Pentoxifylline - a review of its use in osteoradionecrosis.

Pentoxifylline has been used to treat complications related to fibrosis for over 20 years. Formerly used to treat those after radiotherapy such as osteoradionecrosis (ORN), it is now being tried for medication-related osteonecrosis of the jaw (MRONJ), which can occur after prolonged use of bisphosphonates. We review theories on the formation of fibrosis in patients with ORN, discuss the pharmacology of pentoxifylline and vitamin E, and report published outcomes. To our knowledge no prospective randomised controlled trial has investigated the benefits of these agents in cases of ORN, but reported outcomes in many published case series are encouraging.

Cell adhesion molecules, the extracellular matrix and oral squamous carcinoma.

Carcinomas are characterized by invasion of malignant cells into the underlying connective tissue and migration of malignant cells to form metastases at distant sites. These processes require alterations in cell-cell and cell-extracellular matrix interactions. As cell adhesion molecules play a role in cell-cell and cell-extracellular matrix adhesion and interactions they are involved in the process of tumour invasion and metastases. In epithelial tissues, receptors of the integrin family mediate adhesion to the adjacent matrix whereas cadherins largely mediate intercellular adhesion. These and other cell adhesion molecules such as intercellular adhesion molecule-1, CD44, dystroglycans and selectins, are involved and undergo changes in carcinomas, which provide possible targets for anti-cancer drug treatments. In the extracellular matrix that is associated with tumours, laminin 5, oncofetal fibronectin and tenascin C appear. The degree of expression of some of these moieties indicates prognosis in oral cancer and offer targets for antibody-directed radiotherapy. Metalloproteases which degrade the extracellular matrix are increased in carcinomas, and their activity is necessary for tumour angiogenesis and consequent invasion and metastases. Metalloprotease inhibitors have begun to produce decreases in mortality in clinical trials. This report provides a brief overview of our current understanding of cell adhesion molecules, the extracellular matrix, tumour invasion and metastasis.

Perforator flaps in head and neck surgery.

A 'perforator flap' is a flap of skin or subcutaneous tissue that is based on the dissection of a 'perforating vessel'. Over the past few years a large number of 'perforator flaps' have been devised and described. By reducing any muscle harvest and trauma to a minimum, perforator flaps aim to minimize donor site morbidity whilst providing the reconstructive surgeon with more versatility than other flap types. The principal perforator flaps are discussed, particularly those employed in head and neck reconstruction including 'free style perforator flaps'. Methods of locating perforating vessels for the use of perforator flaps are described. The technique of perforator flap harvest is illustrated as exemplified in the anterolateral thigh perforator flap. Advantages in the use of this flap for head and neck reconstruction are discussed and are compared with that of non-perforator flaps, particularly the Radial Forearm Flap. The role of the primary thinning of perforator flaps is discussed. The versatility of the anterolateral flap is discussed, which may well supersede the Radial Forearm Flap as the principal soft tissue flap used in head and neck surgery.

Integrins in metastatic adenoid cystic carcinoma.

Adenoid cystic carcinoma exhibits a diverse clinical behaviour from very localised invasion to widespread metastatases. Recently two adenoid cystic carcinoma cells lines have been isolated and cultured which distinctly show either a low metastatic tendency (Acc-2) or a highly metastatic behaviour (Acc-M). It was hypothesised that these two types of behaviour may at least in part be explained by the different integrin profile on the cells' surface membrane. The integrins represent the largest known family of cell adhesion molecules and a number of tumour cell processes have been shown to be dependant on their integrin expression. Adenoid cystic carcinoma cells of both types were obtained and successfully cultured. These were then subjected to integrin analysis by a number of monoclonal antibodies to alpha(1), alpha(2), alpha(3), alpha(v), alpha(6), beta(1), alpha(v)beta6, alpha(v)beta4 using a fluorescence activated cell sorter. Although there was an apparent difference of integrin expression in the Acc-M group as compared to the Acc-2 group, this was not statistically significant. It is still possible though, that this might account for the differences in behaviour of the two cell lines, and the relationship between integrins, and invasion and metastases in other tumours is discussed. The pattern of integrin expression in Acc may be prognostically significant and useful for treatment planning in the future.

Oncofetal fibronectin and oral squamous cell carcinoma.

