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Biomedical subjects

T Morgan

Publications and source records attributed to T Morgan.

At least 73 records · Page 4Linked to original sources
PubMed1994

Efficacy and safety of controlled-release niacin in dyslipoproteinemic veterans.

OBJECTIVE: To evaluate the safety and efficacy of controlled-release niacin in patients with hyperlipoproteinemia. DESIGN: A retrospective cohort study. SETTING: A Department of Veterans Affairs Medical Center. PATIENTS: A consecutive sample of 969 predominantly elderly male veterans treated for dyslipoproteinemia with controlled-release niacin between October 1988 and October 1991. MAIN OUTCOME MEASURES: Primary outcomes were lipid levels and lipoprotein cholesterol response, alternations in levels of hepatic enzymes and blood chemistry test results, and characterization of niacin-induced hepatotoxicity abstracted from the patient's medical, laboratory, and pharmacy records. RESULTS: 93% (896 of 969) of the cohort was evaluable. Patients (age, 61.7 years [9.4 years], mean [SD]) were treated for 1 to 36 months (13.0 months [9.7 months]) with an average maintenance dose of 1.67 g/d (0.8 g/d). Niacin was discontinued in 48.5% (435 of 896) of the patients primarily because of adverse effects. Poor glycemic control led to discontinuation in 40.6% (43 of 106) of the patients with diabetes mellitus. The lipoprotein response was dose-related and favorable (levels of total cholesterol, -19.1%; low-density lipoprotein cholesterol, -24.0%; high-density lipoprotein cholesterol, +5.7%; and triglycerides, -32.5%). Statistically but not clinically meaningful dose-related increases were seen in levels of liver enzymes and serum glucose (aspartate aminotransferase, +29%; alanine aminotransferase, +23%; alkaline phosphatase, +25%; and glucose, +7%; P = 0.0001). Twenty of 896 (2.2%) and 42 of 896 (4.7%) patients met biochemical criteria for probable and for possible or probable niacin-induced hepatotoxicity, respectively. Predisposing factors included high dose, alcohol use, preexisting liver disease, and concurrent oral sulfonylurea therapy. CONCLUSIONS: Controlled-release niacin is effective in treating dyslipoproteinemia in selected middle-aged and elderly veterans, but approximately one half of patients discontinued the drug because of adverse effects or other causes including noncompliance. Niacin should be avoided in patients with hepatic dysfunction or a history of liver disease, patients with diabetes mellitus, and patients who abuse alcohol. Because controlled-release niacin seems to be more potent than crystalline niacin, product substitution without dose adjustment should be avoided.

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PubMed1994

Effectiveness of blood pressure control with once daily administration of enalapril and perindopril.

Ten patients who had their blood pressure controlled with enalapril (10 mg, n = 4; 20 mg, n = 6) and 10 control subjects on perindopril (4 mg, n = 6; 8 mg, n = 4) entered a double-blind crossover study. They received placebo or the active drug 1 week apart and had their blood pressure measured at 0, 2, 3, 4, and 24 h. Then they crossed over to the other angiotensin-converting enzyme inhibitors (4 mg perindopril congruent to 10 mg enalapril) and the double-blind study was repeated. Blood pressure control 2 to 4 h after drug administration was similar with both drugs (perindopril = 150 +/- 2/80 +/- 1; enalapril = 150 +/- 2/81 +/- 1). Twenty-four h after administration of perindopril blood pressure was lower than on enalapril (perindopril = 154 +/- 3/85 +/- 2; enalapril = 159 +/- 3/89 +/- 2). Enalapril, 2 to 4 h after administration, caused a greater decrease than placebo, whereas the change with perindopril did not differ from placebo. Twenty-four hours after receiving the active drug the blood pressure of subjects on perindopril did not differ from the peak effect when corrected for placebo and circadian variation, whereas the blood pressure on enalapril was higher. This study indicates that perindopril in the doses used has a longer duration of action than enalapril and is more suited to once daily use.

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PubMed1994

Role of the macula densa in renin synthesis and secretion.

