Surgical decision-making in superior canal dehiscence syndrome with concomitant otosclerosis.

OBJECTIVE: The diagnosis and management of Superior Canal Dehiscence Syndrome (SCDS) with concomitant otosclerosis can be a challenge. Otosclerosis can mask SCDS symptoms and stapes surgery may reveal or exacerbate vestibular symptoms. Our aim is to present four cases of SCDS with concomitant otosclerosis and thereby informing the reader about the possibility of this dual occurrence and its implications for treatment. CASES: Four patients with SCDS and concomitant otosclerosis are presented. Two patients underwent surgical treatment for both SCDS and otosclerosis and two patients opted for conservative management. OUTCOMES: The main differences between surgically and non-surgically treated cases are the presence of autophony and pressure-induced vertigo and a more severe experience of symptoms in surgically treated cases. Surgically treated cases achieved a sizeable reduction in postoperative air-bone gap and resolution of vestibular symptoms. CONCLUSION: The subjective severity of symptoms in combination with shared decision-making is key in determining the appropriate treatment plan for SCDS and concomitant otosclerosis.

Positional cranial deformity--the parents' point of view.

The parents' point of view regarding positional cranial deformities and helmet therapy has not been the subject of scientific interest yet. However, carer acceptance is a key factor for therapeutic success. We therefore investigated parental perception. The parents of 218 infants were included in a telephone survey; 122 children had undergone helmet therapy and 96 had not. Satisfaction with the outcome, treatment-associated problems, and parental stress were investigated using a structured questionnaire. The great majority (90.8%) of caregivers were satisfied with the outcome, regardless of whether or not helmet therapy was used. Retrospectively, 76% of the parents of infants who had not undergone helmet therapy would decide against helmet therapy again. Therapy was either temporarily stopped (27.0%) or terminated (4.9%) in 31.9% of infants treated with a helmet. Major problems were sweating (51.1%) and skin lacerations (30.9%). The parents indicated minor (54.9%) or even great (25.4%) personal strain. Conflict with others (38.5%), stress for the child (30.3%), and a financial burden (36.9%) were mentioned most frequently. There appear to be more parental problems than expected associated with helmet therapy. Medical experts should take this into consideration. The indication for a helmet should be evaluated critically and the potential parental burdens should be addressed during counselling.

Detection of mutation-specific epidermal growth factor receptor (E746-A750del) and lack of detection of human papillomavirus in oral squamous cell carcinoma.

The clinical impact of epidermal growth factor receptor (EGFR) (E746-A750del) mutation and human papillomavirus (HPV) in oral squamous cell carcinoma (OSCC) is unclear. EGFR (E746-A750del) expression was analyzed in OSCC specimens (n=161) by immunohistochemistry. The expression results were correlated with clinical characteristics and impact on survival. Using INNO-LiPA Extra, high-risk HPV types were genotyped and analyzed in 211 OSCC specimens. Positive EGFR (E746-A750del) expression (n=40/161, 25%) was not associated with any clinicopathological characteristics, prognostic factors, social habits (smoking, alcohol consumption), or tumour-specific survival. HPV16 DNA was detected in three out of 211 samples (HPV16-positive: n=3/211, 1.4%). This study shows that mutation-specific EGFR (E746-A750del) expression and HPV do not appear to be relevant to the survival of patients with OSCC.

EGFR-inhibition enhances apoptosis in irradiated human head and neck xenograft tumors independent of effects on DNA repair.

