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At least 451 records · Page 25Linked to original sources
PubMed1998

Effect of dopamine and atrial pacing on stunned myocardium.

OBJECTIVE: Post-ischaemic stunned myocardium shows an impaired function at restored coronary blood flow, but performance can be normalized by positive inotropic stimulation. The power of stunned myocardium, however, is not augmented with increasing heart rate by atrial pacing, which is in contrast to intact areas. This pathological response is mitigated by inhibiting the degradation of cyclic AMP. The present experiments studied the effect of stimulating cyclic AMP formation by dopamine on the response of stunned myocardium to atrial pacing. METHODS: In anaesthetized (piritramide) open chest pigs, heart rate, left ventricular and aortic pressure, left descending (LAD) and circumflex (LCX) coronary artery and aortic blood flow, myocardial systolic shortening in the LAD and LCX area were monitored, and myocardial power was calculated. The LAD region was subjected to ischaemia and reperfused for 2 h. Subsequently, heart rate was raised by right atrial pacing before and during intravenous infusion of dopamine (10 microg/kg per min). The ischaemic/reperfused area was sliced post mortem and stained by triphenyl tetrazolium chloride to exclude myocardial infarction. Data from 11 experiments are presented. RESULTS: After 2 h LAD reperfusion, LAD blood flow and power were 100% and 36% of pre-ischaemic control, respectively, indicating myocardial stunning. The power of the intact area was not changed significantly (111% of control). Increasing heart rate by +36 and +70 from 94 beats/min increased the power of the intact area to 161% and 183% of control; the power of the stunned myocardium decreased to 34% and 19% of pre-stunning control. Dopamine increased the power of the stunned region to 143% of the pre-stunning level and the power of the intact area to 206% of control. Increasing heart rate by +34 and +70 from 113 beats/min during dopamine, increased the power of the intact myocardium to 288% and 344% of control and the power of the stunned region to 177% and 174% of the pre-stunning level. CONCLUSIONS: The data confirm the pathological response of stunned myocardium to atrial pacing and the recruitment of a functional reserve by catecholamines. The adverse effect of pacing on the function of stunned myocardium is abolished by positive inotropic stimulation. Possibly, the cyclic AMP system is involved in the normal response to pacing and this pathway is disturbed in stunned myocardium; other defects are not excluded or supported, however. Physiologically increased heart rate by an increased activity of the sympathetic nervous system, is probably not accompanied by a reduced power of stunned myocardium, due to the associated positive inotropic stimulation.

Animals↗
PubMed2005

Prognostic significance of a combined clinicopathologic score for response to primary systemic therapy in locally advanced breast cancer.

The response to chemotherapy is one of the best indicators of prognosis in locally advanced breast cancer (LABC). The pathologic response (pR) of 108 LABC patients was analysed and compared with their clinical response (cR). Our aim was to define a new combined clinicopathologic response score (cpR) and to explore its correlation with survival data. The 108 stage IIB to IIIB breast carcinomas were first treated with high-dose anthracycline-based chemotherapy. Standard criteria were used to assess cR. Pathologic analysis of surgical specimens allowed the definition of 5 types of pR. Three groups of combined clinicopathologic response were defined. Twenty-two patients (20%) had complete or almost complete pR. Most patients (88, 81%) had partial cR. This large group of partial cR was very heterogeneous, ranging from pR1 to pR5 and from cpR1 to cpR3. In univariate analysis, pR and cpR both strongly correlated with EFS. cR, pR and cpR all correlated with OS. Subgroups of incomplete pathologic responses were not prognostically different. In multivariate analysis, only cpR correlated strongly with both EFS and OS (p<0.002), identifying good (20%), intermediate (61%) and poor (19%) prognosis patients. In conclusion, in 108 stage IIB to IIIB breast cancer patients initially treated by high-dose chemotherapy, combined grading of clinical and pathologic responses in a single score allowed accurate prediction of outcome.

Adolescent↗
PubMed2007

Kinetics of serum HER-2/neu changes in patients with HER-2-positive primary breast cancer after initiation of primary chemotherapy.

BACKGROUND: The purpose of the study was to determine the utility of quantitation of the extracellular domain (ECD) of the HER-2/neu receptor in the serum for predicting response to treatment in patients with primary breast cancer receiving neoadjuvant therapy. METHODS: HER-2/neu ECD was measured in sera obtained from 39 patients with HER-2-amplified stage II-III primary breast cancer undergoing neoadjuvant chemotherapy. Patients were randomly assigned to either 4 cycles of paclitaxel followed by 4 cycles of fluorouracil, epirubicin, and cyclophosphamide (FEC) (n = 10) or to the same chemotherapy with simultaneous weekly trastuzumab for 24 weeks (n = 29). Changes in HER-2 ECD were monitored with the Bayer HER-2/neu assay over 6 months and correlated with pathological response to treatment. RESULTS: Before initiation of chemotherapy, 28.2% of patients had elevated concentration of the HER-2 ECD (>15 ng/mL). The median baseline serum HER-2 ECD concentration was 13.6 ng/mL (mean +/- SD, 20.3 +/- 35.5 ng/mL). A decrease in the median HER-2 ECD levels from baseline to Week 3 and from baseline to Week 6 of chemotherapy was seen regardless of treatment regimen. No significant difference in baseline HER-2 ECD levels was observed between the groups who achieved pathological complete response (pCR) and the group with residual disease (P = .41). However, a 9% drop from Week 3 to Week 6 after initial chemotherapy was predictive of pCR (P = .04). CONCLUSION: A decrease in serum HER-2 ECD levels early during treatment was associated with pathological response in patients receiving primary chemotherapy, particularly trastuzumab-based regimens. Serum HER-2 ECD levels may serve to monitor neoadjuvant therapy in HER-2-positive primary breast cancer.

