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Biomedical subjects

D S Rao

Publications and source records attributed to D S Rao.

At least 19 recordsLinked to original sources
PubMed1992

Functional studies on long-term cryopreserved peripheral blood mononuclear cells from patients with lung cancer and from healthy subjects.

To determine the functional abilities of long-term cryopreserved peripheral blood mononuclear cells (PBMCs) from patients with lung cancer and from healthy subjects, we assayed the proliferative and plaque-forming cell (PFC) responses of cells from these individuals after the cells had been cryopreserved for up to 31 months. The stability of these cells for B and T cell quantitative assays was also determined by using their respective monoclonal antibodies. The patients' results were compared with those in healthy subjects to ascertain whether the conclusions derived from the assay of cryopreserved cells are consistent with our earlier studies on fresh cells from similar patients. The results show that proliferative and PFC responses of the frozen cells were not significantly affected by further storage, despite an initial, irreversible functional loss in some subsets of T lymphocytes and monocytes during the process of freezing. They also demonstrate that cryopreserved PBMCs from both patients and controls can be successfully utilized for B and T cell quantitative assays. The conclusions derived from the assay of cryopreserved cells are also consistent with our earlier observations on fresh cells from patients with lung cancer; those studies indicated a B cell functional abnormality caused in part by increased suppressor T cell and monocyte activity.

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PubMed1991

Structural and geometric changes in iliac bone: relationship to normal aging and osteoporosis.

We measured indices of bone volume (cancellous and cortical) and bone surface (cancellous, endocortical, and intracortical) in intact, full-thickness transiliac bone biopsies obtained from 47 healthy white women (23 premenopausal and 24 postmenopausal) and 82 patients with postmenopausal osteoporosis. In the normal subjects there was the expected loss of cancellous bone with age, best shown by a reduction in bone surface/tissue volume, but no fall in cortical thickness with age despite a significant reduction in forearm bone density measured by single-photon absorptiometry. Bone surface/bone volume was about four times higher in cancellous than in cortical bone, and cancellous bone contributed about one-third of the total bone volume and about two-thirds of the bone surface when related to the core volume referent. In the osteoporotic patients, core width, an index of iliac bone thickness at the biopsy site, was reduced by 10%, but we could not determine whether this was the result of compaction of the core or of bone slenderness. All indices of bone volume, cortical as well as cancellous, were significantly smaller, as were the values for forearm bone densitometry; the relative deficits at different sites depended on whether they were expressed as percentages or as zeta scores. Bone surface/bone volume was increased in both cancellous and cortical bone, but bone surface/tissue volume was reduced in cancellous bone and increased in cortical bone. The proportions of total bone volume and surface contributed by cancellous and cortical bone were almost the same as in normal postmenopausal women.(ABSTRACT TRUNCATED AT 250 WORDS)

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PubMed1991

Asymptomatic primary hyperparathyroidism discovered by multichannel biochemical screening: clinical course and considerations bearing on the need for surgical intervention.

The sustained effects of biochemical screening to increase both apparent incidence and age at diagnosis indicate that, without screening, most patients with primary hyperparathyroidism would would never be diagnosed. This suggests that asymptomatic patients discovered as a result of screening have a nonprogressive form of the disease, with adverse health effects that are few or nontraditional, for which treatment policies validated only in symptomatic patients may be inappropriate. Accordingly, in 1975 we formulated criteria for withholding surgical treatment from such patients. Of 174 who were eligible for study over a 10 year period, clinical, biochemical, and densitometric assessment was repeated after at least 1 year (mean 52 months) in 106 patients who did not differ in any initial characteristic from 68 patients in whom follow-up was inadequate. There was no change in symptoms, no disease complications, and no change in any index of hormone secretion or disease severity. In 30 patients, individual regression slopes against time were not significant for any serum measurement. In these patients the disease appeared to have stopped progressing by the time the diagnosis was made, most likely because of cessation of tumor growth. There was a significant deficit in appendicular cortical bone at the time of diagnosis but no further acceleration of bone loss thereafter. In an earlier study, surgical cure was followed by a modest increase in forearm bone density for the first 6 months, but even after 3 years only about 20% of the deficit was corrected. The deficit in bone density is smaller in the spine than in the forearm and is not accompanied by any increase in vertebral fracture risk.(ABSTRACT TRUNCATED AT 250 WORDS)

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PubMed1991

Primary hyperparathyroidism and monoclonal gammopathy.

