Infection by Mycobacterium szulgai in a patient with pulmonary tuberculosis.
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Biomedical subjects
Publications and source records attributed to J M Olmos.
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Bone mineral density (BMD) at the lumbar spine, quantified by dual energy X-ray absorptiometry, and biochemical bone remodeling markers (serum alkaline phosphatase, osteocalcin, tartrate-resistant acid phosphatase and urinary hydroxyproline) have been studied in 94 patients with diabetes mellitus aged 18-62 years. BMD was normal (1.13 +/- 0.02 g/cm2 in patients vs. 1.16 +/- 0.12 g/cm2 in controls), although it was found to be negatively correlated with HbA1, microalbuminuria, age and the duration of the disease. Serum alkaline phosphatase (188 +/- 75 I.U./l vs. 168 +/- 42 I.U./1; P < 0.03), serum tartrate-resistant acid phosphatase (14.3 +/- 4.3 I.U./l vs. 11.7 +/- 3.7 I.U./l; P < 0.0001) and urinary hydroxyproline (0.018 +/- 0.016 mmol/mmol creatinine vs. 0.011 +/- 0.008 mmol/mmol creatinine; P < 0.001) were higher in diabetics than in controls. Serum osteocalcin was lower (2.5 +/- 1.3 ng/ml vs. 3.4 +/- 1.2 ng/ml; P < 0.0001). No relationship was found between bone remodeling markers and BMD. It is concluded that lumbar BMD is normal in type 1 diabetic patients, although the degree of metabolic control, age and duration of the disease may affect it. In the light of the biochemical markers, bone remodeling may be disturbed in diabetes, but such disturbance seems to be unimportant regarding BMD.
A decreased number of calcitriol (1,25(OH)2D3) receptors has been observed in parathyroid glands of uremic animals. In humans, studies carried out in surgically removed parathyroid glands have shown that calcitriol binding is higher in primary than in secondary hyperparathyroidism. Since specific receptors for calcitriol have been described in peripheral blood mononuclear cells (PBMC), we have investigated the specific uptake of 3H-labelled 1,25(OH)2D3 in PBMC of 12 women with primary hyperparathyroidism (PHP), 8 women with hyperparathyroidism secondary to chronic renal failure (SH), 9 women with renal transplant (RT), and 23 healthy women. The median dissociation constant (Kd) was similar in all three groups of patients and in healthy women (mean +/- S.D. (range): PHP, 1.2 +/- 1.0 (0.2-4) x 10(-10) M; SH, 0.6 +/- 0.4 (0.2-1.2) x 10(-10) M; RT, 1.1 +/- 0.5 (0.4-1.9) x 10(-10) M; controls, 1.0 +/- 0.6 (0.3-2.6) x 10(-10) M). However, the maximal binding capacity (Nmax) was significantly enhanced in PHP (3.9 +/- 1.9 (1.3-7.6) fmol/10(7) cells vs. 2.3 +/- 0.9 (1.1-4.4) fmol/10(7) cells in controls; P = 0.0006) and decreased in SH (0.8 +/- 0.5 (0.2-1.6) fmol/10(7) cells vs. 2.3 +/- 0.9 (1.1-4.4) fmol/10(7) cells in controls; P = 0.0001), whereas no changes were seen in RT (2.3 +/- 0.7 (1.2-3.3) fmol/10(7) cells vs. 2.3 +/- 0.9 (1.1-4.4) fmol/10(7) cells in controls). In three patients with PHP who were subjected to parathyroidectomy, the calcitriol number came down to normal. Changes of calcitriol receptors in primary and secondary hyperparathyroidism could magnify the consequences of disturbances in serum concentration of calcitriol itself and might play an important role in the development of secondary hyperparathyroidism in uremia.