Epidermal growth factor receptor (EGFR) inhibition using cetuximab improves the efficacy of radiotherapy in only a subgroup of head and neck squamous cell carcinoma (HNSCC) patients. Therefore, to improve patient selection a better understanding of tumor characteristics that affect treatment is necessary. Here, we investigated the effect of cetuximab on repair of radiation-induced DNA damage in a HNSCC xenograft model, which shows a synergistic effect to cetuximab and radiotherapy (SCCNij185) and a HNSCC model, which shows no additive effect of cetuximab to radiotherapy (SCCNij153). In both tumor models, clear increases were seen in the number of 53BP1 and Rad51 foci after irradiation. 53BP1 foci were present at comparable levels in hypoxic and normoxic tumor areas of the tumor xenografts, while the number of Rad51 foci was significantly higher in normoxic areas compared to hypoxic areas (P < 0.05). In both SCCNij185 and SCCNij153 xenografts an increased number of 53BP1 foci was observed in tumors treated with cetuximab and radiotherapy compared to radiotherapy alone. In SCCNij185 this increase was statistically significant in normoxic tumor areas (P = 0.04) and in SCCNij153 in both hypoxic and normoxic areas (P = 0.007 and P = 0.02, respectively). The number of Rad51 foci was not significantly different when cetuximab was added to radiotherapy compared to radiotherapy alone. Levels of pEGFR and pERK1/2 were decreased when cetuximab was added to radiotherapy in SCCNij185, but not in SCCNij153. Apoptosis was also only increased in SCCNij185 tumors at 4 days after cetuximab and radiotherapy treatment (P < 0.01). In conclusion, cetuximab inhibited DNA repair in both HNSCC models, but this effect was not predictive for the radiosensitizing effect of cetuximab in vivo. This lack of correlation may be related to differential effects of cetuximab and radiotherapy on ERK1/2 signaling and a decreased induction of apoptosis by cetuximab and radiotherapy in the resistant model.

Angiogenesis, hypoxia and VEGF expression during tumour growth in a human xenograft tumour model.

Tumour growth and spread of tumour cells requires angiogenesis. Incipient angiogenesis is not induced by tumour cell hypoxia but probably by proangiogenic factors. During growth tumours depend on a further induction of vascular development for adequate oxygen and nutrient supply. If the oxygen supply is insufficient, the resulting hypoxia stimulates angiogenesis through upregulation of HIF-1 alpha and VEGF. VEGF upregulation is associated with a poor response to treatment and poor prognosis. The aim of the study was to analyze the interrelationship between hypoxia and angiogenesis during tumour growth. Therefore the tumour vasculature architecture and functional properties of the vessels were studied during subsequent phases of tumour growth in relation to hypoxia and VEGF-expression. Tumours from the human glioblastoma multiforme tumour line E106 were transplanted in athymic mice. Tumours were harvested at 2 days after transplantation and when tumours reached a mean size of 2, 4, 6, 8 and 10 mm. VEGF was present early in the onset of angiogenesis independent of HIF-1 alpha. During tumour growth VEGF increased from 0.94 to 7.27 ng/mg assessed by ELISA. However, there was increasing intratumoural heterogeneity in the architecture of the tumours, even in the largest tumours small well oxygenated areas were detected resembling the relatively well organized architecture of the smallest tumours. The observation that tumour vasculature develops in early phases under normoxic and at later phases under hypoxic conditions with the presence of both conditions in the larger tumours, suggested that anti-angiogenic therapy should be directed towards HIF-1 alpha dependent and HIF 1-alpha independent pathways.

Pimonidazole binding in C6 rat brain glioma: relation with lipid droplet detection.

In C6 rat brain glioma, we have investigated the relation between hypoxia and the presence of lipid droplets in the cytoplasm of viable cells adjacent to necrosis. For this purpose, rats were stereotaxically implanted with C6 cells. Experiments were carried out by the end of the tumour development. A multifluorescence staining protocol combined with digital image analysis was used to quantitatively study the spatial distribution of hypoxic cells (pimonidazole), blood perfusion (Hoechst 33342), total vascular bed (collagen type IV) and lipid droplets (Red Oil) in single frozen sections. All tumours (n=6) showed necrosis, pimonidazole binding and lipid droplets. Pimonidazole binding occurred at a mean distance of 114 microm from perfused vessels mainly around necrosis. Lipid droplets were principally located in the necrotic tissue. Some smaller droplets were also observed in part of the pimonidazole-binding cells surrounding necrosis. Hence, lipid droplets appeared only in hypoxic cells adjacent to necrosis, at an approximate distance of 181 microm from perfused vessels. In conclusion, our results show that severe hypoxic cells accumulated small lipid droplets. However, a 100% colocalisation of hypoxia and lipid droplets does not exist. Thus, lipid droplets cannot be considered as a surrogate marker of hypoxia, but rather of severe, prenecrotic hypoxia.

