SEARCH · PubMed Health

Results for “Pathologic response”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 901 records · Page 50Linked to original sources

PubMed2004

Acquiring signalling specificity from the cytokine receptor gp130.

Repeated use of a relatively small number of intracellular signalling molecules specifies tissue- and cell-type-specific responses to pleiotropic-acting growth factors and cytokines. Currently, gaining a better understanding of these mechanisms is a major challenge. The IL-6 family of cytokines shares a common receptor subunit called gp130. Phenotypic comparisons of mice with amino acid knock-in substitutions that disable individual signalling modules in gp130, with knockout mice lacking ligand-specific gp130 activation or transgenic mice with constitutive gp130 activation, has led to the identification of two molecular mechanisms. One mechanism is based on differential target-gene responsiveness to signalling threshold levels transduced by either the STAT1/3 or the SHP2/ERK cascade, which are under reciprocal negative regulation and together account for the majority of intracellular gp130 signalling. The second mechanism is based on the capacity of certain cell types to integrate the often-conflicting information transduced by these two pathways, and to prevent pathological responses.

Animals↗

PubMed1993

Particle repositioning maneuver for benign paroxysmal positional vertigo.

Benign paroxysmal positional vertigo is a common, most often self-limited, vestibular end organ disorder that in some cases may be quite disabling. Recent evidence suggests that some, if not most, cases result from free-floating posterior semicircular canal endolymph particles. We postulate that the particle repositioning maneuver displaces these particles from the posterior canal through the common crus into the utricle, where they no longer induce pathologic responses. Our report focuses on 38 consecutive patients treated with this simple bedside technique during a 10-month period. On follow-up, 26 patients (68.4%) were free of disease, 4 (10.5%) were significantly improved, 4(10.5%) remained unchanged, and 4(10.5%) were lost to follow-up. Of the 4 patients who remained unchanged, 2 underwent successful posterior semicircular canal occlusions. The direction of the nystagmus during the second stage of the maneuver appears important in predicting the efficacy, with reversal of nystagmus denoting a poor response. These findings provide additional insight into the pathophysiology of this disorder.

Adult↗

PubMed1998

Short-course induction chemoradiotherapy with paclitaxel for stage III non-small-cell lung cancer.

BACKGROUND: This study assessed toxicity, tumor response, disease control, and survival after short-course induction chemoradiotherapy and surgical resection in patients with stage III non-small-cell lung carcinoma. METHODS: Forty-five patients with stage III non-small-cell lung carcinoma received 12-day induction therapy of a 96-hour continuous infusion of cisplatin (20 mg/m2 per day), 24-hour infusion of paclitaxel (175 mg/m2), and concurrent accelerated fractionation radiation therapy (1.5 Gy twice daily) to a dose of 30 Gy. Surgical resection was scheduled for 4 weeks later. Postoperatively, a second identical course of chemotherapy and concurrent radiation therapy (30 to 33 Gy) was given. RESULTS: Induction toxicity resulted in hospitalization of 18 (40%) patients for neutropenic fever. No induction deaths occurred. Of 40 (89%) patients who underwent thoracotomy, resection for cure was possible in 32 (71%) patients. Pathologic response was noted in 21 (47%) patients, and 14 (31%) were downstaged to mediastinal node negative (stage 0, I, or II). At a median follow-up of 19 months, 24 patients were alive, 10 with recurrent disease. Of 21 deaths, 16 were from recurrent disease, three were from treatment, and two were unrelated. Recurrent disease was distant in 21 patients, distant and locoregional in 2, and locoregional in 3. The Kaplan-Meier projected 24-month survival is 49%. Projected 24-month survival is 61% for stage IIIA, 17% for stage IIIB (p = 0.035); 84% for pathologic responders, 22% for nonresponders (p<0.001); 83% for downstaged patients (stage 0, I, or II), 33% for those not downstaged (p = 0.005); and 63% for resectable patients, 14% for unresectable patients (p = 0.007). CONCLUSIONS: We conclude that short-course neoadjuvant therapy with paclitaxel (1) has manageable toxicity and a low treatment mortality, (2) results in good tumor response and downstaging, (3) provides excellent locoregional control with most recurrences being distant, and (4) has improved the median survival compared with historical controls. Survival was better in stage IIIA patients, resectable patients, pathologic responders, and patients downstaged to mediastinal node negative disease (stage 0, I, or II).

