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Biomedical subjects

S Anderson

Publications and source records attributed to S Anderson.

At least 487 records · Page 27Linked to original sources
PubMed1986

The role of intraglomerular pressure in the initiation and progression of renal disease.

Reduction in functioning nephron number leads to progressive renal disease. A haemodynamic basis for this process has been suggested by studies of partially nephrectomized rats. In this model compensatory hyperfiltration in the remnant nephrons due to increases in the glomerular capillary hydraulic pressure (-PGC) and plasma flow rate is associated with eventual glomerular sclerosis. Therapeutic attenuation of these haemodynamic adaptations protects against glomerular injury. One such therapy is angiotensin converting enzyme (ACE) inhibition, which lowers systemic blood pressure and -PGC and prevents sclerosis in rats with renal ablation, as well as in the hyperfiltering kidneys of normotensive rats with diabetes mellitus. Control of -PGC with ACE inhibitor is also protective even when therapy is delayed until systemic hypertension and glomerular injury are established. In contrast, the control of systemic hypertension but not -PGC affords no protection in remnant kidney rats. Thus, control of glomerular hypertension slows the progression of renal disease.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1986

Reversing glomerular hypertension stabilizes established glomerular injury in renal ablation.

Male Munich-Wistar rats were studied 18 weeks after 1 2/3 nephrectomy. One group received no therapy. A second group received the angiotensin converting enzyme (ACE) inhibitor enalapril, starting 1 week after ablation. Two additional groups received no therapy during the first 8 weeks, and then received ACE inhibitor or a low (12%) protein diet. Early ACE inhibitor therapy resulted in control of systemic and glomerular hypertension (HTN), and a striking limitation of proteinuria and glomerular sclerosis. During the first 8 weeks untreated rats developed severe systemic HTN and increasing proteinuria. After 8 weeks proteinuria increased further in untreated rats, and widespread sclerosis resulted. Late ACE inhibition reversed systemic HTN. Both late ACE inhibition and late protein restriction reversed glomerular HTN and prevented further increases in proteinuria and sclerosis. Thus, control of glomerular HTN can stabilize renal injury even when therapy is delayed until hypertension and glomerular injury are established.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1986

Prevention of glomerular capillary hypertension in experimental diabetes mellitus obviates functional and structural glomerular injury.

Streptozotocin-diabetic rats kept moderately hyperglycaemic by daily injections of ultralente insulin for 4-6 weeks (group DM) demonstrated a higher glomerular transcapillary hydraulic pressure gradient (delta P), glomerular plasma flow rate and single-nephron glomerular filtration rate (GFR) than was observed in age- and weight-matched non-diabetic controls (group C). This rise in delta P was prevented by therapy with the angiotensin I converting enzyme inhibitor enalapril (15 mg/l drinking water, group DM + E) even though glomerular hyperperfusion and hyperfiltration persisted. Fourteen months after induction of diabetes, animals in group DM displayed high levels of albuminuria and an increased incidence of focal glomerular sclerosis; treatment with enalapril maintained these parameters at levels which did not differ from those observed in group C. We conclude that prevention of glomerular capillary hypertension with enalapril therapy obviates functional and structural glomerular injury in experimental diabetes mellitus.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1986

Antihypertensive therapy must control glomerular hypertension to limit glomerular injury.

Male Munich-Wistar rats wer subjected to 1 2/3 nephrectomy. One group received no therapy. A second group received the angiotensin converting enzyme (ACE) inhibitor enalapril. A third group received triple therapy (TRX) with reserpine, hydralazine and hydrochlorothiazide. Half of the rats underwent micropuncture study 4 weeks after nephrectomy. Untreated rats exhibited high systemic blood pressure (SBP) and single-nephron hyperfiltration due to high values for the mean glomerular capillary hydraulic pressure (-PGC) and glomerular capillary plasma flow rate (QA). The ACE inhibitor therapy controlled both SBP and -PGC. In contrast, TRX normalized SBP but failed to lower -PGC. After 12 weeks untreated rats demonstrated systemic hypertension, progressive proteinuria and extensive glomerular sclerosis. The ACE inhibitor dramatically limited proteinuria and sclerosis. Despite equivalent SBP control with TRX, failure to control -PGC resulted in proteinuria and sclerosis comparable with the untreated rats. Thus unless -PGC is controlled, SBP control may be insufficient to prevent renal injury.

