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M Merino

Publications and source records attributed to M Merino.

At least 37 records · Page 2Linked to original sources
PubMed1998

[Ambulatory monitoring of A/EEG in the preoperative assessment of partial epilepsy].

INTRODUCTION: Electroencephalography, together with new neuroimaging techniques is still the main diagnostic tool for pre-operative assessment of epilepsy. The electrical episodes, both ictal and intercritical, are random paroxystic phenomena with regard to presentation, so the conventional EEG is sometimes of limited value. Therefore, in recent years, long duration EEG monitoring techniques have been favoured, with or without simultaneous recording of clinical behaviour, permitting recording for an indefinite period. Amongst these techniques, monitoring using cassette recording (A/EEG) if of specific interest since it permits the study of outpatients. OBJECTIVE: The main aim of surgical treatment of epilepsy is to abolish or reduce the number of crises. Therefore it is essential to localize the epileptogenic area as precisely as possible. The A/EEG has made a major contribution to the procedure of pre-operative assessment because of the considerable information it gives regarding the recording and character of the crises. MATERIAL AND METHODS: During the past three years, preoperative assessment has been carried out in our hospital on 44 patients with drug-resistant partial epilepsy. A total of 103 long duration cassette recordings (A/EEG) were done. Of these, 58 were done with surface electrodes and individualized set-up depending on the EEG findings, 8 with semi-invasive (sphenoid) electrodes, and 37 recordings used implanted sub-dural electrode strips. RESULTS: Combined study of the results obtained with these techniques permitted localization of the lesive-epileptogenic complex in 42 of these patients. We present the results obtained and conclude that A/EEG monitoring is useful in the pre-operative assessment of epilepsy.

Adolescent↗
PubMed1997

In vivo protection of striatal dopaminergic system against 1-methyl-4-phenylpyridinium neurotoxicity by phenobarbital.

We have studied the effect of a semichronic and acute treatment of phenobarbital on in vivo 1-methyl-4-phenylpyridinium ion- (MPP+)-induced neurotoxicity. A group of rats were intraperitoneally injected for 12 days with phenobarbital (80 mg/Kg of body weight, semichronic treatment) in order to induce cytochrome P450 levels in brain. At day 10 of treatment, rats received unilateral left striatal injections of 1 or 2 microg of MPP+. Two days after the injection of the toxin a dose-dependent loss of dopamine uptake along with a concomitant decrease of dopamine levels and its metabolites was produced in control rats. In phenobarbital treated animals striatal injection of 1 microg of MPP+ did not produce any effect on dopaminergic parameters but injection of 2 microg of MPP+ caused losses of dopamine levels and dopamine transporter although smaller than in control rats. TH immunohistochemistry in semichronic phenobarbital treated rats also demonstrated the protective effect of this drug against MPP+ toxicity. Dopamine uptake in synaptosomes from semichronic phenobarbital treated rats did not change with respect to the controls, thereby diminished MPP+ toxicity in phenobarbital treated rats is not due to an alterated uptake of the toxin. Neuroprotection found by intraperitoneal injection of phenobarbital 30 min before MPP+ intrastriatal injection (acute treatment) could discard the induction of cytochrome P450 as responsible for this suppressed neurotoxicity of MPP+. The neuroprotective effect of phenobarbital could be produced by its action as an excitatory amino acid antagonist or as a GABA agonist.

1-Methyl-4-phenylpyridinium↗
PubMed1997

Intestinal absorption kinetics of amiodarone in rat small intestine.

Amiodarone is a widely used antiarrhythmic agent with highly variable therapeutic effects. These seem to be related, at least in part, to the pharmacokinetics of the drug and particularly to some features of its gastrointestinal absorption process. The drug exhibits physico-chemical properties highly suitable for diffusion across lipophilic absorbing membranes, but its low aqueous solubility can act as the rate limiting step for absorption, making the process erratic and variable. In order to gain an insight into the intestinal absorption mechanism of the drug and detect possible non-linearities, a series of experiments using a classical rat gut in situ preparation were carried out with three amiodarone hydrochloride solutions (10, 75, and 200 micrograms mL-1). A synthetic non-ionic surfactant, polysorbate 80, at supramicellar concentration (2 mM) was used as the drug solubilizer. Amiodarone was assayed in biological samples by HPLC using a rapid, sensitive technique that was validated. The amiodarone first-order absorption rate constants obtained in these conditions were similar. No significant differences between ka values were found. Amiodarone absorption was clearly identified as a passive diffusion process.

Administration, Oral↗
PubMed1997

Nonlinear intestinal absorption kinetics of cefuroxime axetil in rats.

