In vivo effects of delta 1-testololactone on peripheral aromatization.

To evaluate the in vivo effect of delta 1-testololactone on peripheral aromatization, studies were performed on seven postmenopausal women with metastatic breast cancer. Analysis of variance indicated that there were significant increases of circulating androstenedione (p less than 0.05) and estradiol (p less than 0.001) during administration of different doses of testololactone. Androstenedione levels were increased with all doses of testololactone tested (50, 100, 250, and 500 mg every 6 hr for 14 days each), while estradiol rose with only the 250- and 500-mg dosages. With administration, there was a significant decrease of estrone (p less than 0.001) with the mean level falling from 26 +/- 3 (S.E.) to 11 +/- 2 pg/ml. The addition of adrenal suppression (dexamethasone, 1 mg nightly at 11 p.m.) significantly lowered androstenedione (p less than 0.05) but had no effect on estrone or estradiol levels. Long-term therapy (up to 6 months) with the 250-mg dosage showed continual suppression of estrone with no escape being observed. Studies to determine the reason for the increase of estradiol with testololactone suggested cross-reactivity of the antibody with in vivo metabolites of the drug. However, these possible metabolites did not bind to uterine cytosol estrogen receptors. The decrease in estrone with testololactone administration presumably explains its antitumor properties.

Ultraviolet-B (290-320 nm)-irradiation inhibits epidermal growth-factor binding to mammalian cells.

Mitogens, such as polypeptide growth factors and phorbol ester tumor promoters, act by binding to specific receptors and inducing a pleiotropic response in cultured mammalian cells, which results in the induction of cellular proliferation. An early effect of such agents is the inhibition of binding of epidermal growth factor (EGF) to its receptor. Ultraviolet radiation has also been shown to induce a proliferative response in vivo and in vitro and to act as a tumor promoter in animal skin. We, therefore, examined the effect of ultraviolet radiation (UVB - 290-320 nm) on EGF binding to cells in culture. We found that UVB (100-300 J/m2) induced a rapid, dose-dependent inhibition of EGF binding in a mouse fibroblast cell line, which resulted from a decrease in both number and affinity of binding sites. Phosphorylation of the EGF receptor by protein kinase C (PKC) is not likely to be the mechanism for inhibition, since UVB treatment did not result in PKC activation or modulation of phorbol diester binding.

Further delineation of hypothalamic dysfunction responsible for menopausal hot flashes.

An association exists between pulsatile LH release and hot flashes (HFs). To further delineate the hypothalamic mechanism(s) responsible for HF, the basal levels and pulsatile release of LH, FSH, estradiol, and estrone and the rate of occurrence of HFs (measured objectively) were evaluated in patients with a defect of GnRH secretion [isolated gonadotropin deficiency (IGD)], patients with abnormalities of afferent input to GnRH neurons [hypothalamic amenorrhea (HA)], and postmenopausal women with severe HFs. Patients with IGD had received estrogens, which were discontinued before study. Patients with HA had experienced regular menses before disease onset, which followed emotional stress or weight loss. Studies were limited to HA patients with estrogen levels in the postmenopausal range. Pulsatile LH release was absent in patients with IGD and was absent or greatly reduced in women with HA. Objectively measured and subjectively experienced HFs occurred in IGD but not in HA patients. These results suggest that HFs are not an obligatory consequence of low endogenous estrogen levels and that the absence of episodic LH and GnRH release (IGD) does not influence the occurrence of HFs. It is possible that the dysfunction of afferent input to GnRH neurons in HA somehow prevents HFs in these women with low endogenous estrogen secretion.

The effect of membrane permeability and binding by human serum proteins on sex steroid influx into the uterus.

