Search PubMed⌕ Search

Biomedical subjects

S M Ott

Publications and source records attributed to S M Ott.

70 records · Page 4Linked to original sources
PubMed1985

Effect of parathyroidectomy on bone aluminum accumulation in chronic renal failure.

In some patients with chronic renal failure, bone mineralization becomes defective after parathyroidectomy for secondary hyperparathyroidism. Because aluminum deposition in bone is associated with impaired bone formation and osteomalacia, we retrospectively studied bone-biopsy specimens from patients on hemodialysis who were not exposed to dialysate contaminated with aluminum, to determine whether aluminum accumulation on bone surfaces was enhanced by parathyroidectomy. Serial biopsy specimens taken before and after parathyroidectomy revealed an increase in the rate of aluminum deposition on the surface of mineralized bone after parathyroidectomy in each of the six patients studied. The accelerated rate of aluminum accumulation could not be explained by changes in the oral aluminum intake. The mean rate of bone formation (+/- S.E.M.) before parathyroidectomy was higher in the six patients than in six control patients who did not undergo parathyroid surgery (586 +/- 147 vs. 237 +/- 85 micron2 per square millimeter per day; P less than 0.05). After parathyroidectomy, the rate of bone formation fell to levels below normal (148 +/- 32 vs. 311 +/- 29 micron2 per square millimeter per day; P less than 0.05) but was not significantly different from the rate in the control group (319 +/- 126 micron2 per square millimeter per day). We conclude that parathyroidectomy in patients with chronic renal failure is associated with enhanced aluminum deposition on the bone surface, possibly as a result of low bone formation. Patients with secondary hyperparathyroidism who may be candidates for parathyroidectomy should be evaluated for aluminum excess before surgery, so that treatment with aluminum chelation may be considered.

Aluminum↗
PubMed1985

Pseudohyperparathyroidism. Syndrome associated with aluminum intoxication in patients with renal failure.

Aluminum intoxication is an increasingly frequent complication of chronic renal failure. Because hypercalcemia, elevated parathyroid hormone levels, and radiologic changes said to be typical of osteitis fibrosa commonly occur with aluminum intoxication, it is frequently confused with hyperparathyroidism. In this report, examples of this dilemma are described. The pathophysiology leading to the confusing clinical picture is discussed, with a suggested approach to the problem.

Adolescent↗
PubMed1985

Aluminum accumulation in individuals with normal renal function.

In individuals with normal renal function, oral aluminum may be absorbed, but the kidneys are able to excrete the load, and significant pathology is not seen. If aluminum is given parenterally, however, it can accumulate in tissues and lead to osteomalacia or aplastic bone lesions. Low calcitriol and PTH levels are often seen, and may contribute to the bone disease. These findings in individuals with normal renal function add to the growing body of evidence that aluminum is toxic to bone.

Aluminum↗
PubMed1984

Inert gas analysis of ventilation-perfusion matching during hemodialysis.

The mechanism of hypoxemia during hemodialysis was investigated by the multiple inert gas elimination technique in anesthetized, paralyzed, mechanically ventilated dogs. Profound leukopenia occurred in the first hour of a 2-h hemodialysis with a cuprophan membrane and dialysate that contained acetate. Arterial partial pressure of O2 and CO2 and oxygen consumption remained unchanged during dialysis. Pulmonary carbon dioxide elimination and lung respiratory exchange ratio decreased with the initiation of dialysis, remained depressed throughout the duration of dialysis, and returned to predialysis levels after the cessation of dialysis. Cardiac output diminished during dialysis but did not return to base-line levels after dialysis. Multiple indices calculated from inert gas analysis revealed no ventilation-perfusion mismatching during dialysis. The shunt and perfusion to regions of low alveolar ventilation-to-perfusion ratio (VA/Q) were unchanged during dialysis. There was no change in the mean or standard deviation of the profile of the percentage of total perfusion to regions of the lung that had VA/Q near 1.0; nor was there any increase in the directly calculated arterial-alveolar partial pressure differences for the inert gases during dialysis. Dead space became mildly elevated during dialysis. These results show that during dialysis with controlled ventilation there is no ventilation-perfusion mismatching that leads to hypoxemia. During spontaneous ventilation any hypoxemia must occur due to hypoventilation secondary to the CO2 exchange by the dialyzer and subsequent reduction in pulmonary CO2 exchange.

Animals↗
PubMed1984

Use of the deferoxamine infusion test in the diagnosis of aluminum-related osteodystrophy.

