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Biomedical subjects

I Moreno

Publications and source records attributed to I Moreno.

At least 55 records · Page 3Linked to original sources
PubMed1997

Prognostic value of replication errors on chromosomes 2p and 3p in non-small-cell lung cancer.

As chromosomes 2p and 3p are frequent targets for genomic instability in lung cancer, we have addressed whether alterations of simple (CA)n DNA repeats occur in non-small-cell lung cancer (NSCLC) at early stages. We have analysed by polymerase chain reaction (PCR) assay replication errors (RER) and loss of heterozygosity (LOH) at microsatellites mapped on chromosomes 2p and 3p in 64 paired tumour-normal DNA samples from consecutively resected stage I, II or IIIA NSCLC. DNA samples were also examined for K-ras and p53 gene mutations by PCR-single-stranded conformational polymorphism (PCR-SSCP) analysis and cyclic sequencing, as well as their relationship with clinical outcome. Forty-two of the 64 (66%) NSCLC patients showed RER at single or multiple loci. LOH was detected in 23 tumours (36%). Among patients with stage I disease, the 5-year survival rate was 80% in those whose tumours had no evidence of RER and 26% in those with RER (P = 0.005). No correlation was established between RER phenotype and LOH, K-ras or p53 mutations. RER remained a strong predictive factor (hazard ratio for death, 2.89; 95% confidence interval, 2.23-3.79; P = 0.002) after adjustment for all other evaluated factors, including p53, K-ras, LOH, histological type, tumour differentiation and TNM stage, suggesting that microsatellite instability on chromosomes 2p and 3p may play a role in NSCLC progression through a different pathway from the traditional tumour mechanisms of oncogene activation and/or tumour-suppressor gene inactivation.

Adult↗
PubMed1997

Etiology of solitary pulmonary nodules in patients with human immunodeficiency virus infection.

We assessed 10 patients with human immunodeficiency virus (HIV) infection (nine of whom had AIDS) and solitary pulmonary nodules (SPNs) that were detected on roentgenograms. Five of the patients presented with respiratory symptoms. The etiology of the SPN was determined for eight of these patients: six had infections (hydatidosis, mucormycosis, or infection with Nocardia asteroides, Cryptococcus neoformans, cytomegalovirus, or Pneumocystis carinii), one had non-Hodgkin's lymphoma, and the remaining patient had round atelectasis. Sputum studies were of no diagnostic value in any of these cases. Fiberoptic bronchoscopy with bronchoalveolar lavage and transbronchial biopsy was diagnostic in two of seven cases, and percutaneous transthoracic needle biopsy (PTNB) was diagnostic in one of four cases. Several microorganisms that were not the cause of the SPNs were observed in samples of sputum, bronchoscopic specimens, and PTNB specimens. Thoracotomy was diagnostic in the three cases in which it was performed. We conclude that the management of SPNs in HIV-infected patients is complicated by the low sensitivity and specificity of the diagnostic tests used.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Low-grade, malt-type, primary B-cell lymphoma of the conjunctiva.

Although primary ocular lymphomas may be found in the conjunctiva, eye lids and lacrimal glands, the majority nevertheless occur in the orbit. Only a few cases of primary conjunctival lymphoma have been described in the literature. A 68-year-old man presented with a painless swelling of the epibulbar conjunctiva of the right eye. A diffuse lymphoid infiltrate consisting of small-sized lymphoid cells with the morphology and distribution characteristics of mucosa-associated lymphoid tissue was observed. Immunohistological study demonstrated the B lymphocyte lineage of tumor cells and Bcl-1 and bcl-2 rearrangements were negative. After clinical staging including thoracic, abdominal, brain and orbital CT scans, fiberoptic gastroscopy and bone marrow biopsy, no other foci of this lymphoma were found. Radiation therapy was given and the patient currently remains free of lymphoma 30 months after diagnosis.

Aged↗
PubMed1996

Glucose tolerance, insulin secretion, insulin sensitivity and glucose effectiveness in normal and overweight hyperthyroid women.

