Oral lichen planus: Causes, diagnosis and management

Oral lichen planus (OLP) is a chronic inflammatory disease of unknown etiology. In this paper we review the clinical and histological features of OLP, process of OLP diagnosis, causes of OLP, management of OLP patients and medical treatment of OLP lesions. Approximately 0.2 per cent OLP patients develop intra-oral carcinoma each year compared with approximately 0.005 per cent Australian adults. Possible mechanisms of increased oral cancer risk in OLP patients are presented. The aims of current OLP therapy are to eliminate mucosal erythema and ulceration, alleviate symptoms and reduce the risk of oral cancer. Patient education may improve the outcomes of OLP therapy and further reduce the risk of oral cancer in OLP patients. Although OLP may be diagnosed clinically, appropriate specialist referral is required for: (i) histological diagnosis; (ii) assessment of causative/exacerbating factors, associated diseases and oral cancer risk; (iii) patient education and management; (iv) medical treatment; and (v) long-term review and re-biopsy as required.

Detection and stability of Japanese encephalitis virus RNA and virus viability in dead infected mosquitoes under different storage conditions

A semi-nested polymerase chain reaction (PCR) was evaluated for detection of Japanese encephalitis (JE) virus in infected mosquitoes stored under simulated northern Australian summer conditions. The effect of silica gel, thymol, and a combination of the two on RNA stability and virus viability in dead mosquitoes were also examined. While JE virus RNA was relatively stable in mosquitoes held for up to 14 days after death, viable virus was not detected after day 1. Thymol vapor inhibited fungal contamination. Detection of single mosquitoes infected with JE virus in large pools of mosquitoes was also investigated. Single laboratory-infected mosquitoes were detected in pools of less than or equal to200 mosquitoes and in pools diluted to 0.2/100 and 0.1/100 mosquitoes, using the semi-nested PCR. However, the ability to detect live virus decreased as pool size increased. The semi-nested PCR proved more expensive than virus isolation for pools of 100 mosquitoes. However, the semi-nested PCR was faster and more economical using larger pools. Results indicate that surveillance of JE virus in mosquitoes using the semi-nested PCR is an alternative to monitoring seroconversions in sentinel pigs.

Partitioned Bremer support and multiple trees

Partitioned Bremer support (PBS) is a valuable means of assessing congruence in combined data sets, but some aspects require clarification. When more than one equally parsimonious tree is found during the constrained search for trees lacking the node of interest, averaging PBS for each data set across these trees can conceal conflict, and PBS should ideally be examined for each constrained tree. Similarly, when multiple most parsimonious trees (MPTs) are generated during analysis of the combined data, PBS is usually calculated on the consensus tree. However, extra information can be obtained if PBS is calculated on each of the MPTs or even suboptimal trees. (C) 2002 The Willi Hennig Society. Published by Elsevier Science (USA). All rights reserved.

Testing the relationship between morphological and molecular rates of change along phylogenies

Molecular evolution has been considered to be essentially a stochastic process, little influenced by the pace of phenotypic change. This assumption was challenged by a study that demonstrated an association between rates of morphological and molecular change estimated for total-evidence phylogenies, a finding that led some researchers to challenge molecular date estimates of major evolutionary radiations. Here we show that Omland's (1997) result is probably due to methodological bias, particularly phylogenetic nonindependence, rather than being indicative of an underlying evolutionary phenomenon. We apply three new methods specifically designed to overcome phylogenetic bias to 13 published phylogenetic datasets for vertebrate taxa, each of which includes both morphological characters and DNA sequence data. We find no evidence of an association between rates of molecular and morphological rates of change.

GH treatment in adults with chronic liver disease: A randomized, double-blind, placebo-controlled, cross-over study

