Hypotension induced by sodium nitroprusside administered via an automatic-adaptive dose regulating system. Experimental development

Sodium nitroprusside (NPS) is a potent vasodilator which is frequently administered for the control of arterial blood pressure and peripheral resistances. Manual regulation of the dose is difficult and requires a permanent surveillance of patients under treatment. Several attempts have been made to develop an automatized system able to safely control the dose of the drug in clinical practice. However, since now the results have not been completely satisfactory. The aim of our study was to develop of a new automatic-adaptative system able to continuously control the dose of NPS. The system consists of a high precision infusion pump controlled by a microprocessor. Arterial blood pressure is continuously monitorized and according to its values NPS is automatically regulated to maintain blood pressure within a preselected range. A control "fuzzy logic" algorithm was used. We have assessed the efficacy, adaptability, and safeness of the system. The system was tested in 15 mongrel dogs. The protocol was divided into two parts. During the first part a 25% to 30% reduction in blood pressure from baseline values lasting for a period of 4 hours was attempted. The second part was devoted to test the adaptability of the control unit during induced unstable hemodynamic situations. Group I dogs were subjected to volume overload. Group II were treated with noradrenaline to increase blood pressure, and group III underwent a venous bleeding to produce arterial hypotension. Control of arterial blood pressure was achieved after a minimum of 5 min and a maximum of 19 min (mean values = 13.3 min).(ABSTRACT TRUNCATED AT 250 WORDS)     

Hospital comparisons using a Euro Health Data Base for resource management and strategic planning

A European approach for resource management and strategic planning has been implemented in the HOSCOM project of AIM by defining information standards needed across countries, as well as a methodology to measure resources and costs at the institutional and interinstitutional level. A Euro Health Data Base (EHDB) has been obtained in order to test data availability and comparability as well as to validate models through macrocomparisons using case-mix (DRG's, refined grouping, disease staging) and microcomparisons based on three diseases (cardiac valve replacement, diabetes mellitus and hip fracture). The EHDB's presently based on 274 164 medical record summaries sampled from 7 countries allowed us to build prototypes (using Clipper, Prolog and SQL) in order to export uniform aggregates in the different countries, with standard software tools for statistical comparisons. It showed the present feasibility of using case-mix based on the European Minimum Basic Data Set (MBDS) and the difficulty of obtaining uniform data on resources and costs other than length of stay across countries. Medical data confidentiality was assured but not yet population-based representativity. Given the present state of the EHDB, problems have been clearly identified in order to be solved by international research and development projects in the near future.     

Cancer in Spain (1977-1987): an analysis of the Hospital Morbidity Survey]

The aim of the present work is to evaluate the usefulness of the Hospital Morbidity Survey for the study of cancer morbidity in Spain. The study covers the period 1977-1987. Age-standardized rates for the following groups have been estimated: "hospital admissions by sex, age and final diagnosis" and "hospital admissions (new cases) by age, sex and final diagnosis". During the period 1983-84 an important increase in the frequency of all malignant tumours has coincided with an equivalent decrease in the non-specified category, leading to the conclusion that an information bias is present. This bias limits the study of temporal series of cancer morbidity in Spain and suggests that a modification of the Spanish Hospital Morbidity Survey is urgently needed.     

Insulin-like growth factor I correlates with lean body mass in cystic fibrosis patients.

BACKGROUND: A major consequence of malnutrition in cystic fibrosis (CF) patients is the loss of lean body mass (LBM) and the subsequent impairment of respiratory muscle function. AIM: To determine whether insulin-like growth factor I (IGF-I) could be related to the LBM depletion and the evolution of respiratory disease in CF patients. METHODS: LBM was evaluated by dual energy x ray absorptiometry; serum concentrations of IGF-I were measured in 24 CF patients twice with a one year interval. Both values were expressed as SD score (SDS) calculated from normal data for age, sex, and pubertal stage and analysed with respect to anthropometric evaluation and disease related conditions. RESULTS: At the initial evaluation, IGF-I SDS had a mean value of -0.98 (range -3.6 to 3.2) and correlated with weight for age index, LBM SDS, and lung disease related conditions. Multiple regression analysis showed that only LBM remained independently related to IGF-I, suggesting that the relation of IGF-I to LBM was independent of weight and that the correlation between IGF-I and the respiratory conditions was related to the level of LBM. IGF-I SDS at the first evaluation was lower for the patients who lost > or =5% of weight for age index or > or =1 SD of LBM between the two evaluations. CONCLUSION: Low levels of IGF-I could be crucial for clinical outcome by impairing LBM and respiratory function. IGF-I could be a tool for nutritional evaluation by identifying the CF patients at risk of LBM depletion.     

Absorptive hypercalciuria type III or caused by renal loss of phosphates

Contribution of a retrospective series of 16 patients with type II absorptive hypercalciuria over a total of 1.041 patients undergoing metabolic study due to relapsing renal lithiasis. Clinical history of lithiasis, biochemistry prior to treatment and instituted therapy were examined in all cases. Stones composition, radiologic appearance of lithiasis and evolution of biochemical parameters after medical treatment with a mixture of phosphates were also studied.     

