Imaging of respiratory network topology in living brainstem slices.

Topology of neuronal networks contributes to their functioning but the structure-function relationships are not yet understood. In order to reveal the spatial organisation of the respiratory network, we expressed enhanced green fluorescent proteins in neurons in brainstem slices containing the respiratory kernel (pre-Bötzinger complex). The expression was neuron specific due to use of adeno-associated viral vector driving transgene expression from synapsin 1 promoter. Both neuronal cell bodies and their dendrites were labelled with high efficacy. This labelling allowed for enhanced spatial resolution as compared to conventional calcium-sensitive dyes. Neurons occupied about 10% of tissue volume and formed an interconnected network. Using custom-developed software, we quantified the network structure that had a modular structure consisting of clusters having transverse (dorso-ventral) orientation. They contained in average seven neurons and connections between the cells in different clusters were less frequent. This novel in situ imaging technique is promising to gain new knowledge about the fine structure and function of neuronal networks in living slice preparations.

Technical considerations in distraction osteogenesis.

Five cases are presented to exemplify technical difficulties and complications which may be encountered when performing distraction osteogenesis in the facial skeleton. The procedure should be performed under close supervision by the surgical and orthodontic colleagues. Errors in the choice of vector may be managed by earlier removal of the distractor and subsequent traction on the previously osteotomized segments using orthodontic appliances and principles. Multiple distractors may be inserted in the same jaw and bimaxillary procedures are possible, increasing the likelihood of encountering technical difficulties. Detailed planning and close follow-up, with early recognition and active management of the complications, may be useful in ensuring a successful outcome of this versatile procedure.

Metastatic malignant solitary fibrous tumour to the infra-temporal fossa.

Malignant solitary fibrous tumours (MSFTs) are rare tumours of fibrous origin, which can occur at all anatomical sites and represent 20% of solitary fibrous tumours. Fine-needle aspiration cytology is not able to distinguish benign from malignant disease, and sufficient tissue has to be obtained for accurate histological diagnosis to be made. Lesions > 10 cm in diameter and incomplete resection or non-resectability are predictive factors for poor long-term survival. We present a 57-year-old patient with a presumably metastatic MSFT from the peritoneal cavity to the skull-base who is in a stable state 17 months after surgical debulking of the skull-base and removal of the peritoneal lesion, followed by post-operative chemotherapy. We suggest the terminology metastatic malignant solitary fibrous tumour for a description of this disease.

Follow-up of collagen crosslink excretion in patients with oral squamous cell carcinoma and analysis of tissue samples.

The presence of an oral squamous cell carcinoma (OSCC) may be associated with increased urinary excretion of the markers of collagen degradation, hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP). We investigated the possibility of these markers predicting the presence of active disease. Patients from a current study on HP and LP were included as follows: Group 1a (OSCC with confirmed mandibular bony infiltration, n=12), group 1b (group 1a patients >6 months after successful treatment), group 2a (OSCC without evidence of mandibular bone infiltration, n=8), group 2b (group 2a patients >6 months after successful treatment), group 3a (recurrent OSCC, n=8), group 3b (group 3a patients >6 weeks later, symptoms unchanged) and group 4 (control group, n=74). Tissue samples from tumour tissue and adjacent healthy mucosa were additionally investigated for HP and LP concentrations (n=8). The decrease in the urinary concentrations of HP and LP was statistically significant between groups 1a and 1b (P<0.001 for HP and LP), but not between groups 2a and 2b (P=0.07 for HP and LP), while values in groups 1b and 2b were within the normal range. When comparing groups 3a and 3b, a significant increase was observed for LP (P=0.050), but not HP (P=0.208). In conclusion, successful treatment of OSCC with bony involvement may be associated with a reduction of urinary HP and LP, whereas ongoing disease may result in an increase of LP. HP and LP may both be useful markers of tumour progression in patients with OSCC.

Collagen crosslink excretion and staging of oral cancer.

