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Biomedical subjects

R Molina

Publications and source records attributed to R Molina.

At least 91 records · Page 5Linked to original sources

Clinical usefulness of free PSA fraction as an indicator of prostate cancer.

The usefulness of the fPSA fraction in the differential diagnosis of benign prostate hyperplasia (BPH) and prostate cancer was evaluated, with the aim of improving the diagnostic efficacy of PSA. Serum PSA and fPSA determinations were performed by an enzymoimmunoassay technique on an ES-300 system. fPSA constitutes a minor fraction both in normal subjects and in patients with prostate disease, being significantly lower in patients with untreated prostate cancer than in patients with BPH. Likewise, the authors have observed that the sensitivity of the fPSA/PSA ratio has an inversely proportional relationship with the stage of the disease. The results obtained in patients with PSA levels between 4 and 20 micrograms/l are also of note. In this series of patients, the efficacy of the fPSA/PSA ratio was higher than that of PSA, showing a sensitivity of 44% and a specificity of 95% at the cut-off of 0.08.

Biomarkers, Tumor↗

An association between clotting factor concentrates use and mortality in human immunodeficiency virus-infected hemophilic patients.

There is much evidence that clotting factor concentrates (CFC), especially the so-called intermediate-purity preparations, exert an immunomodulating effect in vitro. The impact of this effect on the outcome of human immunodeficiency virus (HIV) infection in hemophiliacs is still controversial. In this retrospective cohort study, the effects of treatment with CFC on mortality and progression to acquired immunodeficiency syndrome (AIDS) were estimated while controlling for individual risk factors. Logistic regression and survival analysis, including the Cox proportional-hazards regression model, were performed with data from a 11-year follow-up of 225 hemophilic patients seropositive for HIV type 1 (HIV-1) of two hemophilia centers. Mortality and progression to AIDS rates were strongly associated with lower administration of CFC. After adjusting for age, a statistically significant and robust association was observed. The use of CFC was negatively associated with progression to AIDS (P = .0252) and mortality (P = .0033). The adjusted relative hazards of mortality and progression to AIDS rate between the most treated patients (> 700 IU/kg/yr) versus the least treated (< or = 700 IU/kg/yr) were 0.53 (confidence limits, 0.33 to 0.86) and 0.57 (0.39 to 0.84), respectively. Although the effects of other unmeasured risk factors cannot be excluded with certainty, these results suggest that there is a negative association between treatment with CFC and progression to AIDS and mortality.

Acquired Immunodeficiency Syndrome↗

Variability of Leishmania (Leishmania) infantum among stocks from immunocompromised, immunocompetent patients and dogs in Spain.

Leishmania (Leishmania) infantum is the causative agent of both the cutaneous and visceral forms of leishmaniasis in southwest Europe; the dog is the main reservoir. In order to identify the L. (L.) infantum zymodemes present in Spain, a total number of 85 Leishmania stocks isolated from dogs (31), HIV-positive patients (46) with visceral or cutaneous leishmaniasis, a patient with visceral leishmaniasis complicating renal transplantation (1) and immunocompetent patients (7) with visceral or cutaneous leishmaniasis, have been characterized by isoenzyme typing. All canine stocks were MON-1, which is the most widespread zymodeme in the Mediterranean area. In immunocompetent patients three zymodemes were found: MON-1 (2), MON-24 (2) and MON-34 (3). Nine different zymodemes were obtained in stocks from HIV co-infected patients, indicating a higher variability of L. (L.) infantum amongst them: MON-1 (in 21 stocks), MON-24 (7), MON-28 (1), MON-29 (3), MON-33 (7), MON-34 (1) and MON-183 (4). Two new zymodemes, MON-198 (1) and MON-199 (1), were described among HIV patients from Spain. The stock from the renal transplanted patient was MON-1. The exclusive presence of certain zymodemes in immunocompromised patients and their absence in typical cases of cutaneous and visceral leishmaniasis and in infected dogs suggests two possibilities: (i) an anthroponotic pattern of leishmaniasis where intravenous drug user-infected patients act as potential reservoir for these new zymodemes. In the latter, syringes could act as the vehicles for infected monocytes; (ii) the cellular immune system could select virulent from non-virulent zymodemes in immunocompetent visceral leishmaniasis patients.

