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Biomedical subjects

M Kaye

Publications and source records attributed to M Kaye.

At least 55 records · Page 3Linked to original sources

When is it an osteoclast?

Using acid phosphatase as a marker, osteoclasts were examined from single sections of undemineralised iliac crest biopsies from patients with renal failure and from normal controls. Eighty one per cent of the cells from controls and 56% of the cells from patients with renal failure appeared to be non-nucleated or mononucleated. Serial sections showed, however, that 73% of the control cells were actually multinucleated as were 91% of the patients' cells. Howship's lacunae were present in similar proportions in the controls whether the cells were multinucleated or not, suggesting that they should all be classed as osteoclasts. More multinucleated cells and lacunae were present in the patients with renal failure. It is concluded that all acid phosphatase cells adjacent to bone are osteoclasts and that the presence of more lacunae and multinucleated cells in renal failure is compatible with enhanced cellular resorption.

Bone Resorption

Hemodialysis neutropenia and dialyzer reuse: role of the cleansing agent.

As part of a study to evaluate the safety and efficacy of dialyzer reuse, a comparative study of two methods of dialyzer reprocessing, manual and automated, was conducted. Five stable end-stage renal disease patients on center hemodialysis were evaluated as to hematological and metabolic parameters throughout two series of three consecutive dialyses using first new and then reused dialyzers reprocessed according to each of the two methods. New dialyzers and reused dialyzers following automated reprocessing always induced a profound fall in circulating neutrophil counts shortly after the start of dialysis. Hemodialysis neutropenia was not observed, however, with reused dialyzers reprocessed manually unless the concentration of sodium hypochlorite (bleach) employed was made equal to that required in automated reprocessing by being raised from 1.0 to 4.3%. It would be reasonable to conclude from these results that among the various differences between the two dialyzer reprocessing methods, restoration of the original level of biocompatibility of the reused dialyzer's membrane is related to the concentration of the cleansing agent.

Adult

Prolonged dialyzer reuse.

Clearance of urea, creatinine, phosphate and B12 in dialyzers reused up to 30 times were unchanged from the initial values. Residual formalin values were within acceptable levels and in several thousand dialyses no untoward reactions of any sort attributable to reuse were encountered. Neutropenia was constantly present with dialyzers prepared by automated reuse.

Creatinine

Bone marrow aluminium storage in renal failure.

Using the staining method for aluminium with the ammonium salt of aurine tricarboxylic acid, aluminon, 18 patients with end stage renal disease gave positive reactions in iliac crest bone biopsies and 11 of these had positive staining in the bone marrow. In one the marrow was positive and the bone negative. The marrow reaction is putatively regarded as caused by aluminium storage in unidentified cells, possibly of the macrophage system which are strongly fluorescent when examined after prior tetracycline labelling. Marrow storage should be considered when assessing the bone aluminium burden.

Aluminum

Hypophosphatemia-induced hypercalcemia during acute renal failure.

A case of hypophosphatemia-induced hypercalcemia during post-traumatic acute renal failure is described. Proposed causes for the hypophosphatemia include changes in tissue distribution of phosphate associated with hyperalimentation and phosphate losses during hemodialysis. In the absence of hyperparathyroidism the hypercalcemia as well as changes in osteoclast morphology found on bone biopsy are ascribed to a direct effect of hypophosphatemia on bone.

Acute Kidney Injury

Auto-immunity in patients with end-stage renal disease maintained on hemodialysis and continuous ambulatory peritoneal dialysis.

