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PubMed2006

Randomized Phase II Trial of weekly paclitaxel alone versus trastuzumab plus weekly paclitaxel as first-line therapy of patients with Her-2 positive advanced breast cancer.

BACKGROUND: A randomized Phase II study evaluated the activity of weekly paclitaxel versus its combination with trastuzumab for treatment of patients with advanced breast cancer overexpressing HER-2. PATIENTS AND METHODS: Among 124 patients randomized, 123 are assessable for toxicity and 118 for response. Patients received weekly paclitaxel single agent (80 mg/m2) or combined with trastuzumab (4 mg/kg loading dose, then weekly 2 mg/kg). HER-2 overexpression was determined by immunohistochemistry (IHC). Patients with 2+/3+ IHC scores were eligible. IHC was compared with HER-2 serum extracellular domain (ECD). RESULTS: Patient characteristics were similar in the two arms. Both treatments were feasible and well tolerated with no grade 4 hematologic toxicity. No patient developed cardiac toxicity. The combined treatment was statistically significant superior for overall response rate (ORR) (75% vs. 56.9%; P = 0.037), particularly in the subset of IHC 3+ patients (84.5% vs. 47.5%; P = 0.00050). A statistically significant better median time to progression was seen in the subgroup with IHC 3+ (369 vs. 272 days; P = 0.030) and visceral disease (301 vs. 183 days; P = 0.0080) treated with combination. Multivariable analysis of predictive factors showed that only IHC score retained statistically significant value for ORR (P = 0.0035). CONCLUSION: Weekly paclitaxel plus trastuzumab is highly active and safe and it is superior to paclitaxel alone in patients with IHC score of 3+.

Adult↗

PubMed1981

Long-term evaluation of persistent supraventricular tachycardia in children: clinical and electrocardiographic features.

Although the long-term prognosis of children with persistent supraventricular tachycardia (SVT) has been generally considered benign, recent reports have suggested that some of these patients may develop cardiac dysfunction secondary to their persistent SVT. The clinical course of six children demonstrating ECG criteria of persistent SVT are presented herein with follow-up data for 5 to 20 years. Persistent SVT was present in each patient from 2 to 19 years. Two patients had transient congestive heart failure early in their course of persistent SVT, and two others demonstrated continued roentgenographic evidence of mild cardiomegaly without associated symptomatology. Conventional antiarrhythmics administered briefly in five patients and chronically in two were without effect on their arrhythmias. Persistent SVT remains in three patients and a fourth continues to exhibit intermittent episodes of SVT; however, all six patients are currently asymptomatic with two in stable normal sinus rhythm. This investigation indicates that the persistent form of SVT (lasting more than 1 year) is uncommon among children with paroxysmal SVT, and long-term observation of the consequences of persistent SVT supports the view that this rhythm disturbance is generally well tolerated in such patients.

Adolescent↗

PubMed1988

Prevalence and significance of gallium-67 uptake in the heart after open-heart surgery.

Radioactive gallium-67 (Ga-67) has been shown to accumulate within areas of pericardial inflammation. The present study estimated prospectively the prevalence and clinical significance of Ga-67 uptake in the heart in 62 patients 10 to 16 days after open-heart surgery. Of 62 patients studied, markedly diffuse Ga-67 uptake was detected in 21 (34%) and focal or mild diffuse uptake in 23 (37%). Results were negative in 18 (29%). Nine patients with a negative scan result (50%) had received corticosteroid therapy before imaging, whereas only 2 patients with a positive scan result (5%) were receiving steroids. The erythrocyte sedimentation rate and C-reactive protein level were both higher in patients with Ga-67 uptake compared with those with a negative scan result (p less than 0.01 in both). No other clinical, echocardiographic or electrocardiographic indicators of postpericardiotomy syndrome were related to Ga-67 uptake. No patient developed cardiac tamponade or constrictive pericarditis during the 12-week follow-up and the Ga-67 scan results did not predict the occlusion of coronary artery bypass grafts. Thus, pericardial inflammation manifested as Ga-67 uptake is a common finding after open-heart surgery and appears to be a benign condition.

