Correlations between bone mineral density, insulin-like growth factor I and auxological variables.

Recent studies have shown growth-related changes in spinal bone mineral density (BMD) in children; however, there is less information available on the relationship between BMD and insulin-like growth factor I (IGF-I). The aim of this study was to relate the BMD of the spine and radius with serum IGF-I levels and auxological variables in normally growing children. We used dual X-ray absorptiometry to measure the BMD in the lumbar spine (L1-L4) and distal radius of 121 children (69 boys, 52 girls) aged 3-18 years whose growth velocity was normal. Lumbar and radial BMD increased with age (p < 0.001) and puberty (p < 0.001) and was highly correlated to age, weight, height, body surface and bone age (r = 0.70-0.89 and p < 0.001 for all variables). Partial correlation, with age held constant, was weaker but still significant for most auxological variables. Serum IGF-I concentrations increased slowly during childhood and markedly during early stages of puberty, and correlated with lumbar and radial BMD (r = 0.55 and 0.45, respectively; p < 0.001) and with the auxological variables (p < 0.001). When age was held constant, IGF-I levels still correlated significantly with the auxological variables and with BMD, except in the case of radial BMD in boys. By multiple regression analysis IGF-I, unlike auxological variables, did not reach significance in the ability to predict BMD. Therefore, in healthy children, serum IGF-I levels show a weaker relationship to BMD than do auxological variables.

Study of bone loss in diabetes mellitus type 1.

While people with type 1 diabetes mellitus (DM) often have bone deficiency, the relation between this deficiency and the duration or control of diabetes remains controversial. To assess the possibility of such an interrelationship, we studied parameters relating to mineral metabolism (Ca, P, alkaline phosphatase, Mg, PTH, and hydroxyproline (OHP)); bone remodeling (osteocalcin); diabetic control (HbA1c); and radiological study of the second metacarpal of the left hand and of bone age in 87 children with type 1 DM. The mineral parameters were not abnormal among the diabetics. Diabetic children had similar levels of fasting osteocalcin as normals (10.05 +/- 4.9 vs. 9.79 +/- 3.34 ng/ml, mean +/- SD); this did not differ by sex. The bone age fell within two standard deviations of the mean, and 9.5% of the diabetics had a bone mass deficit (less than the mean cortical thickness) greater than 2 SD. There was no correlation between osteocalcin and Ca, P, glycemia, HbA1c, PTH, Mg, or OHP. Our results do not support any association between bone mass loss and the severity or duration of type 1 diabetes. Bone turnover, measured by serum osteocalcin, was normal. Therefore the pathogenesis of osteopenia in type 1 DM remains unclear, and requires further investigation.

Pituitary-thyroid function in patients with septic shock and its relation with outcome.

OBJECTIVE: To study the time course of thyroid function abnormalities and their relation to outcome in patients with septic shock. DESIGN: Prospective study in a cohort of consecutive patients. SETTING: Intensive Care Unit in a University Hospital. PATIENTS AND METHODS: We studied 27 patients (mean age 50 +/- 19 years, Apache II score 18.4 +/- 5.2, 15 survivors) diagnosed of septic shock. Total T4 (T4) and total T3 (T3) (RIA) were determined on days 1 and 5 after admission. We also measured TSH (ultrasensitive RIA) at 08.00, 20.00 and 01.00 hours (on days 1 and 5), and the TSH response to TRH (400 microg intravenous) on days 2 and 6. Data are mean +/- SD. RESULTS: Whereas low thyroid hormones concentrations were present on day 1 in all patients, only survivors presented a significant increase in T3 and T4 on day 5. Basal TSH levels and the area under the curve of the TSH response to TRH on day 2 were significantly higher in survivors than in non survivors (0.89 +/- 0.63 vs. 0.34 +/- 0.42 microIU/ml, and 229 + 157 vs. 101 + 101). The normal nocturnal (01.00 hr) surge of TSH (the difference between TSH concentrations at 8 am and at 1 am) was abolished in both survivors and non survivors on day 1 but it was recovered on day 5 only in survivors. CONCLUSIONS: Our data indicate that patients with septic shock present an altered hypothalamic-pituitary-thyroid axis, and that survivors thyroid function differs from that of non survivors shortly after diagnosis. Survivors are characterised by a greater TSH response to TRH, indicating a less deranged hypothalamic-pituitary-thyroid axis. Thyroid function improves in survivors, but not in non survivors, during the course of their illness.