Antineoplastic Agents, Phytogenic↗

PubMedDate not supplied

Clinical and instrumental diagnosis of autonomic neuropathy in insulin-dependent diabetes.

The author report a study of the relationship between symptomatic autonomic neuropathy and the response to simple cardiovascular autonomic tests (Valsalva maneuver, handgrip-test, detection of postural hypotension), in a large series of insulin-dependent diabetics (IDD). Symptoms of autonomic neuropathy were referred by 28 out of 130 IDD, prevalence and severity showed a clear relationship with the duration of diabetes. Only 4 out of 36 patients examined showed a pathologic response to the handgrip-test, while an abnormal Valsalva maneuver was evident in 24 out of 113 IDD. The data show that while the recognition of symptoms indicating a widespread autonomic derangement is rather easy, the diagnosis of autonomic neuropathy may be more difficult in the presence of mild or unspecific symptoms. The Valsalva maneuver exhibited the higher frequency of abnormal responses suggesting that the parasympathetic cardiovascular regulation may be impaired earlier than the sympathetic one. This early subclinical autonomic neuropathy may be due to metabolic or functional factors. Even if clinical consequences of an autonomic derangement of cardiovascular regulation may be serious, in our opinion subclinical impairment, being detectable in a large proportion of patients within the first year of disease, is unlikely to have a short-term severe prognostic value.

Adolescent↗

PubMed1996

Arthroscopic transglenoid suture capsulorrhaphy for anterior shoulder instability.

The role of arthroscopic procedures in the management of glenohumeral stability continues to evolve. Arthroscopic transglenoid suture capsulorrhaphy, as described, is an effective alternative for correcting the pathology of anterior and anteroinferior shoulder instability. The procedure avoids the morbidity associated with open repairs as a result of anterior soft tissue dissection and division of the subscapularis. The procedure, however, is technically demanding. To achieve predictable and reproducible results that approach those seen in comparable patient populations undergoing open Bankart stabilization, recognition of, and addressing, the responsible pathology is essential, as is appropriate patient selection. Based upon experience to date, arthroscopic transglenoid suture capsulorraphy is best indicated for traumatic anterior dislocators with a Bankart lesion and good quality glenohumeral ligaments. Arthroscopic suture capsulorrhaphy is not recommended for patients involved in upper extremity collision sports, those with a large glenoid rim defect, habitual luxators, patients younger than 18 years of age, and for surgeons whose experience with operative arthroscopy of the shoulder is limited. The procedure has an unresolved role, due to lack of sufficient long-term data in acute dislocations, multidirectional instability, those with previously failed open or arthroscopic repairs, and those with generalized joint hyperlaxity. The eventual role of arthroscopic transglenoid suture capsulorrhaphy in the treatment of anterior shoulder instability awaits further studies and technological innovation.

Adolescent↗

PubMed1995

Tissue changes at different periods of ischemia.

A multidisciplinary study was done to examine the following: (a) pathophysiological changes in muscle and nerve response following different periods of normothermic and cold ischemia; (b) alterations in the release of enzymes (K, LDH), CA++, K=and lactate under these conditions; and (c) histological alterations of vessels, nerves and muscles after different periods of normothermic and cold ischemia. The results demonstrate that hypothermic ischemia greatly reduces both the leakage of enzymes, cellular damage and pathological responses. We infer that amputated parts containing muscular masses may be replanted with good prognosis for satisfactory functional results within 4-5 hours at room temperature. By reducing the temperature, the time between cooling and revascularization may be doubled. Parts without muscles may be replanted 10-12 hours after normothermic ischemia and up to 24 hours or even longer after cold ischemia.

Animals↗

PubMed2006

Success of neoadjuvant chemotherapy in conversion of mastectomy to breast conservation surgery.

