Characteristics of disease related to mesio-angular mandibular third molar teeth.

The aim of this study was to identify the indications for the removal of mesio-angular mandibular third molars based on age and dental health as measured by the DMFT (decayed, missing, and filled teeth) score, and to find out if early intervention should be considered. We studied 319 patients who had 431 mesio-angular mandibular third molars removed. Variables recorded were age, primary indication for removal, and the DMFT score. Indications for removal included distal cervical caries (DCC) in the mandibular second molar (n=180, 44%), pericoronitis (n=131, 32%), and caries and related disease (n=62, 15%). The frequency of distal cervical caries (DCC) in the mandibular second molar increased linearly as patients became older and was the most common reason why mesio-angular third molar teeth were removed. This suggests that patients should be advised of the consequences of retaining thesetypes of third molars, and offered prophylactic removal of asymptomatic teeth.

The effects of NICE guidelines on the management of third molar teeth.

BACKGROUND: Third molar surgery (TMS) is probably one of the most commonly performed surgical procedures undertaken in the NHS. In 2000, the National Institute of Clinical Excellence (NICE) introduced guidelines relating to TMS. These recommended against the prophylactic removal of third molars and listed specific clinical indications for surgery. The impact of these guidelines has not been fully evaluated and this research hopes to focus the effect of these guidelines over the last ten years. METHODS: Using data obtained from a variety of NHS databases such as HES (Eng & Wales), the NHSBSA and data from NHS Scotland, we looked at the age range of patients requiring third molar removal and the number of patients having third molars removed in both primary and secondary care environments from 1989 to 2009. In addition we looked at the clinical indications for TMS activity in secondary care. FINDINGS: The mean age of patients increased from 25 years in 2000 to 32 years in 2010, with the modal (most common) age increasing from 26 to 29 years. After the introduction of clinical guidelines the number of patients requiring third molar removal in secondary care dropped by over 30%, however, since 2003 the number of patients has risen by 97%. There is also a significant increase in caries as an indication for third molar removal. CONCLUSIONS: More patients are requiring third molar removal with an increasing number of patients having caries related to their third molars. Patients are, on average, older confirming that the removal of third molars is shifting from a young adult population group to an older adult population group. NICE guidelines did appear to have contributed to a fall in the volume of third molars removed within the NHS post 2000. However, concluding that this reduction demonstrates the success of NICE's guidance would be a premature assumption. The number of patients now requiring third molar removal is comparable to that of the mid 1990s. NICE has influenced the management of patients with third molars but this has not resulted in any reduction in the number of patients requiring third molar removal. Coding and data collection for third molars is not uniform, leading to potential misrepresentation of data. This perhaps raises the issue that an improved universal coding system is required for the NHS and that the NICE guidelines need review.

Microarray analysis of phosphatase gene expression in human melanoma.

BACKGROUND: Tyrosine phosphate is abnormally elevated in malignant melanoma, and this has been interpreted to reflect the activity of oncogenic protein tyrosine kinases. However, elevation may also arise due to decreased protein tyrosine phosphatase (PTP) expression. OBJECTIVES: To survey phosphatase gene expression in melanoma cell lines, a benign naevus and normal melanocytes: we searched for downregulation of phosphatase gene expression in malignant cells that may indicate a role as melanoma suppressor genes. METHODS: Microarray analysis was used to compare gene expression for 133 phosphatase genes, comprising 39 PTPs, 16 dual-specificity phosphatases (DSPs), 47 serine/threonine phosphatases and 31 acid/alkaline and lipid-based phosphatases. Northern blotting analysis was used to study gene expression in human melanoma biopsies. RESULTS: There was decreased expression of four DSP genes (including PTEN); eight receptor PTP genes were downregulated in melanoma, among which were PTP-KAPPA and PTP-PI (consistent with our previous data). In addition, PTP-RF/LAR was downregulated in 13 of 22 metastatic melanomas. CONCLUSIONS: The expression of multiple PTP receptors is decreased in melanoma; this may be a mechanism which stimulates autonomous growth in advanced melanoma.

Molecular cytogenetic analysis of recurrent unbalanced t(11;17) in neuroblastoma.

