Search

High-grade glioma is the most common brain tumor in adults, and the prognosis for patients diagnosed with this type of cancer is still poor. The biological behavior of the tumors is correlated to t ...

The width of the third ventricle, the length of the anterior commissure-posterior commissure line (AC-PC line), the spatial position of the midplane of the third ventricle, and the co-ordinates of the AC, the PC, and of 17 brain targets in the thalamus, hypothalamus and pallidum, were assessed on a pre-operative stereotactic computed-tomography (CT) study and compared to measurements on intra-operative air-ventriculography, using a non-invasive relocatable stereotactic frame. There were no significant differences in the length of the AC-PC line, in the position of the midsagittal plane of the third ventricle, or in the vertical or lateral co-ordinates of the AC, the PC and the cerebral targets, between measurements on CT and on air-ventriculography. However, the width of the third ventricle was significantly larger, and the spatial positions of both AC and PC were significantly more anterior on air-ventriculography than on the CT study. This anterior dislocation of the commissures was presumably due to the insufflation of air into the ventricles of patients being in the supine position during surgery.

The possibility of obtaining a selective effect on different trigeminal branches by glycerol rhizotomy was studied in the treatment of trigeminal neuralgia. Transcutaneous electrical stimulation was used to quantify sensory impairment. An attempt was made to direct the neurotoxic effect by maintaining the patient's head in different positions during and after glycerol injection. The amount of glycerol injected varied according to the estimated size of the trigeminal cistern and/or to which branch that was involved. The study demonstrated a good selective effect on the ophthalmic branch, less selective on the maxillary, and a poorly selective effect on the mandibular branch. However, the clinical result following glycerol rhizotomy was equal regardless of the affected trigeminal branch.

The health professional caring for the unconscious patient is inclined to assume that it will be pointless to attempt to communicate with him or her. There are however valid reasons to talk to the unconscious individual. On the one hand it is a sign of respect and proper care and concern towards both the patient and the family. On the other hand evidence exists in various forms that speech can affect physiological function even in the unconscious and that in some instances there is even a potential for cortical response. Although one cannot know to what extent an unconscious patient experiences the voice, it has been suggested that talking to the unconscious patient could favourably affect the recovery process.

The accuracy of estimating intracranial pressure in brain tissue (ICP BT ) via lumbar space was investigated using preset pressure levels in the interval 0 to 600 mm H 2 O in patients with communicating hydrocephalus. Lumbar space ICP correlated excellently to ICP BT , demonstrated by a measured mean difference of 10 mm H 2 O (0.75 mm Hg) and a regression coefficient of 0.98. The concurrence supports the lumbar puncture as an accurate technique to determine ICP in patients with communicating CSF systems.

Hemicraniectomy in patients with malignant middle cerebral artery (mMCA) infarct may be life-saving. The long-term prognosis is unknown.Patients with mMCA infarct treated with hemicraniectomy between 1998 and 2002 at three hospitals were included. The criterion for surgical intervention was if the patients deteriorated from awake to being responding to painful stimuli only. All patients were followed for at least 1 year. Outcome was defined as alive/dead, walkers/non-walkers or modified Rankin Scale (mRS) scoreor=2.Thirty patients were included (median age at stroke onset 49 years, range 17-67 years). Fourteen patients had mMCA infarct on the left side and 16 patients on the right side. Fourteen patients had pupil dilatation before surgery. Hemicraniectomy was performed at a median of 52 h (range 13-235 h) after stroke onset. Nine patients died within 1 month after surgery because of cerebral herniation (n = 6), myocardial infarction (n = 1) or intensive care complications (n = 2). No further deaths occurred during follow-up, which was at median 3.4 years after surgery. Status for the 21 survivors at the last follow-up was: mRS 2 or less (n = 6) and mRS 3-5 (n = 15). The oldest patient with mRS 2 or less was 53 years at stroke onset. Thirteen patients (43%) could walk without substantial aid.The long-term survival after mMCA infarction treated with hemicraniectomy seems to be favourable if the patient survives the acute phase. The outcome as measured with mRS may be better among younger patients.