Neoadjuvant chemotherapy (NC) in patients with breast cancer results in high response rates and has been used with the purpose of reducing tumor size and achieving breast conservation (BC) in individuals who initially require mastectomy. Our objective is to determine the success of NC in achieving BC in women who initially were not candidates for BC. We conducted a cohort study of women with invasive breast cancer who required mastectomy but desired BC surgery. Outcomes measured were tumor response and rates of BC. Thirty-seven women had a mean age of 45 years. Mean tumor size was 51 mm, and 62 per cent were larger than 4 cm. Tumors were predominantly infiltrating ductal carcinoma (83.3%) and high grade (62.2%). Cyclophosphamide, doxorubicin, and 5-fluorouracil with or without taxotere were most commonly used (86%). Complete clinical and pathologic responses were seen in 32.4 per cent and 10.8 per cent of patients, respectively. BC was achieved in 56.7 per cent of cases. Only initial tumor size predicted tumor regression and success of BC (P = 0.014). Neither tumor histology nor biologic markers predicted tumor response. In conclusion, NC is an effective alternative in achieving tumor reduction and BC in selected patients who require mastectomy but desire BC surgery.

Antibiotics, Antineoplastic↗

PubMed1999

HIF-1alpha and p53 promote hypoxia-induced delayed neuronal death in models of CNS ischemia.

Brain ischemia is a cause of substantial morbidity and mortality during the later decades of life. In light of this, many studies have used in vitro and in vivo models of acute necrosis to test candidate therapeutic agents. More recently, the existence of a genetically programmed component of ischemic death has become widely accepted. We have used molecular genetic approaches to investigate the potential link between hypoxia-induced gene transcription and the delayed death of ischemic neurons. Hypoxia-induced gene expression is an evolutionarily conserved response comprising both transcriptional activation and posttranscriptional and posttranslational stabilization events. Members of the PER-ARNT-SIM (PAS) family of basic helix-loop-helix transcription factors have been shown to regulate hypoxic transcripts in nonneuronal cultured lines. However, evidence for ischemic activation of PAS proteins within the neuronal compartment or possible involvement in neuronal death is lacking. The tumor-suppressor protein p53 is a known transcriptional activator within the central nervous system that is clearly involved in the pathologic response to ischemia. This article will provide data that implicate the coordinate activities of p53 and the PAS protein HIF-1alpha in driving ischemia-induced delayed neuronal death. Background regarding mechanisms of ischemic neuronal death will also be provided with special attention paid to the role of de novo gene expression in promoting this pathologic sequence. The identification of the HIF-1alpha/p53-mediated signaling pathway in neurons highlights a novel target toward which anti-ischemic neuroprotective drug discovery can be applied.

Animals↗

PubMed2006

Complement mediators in ischemia-reperfusion injury.

BACKGROUND: Ischemia-reperfusion (I/R) injury occurs when a tissue is temporarily deprived of blood supply and the return of the blood supply triggers an intense inflammatory response. Pathologically, increased complement activity can cause substantial damage to blood vessels, tissues and also facilitate leukocyte activation and recruitment following I/R injury. Herein, previously published studies are reported and critically reviewed. METHODS: Medline and the World Wide Web were searched and the relevant literature was classified under the following categories: (1) Complement pathways; (2) The complement system and the inflammatory response; (3) Complement in ischemia-reperfusion injuries; and (4) Therapeutic approaches against complement in I/R injuries. RESULTS AND CONCLUSIONS: I/R injury is a common clinical event with the potential to seriously affect, and sometimes kill, the patient and is a potent inducer of complement activation that results in the production of a number of inflammatory mediators. Complement activation leads to the release of biologically active potent inflammatory complement substances including the anaphylatoxins (C3a and C5a) and the cytolytic terminal membrane attack complement complex C5b-9 (MAC). The use of specific complement inhibitors to block complement activation at various levels of the cascade has been shown to prevent or reduce local tissue injury after I/R. Several agents that inhibit all or part of the complement system, such as soluble complement receptor type 1 (sCR1), C1 inhibitor (C1-INH), C5a monoclonal antibodies, a C5a receptor antagonist and soluble CD59 (sCD59) have been shown to reduce I/R injury of various organs. The novel inhibitors of complement products may eventually find wide clinical application because there are no effective drug therapies currently available to treat I/R injuries.

