pressure (BP), it is often essential to add a second drug for adequate control. This study examined in a factorial fashion the interaction of enalapril with some commonly used antihypertensive therapies. There were between 10 and 16 patients in each study, and the patients had responded in part to the two drugs used. Enalapril and sodium restriction lowered BP 12 +/- 3/11 +/- 2 and 4 +/- 2/3 +/- 1 mm Hg, respectively. The effects of the two therapies were additive, and there was no interaction. Enalapril and hydrochlorothiazide lowered BP 11 +/- 3/8 +/- 3 and 8 +/- 2/6 +/- 2 mm Hg, respectively. The effect of the two drugs together indicated a positive interaction of 4 +/- 2/3 +/- 1 mm Hg (p less than 0.05). Enalapril and nifedipine both lowered BP (10 +/- 2/8 +/- 1 and 11 +/- 3/8 +/- 1 mm Hg). The two drugs combined had a strongly positive interaction of 10 +/- 3/7 +/- 2 mm Hg (p less than 0.001). Enalapril can be used with the other therapeutic methods tested. If a converting enzyme inhibitor does not reduce BP adequately, it appears appropriate to add a thiazide diuretic or a slow-channel calcium-blocking drug. The mechanism of the positive interaction with diuretics probably reflects an effect on the renin-angiotensin system, but the explanation for the synergism with slow-channel calcium-blocking drugs is unclear.

Blood Pressure↗
PubMed1990

Pharmacokinetics of carvedilol in older and younger patients.

Carvedilol, a combined beta- and alpha 1-blocking drug, was given to 8 young (age 39-47) and 21 old (age 64-79) patients with essential hypertension. Clinical and pharmacokinetic responses to 12.5, 25 and 50 mg were determined and compared. In both age groups, pharmacokinetic data were similar with all three doses of carvedilol. Peak blood levels were reached within 90 minutes and at 24 hours the trough blood level was less than 10% of the peak level. Carvedilol or its metabolite did not accumulate. Falls in systolic and diastolic BP were greater than 7 mmHg in 28 of the 29 patients. The falls in diastolic BP did not differ between groups but the older group had a greater fall in systolic BP. However, the systolic BP of the older group was higher and expressed as a percentage, the falls in BP did not differ. The time to peak fall in BP was about 4 hours and was always after the time to peak blood level. There was no correlation between blood level and BP fall. When the drug was administered 24 h after the previous dose, a further fall in BP was seen indicating a greater effect at peak drug levels. Side effects were few and, during the chronic study, there was no postural hypotension or postural hypotensive symptoms. On the study days, five patients developed postural hypotension with symptoms. These were not observed at other times and may have been due to decreased sympathetic outflow on the study days. Carvedilol lowered BP in order and younger patients. There were no significant effects of age on its pharmacokinetics. Carvedilol is an effective antihypertensive agent that can be used in people with essential hypertension in all age groups.

Adult↗
PubMed1989

Modulation of the metabolism and pharmacokinetics of 1-beta-D-arabinofuranosylcytosine by 1-beta-D-arabinofuranosyluracil in leukemic mice.

