The role of multimodal adjuvant therapy for FIGO I-II carcinosarcoma of the uterus: a systematic review.

The uterine carcinosarcoma (UCS) is a rare entity with poor prognosis. Treatment of FIGO I-II UCS usually consists of surgery with or without adjuvant treatment. Due to the high metastatic potential, aggressive combined modality adjuvant treatment approaches, consisting of chemo- and radiotherapy, have been of interest. Our systematic review aims to compare survival, disease control and toxicity profiles in patients receiving adjuvant chemoradiation to other adjuvant strategies (e.g.observation, chemotherapy or radiotherapy). A total of ten studies were included for a combined cohort size of 6520 patients. Generally, the studies showed a trend towards improved disease control and survival in patients undergoing adjuvant multimodal treatment, although statistical significance was often not reached. Selection bias and non-randomized treatment allocation pose serious challenges to extrapolate these outcomes to clinical practice. We recommend additional prospective research on the role of adjuvant chemoradiation in FIGO I-II UCS.

Digitalis, digitalis antibodies, digitalis-like immunoreactive substances, and sodium homeostasis: a review.

Most pharmacokinetic and biologic attributes of digitalis are age dependent. They are determined in great measure by the chemical structure of the specific cardiac glycoside being used. These effects differ in the intact normal circulation and in heart failure because of the altered autonomic nervous system and hormonal control that exist in the latter. Digitalis is effective only in the presence of myocardial dysfunction, but in a clinical setting, cardiac performance may be difficult to gauge; improved tools are needed for this purpose. The dosages of digoxin recommended for infants and children have been steadily reduced in the past decade, and there is no good evidence that more favorable risk-to-benefit ratios are achieved when higher doses are used or when higher plasma concentrations are sought. Massive digitalis toxicity is a serious, often fatal, complication in young infants, especially when the drug is given parenterally; it may be difficult to diagnose early. The only reliable deterrent for this complication is the adoption of careful safety standards whenever the drug is employed. Experience with digoxin antibodies is still scarce in children, especially in infancy, but their use generally has been associated with a favorable outcome. Endogenous substances that interfere with the digoxin radioimmunoassay (DLIS) occasionally yield clinically relevant, erroneously high, plasma digoxin concentration readings in neonates. An interesting hypothesis currently being investigated is the physiologic and pathologic role of these compounds in sodium hemostasis; they may be part of a putative endogenous NaK-ATP-ase inhibitor involved in the pathogenesis of hypertension and renal diseases.

Digoxin intoxication in children and young adults.

Acute digoxin intoxication in children and young adults generally occurs in three distinct age groups: in infants, a pharmacokinetically disadvantaged age group, who are given an excessive dose parenterally and invariably die from the overdose; in toddlers, a pharmacokinetically favored age group, who ingest the drug accidentally and usually recover from the overdose, and in older children and young adults, who occupy an intermediate position with respect to pharmacokinetics and prognosis.

The pattern and frequency of congenital heart disease among blacks.

The types of cardiac malformations in 804 black patients of all ages in whom the diagnosis was confirmed by cardiac catheterization, surgery or autopsy are reported. The most frequent anomalies were ventricular septal defect, patent ductus arteriosus and tetralogy of Fallot. Among infants under 1 year of age, complete transposition of the great vessels accounted for the third-largest group of malformations. While pulmonary venous anomalies were extremely rare and hypoplastic left heart defects rare in the neonate, it is not considered that a racial predilection for differences in the frequency of various cardiac malformations exists. The frequency of coarctation of the aorta in the group as a whole was not lower than that found in studies among whites. Among black patients of all ages with heart disease (studied in a hospital environment) congenital cardiac malformations ranked as the second most common form of heart disease with a frequency of 26%. Among children aged 15 years or less, congenital heart disease ranked first with a frequency of 53%. It is suggested that a diagnosis of congenital heart disease is not made in the majority of blacks born with such malformations.

Maintenance digoxin dosage and steady-state plasma concentration in infants and children.

To define the relationship between digoxin dose and plasma concentration and the changes in body growth, 1181 plasma digoxin levels were measured in 644 infants and children receiving maintenance digoxin therapy. The drug was given intravenously to 166 patients and orally to 478. A significant linear correlation between dose and plasma concentration was observed (r 0.346 to 0.767 in the intravenous and 0.264 to 0.664 in the oral groups). Dosage differences explained 7% to 60% of the variability in digoxin plasma concentrations in various age and weight groups. The linear regression slope was greater in younger age groups, especially preterm infants weighing less than 1500 gm, and tended to decrease with age. The data (1) allow an approximate prediction of plasma concentrations of digoxin and their variability associated with changes in dosages in various pediatric age and weight groups, (2) permit an estimate of other pharmacokinetic determinants of digoxin plasma concentration and their changes with age, and (3) suggest that larger changes in digoxin doses in older children are necessary to achieve the same change in serum concentration that is achieved with smaller dose changes in the young infant. As a result, premature infants are more sensitive to and require smaller digoxin doses.

The frequency of different types of heart disease in South African Blacks at a cardiac referral center.

Cardiomyopathy has been considered to be the most prevalent form of heart disease amongst Blacks in Southern Africa. In the present study we evaluated 5725 patients with heart disease. Rheumatic heart disease was most prevalent accounting for 42% of cardiac diseases. Ischemic heart disease was extremely rare.

Digitalis toxicity in infants and children.

There is a narrow difference between the therapeutic and toxic ranges of cardiac glycosides. The availability in the past decade of radioimmunoassays for accurate measurement of these glycosides has resulted in an improved understanding of their pharmacokinetics and clinical use. Despite these advances, however, digitalis toxicity is still a common problem in infants and children.