Quantitative analysis of varying profiles of hypoxia in relation to functional vessels in different human glioma xenograft lines.

Tissue oxygenation influences the radiation response of tumors. To further investigate the underlying mechanisms of tumor hypoxia, the spatial distribution of hypoxic cells in relation to the vasculature was studied. In a panel of three human glioma xenograft lines (E2, E102, E106) with different growth characteristics, tumor line-specific patterns of hypoxia (pimonidazole) and (functional) vasculature (Hoechst 33342) were observed. Two of the three glioma lines showed a more homogeneous distribution of perfused vessels (E102 and E106) than the third glioma line (E2). Although all tumors showed hypoxia, the distance at which the steepest part of the gradient of the hypoxia marker was found varied significantly among the different glioma lines. The faster-growing E102 tumors had the longest distance (>300 microm). These results indicate that tumor line-specific factors, rather than vascular geometry alone, may determine the oxygenation status of a tumor. As a consequence, vascular density cannot be used as a surrogate parameter for tumor hypoxia when comparing different tumors. Additional hypoxia and perfusion markers will further improve our understanding of changes in tumor physiology at the microregional level explaining the relationship between the low oxygen levels and the response of tumors to treatment.

Spatial relationship between hypoxia and the (perfused) vascular network in a human glioma xenograft: a quantitative multi-parameter analysis.

PURPOSE: To quantitatively study the spatial distribution of tumor hypoxia in relation to the perfused vasculature. METHODS AND MATERIALS: Using a human glioma xenograft model, nude mice were administered two different hypoxia markers (NITP or pimonidazole) and the perfusion marker Hoechst 33342. Frozen tumor sections were sequentially scanned for perfusion, hypoxia, and vasculature, respectively, to quantitate perfusion, vasculature, and hypoxia parameters in the same section. RESULTS: All tumors showed incomplete perfusion. Both NITP and pimonidazole stained the same hypoxic tumor areas. No statistically significant differences between the two markers were observed. The density of the perfused vessels was inversely related to the hypoxic fraction. At critical distances from perfused vessels, hypoxia occurred. These data suggest that predominantly diffusion-limited hypoxia was detected, based on the spatial distribution of nearby vessels. Also, the proportion of hypoxia distributed over arbitrary zones of 50 microm around perfused vessels was calculated. The largest proportion of hypoxia was found at distances beyond 100 microm from perfused vessels. CONCLUSION: With the multiple staining and functional microscopic imaging technique described here, the spatial relationship between perfused vessels and hypoxia was quantified in whole tumor cross-sections. The usefulness of this histologically-based method to quantitate morphological and physiological aspects of the tumor microenvironment was evaluated.

Evaluation of models of acute and subacute acidosis on dry matter intake, ruminal fermentation, blood chemistry, and endocrine profiles of beef steers.

Crossbred steers (n = 20; 316 +/- 4 kg BW), each fitted with a ruminal cannula, were used to evaluate the effects of acute acidosis (AA) and subacute acidosis (SA) on DMI, ruminal fermentation, blood chemistry, and endocrine profiles. Animals were blocked by BW and assigned to treatments including 1) intraruminal (via cannula) steam-flaked corn (3% of BW; AA); 2) intraruminal dry-rolled wheat:dry-rolled corn (50:50; 1.5% of BW; SA); 3) offering forage-adapted steers ad libitum access to a 50% concentrate diet (AA control; AC); and 4) offering 50% concentrate diet-adapted steers ad libitum access to a 50% concentrate diet (SA control; SC). Samples of ruminal fluid and whole blood were collected on the day of the challenge (d 0) and 3, 7, 10, and 14 d after the challenge. Daily DMI responded quadratically (P < 0.01) through d 7 for AA and SA steers and increased linearly (P < 0.01) for AC steers. Dry matter intake by AA steers reached a nadir (< 3 kg/d) on d 3 and gradually increased to a level similar to other treatments (7 kg/d) by d 10, whereas DMI by SA steers increased through d 3. Blood pH, bicarbonate, base excess, and total CO2 were decreased (P < 0.03) for AA steers and increased (P < 0.03) for SC steers through d 7. Ruminal pH decreased quadratically (P < 0.01) in AA and AC steers and increased (P = 0.01) in SA steers through d 7. Ruminal total lactate concentration and osmolality responded quadratically (P < 0.01) for AA and AC steers. Ruminal total lactate peaked on d 3 for AA steers and on d 0 for AC and decreased to basal concentrations by d 7. Plasma NEFA concentration increased (P < 0.04) on d 3 and 7 for AA steers. Serum Na decreased (P < 0.05) on d 0 for AA and SA steers and on d 7 and 14 for AA steers. Serum P decreased (P = 0.01) for AA steers through d 7 and decreased quadratically (P = 0.01) for AC steers through d 7. Serum albumin and cholesterol decreased (P < 0.02) for AA and AC steers through d 7. Area under the GH curve decreased (P = 0.02) for AA and AC steers through d 7. Considerable variation was evident in the ability of an animal to cope with a carbohydrate challenge. Results of data modeling generally suggest that serum amylase activity, cholesterol and potassium concentrations, and plasma NEFA concentrations were useful in distinguishing between steers classified as experiencing subacute acidosis or not affected by a carbohydrate challenge.

