Reduced metabolic clearance of acidic variants of human choriogonadotropin from patients with testicular cancer.

We investigated the plasma disappearance of purified urinary human choriogonadotropin (hCG) and acidic variants of hCG (AV-hCG) that are excreted in the urine of patients with testicular cancer to determine if there are differences in their disappearance rates. All cancer patients had relatively increased fractions (10% to 46%) of AV-hCG in their serum when compared with hCG from pregnant control subjects (less than 4% present as AV-hCG). After initiation of therapy in 12 patients with nonseminomatous testicular tumors, the proportion of hCG present as acidic variants in serum rose despite lower serum total hCG concentrations. Samples of highly purified AV-hCG (pI, 3.3 to 4.0) obtained from three patients by concentration from urine and isoelectric focusing were evaluated for their disappearance from serum after injection into rats. All AV-hCG samples had decreased clearance rates when compared with that of highly purified hCG (CR123). These data indicate that acidic forms of hCG have a delayed clearance that contributes to the increased proportion of AV-hCG in the serum of patients with hCG-producing neoplasia after therapy.

Structure-kinetic relationships of choriogonadotropin and related molecules.

To assess how profound differences in carbohydrate and/or polypeptide structures affect parameters of plasma disappearance of glycoprotein hormones, we calculated and compared the initial volume of distribution, rate constants, and metabolic clearance rates of several highly purified human choriogonadotropin (hCG) analogues in monkeys. hCG, deglycosylated hCG, desialylated hCG, or core fragment of hCG-beta purified from pregnancy urine (beta-core) was administered as a rapid intravenous injection to adult male cynomolgus monkeys (n = 3/group). The metabolic clearance rates of deglycosylated hCG, beta-core fragment, and desialylated hCG were increased 15-, 47-, and 152-fold, respectively, over that of hCG. Their corresponding initial volumes of distribution, however, remained essentially unchanged compared with that of hCG and approximated the estimated plasma volume. In contrast, the fast and slow rate constants of plasma disappearance of the hCG analogues were increased as much as 18- and 23-fold, respectively, relative to those of hCG. These studies of structure-kinetic relationships in primates show that major carbohydrate and polypeptide modifications of a glycoprotein hormone cause profound changes in the rate constants of the disappearance curves without changes in the initial volume of distribution.

Pelvic tamponade in puerperal hemorrhage. A case report.

A case of puerperal hemorrhage was associated with disseminated intravascular coagulation following hysterectomy. Following unsuccessful surgical intervention, pelvic tamponade was accomplished via use of the Logothetopulos pack.