From 1983 to 2003, 131 patients were operated on in the head and neck region with 139 free flaps. They were operated on using a team approach of ear, nose, and throat surgeons and plastic surgeons, and sometimes maxillofacial surgeons. The tumours were squamous cell carcinoma (SCC) 104 (80%), salivary gland cancer 13 (10%), sarcoma 5 (4%), basal cell carcinoma 4 (3%), and others 4 (3%). The staging of the primary intraoral SCC tumours (n=79) was 42% in stage II, 28% in stage III, and 30% in stage IV. The survival of patients with primary oral SCC was compared with a previously treated previous series that gave an increase in tumour-related five-year survival from 48% to 58%. Most flaps were radial forearm flaps (73%). Fifteen percent were vascularised bone transfers. A questionnaire was sent to patients who had had oral/oropharyngeal tumours to measure function and satisfaction, to which 47/49 responded. The results including ability to chew and swallow, speech was good, with a median score of 0.78 (range 1-0).

The vestibular and opto-ocular motor (VOOM) system in pigmented rats was investigated. Horizontal eye movements were recorded by the magnetic search coil technique during different kind of stimulations. The dynamics of the vestibular ocular reflex (VOR) and the optokinetic reflex (OKR) as well as the interaction of the two rel1exes were analysed. The ability to cancel nystagmus during vestibular and optokinetic stimulation was found to be comparable to "higher" animals.

The experimental model was used to study the effects of toxicants and drugs on the VOOM system. Four different solvents, known to cause disturbances of the central nervous system (CNS), were tested. Acute exposure by inhalation of each solvent gave specific dose-response related effects in the VOOM system, most of which could be explained by an alteration of the cerebellar-vestibular circuit. However there were differences among the four solvents, the results indicating that different solvents should be considered as individual substances in toxicological CNS research.

The effects of drugs, related to GABA_B-transmission, were investigated.Baclofen, a GABA_B-agonist, affected the VOR, the OKR and the interaction of these two in a dose-related way. All these effects could be blocked by CGP 35348, a GABA_B-antagonist.

The similarities in the effects of baclofen to the effects of toluene were striking. It was demonstrated that effects of toluene on the VOR could be blocked by CGP 35348 at a dose which did not cause any effects per se. It was concluded that some of the effects of toluene on the VOOM system were related to GABA-transmission, directly or indirectly.

The VOOM system was also used in an otoneurological test battery to investigate the effects on the CNS in workers, long-term exposed to solvents. Dynamic posturography was also performed to obtain an indication of the integration of somatosensory, visual, and vestibular stimuli in the equilibrium system. Reduced ability to visual suppression, prolonged latency of saccades and pathology in the posturography tests were found in the solvent exposed group compared to results of a non-exposed healthy control group.

All exposed worker had been evaluated for a possible chronic toxic encephalopathy (CTE) and were categorized in three groups non-CTE, incipient CTE, and CTE. These categories, based on psychometric test results and case histories of exposure and symptoms, were poorly correlated to the otoneurological findings. Even in the non-CTE group pathological findings were present. Lesions in the CNS revealed by an otoneurological investigation were apparently not found in the neuropsychological investigation. This indicates that an otoncurological test battery could contribute valuable information in the evaluation of long-term solvent exposed people suspected for CTE.

The studies related above, demonstrate that the VOOM system is an useful tool in evaluating toxicological effects in the CNS.

The effects of the GABAB agonist baclofen and the GABAB antagonist CGP 35348, given separately or simultaneously, on the central vestibular system of pigmented rats have been evaluated. Drugs were administered either intramuscularly or intracerebroventricularly. Eye movements were recorded during vestibular, optokinetic and combined visual-vestibular stimulation. Activation of the GABAB receptors by baclofen caused a dose related disturbance of the system, manifested by (1) a decrease of the optokinetic gain, (2) a reduced ability to suppress nystagmus during conflicting vestibular and visual input, and (3) a disability to maintain the eccentric eye position upon a spontaneous saccade. All these effects could be inhibited in a dose-dependent fashion by CGP 35348, suggesting that the findings are specifically related to the GABAB receptor. Given separately, the antagonist did not affect the mentioned parameters. During horizontal acceleratory/deceleratory stimulation in darkness baclofen caused a biphasic pattern in the dose-response curves. Small amounts of baclofen caused an increase of the gain and of the duration of poststimulatory nystagmus, while high doses had a depressive action on the same parameters. The stimulating effect of baclofen could be inhibited or even reversed by CGP 35348, which has a depressive effect per se, similar to the effects of baclofen given in the upper range of doses.

The acute effects of inhalation of four solvents on the central vestibular system of rats were analyzed by recording eye movements upon different stimuli. The dose-response relationship was investigated. Optokinetic stimulation was obtained by placing the animals in front of a surrounding visual pattern, moving at different velocities. The slow-phase eye velocity (SPV) of nystagmus was calculated and divided by the stimulus velocity, giving the gain. All the solvents caused a decrease of the gain. Vestibular stimulation was performed on a turntable by an angular acceleration/deceleration in darkness. The SPV and the duration of the post-stimulatory nystagmus were calculated. The shape of the SPV dose-response curves differed among the four solvents. Toluene, styrene, and trichloroethylene prolonged the duration of nystagmus while trichloroethane did not. A conflicting vestibular and optokinetic stimulation was performed by an angular acceleration/deceleration with a surrounding visual pattern moving with the turntable. All solvents decreased the ability to cancel nystagmus, elicited by vestibular stimulation in conflict with a visual input. Quick movements of the eyes, saccades, were elicited by tactile stimulation. Toluene, styrene, and trichloroethylene changed the generation of the saccades while trichloroethane did not. Most of the findings indicate a common site of action in the central vestibular system, viz., the cerebellar-vestibular circuit. However, within this domain, there are evident differences in the effects among the solvents. This finding, together with previous results obtained in other experimental models of the central nervous system (CNS), suggest that different solvents should be considered as individual compounds. While the current results are consistent with the notion that solvents affect cerebellar-vestibular function, they also demonstrate differences on selected components of this system which may be of concern.

Eye movements were recorded in the pigmented rat during vestibular, optokinetic and combined visual-vestibular stimulation. The dominant time constant in pigmented rats, tested during angular vestibular stimulation in darkness, is about two times longer than the cupular time constant. The gain and the duration of nystagmus, achieved by angular vestibular stimulation, can be enhanced by visual impulses. This is most evident during an optokinetic temporonasal stimulation, but is also seen with a nasotemporal stimulation. A mere optokinetic monocular stimulation without a synchronous vestibular excitation causes nystagmus only when the stimuli has a temporonasal direction. The duration of nystagmus, achieved by angular vestibular stimulation, is prolonged by disturbances of the neck proprioceptive system. This is more evident during a simultaneous visual input than in darkness. The ability to cancel nystagmus during conflicting vestibular and optokinetic impulses is well developed in the pigmented rat.

Toluene, an aromatic solvent, prolongs the duration of nystagmus induced by a rotatory acceleration or by an optokinetic stimulation in the pigmented rat. Baclofen, an agonist of GABA_B receptors, and 4,5,6,7-tetrahydroisoxazolo[5,4-c]-pyridin-3-ol (THIP), an agonist of GABA_A receptors are able to block this toluene effect on the vestibular system. On the contrary diazepam, which by itself causes an evident reduction of the duration of acceleratory nystagmus, is not able to block the toluene effect. The results indicate that the toluene effect is related to GABA transmission and that the solvent interacts by a rather receptor specific mechanism of action.