Plasma arginine vasopressin concentration during laparoscopy.

Plasma arginine vasopressin concentration (pAVP) was determined in 47 patients during the insufflation stage of laparoscopy. Laparoscopy was performed under local anesthesia in 39 patients, and under general anesthesia in 8. Pneumoperitoneum was induced with 3-4 1 nitrous oxide to a maximum intra-abdominal pressure of 10 mm Hg. Induction of pneumoperitoneum resulted in a prompt and significant increase in pAVP in every case. In 34% of cases, pAVP increased two- to fivefold as compared with preinduction levels; in 44.7% of cases, elevations of more than fivefold were seen. Increased arginine vasopressin secretion was not related to underlying liver disease, degree of anxiety, changes in blood pressure, heart rate, pCO2, pO2, serum bicarbonate or plasma osmolality. Elevated pAVP was associated with a significant increase in right atrial pressure. In conclusion, abdominal distension during laparoscopy was accompanied by an increase in pAVP. It seems likely that arginine vasopressin response could be due to a decrease in the left atrial transmural pressure gradient.

Bone loss and turnover in patients with liver transplantation.

We have studied bone turnover markers and bone mineral density (BMD) in 82 patients (26 females and 56 males) that underwent orthotopic liver transplantation in our center. Follow-up was for a median of 19.2 months (range 1-60 months). During this period they were treated with prednisone, azathioprine and cyclosporine in accordance with protocols. Spinal bone loss was measured with a dual energy X-ray densitometer (precision 1.3%), and, depending on Z score and BMD values, two groups were distinguished: A) Without osteoporosis: 47 patients, Z = -0.98 +/- 0.09 and BMD 0.899 +/- 0.098 g/cm2, and B) With osteoporosis: 35 patients, Z = -2.71 +/- 0.55 and BMD 0.739 +/- 0.080 g/cm2 (X +/- SD). Serum bone markers such as osteocalcin (BGP) 10.0 +/- 0.8 ng/ml and procollagen-I (pColl-I) 268.1 +/- 32.1 micrograms/ml, were found to be increased. Serum PTH was within the normal range. No significant differences were found between the etiologic subgroups studied with respect to bone loss. Also, no correlation was found between bone loss and duration of follow-up or other factors, such as immunosuppressant drugs or acute rejection. Our study confirms an increased prevalence of bone loss in patients with liver transplantation, which is associated with a high bone turnover, indicating that earlier diagnosis and treatment is necessary to improve survival and quality of life in these patients.

[Effect of total parenteral nutrition on bone metabolism]. / Efecto de la nutrición parenteral total en el metabolismo óseo.

Total parenteral nutrition (TPN) for a prolonged period of time can be associated with bone pain and osteomalacia. We performed a study on the phosphorus/calcium metabolism and serum levels of osteocalcin (BGP), a protein proposed as constituting the bone turnover index in 31 patients receiving TPN (age 57 +/- 14 years, 22 males and 9 females) diagnosed as suffering from pathology of the digestive tract or geno-urinary pathology. The duration of the TPN was from 9.1 +/- 6.6 days (range 2-31 days). We observed and increase of FA (178 +/- 101 U/l), with a significant decrease of BGP (2.2 +/- 2.0 ng/ml vs. 3.7 +/- 1.3 ng/ml in controls; p less than 0.001). Serum levels of phosphorus and calcium corrected according to proteins were within normal limits. Hypercalciuria was detected in the urine (328 +/- 278 mg/24 hours), and phosphaturia (607 +/- 522 mg/24 hours). Based on the BGP results, we can conclude that patients subjected to TPN for a short period of time undergo a decrease in bone turnover.

[Plasma histamine levels after the administration of atracurium or pancuronium in patients undergoing general anesthesia]. / Niveles plasmáticos de histamina tras la administración de atracurio o pancuronio en pacientes sometidos a anestesia general.

