Production of urokinase-type plasminogen activator (u-PA) and plasminogen activator inhibitor-1 (PAI-1) in human brain tumours

We investigated the role of plasminogen activators (PAs) and their inhibitor (plasminogen activator inhibitor-1, PAI-1) in human brain tumours. The amounts of urokinase-type plasminogen activator (u-PA), tissue-type plasminogen activator (t-PA), and plasminogen activator inhibitor-1 (PAI-1), and the activity of u-PA and t-PA were determined by enzyme-linked immunosorbent assay (ELISA), and u-PA and PAI-1 were immunolocalized using monoclonal antibodies in human brain tumours and normal brain tissues. The tissues were surgically removed from 64 patients; normal brain tissue (5 cases), low-grade glioma (4 cases), high-grade glioma (17 cases), metastatic tumour (9 cases), meningioma (benign 12 cases, malignant 6 cases), acoustic schwannoma (11 cases). u-PA activity and u-PA and PAI-1 antigen levels were significantly elevated in malignant brain tumours (malignant meningiomas, high-grade gliomas, and metastatic tumours) and acoustic schwannomas but very low in benign meningiomas, low-grade gliomas and normal brain. There was no difference in t-PA antigen levels among normal and malignant tissues, however levels of t-PA activity were markedly decreased in metastastic tumours. All malignant brain tumour tissues showed positive immunostaining for u-PA and PAI-1, however, some tumour cells showed negative intensity while others showed strong intensity for these antibodies. This contrasts to the homogeneous staining pattern found in acoustic schwannoma. These findings indicate that malignancy in human brain tumours is associated with elevated levels of u-PA and PAI-1 and that an imbalance between these proteins in a micro-environment contributes (ascribes) to tumour cell invasion.     

Hyaluronan in human cerebrospinal fluid

We studied the concentration of hyaluronan in cerebrospinal fluid (CSF) in various diseases and attempted to define its reference interval. A radioassay utilizing cartilage proteins with affinity for hyaluronan was used in determining the concentration of 200 lumbar and 27 ventricular CSF specimens and 11 brain cyst fluids. Molecular weight distributions were determined by gel chromatography and localization in brain tissue by histochemistry. The hyaluronan level of lumbar CSF showed an increase with age; comparatively healthy children had (mean +/- SD) 50 +/- 41 micrograms/L (n = 40) and adults 166 +/- 77 micrograms/L (n = 9); i.e. significantly different values. The highest level was recorded in a patient with meningitis (> 8000 micrograms/L). More than 4000 micrograms/ L was noted in a patient with tumour metastasis in the cerebellum. Significantly elevated levels were especially found with spinal stenosis, head injury and cerebral infarction, but also in inflammatory medical disorders, hydrocephalus and encephalitis. We found no significant increase in multiple sclerosis and some other neurological diseases. Ventricular CSF of adults contained significantly less hyaluronan (53 +/- 73 micrograms/L; n = 16) than lumbar CSF. Hyaluronan in cyst fluids varied from 31 to 25,000 micrograms/L. Weight average molecular weight of hyaluronan in CSF was 2.9-3.0 x 10(5) and in brain tumour cyst fluid 2.4 x 10(6). In search for the origin of hyaluronan in CSF it was found that its concentration in the choroid plexus and leptomeninges was low, but that hyaluronan was accumulated in the superficial layer of the cerebral cortex. Continued screening for hyaluronan in CSF may be valuable in cases of inflammatory diseases, tumours and obstruction to CSF flow.     

Computerized axial transverse tomography in cerebrovascular disease

One hundred eleven patients with supratentorial cerebrovascular disease were studied by computerized axial tomography (CT scanning). With one exception, every patient who had a normal scan 48 hours after the onset of symptoms was ultimately diagnosed as having had transient ischemic attack, although in nearly one-third, the clinical diagnoses at the time of the scan was infarction. A normal CT scan, therefore, augurs a good outcome of supratentorial cerebrovascular disease. Ninety-eight percent of the patients with infarction had abnormal scans, with areas of decreased density in a vascular distribution. Pitfalls in the diagnosis of infarction were (1) initially normal CT scans that changed to abnormal after 48 hours, and (2) mass effect of infarction leading to misdiagnosis of brain tumor. Serial studies eliminated both pitfalls. Intracerebral hemorrhages had a distinctive high density appearance. In 43 percent of patients whose scans showed hemorrhage, the clinical diagnosis was thrombosis. Many did not have symptoms, signs, or outcome of cerebral hemorrhage, and the diagnosis would not have been suspect were it not for the CT scan.     

