Bilateral thalamic lesions.

OBJECTIVE: Bilateral thalamic lesions are rare and relatively obscure neoplasms. We present our experience with nine cases of bilateral thalamic lesions and attempt to analyse them in the background of available literature. MATERIALS AND METHODS: Retrospective analyses of the case records of 9 cases of bilateral thalamic lesions treated in our department since January 2002, which have a minimum of 1 year follow-up. RESULTS: The study group included four males and five females with a mean age of 14.6 years (5 years to 29 years). Seven of these patients had radiological evidence of bilateral thalamic lesions at presentation and 2 patients had involvement of the opposite thalamus at a later stage of the disease. All patients except one presented with raised intracranial pressure symptoms. Focal motor deficits (4/9), behavioral and memory disturbances (3/9) were the other major presenting symptoms. Biopsy confirmation was possible in six patients and histopathology was suggestive of low grade fibrillary astrocytoma in all six patients. Seven patients required CSF diversion procedure for associated hydrocephalus. Eight of our nine patients underwent radiotherapy. On last follow-up, 3 patients were clinically stable with images suggestive of arrested disease, four patients had evidence of progressive disease both clinically and radiologically and there were two recorded cases of mortality. CONCLUSION: Primary bilateral thalamic lesions have characteristic neuroradiological properties and are distinct from unilateral thalamic tumours with bilateral progression. Almost all of these lesions on histology prove to be gliomas but decompressive surgery is seldom feasible. Surgical intervention is limited to biopsy and CSF diversion for hydrocephalus. Bilateral thalamic lesions remain unresponsive to adjuvant therapy and generally carry a poor prognosis.

Childhood and adolescent meningiomas: a report of 38 cases and review of literature.

BACKGROUND: The aim is to study the clinical, radiological and pathological features of childhood and adolescent meningiomas and analyse outcome prognosticators. METHOD: A retrospective analysis of the case records of patients less than 20 years of age operated for a meningioma in our institute since 1982 was performed. The variables analysed included age, sex, presentation, associated neurofibromatosis (NF), imaging characteristics, extent of resection and histopathology. RESULTS: The study group included 20 males and 18 females with a mean age of 15.53 years. Eleven children (28.9%) had evidence of NF of whom three had NF2 with bilateral vestibular schwannomas. The common presenting symptoms were seizures (76.3%), raised intracranial tension (71%), and focal neurological deficits (39.4%). The location of the operated tumours were as follows: ten skull base (24.4%), ten falx/parasagittal (24.4%), eight spinal (19.5%), five convexity (12.2%), three posterior fossa (7.3%), three intraventricular (7.3%) and two optic nerve sheath (4.9%). Two children (4.9%) had cystic meningiomas. Grade I excision was achieved only in twenty tumours (48.8%). On histopathology, thirty (73.2%) were grade I, nine (21.9%) were grade II and two (4.9%) were grade III meningiomas. Seven tumours recurred of which six were located at the skull base. During the mean follow up period of 4.74 years, the majority, 32 (84.2%) had a good outcome and five (13.2%) had a poor outcome. One child (2.6%) expired due to post-operative sepsis. CONCLUSION: Childhood meningiomas are uncommon but not rare lesions with a marginal male predominance. Absence of large series with long follow up precludes any definite conclusions on the clinical course and outcome. Uniform observations made in different series including ours, include a higher incidence of the skull base location and tumours with atypical histopathology. Favourable prognostic factors include younger age (< than 10 years), superficial location, total excision and absence of neurofibromatosis. Location and extent of excision appear to be more important than histopathology grade in predicting outcome.

Intracranial intradural aneurysmal bone cyst: a unique case.

Aneurysmal bone cyst (ABC) of the skull is exceedingly rare. We report a unique case of an intradural ABC without bone involvement presenting with raised intracranial pressure. The patient was a 14-year-old boy who presented with headache, vomiting and right focal seizure. Imaging showed a large multicystic left frontal lesion without any evidence of bone involvement. The lesion adherent to an intact sphenoid wing dura was completely excised. The histopathology report was consistent with an ABC. This case represents the first report of an ABC without involvement of the skull bones or any evidence of dural erosion. The possible mechanism of origin at this unusual location is hypothesized.