Cefuroxime is commercially available for parenteral administration as a sodium salt and for oral administration as cefuroxime axetil, the 1-(acetoxy)ethyl ester of the drug. Cefuroxime axetil is a prodrug of cefuroxime and has little, if any, antibacterial activity until hydrolyzed in vivo to cefuroxime. In this study, the absorption of cefuroxime axetil in the small intestines of anesthetized rats was investigated in situ, by perfusion at four concentrations (11.8, 5, 118 and 200 microM). Oral absorption of cefuroxime axetil can apparently be described as a specialized transport mechanism which obeys Michaelis-Menten kinetics. Parameters characterizing absorption of prodrug in free solution were obtained: maximum rate of absorption (Vmax) = 289.08 +/- 46.26 microM h-1, and Km = 162.77 +/- 31.17 microM. Cefuroxime axetil transport was significantly reduced in the presence of the enzymatic inhibitor sodium azide. On the other hand, the prodrug was metabolized in the gut wall through contact with membrane-bound enzymes in the brush border membrane before absorption occurred. This process reduces the prodrug fraction directly available for absorption. From a bioavailability point of view, therefore, the effects mentioned above can explain the variable and poor bioavailability following oral administration of cefuroxime axetil. Thus, future strategies in oral cefuroxime axetil absorption should focus on increasing the stability of the prodrug in the intestine by modifying the prodrug structure and/or targeting the compound to the absorption site.

Animals↗
PubMed1996

Differential immunohistochemical detection of transforming growth factor alpha, amphiregulin and CRIPTO in human normal and malignant breast tissues.

The expression of growth factors, such as transforming growth factor alpha (TGF alpha), amphiregulin (AR) and CRIPTO, a type-1 tyrosine-kinase growth factor receptor (erbB-2), and a tumor-suppressor gene (p53), that have been implicated in the development and/or the progression of breast cancer, was evaluated by immunohistochemistry in 100 human primary infiltrating breast carcinomas (IBC). AR and CRIPTO immunoreactivity was also assessed in 55 human breast ductal carcinomas in situ (DCIS). Within the 100 IBC, 80, 50, 73, 17, and 34 tumors expressed moderate to high levels of TGF alpha, AR, CRIPTO, erbB-2, and p53 respectively. In addition, AR and CRIPTO immunoreactivity were found in 11 and in 26 out of 55 DCIS respectively. In contrast, only 4, 3, and 2 out of 10 normal mammary-gland samples were weakly positive for TGF alpha, AR, and CRIPTO expression, respectively, whereas none was positive for erbB-2 or p53. Within the 100 IBC, expression of erbB-2 significantly correlated with high histologic and nuclear grading, with high growth fraction, and with estrogen-receptor (ER)- and progesterone-receptor (PgR)-negative tumors. A statistically significant correlation was also observed between p53 expression and high histologic grading, high growth fraction, and PgR-negative tumors. In contrast, no significant correlations were found between TGF alpha, AR, and CRIPTO immunoreactivity and various clinicopathological parameters, with the exception of a positive correlation between TGF alpha and ER expression. These data demonstrate that TGF alpha, AR, and CRIPTO expression are significantly increased in malignant mammary epithelium relative to normal epithelium. In particular, the differential expression of CRIPTO may serve as a potential tumor marker for breast carcinogenesis.

Adult↗
PubMed1996

Interaction of taurine on baclofen intestinal absorption: a nonlinear mathematical treatment using differential equations to describe kinetic inhibition models.

