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Biomedical subjects

R Molina

Publications and source records attributed to R Molina.

At least 19 recordsLinked to original sources

Usefulness of prostate-specific antigen density as a diagnostic test of prostate cancer.

To evaluate the diagnostic usefulness of prostate-specific antigen density (PSAD) in prostate cancer (PC) prostate-specific antigen (PSA) concentrations were measured in 175 patients with benign prostatic hypertrophy (BPH) and 50 patients with PC. Patients with BPH were classified according to the presence of complications of the disease: urinary infection or the presence of a bladder catheter. PSAD levels were observed to be greater than 0.15 in 3% of the patients with uncomplicated BPH and in 40% of the patients with complicated BPH. PSA levels were higher than 10 micrograms/l in 3 and 27% of these patients, respectively. High levels of PSAD were observed in 80% of the patients with cancer. Sixty-four percent of the patients with cancer presented PSA levels greater than 10 micrograms/l. These results indicate that PSAD is a useful parameter in the differential diagnosis of PC and BPH with the diagnostic efficacy of PSAD being greater than that of the serum determination of PSA.

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

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

Canine leishmaniasis: clinical, parasitological and entomological follow-up after chemotherapy.

Six naturally infected dogs [two with no signs of leishmaniasis ('asymptomatic'), two with a few signs ('oligosymptomatic') and two with many signs ('polysymptomatic')] were studied before and after chemotherapy. Another two, non-infected dogs were kept as controls. The dogs were studied clinically, haematologically and parasitologically five times over 11 months and their infectivity to sandflies was evaluated before and after the treatment. The 'asymptomatic' dogs were as infective to sandflies as the 'symptomatic' before treatment but all dogs were un-infective for at least a few months following chemotherapy. Treatment led to a temporary improvement in the clinical and biochemical condition of most of the dogs, the symptomatic dogs becoming asymptomatic, but parasitological cure was uncommon after 10 months' follow-up. There was often no correlation between clinical condition, parasitological condition and infectivity to sandflies. Some dogs from both the 'asymptomatic' and 'symptomatic' groups became infective to sandflies several months post-treatment.

Animals

Serum cytokines (IL-6, TNF-alpha, IL-1 beta and IFN-gamma) in ankylosing spondylitis: a close correlation between serum IL-6 and disease activity and severity.

The aim of our study was to analyse the serum interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and interferon-gamma (IFN-gamma) levels in patients with AS and their relationship with disease activity. An ELISA test was used to analyse serum cytokine (IL-6, TNF-alpha, IL-1 beta and IFN-gamma) levels in 69 patients with AS. Results were compared with those from 43 patients with RA and 36 patients with non-inflammatory back pain. The relationship between serum concentrations of the different cytokines and parameters of disease activity and severity in AS patients was also evaluated. IL-6 and TNF-alpha serum levels, but not IL-1 beta and IFN-gamma, were significantly higher in AS than in NIBP. However, patients with RA showed higher serum levels of IL-6, TNF-alpha and IFN-gamma than both AS and NIBP patients. In AS, IL-6 correlated with clinical parameters of disease activity with significant correlation being observed with laboratory parameters of inflammation such as ESR, CRP, platelet count and clinical parameters of severity such as vertebral mobility. TNF-alpha did not correlate with laboratory or clinical parameters of activity. Macrophagic cytokines (TNF-alpha and IL-6), are increased in AS patients and IL-6 closely correlated with the activity of the disease.

Adult