Lysylpyridinoline (LP) and hydroxylysylpyridinoline (HP) are collagen crosslink residues of which the urinary concentration reflects the level of connective-tissue turnover. HP is ubiquitous in tissue, whereas LP is specific for bone. The purpose of this investigation was to assess the sensitivity and specificity of an increased urinary concentration of both HP and LP in indicating infiltration of mandibular bone by an oral squamous cell carcinoma (OSCC) or recurrence of the disease after successful therapy. We investigated the history and urine levels in 116 adult patients, who were divided into the following groups. Group 1: patients with OSCC with bone infiltration (n=17); group 2: patients with confirmed OSCC (n=12) without evidence of bone infiltration; group 3: patients with recurrence of an OSCC (n=13); group 4: patients without clinical evidence of disease (n=74). The range and upper limit of normal values (HP(max) and LP(max)) were measured from the normal controls in group 4. Levels of LP and HP were measured by HPLC and fluorescence detection. There was a significant difference in the average urinary levels of LP and HP between groups 1-4 (P<0.001). The presence of mandibular bone infiltration could be detected with a sensitivity and specificity of 100% when comparing groups 1 and 2. Presence of tumour tissue could be detected with a sensitivity of 90%. In conclusion, a normal LP concentration in patients with an OSCC strongly suggests that bone invasion by the disease has not taken place. If both urinary HP and LP are elevated, disease recurrence is highly likely.

[Clinical pilot study of interstitial photodynamic therapy for treatment of advanced head and neck tumors]. / Klinische Pilotstudie zur interstitiellen photodynamischen Therapie für die Behandlung von fortgeschrittenen Kopf-Hals-Tumoren.

BACKGROUND: Photodynamic therapy is a new treatment modality which uses a photochemical reaction to destroy tumour tissue. To date this treatment has only been applied effectively to the surface of small, superficial tumours due to the limitations imposed by light penetration. With the use of fibres introduced into the substance of the tumour, more bulky lesions can be treated successfully. STUDY: We describe the first clinical use of such a treatment in the management and, specifically, the amelioration of advanced head and neck cancer. We describe our results in 12 patients, in 11 of whom we were able to improve quality of life. In one patient there was no observable effect. The side-effects were minimal. DISCUSSION: We suggest that interstitial photodynamic therapy may be of use in the palliative care of patients with advanced disease and bulky tumours. It may also be of use in benign, bulky tumors, but this point requires further study.

Cellular neurothekeoma of the oral mucosa.

Cellular neurothekeoma is an unusual benign neoplasm which, despite its name, is of uncertain origin. This report describes a cellular neurothekeoma of the cheek mucosa, the first at this site. The tumour presented in a 29-year-old man as a discrete mucosal thickening. Histology showed a generally well circumscribed, but unencapsulated, solid tumour which replaced the entire lamina propria and permeated between minor salivary glands and bundles of striated muscle in the submucosa. There was a sub-epithelial Grenz zone. The tumour was composed of nodules of pale, epithelioid cells separated by fascicles of spindle cells, with smaller strands and nests superficially. The nuclei were vesicular and, though mainly bland, occasionally atypical. The stroma was moderately infiltrated by mixed chronic inflammatory cells. Prominent nerves and blood vessels were seen at the periphery of the lesion, and neoplastic cells were noted within intact striated muscle fascicles. With immunohistochemistry, all the neoplastic cells strongly expressed NKI/C3, synaptophysin, neurone-specific enolase and vimentin, some expressed smooth muscle actin and PGP 9.5, but all were negative for S100, factor XIIIa, CD34, CD56, CD57, CD68, chromogranin A, desmin, epithelial membrane antigen and von Willebrand factor. The origin of the lesion is thus speculative. It was, however, completely excised and in 12 months there has been no recurrence.

Optical biopsy systems for the diagnosis and monitoring of superficial cancer and precancer.

Histopathology is the gold standard in the diagnosis of cancer and dysplasia. Screening for the disease in high-risk populations(6,15) and choosing the correct site for biopsy have implications for the choice of follow-up intervals and therapy. Sully & Field(12) suggest that molecular genetic analysis, such as the polymerase chain reaction, for detecting progressive loss of heterozygosity, may be a more accurate predictor of the clinical course of oral cancer. This technique is now semi-automated and compares favourably with the time taken for histopathology (commonly 1-2 weeks). Recent developments suggest that the fluorescent and spectroscopic features may distinguish diseased from healthy tissue, and below follows an introduction for the clinician to this fascinating and complex field. It is possible to obtain a diagnosis in real-time and, with the appropriate use of photochemicals and image enhancement, it may be possible to treat and monitor the effects of treatment in real-time.

Ocular psychiatric disorders in maxillofacial injuries. Two case reports and a review of psychogenic ocular symptoms.

Ocular signs and symptoms associated with facial trauma can be a manifestation of an underlying psychiatric disorder which may exist prior to the traumatic incident, or even develop as a result of the stressful traumatic experience in a psychologically vulnerable individual. Two such cases are presented. A brief review of psychogenic ocular symptoms as well as suggestions for evaluation and treatment are discussed.