Does traumatic subarachnoid hemorrhage caused by diffuse brain injury cause delayed ischemic brain damage? Comparison with subarachnoid hemorrhage caused by ruptured intracranial aneurysms

OBJECTIVE: To examine whether traumatic subarachnoid hemorrhage (TSAH) caused by severe diffuse brain injury leads to delayed ischemic brain damage and secondary deterioration of outcome, as does aneurysmal subarachnoid hemorrhage (ASAH). METHODS: We examined 99 patients with diffuse brain injury with TSAH and 114 patients with ASAH. Computed tomographic (CT) findings, cerebral blood flow, and neurological outcomes were assessed during the acute and subacute phases and were compared between the two groups. RESULTS: The distribution of subarachnoid hemorrhage on the CT scans differed between the two groups. Unlike ASAH, TSAH was not limited to cisterns surrounding the circle of Willis but extended to supratentorial regions and interhemispheric fissures. Computed tomography-detected subarachnoid hemorrhage disappeared very early with TSAH and gradually with ASAH. In the ASAH group, mean cerebral blood flow decreased to 75% of normal during the acute phase and decreased a further 10% during the subacute phase. In the TSAH group, mean cerebral blood flow decreased to 85% of normal during the acute phase and increased slightly during the subacute phase. Neurological deterioration and in-hospital death peaked on Day 0 in association with TSAH and showed twin peaks in association with ASAH. The incidence of low-density areas on the CT scans was significantly higher with ASAH than with TSAH. All low-density areas on the CT scans of patients with ASAH corresponded to vascular territories, but low-density areas on the CT scans of patients with TSAH were rarely associated with vascular territories and contained deep-seated or gliding contusion types. CONCLUSION: The findings suggest that the incidence of vasospasm is low in association with TSAH and that the cause is different compared with ASAH. There is no evidence that the presence of TSAH in cases of diffuse brain injury leads to delayed ischemic brain damage and secondary deterioration of outcome.     

Intravenously injected radiolabelled fatty acids image brain tumour phospholipids in vivo: differential uptakes of palmitate, arachidonate and docosahexaenoate

This paper investigates the incorporation of intravenously (i.v.) administered radiolabelled fatty acids--[9,10(3)-H]palmitate (3H-PA), [1-14C]arachidonate (14C-AA) and [1-14C]docosahexaenoate (14C-DHA)--into intracerebrally implanted tumours in awake Fischer-344 rats. A suspension of Walker 256 carcinosarcoma tumour cells (1 x 10(6) cells) was implanted into the right cerebral hemisphere of 8- to 9-week-old rats. Seven days after implantation, the awake rat was infused i.v. for 5 min with 3H-PA (6.4 mCi/kg), 14C-AA (170 microCi/kg) or 14C-DHA (100 microCi/kg). Twenty minutes after the start of infusion, the rat was killed and coronal brain sections were obtained for quantitative autoradiography and histology. Each fatty acid showed well-demarcated incorporation into tumour tissue. Areas of necrosis or haemorrhage showed no or small levels of incorporation. The ratios of incorporation into the tumour to incorporation into contralateral brain regions were 2.8-5.5 for 3H-PA, 2.1-3.3 for 14C-AA and 1.5-2.2 for 14C-DHA. The mean ratios differed significantly between the fatty acids (P < 0.01). 3H-PA was not incorporated into necrotic tumours despite the presence of an open blood-tumour barrier, indicated by extravasated horseradish peroxidase. The incorporation rate constant of 3H-PA was similar for small intracerebral and large extracerebral tumours. The results show that 3H-PA, 14C-AA and 14C-DHA are incorporated more readily into tumour tissue than into brain, and that the increase is primarily due to increased utilization of fatty acids by tumour cells and not due to a high blood-tumour permeability. The relative increases in rates of incorporation for the different fatty acids may be related to lipid composition of the tumour and to the requirement of and specific role of these fatty acids in tumour cell growth and division.     