OBJECTIVES: To compare the release of histamine induced by atracurium and pancuronium. MATERIAL AND METHODS: We studied 20 patients ASA III undergoing vascular surgery under etomidate anesthesia. Patients were randomly treated with either 0.5 mg/kg of atracurium or 0.1 mg/kg of pancuronium as muscle relaxant agents. Plasma histamine concentration, heart rate, arterial blood pressure, PaO2, and PaCO2 were measured at the basal state and 1.2 and 5 min after administration of the muscle relaxant drug. RESULTS: Plasma histamine concentration at baseline were 0.691 +/- 0.6 ng/ml in the atracurium group and 0.756 +/- 0.612 ng/ml in the pancuronium group. These levels raised up to 2.748 +/- 6.278 ng/ml (atracurium) and 2.553 +/- 5.454 ng/ml (pancuronium). These differences were not statistically significant. The course of the remaining parameters studied in these patients was also comparable between the two groups. There were no clinical manifestations associated with the release of histamine. CONCLUSIONS: Plasma levels of histamine after administration of atracurium were not significantly different from those induced by pancuronium.

[Study of bone involvement in hypothyroidism determining the blood levels of osteocalcin]. / Estudio de la repercusión ósea en el hipotiroidismo mediante la determinación de osteocalcina sérica.

Several bone abnormalities, characterized by a decreased bone turnover, may develop in patients with hypothyroidism. We have used the measurement of serum Osteocalcin (BGP), a protein synthesized by osteoblasts and proposed as a marker of bone formation, in order to elucidate the bone status in 62 hypothyroid patients, mean age 52 +/- 15 (SD) years. As a group, BGP results in hypothyroidism were not different from normal (3.6 +/- 3.2 vs 3.7 +/- 1.3 ng/ml). However, we were able to differentiate 3 groups: 1) patients with significantly lower BGP values (p less than 0.01) (primary hypothyroidism and total thyroidectomy with body scan); 2) patients with antithyroid drugs had significantly higher BGP levels (p less than 0.05); 3) in the other groups (post-1311, post-surgery, and insufficiently treated hypothyroidism) BGP values were within normal limits. In the total group BGP was significantly correlated with T3T, TSH, alkaline phosphatase and age. Lower serum BGP values in some etiologic groups of hypothyroidism may reflect a greater pathologic effect on the bone in these patients, with a decrease in bone formation.

Low levels of basic fibroblast growth factor (bFGF) are associated with a poor prognosis in human breast carcinoma.

It has been suggested that angiogenesis and angiogenic factors may be strong predictors of relapse in patients with breast carcinoma. We measured the levels of the angiogenic peptide basic fibroblast growth factor (bFGF) in 140 breast tumour cytosols using an immunoassay. There were no significant differences in bFGF levels between breast non-malignant lesions and primary carcinomas. In 124 cases with primary breast cancer, we observed an association of low bFGF levels (< 400 pg mg[-1]) with increasing tumour size (P = 0.023) and stage of disease (P = 0.002). bFGF levels did not correlate with other variables, including axillary nodes, hormone receptors, cathepsin D and the serum tumour markers CA15.3 and CEA. With a median follow-up of 44.0 months, breast cancer patients with low levels of bFGF had a significantly shorter disease-free survival (DFS) than patients with elevated bFGF (log-rank, P < 0.0001). In a multivariate analysis of DFS, only bFGF, T-stage and histological grade showed statistical significance. In a parallel evaluation of circulating bFGF, we did not observe a correlation between the serum and tissue bFGF levels in the 29 selected cases with matched determinations. Our results indicate that low bFGF levels in breast carcinoma are an independent prognostic indicator of poor prognosis and disease recurrence.

Calcitonin and bisphosphonates treatment in bone loss after liver transplantation.