The symptoms in idiopathic adult hydrocephalus syndrome (IAHS) are consistent with pathology involving the periventricular white matter, presumably reflecting ischaemia and CSF hydrodynamic disturbance.To investigate whether a change in intracranial pressure (ICP) can affect energy metabolism in deep white matter.A microdialysis catheter, a brain tissue oxygen tension probe, and an ICP transducer were inserted into the periventricular white matter 0-7 mm from the right frontal horn in 10 patients with IAHS. ICP and intracerebral Ptio2 were recorded continuously during lumbar CSF constant pressure infusion test. ICP was raised to pressure levels of 35 and 45 mm Hg for 10 minutes each, after which CSF drainage was undertaken. Microdialysis samples were collected every three minutes and analysed for glucose, lactate, pyruvate, and glutamate.When raising the ICP, a reversible drop in the extracellular concentrations of glucose, lactate, and pyruvate was found. Comparing the values during baseline to values at the highest pressure level, the fall in glucose, lactate, and pyruvate was significant (p0.05, Wilcoxon sign rank). There was no change in glutamate or the lactate to pyruvate ratio during ICP elevation. Ptio2 did not decrease during ICP elevation, but was significantly increased following CSF drainage.Raising intracranial pressure induces an immediate and reversible change in energy metabolism in periventricular white matter, without any sign of ischaemia. Theoretically, frequent ICP peaks (B waves) over a long period could eventually cause persisting axonal disturbance and subsequently the symptoms noted in IAHS.

Brain tumors, in general, display a multidrug-resistant phenotype. This study evaluated the immunohistochemical expression and distribution of P-glycoprotein (Pgp), multidrug resistance protein (MRP1), lung resistance protein (LRP) and O6 methylguanine-DNA methyltransferase (MGMT) in low- and high-grade astrocytoma, oligodendroglioma and in different subgroups of meningioma. The results revealed a marked heterogeneity in the expression and distribution among the analyzed tumors. In astrocytoma and oligodendroglioma, Pgp and MRP1 were observed in the capillary endothelium and in scattered tumor cells, whereas LRP occurred only in tumor cells. A pronounced expression of MGMT was found independent of the histopathological grade. An enhanced expression of MRP1 and LRP in astrocytoma and oligodendroglioma were more often evident in older patients (50 years). Survival analysis suggested a markedly decreased overall survival for patients suffering from low-grade glioma overexpressing Pgp. In meningioma, a heterogeneous expression of Pgp, MRP1, LRP and MGMT was seen with the most prominent staining localized to the capillary endothelium. Pgp was significantly more often overexpressed (p0.05) in transitional compared to meningothelial meningioma. The marked heterogeneity in the expression suggests that analysis of these factors can be of importance in the selection of individualized chemotherapy, regardless of tumor type.

The influence of radiotherapy on malignant glioma multidrug resistance to chemotherapy was evaluated because patients with glioma often are treated with a combination of radiotherapy and chemotherapy. Multidrug resistance gene (MDR1, mdr1a, and mdr1b) transcripts were found in human and rat glioma cell lines. P-Glycoprotein (Pgp) was immunohistochemically detected in glioma cell lines and in the rat brain vascular endothelial cell line (RBE4). A multidrug resistance pump efflux activity assay demonstrated increased calcein efflux of RBE4 endothelial cells, but not glioma cells, 2 h after irradiation and still increased 14 d after irradiation. The increased efflux was equally inhibited by verapamil with or without irradiation. In the rat intracranial glioma model (BT4C), Pgp was demonstrated in capillary endothelial cells of the tumor tissue and surrounding normal brain, but not in tumor cells. The expression of gene transcripts or Pgp was not affected by irradiation. The results indicate that long-lasting verapamil-resistant drug efflux mechanisms are activated in brain endothelial cells after irradiation. The results might explain the poor efficacy of chemotherapy following radiotherapy and contribute to consideration of new treatment strategies in the management of malignant glioma.

