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J Hurtado

Publications and source records attributed to J Hurtado.

At least 19 recordsLinked to original sources
PubMed2004

[Progressive deterioration in an elderly patient].

Vasculitis is diagnosed with increasing frequency in the elderly. We hereby present the case of an 84-year-old male, who had weight loss, low-degree fever, anemia and epigastric pain. After 14 days of study with the tentative diagnosis of digestive neoplasia, a progressive renal insufficiency was detected. This clinical picture was secondary to ANCA-positive vasculitis. The case poses the differential diagnosis of non-oliguric acute renal failure (FRA) in elder people and the systematics of the study of renal insufficiency in individuals with previously unknown renal function. Also, this patient's history emphasizes the importance of acute deterioration of renal function as a guiding symptom for orienting the interpretation of clinical data. In the present case, a diagnostic hypothesis based only in the pursue of an occult digestive tumor misguided the attention from the main cause of the disease.

Abdominal Pain↗
PubMed2002

Treatment of malignant hypercalcaemia.

Hypercalcaemia is a common paraneoplastic syndrome caused by the production by tumours of several factors which affect bone resorption and/or tubular calcium reabsorption. Antihypercalcaemic therapy in cancer patients involves rehydration manoeuvres, as well as the use of a variety of available drugs which inhibit bone resorption, namely plicamycin, calcitonin, bisphosphonates and gallium nitrate. While plicamycin is currently out of use because of its considerable toxicity, bisphosphonates have become the standard therapy in hypercalcaemia of malignancy (HM). These compounds are potent inhibitors of bone resorption but they do not affect tubular calcium reabsorption, which limits their efficacy in humoral HM (HHM) cases. In these patients, gallium nitrate should be the therapy of choice. Among the available bisphosphonates, pamidronate administered in a single infusion of 90 mg, normalises serum calcium levels in > 90% of HM patients. A recently introduced bisphosphonate, zoledronate, is likely to replace pamidronate as a first-line therapy in these patients. The effectiveness of calcitonin in HM treatment is limited, although it seems to be useful at the outset in cases with severe symptomatic hypercalcaemia. Future treatment options of HM are likely to include new bone resorption inhibitors, for example, naturally-occurring osteoprotegerin, or alternate approaches aimed at reducing the tumour production of parathyroid hormone-related protein with noncalcaemic analogues of calcitriol or ras-isoprenylation inhibitors. The development of putative therapeutic agents targeted to inhibit distal calcium reabsorption should be valuable in the management of HHM cases.

Diphosphonates↗
PubMed2000

Parathyroid hormone-related protein, parathyroid hormone, and vitamin D in hypercalcemia of malignancy.

The pathogenesis of cancer-associated hypercalcemia is not yet completely understood. In the majority of cancer patients, hypercalcemia appears to be a consequence of the tumor production of parathyroid hormone (PTH)-related protein (PTHrP). However, patients with humoral hypercalcemia of malignancy, in contrast to those with primary hyperparathyroidism, have an uncoupled bone turnover, and they usually have low circulating levels of 1.25(OH)2D3. We performed a case-control study to assess the relationship of plasma PTHrP, PTH and 1.25(OH)2D3 with hypercalcemia in cancer patients with a variety of tumors. Sixty of these patients had hypercalcemia, and 45 were normocalcemic. We measured PTHrP and PTH by immunoradiometric assay (Nichols), and 1.25(OH)2D3 by radioreceptor assay (Nichols), in plasma in both groups of cancer patients. Using a logistic regression analysis, we found that the higher PTHrP in plasma, the higher association with hypercalcemia occurred in these patients. In addition, the decreased plasma levels of PTH and 1.25(OH)2D3 in the majority of cancer patients were found to be significantly associated with hypercalcemia. Our results indicate that the combined determination of PTH, PTHrP and 1.25(OH)2D3 in plasma represents a more comprehensive approach to the investigation of hypercalcemia in cancer patients. Our data also support the role of PTHrP as a humoral factor responsible for hypercalcemia in these patients.

Adult↗
PubMed2000

Relationship of plasma bone cytokines with hypercalcemia in cancer patients.