Osteopenia is a major complication of orthotopic liver transplantation (OLT). However, no effective therapy for bone disease has been defined. We have studied vertebral bone mineral density (VMD) and fasting serum markers of bone formation [bone gla protein (BGP), procollagen I carboxyterminal peptide (PICP)] and metabolism (serum Ca, P, intact parathyroid hormone (iPTH), 25OHD3 and 1,25(OH)2D3) in 120 patents after OLT. VMD was measured by dual-energy X-ray absorptiometry (DXA) using a Hologic QDR 1000 densitometer on two occasions, 12 months apart. Patients with OLT had a VBD significantly lower compared with age- and sexed-matched Spanish controls (P < 0.05). Prevalence of osteoporosis (Z score below -2 SD) was 35.8%. Serum BGP (8.6 +/- 0.7 ng/ml) and PICP (222.9 +/- 81.9 ng/dl) were higher than those of controls. However, serum calcium, phosphorus, iPTH, 25OHD3, and 1,25(OH)2D3 were within normal range. Patients with osteoporosis were randomly treated with 40 IU/day of calcitonin i.m. (Diatin, Ferrer Int. Laboratories) (n = 17) or 400 mg p.o., 15 days every 3 months, of sodium ethiodronate (Difosfen, Rubio Laboratories) (n = 23). All patients received 500 mg/12 hours of elemental calcium p.o. After 12 months of treatment, a significant increment of vertebral mineral density (VMD) was observed (6.4% and 8.2%, respectively). Serum BGP and PICP values remained elevated without a difference between the two drugs. Our results indicate that antiresorptive drugs may be of benefit in the high turnover osteoporosis of OLT recipients.

[Serum osteocalcin and bone turnover in hyperthyroidism]. / Osteocalcina sérica y remodelado óseo en el hipertiroidismo.

In hyperthyroidism an increased bone turnover may appear, essentially due to a higher bone resorption. In order to evaluate this complication we have measured the serum levels of Osteocalcin (BGP) in 41 patients, mean age 43 +/- 18 (+/- SD) years. BGP is a protein synthesized by osteoblasts which may be employed as an specific and non-aggressive marker of bone turnover. Serum BGP was significantly increased in these patients with respect to normals (6.2 +/- 4.2 vs 3.7 +/- 1.3 ng/ml). The total group was divided according to BGP values higher and lower than 3.7 ng/ml, emerging two groups with BGP 7.9 +/- 3.8 (n = 30) y 2.2 +/- 1.2 ng/ml (n = 11), respectively. There were not differences between these two groups regarding to thyroid hormones or other data of mineral metabolism. In the total group, only serum BGP and T3 were correlated. Our results suggest the existence of a double effect of hyperthyroidism on bone, as well as a temporal dissociation between thyroid synthesis and bone metabolism.

Squamous cell carcinoma of the renal pelvis associated with hypercalcemia and the presence of parathyroid hormone-like substances in the tumor.

A case of hypercalcemia associated with documented squamous cell carcinoma of the renal pelvis without bone metastasis is reported. High levels of cross-reacting parathyroid hormone-like material in serum and its presence in tumoral tissue were detected. To our knowledge this is the fourth case described in the literature and the first in which tumoral production of parathyroid hormone-like material is demonstrated.

Effect of insulin on plasma triglyceride concentration in hepatectomized geese.

The effect of insulin on the removal of plasma triglycerides was tested in hepatectomized geese. In this preparation plasma triglyceride concentration decreases exponentially following hepatectomy. Infusion of insulin (0.001 U/kg/min. for 60 minutes) had no significant effect on the rate of disappearance of plasma triglycerides in the hepatectomized animals. The conclusion is, therefore, reached that insulin does not affect the removal of plasma triglycerides by the extrahepatic tissues in the goose.

Plasma arginine vasopressin response to oral, gastric, and intravenous water load in patients with cirrhosis.

BACKGROUND/AIMS: Hepatic osmoreceptors are sensitive to changes in portal blood osmolality and cause variations in plasma antidiuretic hormone and water diuresis, which prevent major systemic osmotic changes. Insensitivity of hepatic osmoreceptors might contribute to maintaining increased plasma levels of antidiuretic hormone and negative free water clearance after oral hydration in some cirrhotic patients. METHODS: We measured free water clearance and plasma arginine vasopressin levels in basal conditions and after oral, intravenous, and intragastric water overload in control subjects (group I) and patients with cirrhosis (some with a positive [group II] and some a negative [group III] free water clearance). RESULTS: In groups I and II, no significant differences in plasma arginine vasopressin levels were found regardless of the route used for hydration. In group III, plasma levels were significantly higher between 0 and 75 minutes after intragastric hydration than after oral or intravenous hydration. No significant changes in plasma osmolality were detected between minute 0 and 20 after the end of oral or intragastric hydration, although plasma arginine vasopressin decreased significantly only 5 minutes after the oral hydration. Group III patients showed evidence of autonomic neuropathy. However, this dysfunction was unrelated to the insensitivity to gastric hydration. CONCLUSIONS: Hepatic osmoreceptors seem to be disturbed in some cirrhotic patients, although this dysfunction may be compensated for by normally functioning oropharyngeal and hypothalamic osmoreceptors.