OBJECTIVE: Inter-relationships between insulin sensitivity and body weight in patients with hyperthyroidism remain incompletely understood. We have examined whether a mild excess of body weight exacerbates the metabolic abnormalities of spontaneous hyperthyroidism. DESIGN AND PATIENTS: Insulin-modified intravenous glucose tolerance tests were performed on 14 hyperthyroid women with body mass indices (BMI) ranging from 21 to 31 kg/m2. A control group of 19 healthy women matched for age and BMI was also studied. MEASUREMENTS: Intravenous glucose tolerance (KG), first and second-phase integrated insulin responses to glucose, the integrated glucose area under the curve (AUC), and minimal model parameters of insulin sensitivity (SI) and glucose effectiveness (SG) were determined. RESULTS: Hyperthyroid women had mean KG, glucose-induced insulin secretion and SG values similar to those in control women. The mean glucose AUC was higher in hyperthyroid patients (P < 0.05). Lower insulin sensitivity was observed in hyperthyroid patients than in control women (SI = 0.38 +/- 0.07 vs 0.59 +/- 0.07 l/min pmol 10(4) (mean +/- SEM), P < 0.05). A steeper decline in insulin sensitivity with increase in body mass index was found in hyperthyroid women when compared with the control group, after adjusting for age. When groups were compared according to their BMI, hyperthyroid women with normal weight (BMI < or = 25 kg/m2, n = 8) had mean KG, insulin response to glucose, glucose AUC, SG and SI values similar to those in normal weight control women (n = 11). Overweight hyperthyroid patients (BMI > 25 kg/m2, n = 6) had a higher (P < 0.05) second-phase insulin response to glucose than normal weight patients, a higher glucose AUC (P < 0.05) than normal weight patients and overweight controls (n = 8), and a lower SI (P < 0.05) than normal weight patients and overweight controls. SG was not influenced by BMI in hyperthyroid patients. CONCLUSIONS: These results suggest that overall glucose tolerance was not significantly affected in normal weight hyperthyroid women. However, when a moderate excess of weight is also present, a state of clear insulin resistance occurs.

Adult↗
PubMed1996

[Predictive factors of inotropic support in myocardial revascularization surgery].

OBJECTIVES: The use of perioperative inotropics in myocardial revascularization surgery can be considered a marker of ventricular dysfunction, the etiology of which involves a variety of pre- and intraoperative factors. Knowledge of the risk factors and their relative importance can allow them to be modified for improved outcome. This study aims to determine the incidence of and factors that predict the need for inotropic support in order to finalize extracorporeal circulation and in the first 6 hours after myocardial revascularization. PATIENTS AND METHODS: Two hundred forty-two patients who underwent myocardial revascularization were studied retrospectively. The parameters collected were age, sex, NYHA classification, left ventricular telediastolic pressure at baseline and after contrast, ejection fraction, collateral circulation, number of distal anastomoses, time of clamping, time of extracorporeal circulation, need for inotropic support to end extracorporeal circulation and during the first 6 hours after surgery. RESULTS: Inotropics were used in 27.6% of the sample. The need for inotropic support was related to female sex (odds ratio [OR] 3.85 with 95% confidence interval [CI], 1.56-9.49); NYHA class III (OR 2.13 with 95% CI, 1.05-4.32) or IV (OR 10.16 with 95% CI, 3.22-32.13); low injection fraction (OR 2.41 with 95% CI, 1.22-4.76); and prolonged extracorporeal circulation (OR 2.97 with 95% CI, 1.54-5.76). CONCLUSIONS: The independent variables associated with the need for inotropic support during the perioperative period in myocardial revascularization are NYHA functional class III and IV, female sex, low injection fraction and prolonged extracorporeal circulation. New techniques for myocardial protection during extracorporeal circulation, plus adequate peroperative stabilization of patients and shorter time of extracorporeal circulation will probably diminish short term morbidity in revascularization surgery.

Aged↗
PubMed1996

Association of the shared epitope with radiological severity of rheumatoid arthritis.