The pathogenesis of cancer-associated hypercalcemia is not yet completely understood. This syndrome appears to be a consequence of the tumor production of humoral factors, mainly parathyroid hormone related protein (PTHrP). However, patients with humoral hypercalcemia of malignancy have features suggesting that factors other than PTHrP might play a role in this syndrome. We performed a case-control study in cancer patients with and without hypercalcemia. A total of 105 patients with a variety of tumors, 60 of them with hypercalcemia (corrected serum calcium over 2.6 mmol/l), and 45 without hypercalcemia. In a previous study, we demonstrated that plasma PTHrP was highly associated with hypercalcemia in these patients. In the present study, we measured the plasma levels of various bone cytokines: interleukin-1beta (IL-1beta), interleukin-6 (IL-6), transforming growth factor (TGF) alpha, and tumor necrosis factor (TNF) alpha, in these cancer patients. We also determined C-terminal type I procollagen (PICP) and C-terminal telopeptide of type I collagen (ICTP), bone formation and bone resorption markers, respectively, in serum in these patients. We found that these osteolytic cytokines do not increase in plasma by the presence of hypercalcemia. In fact, using a logistic regression analysis, a significant (P<0.02) association was found between the low plasma levels of IL-1beta and TGFalpha and hypercalcemia, independent of plasma PTHrP and the presence of bone metastasis, in these patients. No significant association between the plasma levels of IL-6 or TNFalpha and hypercalcemia was found in these cancer patients. Serum ICTP correlated (r=0.35; P=0.008) with hypercalcemia in these patients, but none of the cytokines studied in plasma correlated with either ICTP or PICP in these hypercalcemic patients. Our data indicate that the circulating levels of several bone cytokines are not enhanced by PTHrP in hypercalcemic cancer patients. The mechanism responsible for the association between the low plasma levels of some of these cytokines and hypercalcemia in these patients remains obscure. However, this finding does not rule out the possible local bone effects of these cytokines, contributing to hypercalcemia in cancer patients.

Adult↗
PubMed1998

Trace metals in oysters and sediments of Botany Bay, Sydney.

Trace metal concentrations (Pb, Cd, Cu and Zn) in Sydney rock oysters (Sacostera commercialis) and sediments (< 53 microns fraction) were determined for six sites in the northern regions of Botany Bay. Levels for lead, cadmium, copper and zinc in oysters ranged (in microgram g-1) from 1.38 to 15.3, 1.81 to 16.3, 56.1 to 212 and 1806 to 2902, respectively. In sediments, levels ranged (in microgram g-1) from 599 to 4081, 3.57 to 91.0, 191 to 1113 and 227 to 1472, respectively. Such values indicated high levels of contamination, especially in the sediments. Indeed, high proportions of the samples displayed metal concentrations that exceeded the prescribed limits for oysters and sediments. No significant correlations in metal concentrations were found between oysters and sediments, suggesting that changes in the sediment metal loading are not solely influencing the levels of bioavailable metal. The results supported the conclusion that different rates and mechanisms of metal accumulation are taking place in the two types of samples. Variability between sites was high, particularly for oysters. Multidimensional scaling identified that the Cooks River (site 3) and La Perouse (site 6) sites were most dissimilar, both to each other as well as to the other four sites. This was a reflection of high contamination in the Cooks River and the generally low levels in the La Perouse reference sample. The configuration was mainly influenced by the sediment parameters, rather than the oyster metal concentrations, indicating the sediment data were better for identifying site similarities. These ordinations provide evidence of the usefulness of multidimensional scaling in elucidating the physico-chemical variability of the sampling sites.

Animals↗
PubMed1998

Comparison of two immunoradiometric assays for parathyroid hormone-related protein in the evaluation of cancer patients with and without hypercalcemia.

