Allergy to human insulin.
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Diabetes Mellitus, Type 2↗
Biomedical subjects
C Montalbán
Publications and source records attributed to C Montalbán.
Perioperative response of leptin and the tumor necrosis factor alpha system in morbidly obese patients. Influence of cortisol inhibition by etomidate.
BACKGROUND: Leptin, tumor necrosis factor alpha (TNFalpha) and soluble TNFalpha receptors are secreted by the adipose tissue. Surgery induces a complex cytokine and neurohormonal response. The aim of our study was to investigate the perioperative response of leptin and the TNFalpha system in morbidly obese patients submitted to gastroplasty, and the possible involvement of cortisol in their responses. METHODS: Serum cortisol, adrenocorticotropic hormone (ACTH), leptin, TNFalpha and soluble TNFalpha receptor I were measured in 22 morbidly obese women (11 anesthetized with thiopental and 11 with etomidate, a well known inhibitor of cortisol synthesis). Samples were collected before anesthesia induction, just before surgical incision, and 2, 4, 6, 12, 24 and 48 h after the start of surgery. RESULTS: Baseline serum leptin correlated with body mass index (r=0.567, P=0.007). Baseline serum leptin and TNFalpha were higher than normal. Cortisol release was inhibited in the etomidate group with a subsequent higher stimulation of ACTH release. A statistically significant decrease in serum leptin levels was observed in both groups at 2, 4, 6 and 48 h, compared with basal values. A similar decrease in serum TNFalpha levels was observed in both groups, but the decrease reached significance only in the etomidate group. Serum soluble TNFalpha receptor I did not decrease. No differences were found between the two groups in leptin, TNFalpha or soluble TNFalpha receptor I concentrations at any time. CONCLUSION: Serum leptin and TNFalpha levels decrease in obese patients during gastroplasty. Transitory inhibition of cortisol release does not alter this response.
Adrenocorticotropic Hormone↗
Patients with poor preoperative ejection fraction have a higher plasma response of adrenomedullin in response to open heart surgery.
BACKGROUND: Adrenomedullin (AM) is a potent vasodilator peptide. Plasma AM levels are increased in heart diseases and in sepsis. Heart surgery under cardiopulmonary bypass (CPB) induces a systemic inflammatory response. METHODS: We measured plasma AM, cAMP (the second messenger of AM), C-reactive protein (CRP) and haemodynamic parameters in 29 patients undergoing elective open heart surgery, before, during and after anaesthesia and CPB as well as on the first morning after surgery. RESULTS: Basal AM levels were higher than normal and correlated with systolic pulmonary pressure and pulmonary capillary pressure, but not with other haemodynamic parameters. AM increased during CPB and remained elevated 24 h after the start of surgery. Plasma cAMP increased only at the end of CPB. CRP was increased only in the last sample. At the end of CPB and at the end of surgery AM levels were higher in patients with basal ejection fraction<40% compared with those with ejection fraction >60% [456+/-386 vs 252+/-343 (P<0.03) and 832+/-781 vs 391+/-356 pg/ml (P<0.05), respectively]. CONCLUSION: We conclude that AM, as inflammation-related cytokines, increases during and after CPB, that cAMP response is unrelated to AM and that AM response is higher in those patients with worse basal ejection fraction.
Adrenomedullin↗
Serum interleukin-6 in renal osteodystrophy: relationship with serum PTH and bone remodeling markers.