The aim of the present study was to compare cytokine secretion in healthy young and old subjects. Peripheral blood mononuclear cells were isolated from 55 healthy volunteers (aged 23-77 years) and cultured for 24 h in the presence or the absence of lipopolysaccharide (LPS) and 1,25-dihydroxyvitamin D3. Interleukin-1 beta (IL-1), tumor necrosis factor a (TNF) and prostaglandin E2 were measured in the culture supernatants with specific immunoassays. The unstimulated and LPS-stimulated production of IL-1 was significantly higher in the group of subjects older than 55 years than in the group aged less than 55 years. Likewise, there were positive correlations between age and the unstimulated and LPS-stimulated IL-1 secretion (r = 0.50 and 0.63, respectively, p < 0.01 in both cases). However, there were no age-related differences in the secretion of IL-1 in the presence of 1,25-dihydroxyvitamin D or in the secretion of TNF or prostaglandin E2 in any culture condition. These results suggest the existence of subtle abnormalities in cytokine secretion in healthy aged subjects, in comparison with younger individuals. In theory, the increased secretion of IL-1 might play a role in the pathophysiology of some diseases which are frequent in old people, such as osteoporosis.
BACKGROUND: Liver cirrhosis, chronic obstructive pulmonary disease (COPD), insulin-dependent diabetes mellitus and primary hyperparathyroidism are frequent diseases which are considered as risk factors for the development of osteoporosis. However, review of the literature has shown that the studies published on the aforementioned are far from conclusive. METHODS: By double energy X-ray absorptiometry the bone mineral density (BMD) of the lumbar spine and neck of the femur were determined in 29 patients with liver cirrhosis, 92 with chronic obstructive pulmonary disease (59 treated with corticoids), 81 with insulin-dependent diabetes mellitus and 30 primary hyperparathyroidism (7 operated). RESULTS: Cirrhotic patients had a normal BMD in both localizations. In patients with COPD, without corticoids, a decrease of 6% was found in the spine and or 13.5% in the neck of the femur while in patients with COPD with corticoids the decrease was of 12% and 7% respectively. Diabetic patients had normal BMD in the spine and a decrease of 6% in the neck of the femur and in patients with hyperparathyroidism a decrease of 6% and normality were found, respectively. CONCLUSIONS: The repercussion of cirrhosis, insulin-dependent diabetes, and primary hyperparathyroidism on bone mineral density is nul or slight. In patients with chronic obstructive pulmonary disease treated with corticoids decrease in density of the spine is approximately that of a standard deviation. In patients with the latter not treated with corticoids a similar decrease is found in the neck of the femur.
In order to evaluate cardiovascular risk, we analyzed the lipid composition of HDL and the presence of lipoprotein(a) [Lp(a)] by both agarose gel electrophoresis and enzyme-linked immunoassay (ELISA). In 681 plasmas we found a close correspondence between the existence of a visible sinking pre-beta lipoprotein band and a concentration of Lp(a) higher than 300 mg/L. In the sinking pre-beta(+) samples, the HDL-cholesterol level obtained by differential ultracentrifugation was significantly higher than that obtained by precipitation with the MgCl2-phosphotungstic acid reagent; and the difference between these HDL-cholesterol values was linearly correlated with plasma Lp(a) concentration. Moreover, the other HDL lipid components and the lipid mass ratios of HDL isolated by ultracentrifugation were significantly different from those of HDL isolated by precipitation, and these changes were also correlated with plasma Lp(a). These differences are attributed to Lp(a) because it was detected in the 1.063-1.21 kg/L plasma fractions, whereas it was absent in the plasma supernates after precipitation with MgCl2-phosphotungstic acid. Although to a lesser extent, Lp(a) was also present in the LDL and VLDL density ranges and it directly depended on both the Lp(a) and the triglyceride plasma concentrations. The proportion of Lp(a) in HDL as related to that in LDL density fractions decreased as Lp(a) plasma levels increased, reflecting an interindividual variation of Lp(a) density species. Since 90% of our study population had detectable Lp(a) in plasma, the results reinforce the concept that the ultracentrifugation method is not equivalent to precipitation in most samples, and the contaminant effect of Lp(a) cannot be predicted because of Lp(a) partition into the different lipoprotein fractions.