Hypercalcemia is a common paraneoplastic syndrome due to the secretion by tumors of parathyroid hormone-related protein (PTHrP) and/or other osteolytic factors. In the present study, we have measured plasma PTHrP using two immunoradiometric assays for PTHrP, assay N (Nichols) and assay I (INCSTAR), recognizing the 1-86 domain of PTHrP, for the evaluation of malignancy-associated hypercalcemia. The study included 25 tumor patients with hypercalcemia (HCa) [corrected serum calcium (SCa) > or = 2.70 mmol/L], 20 normocalcemic patients with cancer (NCa), and ten healthy control subjects. Plasma PTHrP was either undetectable or within the respective normal range in the majority of NCa patients and in the control subjects, with both assays. Plasma PTHrP was increased in 13 and 15 of HCa cases with assay N and assay I, respectively. PTHrP was elevated in plasma in 5/6 (assay N) and 3/6 (assay I) HCa patients with squamous tumors. However, plasma PTHrP was high in only 2/9 (assay N) and 1/9 (assay I) HCa cases with hematological tumors. Less than 40% of HCa patients with bone metastases, and >75% of those without bone involvement, had elevated plasma PTHrP with both assays. Detectable plasma PTHrP and SCa were significantly correlated using assay N (p = 0.025) and assay I (p = 0.01), in the HCa group. A highly significant correlation (p <0.001) was found between detectable plasma PTHrP with both assays, and a high agreement between them based on simple kappa statistics (p < 0.001), in the latter group. Our results indicate that each assay may be similarly useful in detecting PTHrP hyperproduction in cancer patients.

Adult↗
PubMed1997

PEEP-induced tricuspid regurgitation.

OBJECTIVE: To determine the presence of tricuspid regurgitation (TR) in patients affected by acute lung injury (ALI) and the adult respiratory distress syndrome (ARDS) during mechanical ventilation with positive end-expiratory pressure (PEEP). DESIGN: A prospective clinical study. SETTING: 10-bed general intensive care unit in a University Hospital. PATIENTS: 7 consecutive patients an age 44.7 +/- 8.6 years with a diagnosis of ALI or ARDS were studied. All were on mechanical ventilation with PEEP. INTERVENTIONS: PEEP was increased in steps of 5 cm H2O until the appearance of TR or up to a limit of 20 cm H2O. MEASUREMENTS AND RESULTS: Right atrial pressure, pulmonary artery pressure, and wedge pressure were measured and cardiac output was determined by thermodilution. TR was graded from 0 to 3. Standard 2D echocardiographic and pulsed-wave images were obtained at each level of PEEP. PEEP was increased from 4 +/- 3 to 17 +/- 2 cm H2O. Mean PAP increased from 27.7 +/- 2.9 to 36.7 +/- 3.5 mm Hg (p < 0.02) when PEEP was increased. Five patients had competent valves and two had mild TR at baseline. In six out of the seven, TR either developed or increased when PEEP was increased. CONCLUSIONS: Our study demonstrated the development of TR after the use of PEEP in patients with ALI and ARDS as a consequence of pulmonary hypertension and right ventricular overloading. Since TR may randomly affect cardiac output values and derived parameters, the assessment of cardiac performance by some techniques such as thermodilution should be used with caution.

Adult↗
PubMed1997

Cardiopulmonary and haemodynamic changes during total hip arthroplasty.

We report a prospective study of 30 patients who underwent total hip arthroplasty for osteoarthrosis in order to investigate the haemodynamic and respiratory changes which occur during operation. Cement was used in 17 cases and the implants were not cemented in 13. Pulmonary and cardiac function, blood levels of methylmethacrylate monomer, intramedullary pressure and transoesophageal echocardiography were recorded. Two well differentiated echogenic patterns appeared consistently during the operation. The intramedullary pressure became raised as the cement was inserted. The following changes occurred within seconds and continued for some minutes: elevation of mean arterial pressure and mean pulmonary artery pressure; decrease of arterial oxygen tension and of mixed venous PO2, and greater tissue consumption of oxygen. Although we recorded raised concentration of methylmethacrylate monomer in venous blood after the cement was inserted, there is no evidence that the monomer is responsible for the haemodynamic changes which take place.

Aged↗
PubMed1995

Role of 4-1BB ligand in costimulation of T lymphocyte growth and its upregulation on M12 B lymphomas by cAMP.