Animals↗

PubMed1998

A phase II trial of preoperative mitomycin, cisplatin and 5-fluorouracil in adenocarcinoma of the oesophagus.

The effect of neoadjuvant chemotherapy in patients with apparently operable adenocarcinoma of the oesophagus has been investigated. Two courses of mitomycin, cisplatin and 5-fluorouracil (MCF) were given, followed by a radiological evaluation of response. Twenty-two of 25 patients completed both courses. Two showed a complete response and 12 a partial response. There was a pathological complete response of the primary tumour in only one patient (although there was residual secondary tumour in a local lymph node). The main toxicity was myelosuppression, with 9/22 patients having the second chemotherapy course delayed. There were three sudden deaths, one due to a pulmonary embolus and two due to complications of infections. Twenty-one patients underwent surgical exploration; there were 18 resections. Although the radiological response rate of MCF (14/25; 56%; 95% CI 37-75) appeared promising, there were no pathological complete responders. Further Phase II trials are needed to identify more efficacious agents and regimens that will yield a pathological response rate of at least 10%, before proceeding to randomized trials of neoadjuvant chemotherapy for adenocarcinoma of the oesophagus.

Adenocarcinoma↗

PubMed2003

Energy metabolism and the evolution of reproductive suppression in the human female.

Reproduction places severe demands on the energy metabolism in human females. When physical work entails higher energy expenditure, not enough energy will be left for the support of the reproductive processes and temporal suppression of the reproductive function is expected. While energy needed for reproduction may be obtained by increases in energy intake, utilization of fat reserves, or reallocation of energy from basal metabolism, several environmental or physiological constraints render such solutions unlikely. For human ancestors increases in energy intake were limited by availability of food, by labor of food preparation and by metabolic ceilings to energy assimilation. Energy stored as fat may support only a fraction of the requirements for reproduction (especially lactation). Effects of intense physical activity on basal metabolism may also interfere with fat accumulation during pregnancy. Finally, the female physiology may experience demands on increasing the basal metabolism as a consequence of physical activity and, at the same time, on decreasing the basal metabolism, when energy to support the ongoing pregnancy or lactation is inadequate. The resulting metabolic dilemmas could constitute a plausible cause for the occurrence of reproductive suppression in response to physical activity. It is, therefore, likely that allocating enough energy to the reproductive processes during periods when energy expenditure rises may be difficult due to physiological and bioenergetic constraints. Females attempting pregnancy in such conditions may compromise their lifetime reproductive output. A reproductive suppression occurring in low energy availability situations may thus represent an adaptive rather then a pathological response.

Adipose Tissue↗

PubMed1998

A pathological study of experimental long-standing Schistosoma bovis infection in sheep.

The pathological response of sheep to two dose levels (400 or 10,000 cercariae) of Schistosoma bovis was evaluated 24 weeks after infection. The results confirmed that a single low or high dose causes lesions in the liver and intestine, and that the lungs, lymph nodes, pancreas and abomasum are affected in sheep given a single high dose. In addition, the study showed that pathological changes (mainly a granulomatous inflammatory reaction) were induced not only by eggs but also by adult worms, and that their severity was in general related to the dose of S. bovis. Hoeppli reaction product, observed on the surface of adult schistosomes in some parasitic granulomas, showed no immunoreaction for IgG, IgA or IgM.

Animals↗

PubMed2002

Correlation of SPECT with pathology and seizure outcome in children undergoing epilepsy surgery.