Effect of intrathoracic pressure on plasma arginine vasopressin levels.

Abdominal distention during pneumoperitoneum results in a marked increase in plasma arginine vasopressin levels, which has been ascribed to an increase in intrathoracic pressure. Because of this relationship, tense ascites could contribute to nonosmotic release of antidiuretic hormone, to the development of hyponatremia, and eventually to further ascites formation. The effect of pneumoperitoneum, thoracocentesis, and paracentesis on plasma arginine vasopressin levels was studied in three groups of patients, and the mechanism by which these maneuvers may induce these changes was investigated. Patients with pleural effusion, pneumothorax, or ascites showed a significant increase in plasma arginine vasopressin levels, and thoracocentesis or paracentesis resulted in a decrease in these levels. Plasma vasopressin levels increased significantly during pneumoperitoneum, as did intrathoracic and atrial pressures; the atrial transmural pressure gradient declined. However, no changes in plasma levels of norepinephrine, aldosterone, and renin activity were observed during pneumoperitoneum. Changes in plasma arginine vasopressin levels correlated with the changes in intrathoracic and atrial pressures and transmural pressure gradient. The authors conclude that increased intrathoracic pressure is associated with an increase in plasma arginine vasopressin levels and propose that ascites could be a factor promoting vasopressin release by acting on intrathoracic volume receptors in decompensated cirrhotics.

Diagnostic value of three tumor markers determined in pleural effusions.

In order to discriminate between malignant and benign effusions, the values of tissue polypeptide specific antigen,carcinoembryonic antigen and squamous cell carcinoma associated antigen were measured in the pleural fluid of 30 patients with neoplasm, 10 with tuberculous pleurisy, 10 with transudates due to congestive heart failure or cirrhosis, 29 with parapneumonic effusions and 23 with benign diseases other than tuberculosis and pneumonia. Carcinoembryonic antigen and tissue poly-peptide specific antigen levels in effusions due to neoplasms were significantly higher than those in effusions due to other diseases. The areas under Receiver Operating Characteristic curves for carcinoembryonic antigen and tissue polypeptide specific antigen determinations were 0.69 and 0.67, respectively. No significant differences were found in the pleural fluid squamous cell carcinoma associated antigen levels between neoplasms and other diseases. The ability of tissue polypeptide specific antigen and carcinoembryonic antigen to discriminate between benign and malignant effusions may be considered comparable. Although both carcinoembryonic antigen and tissue polypeptide specific antigen showed a low accuracy (the number of undiagnosed pleural effusions is considerably high), both tissue polypeptide specific antigen and carcinoembryonic antigen determinations may contribute to a correct diagnostic classification. Moreover, the combination of these markers provides a specificity of 97.2%. However, the low number of positivities obtained for tissue polypeptide specific antigen and carcinoembryonic antigen together (13 cases in our series) reveals the need for further investigations.

Antidiuretic hormone and renal function after water loading in patients with cirrhosis of the liver.

Renal function and plasma antidiuretic hormone (ADH) levels were studied basally and after oral water load in four groups of subjects: 15 healthy controls (group I), 15 cirrhotics without ascites (group II), 15 cirrhotics with ascites (group III), and 10 decompensated cirrhotics with hyponatremia (group IV). Renal function and ADH levels were normal in group II. In groups III and IV water diuresis and fractional proximal sodium excretion were significantly decreased, whereas fractional distal sodium resorption and fractional excretion of potassium did not differ from those of controls. Basal ADH was significantly increased only in patients of group IV. In these patients ADH remained abnormally high after water loading. ADH did not correlate with water diuresis, plasma osmolality, mean arterial pressure, and plasma renin activity. We conclude that impaired water excretion in decompensated cirrhotics without hyponatremia cannot be ascribed to high serum levels of ADH. On the contrary, it seems to be related mainly to a reduced delivery of filtrate to the diluting segment of the nephron. In cirrhotic patients with hyponatremia high levels of ADH may play an additional role.