Modified repeated intracyclic clomiphene citrate therapy after conventional clomiphene therapy.

PURPOSE OF INVESTIGATION: We compared modified repeated intracyclic clomiphene citrate therapy (RICCT) to gonadotropin therapy to determine whether this modified regimen was an effective alternative after conventional clomiphene therapy. METHODS: Patients with ovulation disorder received treatment with modified RICCT and gonadotropin, and ovulation, pregnancy, total drug cost, and adverse effects were compared. RESULTS: Among a total of 16 patients, 14 successfully ovulated after modified RICCT and 11 ovulated after gonadotropin therapy; two did not respond to either therapy. The total drug cost was US $36.3+/-17.9 for modified RICCT, which was significantly lower than the cost of gonadotropin therapy, US $213.9+/-100.4 (p=0.0001). CONCLUSIONS: Because modified RICCT does not require the discomfort of daily injection and has excellent ovulation-inducing effects, it is a useful treatment after conventional clomiphene therapy.

Repeated intracyclic clomiphene citrate therapy can be more effective than hMG therapy in inducing ovulation: case report.

PURPOSE OF INVESTIGATION: When clomiphene citrate is ineffective in the treatment of anovulation, hMG administration is typically selected. However, high-dose hMG therapy is associated with a variety of adverse events. We describe the use of a modified clomiphene citrate regimen that was successful in increasing the effectiveness of ovulation induction. CASE REPORT: A patient who did not initially respond to clomiphene citrate therapy required a total dose of 2400 IU hMG to prodeuce mature follicles. However, because of the physical and emotional burdens on the patient, and the possibility of multiple pregnancy and ovarian hyperstimulation syndrome, re-treatment with clomiphene citrate was then selected. Two courses of clomiphene citrate administered at a fixed interval during the same cycle safely induced ovulation. After initial induction of ovulation, her ovulatory failure improved and natural ovulation occurred. CONCLUSIONS: Repeated intracycle clomiphene cirate therapy may be more effective than hMG therapy in inducing ovulation in some patients.

Structure-function relationship of islet-activating protein, pertussis toxin: biological activities of hybrid toxins reconstituted from native and methylated subunits.

Islet-activating protein (IAP), pertussis toxin, is a hexameric protein composed of an A protomer and a B oligomer, the residual pentamer having such a subunit assembly that two different dimers, dimer 1 and dimer 2, are connected with each other by means of the smallest C subunit. Incubation of IAP with formaldehyde and pyridine-borane produced the modified toxin in which most of the free amino groups were dimethylated. The methylated and nonmethylated (native) IAP were disintegrated into their respective constituent components, which were then cross combined to reconstitute hybrid toxins with the original hexameric structure. The binding of the B oligomer to the mammalian cell surface via dimer 2 was, but the binding via dimer 1 was not, seriously impaired by methylation of amino groups in the protein. The binding of the B oligomer allowed the A protomer to enter cells and to catalyze ADP-ribosylation of a membrane Mr 41 000 protein. The diverse biological activities of IAP occurring by this mechanism were mimicked by not only methylated IAP but also all hybrid toxins, indicating that the free amino groups in the protein were not essential for the enzyme activity of the A protomer and that the A protomer was able to enter cells if the B oligomer bound to cells "monovalently" via dimer 1. An additional effect of the B oligomer binding, i.e., the direct stimulation, without the transport of the A protomer, of cells leading to mitosis in lymphocytes in vitro or increases in circulating lymphocytes in vivo, was not mimicked by hybrid toxins containing methylated dimer 2.(ABSTRACT TRUNCATED AT 250 WORDS)