The secretion and synthesis of renin were studied in mice by measuring aortic, right and left renal vein renin, renal renin, and mRNA for renin. The role of the macula densa was evaluated in a kidney made hydronephrotic by tying the ureter 6 weeks earlier. There was no net secretion of renin from the left hydronephrotic kidney even when the mice were placed in a high secretory state by sodium restriction or enalapril. Sodium restriction and enalapril increased renin content to a similar extent in the normal and hydronephrotic kidney. High sodium intake decreased renin content in the normal and hydronephrotic kidney and also decreased the enalapril-stimulated renin content. Changes in mRNA in the same direction to renal renin implied that this was due to increased synthesis. Thus secretion and synthesis of renin can be disassociated. The macula densa is important for renin secretion but not for the stimulation of synthesis.

Animals↗
PubMed1994

Effects of enalapril and Dup753 on renin synthesis in mice with one hydronephrotic kidney.

1. Renin synthesis and secretion were investigated in mice with one hydronephrotic kidney. 2. Enalapril and Dup753 stimulated renin synthesis to a similar extent in the hydronephrotic and normal kidney. 3. Hydronephrosis did not prevent an increase in renin mRNA caused by enalapril and Dup753. 4. The results therefore indicate that the macula densa does not appear to be crucial for renin synthesis in the kidney under the inhibition of angiotensin II. 5. Thus angiotensin II plays an important role controlling renin gene expression in both the normal and hydronephrotic kidneys.

Animals↗
PubMed1994

Role of uterine factors in the development of hypertension in SHR.

1. To examine whether the uterine environment plays a role in the development of hypertension in the spontaneously hypertensive rats (SHR), we have compared fetal weight, placental weight, and amniotic fluid composition of SHR and Wistar-Kyoto (WKY) rats after 20 days of gestation. 2. Pregnant SHR and WKY were anaesthetized at 20 days of gestation and the uterus and embryonic sacs removed. Fetal and placental weights were recorded and amniotic fluid collected for measurement of volume, osmolality and electrolyte composition. 3. No significant difference was found in litter size and placental weight between SHR and WKY. Total embryonic sac weight and fetal weight of SHR were significantly lower than WKY. Amniotic fluid volume, sodium concentration and osmolality of SHR were significantly higher than WKY, while amniotic fluid potassium concentration of SHR was significantly lower than WKY. 4. Thus, the SHR foetus was significantly underweight compared to the WKY and was bathed in amniotic fluid with a significantly higher osmolality and sodium concentration. As the mature foetus is known to drink amniotic fluid, it is hypothesized that the elevated Na/K ratio in SHR amniotic fluid may instigate or accelerate the hypertensive process.

Amniotic Fluid↗
PubMed1994

Clinical pharmacokinetics and pharmacodynamics of carvedilol.

Carvedilol is an arylethanolamine that is a racemic mixture of 2 enantiomers. The S-(-)-enantiomer has beta-adrenoceptor blocking activity, while the racemate also has alpha 1-receptor blocking activity due to the activity of the R-(+)-enantiomer. The drug is rapidly absorbed and undergoes extensive first-pass metabolism in the liver. It reaches a peak concentration 1 to 2 hours postdose and has an elimination half-life of about 4 to 7 hours. Absorption is delayed by food. The drug is highly lipophilic and is highly protein bound. The drug is metabolised by the liver, with some metabolites having biological activity. The pharmacokinetic profile is not altered in the elderly or in patients with renal disease. However, bioavailability of the oral medication is greatly increased in patients with liver disease. Carvedilol lowers blood pressure as a result of its beta-blocking and vasodilatory activity. The reduction in blood pressure is similar to that achieved with other antihypertensive drugs, and there are no adverse effects on renal or cerebral blood flow. Carvedilol has been used in small numbers of patients with cardiac failure. It reduces left ventricular hypertrophy and has no significant adverse metabolic effects.

Absorption↗
PubMed1994

[The regulation of renin synthesis].