Interleukin-6, synthesized by osteoblasts in response to PTH, stimulates osteoclastogenesis and bone resorption in vitro, and it has been implicated in the pathogenesis of bone loss in several clinical situations. The aim of this study was to evaluate whether serum levels of interleukin-6 were increased in patients with renal osteodystrophy, and to investigate the possible relationships between serum interleukin-6 and PTH levels on one hand, and serum interleukin-6 and bone remodeling markers on the other. Serum interleukin-6 (IL-6), intact PTH, osteocalcin, bone alkaline phosphatase (BAP) and carboxyterminal telopeptide of Type 1 collagen (ICTP) were measured in 86 uremic patients. IL-6 (median [range] 16.5 [1.0-430] pg/ml), PTH (279.8 [11-2004] pg/ml), osteocalcin (143.8 [8-921] ng/ml), BAP (20.9 [6-169] U/I) and ICTP (38.8 [1.5-181.5] microg/l) were higher than normal. IL-6 levels correlated with PTH (r= 0.22, p = 0.04) and with ICTP (r = 0.31, p = 0.004). A stronger correlation was found between PTH and circulating bone remodeling markers (r = 0.66 for osteocalcin, r = 0.56 for BAP, and r = 0.39 for ICTP). The correlation between PTH and IL-6 was stronger in those patients (n = 15) with severe secondary hyperparathyroidism (r= 0,71, p = 0.003). On the other hand, in the group of patients (n = 41) with PTH lower than 250 pg/ml, there was no correlation between IL-6 and PTH, while IL-6 correlated with ICTP (r = 0.44, p = 0.006). Serum IL-6 correlates with ICTP which suggests that it may mediate bone resorption in renal osteodystrophy.
Adult↗
[Treatment of low-grade gastric MALT lymphoma with Helicobacter pylori eradication. Follow-up of the histological and molecular response].
BACKGROUND: Low grade gastric MALT lymphoma is associated to infection with Helicobacter pylori. Also, H. pylori eradication can produce histologic regression of the lymphoma. PATIENTS AND METHODS: This study reports the follow-up of a prospective series of 11 patients with low grade gastric MALT lymphoma, stage I, treated with eradicative therapy for H. pylori. After treatment, patients were followed up with sequential endoscopies to asses the histological and molecular regression of the lymphoma, using a score of the histological lesions and the amplification of the IgH gene with PCR analysis. RESULTS: Helicobacter pylori was eradicated in all patients. In 10(90.9%) histological regression of the lymphoma was demonstrated, in 6 of them in the first control after treatment. In the 10 patients with histological response, PCR analysis demonstrated a polyclonal rearrangement of the IgH gene in 6 (60%) and a clonal band in 4 (40%), that eventually disappeared at 12 (SD 4) months after treatment. In 4 patients with a previous polyclonal rearrangement, a clonal band was occasionally detected in any sequential controls; in 2 of these cases the clonal band disappeared 5 and 7 months after treatment and in the remaining 2 its evolution is not yet known. Nine patients have been followed up and are in remission 18 (SD 8) months after treatment. CONCLUSIONS: Eradication of H. pylori can produce histologic regression in stage I low grade gastric MALT lymphoma, and should be the first therapeutic option. Despite histological regression of the lymphoma, PCR analysis can detect a clonal rearrangement of the IgH gene in 40% of the cases, but its significance remains unknown. Sequential and prolonged follow-up is essential to assess whether this lymphoma can be actually cured with eradication therapy for H. pylori.
Adult↗
Peripheral T-cell lymphomas: initial features, natural history, and prognostic factors in a series of 174 patients diagnosed according to the R.E.A.L. Classification.