The accumulation of aluminum in bone can cause disabling osteodystrophy in patients with renal failure. Because the chelating agent deferoxamine can mobilize aluminum from tissues, we evaluated the effect of a standard intravenous dose of deferoxamine on plasma aluminum concentrations in 54 patients on hemodialysis. Stainable bone aluminum, bone histologic findings, and bone aluminum content were studied. Baseline plasma aluminum concentrations of greater than 200 micrograms/L were associated with aluminum-related osteodystrophy (specificity, 93%), but concentrations of less than 200 micrograms/L did not exclude the diagnosis (sensitivity, 43%). After administration of deferoxamine, the increase in plasma aluminum concentration was 534 +/- 260 (SD) and 214 +/- 92 micrograms/L in patients with and without aluminum-related bone disease, respectively (p less than 0.001), and correlated with the bone aluminum content (r = 0.64). An increment in plasma aluminum concentration of greater than 200 micrograms/L identified 35 of the 37 patients with aluminum-related osteodystrophy; sensitivity was 94% and specificity, 50%. The deferoxamine infusion test is noninvasive, well tolerated, and of value particularly in excluding the diagnosis of aluminum-related osteodystrophy.

Aluminum↗
PubMed1983

Aluminum is associated with low bone formation in patients receiving chronic parenteral nutrition.

Patients treated with chronic total parenteral nutrition may develop metabolic bone disease. We evaluated 22 bone biopsy specimens from 16 patients. Compared with those of age- and sex-matched normal controls, these specimens had significantly higher osteoid area and lower total bone area and bone formation rate, as measured by double tetracycline labels. Aluminum was found in specimens from the 14 patients receiving casein hydrolysate but not in the two receiving amino acids as their nitrogen source. The reduced bone formation correlated inversely with the logarithm of the aluminum level. Aluminum was localized to the surface of mineralized bone; tetracycline uptake was absent at those sites. These bone findings are similar to those from aluminum intoxicated patients on hemodialysis. Both groups also have low parathyroid hormone levels. Thus, aluminum appears to be an important pathogenic factor in the osteodystrophy of patients receiving dialysis or total parenteral nutrition.

Adult↗
PubMed1983

Total body calcium by neutron activation analysis in normals and osteoporotic populations: a discriminator of significant bone mass loss.

This paper reports total body calcium by neutron activation (TBC) measurements in 94 normal individuals and 86 osteoporotic patients. The ability of TBC to discriminate normal from osteoporotic females was evaluated with decision analysis. Bone mineral content (BMC) by single-photon absorptiometry was also measured. TBC was higher in males (range 826 to 1363 gm vs 537 to 1054 in females) and correlated with height in all normals (r = 0.55 in males, 0.58 in females; p less than 0.001). In females over age 55 there was a negative correlation with age (r = -0.51, p less than 0.01). Thus, for normals an algorithm was derived to allow comparison between measured TBC and that predicted by sex, age, and height (TBCp). In the 28 normal females over age 55, the TBC was 764 +/- 115 gm vs. 616 +/- 90 in the osteoporotics (p less than 0.001). In 63 of the osteoporotic females an estimated height, from tibial length, was used to predict TBC. In normals the TBC/TBCp ratio was 1.00 +/- 0.12, whereas in osteoporotic females it was 0.80 +/- 0.12 (p less than 0.001). A receiver operating characteristic curve showed better discrimination of osteoporosis with TBC/TBCp than with wrist BMC. By using Bayes' theorem, with a 25% prevalence of osteoporosis (estimate for postmenopausal women), the posttest probability of disease was 90% when the TBC/TBCp ratio was less than 0.84. We conclude that a low TBC/TBCp ratio is very helpful in determining osteoporosis.

Activation Analysis↗
PubMed1982

The prevalence of bone aluminum deposition in renal osteodystrophy and its relation to the response to calcitriol therapy.

