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Biomedical subjects

T Pascual

Publications and source records attributed to T Pascual.

8 recordsLinked to original sources
PubMed2026

Impact of BRCA2 pathogenic variants on outcomes to first-line CDK4/6 inhibitors plus endocrine therapy in HR-positive/HER2-negative metastatic breast cancer.

BACKGROUND: Currently, three cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) are approved in combination with endocrine therapy (ET) as first-line treatment of patients with hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC). The impact of homologous recombination repair (HRR) pathogenic variants (PV) on outcomes with first-line CDK4/6i plus ET in HR-positive/HER2-negative MBC remains uncertain. PATIENTS AND METHODS: We conducted a multicenter, real-world, case-control study including 233 patients with HR-positive/HER2-negative MBC treated with first-line CDK4/6i and ET. Among them, 116 presented HRR PVs and 117 were matched controls with negative germline testing. The primary objective was to compare progression-free survival (PFS) and overall survival among germline-BRCA2 PV carriers, other HRR PV carriers, and controls. To minimize baseline differences in prognostic factors between PV carriers and controls, inverse probability of treatment weighting was applied. Molecular analyses in pre-CDK4/6i samples among patients with BRCA2 PV were carried out, including RAD51-foci, PAM50 intrinsic subtype, and RB1 loss of heterozygosity (LOH). RESULTS: Among the included 233 patients, median age at diagnosis was 45 years (interquartile range 39-56) and 33% had de novo metastatic disease. Primary resistance to adjuvant ET was present in 10% and secondary resistance in 27%. After a median follow-up of 44 months, patients with germline-BRCA2 PVs (n = 67) had significantly shorter PFS [11 versus 27 months; adjusted hazard ratio (aHR) 2.73, 95% confidence interval (CI) 1.65-4.51, P < 0.001] compared with controls. Among patients with endocrine-sensitive disease, germline BRCA2 PV carriers had markedly shorter PFS (median PFS 12 versus 39 months; aHR 4.04; 95% CI 1.82-8.98, P < 0.001). Exploratory analyses revealed RB1 LOH before CDK4/6i-treatment in most evaluable BRCA2 tumors. CONCLUSIONS: BRCA2 PVs were independently associated with poorer outcomes to first-line CDK4/6i plus ET in HR-positive/HER2-negative MBC compared with controls, especially relevant among patients with endocrine-sensitive disease. These findings suggest that patients with a germline PV in BRCA2 may require alternative first-line strategies.

Humans↗
PubMed1995

A protective effect of lithium on rat behaviour altered by ibotenic acid lesions of the basal forebrain cholinergic system.

Lithium was tested on an animal model of a brain cholinergic excitotoxic lesion. Male Wistar rats received unilaterally 50 nmol ibotenic acid in the nucleus basalis magnocellularis. Some were treated intraperitoneally with LiCl from two days before to six days after lesioning. Such treated rats showed less deficits than untreated lesioned animals on passive avoidance, ambulatory behaviour and choline acetyltransferase activity in the lesioned cortex. Lithium protection against excitatory amino acid neurotoxicity is suggested.

Animals↗
PubMed1992

[Single oral dose of phosphomycin trometamol versus pipemidic acid and norfloxacin in treating uncomplicated low-level urinary tract infections].

OBJECTIVE: To make an assessment of the effectiveness and safety of a single oral dose compared with the conventional way of treating low-level Urinary Infections presenting no complications. DESIGN: This was an investigative and prospective study, using a control, a simple blind and randomised sample. SITE. Health Centres in Oviedo and Zaragoza. PATIENTS OR OTHERS PARTICIPANTS: We looked at 150 patients and included 106 females between the ages of 16 and 75 in the study. Their clinical symptoms were compatible with low-level urinary infections presenting no complications. INTERVENTIONS: 49 patients were given Trometamol Phosphomicine (TP) in a single oral dose; 36 took Pipemidic Acid (PA) and 21 Norfloxacine (NFX), both of these in a dose of 400 mg twice a day for 5 to 7 days. MAIN MEASUREMENTS AND RESULTS: Clinical and bacteriological assessments of the results were made 3, 7, and 28 days after treatment. A total of 75 gems were isolated: E. coli was the most common (68%). In all three groups, the main symptoms rapidly disappeared after the start of the treatment. CONCLUSIONS: Having considered the bacteriological and clinical findings, as well as tolerance levels, we are able to conclude that a single oral dose of Trometamol Phosphomicine is a good alternative to conventional therapy for the treatment of low-level Urinary Infections Which present no complications.

Administration, Oral↗
PubMed1987

Urinary enzyme activities in patients treated with gold and other antirheumatic drugs.

We have studied 48 rheumatoid arthritis (RA) patients treated with nonsteroidal antiinflammatory drugs (NSAIDs), except salicylates, in 31 of whom parenteral gold was associated as therapeutic agent. In order to assess initial tubular involvement, the activities of some urinary enzymes were measured: N-acetylglucosaminidase (NAG, EC 3.2.1.30), microsomal amino-peptidase (MAP, EC 3.4.11.2) and gamma-glutamyltransferase (GGT; EC 2.3.2.2). Results were compared with a control group of 51 subjects of similar age, with no rheumatic symptoms and normal renal function. Both groups of patients (31 with gold therapy and 17 without) showed a significantly increased activity of NAG in urine, but the increase was greater in those treated with gold. MAP and GGT were not elevated significantly in either group. There was no correlation, however, between the increase of NAG and the cumulative dose of gold. NAG, MAP and GGT activities in serum yielded no relevant information. All the usual tests of renal function were also normal. Determination of NAG in urine may be regarded as a sensitive test, capable of detecting selective involvement of renal tubular cells, whose final diagnostic and prognostic significance merits further evaluation.

Acetylglucosaminidase↗
PubMed1984

Dose-related hemodynamic and renal effects of dopamine in septic shock.

offstudied hemodynamic and renal effects of increasing the dosage of dopamine (DP) by 5 micrograms/kg X min, in 7 patients with peritonitis and clinical findings of septic shock, all of whom were already receiving variable dosages of DP. Stroke index (SI) (p less than .01), except in 3 cases, and mean arterial pressure (p less than .01) were significantly elevated without significant increases in HR and systemic vascular resistance index (SVRI). Changes in mean pulmonary artery pressure (MPAP) and pulmonary wedge pressure (WP) were insignificant (less than 3 mm Hg). Renal response showed augmentation of diuresis (p less than .01), inulin clearance (Cin) (p less than .05), and fractional excretion of sodium (FENa) (p = .02) without significant changes in either paraminohypurate clearance (Cpha) or filtration fraction. There was no correlation between hemodynamic or renal changes and initial dosage of DP. We conclude that increasing the DP dosage in septic shock patients may be useful even when the patient is already receiving large doses. Increased natriuresis was not due to changes in plasma renal flow.

Aged↗