BACKGROUND: Peripheral T-cell lymphomas (PTCL) account for about 10% of all lymphomas in Western countries. The aim of the present study is to analyze the initial characteristics and prognostic factors in a large series of PTCL patients. PATIENTS AND METHODS: 174 patients (105 male/69 female; median age 61 years) were diagnosed with PTCL according to the R.E.A.L. Classification in nine Spanish institutions between 1985 and 1996. Cutaneous lymphomas and T-cell chronic lymphocytic/prolymphocytic leukemia were excluded from the study. Univariate and multivariate analyses were used to assess the prognostic value of the main initial variables. RESULTS: The distribution according to histology subgroup was: PTCL unspecified, 95 cases (54.4%); anaplastic large-cell Ki-l-positive (ALCL), 30 cases (17%); angioimmunoblastic T cell, 22 cases (13%); angiocentric, 14 cases (8%); intestinal T cell, 12 cases (7%), and hepatosplenic gamma delta T cell, one case (0.6%). As compared to the other types, ALCL presented more frequently in ambulatory performance status, without extranodal involvement, in early stage, normal serum beta 2-microglobulin (B2M) level and low-risk international prognostic index (IPI). Most patients were treated with adriamycin-containing regimens. The overall CR rate was 49% (69% for ALCL vs. 45% for other PTCL; P < 0.02). The risk of relapse was 48% at four years. Median survival of the series was 22 months (65 months for ALCL vs. 20 months for other PTCL; P = 0.03), with a four-year probability of survival of 38% (95% confidence intervals (95% CI): 28-48). In the univariate analysis, in addition to the histology, older age, poor performance status, presence of B-symptoms, extranodal involvement, bone marrow infiltration, advanced Ann Arbor stage, high serum LDH, high serum B2M, and intermediate- or high-risk IPI were related to poor survival. In the multivariate analysis the histologic subgroup (ALCL vs. other PTCL) (P = 0.02; response rate (RR): 4.3), the presence of B-symptoms (P = 0.02, RR: 2.2), and the IPI (low vs. high) (P = 0.04, RR: 2) maintained independent predictive value. When the analysis was restricted to the unspecified subtype, only IPI had independent prognostic value (P = 0.003; RR: 3.5). CONCLUSIONS: PTCL have adverse prognostic features at diagnosis, respond poorly to therapy and have short survival, with no sustained remission. ALCL constitutes a subgroup which responds better to therapy and has a longer survival.
Adolescent↗
Age-related responses of vasoactive factors during acute exercise.
To evaluate the age-related response of vasoactive factors during acute exercise, young (n = 8, aged 23.6+/-2 years) and old (n = 13, aged 77+/-6 years) healthy volunteers performed a stress test using a treadmill, and blood samples were taken before and after exercise. There were neither basal (old people 77+/-53 vs. young people 67.6+/-40 pg/ml) nor peak exercise-related (old people 77+/-43 vs. young people 66.8+/-34 pg/ml) differences in plasma adrenomedullin (AM) between both groups. AM did not increase with exercise in either group. Regarding plasma cAMP, there were neither basal nor exercise related differences, but this nucleotide increased with exercise in both groups (old people p < 0.0001, young people p < 0.05). Plasma Atrial Natriuretic Peptide (ANP) was higher in basal (116.3+/-64 vs. 46.8+/-21 pg/ml, p < 0.003) and after exercise samples (150.2+/-76.5 vs. 68.7+/-29.5 pg/ml, p < 0.004) in old people as compared with young people. Old people showed an increase in ANP with exercise (p < 0.05), but in young people, though there was a trend to increase, it did not reach statistical significance. There were neither basal nor exercise related differences in plasma cGMP, but this nucleotide increased with exercise in both groups. Angiotensin II (AT-II) levels were lower in basal and after exercise samples in old people as compared with young people. AT-II levels did not increase with exercise in either group. These data suggest that, with increasing age, the vascular tree develops resistance to ANP and higher sensitivity to AT-II, while AM levels do not change. Exercise makes ANP changes more evident, while AM and AT-II are not modified.
Adrenomedullin↗
Plasma adrenomedullin levels in type 1 diabetes. Relationship with clinical parameters.