Coexistent primary hyperparathyroidism and monoclonal gammopathy, although rare, has been reported previously by a number of investigators. We report four patients with such an occurrence who were seen between 1976 and 1988. Another patient with primary hyperparathyroidism also had multiple myeloma and was in remission for 12 years. These patients represent approximately 1% of the 386 patients with primary hyperparathyroidism seen during the same 12-year period. Although several mechanisms have been proposed to explain this concurrence, we believe it is the result of a chance occurrence. A review of the literature, an estimate of the chance occurrence of coincidental monoclonal gammopathy, benign or malignant, in patients with primary hyperparathyroidism, and some practical implications of this interesting coexistence are presented.

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PubMed1989

Hypomagnesemia and hypertension in primary hyperparathyroidism.

A retrospective study of 89 patients with surgically proven primary hyperparathyroidism was done to gain insight into the pathogenesis of hypertension associated with this condition. The 43 patients (48%) who were hypertensive did not differ significantly from the normotensive patients with regard to age, sex, serum calcium and phosphate levels, and creatinine clearance. However, the mean serum magnesium level was significantly lower in hypertensive hyperparathyroid patients (1.52 +/- 0.24 mEq/L) than in normotensive hyperparathyroid patients (1.76 +/- 0.18 mEq/L; P less than .001), irrespective of use of diuretics in the former group. Although some studies implicate hypomagnesemia in the pathogenesis of essential hypertension, we are unaware of any previous human study reporting a link between hypomagnesemia and hypertension associated with primary hyperparathyroidism. This study suggests that a low level of serum magnesium may play a role in the pathogenesis of hypertension associated with primary hyperparathyroidism, a finding that needs further evaluation.

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PubMed1989

The functional deficiency of B lymphocytes in patients with lung cancer is due to inadequate T-cell help and excessive suppression by T and non-T cells.

The proliferative and plaque-forming cell (PFC) responses of unseparated mononuclear cells (MNC) and B- and T-cell-enriched populations of cells were analyzed in 15 patients with lung cancer to determine the mechanisms involved in the functional abnormality of their B cells. The PFC responses of the MNC of the patient group were significantly lower than those of normal controls. In addition, the enriched B cells of several patients showed a further decrease in their PFC responses after coculture with autologous T cells compared with their respective MNC responses. The proliferative response against phytohemagglutinin (PHA) was also lower in many of the patients after similar cocultures. Cocultures of patients' B cells with T cells from normal controls significantly enhanced the PFC responses in 7 patients. In most of the normal controls, B lymphocytes showed a significant decrease in their PFC responses after coculture with the patients' T cells. Although the percentages of total T cells, T-helper, and B cells were within the normal range, the number of suppressor T cells was significantly higher in the patient group. These results indicate that a combination of insufficient T-cell help, excessive suppression by both T and non-T cells, and a possible intrinsic B-cell abnormality are responsible for the B-cell functional deficiency observed in patients with lung cancer.

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PubMed1988

Lack of biochemical progression or continuation of accelerated bone loss in mild asymptomatic primary hyperparathyroidism: evidence for biphasic disease course.

We studied the natural history of primary hyperparathyroidism in patients in whom the disease was discovered fortuitously by multichannel biochemical screening and who were selected for conservative management because they were asymptomatic, had no renal stone disease or radiographic osteitis fibrosa, and had serum calcium values below 3.00 mmol/L, serum creatinine levels below 133 mumol/L, and forearm bone density not more than 2.5 SD below the mean expected for age, sex, and race. One hundred and seventy-four patients meeting these criteria were encountered during a 10-yr period, of whom 80 (mean age, 61 yr) had adequate follow-up; they did not differ significantly in any initial characteristic from the remaining 94 patients. These 80 patients were followed for 1-11 yr (mean, 46 months; median, 38 months), during which there was no change, mean or individual, in any index of PTH secretion or any of its biochemical effects and no decline in forearm bone density apart from that expected from increased age. There were 4 deaths from causes unrelated to hyperparathyroidism, and the overall death rate was not increased. The data suggest that no change occurred in either the number of parathyroid cells or secretory set-point, the 2 principal determinants of basal PTH secretion. This implies a biphasic course, with a short period of disease progression followed by a long period of disease stability. Our data support the decision to withhold surgical intervention in such patients, but to establish this as the correct policy for all asymptomatic patients will require a controlled clinical trial.

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PubMed1987

Hypophosphatemic osteomalacia and adult Fanconi syndrome due to light-chain nephropathy. Another form of oncogenous osteomalacia.