Vascular architecture and microenvironmental parameters in human squamous cell carcinoma xenografts: effects of carbogen and nicotinamide.

BACKGROUND AND PURPOSE: A better understanding of the vascular architecture and the microenvironmental parameters (VAMP) will allow the identification of tumours that can be more effectively treated by intensified fractionated radiotherapy or modifiers of blood flow and oxygenation or combinations of these approaches. MATERIALS AND METHODS: Proliferation (BrdUrd), vascular architecture (endothelial marker), perfusion (Hoechst 33342) and oxygenation (NITP) were studied in two human laryngeal squamous cell carcinoma tumour lines grown as xenografts in nude mice. The effects of carbogen and nicotinamide on these parameters were evaluated. RESULTS: Carbogen treatment resulted in a decrease of the number of perfused blood vessels from 66% to 55% in one of the two tumour lines. In this tumour line nicotinamide prevented this reduction of tumour blood flow by carbogen. In both tumour lines the labelling index (LI) decreased after treatment with carbogen for 1 h, from 11-13% to 5-7%. Both tumour lines showed a drastic reduction of hypoxia by carbogen alone or by carbogen plus nicotinamide. CONCLUSIONS: In both laryngeal squamous cell carcinoma xenograft tumour lines carbogen was very effective in reducing diffusion limited hypoxia. Only in one of the two tested tumour lines carbogen also caused a reduction of tumour blood perfusion, which could be compensated for by nicotinamide. In addition, carbogen reduced tumour cell proliferation. The fact that differences in response to nicotinamide and carbogen were observed and that they can be studied in vivo provides a basis for further development of a 'predictive profile' which will guide the clinician to select the optimal treatment for individual patients or groups of patients.

Development of cytochrome P450 as a biomarker of organic pollution in Mytilus sp.: field studies in United Kingdom ('Sea Empress' oil spill) and the Mediterranean Sea.

Literature on the properties, forms and regulation of cytochrome P450 (CYP) in digestive gland of Mytilus sp., including studies indicating the existence of an organic contaminant-inducible CYP1A-like protein, are briefly reviewed. Laboratory and field studies show increases in digestive gland microsomal CYP1A-immunopositive protein levels and/or benzo[a]pyrene hydroxylase (BPH) activity (i.e. metabolism of benzo[a]pyrene to phenols) with exposure of Mytilus sp. to certain polycyclic aromatic hydrocarbons (PAHs) and polychlorobiphenyls. In order to examine further the relationship between these two parameters, M. edulis were collected 25 and 130 days after the release of oil following the grounding of the tanker 'Sea Empress' in South Wales, UK (15 February 1996); and M. galloprovincialis were sampled from sites in south-western France and south-eastern Spain during a cruise aboard the IFREMER Research Vessel 'L'Europe' (2-18 August 1996). In both studies, sites with higher levels of CYP1A-immunopositive protein showed higher levels of BPH activities. Positive correlations were observed between the two measurements - R=0.65 (M. edulis) and 0.68 (M. galloprovincialis), and both fitted linear regression models (P < 0.05). The CYP1A-immunopositive protein levels and BPH activities tended to be highest at sites with greatest PAH body burden for the Mediterranean study. It is concluded that development of the CYP1A-like protein into a robust biomarker of exposure to organic contaminants will depend upon sequencing of the gene/protein and the subsequent production of Mytilus-specific cDNA and antibody probes. Such probes will then allow a full characterization of the enzyme's properties and gene regulation.