Is chromosome 9 loss a marker of disease recurrence in transitional cell carcinoma of the urinary bladder?

Investigation of transitional cell carcinoma of the urinary bladder (TCC) patients classified by recurrence and/or progression has demonstrated that loss of chromosome 9, as detected by FISH analysis of the pericentromeric classical satellite marker at 9q12, occurs early. A total of 105 TCCs from 53 patients were analysed in situ by two independent observers for loss of chromosome 9 using quantitative fluorescence in situ hybridization (FISH). All 53 primary tumours were evaluated for chromosomes 9, 7 and 17. Normal ranges for chromosomal copy number were defined for normal skin epidermis and bladder epithelium. Values for chromosome 9 copy number outwith the range 1.51-2.10 (mean +/- 3 x s.d. of normal values) were significantly abnormal. Twenty-five TCCs were detected with consistent monosomic scores. Of 89 TCCs, in which multiple tumour areas were analysed, 85 tumours (96%) demonstrated the same chromosome 9 copy number in all areas (2-6) analysed; only three tumours demonstrated heterogeneity for this locus. A total of 36% (12 out of 33) of patients with subsequent disease recurrence demonstrated loss of chromosome 9 in their primary and all subsequent TCCs analysed. Only a single patient (n = 20) with non-recurrent TCC showed loss of chromosome 9 (P = 0.0085). Of 53 primary tumours, eight showed significant elevation of chromosome 17. Of these patients, six demonstrated elevation in chromosome 7 copy number. No abnormalities were observed in non-recurrent patients. This study describes rapid quantitation of chromosomal copy number by FISH using a pericentromeric probe for chromosome 9 in TCC of the urinary bladder. Routinely fixed and processed material was evaluated without disaggregation. Strict quality control of FISH demonstrated that this technique was reproducible in a clinical environment and could be used to detect genetic changes relevant to patient outcome. It is proposed that loss of chromosome 9 from primary TCC of the urinary bladder identified patients at high risk of recurrence and possible progression.     

Effect of hyperosmotic solutions on human brain tumour vasculature

Reversible opening of the blood-brain barrier (BBB) has been used to increase delivery of chemotherapeutic agents into brain tumours, but it is complicated and requires general anaesthesia. Without affecting the normal BBB, and avoiding the complications of BBB modification by hyperosmotic solution, we tried an adequate minimal BBB disruption in brain tumours. Although the effect of BBB disruption on normal brain has been described, there are no reports of the effect of an impaired BBB on microcirculation. In this study, four patients underwent surgical resection of a glioblastoma multiforme (GM; n = 1), astrocytoma (n = 2), or metastatic brain tumour (n = 1). Epicerebral microcirculation was observed in the operative field. Serial fluorescein microangiograms of the tumour and peritumoural area were obtained before and after BBB disruption was introduced intra-operatively by retrograde infusion of mannitol introducing a catheter via the temporal superficial artery back to the carotid bifurcation. On the initial microangiogram, staining by the fluorescein dye was observed in the GM and metastatic tumour but not in the astrocytoma; no extravasation of fluorescein dye was observed in the peritumoural areas. After BBB disruption, fluorescein perfusion increased and extravasation of fluorescein dye from the venules was observed in the GM and the metastatic tumour and in the peritumoural area of both lesions; BBB disruption started from venules in the peritumoural area without affecting the normal brain. However, such effects were not observed in the astrocytomas after BBB disruption nor in normal brain tissue in any patient. It appears that the integrity of the BBB is less stable in the peritumoural area of GM and metastatic brain tumours than it is in astrocytomas or normal brain. Osmotic BBB disruption may offer a method for achieving global delivery of therapeutic agents to brain tumours and peritumoural areas.     