Patients with chronic liver disease (CLD) are catabolic and GH-resistant. The effects of supraphysiological recombinant human GH (rhGH; 0.2 IU.kg(-1).d(-1)) treatment in adults with CLD were assessed in a randomized, double-blind, placebo-controlled cross-over trial (4-wk dietary run-in, 4-wk treatment, and 2-wk wash-out phases). Nine adults with mild- to moderate-severity CLD participated (median age, 49 yr; three males and six females; Child's classification A in six and B in three). Biopsy-proven etiologies were: alcohol (four patients), primary biliary cirrhosis (three patients), non-A, non-B, non-C hepatitis (one patient), and cryptogenic (one patient). Treatment with rhGH increased serum IGF-I (median increase over placebo, +93 mug.liter(-1); P = 0.004), IGF-binding protein-3 (+0.9 mg.liter(-1): P = 0.004), and acid labile subunit (+10.7 nM; P = 0.004). Total body potassium (+8.0 g; P = 0.023), body weight (+1.6 kg; P = 0.008), and total body water (by bioelectrical impedance; +4.9 kg; P = 0.004) increased. Resting metabolic rate (+313 ml.kg(-1).min(-1); P = 0.004) and lipid oxidation (+1072.0 kcal.d(-1); P = 0.032) increased. Metabolic changes included increased fasting plasma glucose (+1.2 mm; P = 0.008), insulin (+33.8 mU.liter(-1); P = 0.004), C-peptide (+0.7 nM; P = 0.004), and free-fatty acids (+0.1 mEq.liter(-1); P = 0.04). Clinical side effects included worsening edema and ascites. Hepatocellular function did not change. Therefore, rbGH treatment in CLD: 1) overcame hepatic GH resistance; 2) may have improved whole-body protein catabolism; 3) increased lipolysis and lipid oxidation; 4) increased insulin resistance; and 5) had potent antinatriuretic effects. Long-term safety and efficacy require further assessment.

Expression analysis of delta-catenin and prostate-specific membrane antigen: Their potential as diagnostic markers for prostate cancer

The current approach to prostate cancer diagnosis has major limitations including the inability of prostate-specific antigen (PSA) assays to accurately differentiate between prostate cancer and benign prostate hyperplasia (BPH) and the imprecision of transrectal ultrasound (TRUS) biopsy sampling. We have employed cDNA microarray screening to compare gene expression patterns in BPH and tumour samples to identify expression markers that may be useful in discriminating between these conditions. Screening of 3 individual cDNA arrays identified 8 genes with expression 3-fold greater in 6 tumour tissues than in 1 nontumour sample and I BPH sample. Real-time PCR was used to confirm the overexpression of these 8 genes and 12 genes selected from the literature against a panel of 17 tumours and I 1 BPH samples. Two genes, delta-catenin (delta-catenin; CTNND2) and prostate-specific membrane antigen (PSMA; FOLH1), were significantly overexpressed in prostate cancer compared to BPH. Prostate epithelial cells stained positively for S-catenin and PSMA in our prostate cancer tissues, whereas the majority of our BPH tissues were negative for both markers. Thus we have identified delta-catenin (not previously associated with prostatic adenocarcinoma) and confirmed the potential of PSMA as potential candidates for the diagnosis and management of prostate cancer. (C) 2002 Wiley-Liss. Inc.

Social structure in migrating humpback whales (Megaptera novaeangliae)

Although largely solitary, humpback whales exhibit a number of behaviours where individuals co-operate with one another, for example during bubble net feeding. Such cases could be due to reciprocal altruism brought on by exceptional circumstances, for example the presence of abundant shoaling fish. An alternative explanation is that these behaviours have evolved through kin selection. With little restriction to either communication or movement, diffuse groups of relatives could maintain some form of social organization without the need to travel in tight-nit units. To try to distinguish between these hypotheses, we took advantage of the fact that migrating humpback whales often swim together in small groups. If kin selection is important in humpback whale biology, these groups should be enriched for relatives. Consequently, we analysed biopsy samples from 57 groups of humpback whales migrating off Eastern Australia in 1992. A total of 142 whales were screened for eight microsatellite markers. Mitochondrial DNA sequences (371 bp) were also used to verify and assist kinship identification. Our data add support to the notion that mothers travel with their offspring for the first year of the calf's life. However, beyond the presence of mother-calf/yearling pairs, no obvious relatedness pattern was found among whales sampled either in the same pod or on the same day. Levels of relatedness did not vary between migratory phases (towards or away from the breeding ground), nor between the two sexes considered either overall or in the north or south migrations separately. These findings suggest that, if any social organization does exist, it is formed transiently when needed rather than being a constant feature of the population, and hence is more likely based on reciprocal altruism than kin selection.