Fibronectin is a cell matrix glycoprotein, which exists as a number of isoforms that are often found within the cell matrix that surrounds tumours. Collectively these tumour-associated isomers of fibronectin have been termed oncofetal fibronectin (OFFN). We looked for expression of OFFN within oral squamous cell carcinomas (SCC) and related its presence to prognosis. The investigation used a monoclonal antibody (MoAb 5C10) to the glycosylated variant of OFFN, and 100 archival specimens of oral SSC. Immunostaining for OFFN was intense in the adjacent stroma of 43 squamous carcinomas, weak in 27 and absent in 30. Cervical metastases were found in 17/27 (63%) specimens that stained intensely, 6/17 (35%) that stained weakly and 3/13 (23%) that did not stain. Of the 21 cases which had extracapsular lymph node spread, 81% were from those that stained intensely, 19% from those that stained weakly and none from those that did not stain for OFFN expression. Also, 21/44 patients (49%) died in group with intense OFFN staining, 6/26 (23%) in the group with weak staining and 3/30 (10%) in the group that did not stain. The presence of OFFN glycoprotein in oral SCC as evaluated by immunostaining with MoAb 5C10 correlates strongly with the presence of metastatic lymph node involvement, particularly extracapsular involvement, and mortality. We therefore suggest that the degree of expression of OFFN in tumours is a valuable prognostic indicator.

Hepatitis C virus internal ribosome entry site RNA contains a tertiary structural element in a functional domain of stem-loop II.

The internal ribosome entry site (IRES) of hepatitis C virus (HCV) RNA contains >300 bases of highly conserved 5'-terminal sequence, most of it in the uncapped 5'-untranslated region (5'-UTR) upstream from the single AUG initiator triplet at which translation of the HCV polyprotein begins. Although progress has been made in defining singularities like the RNA pseudoknot near this AUG, the sequence and structural features of the HCV IRES which stimulate accurate and efficient initiation of protein synthesis are only partially defined. Here we report that a region further upstream from the AUG, stem-loop II of the HCV IRES, also contains an element of local tertiary structure which we have detected using RNase H cleavage and have mapped using the singular ability of two bases therein to undergo covalent intra-chain crosslinking stimulated by UV light. This pre-existing element maps to two non-contiguous stretches of the HCV IRES sequence, residues 53-68 and 103-117. Several earlier studies have shown that the correct sequence between bases 45 and 70 of the HCV IRES stem-loop II domain is required for initiation of protein synthesis. Because features of local tertiary structure like the one we report here are often associated with protein binding, we propose that the HCV stem-loop II element is directly involved in IRES action.

Salivary oncofoetal fibronectin and oral squamous cell carcinoma.

Fibronectin (FN) is a multifunctional adhesive glycoprotein that exists in the extracellular matrix and body fluids. As a result of alternative splicing, extra segments (ED-A and ED-B) may be included in the fibronectin molecule. These isoforms of FN, together with FN that has an extra glycosylation (OFFN), are strongly associated with a number of tumours, including oral squamous cell carcinoma (SCC). In view of the likely exfoliation of these cells into the oral cavity from tumours, OFFN might be present in saliva. As such, the presence of OFFN in saliva may be an indicator of oral SCC. The saliva of 12 patients with oral squamous carcinoma and 8 disease-free individuals was measured for OFFN using an enzyme-linked immunoassay. Salivary OFFN levels were similar for patients both with oral SCC and those without, suggesting that this would not be a useful test for the detection of oral SCC.

Anatomical variants of the cervical sympathetic chain to be considered during neck dissection.

Horner's syndrome, as a complication of radical neck dissection, is given little attention in textbooks of head and neck surgery. To investigate which topographical anatomic factors, if any, might influence damage to the sympathetic chain during neck dissection, we undertook a series of 12 cadaveric neck dissections. The axial position of the cervical sympathetic chain varied. The chain could be clearly delineated from the carotid sheath except in two cadavers, in which it was found within the sheath. The presence of cervical ganglia also varied. We suggest that if the chain is within the sheath, it may be more likely to be injured during operation.

Maxillofacial senior house officer posts: the trainee's perspective.

A questionnaire was sent out to all the maxillofacial senior house officers in the UK. The purpose of this was to evaluate their perceptions on working conditions, supervision, education and career aspirations. A high proportion (73 percent) returned questionnaires, and from the results of this it seems apparent that there are shortcomings in the supervision and education of SHOs. Based on these findings, a mandatory education programme is advocated that should be recorded in a logbook together with all operative procedures.