Intratumoral oxygen tension in metastatic melanoma

Tumour hypoxia can lead to a decrease in the biological effectiveness of radiation and alkylating agents. Few data are available on oxygen tension (PO2) in melanoma. In 20 patients with past history of melanoma, PO2 was evaluated in normal tissues and suspected metastatic lesions (nodes and skin metastases). Oxygen tension was measured using a needle probe technique (KIMOC-6650 histograph, Eppendorf, Germany), the day before the surgical removal of the suspected metastatic lesion. Histological confirmation of the malignant origin of the removed lesion was obtained in 18 cases. In two cases invasion by the known melanoma was not seen histologically. The median PO2 for normal tissues was 40.5 mmHg. For tumours, the median PO2 was 11.6 mmHg, and it was 17.1 mmHg in nodes and 6.7 mmHg in skin metastases. Very low values (< 2 mmHg) accounted for 20% of the recorded values in nodes and 15% in skin metastases. When analysed according to the node size (< or > or = 3 cm in diameter), the median PO2 was 10.4 mmHg in large nodes (six patients) and 53.3 mmHg in small nodes (six patients). For the two non-tumoral lesions, the median PO2 values were 20.9 and 25.1 mmHg, with no values below 10 mmHg. Thus a decrease in PO2 values, probably corresponding to tumour hypoxia, was found in most of the metastatic tumours when compared with normal tissues. The prognostic value of these PO2 measurements in melanoma remains to be demonstrated in the tumour response to radiotherapy or alkylating agents. However, tumour hypoxia can already be investigated as a target for new treatment modalities in metastatic melanoma.     

Functional connectivity of the angular gyrus in normal reading and dyslexia

The classic neurologic model for reading, based on studies of patients with acquired alexia, hypothesizes functional linkages between the angular gyrus in the left hemisphere and visual association areas in the occipital and temporal lobes. The angular gyrus also is thought to have functional links with posterior language areas (e.g., Wernicke's area), because it is presumed to be involved in mapping visually presented inputs onto linguistic representations. Using positron emission tomography , we demonstrate in normal men that regional cerebral blood flow in the left angular gyrus shows strong within-task, across-subjects correlations (i.e., functional connectivity) with regional cerebral blood flow in extrastriate occipital and temporal lobe regions during single word reading. In contrast, the left angular gyrus is functionally disconnected from these regions in men with persistent developmental dyslexia, suggesting that the anatomical disconnection of the left angular gyrus from other brain regions that are part of the "normal" brain reading network in many cases of acquired alexia is mirrored by its functional disconnection in developmental dyslexia.     

5-Aminolevulinic acid induced endogenous porphyrin fluorescence in 9L and C6 brain tumours and in the normal rat brain

A new approach in photodynamic therapy is the use of endogenous porphyrins for sensitisation of tumours to light. The induction of endogenous porphyrins after intravenous injection of 5-aminolevulinic acid (ALA, 200 mg kg-1) was studied in 23 rats, bearing intracranial 9L or C6 tumours. After 0, 2, 4, 6, 8, and 22 hours the rats were sacrificed and the fluorescence distribution of endogenous porphyrins was studied in brain tissue sections with a standard fluorescence microscope and a confocal laser scanning microscope. The role of blood-brain barrier disruption on porphyrin production was studied in 2 rats with a cryo-lesion of the cortex. Additionally, 9L and C6 tumour cell cultures were incubated with ALA for 8 hours in vitro. Fluorescence was measured with a fluorescence spectrophotometer in cell cultures and in the brain sections. Porphyrins were detected in vitro in the tumour cells from 2 hours onwards and ex vivo in the tumour sections mainly from 2 to 8 hours, by 22 hours porphyrin fluorescence had almost disappeared. The contralateral brain showed low fluorescence levels between 2 and 6 hours after ALA administration. At the site of the cryo-lesions low fluorescence was measured 6 hours after ALA administration. The 9L tumours fluoresced homogeneously, with a sharp demarcation towards normal brain tissue. Fluorescence in the C6 tumours was patchy, with a poorly fluorescing edge. In both tumour models fluorescence was also detected in brain surrounding the tumour and sometimes in contralateral white matter and ventricle ependyma and pia mater. The slight increase of porphyrin fluorescence in the normal brain of tumour bearing rats, compared to the absence of this in rats without a tumour, was attributed to transport by bulk flow of porphyrins made in the tumours, and possibly also of circulating porphyrins or ALA leaking from the tumour vessels.     