Slowed conduction and ventricular tachycardia after targeted disruption of the cardiac sodium channel gene Scn5a

Voltage-gated sodium channels drive the initial depolarization phase of the cardiac action potential and therefore critically determine conduction of excitation through the heart. In patients, deletions or loss-of-function mutations of the cardiac sodium channel gene, SCN5A, have been associated with a wide range of arrhythmias including bradycardia (heart rate slowing), atrioventricular conduction delay, and ventricular fibrillation. The pathophysiological basis of these clinical conditions is unresolved. Here we show that disruption of the mouse cardiac sodium channel gene, Scn5a, causes intrauterine lethality in homozygotes with severe defects in ventricular morphogenesis whereas heterozygotes show normal survival. Whole-cell patch clamp analyses of isolated ventricular myocytes from adult Scn5a(+/-) mice demonstrate a approximate to50% reduction in sodium conductance. Scn5a(+/-) hearts have several defects including impaired atrioventricular conduction, delayed intramyocardial conduction, increased ventricular refractoriness, and ventricular tachycardia with characteristics of reentrant excitation. These findings reconcile reduced activity of the cardiac sodium channel leading to slowed conduction with several apparently diverse clinical phenotypes, providing a model for the detailed analysis of the pathophysiology of arrhythmias.

Benefits, harms and costs of screening mammography in women 70 years and over: a systematic review

Objective: To assess the (i) benefits, (ii) harms and (iii) costs of continuing mammographic screening for women 70 years and over. Data sources and synthesis: (i) We conducted a MEDLINE search (1966 - July 2000) for decision-analytic models estimating life-expectancy gains from screening in older women. The five studies meeting the inclusion criteria were critically appraised using standard criteria. We estimated relative benefit from each model's estimate of effectiveness of screening in older women relative to that in women aged 50-69 years using the same model. (ii) With data from BreastScreen Queensland, we constructed balance sheets of the consequences of screening for women in 10-year age groups (40-49 to 80-89 years), and (iii) we used a validated model to estimate the marginal cost-effectiveness of extending screening to women 70 years and over. Results: For women aged 70-79 years, the relative benefit was estimated as 40%-72%, and 18%-62% with adjustment for the impact of screening on quality of life. For women over 80 years the relative benefit was about a third, and with quality-of-life adjustment only 14%, that in women aged 50-69 years. (ii) Of 10 000 Australian women participating in ongoing screening, about 400 are recalled for further testing, and, depending on age, about 70-112 undergo biopsy and about 19-80 cancers are detected. (iii) Cost-effectiveness estimates for extending the upper age limit for mammographic screening from 69 to 79 years range from $8119 to $27 751 per quality-adjusted life-year saved, which compares favourably with extending screening to women aged 40-49 years (estimated at between $24 000 and $65 000 per life-year saved). Conclusions: Women 70 years and over, in consultation with their healthcare providers, may want to decide for themselves whether to continue mammographic screening. Decision-support materials are needed for women in this age group.

The 2000 Ogura Lecture: Olfactory neural cells: An untapped diagnostic and therapeutic resource

Objective. This is an over-view of the cellular biology of upper nasal mucosal cells that have special characteristics that enable them to be used to diagnose and study congenital neurological diseases and to aid neural repair. Study Design: After mapping the distribution of neural cells in the upper nose, the authors' investigations moved to the use of olfactory neurones to diagnose neurological diseases of development, especially schizophrenia. Olfactory-ensheating glial cells (OEGs) from the cranial cavity promote axonal penetration of the central nervous system and aid spinal cord repair in rodents. The authors sought to isolate these cells from the more accessible upper nasal cavity in rats and in humans and prove they could likewise promote neural regeneration, making these cells suitable for human spinal repair investigations. Methods: The schizophrenia-diagnosis aspect of the study entailed the biopsy of the olfactory areas of 10 schizophrenic patients and 10 control subjects. The tissue samples were sliced and grown in culture medium. The ease of cell attachment to fibronectin (artificial epithelial basement membrane), as well as the mitotic and apoptotic indices, was studied in the presence and absence of dopamine in those cell cultures. The neural repair part of the study entailed a harvesting and insertion of first rat olfactory lamina propria rich in OEGs between cut ends of the spinal cords and then later the microinjection of an OEG-rich suspension into rat spinal cords previously transected by open laminectomy. Further studies were done in which OEG insertion was performed up to 1 month after rat cord transection and also in monkeys. Results: Schizophrenic patients' olfactory tissues do not easily attach to basement membrane compared with control subjects, adding evidence to the theory that cell wall anomalies are part of the schizophrenic lesion of neurones. Schizophrenic patient cell cultures had higher mitotic and apoptotic indices compared with control subjects. The addition of dopamine altered these indices enough to allow accurate differentiation of schizophrenics from control patients, leading to, possibly for the first time, an early objective diagnosis of schizophrenia and possible assessment of preventive strategies. OEGs from the nose were shown to be as effective as those from the olfactory bulb in promoting axonal growth across transected spinal cords even when added I month after injury in the rat. These otherwise paraplegic rats grew motor and proprioceptive and fine touch fibers with corresponding behavioral improvement. Conclusions. The tissues of the olfactory mucosa are readily available to the otolaryngologist. Being surface cells, they must regenerate (called neurogenesis). Biopsy of this area and amplification of cells in culture gives the scientist a window to the developing brain, including early diagnosis of schizophrenia. The Holy Grail of neurological disease is the cure of traumatic paraplegia and OEGs from the nose promote that repair. The otolaryngologist may become the necessary partner of the neurophysiologist and spinal surgeon to take the laboratory potential of paraplegic cure into the day-to-day realm of clinical reality.