Two patients, one with myeloma (Patient 1) and the other with probable chronic lymphocytic leukemia (Patient 2), had reduced renal tubular phosphate reabsorption in the absence of hyperparathyroidism together with other features of the Fanconi syndrome, as consequences of the nephropathy associated with light-chain proteinuria. Both patients had hypophosphatemic osteomalacia, demonstrated for the first time in this condition by iliac bone histomorphometry after in vivo double tetracycline labeling, despite absence of bone pain or Looser zones. Neither patient was vitamin D-depleted, but plasma calcitriol level was normal in Patient 1 and low in Patient 2; only the latter patient had severe muscle weakness. Complete histologic correction of osteomalacia was achieved by treatment in accordance with the biochemical defects--oral phosphate therapy alone in Patient 1 and combined with calcitriol in Patient 2. Both patients are now symptom-free, five and three years after the initial diagnosis of bone disease and hematogenous malignancy. Thirteen previous instances of the same form of osteomalacia were reviewed; in most cases, the Fanconi syndrome developed before its probable cause became apparent. The Fanconi syndrome has also been reported in two cases of osteomalacia due to mesenchymal tumor, but not in osteomalacia associated with prostatic carcinoma. Light-chain nephropathy and consequent renal tubular dysfunction appears to be a third form of oncogenous osteomalacia.

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PubMed1987

Atypical insufficiency fractures confused with Looser zones of osteomalacia.

Six women, aged 24-67 years, had osteopenia and insufficiency fractures, which suggested a diagnosis of osteomalacia. The insufficiency fractures occurred at traditional sites for Looser zones, were multiple in number, were symmetrically distributed in three patients, and did not heal promptly. Bone mass was low, as assessed by single-energy photon absorptiometry at the midshaft of the radius. Two postmenopausal women had vertebral compression fractures. Biochemical indices and bone histomorphometric analysis excluded osteomalacia, and in vivo double tetracycline labeling in five patients revealed both high and low bone turnover states. We propose more stringent radiographic criteria for the designation of the term "Looser zone" that retains the customary association between the radiologic event and osteomalacia. This paper also outlines a diagnostic strategy for future cases of atypical insufficiency fractures and proposes reasons for their resemblance to true Looser zones.

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PubMed1987

Bone histomorphometry in hypogonadal and eugonadal men with spinal osteoporosis.

We present iliac bone histomorphometric data after in vivo double tetracycline labeling and related biochemical data from 14 nonalcoholic men referred for evaluation of symptomatic spinal osteoporosis. Six patients had previously undiagnosed hypogonadism, and 8 had normal gonadal function and no evident etiology for osteoporosis. Bone histomorphometry revealed no differences in structural measurements or resorption indices between the 2 groups. However, compared to reference values for normal postmenopausal women, osteoblast surface, mineralizing surface, and formation rate were normal or modestly increased in the hypogonadal men and significantly reduced in the idiopathic group. There were significant corresponding differences between the 2 groups in the fasting urinary hydroxyproline to creatinine ratio, an index of bone resorption, and serum total alkaline phosphatase, an index of bone formation. Plasma 25-hydroxyvitamin D levels did not differ between the 2 groups and were above 10 ng/mL in all patients. Plasma 1,25-dihydroxyvitamin D [1,25-(OH)2D] levels were normal in the hypogonadal group and significantly reduced in the idiopathic group, but did not correlate with any histological measurements. The formation indices fell substantially in 3 of 4 hypogonadal men after 7-14 months of therapy with testosterone and a calcium supplement. We conclude the following. In vitamin D-replete hypogonadal men with osteoporosis, 1,25-(OH)2D synthesis is normal, and bone remodeling is modestly increased and correctable by hormone replacement therapy, as in normal postmenopausal women. In middle-aged men with idiopathic osteoporosis, there is impairment of 1,25-(OH)2D synthesis and of the recruitment and activity of teams of osteoblasts, as in postmenopausal osteoporosis.

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PubMed1985

The role of three-dimensional trabecular microstructure in the pathogenesis of vertebral compression fractures.

We compared indices of three-dimensional microstructure of iliac trabecular bone between 26 patients with vertebral compression fractures due to postmenopausal osteoporosis and 24 control subjects without vertebral fracture, who were matched for age, sex, race, menopausal status, and several densitometric and histologic indices of both cortical and trabecular bone mass. The patients with fracture had a significantly lower mean value (1.03 +/- 0.15 vs. 1.26 +/- 0.26; P less than 0.005) for indirectly calculated mean trabecular plate density, an index of the number and connectivity of structural elements, and as a necessary corollary, a significantly higher mean value for the mean thickness of structural elements. Plate density was more than one standard deviation below the age-adjusted mean value for normal postmenopausal white females in 19 (73%) of the fracture cases and in only 5 (21%) of the nonfracture cases (P less than 0.001). We conclude that the biomechanical competence of trabecular bone is dependent not only on the absolute amount of bone present but also on the trabecular microstructure.

