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Biomedical subjects

A Prat

Publications and source records attributed to A Prat.

At least 19 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

Appropriateness of admissions and hospitalization days in an acute-care teaching hospital.

A cross-sectional study was made of the appropriateness of admissions and hospitalization days in an high-technology, acute-care teaching hospital. This 952-bed institution with 31 hospital services is a reference center for the metropolitan area of Barcelona. A systematic random sampling (1:11) of the registers of hospital discharges was carried out during the months of January, February and March 1991 (n = 7,142) excluding discharges from the pediatric, obstetrics and psychiatric departments. A retrospective analysis was made of 639 patients' medical records using the Appropriateness Evaluation Protocol (AEP). The rate of inappropriate hospital admissions was 9.1% (58/639) (95% confidence interval: 6.9-11.5). Inappropriate admissions were primarily attributable to hospitalizations for diagnostic and/or therapeutic services that could have been rendered on an ambulatory basis (70.7% of cases). Overall 29.2% of hospitalization days (1,963/6,731) were inappropriate (95% confidence interval: 28.1-30.3). Inappropriate admissions to hospital, an optimizable health care planning and a conservative physician's attitude (postponed discharge) were the most frequent reasons for unnecessary days of care. The interrater reliability in the use AEP criteria for appropriateness of admission showed a kappa index of 0.5 and that for appropriateness of hospitalization days 0.67. In summary, instruments, such as the AEP protocol, that allow us to determine which patients can be attended at other levels of the health care system and which levels are the most appropriate, are key elements in improving the appropriateness of hospital use in public health care systems.

Acute Disease↗
PubMed1994

N-arginine dibasic convertase (NRD convertase): a newcomer to the family of processing endopeptidases. An overview.

N-arginine dibasic convertase (NRD convertase) (accession number L27124) is a metalloendopeptidase from rat brain cortex and testis which cleaves peptide substrates on the N-terminus of arginine residues in basic doublets. Its predicted amino acid sequence contains the putative zinc binding motif HXXEH in a region which exhibits 35% and 48% similarity with E coli protease III (pitrilysin E.C 3.4.99.44) and rat or human insulinase (E.C 3.4.99.45) respectively. This feature clearly classifies this endopeptidase as a member of the pitrilysin family of zinc-metalloproteases. However, the NRD convertase sequence contains a distinctive additional feature consisting of a 71 acidic amino acid stretch. Its substrate selectivity and the characteristic motifs of its amino acid sequence allow us to propose this new metalloendopeptidase as the first member of a new class of processing enzymes.

Amino Acid Sequence↗
PubMed1994

Cardiovascular and behavioural effects of centrally administered neuropeptide K in the rat: receptor characterization.

1. The cardiovascular and behavioural responses to intracerebroventricularly (i.c.v.) administered neuropeptide K (NPK) were studied in conscious rats. The central effects of NPK were characterized by pretreatment (i.c.v.) with selective antagonists for the NK1 ((+/-)-CP 96345 and RP 67580), NK2 (SR 48968) and NK3 (R 487) receptors. 2. NPK (10-65 pmol) induced tachycardia and dose-dependent increases of mean arterial blood pressure. The cardiovascular responses reached a maximum within 3 min post-injection and lasted for more than 1 h. Concurrently, NPK produced dose-dependent increases of face washing, head scratching, grooming, walking and wet dog shakes. 3. A desensitization of most of the behavioural responses (except head scratching) but not of the cardiovascular response was shown when two consecutive injections of 25 pmol NPK were given 24 h apart. 4. Both the cardiovascular and behavioural responses (except the head scratching) to 25 pmol NPK were blocked by pre-administration (i.c.v.) of 6.5 nmol (+/-)-CP 96345 or RP 67580 given 5 min earlier. No inhibition of NPK responses was observed when 6.5 nmol SR 48968 or R 487 were used in a similar study. Additionally, NPK effects were significantly reduced 24 h after the prior injection of (+/-)-CP 96345 but not of RP 67580. 5. These results support the involvement of NK1 receptors in the cardiovascular and behavioural effects of i.c.v. NPK. Thus, this peptide may play a putative role in central cardiovascular regulation as it is the most potent endogenous tachykinin described centrally, to date.

Animals↗
PubMed1994

[Fissuration of thoracic aneurysm in Horton disease, favourable course after surgery].