Endocrine factors in common epithelial ovarian cancer.

PIP: Ovarian cancer is responsible for 4% of all cancers in females and 6% of all their cancer deaths. Its mortality rate is greater than that of cervical and endometrial cancer together. The concentration of estrogen receptors (ER) rises and progesterone receptors (PR) falls in malignant ovarian tumors. In fact, ER and PR at present in 61% and 49% of malignant ovarian tumors respectively. 36% of these tumors contain both ER and PR. Further 69-90% of such tumors contain androgen receptors (AR). After (anti)hormonal agent therapy fails, physicians use progestins in combination with the synthetic antiestrogen tamoxifen in progressive or recurrent advanced ovarian cancer. The response rate for this treatment of ovarian cancer is only around 15%. Patients with malignant ovarian tumors with PR levels =or+ 50 fmol/mg tend to have a better prognosis than those with PR levels 50 fmol/mg. Neither age, stage of disease, nor tumor histology affect the prognostic value of PR. In vitro studies demonstrate that pure antiandrogens significantly inhibit about 60% of ovarian tumors. Another study also demonstrates that antiandrogen therapy alone may an effective endocrine therapy. As a result, the Gynecologic Cancer Cooperative Group of the European Organization for Research and Treatment of Cancer if conducting a clinical trial on the effect of the antiandrogen flutamide on advanced or recurrent ovarian cancer. Researchers plan to investigate the effect of combining endocrine therapy with current standard chemotherapy. In fact, they intend to learn if combined chemo-endocrine therapy should be used as 1st line treatment for ovarian cancer.^ieng

Dissecting intracranial aneurysms presenting as subarachnoid haemorrhage: report of two cases and review of literature.

Subarachnoid haemorrhage due to intracranial non-traumatic dissecting aneurysms is rare. Most of the published reports refer to dissecting aneurysms in the vertebrobasilar territory. Anterior circulation dissecting aneurysms are rare and their pathogenesis, clinical features, angiographic findings and management are a matter of debate. Management of patients with intracranial arterial dissection is unclear. Unlike the well-established proximal occlusion and trapping approaches to vertebral artery dissections, choices of interventions for anterior circulation and basilar dissecting aneurysms are limited, and most reports have been limited to wrapping techniques for arterial wall reinforcement. The role of anticoagulation therapy in the presence of subarachnoid haemorrhage is also a matter of debate. As no clear-cut guidelines are available, treatment should be tailored to the individual patient. We describe two cases of intracranial dissecting aneurysms, which presented as subarachnoid haemorrhage (SAH) and discuss the management issues.

Composition and larvicidal activity of leaves and stem essential oils of Chloroxylon swietenia DC against Aedes aegypti and Anopheles stephensi.

The laboratory bioassay of the essential oil and the isolated compounds from Chloroxylon swietenia against Aedes aegypti and Anopheles stephensi was carried out to evaluate the larvicidal activity. LC50 value estimated for A. aegypti and An. stephensi were 16.5 and 14.9 microg/ml and 20.2 and 19 microg/ml for leaf and stem oils, respectively. The three sesquiterpenes pregeijerene, geijerene and germacrene D were isolated and their Larvicidal activity was evaluated. Pregeijerene and geijerene were observed for the first time in the volatile constituents of C. swietenia, however, leaves contained higher amount of geijerene compared to stems.

Sex steroids and pulsatile luteinizing hormone release in men. Studies in estrogen-treated agonadal subjects and eugonadal subjects treated with a novel nonsteroidal antiandrogen.