Animals↗
PubMed1986

Alterations in the DNA metabolism of MCa-11 mouse mammary tumor cells grown in vivo and in vitro.

Mouse mammary carcinoma (MCa-11) cells were grown in vitro in exponential, plateau-fed, and starved monolayer cultures or as 100-, 250-, and 500-microns tissue culture spheroids, and in vivo as small (4-mm diameter) and large (12-mm diameter) tumors. In all of these forms, the growth rates of the MCa-11 cells were found to decrease after an initial rapid proliferation of a relatively small number of cells. The DNA distributions of these cells during different rates of growth in vitro and in vivo, as well as the proportion and intensity of labeling of the S-phase cells with [3H]thymidine and [3H]deoxyuridine, were measured by flow and absorption cytometry. We found that significant numbers of MCa-11 cells remained in S phase, even after the growth rates in vivo and in vitro had slowed. However, as growth rates decreased, the intensity and proportion of S-phase cells labeled with exogenous DNA precursors decreased. We conclude that progressive alterations, including possible slowing and cessation, of replicative DNA synthesis occur in S-phase tumor cells as the metabolic constraints on tumor growth are increased.

Animals↗
PubMed1986

VA Cooperative Study on Alcoholic Hepatitis. IV. The significance of clinically mild alcoholic hepatitis--describing the population with minimal hyperbilirubinemia.

As part of a large multicenter Veterans Administration Cooperative Study of Alcoholic Hepatitis, 89 patients with clinically mild biopsy-proven disease were followed for at least 30 months. Although clinical and laboratory abnormalities were minimal, cirrhosis was present in 38%, and mortality was 22% at 30 months. Clinical features suggesting more advanced disease (i.e., ascites and encephalopathy) and laboratory parameters for the diagnosis of alcoholic hepatitis and/or cirrhosis were imprecise and frequently misleading. The histologic diagnosis of cirrhosis correlated best with changes in immunoglobulin A, prothrombin time, and SGOT/SGPT. However, by using logistic discriminant analysis on 26 commonly available laboratory tests to diagnose cirrhosis, only a 72% sensitivity and 88% specificity could be obtained. Mortality in the patients with cirrhosis (10/34) was significantly higher at 1 and 2 yr compared with patients without cirrhosis (10/55, p less than 0.01). The high mortality in noncirrhotics may have resulted from progression to cirrhosis subsequent to the initial evaluation. Thus, liver biopsy in this population with minimal disease seems necessary to establish both an accurate diagnosis and the reversibility of the disease.

Ascites↗
PubMed1985

Converting enzyme inhibitor therapy limits progressive glomerular injury in rats with renal insufficiency.

Sustained increases in glomerular capillary pressure and flow accompany systemic hypertension in rats that have undergone extensive ablation of the renal mass. These intrarenal hemodynamic changes are, in turn, associated with the progressive development of proteinuria and glomerular sclerosis, leading ultimately to failure of remnant nephron units. The efficacy of antihypertensive therapy with enalapril was evaluated in this animal model of chronic renal insufficiency. A dose of enalapril sufficient to prevent systemic hypertension normalized the glomerular capillary pressure without reducing the glomerular filtration rate in the remnant kidney. Maintenance of normal capillary pressure markedly reduced the development of proteinuria and sclerotic lesions in remnant glomeruli. These results suggest that antihypertensive therapy directed at reducing the glomerular capillary pressure could retard the progressive loss of renal function in patients whose functional renal mass has been reduced by disease.

Animals↗
PubMed1985

RO13-6438, a new inotrope-vasodilator: systemic and coronary hemodynamic effects in congestive heart failure.