K46J B lymphomas express a T cell costimulatory activity that is not inhibited by CTLA-4Ig, anti-B7-1, anti-B7-2, anti-intercellular adhesion molecule 1 or antibodies to heat stable antigen. In this paper we report that this costimulatory activity is mediated at least in part by 4-1BB ligand, a member of the tumor necrosis factor (TNF) gene family that binds to 4-1BB, a T cell activation antigen with homology to the TNF/nerve growth factor receptor family. A fusion protein between 4-1BB and alkaline phosphatase (4-1BB-AP) blocks T cell activation by K46J lymphomas in both an antigen-specific system and with polyclonally (anti-CD3) activated T cells. 4-1BB-AP also blocks antigen presentation by normal spleen cells. When the antigen-presenting cells express B7 molecules as well as 4-1BB ligand, we find that B7 molecules and 4-1BB-AP both contribute to T cell activation. These data suggest that 4-1BB ligand plays an important role in costimulation of IL-2 production and proliferation by T cells. The B lymphoma M12 expresses low levels of 4-1BB-L but can be induced to express higher levels by treatment of the B cells with cAMP, which also induces B7-1 and B7-2 in these cells. Thus cAMP appears to coordinately induce several costimulatory molecules on B cells.

4-1BB Ligand↗
PubMed1995

Characterization of human homologue of 4-1BB and its ligand.

The human homologue of 4-1BB (H4-1BB) cDNA was isolated from PMA plus ionomycin-treated human peripheral T-cell cDNA libraries. The amino acid sequence deduced from the nucleotide sequence showed that the protein is composed of 255 amino acids with 2 potential N-linked glycosylation sites. The molecular weight of its protein backbone is calculated to be 27 kDa. The H4-1BB contains features such as signal sequence and transmembrane domain, indicating that it is a receptor protein. This protein showed 60% identity of amino acid sequence to mouse 4-1BB. In the cytoplasmic domain there are 5 regions of amino acid sequences conserved from mouse to human, indicating that these residues might be important in the 4-1BB function. H4-1BB mRNA was detected in unstimulated peripheral blood T cells and was inducible in T-cell lines such as Jurkat and CEM. H4-1BB-AP, a fusion protein between the H4-1BB extracellular domain and alkaline phosphatase, was used to identify the ligand for the H4-1BB. Although the H4-1BB ligand was detected in both T and B cells of human peripheral blood, the ligand was preferentially expressed in primary B cells and B-cell lines. Daudi, a B-cell lymphoma, was one of the B-cell lines that carried a higher number of ligands. Scatchard analysis showed that the Kd = 1.4 x 10(9) M and the number of ligands in Daudi cell was 4.2 x 10(3).

3T3 Cells↗
PubMed1994

4-1BB T-cell antigen binds to mature B cells and macrophages, and costimulates anti-mu-primed splenic B cells.

4-1BB is expressed on activated murine T cells and may function as an accessory signaling molecule during T-cell activation. To identify putative 4-1BB ligands, a fusion protein consisting of the extracellular domain of 4-1BB fused to human placental alkaline phosphatase (4-1BB-AP) was constructed. Alkaline phosphatase activity could then be used as an indicator of the relative amount of bound 4-1BB. These studies indicated that 4-1BB-AP specifically bound to the surface of various mature B and macrophage cell lines. 4-1BB-AP bound at low levels to T cell lines (non-activated and anti-CD3-activated), pre-B-cell lines, and an immature macrophage cell line. 4-1BB-AP did not bind to a glial tumor cell line, HeLa cells, or COS cells. In addition, 4-1BB-AP bound at higher levels to F(ab')2 anti-mu-activated primary B cells compared to anti-CD3-activated primary T cells. Scatchard analysis indicated that the A20 B cell lymphoma expressed 3680 binding sites per cell with a Kd of 1.86 nM. Affinity cross-linking studies demonstrated that a major cell surface species of 120 kDa bound to 4-1BB-AP; 4-1BB-AP also bound to a minor species of approximately 60 kDa. The addition of paraformaldehyde-fixed SF21 cells expressing recombinant 4-1BB synergized with F(ab')2 anti-mu in inducing splenic B cell proliferation suggesting that 4-1BB may function as a regulator of B cell growth.

Animals↗
PubMed1993

Macrophage inflammatory protein-1 alpha rapidly modulates its receptors and inhibits the anti-CD3 mAb-mediated proliferation of T lymphocytes.