To determine the effect of such factors as capillary membrane permeability, plasma protein binding, and capillary transit time on the availability of sex steroids to the uterus, the unidirectional influxes of 3H-labeled steroids from the circulation into the uterus were measured in vivo in anesthetized rats using a tissue-sampling, single injection technique. When dihydrotestosterone (DHT), estradiol (E2), and progesterone (P) were injected with Ringer's solution, the tissue extraction was in excess of 80%; hence, membrane permeability did not play a limiting role. With the more polar steroids, corticosterone and cortisol, uterine extraction was less than 40%. Significant inhibition of tissue extraction of DHT and E2, but not P, occurred with the addition of 4% albumin to the injection solution. Human sera containing increasing concentrations of sex hormone-binding globulin demonstrated inhibition of extraction of DHT and E2. Human sera also inhibited P extraction, presumably secondary to the presence of cortisol-binding globulin and orosomucoid. Large concentrations of unlabeled DHT, E2, and P in the injection solutions did not result in competitive inhibition of labeled steroid extraction. Thus, there is no evidence for a carrier mechanism mediating steroid transport into the uterus. When tissue extraction of E2 from Ringer's solution was compared in liver, brain, and uterus, no difference of tissue permeability could be found. Liver consistently had higher tissue E2 extraction than brain or uterus in the presence of human sera. The results are compatible with the influx of albumin-bound E2 into all three tissues and the influx of sex hormone-binding globulin-bound E2 into the liver.

Treatment of hot flashes with transdermal estradiol administration.

A randomized prospective double blind study was performed to assess the ability of a transdermal therapeutic system (TTS) delivering estradiol (E2) to suppress hot flashes (HFs) in symptomatic postmenopausal women. Patients were given placebo or E2 in four doses for a 20-day period, and serum gonadotropin and estrogen levels and the occurrences of HFs were measured. Administration of placebo had no measurable effect on either estrogen or gonadotropin levels or the occurrence of HFs. A dose-response relationship was found between the rate of E2 administered and the circulating level of E2, with 25, 50, 100, and 200 micrograms/24 h dosages raising the mean E2 concentrations from mean baseline levels of 5-8 pg/ml to 18, 38, 73, and 100 pg/ml, respectively. Estrone levels also increased with TTS application, but to a lesser extent than did E2 levels. Dose-response reductions of FSH and LH with increasing amounts of E2 administration occurred, but gonadotropin levels were not lowered in any of the patients into the ranges found in premenopausal women. TTS application significantly suppressed the occurrence of HFs at the 50 micrograms/24 h dosage and higher. A significant negative correlation (r = 0.6045; P less than 0.001) between E2 levels and the rates of occurrence of HFs was found during hormone administration. Based on this regression, 50% and 100% reductions of HFs should occur at 61 and 122 pg/ml E2. These data indicate that the transdermal delivery of E2 with these systems significantly reduced the occurrence of HFs and allowed definition of the therapeutic range of hormone replacement in terms of lost ovarian function, as reflected by circulating E2 levels.

Induction of hot flashes in premenopausal women treated with a long-acting GnRH agonist.

To examine the relationship between the occurrence of menopausal hot flashes and the pulsatile release of LH, we have investigated the serum hormone levels and the occurrence of hot flashes by objective recordings in five women with endometriosis given daily injections of a long-acting GnRH agonist (GnRH-a) for 28 days. Results were compared to the findings made in 25 young women 6-8 weeks after bilateral oophorectomy. Serum levels of estrone and estradiol were similar in the subjects given GnRH-a and the women who underwent a surgical castration. In comparison with values before GnRH-a administration, the mean FSH level was lower whereas the mean LH concentration was significantly higher (P less than 0.01) on the last day of therapy. The coefficients of variations of both gonadotropins measured during 4-h sampling periods at 20-min intervals before and at the end of GnRH-a administration were significantly reduced (P less than 0.01) with therapy. During the total of 20 h of frequent sampling in the 5 subjects, 15 pulses (20% rise from nadir) of LH and 12 pulses of FSH were detected before GnRH-a, whereas only 2 and 8 pulses, respectively, were observed on day 28 of treatment. Hot flashes were observed in both groups of patients. The proportion of women experiencing hot flashes, the rate of occurrence/h and the characteristics of the physiological changes were similar in the 2 groups of women. These data indicate that hot flashes can occur in the absence of prominent LH pulses, suggesting the pulsatile release of this hormone is merely associated with the hot flash rather than being etiological.

Steroid secretion in polycystic ovarian disease after ovarian suppression by a long-acting gonadotropin-releasing hormone agonist.