OBJECTIVE: To investigate the association between radiological severity of rheumatoid arthritis (RA) and the presence of the shared epitope. METHODS: Ninety unrelated adult Spanish patients with RA with a disease duration of at least 3 years, selected according to the American College of Rheumatology criteria, were radiologically assessed (shoulders, elbows, wrists, hands, hips, knees, and feet) and classified as having severe or nonsevere RA. DNA oligotyping was used to determine DR specificities and to detect DR4 and DR1 alleles. RESULTS: Forty-one patients (45.5%) had severe RA. Sixty-six patients (73.3%) carried the shared epitope and 18 (20%) had double expression of the shared epitope. Thirty-seven (90%) of the 41 patients with severe RA expressed the shared epitope. Logistic regression analysis showed that both single and double expression of the shared epitope were strongly related to the radiological severity of RA (odds ratio = 6.3 and 9.4, respectively). CONCLUSION: Our results show that radiological severity of RA is highly associated to the shared epitope.

Adult↗
PubMed1996

Molecular staging of non-small cell lung cancer according to K-ras genotypes.

We have previously demonstrated a strong association between K-ras gene mutations, as determined by PCR followed by allele-specific oligonucleotide hybridization (ASO-h), and survival in non-small cell lung cancer patients. The purpose of this study was to determine the relationship between tumor aggressiveness and specific-type K-ras point mutations in non-small cell lung cancer. We developed procedures to examine the status of the K-ras gene by ASO-h and by single-strand conformation polymorphism assay of DNA obtained from formalin-fixed paraffin-embedded tumors. K-ras point mutations at codons 12 and 61 were assessed in 275 consecutively treated stage I-IV non-small cell lung cancers. Among patients with stage I disease, median survival time was 41.5 months in those whose tumors had no evidence of K-ras mutations and 27 months in those with K-ras 12 mutations; among patients with stage IIIA disease, median survival time was 7 months in those with K-ras codon 12 aspartic and serine mutations and 15 months for those with other K-ras mutations (P = 0.01). In a multivariate analysis, specific-type K-ras codon 12 point mutation remained a strong predictive factor (hazard ratio for death, 2.06; 95% confidence interval, 1.11-3.81; P = 0.02) after adjustment for other evaluated factors, including TNM stage and histology. Thus, we concluded that in patients with non-small cell lung cancer, specific K-ras 12 point mutations detected by DNA amplification and either ASO-h or single-strand conformation polymorphism methods predicted a significantly increased risk of recurrence and death, independently of stage and histology.

Adult↗
PubMed1995

Mutated K-ras gene analysis in a randomized trial of preoperative chemotherapy plus surgery versus surgery in stage IIIA non-small cell lung cancer.

The observation that the proteins encoded by ras genes play a central role in the signalling pathways used by cells to respond to growth factors and the fact that mutated ras proteins are constantly promoting cell division have led to a PCR-based hunt for additional clinical information. In the present study, K-ras analysis draws the following conclusions: (1) K-ras point mutation frequency was higher in the surgery group (10 of 24 patients) than in the chemotherapy-surgery group (3 of 20 patients). (2) Mutated K-ras was predominantly observed at codon 12 but five mutations appeared at codon 61. (3) Mutations were identified in the squamous cell carcinoma histological NSCLC subtype except in four cases corresponding to adenocarcinoma. (4) A multifarious pattern of substitutions, especially at codon 12, were noted with aspartic K 12 substitutions more prone to develop bone metastases. (5) Although a genotypic K-ras classification of NSCLC may not yet be formulated, our accumulated data (unpublished) suggest a trend toward it. (6) Patients with mutated K-ras tumors in the surgery group had no different survival than those with normal K-ras. However our pooled data as well as other authors' results assert that mutated K-ras constitute an additional prognostic datum that deserves to be included together with TNM classification. In the design of new preoperative (neoadjuvant) chemotherapy trials, stratification of tumors by K-ras status deserves to be further investigated in order to correlate with response, relapse and survival. Mutated K-ras genotype merits further research. Finally, the paradigm of uneven histological distribution and mutated K-ras spectra among researchers should serve as a stimulus to search for further contributions in this field.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Histological and subcellular distribution of 65 and 70 kD heat shock proteins in experimental nephrotoxic injury.