Blood Sedimentation↗

PubMed1992

Safety and clinical use of exercise testing one to three days after percutaneous transluminal coronary angioplasty.

To evaluate both the safety and clinical use of predischarge symptom-limited exercise testing after successful uncomplicated percutaneous transluminal coronary angioplasty (PTCA), 100 patients were randomized to undergo exercise testing (n = 50) or no exercise testing (n = 50). There were no differences in clinical or angiographic characteristics between the groups. Exercise testing was performed 38 +/- 14 hours after PTCA. Patients who exercised achieved 71 +/- 12% of predicted maximal heart rate, with 38% reaching greater than or equal to stage III of the Bruce protocol. No patient in either group developed cardiac complications during 48-hour follow-up. Of the 11 patients with a positive test result, 92% had angiographically incomplete revascularization. Attending physicians (n = 16) were questioned both before and after exercise testing about when, after discharge, they would allow their patient to perform each of 11 specific activities of daily living. Questionnaires were administered to physicians at similar time frames for patients in the no-exercise group. Comparison of the responses between initial and repeat questionnaires showed that patients in the exercise group (with a test result negative for ischemia) were allowed to perform 7 of 11 activities, including return to work, earlier (p less than 0.05) than the no-exercise patients. These data indicate that in this well-defined group of patients, symptom-limited exercise testing early after PTCA appears to be safe, and alters physician management in allowing patients with a negative test result to return to various activities at an earlier date. Such testing may be useful in counseling patients after PTCA.

Activities of Daily Living↗

PubMed1994

Tissue-type plasminogen activator and plasminogen activator inhibitor activities as predictors of adverse events in unstable angina.

Among patients with recent-onset unstable angina and evidence of ischemia or coronary artery disease, the incidence of subsequent cardiovascular events is high. The aim of this study was to investigate, in this high-risk population, whether unstable angina was associated with abnormalities of tissue-type plasminogen activator (t-PA) or plasminogen activator inhibitor (PAI) activities and whether, in a prospective study, any of these parameters would identify patients with an adverse cardiovascular prognosis. A group of 22 high-risk patients with unstable angina (64% event rate at 3 months) was studied prospectively for 12 weeks, and the fibrinolytic parameters measured at presentation were related to subsequent cardiovascular progress. A group of 20 age- and sex-matched healthy subjects acted as control subjects. Patients who had subsequent cardiovascular events (acute myocardial infarction or severe recurrent angina +/- intervention) had significantly elevated PAI activity at presentation compared with both those who remained event-free (p < 0.05) or with control subjects (p < 0.02). In addition, basal activation of fibrinolysis was demonstrated in unstable angina at presentation; this persisted at 9 weeks in patients with a favorable outcome (p < 0.02 vs control subjects), whereas it was no longer evident in those who developed cardiac events. These findings suggest that measurements of t-PA/PAI activity may reflect the underlying pathophysiologic state and relate to subsequent cardiovascular events in unstable angina.

Aged↗

PubMed1984

Myocardial contusion associated with fracture of the sternum: important features of the seat belt syndrome.

Recent legislation has led to increasing numbers of car occupants wearing seat belts and presumably the number of injuries attributable to seat belts will also increase. The commonest such injury is a fracture of the sternum, and blunt myocardial damage is a logical sequel although often unsuspected and therefore unsought. Confirmation is difficult and ECG changes are usually absent or not specific. In three consecutive patients admitted with a fractured sternum we found raised blood levels of CK-MB (creatine kinase-myocardial band) and believe these indicate myocardial contusion. We therefore feel that an isolated fracture of the sternum should be considered a more serious injury than is initially apparent, as these patients are at risk of developing cardiac complications.

Accidents, Traffic↗

PubMed1990

Congenital nemaline myopathy with dilated cardiomyopathy: an autopsy study.