Systemic and coronary hemodynamics and transmyocardial norepinephrine release were determined before and after oral administration of RO13-6438, a new inotrope-vasodilator agent, in 12 patients with severe chronic heart failure unresponsive to conventional and vasodilator therapy. Improvement in left ventricular (LV) function was evident from a marked increase in cardiac index (from 2.09 +/- 0.45 to 3.30 +/- 0.73 liters/min/m2, p less than 0.01), stroke volume index (from 23 +/- 7 to 36 +/- 11 ml/m2, p less than 0.01), and stroke work index (from 23 +/- 11 to 36 +/- 14 g-m/m2, p less than 0.01), and concomitant fall in pulmonary capillary wedge pressure (from 26 +/- 7 to 16 +/- 8 mm Hg, p less than 0.01). Myocardial oxygen consumption did not change significantly (from 15.3 +/- 6.8 to 14.9 +/- 6.8 ml/min), but the ratio of minute work/myocardial oxygen consumption, an index of LV efficiency, increased significantly (p less than 0.05). Although average coronary sinus flow did not change, coronary sinus oxygen increased (from 3.2 +/- 0.8 to 4.2 +/- 1.5 vol%, p less than 0.05), and arterial-coronary sinus oxygen difference decreased (from 11.8 +/- 2.1 to 10.4 +/- 1.9 vol%, p less than 0.05), suggesting a primary vasodilating effect of RO13-6438 on the coronary vascular bed. Net transmyocardial norepinephrine release did not change despite the marked hemodynamic improvement. These findings suggest that RO13-6438 has the potential to cause marked improvement in LV function and LV efficiency in patients with severe, refractory congestive heart failure.

Adult↗
PubMed1985

Lactate provocation of panic attacks. II. Biochemical and physiological findings.

Thirty-one of 43 patients with panic disorder or agoraphobia with panic attacks and none of 20 normal controls panicked in response to infusions of sodium lactate. Before receiving lactate, patients showed higher heart rates than controls and also signs of hyperventilation. During lactate infusion, patients who did not panic, nevertheless, developed higher lactate and pyruvate levels and greater ionized calcium and pH changes than controls. Lactate-induced panic attacks were regularly accompanied by biological changes consistent with hyperventilation and central noradrenergic activation and irregularly by elevation of plasma norepinephrine and cortisol levels. Panic attacks were not associated with changes in epinephrine or calcium levels or pH. Baseline arousal increased the likelihood of panic during lactate infusion. It is hypothesized that lactate-induced panic primarily involves central noradrenergic discharge with inconsistent peripheral manifestations.

Adult↗
PubMed1985

Embryonic development of the mouse mutant pupoid foetus (pf/pf).

The pupoid foetus mutation in the mouse is a recessive lethal mutation causing death of homozygous (pf/pf) embryos immediately after birth. From 11.3 days gestation onwards, these embryos are characterised externally by the development of a tail twist, followed by apparent stunting of the limbs and tail (when compared with the development of these structures in normal embryos), lack of digits, distortion of facial features, and possession of a smooth, mottled skin. Embryos ranging in age from 11.3 days gestation to full term have been examined using light microscopy and scanning and transmission electron microscopy. The skeletal structure and internal organs of the embryo are normal, but abnormalities occur in the external epidermis, the dermis, and the peripheral sensory nerves. Development of the palate and the eyes are affected by the behaviour of these tissues. The epidermis undergoes hypertrophy and fails to differentiate, and, on the basis of morphological criteria and theoretical considerations, it is suggested that the pf gene is activated in the epidermis during the keratinization pathway, preventing differentiation and altering the cell surface characteristics of the cells. Other abnormalities are explained in terms of interactions with the epidermis. This mutant is compared with other similar mutants.

Animals↗
PubMed1985

Efficacy and safety of esmolol vs propranolol in the treatment of supraventricular tachyarrhythmias: a multicenter double-blind clinical trial.