The principal glandular source of increased serum androgens in polycystic ovarian disease (PCO) is controversial), since complete separation of ovarian from adrenal function has not been achieved. The purpose of this study was to determine whether a long-acting GnRH agonist could be used to selectively inhibit ovarian steroid secretion in PCO and ovulatory women. Each of five typical PCO patients and six ovulatory subjects on day 2 of their menstrual cycles received D-Trp6-Pro9-NEt-LHRH (GnRH-a; 100 micrograms) for 28 consecutive days. Their results were compared to basal serum hormone values in eight oophorectomized women. In response to GnRH-a, PCO and normal subjects exhibited sharp and sustained rises of LH and gradual decreases in FSH. These levels were clearly less than basal levels seen in oophorectomized women. Episodic LH release was significantly attenuated in both groups at the end of GnRH-a treatment. After the administration of agonist, serum estradiol (E2), estrone (E1), androstenedione (A), and testosterone (T) were suppressed to castrate levels in both groups. The decrements of E2 and E1 in PCO were gradual and continuous compared to initial dramatic rises, which reached peaks at 14 days, and subsequent abrupt falls in the ovulatory controls. Serum A and T declined steadily in both groups. Basal serum dehydroepiandrosterone and dehydroepiandrosterone sulfate, but not cortisol, levels were elevated in PCO subjects. The 24-h secretion patterns and responses to ACTH of these hormones in PCO and ovulatory subjects were unaltered by GnRH-a administration. These data demonstrate that 1) in PCO subjects, GnRH-a induced complete suppression of ovarian steroid secretion, as circulating levels at the end of treatment were comparable to those seen in our oophorectomy subjects; 2) elevated A and T levels in PCO patients were derived primarily from the ovary; and 3) adrenal steroid secretion was unaltered by GnRH-a in both PCO and normal women.

Effect of clonidine on hot flashes in postmenopausal women.

The effectiveness of clonidine in suppressing the occurrence of postmenopausal hot flashes was examined using a dose-response study design and objective recordings of hot flashes. Patients with frequent flashes were studied before and after oral administration of placebo and 0.1, 0.2, and 0.4 mg of clonidine daily for 2 weeks at each dose level. Finger temperature and skin resistance were recorded as indices of hot flash episodes. Four of 10 subjects beginning the study withdrew because of drug-related side effects. Clonidine was found to reduce significantly the frequency of hot flashes as compared with baseline (P less than .005) and with effects of the placebo (P less than .05). At the maximum dosage the mean rate of hot flash occurrence decreased 46%. It was concluded that clonidine does reduce the frequency of postmenopausal flashes.

Vertebral pneumatocyst. A case report.

STUDY DESIGN: This study illustrates intraosseous pneumatocyst of the vertebral body, a benign lesion. OBJECTIVES: To review the incidence and location of this benign lesion during a 1-year period. SUMMARY OF BACKGROUND DATA: Intraosseous pneumatocyst is a rare benign condition, commonly seen in iliac bone or sacrum. The etiology of this entity is unclear. Other locations of these lesions are very rare, and only a few isolated cases are reported in the literature. METHODS: In the last year (1994-1995), vertebral pneumatocyst was incidentally found in four patients who underwent computed tomography examination for presumptive discal lesion. Axial computed tomography with 2- and 4-mm slice thickness was performed. RESULTS: The typical computed tomography patterns of intraosseous pneumatocyst involving the cervical, dorsal, or lumbar spine were found. The bony structure and joints were normal. To the best of our knowledge, intraosseous pneumatocyst located in the spinal process has not been reported. CONCLUSIONS: Intraosseous pneumatocyst is a benign lesion. Biopsy and follow-up are unnecessary.

A severe form of Sjogren's syndrome.

Sjogren's syndrome is an autoimmune disease characterized by exocrine gland destruction and manifested by parotid, submandibular and lacrimal gland infection. We report a case with recurrent severe parotid gland infections. The sialographic and CT findings are presented.

[Plasma cell granuloma of the chest and lung in childhood].

Plasma cell granuloma is a benign, non-neoplastic lesion rarely found in children. It occurs mainly in the chest and lungs, the right lung mostly. Most cases are asymptomatic and are discovered incidentally on routine chest X-ray, although there may have been atypical upper respiratory symptoms. The X-ray findings, as well as those of other imaging modalities, are nonspecific, making the exact localization and diagnosis of the lesion difficult, as demonstrated in the cases of 2 boys aged 8 and 9 years, respectively. Locating the right diaphragm and its relation to the large lesion by various imaging modalities was unreliable in 1 of the cases. The large, dense, firm, adherent lesions were carefully and completely resected in both cases. In 1 case it was located in the right lung, pulmonary hilum and mediastinum. In the other, in the right pleural space in the supradiaphragmatic region, adherent to the posterolateral aspect of the lower ribs. Biopsies for frozen section should always be taken before deciding on the extent of surgery. Radical resection of normal surrounding tissue should be avoided. Our cases have been followed for 2 and 3 years respectively, with no evidence of recurrence. Prognosis is excellent when lesions are completely removed.