SPECT can be used to image regional cerebral blood flow (rCBF) and has been shown to help localize the seizure focus in partial epilepsies as part of the presurgical evaluation. Few studies have explored the possible relation between preoperative SPECT and underlying pathology, or any relation to postsurgical outcome. In this study preoperative ictal and interictal rCBF in relation to the histopathological diagnosis and outcome in a series of 35 children (24 females, 11 males; mean age 9.6 years, age range 11 months to 18 years) who had undergone resective surgery for epilepsy were retrospectively evaluated. A correlation between ictal hyperperfusion and the underlying responsible pathology was shown, with a consistent ictal increase in perfusion in developmental pathologies and Rasmussen's encephalitis, and consistent interictal hypoperfusion in hippocampal sclerosis (HS). No rCBF study parameter appeared to relate to outcome but in the group with HS the best outcome was seen in those with localizing ictal rCBF. The varied group of pathologies from hemispherectomy had excellent outcome but the SPECT findings had little to contribute over the abnormalities detected on MRI. In conclusion, rCBF studies remain a useful presurgical investigation in children with partial epilepsy, especially where HS, cortical dysplasia, or inflammatory disease are the underlying pathology. However, rCBF studies add little to the investigation of children with seizures secondary to benign tumours or cerebral infarcts, or where hemispherectomy is the likely preferred surgical option.

Adolescent↗

PubMed2001

The mucosal immune system: from specialized immune defense to inflammation and allergy.

The mucosal immune system is a first line of defense against foreign antigens, including microbial and dietary antigens. Under normal circumstances, the mucosal immune system employs tightly regulated dynamic mucosal intra- and internets consisting of inductive and effector sites for the induction of an appropriate immunological homeostasis between the host and mucosal environments. The common mucosal immune system (CMIS), which interconnects between inductive (e.g. Peyer patch) and effector (e.g. intestinal lamina propria) tissues for the induction of the IgA response, is well characterized. Recent results provide strong evidence for the presence of a CMIS-independent IgA induction pathway. Two distinct subsets of mucosal IgA-committed B cells termed B-1 and B-2, are associated with CMIS-independence and CMIS-dependent cascades respectively. In some cases, the breakdown of this tightly regulated mucosal immune system leads to pathological responses to different gut environmental antigens. As a result, disorders such as inflammatory bowel disease (e.g. IBD) and allergic gastroenteropathy can be evoked in the gastrointestinal tissues. Recently, many studies have described possible molecular and cellular mechanisms for this dysfunction in the gastrointestinal tissues by using murine models with specific gene manipulation. In this review we summarize recent findings from our group concerning the CMIS-dependent and CMIS-independent IgA induction pathways and gastrointestinal diseases (IBD and intestinal allergic diseases). These observations may provide useful information for the development of new mucosal immune therapy.

Animals↗

PubMed2001

Paclitaxel in the multimodality treatment for inflammatory breast carcinoma.

BACKGROUND: Inflammatory breast carcinoma (IBC) is a rare but aggressive form of breast carcinoma. Anthracycline-based regimens represent the standard of treatment for IBC. Reports of significant clinical activity of paclitaxel in metastatic breast carcinoma led the authors to investigate the role of this drug in the management of IBC. METHODS: Forty-four patients with IBC were enrolled between February 1994 and January 1998. The treatment plan consisted of induction chemotherapy (IC), mastectomy, adjuvant chemotherapy, and radiotherapy. Forty-two patients received IC with four cycles of fluorouracil, doxorubicin, and cyclophosphamide. If the clinical response was less than partial, patients were "crossed over" to paclitaxel before mastectomy. All patients received adjuvant paclitaxel. Patients unresectable after paclitaxel were offered high-dose chemotherapy with autologous peripheral blood progenitor cell support. RESULTS: Thirty-four patients (81%) achieved an objective clinical remission; 3 patients (7%) achieved a clinical complete remission, 31 (74%) a partial remission. Six patients (14%) achieved pathologic complete remission. Sixteen patients were treated with paclitaxel, 7 of them (44%) were able to undergo mastectomy. Median time to progression (TTP) was 22 months. Median overall survival (OS) was 46 months. Concordance between clinical and pathologic response was documented in only 8 patients (24%). No differences in TTP and OS compared with a historical group of 178 IBC patients treated with anthracycline-based regimens. CONCLUSIONS: Paclitaxel improves tumor resectability in anthracycline-refractory IBC. The impact of paclitaxel on the prognosis of IBC needs to be better evaluated in future trials using more dose-intensive schedules of administration. New imaging modalities may contribute to improve assessment of response to IC.