Secretion and synthesis of renin are stimulated by the lack of angiotensin II and by a low sodium intake. They are inhibited by a high sodium intake, by denervation and by propranolol. A high sodium intake can overcome the effect of the lack of angiotensin II. A low sodium balance and the lack of angiotensin II did not have additive effects. The sodium effects did not appear to depend on the presence of the macula densa, the presence of angiotensin II, or the presence of the nerve supply. It was not evaluated whether baroreceptors may be important in allowing sodium effects to be processed, but in the experiments conducted there were no significant changes in blood pressure associated with alterations in sodium balance. Sodium balance has an important effect on synthesis and secretion. This effect does not appear to be mediated by the usual set of controls and raises questions as to the signal relating sodium balance to renin synthesis. Secretion does appear to depend on macula densa. The role of the macula densa appears to control the basal level of renin secretion and to permit the conversion and processing of prorenin to renin.

Angiotensin II↗
PubMed1994

[The kidney and hypertension].

The kidney and hypertension are critically linked. They appear to be linked particularly by the renin angiotensin system and the control of sodium balance. There are other mechanisms by which the kidney controls hypertension, but there are not as important as the above. In people with intrinsic renal disease hypertension increases the rate of deterioration and such hypertension should be treated energetically to prevent this deterioration. Long-standing chronic mild impairment of renal function leads to hypertension and vascular disease. This hypertension and vascular disease causes further deterioration of renal function, setting up a vicious cycle and an irreversible process unless measures are taken to interrupt the cycle.

Animals↗
PubMed1993

Transforming growth factor beta 1 and fibronectin messenger RNA in rat brain: responses to injury and cell-type localization.

Transforming growth factor-beta 1 rapidly increases in adult rat brain in response to experimental lesions. This study characterized the schedule of changes, regional distribution, and cellular localization of striatal transforming growth factor-beta 1 messenger RNA and fibronectin messenger RNA following partial striatal deafferentation by frontal cortex ablation. Frontal cortex ablation induced striatal transforming growth factor-beta 1 messenger RNA elevations that coincided temporally and overlapped anatomically with the course of degeneration of cortico-striatal afferent fibers. Within three days post-lesioning, transforming growth factor-beta 1 messenger RNA was localized at the cortical wound. By 10 days, the anatomical site of transforming growth factor-beta 1 messenger RNA expression shifted to the dorsal half of the deafferented striatum and co-localized with OX-42+ immunostained microglia-macrophage at the site of degenerating afferent terminals. Similarly, fibronectin messenger RNA also shifted from the cortical wound to the deafferented striatum by 10 days post-lesioning. Fibronectin messenger RNA was localized to glial fibrillary acidic protein+ immunostained astrocytes surrounding degenerating corticostriatal afferents. Infusion of transforming growth factor-beta 1 peptide elevated striatal and cortical fibronectin messenger RNA. These findings suggest that microglia-macrophage associated with degenerating afferent fibres can upregulate transforming growth factor-beta 1 messenger RNA and may influence fibronectin messenger RNA synthesis in reactive astrocytes. This study suggests that transforming growth factor-beta 1 has a role in controlling extracellular matrix synthesis following brain injury, which is analogous to that in peripheral wound healing.

Animals↗
PubMed1993

Somatostatin as a modulator of distal nephron water permeability.

1. Experiments in vivo and in vitro were performed in the rat to define the role of somatostatin in modulating the hydro-osmotic action of arginine vasopressin. 2. Somatostatin had a biphasic effect on basal collecting duct diffusional water permeability with 10(-9) mol/l somatostatin producing a 14% reduction in permeability, whereas concentrations of 10(-6) and 10(-5) mol/l significantly increased basal water permeability by 13% and 22%, respectively. Somatostatin (10(-9) mol/l) also inhibited the increase in water permeability produced by arginine vasopressin, although this inhibitory effect was reduced by a 10-fold increase in arginine vasopressin concentration (5 ng/ml). 3. In the anaesthetized water-diuretic rat, low dose somatostatin (60 micrograms/h) increased free water clearance by 23% (P < 0.01), whereas increasing the somatostatin concentration (600 micrograms/h) produced a transitory 40% fall in free water clearance (P < 0.01). As in the experiment in vitro, somatostatin inhibited the action of arginine vasopressin, although a very high concentration of arginine vasopressin (250 ng/h) partly overcame this effect. 4. Glomerular filtration rate and renal electrolyte excretion (sodium, potassium, calcium, magnesium) were not altered by somatostatin, although renal inorganic phosphate excretion was increased. The papillary solute gradient was unaltered by somatostatin. 5. These results suggest that circulating somatostatin may have a physiological role in modulating distal nephron water transport with a low concentration directly inhibiting and a high concentration facilitating water transport. There is also evidence of competitive binding between somatostatin and arginine vasopressin which antagonizes the hydro-osmotic action of arginine vasopressin.