Sturge-Weber syndrome associated with a large left hemispheric arteriovenous malformation.

A patient with the characteristic changes of Sturge-Weber syndrome on the right side was found to have a large arteriovenous malformation on the left side which involved the superior ophthalmic vein. This association, although previously reported, is extremely rare.

Intrathoracic rib demonstrated by helical CT with three-dimensional reconstruction.

Intrathoracic rib is a rare congenital anomaly. An unusual location with atypical pleural tenting is reported. Helical CT with three-dimensional reconstruction seems the best modality for demonstrating the origin and location of these abnormal ribs. The importance of the diagnosis of intrathoracic rib is to rule out pulmonary lesions and prevent unnecessary investigations.

Purpose in life and occupational interest in a gerontological sheltered workshop.

Measured the concept of purpose-in-life and underlying occupational interests and aspirations of older men (N = 25) and women (N = 29) in a gerontological sheltered workshop. The relationship among the Purpose-in-Life Test, Vocational Preference Inventory, Will-to-Live scale, and demographic information, is explored. Findings, which include that the construct of purpose in life and vocational aspirations are poorly related for workshop participants, are discussed in terms of previous research.

Pelvic granulocytic sarcoma.

Granulocytic sarcoma is an uncommon extraskeletal tumor most frequently associated with leukemia. We present a case of bone location with unusual pattern in a patient with no evidence of myeloproliferative disorder at presentation or follow-up.

Post-traumatic recto-spinal fistula.

Acquired recto-spinal fistula has been described elsewhere as a rare complication of colorectal malignancy and Crohn's enterocolitis. We treated a young man who developed a recto-spinal fistula as a result of a high fall injury. The patient presented with meningeal signs, sepsis and perianal laceration. Computerized axial tomography revealed air in the supersellar cistern. Gastrografin enema showed that contrast material was leaking from the rectum into the spinal canal. Surgical management included a diverting sigmoid colostomy, sacral bone curettage and wide presacral drainage. To the best of our knowledge, rectospinal fistula of traumatic origin has not been previously reported in the English literature.

CT and US features of cervical lymphadenopathy due to kikuchi's disease.

Kikuchi's disease or histiocytic necrotising lymphadenitis is a distinct benign clinicopathologic entity which is to be distinguished from malignant conditions, especially lymphoma.We report a young woman with Kikuchi's disease presenting with cervical lymphadenopathy and mild hepatomegaly. CT and US findings are presented as well as a review of the pertinent literature.

Chronic intussusception in childhood.

A rare case of chronic intussusception is reported. Radiological investigation including ultrasound, CT and barium enema provided the correct diagnosis. Ultrasound revealed a solid mass near the transverse colon in the right lower abdomen. CT demonstrated the real nature of the solid mass as being the classical 'coiled spring' of intussusception. The barium enema was unsuccessful as an attempt at hydrostatic reduction, but confirmed the diagnosis by a 'crescent-shaped' filling defect in the ascending colon. The patient was discharged after an uneventful surgery and recovery. No organic lesion that precipitated the chronic intussusception was discovered at operation. Radiological findings, the typical clinical picture and adequate treatment are discussed.

Pulmonary plasma-cell granuloma.

A large pulmonary plasma-cell granuloma (PCG) mimicking a mediastinal germinal-cell tumor in a 9-year-old boy is presented. The nonspecificity of the tumoral calcifications and of the radiographic and CT findings in pulmonary PCG is demonstrated.

Thoracoabdominal peripheral primitive neuroectodermal tumors in childhood: radiological features.

Peripheral primitive neuroectodermal tumors (PNET) are extremely uncommon, malignant neoplasms affecting mostly children and young adults. We retrospectively reviewed the clinical data and radiological studies of four such cases. All cases were pathologically proven. Plain films, US, and CT scans were used. The youngest child had a huge pelvic tumor and two adolescents each had a chest wall (Askin) tumor. The fourth patient had a most unusual location of the PNET in the anterior mediastinum. The CT findings are emphasized. We emphasize that the markedly abnormal CT findings are not specific for PNET.