Transport and metabolism of xylem cytokinins during lateral bud release in decapitated chickpea (Cicer arietinum) seedlings

Although cytokinins (CKs) are widely thought to have a role in promoting shoot branching, there is little data supporting a causative or even a correlative relationship between endogenous CKs and timing of bud outgrowth. We previously showed that lateral bud CK content increased rapidly following shoot decapitation. However, it is not known whether roots are the source of this CK. Here, we have used shoot decapitation to instantaneously induce lateral bud release in chickpea seedlings. This treatment rapidly alters rate and direction of solvent and solute (including CK) trafficking, which may be a passive signalling mechanism central to initiation of lateral bud release. To evaluate changes in xylem transport, intact and decapitated plants were infiltrated with [H-3]zeatin riboside ([H-3]ZR), a water-soluble blue dye or [H-3]H2O by injection into the hypocotyl. All three tracers were recovered in virtually all parts of the shoot within I h of injection. In intact plants, solute accumulation in the lateral bud at node 1 was significantly less than in the adjacent stipule and nodal tissue. In decapitated plants, accumulation of [H-3]ZR and of blue dye in the same bud position was increased 3- to 10-fold relative to intact plants, whereas content of [H-3]H2O was greatly reduced indicating an increased solvent throughput. The stipule and cut stem, predicted to have high evapotranspiration rates, also showed increased solute content accompanied by enhanced depletion of [H-3]H2O. To assess whether metabolism modifies quantities of active CK reaching the buds, we followed the metabolic fate of [H-3]ZR injected at physiological concentrations. Within 1 h, 80-95% of [H-3]ZR was converted to other active CKs (mainly zeatin riboside-5'phosphate (ZRMP) and zeatin (Z)), other significant, but unconfirmed metabolites some of which may be active (O-acetylZR, O-acetylZRMP and a compound correlated with sites of high CK-concentrations) and inactive catabolites (adenosine, adenine, 5'AMP and water). Despite rapid metabolic degradation, the total active label, which was indicative of CK concentration in buds, increased rapidly following decapitation. It can be inferred that xylem sap CKs represent one source of active CKs appearing in lateral buds after shoot decapitation.

Leaf area development of ABA-deficient and wild-type peas at two levels of nitrogen supply

The ABA-deficient wilty pea (Pisum sativum L.) and its wild-type (WT) were grown at two levels of nitrogen supply (0.5 and 5.0 mM) for 5-6 weeks from sowing, to determine whether leaf ABA status altered the leaf growth response to N deprivation. Plants were grown at high relative humidity to prevent wilting of the wilty peas. Irrespective of N supply, expanding wilty leaflets had ca 50% less ABA than WT leaflets but similar ethylene evolution rates. Fully expanded wilty leaflets had lower relative water contents (RWC) and were 10-60% smaller in area (according to the node of measurement) than WT leaflets. However, there were no genotypic differences in plant relative leaf expansion rate (RLER). Growth of both genotypes at 0.5 mM N increased the RWC of fully expanded leaflets, but did not alter ethylene evolution or ABA concentration of expanding leaflets. Plants grown at 0.5 mM N showed a 20-30% reduction in RLER, which was similar in magnitude in both wilty and WT peas. Thus, leaf ABA status did not alter the leaf growth response to N deprivation.