OBJECTIVE: To assess the relationship between plasma adrenomedullin (AM) levels and the presence of microvascular complications in type 1 diabetic patients. RESEARCH DESIGN AND METHODS: We measured plasma AM and cAMP levels in 103 type 1 diabetic patients (46 without complications, 24 with retinopathy only, 14 with microalbuminuria but normal kidney function, and 19 with renal insufficiency) and 41 matched healthy control subjects. RESULTS: Patients with renal insufficiency had higher levels of AM and cAMP than all other groups. Patients with only retinopathy showed a trend to have higher levels than patients without complications. There were no differences among all other groups. There was a significant correlation between AM and cAMP in the total diabetic group (rs = 0.36, P < 0.001) but not in the control group. In multiple regression analysis, plasma AM demonstrated significant relationships with creatinine clearance (beta = -0.31, P = 0.004) and duration of the disease (beta = 0.28, P = 0.008). CONCLUSIONS: Plasma AM and cAMP are increased in type 1 diabetic patients with renal insufficiency. Creatinine clearance (CrClc) and duration of the disease are related to plasma AM levels in these patients.
Adrenomedullin↗
Increased soluble serum HLA class I antigens in patients with lymphoma.
sHLA are soluble forms of class I histocompatibility antigens detected in human serum and cerebrospinal fluid. These molecules are secreted by B and T lymphocytes and the secretion increases dramatically upon mitogenic activation of these cells. sHLA was quantified by an ELISA sandwich method in sera from healthy blood donors, and from patients with Non Hodgkin's Lymphoma (NHL) and Hodgkin's Disease (HD) both at diagnosis and at remission. Pretreatment sHLA serum levels in NHL and in HD were compared with the values found in controls. sHLA levels are increased in patients with NHL (low grade: 6.68 +/- 1.80; high grade: 2.65 +/- 0.53 microg/ml X +/- S.E.) and HD (6.44 +/- 0.98) at diagnosis and in relapses when compared with controls (0.89 +/- 0.08). This increment is statistically significant (low grade NHL: p = 0.0038; high grade NHL: p = 0.0049 and HD: p = 0.0005 versus control group). No statistical differences between titers of sHLA after complete remission and sHLA in the control group were found. The high levels of sHLA detected in patients with lymphoma are mainly due to low molecular weight HLA molecules (55 KD) (60-75% of the HLA present in serum in the control group and 75-100% in serum of patients with lymphoma).
Chromatography, Gel↗
Pathological, immunological, and molecular features of Hodgkin's disease associated with HIV infection. Comparison with ordinary hodgkin's disease.
The aim of the present study was to analyze in a series of 24 HIV-positive Hodgkin's disease (HD) patients the morphological and immunological features, the presence of rearrangements in the immunoglobulin heavy chain (IgH) gene, expression of the Epstein-Barr virus (EBV) latent membrane protein-1 (LMP-1), and the existence of deletions in the intracytoplasmic domain of the LMP-1 gene. The results obtained were compared with those from a parallel series of 56 patients with ordinary HD. Briefly, comparison of the two series showed a predominance of unfavorable histological subtypes in HIV-positive HD patients. The mixed cellularity subtype was more frequent in HIV-positive than in HIV-negative HD patients: the difference in percentage was statistically significant (p = 0.04). Neoplastic cell-rich cases were significantly more frequent (p = 0.40) in HIV patients (59%) than in ordinary HD patients (34%). In 25% of HIV-infected and in 14% of ordinary HD patients, the neoplastic cells were CD20+, a difference that was not statistically representative. Clonal IgH rearrangements were detected in 33% of HIV-infected patients and in 23% of ordinary HD patients, a nonsignificant difference. LMP-1 expression was detected in 100% of HIV-positive patients and in 57% of ordinary HD patients (p = 0.004). A 30-base-pair deletion in the carboxy-terminal domain of the LMP-1 gene was found in 16 of 18 HIV-infected patients (89%), whereas it was identified in only 8 of 25 ordinary HD patients (32%) (p = 0.008). In conclusion, HD in HIV-infected patients as compared with HD in HIV-negative individuals is associated with morphological features of aggressivity, with a higher frequency of neoplastic cells, and with constant LMP-1 expression. The fact that LMP-1 is expressed in all HIV-infected patients suggests that EBV plays an etiological role in the pathogenesis of HIV-associated HD. Furthermore, the presence of EBV strains carrying deletions near the 3' end of the LMP-1 gene in the majority of cases may be related with the morphological and clinical aggressivity of HD in immunocompromised patients.