Estramustine phosphate (EMP) is an anti-microtubule agent that depolymerizes microtubules and also causes apoptosis of glioma cells. Both of these pharmacological actions have been previously studied within the same cytotoxic range of EMP concentrations. The purpose of this study was to investigate which of these two phenomena occurred before the other. A preliminary MTT assay was done to distinguish non-cytotoxic (0.005-0.1 microM) and cytotoxic (0.5-10 microM) of EMP for BT4C cells. To investigate apoptotic changes, transmission electron microscopy (TEM), DNA laddering, and in situ endo-labeling (TUNEL) method were employed. A chemotaxis assay was used to assess cell motility. Scanning electron microscopy and TEM immunocytochemistry with an anti-beta tubulin antibody were applied to detect morphological changes of the microtubules. Suppression of cell motility by cytotoxic doses of EMP (0.5-10 microM) group was attributed by the cyto-reductive effect, relating to apoptosis. At 0.01-0.1 microM (non-cytotoxic doses), EMP did not indue apoptosis. At these concentrations, TEM and immunohistochemistry revealed the formation of blebs on the tip of the pseudopodia that contained abnormally depolymerized microtubules, a finding that was not observed at a low temperature or during cell migration. Cell chemotaxis was significantly inhibited by cytostatic EMP doses (0.05 and 0.1 microM). Bleb formation of the pseudopodia might be evidence of the abnormal disassembly of microtubules by cytostatic EMP concentrations, prior to the induction of apoptosis. In glioma cells EMP probably initiates apoptosis by causing the depolymerization of microtubules. Inhibition of cell motility by cytostatic doses of EMP could be beneficial to support other therapies.

Estramustine is a chemotherapeutic drug, used in the treatment of prostatic carcinoma. In the prostate, it binds specifically to a 46 kDa glycoprotein called estramustine-binding protein (EMBP), which consists of three polypeptide components; C1, C2, and C3, each coded for by a specific gene. Expression of EMBP and binding of estramustine has also been detected in malignant glioma in both rats and humans. Elevated levels of this protein in astrocytoma have proved to correlate with poor prognosis. In the present work, expression of all three polypeptide components of EMBP was confirmed in an orthotopic rat glioma model with nested reverse transcriptase PCR and Western blot (molecular weights of 8, 10, and 12 kDa). Specific binding of estramustine with a Kd of 40 for male and 50 for female rats, and a total number of binding sites of 0.7 and 0.4 pmol/mg proteins for male and female rats respectively, was demonstrated with Scatchard plot analysis. These binding characteristics are similar to those of prostatic EMBP. Further studies to elucidate how EMBP expression affects the effect of estramustine treatment, and its putative prognostic value is of special clinical interest. The confirmation of BMBP expression in BT4C rat glioma demonstrates its suitability as a model system for such studies.

Forty patients with Parkinson's disease without mental deterioration who were scheduled for ventroposterolateral (VPL) pallidotomy were randomly selected for retrospective stereotactic magnetic resonance image (MRI) analysis. The preoperative MRI study was performed on a 1.0-T MRI machine with a three-dimensional gradient-echo sequence. The MRI analysis was focused on five consecutive 2 mm thick axial slices without gap and parallel to the intercommissural line, starting from the level of the foramen of Monro and continuing in a ventral direction. Lacunar cysts of varying sizes (4-424 mm3) were seen at least in one hemisphere of all patients. The cysts had a clear dominance in posteroventral regions of the lateral-most pallidal regions (GP) and posteroventral regions of the putamen (PUT). No statistical correlation was found between the number or volume of the cysts and the sex, age, or duration of illness of the patients. Patients with predominantly left-sided clinical symptoms had a concentration of the cysts in the left GP, whereas those with predominantly right-sided symptoms had cysts significantly larger and more frequent in the right than the left GP. The cysts did not seem to affect the clinical outcome of pallidotomy. The authors think striatopallidal cysts develop from dilated perivascular spaces of the lenticulostriate vessels in the posteroventral regions of the GP and PUT. They are not pathognomonic for PD, but they may play some role in lateralization of the clinical symptoms in this classically asymmetric condition.