The cellular distribution of 65 and 70 kD heat shock proteins (HSPs) was studied in the normal rat kidney and after acute tubular necrosis (ATN) induced by inorganic mercury (HgCl2). In the normal kidney the 65 kD HSP was found in the cytoplasm of podocytes and proximal convoluted tubules, whereas the 70 kD HSP was located in nuclei and cytoplasm of podocytes, cortical convoluted, and collecting tubules. The distribution of both HSPs along ATN changed as a function of time. In the early phase, before evidence of histological damage, both HSPs were found in the pielocaly ceal epithelium and medullary collecting tubules. During the necrotic phase, HSPs coexisted with sites of severe damage (i.e. cortical tubules). With immunoelectron microscopy damaged cells showed an abundance of 65 kD HSP-I in mitochondria, as well as in chromatin and nucleoli, while 70 kD HSP-I was overexpressed in the cytoplasm, mito chondria, lysosomes, cytoskeleton, chromatin, and nucleoli, and coincided with urinary excretion of HSPs. In the postregenerative phase, the distribution of HSPs was similar to that found in the normal kidney. HSPs of 65 and 70 kD were encountered constitutionally and their immunolabeling is correlated with the magnitude of cell injury.

Animals↗
PubMed1995

K-ras genotypes and prognosis in non-small-cell lung cancer.

BACKGROUND: Despite major advances in the treatment of many kinds of cancer over the past 25 years, the overall 5-year survival of non-small-cell lung cancer patients has scarcely improved. Even in stage I which has the best outcome long-term survival still falls below 70%. Since intriguing data suggest that the identification of genetic markers might allow prognosis to be assessed case by case. We were prompted to evaluate K-ras gene mutations as a putative prognostic marker in this neoplasm. MATERIALS AND METHODS: We used the polymerase chain reaction (PCR) followed by allele specific oligonucleotide (ASO) hybridization or single-strand conformation polymorphism (SSCP) assays, to detect K-ras mutations in DNA from formalin-fixed, paraffin-embedded tumor samples. K-ras mutations were examined in 192 stage I to IV non-small-cell lung cancer patients. RESULTS: K-ras mutations were detected in 51 of 192 of the cases studied (27%). All K-ras mutations detected by PCR/ASO hybridization were also identified by SSCP. In stage I disease, the median survival was 46 months in those patients whose tumors had no K-ras mutations and 21 months in those with aspartic acid and serine mutations at K-ras codon 12; in patients with stage IIIA disease, median survival time was 16 months in the K-ras negative group and 7 months in the aspartic acid and serine mutation group. No significant differences were observed for the remaining amino acid substitutions of K-ras, nor were they observed at all in more advanced disease. CONCLUSIONS: K-ras gene status has strong prognostic value in patients with stage IIIA non-small-cell lung cancer. The survival curve for patients with stage I and K-ras codon 12 aspartic or serine mutations is close to that of patients with stage IIIA without K-ras mutations. However, a non-small-cell lung cancer K-ras genotypic classification should be validated in larger studies.

Aged↗
PubMed1995

Delayed papillary muscle rupture following mild chest trauma.

A case of delayed papillary muscle rupture is reported, which developed 24 hours following a mild chest trauma. Transthoracic echocardiography established the diagnosis; immediate mitral valve replacement was carried out. The postoperative course was uneventful.

Accidental Falls↗
PubMed1994

Frequency of HLA-DPB1 alleles in a Spanish population: their contribution to rheumatoid arthritis susceptibility.