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PubMed1985

Irreversible bone loss in osteomalacia. Comparison of radial photon absorptiometry with iliac bone histomorphometry during treatment.

We examined the relationships between the changes in bone mineral deficit in the radius, determined by single-energy photon absorptiometry at standard proximal and distal sites, and in the ilium, determined by bone histomorphometry, during the treatment of osteomalacia of diverse etiology in 28 patients. In the ilium, relative osteoid volume decreased by 75-80% in both cortical bone (from 6.0% to 1.5%) and trabecular bone (from 30.1% to 6.6%) during a mean treatment duration of 2 yr. There was also a significant fall in iliac cortical porosity from 10.3% to 7.8%. As a result, mineralized bone volume increased by 7.5% in cortical and by 40.1% in trabecular bone; the cortical and trabecular increments were correlated (r = 0.69, P less than 0.001). The properly weighted increase for the entire tissue sample was 18.6%. By contrast, there was no change in bone mineral at either radial site, although there was a 2% increase at both sites when allowance was made for age-related bone loss during treatment. The proximal and distal age-adjusted increments was correlated (r = 0.76, P less than 0.001), but there was no correlation between the changes in any photon absorptiometric and any histomorphometric index. In that iliac cortical bone turnover in normal subjects was 7.2%/yr, we estimated the rate of bone turnover to be less than 2%/yr at both proximal and distal radial sites, including any trabecular bone present at the distal site. Compared to appropriate control subjects, the bone mineral deficits fell during treatment from 19.2% to 17.1% at the proximal radius (greater than 95% cortical bone) and from 20.5% to 18.5% at the distal radius (greater than 75% cortical bone). In the ilium the deficits, assuming attainment of normal values for osteoid volume and cortical porosity, fell from 41.7% to 36.1% in cortical and from 31.5% to 6.3% in trabecular bone, the properly weighted combined deficit falling from 38.6% to 27.7%. The irreversible iliac cortical deficit was entirely due to cortical thinning because of increased net endosteal resorption; the resultant expansion of the marrow cavity offset the modest loss of fractional trabecular mineralized bone. We conclude: in osteomalacia there is a large irreversible and a small reversible bone mineral deficit at both proximal and distal radial sites, in similar proportion to the iliac cortex but of smaller magnitude; the anatomic basis of the irreversible bone mineral deficit at all three sites that persists despite correction of the mineralization defect by appropriate treatment is thinning of cortical bone, most likely owing to prolonged secondary hyperparathyroidism; (c) there is no evidence that the proportion of trabecular bone in the distal radius at any site proximal to the radioulnar joint has any relevance to the interpretation of measurements made at that site; (d) there are at least three functional subdivisions of trabecular bone depending on proximity to hematopoietic marrow, fatty marrow, or synovium; and (e) single photon absorptiometry of the radius is an excellent method for measuring cortical bone mass in the appendicular skeleton, but is of little value for the assessment of changes in trabecular bone status.

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PubMed1985

Dissociation between the effects of endogenous parathyroid hormone on adenosine 3',5'-monophosphate generation and phosphate reabsorption in hypocalcemia due to vitamin D depletion: an acquired disorder resembling pseudohypoparathyroidism type II.

In 6 of 8 adults with severe hypocalcemia and osteomalacia due to vitamin D depletion, basal excretion of nephrogenous cAMP (NcAMP) was increased, but the mean renal phosphate threshold (TmP/GFR) was normal, indicating that the steady state phosphaturic response to cAMP generated by endogenous PTH was impaired, as in pseudohypoparathyroidism type II. In all 6 patients, correction of hypocalcemia by administration of vitamin D and calcium restored the normal relationship between NcAMP and TmP/GFR. By contrast, in 13 patients with normocalcemic osteomalacia due to vitamin D depletion, TmP/GFR was reduced, with a significant negative regression on NcAMP, and rose to normal after treatment. Bone histomorphometry after double tetracycline labeling did not differ significantly between the 2 groups. In 72 patients with primary hyperparathyroidism, the slope of the negative regression of TmP/GFR on NcAMP was the same as in normocalcemic secondary hyperparathyroidism, but the adjusted mean for TmP/GFR was significantly lower. We conclude that the effect of endogenous PTH on phosphate reabsorption varies with the level of plasma calcium, and that dissociation between this effect and the generation of cAMP is nonspecific and can be a consequence of hypocalcemia. Exclusion of vitamin D depletion should be an additional diagnostic criterion for pseudohypoparathyroidism type II.

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