Diagnóstico tardío de un caso de porfiria aguda intermitente en una unidad de cuidados intensivos / Late diagnosis of a case of acute intermittent porphyria in the ICU

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[Markers of airway remodeling in induced sputum from healthy smokers]. / Marcadores de remodelado bronquial en el esputo inducido de fumadores sanos.

OBJECTIVE: Airway remodeling in chronic obstructive pulmonary disease (COPD) has been linked to the equilibrium between matrix metalloproteinase (MMP) 9 and its inhibitor, tissue inhibitor of metalloproteinase (TIMP) 1. However, that equilibrium has not been analyzed in healthy smokers. The aim of this study was to assess the equilibrium between MMP-9 and TIMP-1 in induced sputum from healthy smokers, healthy nonsmokers (controls), and patients with COPD. PATIENTS AND METHODS: Samples of induced sputum were obtained from 35 individuals: 12 healthy smokers, 12 controls, and 11 patients with COPD. In each sample, a differential cell count was performed and enzyme-linked immunosorbent assays were used to analyze the concentrations of MMP-9 (total and active fraction) and TIMP-1. RESULTS: Compared with controls, healthy smokers were found to have a higher mean (SD) concentration of total MMP-9 (273 [277] ng/mL vs 128 [146] ng/mL) and a higher ratio of total MMP-9 to TIMP-1 (0.16 [0.14] vs 0.08 [0.06]). However, the ratio of active MMP-9 to TIMP-1 was similar in the 2 groups. Samples from patients with COPD had the highest concentrations of total MMP-9 (477 [262] ng/mL) and active MMP-9 (178 [126] ng/mL) and the lowest concentrations of TIMP-1 (1.044 [1.036] microg/mL). When all groups were considered together, there was an inverse relationship between the MMP-9/TIMP-1 ratio and the forced expiratory volume in the first second (FEV1). The relationship between the active MMP-9/TIMP-1 ratio and FEV1 was even stronger, and the relation of both ratios with FEV1 became stronger still when smoking was considered. CONCLUSIONS: Healthy smokers had a higher concentration of total MMP-9 and that concentration was correlated with their exposure to tobacco smoke. Maintenance of the active MMP-9/TIMP-1 ratio in healthy smokers may explain the absence of progressive airway obstruction. Measurement of active MMP-9 concentration could be useful for assessment of airway remodeling.

Marcadores de remodelado bronquial en el esputo inducido de fumadores sanos / Markers of airway remodeling in induced sputum from healthy smokers

Objetivo: El remodelado bronquial en la enfermedad pulmonar obstructiva crónica (EPOC) se ha relacionado con el equilibrio entre la metaloproitenasa (MMP) 9 y su inhibidor, el inhibidor tisular de MMP tipo 1 (TIMP-1). Dicho equilibrio no se ha analizado en fumadores sanos. Nuestro objetivo ha sido estudiar dicho equilibrio en el esputo inducido de fumadores sanos respecto a sanos no fumadores (controles) y pacientes con EPOC. Pacientes y métodos: Se obtuvieron 35 muestras de esputo inducido, de las que 12 provenían de fumadores sanos, otras 12 de controles y 11 de pacientes con EPOC. Se estudiaron la celularidad de las muestras y la concentración de MMP-9 (total y fracción activa) y TIMP-1 mediante enzimoinmunoanálisis. Resultados: Los fumadores sanos mostraron mayor concentración media (± desviación estándar) de MMP-9 total (273 ± 277 ng/ml) y una ratio mayor (0,16 ± 0,14) que los controles (128 ± 146 ng/ml y 0,08 ± 0,06, respectivamente). Sin embargo, la ratio MMP-9 activa/TIMP-1 fue equiparable en ambos grupos. Los pacientes con EPOC mostraron los valores más altos de MMP-9 total (477 ± 262 ng/ml) y activa (178 ± 126 ng/ml) y los más bajos de TIMP-1 (1.044 ± 1.036 ng/ml). Globalmente, la ratio mostró una relación inversa con el volumen espiratorio forzado en el primer segundo. Dicha relación fue aún superior con la MMP-9 activa y con el grado de tabaquismo. Conclusiones: Los fumadores sanos presentaron una mayor concentración de MMP-9 total en relación con el grado de exposición tabáquica. Una ratio MMP-9 activa/TIMP-1 conservada en fumadores sanos podría explicar la ausencia de obstrucción progresiva de la vía aérea. La medida de la MMP-9 activa puede ser útil en la determinación del remodelado bronquial