Adenocarcinoma↗

PubMed2025

Molecular Landscape, Genomic Shift, and Prediction in the Neoadjuvant Setting of Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer.

The amplification or overexpression of human epidermal growth factor receptor 2 (HER2) defines a breast cancer subtype, which benefits from neoadjuvant HER2-targeted therapy. However, at least 40% of patients respond poorly or do not respond to treatment. We analyzed the main genomic alterations of 64 HER2+ patients by next-generation sequencing to identify new predictors of response and correlate them with clinicopathological parameters. We also compared the genomic alterations between primary and residual tumors after neoadjuvant treatment. The TP53 gene was the most frequently mutated gene, and in combination with ERBB2 overexpression, the 2 were predictive of residual cancer burden (P = .001). Furthermore, the combination of their immunohistochemical counterpart (p53 mutant and score 3+ for HER2) can predict complete pathological response and the grade of response (P = .038 and P = .031, respectively). Therefore, p53 could be included in the initial panel of breast cancer biomarkers to help therapeutic decision-making in HER2+ cases.

Humans↗

PubMed2003

Post-natal endothelial progenitor cells for neovascularization in tissue regeneration.

The isolation of endothelial progenitor cells (EPCs) derived from bone marrow (BM) was an outstanding event in the recognition of 'de novo vessel formation' in adults occurring as physiological and pathological responses. The finding that EPCs home to sites of neovascularization and differentiate into endothelial cells (ECs) in situ is consistent with 'vasculogenesis', a critical paradigm well described for embryonic neovascularization, but proposed recently in adults in which a reservoir of stem or progenitor cells contributes to vascular organogenesis. EPCs have also been considered as therapeutic agents to supply the potent origin of neovascularization under pathological conditions. This review provides an update of EPC biology as well as highlighting their potential use for therapeutic regeneration.

Adult↗

PubMedDate not supplied

Breast-conserving therapy after neoadjuvant chemotherapy: long-term results.

The purpose of this study was to determine patterns of ipsilateral breast tumor recurrence (IBTR) and local-regional recurrence (LRR) after neoadjuvant chemotherapy and breast-conserving therapy (BCT). A total of 153 breast cancer patients were treated with neoadjuvant chemotherapy followed by conservative surgery and radiation therapy between 1980 and 2002. The clinical stage (American Joint Committee on Cancer [AJCC] 1997) at diagnosis was IIA in 22%, IIB in 28%, IIIA in 39%, and IIIB in 11%. The prechemotherapy T size distribution was less than 2 cm in 5 patients, 2.1-5 cm in 100 patients, and greater than 5.1 cm in 48 patients. Sixty-seven patients (44%) underwent cyclophosphamide, methotrexate, and 5-fluorouracil (CMF)-based chemotherapy and 86 (56%) underwent Adriamycin-based chemotherapy. Thirty-seven patients (24%) had a complete pathologic response in the breast. All procedures were performed by a single surgeon (G.F.S.). The surgery was local excision alone in 19 patients, local excision and axillary lymph node dissection (ALND) in 130 patients, and ALND alone in 4 patients. Eleven patients had positive surgical margins. Rates of LRR-, IBTR-, and distant metastasis (DM)-free survival were calculated by the Kaplan-Meier method. Patient and pathologic variables were then analyzed in an attempt to identify predictors of clinical outcome. With a median follow-up period of 55 months (range 6-200 months), eight patients developed LRR, five of which were classified as IBTR. Five- and 10-year actuarial rates of LRR-free, IBTR-free, and DM-free survival were 93% and 88%, 96% and 91%, and 70% and 58%, respectively. Pretreatment and pathologic parameters that positively correlated with IBTR were advanced stage (p = 0.03) and margin positivity (p = 0.04). No other clinical factors were predictive of higher recurrence. BCT results in a low rate of IBTR and LRR in appropriately selected patients. Advanced stage at presentation is associated with increased risk of IBTR, although overall recurrence is low. In selected cases, BCT is safe and an effective alternative to mastectomy.

Adult↗