Previous studies showed that the in situ absorption of baclofen in rat jejunum was inhibited by beta-alanine, a nonessential amino acid, and therefore mediated, at least in part, by some beta-amino acid carrier. In this paper a similar study was undertaken using taurine, a sulfonic beta-amino acid, in order to evaluate its effect and to establish a general inhibition model. To achieve this goal, remaining concentrations of inhibitor were also measured and incorporated into the model. Previously, kinetic absorption in situ parameters for taurine in free solution were obtained: Vm = 27.73 +/- 9.99 mM h-1, K(m) = 8.06 +/- 2.82 mM, Ka (passive difussion component) = 0.40 +/- 0.28 h-1. Isotonic solutions containing 0.5 mM baclofen with starting taurine concentrations ranging from 0 to 100 mM were perfused in rat jejunum, and the remaining concentrations of both compounds were measured. The apparent rate pseudoconstant of the drug clearly decreased as the remaining taurine concentration increased. The interaction can be described as a complete competitive inhibition plus a second component, K, noninhibited, K = 0.58 (+/- 0.03) h-1, Ki = 20.62 (+/- 4.04) mM, Vmi = 28.12 (+/- 6.12) mM h-1, Kmi = 11.71 (+/- 2.53) mM, Kai = 0.47 (+/- 0.10) h-1. A residual absorption of baclofen in the presence of high taurine concentrations was observed, which should be attributed to another transport system not associated with the taurine carrier. In order to elucidate whether or not taurine and beta-alanine carriers are two separate entities that baclofen can use for absorption, further experiments using beta-alanine and taurine together as inhibitors (baclofen, 0.5 mM; beta-alanine, 50 mM, and taurine, 50 mM) were developed. Results indicated that baclofen and both amino acids share the same carrier in the intestinal absorption process. We have completed studies using leucine, taurine, and GABA together as inhibitors of drug absorption. An isotonic perfusion solution of 0.5 mM baclofen in the presence of 50 mM leucine, 25 mM taurine, and 25 mM GABA was perfused. Under these conditions the absorption rate pseudoconstant of baclofen decreases until 0.080 h-1 (+/- 0.069). Practical implications of these phenomena are briefly discussed.

Animals↗
PubMed1996

Ossifying fibroma of the skull in a patient with neurofibromatosis type 1. Case report.

Ossifying fibroma is a rare, benign, primary bone tumor that occurs most commonly in the mandible; a cranial vault location is extremely rare. In this report a case of symptomatic frontoparietotemporal ossifying fibroma with intracranial growth and cerebral displacement in a 12-year-old boy with neurofibromatosis type 1 (NF1) is described. Once excised the lesion did not recur. The skeletal system is frequently affected in NF1, and bone abnormalities are present in 50% to 70% of patients with this condition. The etiology of such lesions in NF1 is still controversial. To the authors' knowledge, ossifying fibromas of calvarial bones have not been described in NF1.

Child↗
PubMed1995

Influence of leucine on intestinal baclofen absorption as a model compound of neutral alpha-aminoacids.

The inhibitory effect of the essential alpha-aminoacid L-leucine on the intestinal absorption of the antispastic drug baclofen was examined by means of an in situ rat gut perfusion technique. When 0.5 mM baclofen solutions were perfused in the presence of increasing concentrations of the aminoacid (5-100 mM), the apparent absorption rate constant of the drug decreased as the initial leucine concentration increased. Higher leucine concentrations however did not completely abolish the absorption of the drug (at 100 mM of leucine, only 76% inhibition was observed). The interaction can be mathematically described as a complete competitive inhibition with a second component, K = 0.35 (+/- 0.08)h-1, Ki = 0.25 (+/- 0.09)mM, AIC = -97.02. In the light of some of the absorption features of the drug, however, the residual absorption of baclofen in the presence of high leucine concentrations should be attributed to another transport system not used by leucine. Apparent parameters characterizing absorption of leucine in the presence of baclofen (0.5 mM) were Vm = 61.02 (+/- 5.46)mM h-1; Km = 8.04 (+/- 0.89)mM, and AIC = -62.25. The results indicate that baclofen and leucine share some carriers in the intestinal absorption processes. Since leucine is an essential dietary aminoacid, and therefore a normal food component, this finding could be relevant in preventing interactions that would lead to a reduced oral bioavailability during baclofen therapy.

Amino Acids↗
PubMed1994

Intestinal absorption pathway of gamma-aminobutyric acid in rat small intestine.

Intestinal absorption of gamma-aminobutyric acid (GABA), as a model compound for gamma-aminoacids, has not been extensively studied from the kinetic viewpoint. Since data from our laboratory suggested that some competition arises between intestinal absorption of beta-alanine and GABA and since our intent was to maintain the aqueous stagnant diffusion layer in order to approach absorption tests to in vivo physiological conditions, a rat jejunum in situ study was undertaken in order to gain an insight into the mechanism of GABA absorption. In the present paper, results from assays using isotonic perfusion solutions with starting GABA concentrations ranging from 1 to 50 mM are reported. They show that the intestinal absorption of the gamma-aminoacid can be apparently described as a specialized transport mechanism which obeys Michaelis-Menten and first-order kinetics. Parameter values found were Vm = 13.99 +/- 2.37 mM h-1, Km = 3.87 +/- 0.63 mM, and ka(passive) = 0.362 +/- 0.120 h-1. Through the perfusion of 5 mM beta-alanine solutions containing variable concentrations of GABA (from 5 to 50 mM), a partially competitive inhibition of beta-alanine absorption was apparently characterized.