✓ Estramustine, an estradiol-17β and nornitrogen mustard complex, is used in the treatment of advanced prostatic carcinoma. A specific estramustine binding protein (EMBP) is important for its cytotoxic action, and the presence of EMBP has previously been demonstrated in rat and human prostatic cancer tissue. Significant levels of EMBP were detected by radioimmunoassay in human brain-tumor tissue. The EMBP concentrations (expressed as ng/mg protein) in 16 astrocytomas (mean 2.6 ng/mg, range 0.5 to 6.2 ng/mg) and seven meningiomas (mean 5.1 ng/mg, range 0.3 to 9.3 ng/mg) were significantly higher than that found in four samples of epileptic brain (mean 0.7 ng/mg, range 0.5 to 1 ng/mg) and 18 samples of normal brain (mean 0.5 ng/mg, range 0.2 to 1.0 ng/mg). The uptake, metabolism, and antiproliferative effects of the prostatic anticancer agent estramustine have been previously demonstrated in cultured glioma cells. The presence of EMBP may suggest a selective binding and effectiveness in human brain-tumor tissue.

To examine the prevalence of diabetic retinopathy and its relation to certain risk factors (glycosylated hemoglobin, blood pressure, serum creatinine, proteinuria, smoking) in a population-based study on a specific age-group of patients with diabetes mellitus in the county of Umeå, Sweden.All diabetic patients aged 15-50 years living in the county of Umeå were invited to the study. A standard clinical and eye examination was performed, and seven-field stereoscopic photographs were taken of each eye. Blood and urine samples were collected. Univariate and multivariate statistical analyses were performed.Of the eligible 395 patients 285 (91%) participated in the study. 285 patients (79%) had diabetes mellitus type 1, 71 (20%) subjects had diabetes mellitus type 2, and 3 patients (1%) had secondary diabetes. In the statistical analysis performed on patients with type 1 diabetes mellitus, duration, presence of hypertension, systolic blood pressure, plasma glucose, glycosylated hemoglobin, serum creatinine, proteinuria and smoking all were significantly related to increasing degree of retinopathy when a univariate model was applied. However, when a multivariate analysis was performed only duration, proteinuria, glycosylated hemoglobin and male gender were statistically significantly associated with severeness of retinopathy.Increased duration of diabetes, inadequate metabolic control as measured by glycosylated hemoglobin, proteinuria and male gender are factors that are associated with a higher incidence of diabetic retinopathy in diabetes mellitus type 1.

As health care resources are held to be insufficient to permit free choice of available treatment options, prioritizing is necessary. A precondition of careful prioritizing is comprehensive knowledge of the consequences, both for the patient and the community, of adopting each of the available options in a given case. A tool used in setting priorities is cost-benefit analysis, based on the utilitarian principle of health maximisation. However, it is evident from findings in recent studies that equity is widely considered a factor which ought to be included in the analysis. The article presents a method for correcting the variable, quality-adjusted life years (QALY), by introducing an equity factor, yielding a new variable, equity-adjusted QALY (EQALY). Use of the method is illustrated by comparison of the cost-effectiveness of two procedures, hip replacement and the treatment of malignant glioma, and showing how priority ranking of the two procedures is reversed if the EQALY variable is used instead of QALY.

The chemoprotective effect of amifostine (WR2721) was studied in a BDIX rat model with intracerebral BT4C glioma implants. Twenty-one rats were given cisplatin 5 mg/kg i.p., 21 were given amifostine 200 mg/kg i.p. + cisplatin 5 mg/kg i.p. Ten rats served as untreated controls. An immunohistochemical method for analysis of cisplatin-DNA adducts was used to elucidate the adduct formation in tumor, normal brain and kidney. Tumor volume and serum creatinine level were analysed 10 days after treatment. In animals pretreated with amifostine there was a delayed adduct formation rate in the normal brain, and in the kidney cortex the number of tubular cells with extremely high adduct level was reduced. No difference in adduct formation was seen in tumors. Tumor volume was significantly larger following amifostine + cisplatin (66% of controls) compared to cisplatin alone (38% of controls). Weight loss was, however, severe in rats given cisplatin alone. In the tumor growth study only 3 out of 11 rats treated with cisplatin 5 mg/kg alone survived until time of sacrifice at 10 days, whereas all those pretreated with amifostine survived. Mean serum creatinine was 48 micromol/l (controls), 146 micromol/l (cisplatin) and 59 micromol/l (amifostine + cisplatin). A marked reduction of histopathological renal changes was found when amifostine was added. Amifostine thus significantly reduced general and renal toxicity of cisplatin. The tumor growth retardation was stronger when cisplatin was given alone but this is probably related to general toxicity and malnutrition indirectly supported by the fact that amifostine did not significantly reduce cisplatin-DNA adduct formation in tumors. The results of the present study suggest that amifostine may have a role in increasing the therapeutic ratio of cisplatin, also in the treatment of malignant glioma.

