Thomas-Marc Markwalder

Dependency of Blood Flow Velocity in the Middle Cerebral Artery on End-Tidal Carbon Dioxide Partial Pressure—A Transcranial Ultrasound Doppler Study:

The end-tidal carbon dioxide partial pressure (PCO2) response curves for the flow velocity in the middle cerebral artery were studied in 31 normal subjects with transcranial Doppler techniques. An exponential curve with an exponent of 0.034 mm Hg−1 was found to be a good fit to the recorded data. By means of this relationship, recordings of flow velocity in cerebral arteries can be normalized to a standard value of PCO2. Physiological aspects of cerebrovascular reactivity to PCO2 and the clinical implications of the PCO2 response curve are discussed. The normal material provides a reference for assessing pathological responses.

Endocrine Manipulation of Meningiomas with Medroxyprogesterone Acetate

Intracranial meningiomas from patients treated with medroxyprogesterone acetate as well as from untreated patients were studied in monolayer tissue culture with trials of in vitro hormonal modulation with medroxyprogesterone acetate. The following conclusions were drawn from investigations which comprise 37 cell culture assays: (a) tissue cultures of meningiomas inherit the disadvantages of loss of the progesterone receptor and frequent transformation to cells resembling fibroblasts after three to four passages. For these reasons, drug testing as well as the establishment of cell cultures that exhibit the characteristics of meningioma are impeded; (b) the progesterone receptor-content of the solid tumors does not reflect the response to medroxyprogesterone acetate-therapy in vitro; (c) medroxyprogesterone acetate-pretreated meningiomas showed sufficient in vitro growth in 38%, and untreated meningiomas grew well in 56% of the cases; (d) medroxyprogesterone acetate-induced inhibition or delay of growth was observed in 35%. These findings have resulted in criticism with respect to the value of meningioma tissue cultures for trials of hormonal manipulation and it is thought that another method, which consists of immunostaining of cycling cells, and has been tested in another study, may be superior to cell culture assays with respect to evaluation of the effect of hormonotherapy in meningiomas. Medroxyprogesterone acetate holds an interesting position because it reduces cell growth in some meningiomas in vitro.

Estrogen and progestin receptors in meningiomas: clinicopathological correlations.

Estradiol and progesterone receptors were studied in 44 patients with meningiomas and correlated to the clinicopathological features and amount of preoperative corticosteroid therapy. Thirty-four (77%) of the meningiomas contained high tilers of specific high-affinity cytosol [3H]promegestone (R 5020) binding sites (mean 2,902 fmol/g tumor; range 0–9,598 fmol/g tumor) whereas only minuscule amounts of a nonspecific cytoplasmic [3H]estradiol binding component (mean 48 fmol/g tumor; range 0–201 fmol/g tumor) were detectable. No nuclear binding activity for [3H]estradiol was demonstrable. There was no convincing correlation between high PR activity and the age, sex, or menopausal status of the patients. The correlation study between the amount of preoperative corticosteroid therapy with the amount of [3H]promegestone binding revealed no dose relationship. Correlating [3H]promegestone content with the histologic type, we found 96% of meningothelial, 71% of transitional, and 40% of fibroplastic; meningiomas to contain progesterone receptors. The necessity of in vitro studies is stressed to assess the biosynthesis and biological activity of the progesterone receptor in meningiomas, which is apparently not estrogen regulated, as is the case in other estrogen target tissues.

Biological expression of steroid hormone receptors in primary meningioma cells in monolayer culture.

Primary meningiomas have been grown in monolayer culture and tested for the presence of steroid hormone receptors and sensitivity to various steroids and steroid antagonists. None of the 10 solid tumors or the primary cultures derived from them contained estrogen receptors, either in the cytoplasm or in the nucleus. Progesterone receptors were present in 50–70% of the solid tumors and some of the primary cultures. Four of four and five of five primary cultures contained, respectively, androgen and glucocorticoid receptors. When one of the primary cultures was tested for growth sensitivity to estrogen, tamoxifen, progesterone, hydrocortisone, and dihydrotestosterone, the last two had noticeable stimulatory effects on growth by day 5. Interestingly, only androgen and glucocorticoid receptors were present in the primary tumor cells in culture, suggesting that these receptors mediated the effects of their respective hormones on growth.

Hormonotherapy of meningiomas with medroxyprogesterone acetate: Immunohistochemical demonstration of the effect of medroxyprogesterone acetate on growth fractions of meningioma cells using the monoclonal antibody Ki-67

The effect of medroxyprogesterone acetate (MPA) on growth fractions of ex vivo meningiomas is demonstrated in using the Ki-67 monoclonal antibody in three cases of meningiomas operated on in two stages and in meningioma specimens from a group of eight patients operated on in one single stage after MPA therapy. Growth fractions in samples from five meningioma patients not treated with MPA were determined for comparison. In the three cases of two-stage operation of the tumors, the percentage of Ki-67-positive cells in meningioma tissue was lower by a factor of 6, 5, and 3, respectively, after MPA therapy. In meningioma specimens from patients receiving no MPA therapy, Ki-67-positive cells were present in 1.02 +/- 0.48%; in samples from MPA-treated tumors the percentage of Ki-67-positive cells was 0.41 +/- 0.40 (different at p less than 0.02 [Wilcoxons test]). In comparison to our previously published data on untreated meningiomas analyzed for progesterone receptors (PR), MPA significantly reduced the PR activity. There was no obvious correlation between PR activity and potential suppression of the tumor growth fraction. It is concluded that MPA is attractive because it reduces the growth fractions of most meningiomas and might be suitable for adjuvant hormonotherapy.