Auto-immunity as assessed by rheumatoid factor, anti-DNA, antinuclear, smooth muscle and mitochondrial circulating antibodies was evaluated in 2 groups of 25 patients with end-stage renal disease (ESRD) being maintained either on hemodialysis or on continuous ambulatory peritoneal dialysis (CAPD). In the group of hemodialysis patients, 56% showed at least one serological abnormality on pre-dialysis samples: anti-DNA (8%), antinuclear (8%), smooth muscle (40%) and mitochondrial (4%) antibodies; on post-dialysis samples, 64% of the patients demonstrated abnormalities due to a rise in the incidence of anti-DNA antibodies from 8-24%. In the group of CAPD patients, 44% showed at least one serological abnormality: rheumatoid factor (4%), anti-DNA (16%), antinuclear (24%) and smooth muscle (4%) antibodies. These serological changes were generally scattered randomly within both groups. In the hemodialysis group, 2 abnormalities were present in 1 patient pre-dialysis and in 3 post-dialysis. One CAPD patient had 2 abnormalities. No correlation of these findings with age, sex, duration of dialysis and nature of renal disease could be found. The results are discussed in the context of possible abnormal antigenic stimulation in ESRD patients maintained on either form of dialysis.

Adult

Oral aluminum toxicity in a non-dialyzed patient with renal failure.

A patient is described with chronic renal failure who developed toxic levels of aluminum in bone after one year of oral aluminum hydroxide ingestion with a total dose of 711 grams. Caution in the use of oral aluminum compounds is recommended in patients with renal failure.

Administration, Oral

Action of phosphorus on calcium release in isolated perfused rat tails.

A bone perfusion system using isolated rat tails was developed to study the action of inorganic phosphorus (Pi) on calcium (Ca) release in bone. Rats were either pre-labelled with 45Ca to study calcium removal from bone or 45Ca was added to the perfusate to study Ca deposition into bone. When perfusate Pi was increased from 3.5 to 5.25 mg/dl, a marked inhibition of 45Ca release was demonstrated. 85Sr microspheres, used to demonstrate differences in the flow of perfusate between bone and soft tissue, showed that the Pi effect was not due to alterations in perfusate flow to bone. Increasing the perfusate Pi concentration from 3.5 to 7 mg/dl did not increase 45Ca deposition into bone, nor did it affect baseline or PTH-stimulated cyclic AMP production. The Pi effect was inhibited by reducing the perfusate temperature to 4 degrees C, by using an anerobic perfusate, adding iodoacetate to the perfusate, and finally, by pre-treating the rats with actinomycin D prior to the experiment. Thus, in this model an increase in the Pi concentration of the perfusate inhibits Ca release from bone but does not increase Ca uptake by bone. The inhibitory effect appears to be dependent on normal cell metabolism.

Animals

Evidence that resistance to the calcemic action of parathyroid hormone in rats with acute uremia is caused by phosphate retention.

An animal model was developed to examine the cause of resistance to the calcemic action of PTH in renal failure. Thyroparathyroidectomized (TPTX) rats were repeatedly reinfused with their excreted urine, over a 5-hour period, to produce an acute uremic animal with normal kidneys. Nonuremic controls were infused with equivalent volumes of a simple electrolyte solution. Using this model, we have demonstrated impaired calcemic response to PTH (Lilly Parathyroid Extract, 80 U/100 g) in urine-infused rats compared with electrolyte-infused rats. The final plasma calcium concentrations were 12.0 +/- 0.3 and 14.9 +/- 0.3 mg/dl, respectively (P less than 0.001). The cause of this impaired calcemic response was investigated by reinfusing rats with their own urine that had been pretreated with either activated charcoal or zirconium oxide in two different anionic forms, or urine that had been ultrafiltrated through an Amicon membrane of which the stated molecular-weight cut-off of the smallest pore-size membrane was 500 daltons. It was found that charcoal and ultrafiltration techniques had no effect, whereas the zirconium oxide treatment completely corrected the impaired calcemic response and returned the plasma phosphorus to a concentration similar to that in nonuremic controls. This can be explained by the fact that the principal effect of zirconium oxide on urine is to remove inorganic phosphate. Other groups of TPTX rats given PTH extract were infused with an electrolyte solution containing varying amounts of phosphate up to a maximum similar to the amount that a urine-infused rat would receive. A highly significant inverse relationship was found between the dose of phosphate infused with the electrolyte solution and the measured calcemic response to PTH. This relationship is represented by the following equation: calcium (mg/dl) = 14.84 - 0.139 inorganic phosphate; r = 0.915, P less than 0.001. From these series of studies, we conclude that phosphate retention is the cause of resistance to the calcemic action of PTH extract in this acute uremic model.