This population-based cohort study investigated the occurrence of familial astrocytoma among first-degree relatives of patients with astrocytoma diagnosed between 1985 and 1993 in the northern region of Sweden. The 432 cases received a questionnaire. They were asked to provide names and cancer diagnoses of first-degree relatives. Of the 297 answering, a cohort was constructed of their 1,890 first-degree relatives (FDR). A significantly increased risk [standardized incidence ratio, SIR = 2.12, 95% confidence interval (CI) = 1.18-3.49] was shown for developing primary brain tumors (PBT). In 4.7% (14/297) of the families, a PBT was found. Interestingly, the increased risk was for astrocytoma only (SIR = 3.12, 95% CI 1.42-5.92), and not for other PBT (SIR 0.90, 95% CI 0.18-2.64). When the cohort was divided according to the median age of proband, most of the increased risk was restricted to the younger cohort (SIR = 4.71, 95% CI 1.52-10.99). Surprisingly, a significantly decreased risk for breast cancer and colon cancer was shown. The finding that the increased risk is restricted to astrocytoma only is a novel one. This study implies that familial aggregation of astrocytoma exists; the familial clustering occurs in a small fraction of astrocytoma, and might be explained by inherited factors.

Estramustine phosphate (EMP), a cytotoxic drug used in the treatment of prostatic carcinoma, is metabolized and exerts specific cytotoxic effects in malignant glioma in vitro and in vivo. In the present study, we have evaluated the cytotoxic effect of EMP in the clinical situation with regard to appearance of DNA damage and its correlation to the uptake of estramustine (EaM) in human malignant astrocytoma tissue. Ten patients were given 280 mg of EMP p.o. 12 h before surgery. Specimens from brain tumor tissue were collected during surgery and used for detection of fragmented DNA, a hallmark of apoptosis, with in situ end labeling (ISEL) and agarose gel techniques. The main metabolite of EMP in glioma tissue, EaM, was analyzed with gas chromatography. It was demonstrated that EMP induced clusters of ISEL-positive tumor cells and fragmentation of DNA on agarose gels in patients treated with EMP. In the same patients, a significant uptake of EaM in tumor tissue was demonstrated. In control patients, who were not treated with EMP, and in two EMP-treated patients with no uptake of EaM, no signs of fragmented DNA and only a few scattered ISEL-positive cells were seen in the tumor tissue. Signs of apoptosis were also seen in two different experimental models, i.e., in vitro cell cultures of rat glioma cells and an in vivo rat glioma model. It is suggested that EaM can induce apoptosis by a direct effect on a subpopulation of glioma cells in human brain tumors in the clinical situation.

Because microtubules are important components of cell motility and intracellular transport, it is reasonable to propose that the depolymerizing effect of an antimicrotubule agent, estramustine, on glioma microtubules would modulate cell invasiveness. To determine whether matrix metalloproteinases, key factors in cell invasion, are affected by exposure to estramustine, a cell proliferation assay, a zymogram, a collagenolysis assay and a haptoinvasion assay were used in this study. The zymogram revealed that an activated (62 kDa) form of matrix metalloproteinase-2 diminished with increasing estramustine concentrations. The collagenolysis assay demonstrated approximately 2.5- to 21-fold lower rates of enzymatic activity suppressed by estramustine in a dose-dependent manner at estramustine concentrations of 1, 5, and 10 microM, compared with the control group. On the haptoinvasion assay, no statistically significant difference was seen in the 0.5 microM estramustine group, whereas 1-10 microM estramustine groups revealed significant suppression of invasion from 6 to 24 h in a dose-dependent manner. The results suggest that estramustine suppresses the invasion of U87MG cells in vitro using the decreasing available matrix metalloproteinase-2, an effect caused by the disassembly of microtubules. Suppression of the infiltrative capacity of malignant glioma cells could be of significant value in the treatment of this disease. Images Figure 2

