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Biomedical subjects

T Morgan

Publications and source records attributed to T Morgan.

At least 37 records · Page 2Linked to original sources
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.

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↗