Loss of 11q material occurs in approximately 30% of advanced stage neuroblastoma and defines a distinct genetic subtype of this disease. These tumors almost always possess unbalanced gain of the 17q, along with many additional recurrent chromosomal imbalances. Loss of 11q and gain of 17q is often the consequence of an unbalanced translocation between the long arms of both chromosomes, but because of the involvement of other chromosomal mechanisms, the actual frequency of t(11;17) is unknown. In addition, chromosomal breakpoint positions for the t(11;17) are variable in different tumors, with breakpoints on neither the 11q nor 17q being well defined. We have used interphase fluorescence in situ hybridization analysis to detect a der(11)t(11;17) in a series of neuroblastomas with 11q loss/17q gain using a statistical approach which could be applicable to the detection of translocations in other solid tumors. The frequency of der(11)t(11;17) was approximately 90% in our neuroblastoma series. A balanced t(11;17) was also detected in a MYCN amplified tumor, which is a distinctly different genetic subtype from the 11q- tumors. Breakpoint positions on 11q were determined to be variable, whereas all breakpoints on 17q appeared to cluster proximal to position 43.1 Mb on the DNA sequence map. The majority of tumors had large numbers of nuclei with 2 or more copies of der(11)t(11;17), which led to unbalanced gain of 11p, and further increases in 17q imbalance. The prevalence of t(11;17) in neuroblastoma warrants additional studies to further define the range in variation in breakpoint positions on both chromosomes and to elucidate the molecular mechanisms that lead to this important and interesting recurrent genetic abnormality.

Evolution of unbalanced gain of distal chromosome 2p in neuroblastoma.

Neuroblastoma, one of the most common tumors of childhood, presents at diagnosis with a vast number of recurrent chromosomal imbalances that include hyperdiploidy for whole chromosomes, partial loss of 1p, 3p, 4p, 11q, 14q, partial gain of 1q, 7q, 17q and amplification of MYCN. These abnormalities are nonrandomly distributed in neuroblastoma as loss of 3p and 11q rarely occur in MYCN amplified neuroblastomas. Here, we report on a patient who had a non-MYCN amplified 3p-/11q- neuroblastoma at diagnosis who subsequently developed a high level of MYCN amplification in bone marrow metastases 41 months after induction of complete remission. The tumor at diagnosis had low level unbalanced gain of distal 2p. In order to assess the frequency of low level gain of distal 2p in neuroblastoma, we examined the comparative genomic hybridization results from 60 neuroblastomas. Among non-MYCN amplified neuroblastomas, 8/45 (18%) had low level gain of distal 2p. Low level gain for a segment of 2p (i.e. a region larger than the 2p23-->p24 undergoing amplification) was also detected in five of the 15 tumors that had high level MYCN amplification. The possibility that low level gain of distal 2p is a risk factor for high level MYCN amplification is discussed.

Oligonucleotide microarray analysis of gene expression in neuroblastoma displaying loss of chromosome 11q.

A number of distinct subtypes of neuroblastoma exist with different genetic abnormalities that are predicative of outcome. Whole chromosome gains are usually associated with low stage disease and favourable outcome, whereas loss of 1p, 3p and 11q, unbalanced gain of 17q and MYCN amplification (MNA) are indicative of high stage disease and unfavourable prognosis. Although MNA and loss of 11q appear to represent two distinct genetic subtypes of advanced stage neuroblastoma, a detailed understanding of how these subtypes differ in terms of global gene expression is still lacking. We have used metaphase comparative genomic hybridization (CGH) analysis in combination with oligonucleotide technology to identify patterns of gene expression that correlate with specific genomic imbalances found in primary neuroblastic tumours and cell lines. The tumours analysed in this manner included a ganglioneuroma, along with various ganglioneuroblastoma and neuroblastoma of different stages and histopathological classifications. Oligonucleotide microarray-based gene expression profile analysis was performed with Affymetrix HU133A arrays representing approximately 14 500 unique genes. The oligonucleotide microarray results were subsequently validated by quantitative real-time PCR, immunohistochemical staining, and by comparison of specific gene expression patterns with published results. Hierarchical clustering of gene expression data distinguished tumours on the basis of stage, differentiation and genetic abnormalities. A number of genes were identified whose patterns of expression were highly correlated with 11q loss; supporting the concept that loss of 11q represents a distinct genetic subtype of neuroblastoma. The implications of these results in the process of neuroblastoma development and progression are discussed.

Tyrosine phosphate in melanoma progression.

BACKGROUND: Cellular tyrosine phosphorylation is regulated by two large families of enzymes. Protein tyrosine kinases (PTK) mediate addition, and protein tyrosine phosphatases (PTP), removal of phosphate from protein substrates. PTKs are oncogenes and PTPs have been hypothesized to function as tumour suppressor genes. OBJECTIVES: To determine changes in tyrosine phosphate and PTP activity that occur during melanoma progression. METHODS: Immunohistochemistry was used to study phosphotyrosine in melanocytic lesions. In addition, PTP activity of normal melanocytes and melanoma cell lines was measured using an enzyme-linked immunosorbent assay-based system. RESULTS: Melanocytes in normal skin and most (67%) benign naevi were not immunostained. Neither were early malignant lesions (80% of malignant melanoma in situ and radial growth phase melanomas) stained. However, most advanced melanomas (100% of vertical growth phase, and 90% of metastatic melanomas) were immunoreactive. When total PTP enzyme activity was assayed in normal melanocytes and malignant melanoma cell lines, there was a significant increase in activity associated with melanoma progression. CONCLUSIONS: Taken together, the data suggest increased phosphotyrosine signalling occurs during melanoma progression at the stage when cells first become competent for metastasis.