This study evaluated the effects of estrogens and androgens on LH pulse frequency and amplitude in male subjects. To assess the role of estrogens we compared the serum LH pulse frequency and amplitude between 3 groups: 8 agonadal subjects receiving no steroid treatment; 6 agonadal subjects continuously treated with 50 micrograms ethinylestradiol/day; and 17 eugonadal men. Mean serum LH levels and LH pulse amplitude were significantly lower in the agonadal subjects receiving estrogens (14.8 +/- 5.4 (SD) U/L and 4.1 +/- 1.5 U/L, respectively) than in the group of agonadal subjects not receiving sex steroid treatment (35.7 +/- 8.4 U/L and 7.3 +/- 2.0 U/L, respectively). The mean LH pulse frequency was 7.1 +/- 1.5/7 h in the group not receiving sex steroid treatment and 6.0 +/- 1.4/7 h in the group receiving estrogens (P NS). The LH pulse frequency in the eugonadal men (3.8 +/- 1.3/7 h) was significantly lower than the frequency in both groups of agonadal subjects. The LH pulse amplitude was of the same magnitude in the estrogen-treated agonadal subjects and in eugonadal men (4.1 +/- 1.5 U/L and 3.5 +/- 1.2 U/L, respectively). The role of androgens was studied in 15 eugonadal male subjects (who presented for female role reassignment) by determining the effects of a novel nonsteroidal androgen receptor blocker, Anandron, on basal and LH-releasing hormone (LHRH)-stimulated serum LH/FSH levels; LH pulse frequency and amplitude; sex steroid and sex hormone-binding globulin levels; and serum PRL levels during an 8-week period. Basal and LHRH-stimulated LH levels and testosterone rose progressively during the first 6 weeks and reached a plateau thereafter, while estradiol levels continued to increase somewhat. The LH pulse amplitude and frequency had increased after 6 weeks (3.1 +/- 0.6 vs. 4.5 +/- 1.2 U/L and 4.4 +/- 2.4 vs. 6.6 +/- 1.1 pulses/7 h, respectively). Basal FSH levels were not affected while LHRH-stimulated FSH levels progressively decreased from 2 to 6 weeks, after which they did not change. Along with the rise of estradiol levels an increase of sex hormone-binding globulin and PRL levels occurred.(ABSTRACT TRUNCATED AT 400 WORDS)

The metastatic potential of rat prostate tumor variant R3327-MatLyLu is correlated with an increased activity of N-acetylglucosaminyl transferase III and V.

Enzyme activities of N-acetylglucosaminyltransferase (GlcNAc-Tase) I-V involved in N-linked complex-type carbohydrate synthesis were determined in a non-metastatic hormone-dependent rat prostate tumor (R3327-H) and a related, hormone-independent variant metastasizing to lymph nodes and lungs (R3327-MatLyLu). In the metastasizing variant a significantly increased activity of both GlcNAc-Tase III and GlcNAc-Tase V was observed, whereas the activities of GlcNAc-Tase I and II were essentially unchanged. The increase in activity of GlcNAc-Tase III is particularly noteworthy since it indicates that elevated expression of this enzyme cannot be considered as an exclusive marker of hepatic malignancy.

Pregnancy-related primary brain and spinal tumors.

We reviewed the literature concerning primary brain and spinal tumors with first manifestation or acceleration of symptoms during pregnancy or within the first postpartum week and encountered four new cases in our center. The incidence of brain tumors that become symptomatic during pregnancy appears to be decreased compared with that in age-matched women. The relative frequency of the different primary brain tumor types is not changed by pregnancy. The number of meningiomas gradually tends to increase during pregnancy, with gliomas and spinal vascular tumors accumulating in the first and third trimesters, respectively. Postpartum amelioration of symptoms has especially been described for meningiomas and spinal vascular tumors. We conclude that different types of tumors are influenced at different stages of pregnancy. Although progesterone receptors predominate compared with estrogen receptors, no definite causal relationship with progesterone has been established.

Phase II trial of flutamide in advanced ovarian cancer: an EORTC Gynaecological Cancer Cooperative Group study.

New active non-toxic therapeutic regimens are warranted in ovarian cancer relapsing after platinum-based chemotherapy. Some investigators have determined that androgen receptors predominated over oestrogen and progesterone receptors in untreated common epithelial ovarian cancer tissue cytosols. In an effort to test its antitumoural activity, 68 pretreated patients with epithelial ovarian cancer were given flutamide 750 mg/day orally for at least 2 months. Of 32 patients who received a minimum of 2 months of therapy, pretreated with at least one platinum-based chemotherapy, and a median of two chemotherapy regimens, two (6.3%) objective responses (one complete and one partial) and nine (28%) disease stabilisations were observed; these lasted 44 and 72 weeks, respectively (for the complete and partial response), and for a median of 24 weeks for stabilisations (range 12-48+). Nausea and vomiting were the most frequent side-effects. These occurred in 19/55 (34.5%) patients evaluable for toxicity. Flutamide has to be considered ineffective in patients extensively pretreated with chemotherapy, and it is not devoid of side-effects.