Objective: Airway remodeling in chronic obstructive pulmonary disease (COPD) has been linked to the equilibrium between matrix metalloproteinase (MMP) 9 and its inhibitor, tissue inhibitor of metalloproteinase (TIMP) 1. However, that equilibrium has not been analyzed in healthy smokers. The aim of this study was to assess the equilibrium between MMP-9 and TIMP-1 in induced sputum from healthy smokers, healthy nonsmokers (controls), and patients with COPD. Patients and methods: Samples of induced sputum were obtained from 35 individuals: 12 healthy smokers, 12 controls, and 11 patients with COPD. In each sample, a differential cell count was performed and enzyme-linked immunosorbent assays were used to analyze the concentrations of MMP-9 (total and active fraction) and TIMP-1. Results: Compared with controls, healthy smokers were found to have a higher mean (SD) concentration of total MMP-9 (273 [277] ng/mL vs 128 [146] ng/mL) and a higher ratio of total MMP-9 to TIMP-1 (0.16 [0.14] vs 0.08 [0.06]). However, the ratio of active MMP-9 to TIMP-1 was similar in the 2 groups. Samples from patients with COPD had the highest concentrations of total MMP-9 (477 [262] ng/mL) and active MMP-9 (178 [126] ng/mL) and the lowest concentrations of TIMP-1 (1.044 [1.036] µg/mL). When all groups were considered together, there was an inverse relationship between the MMP-9/TIMP-1 ratio and the forced expiratory volume in the first second (FEV1). The relationship between the active MMP-9/TIMP-1 ratio and FEV1 was even stronger, and the relation of both ratios with FEV1 became stronger still when smoking was considered. Conclusions: Healthy smokers had a higher concentration of total MMP-9 and that concentration was correlated with their exposure to tobacco smoke. Maintenance of the active MMP-9/TIMP-1 ratio in healthy smokers may explain the absence of progressive airway obstruction. Measurement of active MMP-9 concentration could be useful for assessment of airway remodeling

Prospective randomized trial comparing conventional laparoscopic colectomy with hand-assisted laparoscopic colectomy: applicability, immediate clinical outcome, inflammatory response, and cost.

BACKGROUND: Hand-assisted laparoscopic surgery (HALS) represents a useful alternative to conventional laparoscopic surgery (LS). Its potential advantages--(a quicker, safer procedure and less need to convert to open surgery) are due to the recovery of tactile feedback. However, HALS requires the performance of a mini-laparotomy when surgery commences, and the wound is stretched and compressed throughout the procedure. In addition, it is associated with a more intense manipulation of the intraabdominal viscera. All of these factors increase the surgical trauma, it is not known whether HALS maintains the minimally invasive characteristics of conventional LS. Therefore, we set out to study the applicability, immediate clinical outcome, inflammatory response, and cost of HALS compared with conventional LS using colectomy as a model. METHODS: We performed a prospective randomized trial comparing laparoscopic-assisted colectomy with HAL colectomy. The aims of the study were to assess (a) perioperative features, including time, advantages, and conversion; (b) the patient's immediate clinical response, including recovery of bowel sounds, refeeding time, postoperative pain, local and general morbidity, and hospital stay; (c) the effect on the inflammatory response, using interleukin-6 (ILG) and C-reactive protein (CRP) measurements; (d) oncological issues, including intraoperative cytology and features of the specimen; and (d) the relative costs of the two procedures. RESULTS: A total of 54 patients were enrolled in the study, 27 laparoscopic and 27 HALS. The operative times were similar, but HALS was associated with a far lower conversion rate--7% vs 23%. Immediate clinical outcomes, oncological features, and costs were similar for the two procedures, but HALS was associated with a significantly greater increase in IL6 and CRP than the conventional laparoscopic procedure. CONCLUSION: This comparative study shows that HALS simplifies difficult intraoperative situations, reducing the need for conversion. Although it is a more aggressive procedure, HALS preserves the features of a minimally invasive approach, maintains all of the oncological features of conventional laparoscopic surgery, and does not increase the cost. HALS should therefore be considered as a useful adjunct when difficult situations arise during conventional laparoscopic colectomy.

Beta 2-microglobulin and immunoglobulins are more useful markers of disease progression in HIV than neopterin and adenosine deaminase.