A 5-year audit of outcome of apicectomies carried out in a district general hospital.

Success rates of up to 90% have been claimed for apicectomy. However, the conditions that this procedure is carried out under at district general hospitals may be at variance with such studies. A 5-year audit of outcome was therefore carried out within a district general hospital. It was found that 89% of apicected teeth still remained at 5 years. Outcome was not influenced by any of the factors examined, and could not be predicted radiographically. Most failures occurred after the average postoperative review period of 10.5 months. Patient satisfaction with the procedure was high at over 90%. Based on these results it was concluded that apicectomy was an effective procedure when carried out by staff of all grades within the district general hospital, and that repeated follow-up appointments with radiographs over the first postoperative year were not useful.

DNA relatedness among strains of the sweet potato pathogen Streptomyces ipomoea (Person and Martin 1940) Waksman and Henrici 1948.

DNA relatedness among 28 putative strains of Streptomyces ipomoea from geographically diverse locations and the type strain, NRRL B-12321, was determined spectrophotometrically. The data confirm that these 28 strains are not closely related genetically to the plant-pathogenic species Streptomyces scabies (39% DNA relatedness) or Streptomyces acidiscabies (17% DNA relatedness) or any other major blue-spored Streptomyces species (less than 30% DNA relatedness). Of the 29 strains examined, 4 could be clearly distinguished from S. ipomoea on the basis of morphological criteria, i.e., they had gray rather than blue spores and produced melanin pigment, and their low DNA relatedness to authentic S. ipomoea strains confirmed their original misidentification. The remaining 25 S. ipomoea strains exhibited high DNA relatedness among themselves (76 to 100% homology), even though they had been isolated in different locations throughout the United States and Japan. The avirulent type strain, NRRL B-12321, exhibited slightly lower DNA relatedness with the virulent strains of S. ipomoea (85% average DNA relatedness) than was observed among the virulent strains (average of 96% DNA relatedness).

An investigation into the effect of traumatically produced cerebrospinal fluid fistulae on the passage of Augmentin across the blood-brain barrier.

In the management of cerebrospinal fluid (csf) fistulae, associated with head and facial injury, prophylactic antimicrobial drugs are employed commonly to prevent the occurrence of bacterial meningitis. Under normal circumstances, penicillins achieve a low csf/plasma concentration ratio, but trauma may reduce the efficacy of the blood-brain barrier and permit increased amounts of penicillins to enter the csf. To test this hypothesis, with respect to Augmentin (amoxycillin and clavulanic acid), an animal study was undertaken. Under general anaesthesia, the brains and meninges of a group of 10 rabbits were traumatised to produce csf fistulae. Following the administration of an intravenous bolus of Augmentin, the blood and csf concentrations of Augmentin were measured over a period of 6 h and compared with those measurements from an untraumatised control group of 10 rabbits. No difference in the csf/plasma ratio was apparent between the two groups. The results of this study, therefore, suggest that trauma to the brain and meninges does not increase the permeability of the blood-brain barrier to Augmentin.

Laboratory screening for zearalenone formation in corn hybrids and inbreds.

Grains from 14 corn inbreds and 4 single cross hybrids were inoculated with 3 isolates of Gibberella zeae to determine their inhibition of zearalenone production. The corn hybrids: Pa762 x A632 (50 mg/kg zearalenone production), A619 x A632 (17 mg/kg zearalenone production), H95 x Mo17 (132 mg/kg zearalenone production), and B73 x MO17 (33 mg/kg zearalenone production) appear to have less resistance than the inbreds to toxin formation. Inbred H95 (64 mg/kg zearalenone production) supported the highest toxin production of all inbreds. The remaining 13 inbreds did not exceed 15 mg/kg zearalenone production. The inbreds A632 (4 mg/kg zearalenone production) and Pa762 (2 mg/kg zearalenone production) demonstrated some resistance; the resulting cross, hybrid Pa762 x A632 (50 mg/kg zearalenone production), does have greater resistance than hybrid H95 x Mo17 (132 mg/kg zearalenone production). Analysis of variance indicated highly significant variation between corn varieties and fungal isolates. The coefficient of variation for 29 fermentations run in duplicate on inoculated control corn to produce zearalenone (212 mg/kg) was 37%, which would include variation in both the fermentation and analysis. Isolate and variety interaction is not significant.