Alanine↗
PubMed1994

Influence of gamma-aminobutyric acid on baclofen intestinal absorption.

Since previous studies suggested that baclofen absorption in the rat middle intestine was inhibited by beta-alanine and therefore mediated, at least in part, by the beta-aminoacid carrier, we focused our new studies on the analysis of the possible inhibition of the drug by a gamma-aminoacid model compound, gamma-aminobutyric acid (GABA). A rat jejunum in situ study was undertaken in order to evaluate the effect of GABA on baclofen absorption and to establish the inhibition model. Assays using isotonic perfusion solutions of 0.5 mM baclofen with starting GABA concentrations ranging from 0 to 100 mM are reported. The results show that the absorption rate pseudoconstants of the drug decrease at the GABA concentration increases, with a limiting value of 0.65 h-1 (+/- 0.01). A partial competitive inhibition or complete competitive inhibition in the presence of a passive component could define the interaction phenomena between the two substances. Kinetic absorption parameters for GABA in the presence and absence of baclofen (Ki = 5.67 +/- 1.54, Km = 3.87 +/- 0.63) suggest the existence of more than one intestinal carrier system for baclofen or GABA.

Animals↗
PubMed1994

Hereditary papillary renal cell carcinoma.

We describe a 3 generation family with members affected with papillary renal cell carcinoma, an uncommon histological type of renal cell carcinoma. Multiple tumors of varying size were present in both kidneys of affected family members. The disorder was not linked to polymorphic markers on chromosome 3p and there was no loss of heterozygosity at loci on 3p in renal tumors. The results suggest the presence of a renal cell carcinoma gene not located on 3p that predisposes to renal cell carcinoma with a distinct histological appearance. The inherited disorder in this family appears to be different from recognized hereditary cancer syndromes.

Adolescent↗
PubMed1994

Effects of surfactants on amiodarone intestinal absorption. I. Sodium laurylsulfate.

Amiodarone is a widely used antiarrhythmic agent with high variability in therapeutic effects, which appears to be related, at least in part, to its pharmacokinetics, and in particular, gastrointestinal absorption. The drug exhibits physico-chemical properties highly suitable for diffusion across lipophilic absorbing membranes but its low aqueous solubility can act as the rate limiting step for absorption, making it erratic and variable. In studying the intestinal absorption mechanism of amiodarone, a series of experiments using a rat gut in situ preparation was performed in the presence of a synthetic anionic surfactant, as a drug solubilizer, i.e., sodium laurylsulfate, at variable supramicellar concentrations (from 2.6 to 104 mM). Absorption rate constants of amiodarone decreased as surfactant concentration increased, the absorption being unusually fast at lower surfactant concentrations. Equations were developed to evaluate the relationship between absorption rate constant and surfactant concentration in the intestinal luminal fluid.

Amiodarone↗
PubMed1993

Flow cytometric DNA analysis of interleukin-2 responsive renal cell carcinoma.

Adoptive immunotherapy using interleukin-2 (IL-2) based therapy can result in marked tumor regression in some patients with metastatic renal cell carcinoma. DNA flow cytometry has not been previously studied as a predictor of outcome of this therapy. Archival paraffin embedded tumors were studied in 23 IL-2 treated patients with metastatic renal cell carcinoma. Eleven patients were complete responders (CR) and 12 were nonresponders (NR). In the CR group, 4/11 (40%) were diploid and 7/11 (60%) were aneuploid. In the NR group, 9/12 (75%) were diploid and 3/12 (25%) were aneuploid. Although there was a trend that patients with an aneuploid DNA pattern were more likely to undergo a complete response, ploidy pattern alone was not significantly predictive of response (p2 = 0.10, Fischer's exact test). When combining ploidy pattern with other variables that were predictive for complete response, such as good performance status and a higher pretreatment weight, prediction of complete response was not improved by including ploidy. This preliminary report suggests that DNA ploidy does not appear to provide any additional information concerning responsiveness to IL-2 based immunotherapy beyond that obtained by performance status and pretreatment weight in this patient population.

Carcinoma, Renal Cell↗
PubMed1993

A pilot study of pi-class glutathione S-transferase expression in breast cancer: correlation with estrogen receptor expression and prognosis in node-negative breast cancer.