Necrotizing histiocytic lymphadenitis (Kikuchi-Fujimoto disease) in a 7-year-old girl

Kikuchi-Fujimoto's disease is a rare self-limited condition of young adults that usually involves the cervical lymph nodes and is associated with fever, rash and some haematological alterations. Diagnosis is based on characteristic pathologic findings that permit differentiation of this disease from lymphoma, systemic lupus erythematous and infectious lymphadenopathies. We describe a case of 7 year-old female presenting with cervical localization of Kikuchi-Fujimoto's disease. To our knowledge, this case results the earliest affection of this disease. Our proposal with this article is to remind the pediatricians and pediatric surgeons of this poorly recognized entity when children ask for cervical masses and fever.     

Progressive acquired lymphangioma: report of a case and review of the literature

We present 2-year-old patient with a allopecia lesions in scalp, and clinique diagnostic of Cutis Aplasia. The anatomopathologic study have diagnosed the lesions as Acquired Progressive Lymphangioma (APL). Is a rare vascular tumour that has a tendency to appear in childhood an to progress slowly over the years. It could present as a solitary erythematous macule or plaque and a simple excision is usually curative. Our patient is the youngest reported in the literature.     

Identification and characterization of a T-helper peptide from carcinoembryonic antigen.

PURPOSE: The purpose of this research was to identify promiscuous T-helper cell determinants (THd) from carcinoembryonic antigen (CEA) to be used to prime T-cell help for cancer therapy. CEA was selected because this antigen is expressed in an important variety of carcinomas. EXPERIMENTAL DESIGN: Potential promiscuous THd from CEA were predicted using available computer algorithms. Predicted peptides were synthesized and tested in binding experiments to different HLA-DR molecules. Binder peptides were then used to prime T-cell responses both in vitro and in vivo. RESULTS: Twenty 15-mer peptides from CEA were predicted to bind to different HLA-DR molecules. The promiscuous character of these peptides was demonstrated in binding experiments. Fifteen of 20 peptides tested were able to bind to HLA-DR4, but only CEA (625-639) was shown to be presented after processing of recombinant CEA. CEA (625-639) was also found to be presented by HLA-DR53. Moreover, immunization of HLA-DR4 transgenic mice with CEA (625-639) in conjunction with class I epitope OVA (257-264), induced a CTL response specific of OVA (257-264). CONCLUSIONS: CEA (625-639) might be a relevant promiscuous THd peptide for cancer therapy.     

Exposure of melanoma cells to dacarbazine results in enhanced tumor growth and metastasis in vivo.

PURPOSE: In recent years, the incidence of cutaneous melanoma has increased more than that of any other cancer. Dacarbazine is considered the gold standard for treatment, having a response rate of 15% to 20%, but most responses are not sustained. Previously, we have shown that short exposure of primary cutaneous melanoma cells to dacarbazine resulted in the upregulation of interleukin-8 (IL-8) and vascular endothelial growth factor (VEGF). The purpose of the present study was to determine how long-term exposure of melanoma cells to dacarbazine would affect their tumorigenic and metastatic potential in vivo. MATERIALS AND METHODS: The primary cutaneous melanoma cell lines SB2 and MeWo were repeatedly exposed in vitro to increasing concentrations of dacarbazine, and dacarbazine-resistant cell lines SB2-D and MeWo-D were selected and examined for their ability to grow and metastasize in nude mice. RESULTS: The dacarbazine-resistant cell lines SB2-D and MeWo-D exhibited increased tumor growth and metastatic behavior in vivo. This increase could be explained by the activation of RAF, MEK, and ERK, which led to the upregulation of IL-8 and VEGF. More IL-8, VEGF, matrix metalloproteinase-2 (MMP-2), and microvessel density (CD-31) were found in tumors produced by SB2-D and MeWo-D in vivo than in those produced by their parental counterparts. No mutations were observed in BRAF. CONCLUSION: Our results have significant clinical implications. Treatment of melanoma patients with dacarbazine could select for a more aggressive melanoma phenotype. We propose that combination treatment with anti-VEGF/IL-8 or MEK inhibitors may potentiate the therapeutic effects of dacarbazine.     

Expression profiling of T-cell lymphomas differentiates peripheral and lymphoblastic lymphomas and defines survival related genes.

PURPOSE: T-Cell lymphomas constitute heterogeneous and aggressive tumors in which pathogenic alterations remain largely unknown. Expression profiling has demonstrated to be a useful tool for molecular classification of tumors. EXPERIMENTAL DESIGN: Using DNA microarrays (CNIO-OncoChip) containing 6386 cancer-related genes, we established the expression profiling of T-cell lymphomas and compared them to normal lymphocytes and lymph nodes. RESULTS: We found significant differences between the peripheral and lymphoblastic T-cell lymphomas, which include a deregulation of nuclear factor-kappaB signaling pathway. We also identify differentially expressed genes between peripheral T-cell lymphoma tumors and normal T lymphocytes or reactive lymph nodes, which could represent candidate tumor markers of these lymphomas. Additionally, a close relationship between genes associated to survival and those that differentiate among the stages of disease and responses to therapy was found. CONCLUSIONS: Our results reflect the value of gene expression profiling to gain insight about the molecular alterations involved in the pathogenesis of T-cell lymphomas.