Endocrine manipulation of meningiomas with medroxyprogesterone acetate: effect of MPA on receptor status of meningioma cytosols

Fifteen patients with intracranial or spinal meningiomas have been treated with the semisynthetic progestational agent medroxyprogesterone acetate (MPA, Depo-Provera) prior to surgical removal of the tumors in order to investigate the influence of MPA on the progesterone receptor (PR) status of meningioma cytosols. MPA acted as a competitive binder to meningioma-PR: The mean PR values were 15.6 fmol/mg protein (range 0-69) and 338.3 fmol/g tumor (range 0-1190), respectively. In comparison, mean PR values of our untreated meningioma series (n = 58) were 54.9 fmol/mg protein (range 0-586) and 2813 fmol/g tumor (range 0-17,168), respectively. In cases of two-stage resection of meningiomas MPA significantly decreased PR activity in the cytoplasm of meningioma cells. We conclude that MPA binds to meningioma PRs, however, its effect on the growth rate of meningiomas has still to be elucidated.

Bryan cervical disc prostheses: preservation of function over time

Preserving the function of cervical disc prostheses, even over the short term, is a matter of concern among surgeons. Our case series highlights our results and protocol for increasing the probability of continued device function. Twenty-five consecutive patients with a mean (+/-SEM) age of 44.3+/-8.3 years underwent 29 cervical total disc arthroplasties for disc herniations. Three patients underwent primary bilevel arthroplasty, and one patient underwent a second arthroplasty for another herniation 2 years after the first. Prosthesis ranges of motion were measured using dynamic plain X-ray studies and compared to the ranges of motion of adjacent segments. At follow-up, all prostheses were in the correct location and without subsidence. All displayed firm secondary stability. One segment had fused. Twenty-eight of 29 devices were mobile an average of 9.5 degrees +/-4.7 degrees (range 3 degrees to 20 degrees ) (for all 29 devices the average movement angle was 9.2 degrees +/-5 degrees ; range 0 degrees to 20 degrees ), 25 upper adjacent segments were mobile an average of 10.9 degrees +/-4.5 degrees (range 2 degrees to 20 degrees ) (excluding the fused prosthesis: 11 degrees +/-4.6 degrees ) and 15 lower adjacent segments were mobile an average of 9.8 degrees +/-6 degrees (range 1 degrees to 21 degrees ). With our protocol, 28 of 29 cervical disc prostheses in 25 consecutive patients were mobile after an average of 22.3+/-9.4 months. Prosthesis motion was physiological and very similar to that of the healthy adjacent segments. Long-term studies including larger numbers of patients are required to validate our initial observations.

Isthmic spondylolisthesis : an analysis of the clinical and radiological presentation in relation to intraoperative findings and surgical results in 72 consecutive cases

Summary72 patients with isthmic Spondylolisthesis have been analyzed prospectively with respect to their clinical presentation, radiological and intraoperative findings, operative techniques and surgical results.Excellent, good and satisfactory results have been obtained in 59 (82%), 10 (14%) and 3 patients (4%), respectively, by use of microsurgical techniques in combination with Louis-plate-fixation in Grade I and double arthrodesis/Cotrel-Dubousset-instrumentation in Grade II Spondylolisthesis.

Estrogen and progestin receptors in acoustic and spinal neurilemmomas.: Clinicopathologic correlations

Estradiol and progestin receptors were studied in 20 patients with neuraxial Schwann cell tumors, and their presence was correlated to the clinicopathologic features and the amount of preoperative corticosteroid therapy. Based on an arbitrary cutoff value of 200 fmol per gram of tumor as indicative of a positive receptor value in breast cancer, 4 and 13 of the neurilemmoma tissue samples could be considered as positive for estrogen and progesterone receptors, respectively. Whereas there was no convincing correlation between the estrogen and progestin receptor activity and the age, sex, or menopausal status of the patients, overweight patients had significantly higher estrogen and progestin binding values. The correlation between the amount of preoperative prednisone therapy and the amount of [3H]estradiol and [3H]promegestone binding revealed no dose relationship. Correlating [3H]estradiol and [3H]promegestone content with the histologic type of the schwannomas (Antoni types A and B, respectively), we were not able to draw conclusions, because of the predominance of Antoni type A over Antoni type B tissues in our material. The necessity of nuclear receptor assays, ligand specificity testing, and in vitro studies is stressed as a prerequisite for answering the questions whether neurilemmomas contain genuine sexual steroid hormone receptors and whether these receptors are regulated via an estrogen-estrogen-receptor system as is the case in classical sexual steroid hormone target tissues.

Intradural extramedullary arachnoid cyst of the thoracic spine associated with cord compression

In this report, a 55-year-old Caucasian women with an arachnoid cyst of the thoracic spine is presented. This cyst remained undiagnosed because of the nonspecific nature of her symptoms over approximately three months. Only when she started to complain of ataxia, a posterior fluid collection compressing the spinal cord was found in MRI. Even though preoperative diagnosis remained uncertain, this additional neurological dysfunction warranted surgical treatment. Surgery was successful with respect to in-toto removal of the intradural, extramedullary cyst, reversal of cord compression and symptoms. Histological diagnosis was of an arachnoid cyst.