Partial simple vegetative crisis: importance of electroencephalographic findings

INTRODUCTION: 50% of the patients with cerebral tumours present with epileptic crises, which may be partial or generalized. The commonest partial crises have motor symptoms. These make up 30% of the simple partial crises. Partial simple crises with purely vegetative-type symptoms are very uncommon (less than 5%). They are considered to be caused by discharges in the internal regions of the temporal lobes, mainly in the limbic system. This means that it is very difficult to identify them using techniques of surface EEG. CLINICAL CASE: We describe the case of a patient with a cerebral tumour. The initial clinical features were short episodes of generalized coldness and sweating which had been present for the previous two weeks, without any other symptoms. During a routine EEG, focal critical paroxystic activity was recorded in the right temporal region. This coincided with a clinical episode similar to those described. CONCLUSIONS: The episodes were labelled partial simple vegetative crises. In this case the EEG was crucial for diagnosis and subsequently to recommend suitable treatment. However, difficulty in recording this type of crisis with a surface EEG makes correct diagnosis of these patients very difficult, since the epileptogenic focus is deeply situated.     

Radioprotection of normal and malignant tissue in the mouse by diethylaminoreserpine

The protective effect of pre-irradiation injections of diethylaminoreserpine (DL-152) for normal and malignant tissues in the mouse has been investigated. Dose modifying factors (DMFs) obtained for normal tissue ranged from 1.0 for bone marrow CFUs to more than 1.8 for skin. The DMFs for two transplantable tumours investigated were 1.0 for the EMT6 adenocarcinoma and 1.70 for the KHT fibrosarcoma (at a surviving fraction of 0.1. Acutely hypoxic KHT tumours were protected to a slightly lesser extent than were aerated tumours. For the KHT tumour, the number of clonogenic cells recovered from non-irradiated tumours one hour after DL-152 injection was reduced to 60 per cent of the number covered fro saline-injected controls, while, if DL-152 injected mice were acutely hypoxic at the time of sacrifice, the number of clonogenic cells was further reduced. The survival of non-irradiated EMT6 tumour cells was unaffected by DL-152 injection prior to sacrifice.     

Congenital absence and aberrant course of the internal carotid artery

OBJECTIVE: To evaluate the extent of vascularization by assessing vascular surface density in renal cell carcinomas (RCCs) of different nuclear grades, and in normal renal cortex and medulla. MATERIALS AND METHODS: Specimens of 79 RCCs of different nuclear grades (16 of G1, 42 of G2 and 21 of G3) were immunostained with the lectin Ulex europaeus agglutinin-I (UEA I). The vascular surface density of tumour tissue was assessed stereologically using a test grid at x400 magnification and compared to the values obtained in normal renal tissue. RESULTS: G3 tumours had a lower vascular surface density than had G1 and G2 RCCs and normal renal tissue of the cortex and medulla (P < 0.001, respectively). G1 tumours had a significantly higher vessel density than had normal medullary parenchyma and G2 carcinomas (P < 0.001). Vessel density was not significantly different among G1 tumours and cortical parenchyma in controls and among normal medullary tissue and G2 tumours. Statistical analysis showed that the vascular surface density was independent of tumour stage and size and the age and sex of the patients. CONCLUSION: The degree of vascularization in RCCs decreased with their grade of differentiation, suggesting that the extent of neovascularization in tumour tissue reflects the relationship between tumour cell proliferation and vascular growth. The values of vascular surface density in normal renal tissue of the cortex and medulla partially overlapped with those obtained in tumour tissue.     