AIDS-Related Opportunistic Infections↗

Tumor antigens CA 19.9, CA 125, and CEA in carcinoma of the uterine cervix.

Serum levels of carcinoembryonic antigen (CEA) and cancer antigens CA 125 and CA 19.9 were determined by immunoradiometric assay in 96 patients diagnosed of invasive carcinoma of the uterine cervix and 7 patients of cervical intraepithelial neoplasia. Elevated CEA levels were found in 33%, CA 19.9 in 32%, and CA 125 in 21.5% of invasive carcinoma patients. Specificity for each tumor marker was 98%. Increased CEA and CA 19.9 levels were found in relation to clinical stage. CA 125 and CA 19.9 mean levels were significantly higher in patients with adenocarcinoma compared with squamous cell carcinoma. Detection rate of CA 19.9 in stage III adenocarcinomas was higher than in stage III squamous cell carcinoma (50 vs 21%). Sensitivity of combined antigens was also higher for adenocarcinomas increasing 60% for CA 19.9 and/or CA 125 and to 70% of cases for one of the three tumor antigens. During follow-up of cases with no evidence of disease, antigen levels showed a tendency to decrease, but all cases with progressive disease, recurrence, or metastasis were detected by elevation of one of these three tumor antigens. In conclusion, CEA, CA 125, and CA 19.9 are useful markers for detection of cervical cancer and monitorization of clinical course of disease. CA 19.9 and CA 125 have been shown to be particularly useful in patients with adenocarcinoma.

Adenocarcinoma↗

Use of serial carcinoembryonic antigen and CA 15.3 assays in detecting relapses in breast cancer patients.

UNLABELLED: To evaluate the utility of CEA and CA 15.3 for early diagnosis of recurrence, serial serum determinations of both antigens were performed in 1023 patients (follow-up: 1-10 years, mean 6.2 years) with primary breast cancer (CA 15.3 in 533 cases) and no evidence of residual disease (NED) after radical treatment (radical mastectomy or simple mastectomy and radiotherapy). 246 patients developed metastases during follow-up. RESULTS: CEA and CA 15.3 were elevated ( > 10 ng/ml or > 60 U/ml, respectively) prior to diagnosis in 40% (98/246) and 41% (37/91) of the patients with recurrence, with a lead time of 4.9 +/- 2.2 and 4.2 +/- 2.3 months, respectively. When patients with locoregional recurrences were excluded, sensitivity improved to 46% (CEA) and 54% (CA 15.3), and to 64% with both tumor markers (CEA and/or CA 15.3). Higher levels of both CEA and CA 15.3 at diagnosis of recurrence, higher sensitivity in early diagnosis of relapse, and a higher lead time were found in ER+ (CEA) or PgR+ patients (CA 15.3) than in those that were negative for these receptors in the primary tumor (p < 0.001). Specificity of the tumor markers was 99% for both CEA (777 NED patients) and for CA 15.3 (444 NED patients), respectively. In conclusion, CEA and CA 15.3 are useful tools for early diagnosis of metastases, mainly in those patients with ER+ or PR+ tumors.

Antigens, Tumor-Associated, Carbohydrate↗

Effects of preanesthetic and anesthetic drugs on endothelium-dependent responses in the rat aorta.

1. Acetylcholine often fails to induce endothelium-dependent relaxation in human vessels in vitro. Due to the fact that most of these vessels come from surgery, we examined the influence of drugs used in anesthesia on endothelium-dependent responses in rat aorta. 2. Groups of male Wistar rats of the following treatments were utilized: P group, diazepam+promethazine+atropine; I group, pentothal+succinylcholine; IG group, halothane+nitrous oxide; M group, morphine+pancuronium; C group, untreated rats. Dose-response curves to noradrenaline and acetylcholine were determined in rat aorta in vitro, in the presence and absence of endothelium. 3. Acetylcholine induced more relaxation (P < 0.05) in the rat aorta of IG group compared with that of the C group. 4. In the rat aorta from P and IG groups, the contractions produced by several concentrations of noradrenaline were significantly smaller (P < 0.05) when the endothelium was removed. Similar effects occurred in aorta strips of animals previously treated with either atropine, promethazine, cimetidine or halothane. 5. Our results suggest that drugs currently used in anesthesia interfere with some endothelium-dependent effects on isolated rat aorta but according to these results they do not seem to be responsible for the lack of acetylcholine relaxation sometimes described in human vessels in vitro.