During a study undertaken to characterize the time course of the osteocalcin response to bone fractures, lower than normal values of serum osteocalcin (1.7 +/- 0.9 vs. 3.3 +/- 1.3 ng/ml, P < 0.001) were found in the basal samples (blood obtained 48-72 h after fracturing). Suspecting that such a decrease could be due to the stress response induced by the fracture, for corticosteroids are known to diminish serum osteocalcin, we extended our study to another two stressful situations of high stress: acute myocardial infarction and elective abdominal surgery. Indeed, the concentration of osteocalcin was also significantly diminished in both of these (2.0 +/- 0.9 ng/ml, P < 0.0005; 1.5 +/- 1.0 ng/ml, P < 0.0001). To further characterize this phenomenon, the time course of osteocalcin changes during the 24 h following abdominal surgery was studied in a second group of patients. The decrease was found to begin soon after surgery. In order to exclude the immobilization present in those three situations as the cause of the decrease in serum osteocalcin, a group of patients with retinal detachment was studied. Their serum osteocalcin levels were normal. It is concluded that serum osteocalcin levels decrease in stressful situations. Therefore, they should be interpreted cautiously when used as a marker of osteoblastic activity in this setting.
A decrease in intestinal calcium absorption, in spite of normal serum calcitriol levels, has been reported in postmenopausal osteoporotic women, raising the possibility of an intestinal resistance to the hormone. The mechanism responsible for it could lie at the receptor or postreceptor level. Intestinal receptors are difficult to study on clinical settings, but calcitriol receptors have been found in peripheral blood mononuclear cells (PBMC). We have studied the PBMC calcitriol receptors by means of Scatchard analysis in 11 postmenopausal osteoporotic women without any treatment and in 12 normal postmenopausal women of similar age. No differences were found in the dissociation constant (Kd) or the concentration of binding sites (Nmax) (Kd in patients: 0.90 +/- 0.75 x 10(-10) M; Kd in controls: 0.85 +/- 0.40 x 10(-10) M; Nmax in patients: 2.4 +/- 1.2 fmol/10(7) cells; Nmax in controls: 2.1 +/- 0.6 fmol/10(7) cells), supporting the contention that the disorder responsible for the resistance to calcitriol in postmenopausal osteoporotic women is located at the postreceptor level. In addition, our study included five postmenopausal osteoporotic women treated with calcitriol (0.5 microgram/day). The number of calcitriol receptors was increased in this group (Nmax: 3.9 +/- 2.0 fmol/10(7) cells vs. 2.1 +/- 0.6 fmol/10(7) cells; P = 0.02).
Interleukin-4 (IL-4) modulates the activity of a variety of lymphoid, hemopoietic and mesenchymal cells, but little is known about its influence on bone cells. We have studied the effects of IL-4 on the human osteoblast-like cell line MG63. IL-4 (0.1-50 ng/ml) inhibited cell proliferation. The effect did not depend on cell density, but it was more marked in serum-free cultures than in the presence of serum. IL-4 also induced a dose-dependent increase in the expression of alkaline phosphatase stimulated by 1,25-dihydroxyvitamin D3, a marker of differentiated osteoblast activity. However, IL-4 did not modify the secretion of interleukin-6 or tumor necrosis factor. These results suggest that interleukin-4 may play a role as a modulator of osteoblast activity.
BACKGROUND: Fracture of the hip constitutes a serious social/health care problem with very little information concerning incidence in Spain being available. METHODS: The diagnosis of hospital admissions and the diagnosis of release from the traumatology units of health care centers for acute patients in Cantabria were reviewed. The study was carried out from the 1st of January to the 31st of December 1988 and only included patients over 49 years of age. Patients who did not habitually reside in the region were excluded. The following data were collected in each case: age, sex, place of residence (urban or rural), time of the year, side fractured, type of injury, previous contralateral fracture and perioperative mortality. RESULTS: The rate of fracture referred to the population of more than 49 years of age was 277/100,000 in the case of females and 100/100,000 for males. The mean age of women was 80.4 +/- 8.5 years and of men was 76.9 +/- 10.9 years (p > 0.02), respectively. No differences were observed with regard to the place of residence or the time of year. The fracture was left sided in 61% of the females and 58% of the males. The injury was almost always due to a fall. Six percent of the patients had a previous contralateral fracture. Perioperative mortality was 6%. CONCLUSIONS: The incidence of hip fracture in Cantabria is similar to that of other regions in Spain and lower to that of parts of central and northern Europe and the United States.
