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10 recordsLinked to original sources
PubMed1992

Predictive binding of beta-carboline inverse agonists and antagonists via the CoMFA/GOLPE approach.

The synthesis and affinities of six new 3-substituted beta-carbolines (6-10, 12) for the benzodiazepine receptor (BzR) are described. These analogs were used both to probe the dimensions of the hydrophobic pocket in the benzodiazepine receptor and to test the predictive ability of a previously reported 3D-QSAR regression model. Of the new analogs synthesized, the gamma-branched derivatives (isobutoxy, 7, IC50 = 93 nM; isopentoxy, 9, IC50 = 104 nM) display significantly higher affinity for the BzR than either the beta-branched (sec-butoxy, 6, IC50 = 471 nM; tert-butyl ketone, 12, IC50 = 358 nM) or delta-branched (isopentoxy, 8, IC50 = 535 nM) analogs. An exception to this rule is the gamma-branched 3-benzyloxy derivative 10 (IC50 > 1000 nM) which appears to have a chain length that is too long to be accommodated by the BzR. The standard error of prediction for these six new beta-carbolines using the original regression model is significantly lower than the standard error estimate of the cross validation runs on the training set, hence the predictions made using this model are much better than expected. In order to obtain more credible predictions, a new procedure called GOLPE (generating optimal linear PLS estimates) was used to eliminate irrelevant electrostatic and steric descriptors from the regression equation. A substantial reduction in the standard error estimate resulted. The predictions from this new regression equation were somewhat less accurate than the ones obtained with the original regression equation; however the standard error of prediction and the standard error estimate are in much closer agreement. Finally, to probe the effect that the quality of the steric and electrostatic potentials has on 3D-QSAR analyses, the semiempirical MNDO parallel PRDDOE geometries and Mulliken charges used in the original analyses were replaced with ab initio 3-21G parallel 6-31G* geometries and electrostatic potential fit charges. A modest decrease in the standard error estimate and increase in cross validated R2 resulted.

Animals↗
PubMed1991

Lymphangioleiomyomatosis: the effectiveness of radiotherapy-induced ovarian function annulment. A case report.

Lymphangioleiomyomatosis is an unusual disease characterized by atypical smooth muscle hyperplasia especially of the lymphatic system and affecting females in their child-bearing years. We present a case in which ovarian function was annuled through radiotherapy, instead of resorting to the most commonly used oophorectomy, since the patient's severe respiratory dysfunction made surgery inadvisable. The clinical, radiological and functional characteristics of this entity are discussed, and the therapeutic possibilities are reviewed.

Adult↗
PubMed2026

Neoadjuvant Systemic Therapy for Resectable Intrahepatic Cholangiocarcinoma: From Retrospective Studies to Randomized Evidence.

Complete resection remains the only potentially curative treatment for localized intrahepatic cholangiocarcinoma (iCCA), yet postoperative recurrence is common, particularly in patients with high-risk disease. Neoadjuvant systemic therapy may permit earlier control of occult micrometastatic disease, optimize the delivery of systemic treatment, and provide an in vivo assessment of tumor biology prior to major hepatectomy. These potential benefits must be balanced against treatment-related toxicity, surgical delay, and the risk of disease progression precluding resection. Early evidence was primarily derived from retrospective studies, which yielded inconsistent survival outcomes and exhibited substantial vulnerability to confounding and treatment-selection bias. The single-arm NEO-GAP trial subsequently demonstrated the feasibility of administering neoadjuvant gemcitabine, cisplatin, and nab-paclitaxel followed by surgical resection. More recently, the randomized phase II-III ZSAB-neoGOLP trial showed that neoadjuvant gemcitabine-oxaliplatin, lenvatinib, and toripalimab followed by surgery prolonged median event-free survival compared with upfront surgery (median: 18.0 vs. 8.7 months) without substantially compromising surgical feasibility. However, the interim overall survival analysis was inconclusive, and the generalizability of these findings beyond selected, medically fit patients treated at Chinese centers remains uncertain. This narrative review critically appraises the evolving evidence, discusses patient selection and perioperative treatment, and identifies priorities for future research. Current evidence supports the selective consideration of neoadjuvant therapy in medically fit patients with technically resectable but oncologically high-risk iCCA, rather than its routine use in all resectable cases.

GOLP↗
PubMed1976

[Platelet anti-aggregating activity of furosemide (author's transl)].

The effect of furosemide on platelet aggregation, factor 3 availability, and response to hypotonic stress has been studied. Furosemide greatly inhibits platelet aggregation, with ADP, epinephrine, collagen, ristocetin, thrombin and serotonin. The use of heparin as anticoagulant does not alter this effect. Furosemide action is not conducted through calcium chelation. Platelet factor 3 availability is not modified by furosemide. There is a direct correlation between furosemide concentration and inhibition in the second phase of platelet response to hypotonic stress. The possibility of a disorder furosemide induced on the platelet metabolism, is suggested.

Adult↗
PubMed1990

[Pseudotumoral bronchial tuberculosis].

We analyse our own experience of a rare tuberculosis presentation that we call pseudotumoral bronchial tuberculosis. 9 cases were studied, which due to radiological, endoscopic and clinical features, a diagnosis of bronchogenic carcinoma was made. The median age was 63.7 years, 7 were male and 2 were female. The hilar or mediastinic radiological pattern was frequent. The bacterial diagnosis was made through the study of the samples obtained by bronchoscopy, except in 2 cases which were diagnosed through post-bronchoscopy sputum examination. The bronchial biopsy showed the typical necrotic granulomas of tuberculosis in only one case. Supported by the bad evolution of our patients treated without steroids, the possible efficacy of early use of steroid is suggested to avoid the most important sequelae, bronchial stenosis.

Adult↗
PubMed1989

[Osteochondroplastic tracheopathy. Diagnostic confirmation. Experience with 8 cases].

We report our experience in 8 patients with osteochondroplastic tracheopathy and consider the importance of its diagnosis y biopsy in order to confirm histology and if possible etiology, because specific treatment could change the course of the disease. Methods such as radiology, CT-scan, respiratory function tests only give diagnostic suspicion, which is a previous step before confirmation by bronchoscopy with biopsy. To date, with the exception of a few cases, the diagnosis is made by necropsy. Thus, this justifies our emphasis in the diagnosis of this rare disease when it is suspected in living patients.

Adult↗
PubMed1989

[Intracranial complications of otitis: the present-day situation].

The increasing number of intracranial complications of otic origin seen by the AA. in the previous 6 years, prompted them to make a survey of the respective files. In all, 9 patients were included in the group, with ages ranging from 18 to 72 years. Everyone showed marginal tympanic perforations with cholesteatoma. At their first visit to the office neurologic symptoms were present (mean time from beginning was 12 days) as an aftermath of chronic otitis. Meningitis, brain (temporo-parietal, temporal) and cerebellar abscesses of the implicated side were the diagnosis. Decisive for diagnosis was the CAT examination, being much better than the NMR (done once). Cases were managed in cooperation with the neurosurgical team. The mean time of hospitalization was 1 month. Eight cases did well (2 with neurologic sequels); the follow-up of the ninth patient is unknown.

Adolescent↗