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Biomedical subjects

R G Fassett

Publications and source records attributed to R G Fassett.

15 recordsLinked to original sources
PubMed1998

A critique of the overfill hypothesis of sodium and water retention in the nephrotic syndrome.

Recent reviews have claimed that the majority of patients with the nephrotic syndrome have plasma volume expansion (that is, they are overfilled). Here we attempt to re-establish balance to the debate on body fluid volume status in nephrotic patients by: (a) discussing the conflicting literature on plasma volume measurements in the nephrotic syndrome; (b) providing alternate explanations for data purporting to support an overfill hypothesis in the nephrotic syndrome; (c) emphasizing secondary neurohumoral responses that support underfilling at least as frequently as overfilling; and (d) emphasizing the clinical importance of fluid assessment in the individual patient with the nephrotic syndrome particularly in relation to diuretic use.

Aldosterone↗
PubMed1998

Pathophysiology of renal fluid retention.

Central to a unifying hypothesis of body fluid regulation is maintenance of arterial circulatory integrity. This may be disturbed by arterial underfilling, either from reduction in cardiac output or by peripheral arterial vasodilation. In cardiac failure (CF), cardiac output falls and the nonosmotic release of arginine vasopressin (AVP) and expression of AVP mRNA in the hypothalamus are stimulated. V2 AVP receptor antagonists correct the impaired water excretion in rats with low-output CF, increase solute free water clearance, correct the hyponatremia in congestive CF patients, and normalize urinary concentrations of the aquaporin-2 (AQP-2) water channels. In conditions associated with peripheral vasodilation, such as cirrhosis, nonosmotic release of AVP also occurs, and AQP-2 gene expression in the rat kidney is up-regulated. In cirrhosis, nitric oxide-mediated vasodilation occurs early prior to water retention. V2 antagonists reverse the latter. In normal pregnancy, plasma AVP is relatively high for the degree of hypoosmolality. Pregnant rats up-regulate AQP-2 in the renal papilla, an effect reversed by V2 receptor antagonists. This supports the hypothesis that AVP is an important mediator of renal water retention in pregnancy. In summary, AVP-mediated water retention through collecting duct AQP-2 water channels is important in both low-output CF and high-output states such as cirrhosis and pregnancy. V2 receptor antagonists reverse the water retention and down-regulate AQP-2 water channels.

Animals↗
PubMed1998

Pathogenesis of sodium and water retention in cardiac failure.

The pathophysiology of sodium and water retention in heart failure is discussed in the context of a unifying hypothesis of body fluid volume regulation. Critical to this hypothesis is the maintenance of arterial circulatory integrity, which can be disturbed by either a reduction in cardiac output or a fall in systemic vascular resistance secondary to arterial vasodilatation, as seen in high output heart failure. The filling of the arterial circulation is sensed by receptors in the left ventricle, carotid artery, aortic arch and renal afferent arteriole. Effector mechanisms involve non-osmotic vasopressin synthesis and release, the renin-angiotensin-aldosterone system and the sympathetic nervous system. In low output heart failure non-peptide selective orally active vasopressin V2-receptor antagonists correct the hyponatremia, hypoosmolality, and water retention and decrease urinary aquaporin-2 water channels, supporting the role of vasopressin in the water retention seen in heart failure. In advanced heart failure aldosterone escape does not occur because of diminished distal delivery of sodium which also contributes to the resistance to atrial natriuretic peptide seen in heart failure. In high output cardiac failure arterial underfilling associated with arterial vasodilation stimulates activation of neurohumoral systems. Tailored specific selective inhibition of these neurohumoral systems, perhaps in combination, may enable more effective treatment of cardiac failure.

Heart Failure↗
PubMed1989

Mesangiocapillary glomerulonephritis type II (dense-deposit disease): clinical features of progressive disease.

Twenty-seven patients presenting to the Royal Melbourne Hospital between 1968 and 1988 with mesangiocapillary glomerulonephritis type II with intramembranous dense deposits (dense-deposit disease, DDD) are analyzed. Patients were divided into two groups on the basis of whether renal function deteriorated (14 patients) or remained stable (13 patients). At presentation or during the course of the disease, heavy proteinuria, macroscopic hematuria, and high quantitative urinary red cell or white cell counts characterized patients with progressive disease. Patients with crescents on their initial renal biopsy or with large numbers of polymorphs in glomerular capillaries corresponding with sterile pyuria were more likely to have deterioration of renal function. The average time from onset of symptoms to development of end-stage renal disease was over 16 years. The patient's clinical course could not be anticipated by serum complement profiles, the presence of C3 nephritic factor, or partial lipodystrophy. Pregnancy did not affect the course of the disease. Six patients underwent renal transplantation and the disease recurred on renal biopsy in four. However, only two individuals lost renal allografts due to recurrent DDD.

Adolescent↗
PubMed1985

Left ventricular function in uremia: echocardiographic and radionuclide assessment in patients on maintenance hemodialysis.