Acetylcholine↗

Phenotype of glutathione S-transferase Mu (GSTM1) and susceptibility to malignant melanoma. MMM group. Multidisciplinary Malignant Melanoma Group.

The isoenzyme Mu of glutathione S-transferase (GSTM1) is dominantly inherited, and the prevalence of this isoenzyme in the population is about 60%. The lack of GSTM1 has been linked with cancer risk. The frequency of the phenotypes of this isoenzyme in melanoma (MM) patients (n = 197) is reported here. A significantly higher proportion of individuals in the control group (n = 147) had measurable GSTM1 than MM patients (59.1% vs 42%, P = 0.002); there was a higher proportion of positive phenotypes in general among women than among men. Odds ratio analysis indicated that individuals with this polymorphic variant have an approximately 2-fold risk of developing these cancers. GSTM1 phenotype distribution depends on age, smoking habit and tumour pathology. A group of MM patients with dysplastic naevi was also studied.

Adult↗

Complement-mediated lysis and infectivity for mouse macrophages and sandflies of virulent and attenuated Leishmania major promastigotes varying in expression of the major surface protease and lipophosphoglycan.

The infectivity to mouse macrophages and sandflies, the expression and enzymatic activity of the major surface glycoprotein (gp63), the developmental modification of lipophosphoglycan (LPG) and three metacyclogenesis markers (promastigote body size, lectin agglutination and complement resistance) were compared in four related Leishmania major promastigote lines. The lines, which differed in their virulence for BALB/c mice, were examined in both logarithmic and stationary phase. Although the two non-virulent lines were unable to survive and multiply within the macrophages, they were better at attaching to the macrophages and infecting sandflies than the two virulent lines, which were highly infective for macrophages. Except for the higher resistance of the attenuated parasites to complement-mediated lysis, there were no clear differences between the metacyclogenesis markers of the four lines. The amount and enzymatic activity of surface gp63 was relatively high in the attenuated promastigotes and this appears to be related to a higher expression of gp63 genes. In terms of LPG, cells of all the lines had approximately twice the number of galactose and mannose residues per molecule when in logarithmic phase than when in stationary phase. LPG of the virulent lines also contained approximately twice the mannose and galactose residues of the attenuated line. Although L. major gp63 could therefore be important for promastigote survival in the sandfly and for the resistance to complement-mediated lysis, there was no apparent correlation between gp63 expression and promastigote survival in the macrophage. A very elongated LPG could be necessary for the survival and proliferation of the parasite in macrophages.

Animals↗

Parasitic culture of buffy coat for diagnosis of visceral leishmaniasis in human immunodeficiency virus-infected patients.

Two samples of buffy coat from the peripheral blood of 25 human immunodeficiency virus-positive patients with proven visceral leishmaniasis, as determined with a bone marrow aspirate (stain and culture), were cultured onto Schneider's and Novy-McNeal-Nicolle media. Hemoculture positivity was 67%. The average growing time was 10 days. This is an easy, noninvasive, and sensitive technique.

AIDS-Related Opportunistic Infections↗

Carcinoembryonic antigen in staging and follow-up of patients with solid tumors.