A 3-year-old boy with congenital nemaline myopathy had generalized muscle weakness and hypotonia since birth. He developed cardiac symptoms at 2 years of age and died from congestive heart failure. At autopsy, the heart was markedly dilated, involving both ventricles. Rod bodies were recognized not only in skeletal muscles but in cardiac muscles on light and electron microscopy. Desmin and alpha-actinin, which constitute Z-line protein, were shown to localize in the rod structures in both skeletal and myocardial cells by immunohistochemistry. Seven cases of nemaline myopathy with cardiomyopathy have been reported in the literature. All of these patients were over 20 years of age, and the condition appeared mostly in the adult onset and the asymptomatic forms. This is the first infantile case of congenital nemaline myopathy which showed dilated cardiomyopathy with a fatal outcome.

Cardiomyopathy, Dilated↗

PubMed1991

Effects of Ph CL 28A on eicosanoid synthesis in rat isolated hearts.

The effects of Ph CL 28A, a derivative of sulphasalazine, on cardiac function and eicosanoid synthesis were examined in rat isolated hearts perfused via the coronary circulation. Two stimuli for eicosanoid synthesis were used: exogenous arachidonic acid (AA) or the calcium ionophore, A23187. Following exogenous AA, coronary perfusion pressure (CPP) and cardiac developed tension (CDT) increased transiently; only the CPP response was diminished by Ph CL 28A. The output of TxB2 but not that of 6-oxo-PGF1 alpha from the heart after exogenous AA was inhibited by Ph CL 28A. The ionophore, A23187, increased CPP with minor changes in CDT; Ph CL 28A did not affect either response. The ionophore released 6-oxo-PGF1 alpha, TxB2 and LTC4 from the heart but only LTC4 output was decreased by Ph CL 28A. We conclude that, although Ph CL 28A did not increase output of 6-oxo-PGF1 alpha from rat heart with either of the stimuli used, its inhibition of the output of vasoconstrictor eicosanoids could be of benefit to the coronary circulation.

Animals↗

PubMed1988

Malignant pericardial effusion in endometrial adenocarcinoma.

A case of endometrial adenocarcinoma in a 62-year-old woman with malignant pericardial effusion is presented. The patient underwent a total abdominal hysterectomy, bilateral salpingo-oophorectomy, pelvic node dissection, and paraaortic node biopsy. Postoperatively, she was placed on a combination chemotherapy regimen of cisplatin, doxorubicin, and cyclophosphamide. The patient developed cardiac tamponade during the course of chemotherapy. Although we first suspected cardiotoxic effect of doxorubicin, cytologic examination revealed adenocarcinoma cells in the pericardial fluid. A review of the literature revealed no other cases of cardiac metastasis from endometrial carcinoma diagnosed during life.

Adenocarcinoma, Papillary↗

PubMed1986

The evolution of experimental Trypanosoma cruzi cardiomyopathy in rabbits: further parasitological, morphological and functional studies.

Young rabbits (1-2 months of age) inoculated with trypomastigote forms of the Colombia strain of Trypanosoma cruzi have been shown to develop cardiac pathological changes (together with parasitological and immunological alterations) which are very similar to those observed in the acute and chronic phases of Chagas' disease in man. The cardiac alterations in the acute phase are characterized grossly by slight cardiomegaly with dilatation of the right-sided chambers. Microscopically they are characterized by mild focal myocarditis. The chronic phase is characterized by moderate to marked cardiomegaly with hypertrophy and dilatation of both ventricular chambers. There is thinning of the apical region (apical aneurysm), particularly of the left ventricle. Focal myocarditis is seen microscopically with areas of myocytolytic necrosis, atrophic and hypertrophic myofibers, an inflammatory response predominantly composed of mononuclear cells and interstitial fibrosis. Cineventriculography in the left ventricle of rabbits during the chronic phase disclosed regional myocardial dysfunction, with typical apical systolic bulging. The pathogenesis of Chagasic cardiomyopathy is briefly discussed in the light of these findings. Our investigation has further shown that this animal model is particularly suitable for studies on on the mechanisms, pathology and treatment of Chagas' heart disease.

Actin Cytoskeleton↗

PubMed1990

Atrial strain is the main determinant of release of atrial natriuretic peptide.