Cells of the monocyte/macrophage lineage express specific receptors for calcitriol (1,25-dihydroxyvitamin D3) and secrete prostaglandins and several cytokines with potent effects on bone metabolism. The aim of this study was to determine the effect of calcitriol on the secretion of prostaglandin E2 (PGE2), interleukin-1 (IL-1), and tumor necrosis factor (TNF alpha). Monocyte-enriched peripheral blood mononuclear cells (PBMC) from healthy subjects were cultured in the presence or absence of calcitriol (10(-11)-10(-7) M) and several stimulating agents. After 24 h, PGE2, IL-1, and TNF alpha were measured in the culture supernatants or lysates with specific immunoassays. Calcitriol induced a biphasic effect on PGE2 production by unstimulated cells and increased PGE2 synthesis by cells stimulated with either endotoxin or tau-interferon (IFN-tau). On the other hand, calcitriol inhibited the production of TNF alpha by monocytes stimulated with either IFN-tau or phorbol esters. This effect was not prevented by the addition of indomethacin, IL-1, or IL-2. Under the conditions used, we observed no effect of calcitriol on IL-1 alpha or IL-1 beta production. These results indicate that calcitriol induces in vitro marked changes in the secretion of monocyte products with known activity on bone cells. Further studies are needed to elucidate whether some effects of calcitriol on bone metabolism are mediated by the interaction of the sterol with cells of the immune system.
The interference of dextran sulfate with the colorimetric determination of free cholesterol causes an increase in the absorbance that is proportional to the dextran sulfate concentration in the sample. This makes estimation of the free cholesterol concentration unreliable in high-density lipoprotein-containing supernates obtained after plasma precipitation with dextran sulfate/MgCl2. Analysis of the absorption spectrum demonstrated that the absorbance increase was due to turbidity. We observed this effect with colorimetric reagents based on potassium phosphate buffer but not with those based on sodium phosphate or Tris buffers. This effect is ascribed to dextran sulfate because neither the omission of Mg2+ ions nor their chelation with EDTA prevented turbidity, whereas precipitation of dextran sulfate with Ba2+ counteracted this effect. Therefore, potassium phosphate-buffered reagents appear unsuitable for colorimetric lipid determinations in samples containing dextran sulfate.
Several parameters of phosphocalcic metabolism were evaluated in 21 patients with active pulmonary tuberculosis. The serum levels of total calcium, ionic calcium, phosphorus, albumin, magnesium and alkaline phosphatase, and calciuria and calcium/creatinine ratio in 24-hour urine were normal and not change during therapy. The patients with tuberculosis showed a significant reduction in the 250HD concentrations (8.8 +/- 5.2 ng/ml vs 19.2 +/- 10.7 ng/ml; p = 0.002), 1.25(OH)2D (25 +/- 8 pg/ml vs 34 +/- 9 pg/ml; p = 0.002) and parathyroid hormone (intact molecule) (1.9 +/- 0.9 pmol/l vs 5.9 +/- 2.0 pmol/l; p = 0.0001). By contrast, the levels of calcitonin (65 +/- 30 pg/ml vs 36 +/- 17 pg/ml; p = 0.001) and tartrate-resistant acid phosphatase (17.3 +/- 2.3 U/l vs 11.8 +/- 1.8 U/l; p = 0.0001) were increased. There also was a mild increase of vitamin D carrier protein (532 +/- 109 mg/l vs 480 +/- 37 mg/l; p = 0.04). These data are consistent with a partial inhibition of parathyroid hormone, associated with vitamin D deficiency. The inhibition of the axis of parathyroid hormone--1.125(OH)2D resulting from calcium release from the bone is advanced as an explanation. This release might be due to the action on the bone of cytokines produced within the inflammatory process itself. The reduction in 250HD could presumably be related with the lower exposure to sun, which is common in sick persons.