Reference change values of six biochemical quantities (beta 2-microglobulin, neopterin, adenosine deaminase and immunoglobulins IgA, IgG and IgM) have been established in asymptomatic human immunodeficiency virus (HIV)-infected patients following the method described by Harris and Yasaka in 1983. Patients included in the evaluation were classified as A1, A2 or A3 according to the classification of the Centers for Disease Control (CDC) (January 1993). All patients were followed-up quarterly, with a minimum of four samples each available for statistical analysis. The main objective of this paper was to study whether differences found to be greater than calculated reference change values could predict clinical or immunological worsening in patients' status. Retrospective analysis was made in asymptomatic patients (n = 256) included in an HIV infection protocol carried out in our hospital. Of these patients, 179 showed clinical or immunological worsening during the study period and 77 maintained their clinical and immunological status. Changes in beta 2-microglobulin showed the greatest sensitivity to detect clinical or immunological worsening (43.0%), whereas changes in adenosine deaminase showed the lowest (21.8%). Clinical or immunological worsening in 169 of the 179 patients was detected by one of the six biochemical quantities evaluated. Ten patients showed clinical or immunological worsening, although differences between measurements were lower than the reference change values calculated. Of 77 patients whose clinical state did not deteriorate, there was a change in biochemical analytes greater than the reference value calculated in 29 patients (a period of 12 months had elapsed since detection). In 48 patients, no increases greater than calculated reference change values were detected. The sensitivity obtained using the six analytes was 94.4% and the specificity was 62.3%.

The predictive value of several markers in the progression to acquired immunodeficiency syndrome.

Serum beta 2-microglobulin, neopterin, immunoglobulins A, G and M, adenosine deaminase and CD4+ lymphocyte count were evaluated as predictors of progression of HIV-1 infection to AIDS. A population of HIV-1 seropositive, initially asymptomatic men (n = 213) and women (n = 101) was followed up quarterly. We estimated the AIDS-free time using the actuarial method (median survival time 47.2 months). Cox proportional hazard analysis revealed that all markers studied were significant (p < 0.05) in relation to progression to AIDS. The best markers for predicting progression to AIDS were, in descending order, CD4+ lymphocyte count, beta 2-microglobulin, IgA, neopterin, IgG, IgM and adenosine deaminase. On stratifying population into four groups (divided at percentiles 25, 50 and 75--from group 1, with values nearest to reference ranges, to group 4, with most abnormal values) we observed statistically significant differences (p < 0.05) for all markers except for adenosine deaminase. The relative risk from the Cox proportional hazards model were used to quantify the effects of the best markers and compared to the risk obtained in group 1. CD4+ lymphocyte count was the best predictor of progression to AIDS. When considering beta 2-microglobulin and CD4+ together, the relative risk in the group with lowest CD4+ cell count (group 4) ranged from 25.6% (with lower beta 2-microglobulin values) to 41.1% (with higher beta 2-microglobulin values). Similar results were obtained when considering neopterin and CD4+ together. The addition of beta 2-microglobulin or neopterin values to CD4+ lymphocyte count improved the predictive value of CD4+ lymphocyte count.

Calculation of LDL-cholesterol by using apolipoprotein B for classification of nonchylomicronemic dyslipemia.

In this paper we propose a calculation of LDL-cholesterol (LDL-C) not affected by hypertriglyceridemia by using lipid quantities directly measured in total serum. We also propose an algorithm for the classification of nonchylomicronemic dyslipemias. Plasma apolipoproteins (apo) A-I, B, total cholesterol (TC), triglycerides (TG), and cholesterol of lipoproteins were measured in a group of 38 normolipemic and 120 dyslipemic patients (42 phenotype IIa, 38 IIb, and 40 IV) classified according to TG and LDL-C values. Discriminant analysis was applied to obtain the best classification with the lowest number of quantities directly measured from total serum (TC, TG, and apo B), and multiple regression analysis was performed to find an equation to calculate LDL-C from these quantities. Apo B seems to be a useful discriminator between normolipemic and phenotype IIa patients, by using a cutoff value of 1.35 g/L obtained by ROC curve analysis. The proposed algorithm, based on lipid quantities measured by easily automated methods, is shown to be a good alternative for the classification of nonhyperchylomicronemic dyslipemia. LDL-C calculated from TC, TG, and apo B proved a better estimate of true LDL-C than the estimate obtained with Friedewald's formula.

Dipyrone interference on several common biochemical tests.

We studied the effect in vitro and in vivo of dipyrone on the determination of several biochemical tests in two analyzers, a Hitachi 747 and a Kodak Ektachem 700. From studies in vitro, we found significant interference by dipyrone (P < 0.05) in the determination of creatine kinase (CK), lactate dehydrogenase (LD), uric acid, triglycerides, cholesterol, aspartate aminotransferase, alanine aminotransferase, and urea nitrogen with both instruments, and in the determination of creatinine in the Ektachem analyzer. We also studied the effect of intravenously administered dipyrone in 14 patients. Dipyrone interfered significantly (P < 0.05) in the determination of CK, LD, uric acid, triglycerides, and cholesterol with both instruments, and creatinine only with the Ektachem analyzer. Using high-performance liquid chromatography (HPLC), we measured concentrations of dipyrone in the serum of patients who had received the drug and observed a negative correlation between the concentrations of dipyrone in the blood and the percentage of each analyte concentration.