Glutathione S-transferases in human renal cortex and neoplastic tissue: enzymatic activity, isoenzyme profile and immunohistochemical localization

1. Glutathione S-transferase (GST) activity in the cytosol of renal cortex and tumours from eight men and eight women was measured using 1-chloro-2,4-dinitrobenzene (CDNB) as a substrate. GST activities ranged from 685 to 2192 nmol/min/mg protein in cortex (median 1213) and from non-detectable (minimum 45) to 2424 nmol/min/mg protein in tumours (median 469). The activities in the tumours were lower than those in the normal cortices (p < 0.05). 2. In men, the activity in the cortical cytosol was in all cases higher than that measured in the corresponding tumours (p < 0.05). In women, the difference in activity between cortices and tumours was not significantly different (p > 0.05). 3. The age of the patients ranged from 42 to 81 years (median 62) and was not found to play a role in the levels of GST activity observed in cortex or in renal tumours from either sex. 4. Immunoblotting and immunohistochemical studies confirmed that GST-alpha was the predominant form expressed both in normal cortex and tumour and probably accounted for most of the GST activity present in these samples. GST-mu and GST-phi were expressed in both tumours and normal cortex and, while in some cases the level of expression in the cortices was higher than that found in the tumours, the reverse was also observed. Within the GST-mu class, GST M1/M2 was only detected in one sample (tumour), which showed the highest overall expression of GST-mu. GSTM3 was the predominant isoenzyme of the mu class in normal and tumour tissue, whereas GTM4 and GSTM5 were not detected. 5. These differences could have functional significance where xenobiotics or cytotoxic drugs are specific substrates for the different classes of GSTs.     

No correlation between phaeochromocytoma catecholamine secretion and granule ultrastructure

BACKGROUND: It is uncertain whether biochemical markers of catecholamine secretion in patients with phaeochromocytoma correlate with tumour ultrastructure granule morphology. METHODS: Fifteen patients with an adrenal phaeochromocytoma (n=13) or paraganglioma (n=2) (three men, 12 women; age 17-79 years) were studied. Catecholamine secretion was estimated by measuring urinary levels of free noradrenaline, adrenaline and dopamine. The number and type of secretory granules were evaluated by two independent observers on electron micrographs (area analysed approximately 70 microm2). Large round or elongated medium-density granules were adrenaline-type granules, whereas electron-dense granules lying in a vacuole were of noradrenaline type. RESULTS: No correlation was found between noradrenaline output and the number or percentage of noradrenaline-type granules, although tumours with normal noradrenaline output had only a minority of this type of granule (less than 25 per cent). Adrenaline-type granules were predominant (77 per cent of 163 granules) in a tumour secreting only adrenaline, but the proportion of adrenaline-type granules in six tumours with normal adrenaline output varied significantly (range 7-89 per cent). It was not possible to evaluate the granule type associated with dopamine secretion because one tumour secreting 14900 nmol dopamine and 1570 nmol adrenaline daily had a predominance of noradrenaline-type granules (63 per cent of 132 granules) and two dopamine-secreting tumours (5500 and 4250 nmol per day respectively) had 93 and 13 per cent noradrenaline-type granules. CONCLUSION: The lack of correlation between hormone output and granularity suggests that other factors determine secretory patterns in these tumours.     

Monitoring aortic root effluent during retrograde cardioplegia delivery

Early signs of brain infarction can be detected by modern CCT technology even within the first 6 h after stroke. Little is known about the prognostic significance of early infarction signs in CCT. We prospectively evaluated clinical and CCT findings of 95 consecutive patients with an acute ischemia in the territory of the middle cerebral artery. All patients were admitted to our stroke unit within 6 h after stroke. In 55 patients CCT was performed within 3 h, and in 40 cases between 3 and 6 h. In all patients the clinical findings were assessed by the Scandinavian Stroke Scale (SSS). The disability due to stroke was evaluated after 4 weeks by use of the modified Rankin Scale. We could demonstrate the following early signs of cerebral infarction: focal hypodensity (23.2%), obscuration of basal ganglia (12.6%), focal brain swelling (22.1%), hyperdense middle cerebral artery sign (HMCA; 11.5%). In 3 patients early edema led to ventricular compression, in 1 patient to midline shift. The occurrence of early infarction signs did not depend on the etiology of ischemia but was significantly associated with a severe neurological deficit at admission and an unfavourable disability status 4 weeks after stroke. Focal brain swelling and HMCA were often followed by extensive infarction lesions on the follow-up CCT. In conclusion, early signs of hemispheric brain infarction visible on CCT scans performed within 6 h after stroke are correlated with severe stroke and an unfavourable functional outcome. However, a substantial part of our patients had a benign course of the disease in spite of early CCT pathology. Decisions on therapy in individual patients therefore should not depend on early CCT findings exclusively.     