Radiation sensitivity of Copenhagen rat prostatic carcinoma (R3327-AT and R3327-MATLyLu).

The radiosensitivity of two variants of the Dunning Copenhagen rat prostatic tumor R3327 was investigated. The R3327-AT variant, which is a poorly differentiated anaplastic, fast-growing tumor, was irradiated both in vivo and in vitro. Following irradiation, monodispersed cells were plated in vitro and colonies were counted after 7 days. The survival curve of R3327-AT cells irradiated in vivo showed an initial shoulder (Dq-value 0.97 Gy), followed by two exponential parts. The D0-value for the first part of the curve (0-10 Gy) was 2.76 Gy and for the second part of the curve (greater than 10 gy) 9.05 Gy. Extrapolation of the second part of the curve to the Y-axis indicated that the proportion of more radioresistant cells was about 10%. The survival curve for R3327-AT cells irradiated in vitro also suggested the presence of a radioresistant subpopulation, although the proportion was lower (about 3%). This difference might be due to the presence of an hypoxic fraction in the tumors irradiated in vivo, but not in vitro. Tumor cells from the R3327 tumor variant metastatic to lymph nodes and lungs (R3327-MATLyLu), were irradiated in vitro. The radiation effect was evaluated by in vitro colony formation in agar and by in vivo lung colony assay. The colony formation in agar yielded a D0-value of 1.09 Gy. No radioresistant subpopulation was identified in this variant. A similar radiosensitivity was observed by the in vivo lung colony assay (D0 1.39 Gy). The mean inactivation dose calculated for R3327-AT cells (3.45 Gy) was significantly higher than for the metastatic variant (2.00 Gy).

Response to inhibition of androgen action of human ovarian cancer cells in vitro.

The effect of androgens, anti-androgens and epostane on the proliferation of three established human ovarian cancer cell lines was investigated. In one cell line, containing androgen receptors, a dose-dependent inhibitory effect of anti-androgens and epostane was observed. Adaptation of this cell line to flutamide resulted in decreased sensitivity to anti-androgens and epostane. Following adaptation of the cell lines to androgen, androgen receptors were present in all of them and an increased sensitivity to higher concentrations of anti-androgens and epostane was observed. These results suggest that androgens may play a role in the proliferation of ovarian cancer cells, and that these cells may respond to blockage of androgen action or synthesis.

Ovarian cancer: radiation sensitivity in vitro.

The radiosensitivity of four human ovarian cancer cell lines was investigated in vitro by a clonogenic assay and analyzed using the linear-quadratic model. Two cell lines were found to be highly radiosensitive (mean inactivation dose (D) 0.82-0.92 Gy; surviving fraction 2 Gy (SF2) less than or equal to 0.13). Two other cell lines were less sensitive to radiation (D 1.31-1.94 Gy; SF2 0.22-0.38). Although the use of external radiotherapy in ovarian cancer has been limited due to the pattern of metastatic spread of this cancer, the present data support the view that ovarian carcinomas are radiosensitive tumors. Investigations on the effects of new approaches, such as delivering radiation more specifically to intraperitoneal ovarian cancer cells, are warranted.

Estrogen positive feedback on LH secretion in transsexuality.

In order to test the hypothesis whether there is variation in hormonal levels or response to hormonal manipulation that could permit a distinction between heterosexuals and transsexuals, we designed the following protocol: Six male-to-female (m-to-f) transsexuals, six heterosexual control females and six female-to-male (f-to-m) transsexuals were given estradiol benzoate (E2B) (4.5 micrograms/kg/12 hr) for five days. In the female population, E2B treatment was initiated on day 5 of the menstrual cycle. In all the subjects blood luteinizing hormone (LH) and follicle stimulating hormone (FSH), estradiol-17 beta (E2) and testosterone (T) levels were measured twice daily. Additionally, LH and FSH responses to LHRH (100 micrograms iv) stimulation prior to and on day 5 of the E2B treatment were evaluated. In the m-to-f transsexuals, T levels decreased sharply and progressively during estrogen treatment, along with a fall in LH and FSH levels. The magnitude of the LH and FSH responses to LHRH stimulation also decreased following estrogen administration. In the heterosexual female controls and in the f-to-m transsexuals, estrogen administration increased LH levels to a minimum of 100% above initial values from day 3 onwards. Interestingly, the magnitude of the LH increase in the f-to-m transsexuals was greater than that of the heterosexual female controls. In both groups, LHRH stimulation resulted in a greater LH response compared to that prior to estrogen treatment. Our present observations, based on blood hormonal levels and responses to hormonal manipulations do not permit a distinction between heterosexual females and f-to-m transsexuals. There was no convincing evidence for the existence of a positive estrogen feedback on LH secretion in m-to-f transsexuals. These results contradict some of the reported hypotheses concerning hormonal alterations in these individuals.