The authors report another case of rupture of the thoracic aorta in Giant Cell arteritis. The progressive nature of the rupture enabled life-saving aortic replacement with a vascular prosthesis. Only one previous report of this type of operation was found in a search of the literature. The prevalence of aortitis in Giant Cell arteritis would appear to be underestimated after autopsy studies. It affects the thoracic aorta mainly in the ascending segment but sometimes involves the whole aorta. It may remain asymptomatic or be complicated by arterial occlusion, aortic regurgitation, aneurysm, dissection or rupture. Effective steroid therapy could prevent these complications.

Aged↗
PubMed1993

Neuropeptide K potently stimulates the hydrolysis of phosphatidylinositol in the rat spinal cord.

The accumulation of total [3H]inositol phosphates stimulated by neuropeptide K was investigated in rat spinal cord slices and compared with that of substance P and carbachol. The rank order of potency of the agonists in stimulating [3H]phosphatidylinositol (PI) hydrolysis was neuropeptide K > substance P > carbachol. The PI responses to neuropeptide K and substance P were significantly (P < 0.01) enhanced when slices were incubated with a mixture of bacitracin (30 microM), captopril (10 microM) and leupeptin (2 micrograms/ml), yet the order of potency remained unchanged. These results show for the first time that NPK can stimulate the PI hydrolysis in the adult rat spinal cord. The relatively greater degree of potency and efficacy of NPK over SP to stimulate PI hydrolysis does not appear to be entirely attributed to the metabolic stability of the peptide.

Animals↗
PubMed1992

Anaesthetic doses of pentobarbital antagonize phosphatidylinositol hydrolysis induced by substance P or carbachol in the spinal cord and cerebral cortex of the rat.

Basal as well as agonist (100 microM substance P or 2 mM carbachol)-stimulated phosphatidylinositol hydrolysis was investigated in slices of rat spinal cord and cerebral cortex, in the presence and absence of pentobarbital (5-50 microM in vitro or 65 mg/kg in vivo) or urethane (0.2 mM in vitro or 1.4 g/kg in vivo). Urethane was without effect; pentobarbital, however, inhibited the basal hydrolysis and the agonist-stimulated phosphatidylinositol hydrolysis (in dose-dependent fashion in vitro). It is suggested that inhibition of phosphatidylinositol hydrolysis may be part of the cellular mechanisms by which pentobarbital produces anaesthesia.

Anesthesia↗
PubMed1992

Use of selective antagonists to dissociate the central cardiovascular and behavioural effects of tachykinins on NK1 and NK2 receptors in the rat.

1. The effects of intracerebroventricular (i.c.v.) pretreatment with selective NK1 ((+/-)-CP 96,345), NK2a (MEN 10,207; MEN 10,376) and NK2b (R 396) tachykinin receptor antagonists on the cardiovascular and behavioural responses to i.c.v. substance P (SP) and neurokinin A (NKA) were studied in conscious rats. 2. SP and NKA (25 pmol) induced mean arterial blood pressure and heart rate increases of the same magnitude and duration. The cardiovascular responses to both peptides were accompanied by excessive face washing, sniffing, grooming and wet dog shakes. 3. The cardiovascular responses to SP but not to NKA were attenuated by pretreatment with a NK1 receptor antagonist, (+/-)-CP 96,345. Of the behavioural responses, only face washing was significantly inhibited. 4. The cardiovascular and behavioural effects of NKA but not of SP were significantly attenuated by pretreatment with the selective NK2b receptor antagonist, R 396. 5. The selective NK2a receptor antagonists, MEN 10,207 and MEN 10,376, did not affect the cardiovascular and behavioural responses to either SP or NKA. 6. These results suggest, firstly, that the cardiovascular and behavioural effects of i.c.v. SP are mediated by NK1 receptors; secondly, that NKA injected i.c.v. does not interact with NK1 receptors but with another type of tachykinin receptor which may belong to the NK2b subclass. These findings provide pharmacological evidence for the existence of functionally active NK2 receptors in the rat brain.

Amino Acid Sequence↗
PubMed1992

[The radiology demand in primary care].

AIM: To contribute a preliminary study, which allows the best use of the demand criteria and acceptance mechanisms of radiological explorations at the primary care level. DESIGN: Retrospective and observational study. SITE. Public Health Care Center Poblenou, in the Barcelona area. PATIENTS: A random sample of patients covering 15,000 X-Ray explorations. MEASUREMENTS AND MAIN RESULTS: The parameters evaluated were: the type of x-ray; the existence of otherwise of pathology; the physician requesting the x-ray; and the patient's age and sex. Results show greater use by the feminine sex (56%), with statistically significant differences (p less than 0.0008) (1 degree of freedom). The overall pathology rate was 43%, also with significant differences between different groups of doctors (p less than 0.0001) (3 degrees of freedom). 52% of the investigations were on patients over 50. CONCLUSIONS: In general, the high percentage in primary care of pathological explorations should be noted; as should the variation in pathology rates between different groups of doctors, which suggests possible differences of criteria in the use of radiological indicators. The high percentage of patients of an advanced age will have to be considered in the planning of radiological services.

