Acute ventricular and aortic thrombosis post chemotherapy.

We present a rare case of spontaneous arterial thrombosis in a 42-year-old male with an acute history of bilateral lower limb pain and weakness. The previous day he had received the first cycle of cisplatin-based chemotherapy for oesophageal adenocarcinoma (T2/3N0/M0). Computed tomography (CT) and angiography showed extensive abdominal aortic thrombus in a native non-aneurysmal or grossly atheromatous aorta with separate thrombus in the left ventricle. We suggest that poor left ventricular function, a hypercoaguable state secondary to malignancy and cisplatin based chemotherapy may have induced severe arterial and intra-cardiac thrombosis.

In vivo rates of erythrocyte glutathione synthesis in children with severe protein-energy malnutrition.

Although the compromised GSH status of children with edematous protein-energy malnutrition (PEM) has been documented, the in vivo kinetic mechanism(s) responsible for this is not known. To determine if decreased synthesis contributes to the alteration of GSH homeostasis, the fractional and absolute rates of synthesis of erythrocyte GSH were determined shortly after admission (study 1), approximately 9 days postadmission (study 2), and at recovery (study 3) in seven children with edematous PEM and seven children with nonedematous PEM. Children with edematous PEM had significantly lower erythrocyte GSH and slower absolute rates of GSH synthesis than children with nonedematous PEM both shortly after admission, when they were both malnourished and infected, and approximately 9 days later, when the infection had resolved but they were still malnourished. At these times, the edematous group also had significantly lower erythrocyte GSH concentrations and absolute rates of synthesis than at recovery. Plasma and erythrocyte-free cysteine concentrations of the edematous group were significantly lower at studies 1 and 2 than at recovery. In contrast, erythrocyte GSH concentrations, rates of GSH synthesis, and plasma and erythrocyte free cysteine concentrations of the nonedematous group were similar at all three time points and greater at studies 1 and 2 than in the edematous group. These results confirm that GSH deficiency is characteristic of edematous PEM and suggest that this is due to a reduced rate of synthesis secondary to a shortage in cysteine.

Acute-phase protein response to infection in severe malnutrition.

It is not known whether malnourished infants can mount a comprehensive acute-phase protein (APP) response and, if so, whether this is achieved by increasing APP synthesis rates. To address these issues, we measured 1) the plasma concentrations of five APPs (C-reactive protein, alpha1-acid glycoprotein, alpha1-antitrypsin, haptoglobin, and fibrinogen) and 2) the synthesis rates of three APPs (alpha1-antitrypsin, haptoglobin, and fibrinogen) using a constant intragastric infusion of [2H3]leucine in nine infected marasmic children at approximately 2 days postadmission (study 1), approximately 9 days postadmission when infections had cleared (study 2), and approximately 59 days postadmission at recovery (study 3). Except for fibrinogen, the plasma concentrations of all APPs were higher in study 1 than in studies 2 and 3. Although the rate of synthesis of haptoglobin was significantly greater in study 1 than study 2, the rates of fibrinogen and alpha1-antitrypsin synthesis were similar in all three studies. These results show that 1) severely malnourished children can mount an APP response to infection which does not include fibrinogen and 2) the APP response is accomplished through different mechanisms.

Repletion of the plasma pool of nutrient transport proteins occurs at different rates during the nutritional rehabilitation of severely malnourished children.

Increased morbidity and mortality are associated with lower plasma protein concentrations in children with severe protein-energy malnutrition. However, the kinetic changes responsible for repletion of the plasma pools of nutrient transport proteins and the rapidity of their replenishment in these children have not been determined. This study was undertaken to determine whether an increased rate of synthesis is the mechanism responsible for repletion of the plasma retinol-binding protein, transthyretin and high density lipoprotein-apolipoprotein A1 concentrations of children with severe malnutrition during nutritional rehabilitation. The plasma concentrations and synthesis rates of retinol-binding protein, transthyretin and high density lipoprotein-apolipoprotein A1 were measured using a constant intragastric infusion of 2H3-leucine in 22 children with severe protein-energy malnutrition, at approximately 2 d postadmission (study 1), approximately 8 d post-admission when infections were under control (study 2) and approximately 59 d postadmission at recovery (study 3). In study 1 the plasma concentrations and rates of synthesis of all the proteins were lower compared with values at recovery. In study 2, retinol-binding protein and transthyretin concentrations and absolute synthesis rates increased to the recovered values seen in study 3, but the high density lipoprotein-apolipoprotein A1 concentration and synthesis rate remained significantly lower. These results suggest that repletion of the plasma pool of these three nutrient transport proteins occurs at different rates, through an increase in the rate of synthesis.

Transferrin kinetics are altered in children with severe protein-energy malnutrition.

This study was undertaken to determine the following: 1) the kinetic changes responsible for the depletion and repletion of plasma transferrin (Tr) concentration in children with protein-energy malnutrition (PEM); 2) the role of infection in mediating these changes; and 3) whether plasma Tr concentration is related to body protein status. We measured plasma Tr concentration, and fractional (FSR) and absolute (ASR) Tr synthesis rates with the use of a constant intragastric infusion of 2H3-leucine in 14 children with PEM, at 2 d postadmission (study 1), 8 d postadmission when infections were under control (study 2), and at recovery (study 3). In studies 1 and 2, the children synthesized less Tr and had lower Tr concentrations compared with values at recovery. When infections were controlled, plasma Tr concentration rose, but Tr synthesis was unchanged. There were only fair correlations (P < 0. 05) between plasma Tr concentrations and indices of wasting. Concerning malnourished children, we reached the following conclusions: 1) changes in the Tr pool size are achieved mainly through changes in synthesis rate; 2) infections play a minor role in reducing the Tr pool through either changes in the rate of catabolism or loss from the intravascular space; and 3) Tr concentration is not a very good indicator of protein nutritional status.

Albumin kinetics in edematous and nonedematous protein-energy malnourished children.

The kinetic changes responsible for decreased plasma albumin and the relation between plasma albumin and the edema of protein-energy malnutrition (PEM) were investigated by measuring the plasma concentration, fractional (FSR) and intravascular absolute (ASR) synthesis rates of albumin in seven edematous and seven nonedematous children with PEM by using constant intragastric infusions of [2H3]leucine. Studies were done 2 d postadmission (study 1), 8 d postadmission (study 2), and at recovery (study 3). In study 1 there were no significant differences in plasma albumin concentrations in nonedematous and edematous children. In both groups, albumin concentrations but not FSRs were lower in studies 1 and 2 than in study 3. The ASR was lower only in edematous patients. These results suggest that repletion of the albumin pool of children with PEM is not mediated by changes in the FSR, and the edema of malnutrition is not solely due to hypoalbuminemia.

Evidence for decidua-trophoblast interactions in early human pregnancy.

Medium conditioned by decidual cells decreased the growth of cultured BeWo choriocarcinoma cells. The degree of inhibition was dependent on the concentration of the conditioned medium used, and suggested that maternal decidua might regulate the growth of the fetal placenta. Medium from BeWo cells and primary trophoblast had the opposing effect and increased the growth of cultured decidual cells for up to 120 h of culture. These results suggest that a regulatory loop to control placental and decidual growth exists at the materno-fetal interface, and this may be an important factor in the development of adequate placentation and the subsequent growth of the placenta during pregnancy.