An immunohistochemical evaluation of androgen and progesterone receptors in ovarian tumors.

To visualize the heterogeneity of androgen receptor (AR) and progesterone receptor (PR) expression in ovarian tumors, 61 specimens were studied immunohistochemically using specific mouse monoclonal antibodies. The tested ovarian tumors included ovarian carcinomas of serous, mucinous, endometrioid, undifferentiated, and clear cell types as well as borderline epithelial tumors, mucinous cystadenomas, granulosa cell tumors, metastatic ovarian tumors, and one case of immature teratoma. Sixty-seven percent of ovarian carcinomas expressed AR, while 46% of the ovarian carcinomas expressed PR. In addition, the three tested borderline epithelial tumors were AR positive. Androgen receptor and PR were primarily localized in the nuclei of ovarian tumor cells. In three tumors focal staining of intervening stroma cells was observed. Interestingly, 35 of the granulosa cell tumors expressed PR as well as AR. All tumor types displayed a wide range in their proportions of AR- and PR-positive tumor cells. A poor correlation, however, was observed when semiquantitative immunohistochemical AR staining results on 17 ovarian carcinomas were compared with biochemical cytosol AR estimations using the dextran-coated charcoal method. Our study indicates that AR as well as PR is expressed by a substantial proportion of ovarian borderline and malignant tumors and that there is a strong heterogeneity in expression of AR and PR. It is possible to evaluate the prognostic significance of these receptors in ovarian cancers on fresh-frozen tumor specimens using a simple immunohistochemical technique.

Consideration of the use of 17 beta-N,N-diethylcarbamoyl-4-methyl-4-aza-5- alpha-androstan-3-one (4MA), a 5 alpha-reductase inhibitor, in prostate cancer therapy.

We investigated the effect of 17 beta-N,N-diethylcarbamoyl-4-methyl-4aza- 5 alpha-androstan-3-one (4MA), a 5 alpha-reductase inhibitor, on growth inhibition of androgen-sensitive rat prostatic tumour (R3327-H) and correlated it with changes in weight of normal androgen target tissues and with levels of androgens. Groups of male Copenhagen rats were treated for 28 days with a daily injection of various, increasing doses of 4MA (0.01-4.0 mg/day) and the results were compared with control (vehicle-treated) and with castrated animals. 4MA decreased tumour growth rate in a dose-dependent manner, which was reflected in a decreased incorporation of BrdUrd in DNA of glandular epithelial cells in the tumour. Normal prostate wet weight was also decreased after high-dose 4MA treatment while serum testosterone levels were not affected by 4MA treatment. Contrary to expectations, however, tissue levels of dihydrotestosterone in tumour and ventral prostate were still considerable in 4MA-treated animals. The tumour-inhibiting action of 4MA, therefore, has to be interpreted as not being purely due to 5 alpha-reductase inhibition. On the other hand, it was not possible to demonstrate any direct tumoricidal effect of 4MA in vitro. The relevance of these findings in terms of the endocrine mechanism of action of 4MA on tumour growth is discussed.

Nerve growth factor stimulates in vitro invasive capacity of DU145 human prostatic cancer cells.