Animals↗
PubMed1993

Effect of chronic portal hypertension on glutamine transport across rat intestinal brush border and basolateral membranes.

The present study examined the effect of chronic portal hypertension on the intestinal transport of glutamine across the brush border membrane (BBM) and the basolateral membrane (BLM) of the rat enterocyte. Chronic portal hypertension was induced by partial portal vein ligation, and the results were compared with results in sham-operated rats. Transport studies were performed by using established techniques of isolated membrane vesicles. In chronic portal hypertensive rats, transport of glutamine in BBM vesicles (BBMVs) exhibited significant inhibition in the maximal velocity (Vmax) of both the Na(+)-dependent and the Na(+)-independent transport processes, with no significant changes in the apparent Michaelis-Menten constant (Km) of the carrier systems. Similarly, chronic portal hypertension caused a significant decrease in the Vmax of the Na(+)-dependent and the Na(+)-independent uptake processes in intestinal BLM vesicles (BLMVs), with no change in the apparent Km of the uptake systems. These changes in glutamine transport in BBMVs and BLMVs brought about by chronic portal hypertension are not due to differences in the relative purity of the vesicular preparations between the portal hypertensive and sham-operated rats, because similar degrees of enrichment and depurification of marker enzyme activities were seen in final vesicular preparations in the two rat groups. These results demonstrate that in chronic portal hypertension, glutamine transport across both poles of the enterocyte is impaired. At both the BBM and BLM domains, the impairment appears to be mediated via a decrease in the number (and/or activity) of the glutamine carrier systems, with no changes in their affinity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Cell function and viability in glucose polymer peritoneal dialysis fluids.

OBJECTIVE: To investigate the biocompatibility profile of a new peritoneal dialysis fluid containing glucose polymer (GPF). DESIGN: Viability and function of peripheral neutrophils (PMN) from healthy donors and cultured human peritoneal mesothelial cells were assessed in vitro after exposure to dialysis fluids. Phagocytosis, leukotriene B4 synthesis, and respiratory burst activation were measured following stimulation with serum-treated zymosan (STZ) or opsonized Staphylococcus epidermidis (S. epidermidis). Bacterial growth in the fluids was also investigated. In vivo pH equilibration of GPF and subsequent respiratory burst activation following incubation in spent dialysate were studied. RESULTS: For all the host defense parameters measured, commercial dialysis fluids (Dianeal; 1.36% and 3.86% glucose) and GPF (pH 5.2) were significantly more inhibitory than the control buffer (pH 7.3). Mesothelial cell viability was reduced by all the fluids tested irrespective of pH. Glucose polymer fluid was significantly more inhibitory than Dianeal 1.36% for STZ phagocytosis and respiratory burst activation. In contrast, it was less suppressive than Dianeal 3.86% for LTB4 synthesis. For all parameters tested, except LTB4 generation, there was a marked effect of pH, with GPF being significantly more inhibitory at pH 5.2 than at pH 7.3. None of the fluids tested supported the growth of S. epidermidis, although the viable counts in GFP were significantly higher than in Dianeal. Fluid inhibition of PMN respiratory burst activation and cytotoxicity were reduced in a time-dependent manner following increasing dwell time in vivo. CONCLUSIONS: GPF does not appear to be significantly different from Dianeal as far as host defense parameters are concerned. However, the cell viability and bacterial survival data suggest some possibly negative aspects of this fluid formation.

Biocompatible Materials↗
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.

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