The efficacy and safety of intravenous esmolol infusion was compared to that of intravenous propranolol injection in patients with supraventricular tachyarrhythmias (SVT) in a multicenter double-blind parallel study. A total of 127 patients were randomized to either the esmolol (n = 64) or propranolol (n = 63) group. Therapeutic response was achieved in 72% of esmolol and 69% of propranolol patients (p = NS). The average dose of esmolol in responders was 115 +/- 11 micrograms/kg/min. Therapeutic response was sustained in the 4-hour maintenance period in 67% of esmolol and 58% of propranolol patients (p = NS). Rate of conversion to normal sinus rhythm was similar in the two treatment groups. After discontinuation, rapid recovery from beta blockade (decrease in heart rate reduction) was observed in esmolol patients (within 10 minutes) compared to propranolol patients (no change in heart rate up to 4.3 hours). The principal adverse effect was hypotension, reported in 23 esmolol (asymptomatic in 19) and four propranolol (asymptomatic in three) patients. In the majority of esmolol patients, hypotension resolved quickly (within 30 minutes) after esmolol was discontinued. It was concluded that esmolol was comparable in efficacy and safety to propranolol in the treatment of patients with SVT. Unlike propranolol, because of the short half-life of esmolol, rapid control of beta blockade is possible with esmolol in clinical conditions when required.

Acute Disease↗
PubMed1985

Effects of ibuprofen, naproxen, and sulindac on prostaglandins in men.

In contrast to other nonsteroidal anti-inflammatory drugs (NSAIDs), sulindac has been reported to inhibit systemic prostaglandins (PGs) while not affecting renal PGs. We studied 11 normal volunteers who received placebo, ibuprofen, naproxen, or sulindac in a randomized, double-blind fashion. After control periods assessing the effect of the NSAIDs alone, 40 mg of furosemide were administered. Overall, each of the drugs appeared similar. Renal function, plasma renin activity (PRA) and urinary PGs were not affected during control collections, while all three NSAIDs decreased thromboxane B2 (TxB2). After furosemide, all NSAIDs decreased fractional excretions of Na+ and Cl-, PRA, and TxB2 by equivalent degrees (P less than 0.05). Sulindac and ibuprofen decreased urinary PGE2 (P less than 0.05) while naproxen had no effect. None of these drugs affected the excretion of furosemide, but all decreased the pharmacodynamics of response to furosemide. In conclusion, the effects of these NSAIDs depended on the conditions of the study. In the basal state there were no renal effects but all decreased the renal response to furosemide.

Adult↗
PubMed1985

Comparison of the cognitive effects of premedication with hyoscine and atropine.

An investigation was carried out comparing the nature and duration of the cognitive effects of atropine and hyoscine. Thirty patients undergoing a minor gynaecological operation were randomly assigned to one of three groups to receive hyoscine, atropine or placebo as premedication. A battery of psychological tests was administered before premedication, 30 min after premedication, and 1 and 3 h following operation. The tests included orientation questions, simple tasks such as reciting the alphabet, memory tests, a reaction-time test and two tests of visuo-motor co-ordination. The results showed that hyoscine had detrimental effects on memory and on motor tasks compared with placebo, while atropine did not. In addition, the effects on motor performance had not disappeared 3 h after operation.

Adult↗
PubMed1985

Differences in response of black hypertensives to alpha vs. beta adrenergic antagonists: preliminary findings.

We tested our clinical impression that black hypertensives in our clinic population responded better to alpha-adrenergic blocking agents (clonidine and prazosin) than to beta-adrenergic blockers (atenolol, nadolol and propranolol). Compared to no effect from eight weeks of therapy with beta-blockers, clonidine significantly decreased erect mean arterial pressure (MAP) when assessed weekly for four weeks (p = 0.027 to 0.046). However, the decrease in supine MAP was not significant. The effects of prazosin were more modest. Supine MAP was significantly less than with beta-blockade (p = 0.032) at two weeks but not at four weeks and decrements in erect MAP were not significant. In this preliminary study, black hypertensives appeared to be more responsive to alpha-adrenergic antagonists than to beta-blockers, with clonidine more effective than prazosin. Elucidation of possible mechanisms of the difference and of its clinical importance warrant further study.

Adrenergic alpha-Antagonists↗