Age Factors↗
PubMed1991

Analysis of risk factors for surgical wound infections following vascular surgery.

Although surgical wound infections (SWI) following implantation of prosthetic devices can be catastrophic and often require removal of the prosthesis, few studies have identified risk factors for these infections. We conducted a prospective multicenter study to identify risk factors for SWI. Of 561 vascular surgery patients enrolled in the study, 23 (4.1%) developed SWI. Multivariate analysis using logistic regression analyses identified surgery on lower extremities, delayed surgery, diabetes mellitus, past history of vascular surgery, and short antimicrobial prophylaxis (three doses of cefamandole) as independent risk factors for SWI. Consequences of SWI were serious; two (9%) died, 11 (48%) required reoperation, and five (22%) had their prosthesis removed. A risk index was developed using the independent risk factors for SWI identified by logistic regression analyses. When no risk factors were present, no SWI was observed (0 of 100), and the rate of SWI increased from 2.5% when one risk factor was present to 53.8% (7 of 13) when greater than or equal to 4 risk factors were present.

Cefamandole↗
PubMed1991

Regulation of cardiovascular sympathetic neurons by substance P and gamma-aminobutyric acid in the rat spinal cord.

The spinal regulation of cardiovascular sympathetic preganglionic neurons by substance P (SP) and gamma-aminobutyric acid (GABA) was investigated in conscious rats. Intrathecal injection at the T-9 spinal level of bicuculline, a GABAA receptor antagonist, evoked increases in mean arterial pressure (MAP) and heart rate (HR) which were maximal at 5.0 and 0.5 nmol, respectively. Phaclofen, a GABAB receptor antagonist, produced no cardiovascular changes up to 2 mumol while 10 mumol evoked a rise in MAP and HR. Muscimol, a GABAA receptor agonist, produced a decrease in MAP which was maximal at 5.0 nmol and had no effect on HR. Baclofen, a GABAB receptor agonist, was without cardiovascular effects up to 5.0 nmol, while 50 and 100 nmol evoked a fall in MAP and HR. The pressor response to SP (16.25 nmol, T-9) was antagonised by 0.5-50 nmol muscimol or baclofen in a dose-related manner and the pressor response to SP was still inhibited by 40 nmol GABA in capsaicin-treated animals. However, when SP was injected at T-2, the rise in both MAP and HR was blocked by 50 nmol baclofen. Similarly, 50 nmol muscimol blocked the rise in both MAP and HR induced by 15 nmol thyrotropin-releasing hormone. In contrast, 50 nmol glycine failed to alter the cardiovascular response to SP co-injected either at T-9 or T-2. Baclofen was found to reduce significantly the basal release of epinephrine when injected at the T-9 level. These results provide pharmacological evidence for a possible tonic GABAergic inhibitory input onto cardiovascular sympathetic preganglionic neurons mediated by GABAA and GABAB receptors.

Animals↗
PubMed1991

Cold blood cardioplegia and warm cardioplegic reperfusion in heart transplantation.

The major cause of early death after heart transplantation is graft failure. In 99 consecutive heart transplantations two protocols of myocardial protection were employed. In group 1 (n = 38) initial cold crystalloid cardioplegia combined with cold saline storage and peroperative surface cooling was used. In group 2 (n = 61) cold crystalloid cardioplegia was injected initially and cold blood cardioplegia (Buckberg) was infused every 30 min as soon as the graft arrived in the operating room. No surface cooling was used. Warm blood cardioplegic reperfusion was administered before removal of the aortic clamp. There were 8 early (within 30 days) deaths in group 1 and 6 in group 2 patients. In group 1 there were 5 cardiac deaths against 3 in group 2. Mean ischemic time was 153 +/- 37 min in group 1 and 158 +/- 51 min (p greater than 0.05) in group 2. The post-transplantation need for catecholamines was ten times higher in group 1 patients than in group 2. The first endomyocardial biopsy (after 1 week) showed cytologic lesions compatible with ischemia in 40% of group 1 and only 9% in group 2 patients. We conclude from this initial experience that intermittent cold blood cardioplegia and warm blood cardioplegic reperfusion are useful in heart transplantation in restoring the damage suffered by the graft during brain death and graft storage.

Adult↗