CV 205-502 treatment of hyperprolactinemia.

CV 205-502 is a nonergot oral dopamine agonist with specific D2 activity, which has a prolonged suppressive effect on serum PRL and may have fewer side-effects than other dopamine agonists. We treated 26 hyperprolactinemic women with this compound given as a single bedtime (hs) dose for up to 12 weeks. All had gonadal dysfunction, either amenorrhea or oligomenorrhea, and 15 had galactorrhea. The initial and subsequent doses were administered in a randomized fashion; the initial dose ranged from 0.01-0.05 mg, and the dose at 12 weeks ranged from 0.03-0.09 mg. The women were evaluated every 2 weeks, and the dose was increased by 0.02 mg every 4 weeks if the serum PRL level was greater than 20 micrograms/L. Of the 26 women initially enrolled, 24 completed 12 weeks of therapy, and 2 discontinued therapy because of side-effects. Thirteen women (54%) had return of menses, and 12 (80%) had either a decrease in or disappearance of galactorrhea. Serum PRL concentrations decreased to a variable degree in all patients; 13 (54%) achieved a normal serum PRL level (less than or equal to 20 micrograms/L). The mean (+/- SE) pretreatment serum PRL concentration was 129 +/- 34, and it was 29.9 +/- 5.9 micrograms/L after 12 weeks of treatment (P = 0.005). The mean (+/- SE) percent reduction in serum PRL was 66.5 +/- 5.0% (median, 78.0%). A dose response was not demonstrated (r = -0.08; P = 0.70) among the 6 dose groups during the last 4 weeks of therapy. In 5 women, serum PRL levels, measured frequently for 24 h after treatment remained low. Side-effects after the initiation of therapy included nausea, headache, and morning fatigue in 10 women. These symptoms caused 2 women to discontinue therapy; they subsided in the other women. An optimal dose was not determined and will probably need to be determined by titration in each patient. CV 205-502, given once daily, appears to be a safe and effective alternative to other dopamine agonists in the treatment of hyperprolactinemia.

Adenocarcinoma in a choledochal cyst during pregnancy: a case report and guidelines for management.

Choledochal cysts, although more common in females than males, have only rarely been encountered in association with pregnancy. We report a patient with a large choledochal cyst that was excised at the time of cesarean section. Pathologically, the cyst wall was found to contain a focus of adenocarcinoma. The development of carcinoma is a recognized risk in patients with choledochal cysts that mandates cyst excision, rather than bypass, whenever possible. The literature regarding choledochal cysts in pregnancy is reviewed. Pregnant patients with choledochal cysts require careful management so as to avoid cyst rupture; and cesarean section is preferable to normal vaginal delivery in most cases. Although the preferred management of a choledochal cyst is excision and Roux-en-Y reconstruction, this may have to be deferred until after delivery, depending on gestation age, because of the risk of fetal mortality and maternal morbidity that is associated with this procedure.

Malignancy arising in endometriosis associated with unopposed estrogen replacement.

Malignant transformation of endometriosis is a well documented phenomenon. Although it occurs most commonly in the ovaries, there have been approximately 50 reported cases of extraovarian malignant transformation of endometriosis. This paper presents two cases of malignancy arising from a dormant focus of endometriosis after total abdominal hysterectomy, bilateral salpingo-oophorectomy, and exogenous estrogen replacement therapy. These malignancies are often well differentiated and may behave similarly to estrogen-induced endometrial carcinomas. After surgical castration of a premenopausal woman with endometriosis, the use of progestins in replacement therapy may reduce the risk of malignancy arising in endometriosis.

Gradient of total [Ca++] in the renal pelvis.

The [Ca++] gradient within the rabbit renal pelvis was compared to its inherent pacemaker frequency. The pelvis was removed from the rabbit, sectioned, and [Ca++] ions assayed using wet ash techniques and atomic absorption spectrophotometry. Contraction frequency was measured isometrically in vitro. In the bisected pelvis it was found that both [Cu++] levels and contraction frequency were highest in the proximal section, 9.02 +/- 4.62 mEq/kg, and lower in the distal section, 6.59 +/- 2.43 mEq/kg wet weight. The mean frequency of contraction decreased from 3.69 +/- 0.81 to 2.41 +/- 0.49 min-1 in the proximal and distal regions, respectively.

Total [Na+] and [K+] gradient in the pyeloureter.

The gradient of cellular [Na+] on [K+] ion within the renal pelvis of the rabbit was correlated with the autorhythmicity of the proximal, middle, distal and ureteropelvic regions of this structure. The results show that the maximum frequency of spontaneous pacemaker contractions occur at the proximal pelvis with a mean frequency of 4.97 +/- 0.85 contractions/min, a mean [Na+] of 91.0 +/- 33.3 mEq/kg net weight, a mean [K+] of 18.9 +/- 6.0 mEq/kg net weight. The frequency of spontaneous activity from the middle pelvis and distal pelvis decreases to mean values of 2.76 +/- 0.60 and 1.82 +/- 0.56 contractions/min. The corresponding values for [Na+] and [K+] are 78.0 +/- 27.7 and 11.8 +/- 4.7 for the middle pelvis and 66.6 +/- 32.7 and 9.75 +/- 3.4 for the distal pelvis, respectively. Normalized regression curves indicate a [Na+]gradient variation of delta [Na+] = 67.1 +/- 0.07 delta F and a [K+] gradient of delta [K+] = 39.8 - 0.06 delta F + 0.01 delta F2. Spatially, the variation of [Na+] and [K+] with distance. D, within the pelvis is given by [Na+] = 119 - 14D + D2 and [K+] = 26 - 11D + 2D2. It is concluded from this study that there is a frequency gradient between proximal renal pelvis and ureteropelvic junction which is significantly interdependent upon the cellular [Na+] on [K+] concentration gradient.