Adult↗
Evaluation of the international index in the prognosis of high grade gastric malt lymphoma.
The International Prognostic Index identifies four risk groups with different survival rates in aggressive non-Hodgkin's lymphoma. We have studied whether a slight modification of this index has prognostic significance in high grade gastric B-cell MALT lymphoma. In 53 patients with high grade gastric B-cell MALT lymphoma the following survival factors were investigated: age over or under 60 years, sex, B symptoms, more than one extranodal site of involvement other than the stomach, serum LDH levels, performance status, stage I/IIE1/IIE2 v.s. stage III/IV, treatment with surgery, chemotherapy or both modalities together and the four risk groups as defined by the Modified International Prognostic Index (MIPI). A multivariate Cox's test was used to evaluate the independent prognostic significance on survival of all the above variables. Advanced stage (III/IV) and involvement of more than one extranodal site not including stomach were the only variables influencing survival. The MIPI was not sufficient to separate groups with significant differences in survival or to stratify prognostic groups. In this series, the MIPI did not show prognostic significance in high grade gastric B-cell MALT lymphoma.
Adolescent↗
Gastric B-cell mucosa-associated lymphoid tissue (MALT) lymphoma. Clinicopathological study and evaluation of the prognostic factors in 143 patients.
BACKGROUND: Gastric MALT lymphoma can be histologically classified into two groups, low-grade (LG) and high-grade (HG); however, their natural history is poorly understood. We have studied a large retrospective series aiming to confirm whether the histological groups confer different clinical features and behavior and to analyze the prognostic factors in these patients. PATIENTS AND METHODS: A series of 143 gastric B-cell MALT lymphomas is reported. Eighty-four were low-grade lymphomas (LG) and 59 were high-grade lymphomas (HG). Median follow-up was 36 months. The clinical and analytical parameters of the 84 LG patients were compared with those of the 59 HG patients. In the patients who had been operated on, the pathological features (macroscopical patterns, tumor size, involvement of resection margins, degree of parietal invasion and involvement of abdominal lymph nodes and adjacent viscera) of the LG patients were compared with those of the HG patients. The sites of relapses were studied. In the 132 treated and followed-up patients the influence of the treatment and that of clinical, analytical and pathological features on survival were investigated with the Kaplan and Meier and log-rank tests. To identify the factors with independent influence on survival, a Cox model was fitted for the whole series and separately for 53 HG patients. RESULTS: HG group differed from the LG group by a significantly higher frequency of weight loss at presentation, palpable abdominal mass, hepatomegaly, peripheral lymphadenopathy, elevated serum LDH, higher incidence of stage III-IV and tumor/mass patterns in the endoscopy and in the gastrectomy specimen. The tumor was significantly larger in the HG group than in the LG and the deeper invasion of the gastric wall, the higher frequency of infiltration of the abdominal lymph nodes and the visceral extension were also significant in the HG group. Complete remission (CR) was achieved in 91% of the patients of the LG group, but was significantly lower, 70%, in the HG group. Relapses occurred in the stomach and also in non-MALT sites. In 132 treated and followed-up patients, elevated serum LDH, absence of CR, HG group and stage III-IV were associated with a worse survival. In the Cox multivariate model, stage was the only variable influencing survival, although stage was related to the histological grade. In the HG group, stage was also an independent significant risk factor, whereas treatment with surgery, chemotherapy or both was not. In the 103 patients treated with surgery, a worse survival was associated with the involvement of the resection borders, depth of the infiltration of the gastric wall, dissemination to distant abdominal nodes and adjacent organs, but not with the addition of chemotherapy. CONCLUSIONS: Histological classification into LG and HG separates distinctive groups of gastric MALT lymphoma that show striking clinical and prognostic differences. Besides histological grade, stage is the most important prognostic feature.