In an attempt to modify the cytotoxicity of cisplatin, amphotericin B (AmB) was given as pretreatment to BDIX rats with intracerebral BT4C glioma implants. Ten animals given AmB 5 mg/kg i.p. followed by cisplatin 5 mg/kg i.p. displayed massive haematuria within 24 h after treatment and died a few days later. The antitumoral effect could not, therefore, be evaluated. Histopathological examination of the kidneys showed extensive tubular necrosis. No signs of apoptotic cell death were found using in situ end labelling with biotin-labelled nucleotides or with DNA integrity analysis in agarose gel electrophoresis. An immunohistochemical method for analysis of cisplatin-DNA adducts was used to elucidate the distribution of cisplatin in brain tumour, normal brain and kidney. Addition of AmB to cisplatin caused increased adduct formation in kidneys, particularly in tubular cells. It seems plausible that the nephrotoxicity, at least in part, was mediated by increased levels of cisplatin-DNA adducts. Pretreatment with AmB did not have any obvious effect on the formation of adducts in the cerebral cortex. The adduct levels in the tumours from animals pretreated with AmB were not significantly increased compared with those treated with cisplatin only. Thus, addition of AmB to cisplatin caused excessive nephrotoxicity suggesting a decrease in the therapeutic ratio of cisplatin.

Trigeminal nerve microvascular decompression (MVD) relieves the pain in a great majority of patients. However, there has been a debate regarding whether the pain-relieving effect is due to the decompression itself or a surgical trauma to the nerve. In 37 consecutive patients, the facial sensibility was quantitatively assessed and the function of other cranial nerves was investigated before and after MVD. The patients were followed for 1-5 years (mean 3.4 years) to assess the surgical outcome. Twelve patients (32%) experienced a mild postoperative sensory deficit assessed by clinical examination. When measured quantitatively with electrical stimulation, sensory thresholds for perception and pain were elevated more than 25% in 16 of the patients (43%). All together 19 patients (51%) did not have any sensory deficit as assessed by either of the two methods used. No severe postoperative cranial nerve dysfunctions were noted in this series. Three patients (8%) had a recurrence of pain at 7-9 months postoperatively. Two of those patients had a moderate elevation of measured sensory thresholds. All 19 patients with no cranial nerve deficits after MVD experienced an excellent pain relief. It seems that trauma to the trigeminal nerve is not a prerequisite for obtaining pain relief after MVD for trigeminal neuralgia.

Estramustine, a combination of 17 beta-oestradiol and nor-nitrogen mustard, has been shown to be metabolised and to induce specific antiproliferative effects in malignant glioma, including arrest of glioma cells in the G2/M phase of the cell cycle, damage to cell membranes and DNA and induction of free oxygen radicals. To evaluate further the effects of estramustine, an in vivo rat glioma model using inbred BD-IX rats and the BT4C cell line was set up. In order to detect cells with fragmented DNA, tumour and brain specimens were, following fixation for histological examination, processed for in situ end labelling (ISEL) with biotin-labelled nucleotides. Fresh tissue fragments were also used for DNA integrity analysis on agarose gels. It was demonstrated that estramustine induced clusters of ISEL-positive cells and a pronounced typical fragmentation of DNA 0.5-8 h after treatment. In tumours examined 24 or 94 h after estramustine treatment, and in untreated tumours, only occasional single ISEL-positive cells were scattered in the tumour. DNA from normal brain tissue did not display any visible sign of fragmentation. These changes are indicative of programmed cell death induced by estramustine in glioma cells but not in normal brain tissue. Further studies are, however, needed to establish in detail the mechanism of cell death following treatment with the antimitotic drug estramustine. Images Figure 1 Figure 2