Echocardiography and radionuclide ventriculography were performed in 37 uremic patients on maintenance hemodialysis with no apparent coronary artery disease, pericardial effusion, valvular heart disease or heart failure. These non-invasive studies were performed during the interdialytic period (about 18 hours after a dialysis). Sixty-two percent of our patients had abnormal left ventricular function with one or more abnormal echocardiographic parameters. The significant abnormalities were enlargement of the left ventricular cavity, a reduction of myocardial contractility, and thickening of the left ventricular posterior wall. Similar findings were found in 10 undialyzed uremic patients. Measurement of cardiac index and ejection fraction were found to be inadequate for a full assessment of left ventricular function and other parameters such as the mean velocity of circumferential fiber shortening and mean normalized posterior wall velocity should be included. There is a significant number of hemodialysis patients (7/37) with congestive cardiomyopathic features on the echocardiogram. Their clinical features are no different from the other patients in this study, except they have a significantly higher prevalence of uremic hyperparathyroidism. Our findings support that the existence of a specific uremic cardiomyopathy and uremic hyperparathyroidism may play an important role in the pathogenesis.

Adult↗
PubMed1984

Changes in bone histoquantitative parameters and histochemical staining reactions for aluminium in a group of patients with chronic renal failure following a reduction in the aluminium concentration of the haemodialysis fluid.

Bone biopsies from a group of 16 patients in chronic renal failure treated by intermittent haemodialysis were available for histoquantitative and histochemical assessment before and after the introduction of reverse osmosis treatment of the dialysis fluid. This treatment reduced the aluminium concentration of the fluid from 1.15 mg/l to less than 0.06 mg/l. After the changeover there was an increase in the extent of calcification fronts. Overall, there was a decrease in the histochemical staining reactions for aluminium, although a few cases showed increased reactions. A large percentage of cases showing decreased reactions also had decreased osteoid volumes. It is concluded that reduction of the concentration of aluminium in the dialysis fluid is associated with an improvement in mineralisation state, and this is further evidence of the importance of minimising the aluminium burden of patients with chronic renal failure.

Aluminum↗
PubMed1983

Bone histoquantitative findings and histochemical staining reactions for aluminium in chronic renal failure patients treated with haemodialysis fluids containing high and low concentrations of aluminium.

A total of 112 undecalcified bone biopsies from 67 patients under treatment for chronic renal failure by maintenance haemodialysis was available for retrospective study. The patients were divided into three groups. Group I (15 cases) had been dialysed for the majority of the time in their own homes with a fluid containing a low concentration of aluminium. Group II (28 cases) had been dialysed exclusively in hospital (prior to 1978) with a fluid containing a high concentration of aluminium and group III (24 cases) had been treated exclusively in hospital (from 1978 onwards) with a fluid of low aluminium concentration. The tissues from these groups were subjected to histoquantitative assessment and stained by a histochemical technique to demonstrate aluminium salt. In group II, 71.4% of cases showed positive aluminium staining reactions (at the osteoid/mineralised tissue interface) compared to 26.6% in group I and 37.5% in group III. Staining reactions were also more extensive in group II cases. The osteoid volume was significantly increased and the calcification front extents significantly decreased in group II compared to both groups I and III. A comparison of histochemically positive with negative cases in each group showed a significantly increased osteoid volume and significantly decreased calcification fronts in the positive cases. It was, therefore, concluded that haemodialysis against a fluid containing a high concentration of aluminium leads to intraosseous aluminium accumulation of greater degree in a larger number of patients than a fluid with low aluminium content and that there is an accompanying osteomalacia manifest by an increase in osteoid volume together with diminution in the extent of the calcification fronts.

Adult↗
PubMed1983

Scanning electron microscopy of glomerular and non glomerular red blood cells.

Phase contrast microscopic examination of the urine has been recently shown to be of value in predicting whether hematuria is due to glomerulonephritis or lesions of the lower urinary tract. Glomerular red cells show variations in size and shape and have distorted surfaces. Non glomerular red cells are uniform in size and shape and have smooth surfaces. Scanning electron microscopy was performed on urine sediment containing either glomerular or non glomerular red cells to better define their surface characteristics. Glomerular red cells exhibited a variety of forms, most cells having lumpy projections from the surface, some showing fragmentation of the membrane and others showing gross distortion. In contrast non glomerular red cells show smooth surfaces and usually maintain the normal biconcave disc shape of peripheral red blood cells. Scanning electron microscopy can better define surface structural abnormalities of urinary glomerular and non glomerular red blood cells.

Analgesics↗
PubMed1982

Urinary red-cell morphology during exercise.