Suramin treatment of human glioma xenografts; effects on tumor vasculature and oxygenation status.

In this study the effect of suramin on tumor growth, vascularity and oxygenation of a human glioma xenografted in the nude mouse was examined. Vascular parameters and oxygenation status of the xenografts were determined immunohistochemically in frozen sections of the tumors, using the hypoxia marker pimonidazole-hydrochloride to detect hypoxic areas. Tumor vessels in these sections were stained by an endothelial cell marker and perfusion of vessels was visualized by administration of the perfusion marker Hoechst 333342 before harvesting the tumors. The vascular parameters were quantified with an image analysis system. The results show that tumor growth was reduced considerably after suramin treatment. This growth suppression was accompanied by marked changes in vascular architecture. Although the total vascular area and perfused fraction of tumor vessels remained unchanged after suramin treatment, vascular density increased, indicating that more but smaller vessel structures had developed during therapy. These vessel structures were also more homogeneously spread over the tumor area. Control tumors showed extensive areas of hypoxia while in treated tumors hypoxic areas had mostly disappeared. This effect was probably due to the higher density of homogeneously distributed perfused vessel structures in the treated tumors, contributing to an increased oxygenation of the tumor. These observations suggest that suramin therapy can result in marked changes not only in tumor vascularity but also in tumor oxygenation status which may have important consequences for sensitivity of these tumors to other therapies such as radiation treatment.

Delayed vascular changes after antiangiogenic therapy with antivascular endothelial growth factor antibodies in human glioma xenografts in nude mice.

OBJECTIVE: The purpose of this study was to examine the delayed effects of antivascular endothelial growth factor treatment on tumor growth and vascularity in a subcutaneous mouse tumor model of human glioblastoma. METHODS: Antivascular endothelial growth factor antibody treatment was administered for a period of 6 weeks, to suppress tumor growth. To detect late vascular effects, tumor vascular parameters for treated tumors and control tumors were analyzed 4 weeks thereafter. By that time, tumors had grown to adequate sizes (diameter, 8-10 mm) for comparison with untreated control tumors. Vascular parameters were quantified by using an image-analysis system. RESULTS: Vascular density was significantly lower in antivascular endothelial growth factor antibody-treated tumors, compared with control tumors of similar size. The vascular architecture of treated tumors was also distinctly different, compared with control tumors, showing larger but sparser vessel structures. CONCLUSION: These findings suggest that antiangiogenic therapy may have a prolonged effect on the vascular architecture of certain tumors, resulting in enduring changes in the tumor vessels. Because tumor vasculature plays an important role in the sensitivity to various treatment modalities, these changes are likely to influence the responses of these tumors to further therapy.

Present state of development of neo-electroencephalography.

Neo-electroencephalography (neo-EEG) is a new technique for recording and analyzing brain activity. Mathematical and computerized reconstitution yields a monopolar-like montage. Given the polymorphism of the brain's electrical activity, the computer detects the correct monopolar-like montage for each activity in steps of 0.25 Hz. Conventional EEG detects the difference in potentials between two electrodes. Through the use of monopolar-like montages neo-EEG analysis reveals the amplitude and phase that actually underlie each electrode. The report describes with precision the features of the recording extracts that have been chosen for the analysis, i.e., the number of dominant frequencies, the frequency to the nearest 0.25 Hz and the frequency spectrum for each dominant frequency, then the amplitude to the nearest 0.1 microv and phase shift to the nearest 0.001 sec at each electrode. Some examples of comparisons between neo-EEG and conventional EEG findings are shown and demonstrate the advantages of neo-EEG in detection and differentiation of organic and functional pathologies.

Effects of varying levels of duodenal or midjejunal glucose and 2-deoxyglucose infusion on small intestinal disappearance and net portal glucose flux in steers.