Estramustine-binding protein (EMBP) is a M(r) 46,000 heterodimeric protein originally isolated from prostatic tissue. It has a demonstrated high affinity for, and selective binding of, estramustine, which is a derivative of 17 beta-estradiol and nornitrogen mustard with antimitotic activity. In this study, we have analysed the expression of an EMBP-like protein in astrocytoma specimens. Immunohistochemistry revealed a pronounced reactivity for EMBP in astrocytoma grades III-IV as well as in metastatic prostatic adenocarcinoma used as positive control. In astrocytoma grades I-II, the expression was weak. The EMBP-like protein was quantified by radioimmunoassay in astrocytoma tumor tissue with higher concentrations in malignant astrocytoma, grades III-IV, compared to grades I-II tumors. Western immunoblotting of immunoaffinity purified EMBP-like protein under nonreducing conditions revealed an immunoreactivity corresponding to M(r) 138,000 and 200,000, indicating a different structure of EMBP in astrocytoma compared to prostatic tissue. Specific binding and the presence of saturable binding sites for 3H-labeled estramustine were demonstrated in astrocytoma tissues expressing EMBP-like protein. Scatchard plot analysis showed a Kd at approximately 30 nM, which suggests a binding affinity for estramustine in the same range as previously reported for EMBP in the prostate. Moreover, the number of estramustine binding sites/g tumor as calculated from the Scatchard plots was well correlated with the EMBP levels determined in the radioimmunoassay. In conclusion, an EMBP-like protein is expressed in astrocytoma. This protein may be responsible for the specific binding of estramustine in the tumor tissue. Whether this specific binding of estramustine is of importance for the cytotoxic effect in glioma cells remains to be evaluated.

Fifteen patients with brain tumours or arteriovenous malformations (AVMs) underwent hypofractionated stereotactic irradiation, 2-5 fractions being delivered using a linear accelerator and a non-invasive stereotactic frame. Results of the treatment of brain metastases were comparable with those reported for single fraction radiosurgery. With the AVMs, the rate of obliteration would seem to be slower than that after radiosurgery, perhaps because the irradiated volumes in our study were significantly larger than those treated with radiosurgery. An advantage of hypofractionated stereotactic irradiation is that larger brain lesions can be treated than is appropriate with radiosurgery.

38 patients with Parkinsonian or essential tremor who underwent thalamotomy based on ventriculographic coordinates were compared to 23 patients whose thalamotomy was performed on the basis of computed tomography (CT)-derived target coordinates. The comparison between the two groups concerned the age, sex, duration of disease, target side, intra-operative target correction, duration of postoperative stay in hospital, transient side-effects, permanent complication, and tremor alleviation. The study showed that the surgical results in terms of tremor control were the same in the two groups. However, the percentage of post-operative transient side-effects was higher and the duration of stay in hospital was longer for the ventriculographic patients than for the CT patients.

This study evaluates the treatment of intracerebral brain metastases with single dose stereotactic radiosurgery in comparison to stereotactic fractionated radiotherapy (SFR). Twenty six patients with 41 lesions were evaluated. Thirty four lesions in 19 patients were treated with radiosurgery, and 7 lesions in 7 patients were treated with SFR. The radiosurgery group was treated with an average number of isocenters of 1.4, and an average of 9 arcs. The average dose was 2140 cGy delivered to the 70% isodose line. The average volume of the lesions was 5.22 cc. The SFR group lesions received a mean dose to the indicated area delivered by 4 to 6 coplanar fields. The dose was 600 cGy per fraction, 2 to 3 fractions were given. The average volume of the treated lesions was 21.2 cc. Follow-up extended from 2-18 months. Twenty five lesions of the radiosurgery group had image follow-up. The overall local control was seen in 92% of the patients. Six lesions of the SFR group had image follow-up, the local control was 83%. The small number in each group, the non-randomized nature of the study, and the relatively short follow-up preclude a definitive conclusion. SFR may be the method of choice for large lesions surrounded by significant edema. The delivery of the dose in large fractions may obviate the transient acute reactions seen when radiosurgical dose is delivered to large lesions surrounded by edema. However, both forms of therapy have proven to be effective in the control of brain metastases.