HLA-DPB1 allele frequencies in 181 unrelated control individuals and 70 rheumatoid factor-positive RA patients from Seville (Spain) were determined using oligonucleotide typing methods. All frequencies shown concern the percentage of individuals positive for a certain allele. HLA-DPB1*0401 was the most common DPB1 allele in the healthy individuals, possessed by 65.7% of them. In addition to HLA-DPB1*0401, only the following alleles were found in normal subjects at frequencies greater than 10%: DPB1*0101 (15.5%), DPB1*0201 (12.2%), DPB1*0301 (16.6), and DPB1*0402 (29.3%). When HLA-DPB1 allelic frequencies were compared between seropositive RA patients and controls, a negative association for DPB1*0301 and DPB1*0401 was found in RA patients, although it failed to reach statistical significance after correction for the number of comparisons made. The other DPB1 alleles exhibited almost identical frequencies in both groups. However, when only DR4+ patients and controls were considered, the decrease in the frequency of the DPB1*0301 and DPB1*0401 alleles lacked statistical significance. On the other hand, when DR4- RA patients and controls were compared, the frequency of DPB1*0301 was found decreased significantly again, even more than in the whole group of patients.

Alleles↗
PubMed1994

Lymphocyte subpopulations in patients with primary fibromyalgia.

OBJECTIVE: Fibromyalgia (FM) is a clinical entity of unknown etiology frequently diagnosed in rheumatology. The potential involvement of the immune system in its pathogenesis has been suggested. Studies of abnormal T cell subpopulations often have been inconclusive. We attempted to clear this point by comparing lymphocyte subpopulations, including some of the newer activation markers, in patients with FM and healthy controls. METHODS: Sixty-five patients with FM and 56 healthy controls were studied. Flow cytometry was used as a quantification technique to measure lymphocyte subpopulations, CD3 (T cells), CD19 (B cells), CD16 (natural killer cells), CD4 (T helper/inducer cells), CD8 (T cytotoxic/suppressor cell), CD25 (interleukin 2 receptor), CD69 (activation inducer molecule marker), CD71 (transferrin receptor) and CD54 (ICAM-1); CD4/CD8 ratios were also estimated. RESULTS: The number of T cells expressing activation markers CD69 and CD25 was decreased in patients with FM; the other subpopulations were similar in patients and controls. CONCLUSION: Our results suggest a defect in T cell activation in patients with FM.

Adolescent↗
PubMed1994

[Asymptomatic bacteriuria and pyuria during pregnancy].

BACKGROUND: The presence of pyuria and the role of mixed culture in the diagnosis of asymptomatic bacteriuria in pregnant women have been evaluated METHODS: One hundred and sixty four pregnant women without any symptomatology have been studied using two cultures of mid-stream urine samples and pyuria quantification. In addition culture of bladder urine has been carried out in 17 of these patients (12 with pure cultures and 5 with mixed cultures). RESULTS: 110 samples were culture negative without pyuria; 7 were pure cultures with pyuria; 19 pure culture without pyuria and the remaining 28 patients yielded mixed culture with or without pyuria in the first culture. Twenty of these 28 mixed cultures were negative in the second culture. A estimated frequency of asymptomatic bacteriuria in pregnancy was 16% and pyuria was only found in 27% of pregnant women with asymptomatic bacteriuria. CONCLUSION: The pyuria is not a useful marker for the diagnosis of asymptomatic bacteriuria in pregnancy.

Bacteria↗
PubMed1994

A randomized trial of mitomycin/ifosfamide/cisplatin preoperative chemotherapy plus surgery versus surgery alone in stage IIIA non-small cell lung cancer.

The efficacy of surgery or radiotherapy as conventional treatment for stage IIIA non-small cell lung cancer (NSCLC) is limited. Recent studies have pointed out that preoperative chemotherapy may improve survival. To reconcile the two approaches, we undertook a multidisciplinary randomized trial to examine the possible synergism between preoperative chemotherapy and surgery in improved survival. Stage IIIA NSCLC patients were randomly assigned to receive either three preoperative courses of mitomycin/ifosfamide/cisplatin chemotherapy and surgery or surgery alone. The median survival was significantly greater in the chemotherapy plus surgery group than in the surgery group (26 months v 8 months; P < .001). However, the prognostic value of the mutated K-ras gene data presented awaits the analysis of larger sample populations. Similarly, the role of high-dose cisplatin in inducing higher pathologic complete remissions has to be corroborated in future randomized trials.

Antineoplastic Combined Chemotherapy Protocols↗