Six crossbred steers (261 +/- 18 kg BW) fitted with hepatic portal, mesenteric venous and arterial catheters, and duodenal, midjejunal, and ileal cannulas were used in a replicated 3 x 3 Latin square design to determine the effect of varying levels and site of glucose plus 2-deoxyglucose (2DG) infusion on net portal-drained visceral flux. Steers were fed chopped alfalfa in six equal portions daily at 1.5% of BW. Glucose (0, 9, or 18 g/h) and 2DG (0, 1, or 2 g/h) were infused continuously through the duodenal or midjejunal cannula (two infusion sites) at total glucose plus 2DG infusion rates of 0, 10, or 20 g/h. Arterial and portal blood samples were taken simultaneously at 20-min intervals from 5 to 9 h of infusion. Portal blood flow was determined by continuous infusion of p-aminohippurate and net flux was calculated as venous-arterial concentration (PA) difference times blood flow. Arterial concentration of glucose was not affected (P > .10) by glucose plus 2DG infusion, whereas arterial concentration of 2DG was greater (P < .05) when glucose plus 2DG was infused into the duodenum and increased (linear, P < .10) as amount of glucose plus 2DG infused into both the duodenum and midjejunum increased. Net portal flux and PA difference of glucose and 2DG were greater (P < .05) when glucose plus 2DG was infused into the duodenum. Although 2DG was infused at 10% of the total glucose plus 2DG infusion, it accounted for only 1.7 and .7% of the glucose plus 2DG appearing in portal blood when glucose plus 2DG was infused at 10 and 20 g/h, respectively. We conclude that glucose is more readily absorbed across the proximal-half than the distal-half of the small intestine, and that passive diffusion is a minor route of glucose absorption.

The effect of slaframine on salivary output and subacute and acute acidosis in growing beef steers.

Experiments were conducted to determine 1) the effect of injecting slaframine (SF) on salivary output in growing beef steers and 2) whether increased salivary output after SF injection would inhibit the decrease in ruminal pH that occurs after experimentally induced subacute and acute ruminal acidosis. In Exp. 1 and 2, we measured ruminal pH and salivary output in ruminally and esophageally cannulated beef steers fed an 88% concentrate diet. Injections of 66 or 100 micrograms of SF/kg BW increased salivary flow approximately 50% compared with controls. Those doses were tested in subacute and acute acidosis models using ruminally cannulated beef steers in Exp. 3 and 4, respectively. In these experiments, salivation was assessed indirectly using a visual scoring system. In the subacute acidosis model, SF reduced (P < .10) the decrease in ruminal pH (1.1, .7, and .6 pH units for control, 66, and 100 micrograms of SF/kg BW doses, respectively), and excessive salivation was observed in all SF-injected steers. In the acute acidosis model, there were no differences (P > .10) in ruminal pH at 12 h after injection between control and SF-treated steers. Mean ruminal lactate concentrations for all treatment groups were between 87 and 112 mM. Although treatment with 66 micrograms of SF/kg BW reduced (P < .10) ruminal lactate concentrations, all ruminal lactate concentrations were indicative of acute acidosis. These results indicate that SF will reduce the decrease in ruminal pH associated with subacute acidosis in growing beef steers, but SF does not attenuate acute ruminal acidosis.

Efferent connections of the hypothalamic "aggression area" in the rat.

The efferent connections of the hypothalamic area of the rat, where attack behaviour can be elicited by electrical stimulation, were studied using iontophoretic injections of Phaseolus vulgaris-leucoagglutinin. Specificity for the hypothalamic "attack area" was investigated by comparison with efferents of hypothalamic sites outside the attack area. The hypothalamic attack area consists of the intermediate hypothalamic area and the ventrolateral pole of the ventromedial hypothalamic nucleus. Fibres from the hypothalamic attack area, as well as fibres from several other hypothalamic sites, form diffuse fibre "streams" running rostrally or caudally. Many varicosities that are found on the fibres suggest, that these fibres are capable of influencing many brain sites along their way. Projection sites were found throughout the brain. In the comparison between attack area efferents and controls, many overlapping brain sites were found. Hypothalamic efferents preferentially originating in the largest part of the attack area, i.e. the intermediate hypothalamic area, were found in the mediodorsal and parataenial thalamic nuclei. Within the septum, a spatial organization of hypothalamic innervation was found. Fibres from the attack area formed specialized "pericellular baskets" in the dorsolateral aspect of the intermediate part of the lateral septal nucleus. Fibres from other hypothalamic sites were found in other septal areas and did not form these septal baskets. Within the mesencephalic central gray, fibres from the attack area were found specifically in the dorsal part and dorsal aspect of the lateral part of the central gray. Physiological and pharmacological studies have shown that several brain sites are involved in different aspects of aggressive behaviour. Some of these areas, as for instance the dorsomedial thalamic nucleus, septum and central gray, are innervated by efferents from the hypothalamic attack area, whereas other sites, like ventral premammillary nucleus and ventral tegmental area, are not. It is concluded from the present findings, that a number of brain sites, that are known to be involved in agonistic behaviour, receive hypothalamic information preferentially from the hypothalamic attack area through diffusely arranged varicose fibres. The function of each connection in the regulation of specific behaviours remains to be further investigated.