We studied the response of atrial natriuretic peptide to the hemodynamic and renin-aldosterone variations occurring in four patients who developed cardiac tamponade, either occurring in idiopathic fashion in one or secondary to metastatic involvement of the pericardium in three. Right atrial pressure, heart rate and arterial blood pressure were monitored and serial blood samples were taken before and over three hours after pericardiocentesis. During cardiac tamponade, normal levels of atrial natriuretic peptide (mean +/- SEM: 54 +/- 7.4 pg/ml) were observed in the plasma despite increased right atrial pressure (23 +/- 3.8 cm H2O) and heart rates (98 +/- 4.4). Removal of pericardial fluid (540 to 1160 ml) was associated at first with a 200% increase in plasma concentrations of atrial natriuretic peptide (108 +/- 8.8 pg/ml; P less than 0.001), then with a gradual decline toward normal levels, simultaneous with the normalization of right atrial pressure and heart rate. Activity of renin and concentrations of aldosterone in the plasma were increased during tamponade and returned gradually to normal after pericardiocentesis (3.8 +/- 0.9 to 1.2 +/- 0.3 ng/ml/h and 20 +/- 4.2 to 9 +/- 3.2 ng/dl, respectively; P less than 0.01). These data confirm that atrial strain, not intracavitary pressure in itself nor heart rate, is the main determinant of the acute release of atrial natriuretic peptide, which is associated with a suppressing effect on the renin-aldosterone system. In addition, our data indicate that secretion of atrial natriuretic peptide during cardiac tamponade is not stimulated by secondary hyperaldosteronism.

Adult↗

PubMed1979

pH homeostasis during cardiopulmonary resuscitation in critically ill patients.

We investigated the effect of repeated administration of sodium bicarbonate on acid-base balance and serum chemistry in a group of patients who developed cardiac arrest. A mixed acidosis persisted throughout the duration of resuscitation in the majority of patients in spite of the large ventilatory volume and multiple doses of bicarbonate they received. However, the repeated administration of bicarbonate prevented a severe fall in serum pH. Our study demonstrated the beneficial role of bicarbonate in the treatment of metabolic acidosis associated with cardiac arrest of prolonged duration. Analysis of our data strongly indicated that the primary factors which determine the serum pH during cardiopulmonary resuscitation are the duration of circulatory arrest, adequacy of ventilation and circulation, pH immediately before arrest, and quantity of bicarbonate administered and its volume of distribution in the various fluid and tissue compartments.

Acid-Base Equilibrium↗

PubMed1991

Interference with neural crest migration by maternal hyperthermia as a cause of embryonic death due to heart failure.

Maternal hyperthermia has been demonstrated to be a teratogen in every animal species studied, and a minimum core temperature rise of 2.5 degrees C can produce a number of developmental defects. However, numerous embryos fail to survive to term. In the guinea-pig, heating the embryos prior to neural tube closure induces significant neural tube defects, but all embryos die within 20 days of heating. A number have aberrant cardiac development and many show spectacular pericardial effusions and congestion in the peripheral circulation. We suggest that maternal hyperthermia has interfered with neural crest migration which is a major component in the induction of these changes.

Animals↗

PubMed1989

Ventricular fibrillation during rectal examination.

The case of a 74-year-old man who developed ventricular fibrillation during a digital rectal examination is presented. The patient was subsequently resuscitated and developed cardiac enzyme elevation without ECG changes, indicating a nontransmural myocardial infarction. Although controlled studies have not shown any ill effects of rectal examination in patients with acute myocardial infarction, there have been multiple case reports of bradycardia, ectopy, and ventricular arrhythmias resulting from rectal examination. The postulated etiology of the ectopy is twofold; increased vagal tone from rectal parasympathetic innervation or increased sympathetic tone from anxiety-stimulated catecholamine release. Rectal examination is definitely indicated in a subset of patients including those with gastrointestinal or genitourinary complaints, unexplained hypotension or anemia, trauma, and neurological deficits, and those who will receive anticoagulation or thrombolytic therapy. In the remaining patients, the decision must be made on a case-by-case basis. Awareness of and precautions for possible ill effects of the examination are prudent.