The prevalence of nerve growth factor (NGF) production in different human prostatic tumor cell lines (DU145, PC-3, LNCaP-FGC) was investigated using a specific enzyme-linked immunosorbent assay (ELISA) and compared to that of different human and rat prostatic tissue samples. In addition, the biological effects of NGF beta addition to the human prostatic cancer cell cultures were investigated. The ELISA technique showed the DU145 cell line to secrete measurable levels of NGF in the culture medium. When neurite-outgrowth determination in a pheochromocytoma cell line was used as a bioassay, the NGF synthesized by DU145 cells was confirmed to exhibit functional biological activity. No effect of exogenously added NGF could be established on tumor cell proliferation, on the basis of either colorimetric tetrazolium-based staining assay or bromodeoxyuridine incorporation. Also the expression of prostate specific acid phosphatase was not influenced by NGF addition. However, the in vitro invasive capacity (Matrigel) of DU145 cells was significantly increased by inclusion of 50 ng or 100 ng NGF beta/ml culture medium. In view of the clinically well-known perineural invasion of prostate cancer cells, the possible involvement of NGF as a (paracrine) factor in prostatic cancer metastatic behavior should be investigated further.

Isolation and characterization of an estrogen binding protein which may integrate the plethora of estrogenic actions in non-reproductive organs.

A putative estrogen receptor (pER) from mouse liver has been characterized. The heterodimer protein (81-84 kDa) consists of two covalently bound subunits (61-67 and 17-27 kDa) with following characteristics: sedimentation constant--4.9 S; IP--4.8; dissociation constant (Kd) for estradiol-17beta binding--0.7 nmol; binding sites--0.746 pmol/mg protein; relative binding affinity--estradiol-17beta--100, estrone--80 and estriol--30; specificity--does not bind, other natural steroids, synthetic estrogens, antiestrogens and bioflavonoids. Importantly, immunosuppressants, neuroleptic and carcinogens influence 3H-estradiol-17beta binding to pER. Interestingly, pER is a serine phosphatase and this may have relevancy to estrogen action in Alzheimer's disease. The polyclonal anti-pER antibody does not react with estrogen receptors (ER). ER antibody does not react with pER. Remarkably, anti-pER antibody reacts with calcineurin, a brain phosphatase and anti-calcineurin antibody reacts with pER. Immunohistochemical analyses showed that pER is undetectable in reproductive organs (except ovary). It is localized on the plasma or the nuclear membranes in some, in cytoplasm and/or nucleus in other cells of non-reproductive organs (skeletal, neural, vascular, hair and retina), and in tumors (mammary, endometrial and prostate cancers, and prostatic hyperplasia). The information presented justifies the proposition that pER may mediate the estrogenic actions in non-reproductive organs.

Progesterone receptor in cystosarcoma phyllodes.

A specific receptor for progesterone has been found in a cystosarcoma phyllodes, as determined by charcoal adsorption and sucrose gradient analysis. Similar assays for estrogen receptors were negative. The tumor consisted almost entirely of stroma that contained the progesterone receptors. The epidemiology and natural history of cystosarcoma do not strongly support the hypothesis that it is controlled by female sex hormones, but the presence of the progesterone receptors suggests that some cystosarcomas are hormonally regulated, and thus may be responsive to therapeutic hormonal manipulation.

Lack of pharmacokinetic interaction between sumatriptan and naproxen.

Sumatriptan is a 5HT1D agonist used in the treatment of migraine. Nonsteroidal anti-inflammatory drugs, beta-blockers, and calcium channel-blocking antagonists are used in the prophylaxis of migraine. Hence, there is a need to investigate the interaction of these prophylactic drugs with sumatriptan. The interaction of sumatriptan with propranolol, flunarizine, pizotifen, and butorphanol were reported earlier. Naproxen is shown to be effective in prophylactic treatment of migraine. In this study, the authors have investigated the circadian rhythm effect of naproxen on the pharmacokinetics of sumatriptan at 1000 and 2200 hours. Twelve healthy volunteers were treated with 100 mg sumatriptan succinate either alone or along with 500 mg naproxen orally at either 1000 or 2200 hours in a randomized Latin square design with a washout period of 10 days. Serum samples were collected at predetermined time intervals and analyzed for unchanged sumatriptan by high-performance liquid chromatography. The pharmacokinetic parameters were calculated by using model-independent methods. Naproxen had no statistically significant (p > 0.05) effect on any pharmacokinetic parameters of sumatriptan both at 1000 and 2200 hours treatment. The results of this study suggest that no alteration in the sumatriptan dosage will be necessary for migraine patients taking naproxen prophylactic therapy.