PURPOSE AND METHODS: Previous studies have indicated that RNA levels for pi-class glutathione S-transferase (GST pi), a phase II, drug-metabolizing enzyme, were inversely related to estrogen receptor (ER) and progesterone receptor (PR) levels in human breast tumors. Because GST pi also is expressed in normal breast epithelium, an immunohistochemical assay that uses affinity-purified polyclonal antibodies to GST pi was developed to examine the possible relationship between GST pi expression in breast cancer cells and hormone receptor expression, as well as prognosis, in patients with primary breast cancer. RESULTS: A strong inverse correlation between GST pi expression and ER (two-sided P [P2] = .002) and PR status (P2 = .023) was found in our study of 189 patients with primary breast cancer. GST pi expression was not related to tumor size, nodal metastasis, nuclear grade, histology, or age of the patient. In node-negative breast cancer (n = 72), increased GST pi expression was associated with decreased disease-free survival (DFS) and overall survival (OS). When GST pi expression was divided into categories of negative (no GST pi-positive tumor cells), intermediate (1% to 70% GST pi-positive tumor cells), and high (> 70% GST pi-positive tumor cells), the relative risk of tumor recurrence in patients with node-negative breast cancer was increased 3.39-fold for each successive category of expression (P2 = .0045; 95% confidence interval, 1.46 to 7.87) and the relative risk of death was increased 4.49-fold for each successive category (P2 = .0003; 95% confidence interval, 2.02 to 10.42). The actuarial 5-year OS was 100%, 79%, and 51%, and the DFS was 94%, 77%, and 44%, for the negative, intermediate, and high tumor groups, respectively. Among the factors studied in multivariate analysis (ER status, PR status, nuclear grade, and tumor size), GST pi expression was the factor that most accurately predicted shorter DFS and OS in node-negative patients. CONCLUSION: GST pi expression is inversely related to hormone receptor status in breast cancer. This pilot study also suggests that increased GST pi expression may be an important predictor of early recurrence and death in node-negative breast cancer patients that merits additional investigation.

Breast Neoplasms↗
PubMed1992

Mastectomy versus breast-conserving therapy in the treatment of stage I and II carcinoma of the breast: a randomized trial at the National Cancer Institute.

PURPOSE: Mastectomy versus excisional biopsy (lumpectomy) plus radiation for the treatment of stage I and II breast cancer was compared in a prospective randomized study. PATIENTS AND METHODS: From 1979 to 1987, 247 women were randomized and 237 were treated on this study. All patients received a full axillary dissection and all node-positive patients received adjuvant chemotherapy with cyclophosphamide and doxorubicin. Radiation consisted of external-beam therapy to the whole breast with or without supraclavicular nodal irradiation followed by a boost to the tumor bed. RESULTS: The minimum time on the study was 18 months and the median time on the study was 68 months. No differences in overall survival or disease-free survival were observed. Actuarial estimates at 5 years showed that 85% of mastectomy-treated patients were alive compared with 89% of the lumpectomy/radiation patients (P2 = .49; 95% two-sided confidence interval [CI] about this difference, 0% to 9% favoring lumpectomy plus radiation). The probability of failure in the irradiated breast was 12% by 5 years and 20% by 8 years according to actuarial estimates. Of 15 local breast failures, 14 were treated with and 12 were controlled by mastectomy; the ultimate local-regional control was similar in both arms of the trial. CONCLUSION: These data add further weight to the conclusion that breast conservation using lumpectomy and breast irradiation is equivalent to mastectomy in terms of survival and ultimate local control for stage I and II breast cancer patients.

Adult↗
PubMed1991

Partially competitive inhibition of intestinal baclofen absorption by beta-alanine, a nonessential dietary aminoacid.

In situ intestinal absorption of baclofen in the rat in the presence of beta-alanine has been investigated. Through the perfusion of 0.50 mM baclofen solutions containing variable concentrations of the aminoacid (from 5 to 100 mM), a partially competitive inhibition of baclofen absorption was characterized: absorption rate pseudoconstants of the spasmolytic drug decrease as beta-alanine concentration increases, until a limiting value is obtained (36.8 per cent of that found for baclofen alone). A computer method was developed in order to calculate parameters governing baclofen absorption in the presence of beta-aminoacid, with the following results: Vm = 11.22 mM h-1; Km = 7.42 mM; Ki = 2.45 mM; alpha = 2.78; r = 0.998. Kinetic absorption parameters for beta-alanine in the presence of 0.50 mM baclofen were also assessed: Vm = 49.88 mM h-1; Km = 12.16 mM; r = 0.998, which, as can be expected, do not significantly differ from those previously found in the absence of the spasmolytic. It is concluded that baclofen and beta-alanine compete for the same intestinal carrier system, although the values of the interaction parameters, particularly Ki, can be more or less biased due to the limitations of the procedure and/or to the existence of some other carrier system for absorption. Possible practical implications of this phenomenon are briefly discussed.

Animals↗