A histochemical stain for bone aluminum allowed us to determine the prevalence and staining characteristics of aluminum in renal osteodystrophy. The staining method correlated well with the results of atomic-absorption studies in 96 samples (r = 0.81; P less than 0.001). We examined 315 bone-biopsy samples. No aluminum was seen in controls or patients with nonrenal bone disease. In renal osteodystrophy, the mean level of stainable aluminum was significantly higher in osteomalacic lesions (1.12 +/- 0.09 mm per square millimeter of tissue area) than in mild, mixed, of fibrotic lesions (0.43 +/- 0.06, 0.34 +/- 0.11, and 0.10 +/- 0.03 mm per square millimeter, respectively; P less than 0.001). Seventy per cent of osteomalacic samples had heavy aluminum staining. The bone-apposition rate, measured by double tetracycline labels, was low in 89 per cent of the samples with high levels of aluminum. The mean level of stainable bone aluminum in patients who had a clinical response to calcitriol was significantly lower than in those who did not respond (0.13 +/- 0.4 vs. 1.06 +/- 0.9 mm per square millimeter; P less than 0.01). We conclude that aluminum deposition is associated with impaired bone formation or mineralization and with a poor response to calcitriol therapy.

Aluminum↗
PubMed1982

Histological quantitation of aluminum in iliac bone from patients with renal failure.

Aluminum in undemineralized, methyl methacrylate-embedded iliac bone from 16 hemodialyzed renal patients and six normal controls was stained by a modification of the aluminon method and quantitated histomorphometrically, and the results were compared with the aluminum values measured by atomic absorption spectrophotometry. There was a high degree of correlation between the two techniques (r = 0.955, p less than 0.0001). The amount of stained aluminum also showed a statistically significant relationship with the amount of bone that is not mineralized (r = 0.840, p less than 0.001), with the TM (r = 0.841, p less than 0.001), and with osteoid width (r = 0.771, p less than 0.0001). The aluminum was found as bright red bands mainly in the junction of mineralized bone and osteoid but was also observed in cement lines of mature bone, on neutral surfaces, and surrounding the osteocytes. Analysis of serial sections for aluminum and tetracycline showed that a majority of the sites with aluminum did not take up tetracycline, implying defective mineralization. Occasionally tetracycline uptake was observed in such places, suggesting that the aluminum "block" might be overcome eventually. The presence of aluminum in cement lines of mature bone supports this hypothesis. The histochemical staining of aluminum provides a quick and easy method for identifying, localizing, and quantifying aluminum within the bone and may prove to be a useful tool in the study of the mechanisms of metabolic bone disease.

Acute Kidney Injury↗
PubMedDate not supplied

D-lactate and metabolic bone disease in patients receiving long-term parenteral nutrition.

D-lactate accumulates in some patients with malabsorption who continue oral intake of carbohydrate leading to a clinical syndrome of acidosis and encephalopathy. To assess the possibility that D-lactate contributes to acidosis and/or metabolic bone disease in patients with malabsorption receiving long-term parenteral nutrition yet maintaining oral intake, D-lactate levels in serum and urine were measured in 14 long-term parenteral nutrition subjects (average duration of support 74 months) and 27 control subjects. Significant elevations in both serum and urine D-lactate were found in only two parenteral nutrition subjects. Both subjects with elevated D-lactate levels had bone pain, x-ray evidence of fractures, and biopsy evidence of osteomalacia. These studies suggest that D-lactate accumulation may be a heretofore unappreciated metabolic abnormality associated with metabolic bone disease and acidosis in patients with malabsorption who are supported by long-term parenteral nutrition.

Acidosis, Lactic↗
PubMedDate not supplied

Metabolic bone disease in adults receiving long-term parenteral nutrition: longitudinal study with regional densitometry and bone biopsy.

A syndrome of bone pain and fractures has been described in patients receiving long-term support from parenteral nutrition containing large quantities of aluminium or vitamin D2. Whether this same syndrome occurs in patients supported by current therapeutic regimens is controversial. In this study, bone health was longitudinally evaluated over 7 to 61 months in 14 subjects maintained on long-term parenteral nutrition. The parameters of bone health evaluated included bone mass as measured by single and dual photon absorptiometry and quantitative histomorphometry of bone biopsies. There was a striking heterogeneity in baseline measures of bone health. Mean bone density of parenteral nutrition patients was significantly below expected values on entry into the study at both the distal radius (z score = -0.76 +/- 0.27) and the lumbar spine (z score = -1.17 +/- 0.27). Mean areal density at the forearm was less severely depressed (z score = -0.62 +/- 0.34). The longitudinal changes in bone density and morphology were heterogeneous, with some subjects showing deterioration, others improvement, and still others no change. We conclude that patients already established on parenteral nutrition frequently have osteopenia. The group as a whole did not demonstrate normalization of the osteopenia, but our results also suggest that current parenteral nutrition formulations low in aluminum and vitamin D2 do not necessarily cause worsening of bone health. The etiology of this clinical syndrome merits additional study.

Adult↗