Potential gradient of spike and wave temporal foci detected by vertical derivation and neo-electroencephalography.

We studied the electrical pattern of spikes and waves and unitemporal foci by compared analysis. One analysis was obtained by two conventional derivations: longitudinal plus triangular and referential to a neck electrode ('vertical derivation'). The other analysis is quantified by the same vertical derivation and by a monopolar-like computerized derivation, the Neo-EEG. With Neo-EEG we obtained a differential dissociation of the spike-and-wave type, and a better analysis of the cerebral dysfunction in temporal foci than in classical EEG. This leads to a sharper diagnosis of the disease it characterizes. This study also shows that one must be aware of the inadequacies and errors resulting from conventional recording because of the bipolar derivations.

Efferent connections of the hypothalamic "grooming area" in the rat.

The efferent connections of the hypothalamic area, where grooming can be elicited by local electrical stimulation or injection of various substances, were studied using iontophoretic injections of Phaseolus vulgaris leucoagglutinin. This hypothalamic "grooming area" consists of parts of the hypothalamic paraventricular nucleus and of the dorsal hypothalamic area. The specificity of these efferents for the hypothalamic "grooming area" was investigated by comparison with efferents of hypothalamic sites adjacent to this area. In addition, the distribution of oxytocinergic fibres was studied, since oxytocinergic neurons are present in the hypothalamic "grooming area" and oxytocin is possibly involved in grooming behaviour. The efferents of the hypothalamic "grooming area" as well as of hypothalamic sites surrounding this area and the oxytocinergic fibres studied do not form well determined bundles, but rather spread out throughout the hypothalamus. Clusters of fibres could be traced rostrally and caudally, forming diffuse fibre "streams". Three rostral, two thalamic and three caudal fibre "streams" have been distinguished along which efferent fibres innervate different brain areas. The many varicosities on labelled fibres "en passant" suggest that hypothalamic fibres are able to influence many parts of the brain along their way. The anterior periventricular area, the median preoptic nucleus, the ventral tegmental area and nucleus of the solitary tract were found to be more or less specifically innervated by hypothalamic "grooming area" fibres and oxytocinergic fibres. Other brain areas, like the septum, the medial amygdaloid nucleus, the central gray and the paraventricular nucleus of the thalamus were found to receive efferent projections from the hypothalamic "grooming area" and hypothalamic loci outside this area, as well as from the oxytocinergic system. Within the septum and the mesencephalic central gray, differences in the spatial organization of terminating fibres from the hypothalamic "grooming area" and hypothalamic "non-grooming" sites have been found. Fibres from the grooming area clustered in the ventral part of the lateral septal nucleus, while fibres from surrounding hypothalamic loci innervated other parts of that brain area. In the central gray, fibres from the hypothalamic "grooming area" clustered in rostrodorsal and caudoventral parts. A number of brain areas, that are innervated by hypothalamic "grooming area" fibres and oxytocinergic fibres, like central gray, ventral tegmental area and the noradrenergic A5 area, have been reported previously to be involved in grooming behaviour. It is concluded from the present findings, that the hypothalamic "grooming area" has preferential connections with a number of brain sites, not shared with hypothalamic projections from outside the "grooming area".(ABSTRACT TRUNCATED AT 400 WORDS)