Adult↗
PubMed1984

Hyperekplexia: a syndrome of pathological startle responses.

We describe a family and three sporadic cases of startle disease, or hyperekplexia. Sudden unexpected noises caused the patients to fall rigidly, often injuring themselves but retaining consciousness. This unusual entity differs from startle epilepsy and cataplexy. Clonazepam proved ineffective in three patients. Valproic acid, 5-hydroxytryptophan, or piracetam markedly reduced the abnormal startle in three patients.

5-Hydroxytryptophan↗
PubMed2000

Estimating normal and pathological dynamic responses in cerebral blood flow velocity to step changes in end-tidal pCO2.

The regulation of cerebral blood flow (CBF) following changes in arterial blood pressure (ABP) and end-tidal pCO2 (EtCO2) are of clinical interest in assessing cerebrovascular reserve capacity. Linear finite-impulse-response modelling is applied to ABP, EtCO2 and CBF velocity (CBFV, from transcranial Doppler measurements), which allows the CBFV response to ideal step changes in EtCO2 to be estimated from clinical data showing more sluggish, and additional random variations. The confounding effects of ABP changes provoked by hypercapnia on the CBFV are also corrected for. Data from 56 patients suffering from stenosis of the carotid arteries (with normal or diminished cerebrovascular reactivity to EtCO2 changes--CVRCO2) were analysed. The results show the expected significant differences (p < 0.05) between EtCO2 steps up and down, the significant contribution from ABP variation, and also differences in the dynamic responses of patients with reduced CVRCO2 (p < 0.01 after 10 s). For the latter the CBFV response appears exhausted after about 15 s, whereas for normals CBFV continues to increase. While dispersion of individual step responses remains large, the method gives encouraging results for the non-invasive study of compromised haemodynamics in different patient groups.

Aged↗
PubMed2000

Conformational changes in albumin molecule: a new response to pathological process.

A new fluorescent test developed at the Institute of Physicochemical Medicine (Ministry of Health of the Russian Federation) allows to determine not only blood concentration of albumin, but also to evaluate the state of its molecule. The test is feasible and enables express-analysis of the plasma and serum without fractionation and other preliminary procedures. This test reveals abnormalities in albumin molecule caused by toxic metabolites or conformational changes. Many diseases are accompanied by conformational changes in albumin, while its concentration often remains unchanged. Changes in albumin conformation can serve a diagnostic and prognostic criterion in some pathologies.

Blood↗
PubMed1997

[The quadri-cusp aortic valve: a congenital defect, responsible for pathologic changes?].

We report on a 61-year-old patient with considerable insufficiency of a quadricuspid aortic valve and coronary three vessel disease. The congenital quadricuspid aortic valve has become symptomatic due to the development of (post-endocarditic) insufficiency only in the advanced stage of life. It was treated by replacement of the aortic valve and bypass myocardial revascularization. The physiopathology of quadricuspid aortic valve will be discussed.

Aortic Valve↗
PubMed2001

P27kip1 expression is associated with tumor response to preoperative chemoradiotherapy in rectal cancer.

BACKGROUND: Our aim was to ascertain whether or not the response to preoperative chemoradiotherapy for rectal cancer is associated with p27kip1 and p53 protein expression. METHODS: Thirty-eight patients (27 male, 11 female) with a mean age of 59 years (age range 33-87) and stage II-III rectal cancer received preoperative chemoradiotherapy (45-50.4 Gy; 5-FU 350 mg/m2/day and leucovorin 10 mg/m2/day). Thirty-one underwent low anterior resection; seven underwent abdominoperineal excision. Endoscopic tumor biopsies, performed before adjuvant therapy, were evaluated for: histologic type, tumor differentiation, mitotic index, and p27kip1 and p53 protein expression which were immunohistochemically determined. p53 expression was graded as: a) absent or present in < or =10% of tumor cells; b) present in 11-25%; c) present in 26-75%; and d) present in >75% of tumor cells. p27kip1 expression was assessed using both light microscopy (percent of stained cells x10 HPF) and cytometry with an image analysis workstation. Tumor response, ascertained with histology, was classified using a scale from 0 (no response) to 6 (complete pathologic response). RESULTS: The mitotic index for the endoscopic biopsies was low in 14 cases, moderate in 17 cases, and high in 7 cases. p53 protein expression was found in 21 (a), 3 (b), 3 (c), and 11 (d) cases. The mean percentage of cells expressing the p27kip1 protein was 34 (range 0-77.14%). A close correlation was found between cytometric and light microscopy findings for p27kip1 (r2 = 0.92, P = .0001). Tumor differentiation was good in 5 cases, poor in 2 cases, and moderate in the remaining 31 cases. While the response to adjuvant therapy was good/complete in 25 (65.78%) cases, it was absent/poor in 13 (34.21%) cases. Univariate analysis associated type of adjuvant therapy (chemoradiotherapy, P = .0428) and p27kip1 protein lower expression (P = .0148) with a poor response to adjuvant treatment. Stepwise linear regression found overexpression of p53 and p27kip1 and young age to be independent variables that were linked to a good response to adjuvant therapy. CONCLUSIONS: Lack of p27kip1 and p53 protein expression in rectal cancer is associated with a poor response to preoperative adjuvant therapy.