Aged↗
Low grade gastric B-cell MALT lymphoma progressing into high grade lymphoma. Clonal identity of the two stages of the tumour, unusual bone involvement and leukemic dissemination.
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Bone and Bones↗
B-cell follicular lymphomas: clinical and biological characteristics.
Seventy cases of follicular B-cell lymphomas were studied: 37 cases derived from the follicular centre [27 centroblastic-centrocytic (CB-CC) and 10 centroblastic (CB)] and 33 from the mantle zone [mantle-cell lymphoma (ML)]. Presenting features as well as response to therapy, time free of symptoms and survival were reviewed. All the cases were diagnosed and classified with routine and immunohistochemistry methods. In 61 cases tumors were studied with specific markers in a CAS-200 Image Analyser. Flow cytometry (FCM) was also done and correlated with proliferative-values and survival. A minor aggressive course of CB-CC and ML was demonstrated, with ML being the most benign form (lower proliferation rate and longest survival). Ploidy did not correlate with histological subtypes, survival or response to therapy. These results confirm the utility of biodynamic studies in lymphoid neoplasias.
Adult↗
Peripheral T-cell lymphoma: a clinicopathological study of 41 cases and evaluation of the prognostic significance of the updated Kiel classification.
A total of 41 non-cutaneous peripheral T-cell lymphomas were classified following the updated Kiel classification. Of these, 20 cases belonged to the low-grade group (T-cell chronic lymphocytic leukaemia, 3; lymphoepithelioid, 5; angioimmunoblastic, 4; pleomorphic small cell, 8) and 21 to the high grade group (pleomorphic medium and large cell, 11; immunoblastic, 3; large-cell anaplastic Ki-1 positive, 7). Seventy per cent showed a CD4+/CD8-phenotype, 39% a defective phenotype and 88% an activation phenotype. Eighty per cent had B-symptoms, 63% hepatomegaly, 48% splenomegaly and 26% had involvement of more than three lymphoid areas. Bone marrow was infiltrated in 34%, central nervous system in 4%, lung in 12% and skin in 14.6%. Seventeen per cent presented with extranodal disease and 82.8% had stage III/IV disease. Hypergammaglobulinaemia was found in 29%, hypercalcaemia in 7%, raised LDH serum levels in 58% and HTLV-I antibodies in only one case. Of the 37 treated patients 18 (48%) achieved a complete remission, but 33% relapsed. Mortality was 59% and actuarial overall survival at 38 months was 0.32. In the comparison of the clinical, analytical and immunophenotypic variables and outcome between low and high grade groups, only the average of bone marrow infiltration in the low grade and stage I-II, presence of defective phenotypes and higher Ki-67 positivity in the high grade group were significantly different.(ABSTRACT TRUNCATED AT 250 WORDS)
Female↗
Metastatic carcinoma of the prostate presenting as a superior vena cava syndrome.
A 75-year-old patient presented with a superior vena cava syndrome (SVCS) lasting 3 years. A prostatic carcinoma was found and a supraclavicular lymph node biopsy specimen disclosed metastasis of the prostatic carcinoma. Antiandrogen and luteinizing hormone-releasing hormone analogue therapy produced a marked improvement. Prostatic carcinoma, although a very rare cause, must be considered in the diagnosis of cases of SVCS with a protracted course, since it is a treatable disease.
Adenocarcinoma↗
The structure of two IgMs showing different activity from a patient with Waldenstrom's macroglobulinaemia.
The two monoclonal IgMs (IgM1 and IgM2) were characterized from a patient Waldenström's macroglobulinaemia that resulted in a gammapathy. Heavy and light chains were isolated from the IgM. The complete primary structure of the two light chains and the NH2-terminal region of the two heavy chain molecules were determined. The sequence data indicated that the heavy and light chains from both IgMs belong to the same (III and II) lambda subgroups. By testing their antibody activity it was found by immunofluorescence and immunoblotting that only IgM2 reacts with an intermediate filament protein.
Adult↗