Aged↗

PubMed1987

The incidence and significance of early pericardial effusion after open heart surgery.

The presence and severity of postoperative pericardial effusions were studied echocardiographically in 114 consecutive patients (70 males, 44 females; mean age 56 +/- 10 years). An effusion was present in 35 patients at 3-5 days. An effusion was less common when a drainage tube was inserted for 24-36 h in the posterior as well as the anterior mediastinum than when only an anterior drain was used. Patients with effusions differed from those without in having more supraventricular arrhythmias, more wound infections, smaller total blood drainage and longer postoperative hospital stay. Three patients with posterior pericardial effusions developed cardiac tamponade 5-18 days postoperatively. The data show that pericardial effusions are associated with postoperative complications and suggest that effusion formation can be reduced by using posterior as well as anterior chest drains.

Cardiac Surgical Procedures↗

PubMed1996

Cardiotrophin-1: a multifunctional cytokine that signals via LIF receptor-gp 130 dependent pathways.

In a search for novel factors that induce cardiac myocyte hypertrophy, cardiotrophin-1 (CT-1) was identified by coupling expression cloning with an embryonic stem cell-based model of cardiogenesis. CT-1 is a new member of the IL-6 family of cytokines that induce their biological effects through the shared signaling subunit, gp 130. The expression pattern of CT-1 and its range of activities in the hematopoietic, neuronal, and developmental assays suggest that CT-1 may play an important role in other organ systems, in addition to its actions in cardiac development and hypertrophy.

Amino Acid Sequence↗

PubMed2005

Profound hypotension and associated electrocardiographic changes during prolonged cord occlusion in the near term fetal sheep.

OBJECTIVE: To determine whether the onset of fetal hypotension during profound asphyxia is reflected by alterations in the ratio between the T height, measured from the level of the PQ interval, and the QRS amplitude (T/QRS ratio) and ST waveform. STUDY DESIGN: Chronically instrumented near-term fetal sheep received complete occlusion of the umbilical cord for either 8 (n=6) or 15-min (n=9). RESULTS: Cord occlusion led to sustained bradycardia and severe acidosis. Mean arterial blood pressure initially rose and then fell to a nadir of 32.6 +/- 2.6 mm Hg in the 8-min group and 9.3 +/- 1.0 mm Hg in the 15-min group (P < .001). The T/QRS ratio rose initially in parallel with mean arterial blood pressure and then reduced as mean arterial blood pressure fell but remained significantly above baseline. Biphasic ST waveforms during occlusion occurred in only 2 fetuses, but biphasic and negative waveforms occurred during reperfusion in the 15-min group, with a significant rise in troponin T levels (0.58 +/- 0.46 versus 0.02 +/- 0.01 ng/mL at 6 h, P < .01). CONCLUSION: Elevation of the T/QRS ratio does not identify fetal hypotension during severe hypoxia, but abnormal waveforms in the recovery phase may indicate developing cardiac injury.

Acidosis↗

PubMed2003

Calreticulin is an upstream regulator of calcineurin.

Ca(2+) is a signalling molecule involved in virtually every aspect of cell function. The endoplasmic reticulum (ER) is an important and dynamic organelle responsible for storage of the majority of intracellular Ca(2+). Within the ER lumen are proteins that function as Ca(2+) buffers and/or molecular chaperones including calreticulin, a multifunctional Ca(2+)-binding protein. Calreticulin-deficiency is lethal in utero due to impaired cardiac development. In the absence of calreticulin Ca(2+) storage capacity in the ER and InsP(3) receptor mediated Ca(2+) release from ER are compromised. Remarkably, over-expression of constitutively active calcineurin in the hearts of calreticulin deficient mice rescues them from embryonic lethality and produces live calreticulin deficient animals. These observations provide first evidence that calreticulin is a key upstream regulator of calcineurin in the Ca(2+)-signalling cascade and they highlight the importance of ER during early stages of cellular commitment and tissue development during organogenesis.

Animals↗