The presence of a tumor antigen in human colonic carcinomas and their metastases was described about 25 years ago. This antigen, called carcinoembryonic antigen (CEA), is one of the first known tumor markers. Since then, many more have been described, but CEA, determined alone or in combination with others, is still one of the most used. CEA is not organ specific and abnormal values may be found in a wide range of carcinomas, especially those with gastrointestinal involvement. CEA assay should not be used for cancer diagnosis because its sensitivity in patients without cancer metastases is low. In addition, abnormal CEA values may be found in patients with benign diseases. However, the probability of malignancy increases directly with CEA concentration. Its main clinical applications are prognosis, early diagnosis of recurrence and follow-up of patients with carcinomas. In a wide range of malignancies, CEA serum levels are clearly related to tumor stage. Presurgical CEA serum levels are a well-established prognostic factor in colorectal, breast and lung cancer. Patients presenting with increased preoperative CEA serum levels have both a shorter disease-free interval and lower survival than those with normal CEA levels. In the early diagnosis of recurrence, CEA also plays an important role: in about 70-85% of patients with colorectal tumors and in 40-50% with breast cancer, CEA serial increase is the first sign of tumor recurrence. In patients with disseminated tumors, serial determinations are also a useful tool for therapy monitoring: CEA values decrease with effective treatment while stable or increasing values are observed when treatment is not effective.

Biomarkers, Tumor↗

In vitro susceptibility of Plasmodium falciparum to chloroquine, amodiaquine, quinine, mefloquine, and sulfadoxine/pyrimethamine in Equatorial Guinea.

Between March 1990 and June 1992, a study was carried out in Equatorial Guinea on the in vitro response of Plasmodium falciparum to different antimalarial drugs. Field work for the study was conducted both in the country's island region as well as on the mainland, and resistant isolates were found to exhibit interregional differences. On the island of Bioko, 204 tests were performed with 16% (11 of 69) resistant to chloroquine, 9% (4 of 46) resistant to quinine, 14% (6 of 43) resistant to a combination of sulfadoxine/pyrimethamine, and 6.5% (3 of 46) resistant to amodiaquine. In the mainland area of Bata, the same antimalarial drugs and mefloquine were tested with the following results: 9% (5 of 58) resistant to chloroquine; 2% (1 of 58) resistant to amodiaquine, and 3% (2 of 58) resistant to a combination of sulfadoxine/pyrimethamine. No isolates resistant to quinine or mefloquine were found. Effective concentrations (EC50, EC90, and EC99) and regression lines (log dose/response) for each antimalarial drug were calculated to establish a surveillance system for antimalarial drug chemosensitivity in Equatorial Guinea. Finally, 12 isolates from 12 patients previously treated with chloroquine were studied to compare both tests (in vivo-in vitro) and obtain a correlation between the RII and RIII types of in vivo and in vitro resistances. No correlation for the RI type was found between the two methods.

Amodiaquine↗

[The incidence of major histocompatibility system antigens in dilated and ischemic myocardiopathies].

AIM: The purpose of this study was to analyze the frequency of the different antigens of HLA in patients with diagnosis of very advanced dilated cardiomyopathy and ischemic heart disease by comparing them with a control group of supposedly healthy subjects. MATERIAL AND METHOD: The group of dilated cardiomyopathy consisted of 35 patients (8 women and 27 men) aged between 14 and 60 years. The group of ischemic heart disease included 32 patients (4 women and 28 men) aged between 34 and 64 years. The control group comprised 1337 subjects of the Spanish Mediterranean area, supposedly healthy and recruited from paternity studies. RESULTS: In dilated cardiomyopathy we found a higher incidence in comparison with the control group of the A-2 (62.86% vs 46.22%), B-12 (60.00% vs 32.38%) and DQ-3 (82.86 vs 49.96%) antigens, and a lower incidence of B-51 (0.00% vs 12.49%). In ischemic heart disease we found, when comparing to the control group, a higher incidence of A-11 (31.25% vs 13.08%) and A-29 (34.38% vs 14.58%) antigens and a lower incidence of DQ-2 (15.63% vs 49.88%). CONCLUSIONS: In the Spanish Mediterranean area, the presence of A-2, B-12 and DQ-3 antigens, as well as the absence of B-51 would favour the appearance of advanced dilated cardiomyopathy. The presence of the A-11 and A-29 antigens would predispose to ischemic cardiomyopathy while the presence of DQ-2 would have a protective effect on the appearance of this cardiopathy.

Adolescent↗

[Role of tissue polypeptide antigen as a marker in bladder cancer].