Macrophage inflammatory protein-1 alpha (MIP-1 alpha) is a member of the intercrine/chemokine family which consists of basic, heparin-binding, small molecular weight proteins. We have previously shown that a T cell line, CTLL-R8, carried high-affinity receptors for MIP-1 alpha and the proliferation of CTLL-R8 cells was inhibited by murine recombinant (mr) MIP-1 alpha. We extended our previous studies to murine resting splenic T lymphocytes to determine whether the inhibition of T cell proliferation is a general property of MIP-1 alpha. The resting splenic T cells carried approximately 680 high-affinity binding sites for mrMIP-1 alpha; more than 90% of the primary T cells carried MIP-1 alpha receptors. When the T cells were stimulated with immobilized anti-CD3 mAb in the presence of accessory cells, the MIP-1 alpha binding was reduced. The lowest binding was obtained 2 h after anti-CD3 mAb stimulation due to the internalization of MIP-1 alpha receptors. mrMIP-1 alpha inhibited the anti-CD3 mAb-mediated proliferation of murine splenic T lymphocytes. The maximum inhibition was obtained when mrMIP-1 alpha was added 30 min before anti-CD3 mAb stimulation. Slight inhibition of T cell proliferation was observed when mrMIP-1 alpha was added at the same time as anti-CD3 mAb stimulation. These results indicate that T lymphocytes are regulated negatively by MIP-1 alpha, which occurs when the T cells are exposed to MIP-1 alpha before activation. The negative effect of MIP-1 alpha seems to be mediated in part by the inhibition of IL-2 production, for there was a reduction in both the IL-2 mRNA levels and the IL-2 activity in supernatants from T cells preincubated with MIP-1 alpha before anti-CD3 mAb stimulation.

Animals↗
PubMed1993

Inducible T cell antigen 4-1BB. Analysis of expression and function.

4-1BB is an inducible receptor-like protein expressed in both cytolytic and Th cells. Optimal induction of 4-1BB mRNA in T cells required both PMA and ionomycin stimulation, indicating that protein kinase C activation and increases in intracellular Ca2+ were required for its expression. 4-1BB was categorized as an early activation gene since the protein synthesis inhibitor, cycloheximide, blocked the induction of 4-1BB mRNA. A rat mAb, 53A2, was generated against recombinant soluble 4-1BB and was used to characterize this molecule. 4-1BB is a 30-kDa glycoprotein and appears to exist as both a monomer and a 55-kDa dimer on the cell surface of a T cell clone. The 4-1BB protein may be post-translationally modified since its predicted backbone is 25 kDa. FACS analysis indicated that 4-1BB was inducible and expressed on the cell surface of activated splenic T cells and thymocytes. Cross-linking of 4-1BB on anti-CD3-stimulated T cells with 53A2 resulted in a dramatic enhancement of T cell proliferation. This suggests that 4-1BB may function as an accessory signaling molecule during T cell activation.

Amino Acid Sequence↗
PubMed1993

IDDM patients' sera recognize a novel 30-kD pancreatic autoantigen related to chymotrypsinogen.

We have examined, by western immunoblot analysis, the sera of 16 insulin-dependent diabetes mellitus patients (IDDM) for the presence of autoantibodies against proteins extracted from islet-cell enriched preparations of normal human pancreata. A novel putative autoantigen recognized by late stage IDDM patients sera was identified, and its amino acid sequence was partially determined. Islets of Langerhans were partially purified by a modified collagenase digestion procedure, and subsequent protein extracts were fractionated by one-dimensional or two-dimensional polyacrylamide gel electrophoresis (1-D or 2-D SDS-PAGE). Immunoblot analysis revealed a 30-kD species which was recognized by 4 of 16 IDDM patients sera, but none of 16 normal sera. The 30-kD protein, appeared as a single band on 1-D SDS-PAGE, but was resolved on 2-D gel electrophoresis as several distinct protein species with different isoelectric points (pI's), ranging from 7 to 9. The amino terminal sequence of one such species was partially determined by microsequencing, and the second through the fourteenth amino acids were found to be identical to the corresponding sequence in human chymotrypsinogen. The fifteenth through the eighteenth amino acids were different from the known chymotrypsinogen sequence. This region corresponds with the site that is cleaved to activate chymotrypsinogen. Based on the size and sequence homology, this antigen appears to be related to chymotrypsinogen. We conclude that this 30-kD species may be an autoantigen in some late stage IDDM patients.