Myoelectric manifestations of sternocleidomastoid and anterior scalene muscle fatigue in chronic neck pain patients

Objective: This study compares myoelectric manifestations of fatigue of the sternocleidomastoid (SCM) and anterior scalene (AS) muscles between 10 chronic neck pain subjects and 10 normal matched controls. Methods: Surface electromyography (sEMG) signals were recorded from the sternal bead of SCM and AS muscles bilaterally during submaximal isometric cervical flexion contractions at 25 and 50% of the maximum voluntary contraction (MVC). The mean frequency, average rectified value and conduction velocity of the sEMG signal were calculated to quantify myoelectric manifestations of muscle fatigue. Results: For both the SCM and AS muscles, the Mann-Whitney U test indicated that the initial value and slope of the mean frequency in neck pain patients were greater than in healthy subjects (P < 0.05). This was significant both at 25 and 50% of MVC. Conclusions: These results suggest: (a) a predominance of type-II fibres in the neck pain patients and/or (b) greater fatigability of the superficial cervical flexors in neck pain patients. These results are in agreement with previous muscle biopsy studies in subjects with neck pain, which identified transformation of slow-twitch type-I fibres to fast-twitch type-IIB fibres, as well as the clinical observation of reduced endurance in the cervical flexors in neck pain patients. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.

Prognostic use of growth characteristics of early gastric cancer and expression patterns of apoptotic, cell proliferation, and cell adhesion proteins

Background and Objectives: Selection of suitable treatment for early gastric cancers, such as endoscopic mucosal resection or the major surgical option of resection of the cancer together with a radical lymph node dissection, may be assisted by comparing the growth characteristics of the cancer with selected molecular characteristics. The results could be used to predict those cases that have a higher risk of developing secondary metastases. Methods: A total of 1,196 Japanese patients with early gastric cancers (648 mucosal cancers and 548 submucosal) were included in the selection of two groups: a metastatic group made up 57 cancers with lymph node metastasis (9 mucosal, 48 submucosal), and a nonmetastatic group of 61 cases (6 mucosal, 55 submucosal) without lymph node metastasis. Growth characteristics of the cancers (superficially spreading, penetrating or invasive, lymph node metastasis) were compared with immunohistochemical expression of single-stranded DNA (ssDNA) protein (apoptosis indicator), bcl-2 and p53 (apoptosis-associated), Ki-67 (cell proliferation), and E-cadherin (cell adhesion) proteins. Results: The lesions in the nonmetastatic group had higher levels of apoptosis and lower expression of bcl-2 than in the metastatic group, indicating an inhibitory role for apoptosis in malignant progression. Apoptosis was also higher in the superficial compared with the invasive lesions of both groups. The lesions in the metastatic group had higher p53 expression than that of the nonmetastatic group, whereas apoptosis in the metastatic group was lower than in the nonmetastatic group. An unproved explanation for this finding may be that, although increased, p53 was mutated and ineffective in promoting apoptotic control of metastatic progression. E-cadherin was decreased in the invasive lesions of both groups, indicating a greater ability of these cells to lose adhesion, to invade the submucosa, and to metastasize. Cell proliferation was highest in the superficial lesions of both metastatic and nonmetastatic groups. Conclusions: Early gastric cancers with low levels of apoptosis, increased bcl-2, and high levels of p53 expression are more likely to invade and metastasize. (C) 2003 Wiley-Liss, Inc.

A partial velocity approach to subcycling structural dynamics

Subcycling, or the use of different timesteps at different nodes, can be an effective way of improving the computational efficiency of explicit transient dynamic structural solutions. The method that has been most widely adopted uses a nodal partition. extending the central difference method, in which small timestep updates are performed interpolating on the displacement at neighbouring large timestep nodes. This approach leads to narrow bands of unstable timesteps or statistical stability. It also can be in error due to lack of momentum conservation on the timestep interface. The author has previously proposed energy conserving algorithms that avoid the first problem of statistical stability. However, these sacrifice accuracy to achieve stability. An approach to conserve momentum on an element interface by adding partial velocities is considered here. Applied to extend the central difference method. this approach is simple. and has accuracy advantages. The method can be programmed by summing impulses of internal forces, evaluated using local element timesteps, in order to predict a velocity change at a node. However, it is still only statistically stable, so an adaptive timestep size is needed to monitor accuracy and to be adjusted if necessary. By replacing the central difference method with the explicit generalized alpha method. it is possible to gain stability by dissipating the high frequency response that leads to stability problems. However. coding the algorithm is less elegant, as the response depends on previous partial accelerations. Extension to implicit integration, is shown to be impractical due to the neglect of remote effects of internal forces acting across a timestep interface. (C) 2002 Elsevier Science B.V. All rights reserved.