The interaction between high concentrations of 1-beta-D-arabinofuranosyluracil (HiCAU) and 1-beta-D-arabinofuranosylcytosine (ara-C) was investigated in vivo with emphasis on cell kinetics, pharmacokinetics, and drug metabolism. Mice bearing L5178Y leukemia were given a 48-h s.c. infusion of high-dose ara-U (HiDAU) to achieve a plasma level of 0.5 to 1 mM. A total dose of 7.35 g/kg/day for 2 days was nontoxic; the mean survival of control (saline treated) leukemic mice was 12.2 +/- 1.8 days and 11.7 +/- 2.0 days for the HiDAU-treated leukemic mice. Using flow cytometry, cell cycle progression of L5178Y ascites cells was monitored during HiDAU infusion. At 48 h, the proliferative index (PI) percentage of the leukemic cells is significantly different (P less than 0.001) in HiDAU-treated leukemic mice (mean = 50.8) versus control (mean = 45.6). A higher PI percentage is associated with accumulation of cells in S phase. This effect was highly variable in the ara-U-treated mice, and the ara-U "perturbed" group was defined as those mice whose cells had an increase in the PI to greater than or equal to 50%. The higher PI percentage in HiDAU-treated mice correlated with HiCAU in ascites fluid, leukemic cells, and kidney of perturbed mice. HiCAU in the "ara-U-perturbed" group altered the plasma pharmacokinetics of high-dose ara-C (HiDAC, 1 g/kg), increased the cellular metabolism of ara-C to 1-beta-D-arabinofuranosylcytidine triphosphate (ara-CTP) (3-fold), and increased ara-C-DNA synthesis (3-fold). In mice bearing the L5178Y leukemia, a 48-h infusion of ara-U followed by a 24-h s.c. infusion of 40 mg/kg resulted in a 260% increase in life span and seven 90-day survivors among 16 treated mice. In contrast, ara-U or ara-C alone had a negligible therapeutic effect. ara-U-induced alterations in the systemic pharmacokinetics of ara-C are the result of inhibition of cytidine deaminase activity by HiCAU in liver and kidneys. This results in a decrease in ara-C catabolism and prolongs the plasma half-life of ara-C. The dual alteration of the pharmacokinetics of ara-C and cytokinetics of the leukemia cells by HiCAU results in enhanced survival of leukemic mice. These results may help explain the clinical utility of HiDAC treatment programs for patients with acute leukemia.

Animals↗
PubMed1989

Effect of mineralocorticoids and salt loading on renin release, renal renin content and renal renin mRNA in mice.

1. DOCA and 9 alpha-fludrocortisone were given to mice on a high-sodium diet for periods of up to 20 weeks, resulting in decreases in plasma renin concentration, renal renin concentration and renal renin mRNA with both treatments. 2. Plasma renin concentration was suppressed prior to suppression of renin mRNA and renal renin levels, indicating that suppression of synthesis and secretion of renin occur separately. 3. The decrease in renal renin concentration that occurred with DOCA was greater and more rapid than the decrease that occurred with 9 alpha-fludrocortisone, suggesting that DOCA caused intra-renal breakdown of renin. 4. When DOCA was given to mice on a low-sodium diet, plasma renin concentration and renal renin concentration increased, indicating that the effects of DOCA on renin levels were dependent on dietary sodium. 5. Renin secretion and synthesis appeared to be controlled by different mechanisms and sodium balance has an important effect on both processes.

Animals↗
PubMed1989

Effect of calcium carbonate on blood pressure in normotensive and hypertensive people.

Forty-seven patients with mild hypertension and 48 normotensive patients entered a blinded, parallel study in which they received a placebo, 10 mmol/day calcium carbonate (CaCO3), or 20 mmol/day CaCO3. There were no significant differences in blood pressure changes among the groups. In the hypertensive group and in patients with the highest blood pressure there were individual falls in systolic pressure, particularly in the group receiving 10 mmol daily CaCO3. In the hypertensive group the changes were: with placebo, -3 +/- 2/-2 +/- 2 mm Hg; with CaCO3 (10 mmol), -7 +/- 3/-2 +/- 2 mm Hg; and with CaCO3 (20 mmol), -2 +/- 3/1 +/- 2 mm Hg. No change was significant, and no pressure changes of patients taking CaCO3 differed significantly from changes of patients taking placebo. Ten of 33 patients taking placebo, 11 of 31 taking 10 mmol/day CaCO3, and nine of 31 taking 20 mmol/day CaCO3 were classified as responders from their systolic blood pressure fall. These response rates did not differ. Eight patients had falls of systolic blood pressure greater than 15 mm Hg. Five were on 10 mmol/day CaCO3 and three on 20 mmol/day CaCO3. This response was significantly different from that with placebo. Univariate analyses failed to reveal any predictive dietary or biochemical parameter. After 3 months of not taking CaCO3, 12 patients classified as responders, including six of the eight with a fall of 15 mm Hg or more, were rerandomized to placebo or to 20 mmol/day CaCO3. In the rechallenge, responses to CaCO3 and placebo were similar, neither causing a significant pressure fall. Calcium carbonate did not reduce blood pressure. The apparent response in a few patients was not verified by rechallenge. The present study does not support calcium supplementation as a useful nonpharmacological measure for reducing elevated blood pressure.

Adult↗