Midstream urine samples were examined by phase-contrast microscopy before and immediately after 48 subjects participated in a long-distance run. Minor abnormalities were found in six samples before exercise. Eighteen subjects developed proteinuria and five haematuria on dipstick testing after exercise. Forty-four subjects had increased urinary red-cell counts after exercise; of these, 33 had counts above the normal range (800/ml). In all subjects urinary red cells were dysmorphic both before and after exercise, indicating a glomerular source. Ten subjects developed red-cell casts and 42 showed an increase in hyaline and hyaline-granular casts after exercise. There were modest increases in urinary white-cell counts in 35 subjects but little change in urine pH or osmolality with exercise. This study confirms that urinary red-cell counts commonly increase appreciably after exercise. The dysmorphic appearance of the red cells together with the presence of red-cell casts indicates a glomerular source for this common form of exercise haematuria.

Adolescent↗
PubMed1982

Detection of glomerular bleeding by phase-contrast microscopy.

Midstream urine specimens from 303 consecutive patients with haematuria were examined with phase-contrast microscopy to determine whether the source of the haematuria could be predicted on the basis of urinary red-cell morphology. In 253 patients a definite diagnosis was made but the data for the other 50 were inadequate to allow a definite diagnosis. With phase-contrast microscopy the origin of haematuria was considered to be glomerular in 120 patients (115 had proven glomerulonephritis and 5 had lesions of the lower urinary tract) and non-glomerular in 105 patients (100 had lesions of the lower urinary tract and 5 had proven glomerulonephritis). A mixed picture of glomerular and non-glomerular red cells was seen in 28 patients, most commonly in association with IgA nephropathy and renal calculi. The assessment of urinary red-cell morphology by means of phase-contrast microscopy can add importantly to clinical information and, together with the presence of red-cell casts and protein in the urine, can help the clinician decide on initial investigations in patients with haematuria.

Erythrocytes↗
PubMed1982

Effect of long-term cimetidine treatment on left ventricular function in haemodialysis patients with active hyperparathyroidism.

1 The effect of long-term oral cimetidine on left ventricular function was evaluated in chronic haemodialysis patients with active hyperparathyroidism. 2 Radionuclide ventriculography (seven patients) and echocardiography (five patients) revealed a significant increase in ejection fraction and mean velocity of circumferential fibre shortening six months after treatment. 3 The improved cardiac performance was associated with improvement of bone histology. C-terminal parathyroid hormone, serum calcium, and mean arterial pressure changed little after treatment. 4 The improved cardiac performance is thought to be related to the suppression of uraemic hyperparathyroidism by cimetidine. 5 The present study suggests that uraemic hyperparathyroidism may play an important role in "uraemic cardiomyopathy".

Cimetidine↗
PubMed1982

Bone disease in analgesic nephropathy.

Clinical, biochemical, radiological and bone biopsy findings were studied in 15 patients with end stage renal disease due to analgesic nephropathy and compared with data from age and sex matched controls who had end stage renal disease from other causes. Patients with analgesic nephropathy had significantly higher osteoid volume (P less than 0.04), reduced calcification fronts (P less than 0.001) and lower percentage mineralization (P less than 0.04). Serum alkaline phosphatase was significantly higher in the analgesic group (P less than 0.005). It is concluded that osteomalacia is more common and severe in the group of patients with end stage renal disease due to analgesic nephropathy. There was no relationship between osteomalacia and the duration of renal failure, acidosis, aluminium deposition or other serum biochemical abnormalities.

Alkaline Phosphatase↗
PubMedDate not supplied

Vasopressin release, water channels, and vasopressin antagonism in cardiac failure, cirrhosis, and pregnancy.

Vasopressin (AVP) is released in response to both osmotic and nonosmotic stimuli. Nonosmotic-stimulated AVP release occurs in cardiac failure, cirrhosis, and pregnancy in response to alterations in arterial circulatory integrity. Cardiac failure in rats is associated with increased plasma AVP and hypothalamic AVP mRNA, and in humans, it is associated with cardiac failure. Plasma AVP concentrations are elevated when measured with a sensitive radioimmunoassay. Urinary concentrations of AVP-responsive aquaporin-2 water channels are also elevated in cardiac failure. V2 receptor antagonists correct the impaired solute-free water excretion seen in rats with low-output cardiac failure and reverse the upregulation of renal aquaporin-2 water channels. Orally active non-peptide-selective V2 receptor antagonists administered to patients with congestive cardiac failure decrease urinary concentrations of aquaporin-2, increase solute-free water clearance, and correct the hyponatremia. Cirrhosis of the liver results in splanchnic arterial vasodilation and increased vascular capacity, most likely secondary to increased nitric oxide production. This relative underfilling of the arterial circulation stimulates nonosmotic AVP release with resultant water retention. Aquaporin-2 gene expression is upregulated in the kidneys of rats with cirrhosis of the liver. AVP-2 receptor antagonists administered to animals with cirrhosis reverse the water retention. Human studies using orally active, non-peptide-selective V2 receptor antagonists in patients with cirrhosis are currently underway. Pregnancy is another state of nitric oxide-mediated arterial vasodilation that is associated with plasma AVP concentrations that are relatively high for the degree of hypoosmolality. Upregulation of the water channel aquaporin-2 in the renal papillae of pregnant rats has also been demonstrated, and this effect is reversed by administration of a V2 receptor antagonist.

Animals↗