Acute Kidney Injury

Assessment of depth perception in cats.

A behavioural method is described for the assessment of depth perception of kittens. Measurement is made of the smallest separation in depth that can be discriminated between two adjacent stimuli under both monocular and binocular viewing conditions. Normal animals can discriminate much smaller separations in depth when using two eyes than with monocular viewing, implying the presence of a cue to depth that is uniquely available with binocular viewing. The test provides a quick and reliable way of screening animals for stereopsis.

Animals

Experience with polytetrafluoroethylene grafts in patients on long-term hemodialysis.

Expanded polytetrafluoroethylene (PTFE) is a new material now being used to create subcutaneous arteriovenous anastomoses for vascular access in hemodialysis. The authors have been impressed with the versatility of grafts made from this material and, where failure occurs, the ease with which surgical revision can be carried out. Two cases are described to illustrate the adaptability of this material to reconstruction. The authors' initial impression based on 22 months' experience is that PTFE grafts have appreciably modified the management with respect to vascular access, of many patients on long-term hemodialysis.

Aged

Two year sequential haemodynamic data on polytetrafluoroethylene (PTFE) grafts used for haemodialysis.

Forty-one PTFE grafts were studied prospectively with measurement of intragraft pressure and flow. As well, cardiac function was assessed by measuring cardiac output, ejection times and ejection fraction. It was shown that graft failure was associated with changes in graft pressures and flow. No untoward effects of graft flows of 1-2L/min were found on cardiac function.

Brachial Artery

Changes in the red cell, plasma and inulin spaces and in the total water contents of rat femurs in cortisone induced osteoporosis.

Measurements of the bone vascular space by use of 99mTc-labelled red cells and 131I-serum albumin, and of the 3H-inulin spaces and total water contents were carried out in female rats treated for four weeks by daily subcutaneous injections of 15 mg cortisone acetate. Significant decreases in bone vascularity, inulin space and water contents were noted as compared to controls. These changes were not associated with differences in plasma calcium values, or parathyroid gland weights. They were found to be present together with significant decreases in bone density and ash contents of the femoral shafts in the steroid-treated animals. It is suggested that the changes in the vascular and extravascular fluid spaces of bones were probably consequent upon a generally depressed level of cellular activity and bone turnover, which could be found in steroid induced osteoporosis.

Animals

Resistance to parathyroid hormone in renal failure: role of vitamin D metabolites.

Resistance to the calcemic action of parathyroid extract (PTE) was shown in thyroparathyroidectomized rats after 5 hr of renal failure that was induced by either bilateral nephrectomy (NPX) or ureter ligation (UL). Studies were carried out to investigate the relationship of parathyroid resistance to the vitamin D status of the animal. Concentrations of 1,25-dihydroxycholecalciferol (1,25(OH)2D3) and 24,25-dihydroxycholecalciferol (24,25(OH)2D3) were similar in pooled sera samples from rats either UL or sham-operated and treated with PTE. Pretreatment with oral 25-hydroxycholecalciferol or with a combination of i.v. 24,25(OH)2D3 and 1,25(OH)2D3 prior to UL failed to alter the resistance. Resistance was also present in a group in vitamin-D-deficient rats. A similar group given 1 microgram of vitamin D2 showed more parathyroid resistance than did the group not given vitamin D2. In chronic renal failure of 28 day's duration, parathyroid resistance was again demonstrated, but, in contrast to the acute renal failure models, this was partly corrected by prior 1,25(OH)2D3 administration. These studies show that parathyroid resistance is not caused by an abnormality of vitamin D metabolism in the acute renal failure model, and we suggest that the phenomenon is due to the accumulation of one or more uremic factors.

Acute Kidney Injury