In the treatment of trigeminal neuralgia, the possibility of obtaining a selective effect on different trigeminal branches by glycerol rhizotomy was studied. Transcutaneous electrical stimulation was used to quantify sensory impairment. An attempt was made to obtain a localized neurotoxic effect of the glycerol on the different trigeminal branches by keeping the patient's head in different positions during and for one hour after glycerol injection. The amount of glycerol injected varied according to the estimated size of the trigeminal cistern and/or to which branch that was involved. The study demonstrated a highly selective effect on the ophthalmic branch, less selective on the maxillary, and a low selective effect on the mandibular branch. However, the clinical results were equal regardless of the affected trigeminal division.

The sensory thresholds for vibration, perception and pain were measured in 375/395 of all diabetic patients aged 15-50 years in Umea county (population 118,500), 79% of whom had type 1 diabetes mellitus (DM). The results were compared with those from 100 healthy control subjects. Both type 1 and type 2 diabetic patients had significantly elevated sensory thresholds compared to control subjects. In multiple regression analysis, patients with type 1 DM had significant associations between elevated sensory thresholds and age, duration of diabetes, height but not with smoking. Type 2 diabetic patients had a significant association only with height and control subjects with age and height. Thresholds were significantly higher in men than in women with type 1 and type 2 DM and in control subjects but were no longer significant after normalizing for height. Thus, age, duration of DM and tall stature appear to be major risk factors and smoking a minor risk factor for elevation of sensory thresholds both in type 1 and type 2 DM and also in healthy control subjects. Gender differences depend on differences in height.

The relation between postoperative sensory deterioration and surgical outcome in 54 patients treated by retrogasserian glycerol rhizotomy for trigeminal neuralgia was studied. The facial sensibility was assessed one day and three months postoperatively. Thresholds for perception and pain were determined quantitatively using transcutaneous electrical stimulation and clinically by light touch and pinprick tests. At a follow-up one year after surgery there was no significant difference in pain relief between patients who did show and patients who did not show sensory deterioration at the one day or three months evaluations. Nevertheless, there was a tendency for higher recurrence rate in patients with mild or no sensory disturbance.

All diabetic patients aged 15–50 years (n = 395) in the county of Umea (population 118 500) were invited to have a standardized foot examination and 380 (96%) attended. Three-quarters (78%) had Type 1 diabetes, 20% Type 2 diabetes, and 1% secondary diabetes. They were compared with 100 healthy control subjects. Both Type 1 and Type 2 diabetic patients had slight or moderate loss of forefoot arches more often than control subjects (57% and 60% vs 31%, p < 0.001). Callosities were not significantly more common in diabetic patients than in control subjects. Lesions observed on the lower legs and feet of the Type 1 and Type 2 diabetic patients were Melin's shin spots (33% and 39%), dry feet (33% and 29%), yellow toenails (27% and 31%), purpura (9% and 5%), ulcers (3% and 0%), necrobiosis (3% and 0%), and diabetic osteopathy (2% and 0%). Intermittent claudication was present in 1% and 3%, respectively. Three Type 1 diabetic patients had undergone below-knee amputation. Two of the control subjects had Melin's shin spots. With the exception of necrobiosis which was only found in women with Type 1 diabetes and Melin's shin spots which were twice as common in diabetic men as women, whether Type 1 or Type 2, lesions were equally distributed between the sexes. Sensory thresholds for vibration, perception, and pain were significantly elevated in Type 1 diabetic patients with dry feet, fallen forefoot arches or hammer toes compared with those without. They were not increased in Type 2 diabetic patients or control subjects with these lesions. In conclusion, foot deformity and lesions of skin and nails are common in the feet of diabetic patients in this age group while macroangiopathy appears to be uncommon.

ICP-monitoring by means of an intraventricular indwelling catheter was introduced for routine clinical work by Lundberg (1960). This technique seems to have comparatively few complications, as shown by Sundbarg (1988) and it is still the “gold standard” with which other methods are compared.