Serum vitamin D metabolites and other parameters of mineral metabolism were measured in 12 patients with anorexia nervosa. Serum concentrations of calcium, phosphate, albumin, alkaline phosphatase, parathyroid hormone, calcitonin, osteocalcin, and 24-hours calcium excretion were normal. Serum 25-hydroxyvitamin D (25OHD) concentration was similar in patients and normal subjects, whereas 1,25-dihydroxyvitamin D (1,25(OH)2D) levels were significantly reduced in patients (62 +/- 17 vs 82 +/- 17 pmol/l); p less than 0.05). The concentration of vitamin D-binding protein (DBP) in patients was normal, but serum binding capacity (Nmax) was diminished in anorectic patients (2.05 +/- 0.50 vs 2.53 +/- 0.51 mumol/l; p less than 0.05). The diminished serum binding capacity, in spite of normal concentrations of albumin and DBP, reflects the presence of qualitative rather than quantitative defects in serum transport proteins. Since the reduction in 1,25(OH)2D and serum binding capacity was quantitatively similar, it is likely that free 1,25(OH)2D levels would be normal.
This study was undertaken to analyse the relationship between total calcium (TCa) and ionized calcium (ICa) in patients with cancer, and to assess the clinical value of routine measurements of ICa in these patients. Serum TCa, ICa, albumin, proteins and creatinine were measured in 188 adult patients with solid malignant tumours. Most of them were out-patients, the Karnofsky score being 80 or above in 67%. The correlation coefficient between ICa and TCa was 0.85 (P less than 0.001) and did not improve after correcting TCa for protein concentration with several published formulae. Although TCa measurements had a global diagnostic accuracy (percent of patients correctly classified) of 90%, they failed to identify a substantial proportion of patients with increased levels of ICa (57% for uncorrected TCa, and 27-57% for protein-corrected TCa). However, the finding of slightly increased ICa levels did not seem to predict the development of frank hypercalcaemia and did not impair the prognosis. According to these results, the routine measurement of ICa in unselected patients with cancer has no clinical usefulness.
Specific receptors for 1,25 Dihydroxyvitamin D3 have been described in human peripheral blood mononuclear cells (PBMC). We have tried to find out whether these receptors could show any difference in sex or age distribution. Twenty two healthy men aged 21-66 yr (mean +/- SD 41.0 +/- 13.6) and nineteen healthy women aged 22-60 yr (38.9 +/- 13.9) have been studied. The mean dissociation constant (Kd) was similar in both sexes (1.35 +/- 0.70 x 10(-10) M in males, 1.13 +/- 0.66 x 10(-10) M in females), but the concentration of binding sites (Nmax) was significantly lower in females (2.32 +/- 0.92 fmol/10(7) PBMC vs 4.43 +/- 1.38 fmol/10(7) PBMC in males; p = 0.0001). Neither Kd nor Nmax were significantly correlated with age. No difference was found between pre and postmenopausal women. Further studies are needed to elucidate if this sex difference in PBMC receptors for 1.25 Dihydroxyvitamin D3 is of any pathophysiological relevance.
It has been observed that anorexia nervosa (AN) patients present osteoporosis (OP) although the mechanism by which it occurs is not well known. The reduction in calcium intake as well as a decrease in estrogen production which is associated with involutive OP, could be involved. We have found in the literature 16 cases of AN and OP, one of which presented a fracture of the sternum. We now present another case of fracture of the sternum. This implies a high incidence of this type of fracture in OP due to AN which is extremely rare in involutive OP, which suggests that the ethiopathogenic factors of the former are different from those of the latter.
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