Presentation of a review of TPA serum levels in 207 patients, 160 of which had vesical carcinoma. This population comprises 37 patients who had suffered vesical carcinoma but whom, at entry in the study, did not display clinic evidence of that: 11 patients with benign vesical pathology; 84 patients with primary vesical tumour, and 76 patients with relapsing vesical tumour. Tumoral staging resulted in 72 Ta, 49 T1, 10 T2, 14 T3, and 15 Ta. Distribution with regard to degree of differentiation was as follows: 52 GI, 61 GII and 40 GIII. Sensitivity of serum TPA in our series was 39% and specificity 94%. When tumours were subdivided into surface and infiltrant tumours, sensitivity was 28% and 72% respectively (p < 0.01). Patients presenting normal levels of serum TPA took longer to relapse than those who had high levels. Mean time to relapse was 17 months for the first group, and 12 months for the second group. Serum TPA increased its performance with carcinomas of higher grade and stage, but it does not have enough sensitivity to be considered a useful marker in low stages. However, serum TPA relationship to the tumour's invasive degree and the disease-free interval are an indication for their likely use as a prognostic factor to delimit the groups with higher risk of relapse.

Biomarkers, Tumor↗

[The diagnostic utility of PSA density].

Recently, the concept of PSA density has been introduced in order to increase the diagnosis sensitivity obtained with serum PSA dosing. The usefulness of this parameter has been assessed in 47 patients with benign prostate hyperplasia (BHP) and 26 patient with non-disseminated prostate adenocarcinoma. Using 0.15 as cut-off value, below which were 97% of patients with uncomplicated BHP, we obtained a 73% overall sensitivity. This sensitivity was stage related, reaching 100% in stage C patients. On the contrary, the test specificity was relatively low, since it considered patients with complicated HPB with urinary infection or with in-dwelling vesical catheter, obtaining 41% false positives. These results suggest a special usefulness of this test for the correct diagnosis of those prostate cases with mild suspicion of cancer.

Adenocarcinoma↗

Estradiol receptors in combination with neu or myc oncogene amplifications might define new subtypes of breast cancer.

Amplifications of neu and c-myc were evaluated in 218 and 145 breast cancers (BC), respectively. Oncogene amplifications were determined for the most part by Southern blot. An association between the proportion of nodes affected and the intensity of neu amplification in estadiol receptor negative (ER-) BC was found (P = 0.028), which was confirmed by the multi-factor analysis of variance (P = 0.05). A significantly greater incidence in neu amplifications among BC with metastases was also found (P = 0.031). A strong association (P = 0.01) between the neu and myc amplification was observed. There is a strong association between myc amplification and ER- BC (P < 0.01). It is concluded that (1) the combination ER- with neu amplification might define a new group of more aggressive BC, as is suggested by their associated nodal involvement; (2) the linkage of myc amplifications with ER- BC and high grade of neu amplification might reflect a trait of tumor aggressivity.

Adult↗

Influences of age and sex on endothelium-dependent vascular responses and arterial blood pressure in the rat.

1. Vascular reactivity related to age and sex on two endothelium-dependent effects in isolated rat aorta (acetylcholine-induced relaxation and modulation of noradrenaline response) and blood pressure decreases by acetylcholine administration were studied. Group of male Wistar rats aged 2, 4, 8, 16 and 24 months plus female rats of 4 months were used. 2. Blood pressure was measured by using a standard tail-cuff technique. Acetylcholine in vivo administration (0.002 mg/kg i.v.) significantly reduced diastolic pressures in the 2 month old males and 4 month old females, but not in other age groups. 3. Isolated helical strips of rat aorta were used to determine the endothelium-dependent reactivity. The maximal relaxation from different groups of male rats induced by acetylcholine was: 100% in those of 2 months; 53.2 +/- 6.0% in those of 4 months; 61.8 +/- 6.1% in those of 8 months; 57.6 +/- 5.0% in those of 16 months and 31.0 +/- 4.9% in those of 24 months. Concentration-response curves to noradrenaline were significantly greater only when endothelial cells were removed from aorta strips of 2 month old rats. In aorta strips with endothelium the maximal contraction to noradrenaline was significantly greater in 2 month old rats when compared with the other groups and smaller in aorta strips from 24 month old rats. 4. These results suggest that the endothelium-dependent effects studied and the noradrenaline-induced contraction decreased according to the age of the rats.

Acetylcholine↗