Adult↗
PubMed2001

Surgical resection is necessary to maximize tumor control in function-preserving, aggressive chemoradiation protocols for advanced squamous cancer of the head and neck (stage III and IV).

BACKGROUND: The role of surgery in aggressive chemoradiation protocols for advanced head and neck cancer has been questioned because of the quoted high clinical response rates in many series. METHODS: The role of surgical resection was examined in an aggressive neoadjuvant protocol of weekly paclitaxel, carboplatin, and radiation for stage III and IV with completion of radiation to 72 Gy if biopsy at the primary site was negative after administration of 45 Gy. Of 43 patients enrolled, 38 completed the protocol. The clinical response was 100% (including 18 complete and 20 partial responses). RESULTS: The complete pathologic response (negative primary site biopsy at 45 Gy) was 25 of 38 (66%). Of patients who presented with N1 to N3 nodes, neck dissection revealed residual nodal metastases in 22%. Surgical resection of the primary site was required in 13 patients, including 5 with larynx cancer and 2 with base of tongue cancers. Four patients had resection with reconstruction for advanced mandible floor of mouth cancer, and one had resection of nasal-maxillary cancer. Functional resection was performed in 9 of 12 patients. The median progression free and overall survival was 64% and 68%, respectively, at median follow-up of 50 months. Nine patients developed recurrence (three local and six distant). There were no failures in the neck. Salvage surgery was performed in one patient with local and one with distant disease. CONCLUSIONS: Surgical resection is an essential component of aggressive chemoradiation protocols to ensure tumor control at the primary site and in the neck.

Adult↗
PubMed1994

Ocular blood flow responses to pathology of the carotid and cerebral circulations.

The eye and the brain are hemodynamically linked by the carotid artery and the autonomic nervous system. A number of case reports are presented that show hemodynamic increase or decrease in the eye secondary to independently proven pathological changes in the carotid, the brain, sympathetic nervous system, and the heart.

Adolescent↗
PubMed1990

Chemotherapy versus radiotherapy in the management of ovarian cancer patients with pathological complete response or minimal residual disease at second look.

The management of patients with epithelial ovarian cancer with no or minimal residual disease at second-look laparotomy after aggressive surgery and platinum-based chemotherapy has not been definitively established. We report the results of a randomized study comparing three more courses of the same chemotherapy inducing the response (21 patients) with whole-abdomen radiotherapy (20 patients). Thirty-eight patients responded to first-line chemotherapy and three had stabilization of disease. In eight patients tumor debulking was performed at second-look laparotomy. No severe toxic effects were noted in both arms. Bowel obstruction occurred in one patient treated with radiotherapy. At a median follow-up of 22 months, 11 of 20 patients in the radiotherapy arm and 6 of 21 in the chemotherapy arm progressed and 9 and 3 patients died, respectively. Although the number of randomized patients is small we stopped the trial because of the survival and progression-free survival advantage of chemotherapy-treated patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Neoadjuvant taxanes in the treatment of non-metastatic breast cancer: a systematic review.

In recent years the role of neoadjuvant (primary, preoperative) chemotherapy has undergone rapid progress. Initially, neoadjuvant chemotherapy use was limited to those patients with inoperable locally advanced breast cancer in an attempt to try to down-size the tumour to make effective surgery possible. The advent of more effective chemotherapy regimens has led to an increased use of neoadjuvant therapy to shrink potentially operable tumours to allow for breast conservation when a mastectomy would have been required previously. While neoadjuvant treatment for operable tumours has indeed allowed increased rates of breast conserving surgery, it has not yet demonstrated any survival benefit over standard postoperative anthracycline-based chemotherapy. Echoing the evolution of taxane based chemotherapy from the metastatic setting through to the adjuvant situation, there has been increased interest in the role of taxanes in neoadjuvant regimens. The use of taxane-based therapies in this setting has so far shown improvements over more standard regimens in terms of clinical response rates, breast conservation, pathologic response rates, disease free survival, and overall survival. The aim of this review is to systematically summarize and interpret the results of published randomized controlled trials of neoadjuvant taxane chemotherapy for women with non-metastatic breast cancer.

Breast Neoplasms↗