Adolescent↗
PubMed1992

[Antifoaming agent microembolism in patients undergoing extracorporeal circulation. Its frequency in post mortem material and its pathogenic potential in vitro].

Antifoam microembolisms in patients that undergo open heart surgery, represent a risk for postoperative complications. We decided to study its frequency in an autopsy population of patients who died after heart surgery. Forty-five patients were selected and histological sections from the kidneys were studied under light microscopy, scanning electron microscopy and X-ray microanalysis. Thirty-six cases (80%) showed microemboli in the glomerular capillaries lumens. There was a positive correlation between the number of particles found and the length of the surgery. Microemboli were composed of an amorphous fraction and a particulated one composed of silicon. In vitro experimentation demonstrated that the particles are capable to induce cell lysis in a dose related manner. They also are susceptible of been phagocitated by macrophages. We conclude that bubble oxygenator are capable to induce microembolisms in a high percentage of the cases studied. Components of the microemboli are cytotoxic. Therefore microembolisms could be participating in the morbidity of patients subjects to cardiopulmonary bypass.

Antifoaming Agents↗
PubMed1991

Relative role of bone and kidney in the hypercalcaemia associated with the rat Walker carcinosarcoma 256.

The rat Walker carcinosarcoma 256 is an animal model for humoral hypercalcaemia of malignancy (HHM). In this model, the relative contribution of bone and kidney in the hypercalcaemia of tumour-bearing rats was investigated. Daily administration of pamidronate, a bone resorption inhibitor, for 2 days prevented the increased fasting Ca2+ excretion observed in the hypercalcaemic rats, although serum Ca2+ remained high. However, the high serum Ca2+ normalised after the acute injection of ethiofos, an inhibitor of renal Ca2+ reabsorption, which was associated with a marked increase of Ca2+ excretion. Changes in Ca2+ were accompanied by similar changes in Mg2+. The results indicate that altered renal Ca2+ handling has a key role in the hypercalcaemia associated with this HHM model.

Amifostine↗
PubMed1991

The dose-to-mother method to measure milk intake in infants by deuterium dilution: a validation study.

A validation study of the dose-to-mother deuterium dilution method to measure breast-milk intake has been carried out on ten infants from a Nutrition Recovery Centre in Santiago, Chile. Formula milk labelled with exponentially decreasing doses of deuterium oxide represented milk from a 'pseudo mother' of these exclusively bottle-fed infants. Unlabelled formula represented milk from other sources. Deuterium levels in the infants' body water were measured on saliva samples by mass spectroscopy. The data were fitted in a two-compartment steady-state model of the mother-child system to estimate the flow of labelled water from the 'mother' to the infant and the 'mother' and infant's water elimination constants. A dose-to-child experiment was also carried out on each infant to determine the deuterium dilution space and total daily water intake. Total and labelled water flows from deuterium dilution were used to calculate total, labelled and unlabelled formula milk intakes which were compared to the same quantities measured by bottle weighing. Water elimination constants calculated from the dose-to-mother experiments underestimated by 17 per cent the initially set mother constant and overestimated by 21 per cent the infant constants calculated from the dose-to-child experiments. Rate constants, however, have little effect on the estimated water flows so that there was good agreement between values from deuterium dilution and from direct weighing. Mean (SD) total formula, labelled formula and unlabelled formula intakes were 865 (129) g/d, 417 (74) g/d and 448 (106) g/d, respectively, when measured by deuterium dilution, compared with 856 (116) g/d, 414 (71) g/d and 441 (68) g/d when measured by direct weighing. The mean per cent differences were 1.1 per cent, 0.7 per cent and 1.6 per cent and the mean absolute differences for individuals, 4.3 (1.9) per cent, 4.8 (3.1) per cent and 9.7 (6.6) per cent, respectively.

Deuterium↗