Tissue concentrations at autopsy in infants and children receiving therapeutic digoxin.

Therapeutic tissue concentrations of digoxin have been reported for relatively small numbers of infants and children. In forensic medicine, knowledge of these concentration ranges is important for confirming or excluding digoxin overdosage in different age groups. In addition to age and weight, other factors such as dosage, duration of treatment, route of administration, sampling site, time of last dose, and death-autopsy interval may influence tissue concentrations. In this paper we report on tissue concentrations in 36 infants and children who received therapeutic digoxin before death.

Pathologic measurements in aortic atresia.

Detailed autopsy measurements were performed in 13 infants with hypoplastic left ventricle and aortic atresia. Emphasis was placed on the evaluation of changes in the right ventricle, since its function may be important in determining surgical survival. Other important aspects were the ascending aortic and transverse aortic arch diameter, the presence of left atrial obstruction, and the size of the left atrium. The development of improved 2DE and Doppler imaging will permit preoperative and sequential evaluation of these parameters. Measurements performed in this study may serve as a basis for selection of infants for palliative surgery; these procedures are being undertaken more frequently in this hitherto fatal lesion. The measurements may also serve as a basis for noninvasive serial studies of these infants postoperatively.

Postmortem digoxin tissue concentration and organ content in infancy and childhood.

The concentration of digoxin in tissues and the content of the drug in various organs are reported in 36 infants and children. Sixteen received the drug on a short-term basis and 20 on a long-term basis. The drug was given intravenously to 12, orally to 17, and by intramuscular injection to 7. The study was conducted to determine distribution of digoxin in infants and children and to examine the forensic implications related to digoxin overdosage. Upper therapeutic concentration thresholds for digoxin were established in various tissues. These are different for preterm and full-term neonates than for older children and adults; for example, adult and neonatal values for postmortem blood specimens are 8 and 15 ng/ml, and for ventricular myocardium are 250 and 450 ng/g, respectively. The chronically digitalized premature infant retains in most tissues a considerably larger fraction of digoxin than more mature infants and children. This is in accord with previously demonstrated lower renal digoxin levels in premature infants attributed to their reduced ability to excrete this drug.

Quantitative angiographic and morphologic aspects of aortic valve atresia.

Quantitative angiographic measurements were performed in 15 infants aged 1 to 35 days who had aortic valve atresia with intact ventricular septum and hypoplastic left ventricle. Thirteen infants had similar measurements performed at autopsy. The latter measurements were smaller than those found at angiography (because of shrinkage), but their relationship was predictable. Angiographic right ventricular (RV) volumes were 2 and 4 times normal in diastole and systole, respectively. The RV volume measured at autopsy was greater than 3 times normal. Mean RV ejection fraction was 0.40; it was below normal in 10 infants. Maximal right atrial volume was greater than 2 times normal, and mean left atrial maximal volume was two-thirds normal. The relation between circumferences of the aortic arch and ascending and descending aorta was similar at angiography and autopsy.

Prostaglandin E1 infusion in newborns with hypoplastic left ventricle and aortic atresia.

Prostaglandin E1 (PGE1) infusion was used in 7 infants with hypoplastic left ventricle and aortic atresia. Of 5 non-operated patients, 4 died shortly after the onset of PGE1 infusion and 1 survived for 30 hours. Of the infants who had surgery, 1 died during the operation and 1 survived for 38 days. In 6 infants, a transient metabolic and/or circulatory improvement could be demonstrated following PGE1 infusion. The lack of response of other infants may be related to the advanced deterioration of their clinical status at the time of study. In the light of recent surgical developments for infants with aortic atresia, support with PGE1 may nevertheless play an important role in their management if started early.

Digoxin pharmacokinetics in premature infants.

An analysis of pharmacokinetic parameters of digoxin was carried out in six premature infants after the administration of a single total digitalizing dose of 20 microgram/kg. The data was analyzed using both a 2 and 3 exponential model. In the premature infant, the plasma half-life of digoxin is prolonged, while the volume of the central compartment, total body clearance, volume of distribution and volume of distribution at steady state are reduced compared to other aged patients.

Congenital interruption of the inferior vena cava.

In the usual form of interruption of the inferior vena cava (IVC), the post-renal IVC continues as the azygos and hemiazygos vein. We report a patient with complete interruption of the IVC in whom no direct continuity existed between the IVC and the azygos system. Connection between these two systems was via the vertebral plexus and ascending lumbar veins. Associated venous malformations included bilateral azygos veins and anomalous connection of pulmonary and hepatic veins.

Anomalous left coronary artery in the infant: recovery of ventricular function following early direct aortic implantation.

A successful direct aortic implantation of an anomalous left coronary artery (ALCA) in an infant is reported. Detailed evaluation of postoperative ventricular function, including repeat cardiac catheterization and serial echocardiography, demonstrated progressive enhancement of ventricular contractility and function. Postoperative angiography confirmed vascular patency. These data support the concept that the ALCA should be corrected by direct aortic implantation early in infancy rather than by expectant treatment or graft interposition.

Surgical palliation in aortic atresia.

In an infant with aortic atresia, two surgical procedures resulted in a 45 day postoperative survival. An atrial septectomy was initially performed. This was followed by the insertion of a Dacron graft from the main pulmonary artery to the descending thoracic aorta; the pulmonary artery was handed distal to the graft and the ductus arteriosus was ligated. Prostaglandin E1 was infused from the time of the diagnostic study to the second surgical procedure, 48 hours later. A postoperative cardiac catheterization was performed 3 weeks following the operation. Death occurred at 67 days of age from renal failure and a low cardiac output state.