Variations in tumour oxygen tension (pO2) during accelerated radiotherapy of head and neck carcinoma

The study was performed to assess the effect of accelerated radiotherapy on oxygenation of primary tumours and metastatic nodes in patients with advanced head and neck tumours. In 14 patients with head and neck tumour, oxygen tension (pO2) was evaluated in normal tissues and tumours (primary tumour or metastatic neck node) before (0 Gy) and after 2 weeks (32 Gy) of accelerated radiotherapy (70 Gy in 3.5 weeks, with three daily fractions). Radiotherapy was combined with carbogen breathing in 5 patients. pO2 was measured using a polarographic technique. For pooled normal tissues, median pO2 was 38 mmHg before treatment and 46 mmHg after 2 weeks. For tumours, very low values (< 2 mmHg) represented 20% of the recorded values before treatment and 10% after 2 weeks. The relative increase in tumour oxygenation was more pronounced for primary tumours (median pO2 12 mmHg before treatment versus 26 mmHg after 2 weeks, P < 0.05) than for metastatic nodes (respectively, 20 and 27 mmHg P = 0.1). For the 5 patients who breathed carbogen during accelerated radiotherapy, the median pO2 was 44 mmHg at 2 weeks, compared with 13.5 mmHg before treatment (P = 0.05). Very low pO2 values, corresponding to tumour hypoxia, were found in the tumours (primary and metastatic neck nodes) prior to accelerated treatment. During the first 2 weeks of accelerated treatment, an increase in median pO2 was found in nine of the 14 tumours, together with a decrease in the frequency of very low values.     

Endothelial-cell proliferation in experimental tumours

The proliferation characteristics of vascular endothelium have been studied in 131 individual experimental tumours, representing 18 transplanted tumour lines. The labelling index (LI) is high in most tumours, with a mean value of 0.9%, regardless of the growth rate of the tumours, or whether different tumour types are considered or individual tumours from within one line are studied in detail. A similar high LI value has been found by others for a human tumour. These high LI values may even underestimate the proliferation in new capillary buds. The high proliferative index of tumour endothelium is in marked contrast with the previously reported low 3HTdR uptake into normal tissue blood vessels. It seems likely that it is the type of new vessels formed that will influence tumour growth rates more than the simple rate of endothelial-cell proliferation. The large difference between the proliferation characteristics of tumour endothelium and normal tissue endothelium, recently identified as a possible approach for tumour therapy, has now been confirmed for a range of animal tumours and a human tumour.     

The ''dropping'' and ''hornblower''s'' signs in evaluation of rotator-cuff tears

Both decreased and increased perfusion and metabolism have been described with PET and SPECT in different areas of the brain in patients with Gilles de la Tourette's syndrome. The aim of this study was to define the regional cerebral perfusion pattern in drug-free patients and the changes in perfusion with the usual neuroleptic treatment. METHODS: A group of 13 normal control subjects and 15 unmedicated Gilles de la Tourette's syndrome patients were studied with 99mTc-HMPAO brain SPECT. Thirteen of the initial group of patients were retested on neuroleptic treatment. A semiquantitative analysis of the images was performed. RESULTS: Decreased perfusion in orbital and anterior medial regions of both frontal lobes as well as in both temporal lobes was observed in the nontreated group compared with control subjects. With treatment, a perfusion increase in these frontal regions and in the left medial temporal cortex was observed. CONCLUSION: Neuroleptic treatment could decrease the hyperactivity of the dopaminergic system leading to improvement of the clinical symptoms and reperfusion of some previously hypoperfused regions.