Protein tyrosine phosphatase genes downregulated in melanoma.

Phospho-tyrosine levels are increased in melanoma, apparently consistent with reports of elevated protein tyrosine kinase activity. Some protein tyrosine kinases are encoded by oncogenes and have been implicated in melanoma genesis. Decreased protein tyrosine phosphatase activity may also increase phospho-tyrosine. Protein tyrosine phosphatase genes are candidate tumor suppressors and loss of expression may contribute to melanoma genesis. Here we survey protein tyrosine phosphatase expression in pigment cells. Protein tyrosine phosphatase genes were cloned by reverse transcriptase polymerase chain reaction using degenerate primers based upon conserved sequences within the phosphatase catalytic domain. Reaction products were cloned and sequenced: 118 and 113 partial protein tyrosine phosphatase products were isolated from normal melanocytes and melanoma cells, respectively. Northern blotting analysis was used to study expression of 15 protein tyrosine phosphatase genes. Expression of PTP-kappa and PTP-pi was absent or downregulated in more than 20% of melanoma cell lines and in some unmanipulated melanoma biopsies. These closely related enzymes are members of the 2B receptor protein tyrosine phosphatase family previously implicated in contact inhibition. Loss of protein tyrosine phosphatase expression may contribute to the abnormal tyrosine phosphorylation seen in melanoma; these genes are candidate tumor suppressors.

Specialisation in oral surgery.

The 1994 report by the chief dental officer on specialist dental training in the UK focuses on the need for a more structured approach to post-graduate education and practice. As the report is designed to produce a broad choice of specialist dental services that will be based in the primary rather than the secondary care sector, specialist services will become more accessible to both the dental profession and patients.

Comparison of patient-controlled sedation with either methohexitone or propofol.

We studied 42 patients undergoing oral surgery under local anaesthesia with i.v. sedation, allocated randomly to receive either methohexitone (group M) or propofol (group P) for patient-controlled sedation (PCS). Group M patients self-administered 2.5-mg (0.5 ml) bolus doses of methohexitone and group P, 5-mg (0.5 ml) doses of propofol, without a lockout. The 0.5-ml bolus dose was delivered over 7.2 s for both drugs. The procedure was completed satisfactorily in all patients. Patients in both groups achieved their desired levels of sedation. No patient lost verbal contact. Group M patients had higher heart rates during the procedure. The lowest SpO2 values recorded were 92% and 95% for group P and group M, respectively. Immediately after operation patients in group M reported that they felt more sleepy than those in group P (P < 0.01) but there were no differences at subsequent times. The results of the psychomotor tests were comparable for the two groups after operation, except for the "posting box task" at 15 min after operation when the mean decrement (compared with preoperative performance) was -3% for group P and -13% for group M (P < 0.05). More patients in group P complained of pain in their hand. We conclude that methohexitone is a suitable alternative drug to propofol for PCS.

Maxillary and mandibular reconstruction in preparation for endosseous implants.

Bony and soft tissue deficiencies can deter esthetic, functional and prosthetic rehabilitation. Modern surgical techniques using bone or composite grafts to reconstruct or augment implant sites are reviewed.

The effects of propofol and thiopentone on forearm circulation.

Some effects of propofol and thiopentone induction on the peripheral circulation of healthy patients are examined using mercury strain gauge venous occlusion plethysmography of the forearm. Results indicate that both drugs produce a statistically significant decrease in mean arterial blood pressure and forearm blood flow. Forearm vascular resistance remains unchanged after either drug. These data suggest that bolus dose induction of anaesthesia with propofol does not cause arterial vasodilatation of the limb and that a cause for the reduction in mean arterial pressure must be sought elsewhere.

Allergy to laboratory animals: a survey by questionnaire.

A survey carried out on a total of 1,487 individuals showed that, of the 585 who worked with laboratory animals, 19.5% developed moderate to severe allergic symptoms some time after starting employment. The corresponding figure for those who had never worked with animals was 13.4%. The animal worker group contained significantly more individuals with asthma, repeated attacks of sneezing, blocked nose or smarting eyes (alone or in combination), than did the control group. There was no significant difference in terms of the incidence or type of allergy developing after employment between those who did and those who did not report pre-employment symptoms of atopy. 9% of the animal workers had to stop work permanently or temporarily because of their allergy.