Burning mouth syndrome as a trigeminal small fibre neuropathy: Increased heat and capsaicin receptor TRPV1 in nerve fibres correlates with pain score.

Burning mouth syndrome (BMS) is often an idiopathic chronic and intractable pain condition, affecting 1.5-5.5% of middle-aged and elderly women. We have studied the heat and capsaicin receptor TRPV1, and its regulator nerve growth factor (NGF), in BMS. Patients with BMS (n=10) and controls (n=10) were assessed for baseline and post-topical capsaicin pain scores, and their tongue biopsies immunostained for TRPV1, NGF, and structural nerve markers neurofilament and peripherin. Nerve fibres penetrating the epithelium were less abundant in BMS (p<0.0001), indicating a small fibre neuropathy. TRPV1-positive fibres were overall significantly increased in BMS (p=0.0011), as were NGF fibres (p<0.0001) and basal epithelial cell NGF staining (p<0.0147). There was a significant correlation between the baseline pain score and TRPV1 (p=0.0143) and NGF fibres (p=0.0252). A significant correlation was observed between baseline and post-capsaicin pain (p=0.0006). Selective TRPV1 and NGF blockers may provide a new therapy for BMS.     

Failure modes of left ventricular reconstruction or the Dor procedure: a multi-institutional perspective.

BACKGROUND: Complex ventricular reconstruction (CVR) is now being employed increasingly thanks to the pioneering work of Dor. However, little is known about the failure mode of CVR. We present experience from three centres with CVR and an analysis of the failure modes. METHODS: Between January 1997 and February 2005, 284 patients underwent CVR in three centres in Australia and USA. All of the procedures were performed as adjuncts to coronary artery surgery and/or valvular surgery. Patients were followed-up clinically and/or echocardiographically. Failure modes were classified as fatal or non-fatal. Non-fatal failure mode (NFM) was defined as either persistent heart failure, recurrence of LV scar, need for ventricular assistance, persistent ventricular arrhythmia, or a combination. RESULTS: Operative mortality rate (OMR) was 8% (23 deaths). This fatal failure mode was most related to urgency of surgery and cardiogenic shock in 15 patients (5.3% of OMR), stroke in 5 patients (1.8%) or postoperative bi-ventricular failure (1%). Non-fatal failure modes accounted for morbidity in 26 patients (9%). This was predominantly due to persistent septal dyskinesis in 7 patients (2.46%), persistent mitral regurgitation in 5 (1.8%), postoperative ventricular tachycardia in 4 (1.4%), sub-optimal myocardial protection in 4 (1.4%) use of a large, stiff patch in 4 (1.4%). One hundred and ninety-nine of the surviving 261 patients (76%) were in NYHA Class I. CONCLUSIONS: Complex ventricular reconstruction is a robust technique that has lasting benefit. Failure modes have been identified and could be minimized by appropriate patient and procedure selection.     

Mapping brain size and cortical gray matter changes in elderly depression.

BACKGROUND: In elderly depression, volumetric brain imaging findings suggest abnormalities of the frontal lobe, particularly the orbitofrontal cortex, and the hippocampus. No studies to date have mapped cortical abnormalities over the entire brain surface in major depression. Here, we conducted detailed spatial analyses of brain size and gray matter within the cortical mantle in elderly patients with major depression. METHODS: High-resolution, three-dimensional, structural magnetic resonance imaging data and cortical pattern matching methods were used in 24 depressed elderly patients and 19 group-matched controls to measure local brain size and proportions of gray matter at thousands of homologous cortical surface locations. RESULTS: Prominent brain size reductions were observed in the depressed subjects in the orbitofrontal cortex bilaterally. Cortical gray matter measurements revealed significant gray matter increases in the orbitofrontal cortex, adjacent to focal trend level significant decreases of gray matter in the same region. Depressed patients also exhibited significant gray matter increases in parietal cortices, as well as the left temporal cortex. CONCLUSIONS: Complex cortical changes may contribute to the brain size reduction of the orbitofrontal cortex and to the gray matter abnormalities detected in orbitofrontal cortex and temporoparietal cortices, thereby providing a potentially new window into the pathophysiology of elderly depression.     

Assessment of cutaneous sensory and autonomic axon reflexes in rheumatoid arthritis.

OBJECTIVE--To assess sensory function in skin overlying the joints of patients with rheumatoid arthritis, in relation to the pain and tenderness which commonly arises in structures not directly involved in the inflammatory process. METHODS--An intradermal injection of capsaicin 0.05 microgram in 10 microliters was made over the wrists and forearms of 40 patients with rheumatoid arthritis and 46 control subjects. Axon reflex vasodilatation was measured using laser Doppler flowmetry. Cholinergic sympathetic function was assessed by measuring axon reflex sweating induced by a single intradermal injection of nicotine 0.5 microgram in 0.1 ml. RESULTS--Capsaicin induced axon reflex vasodilation over the wrists was found to decrease with age in normal subjects (r = -0.62, p < 0.001). In patients with rheumatoid arthritis, capsaicin induced axon reflex vasodilatation was significantly greater over the wrists, but not the forearms, when compared with age matched normal controls (p < 0.01). A minimal correlation between axon reflex vasodilatation and visual analogue pain score was apparent in the rheumatoid group (r = -0.37, p < 0.05). Nicotine induced sweating responses were similar in the rheumatoid and normal groups, and both showed a linear age related decline. CONCLUSIONS--The results show a selective increase of capsaicin induced vasodilatation in skin overlying joints in patients with rheumatoid arthritis. This suggests that the activity of a sub-population of periarticular small sensory fibres is altered, which may explain, at least in part, some of the clinical findings in this disorder.     

Neonatal pain management.

Neonatal pain management is a challenge for the clinician. Research is just beginning to uncover the neonates' capability of expression of pain, explore pharmacologic management strategies, and identify the spectrum of intrusions that may precipitate pain or distress in the critically ill neonate. This article reviews the neonatal biologic, behavioral, and physiologic responses to pain and describes recommendations for clinical management and decision-making.     

Surgical management of trismus due to Oral Submucous Fibrosis — Lysis of fibrotic bands with the KTP-532 Laser

Oral Submucous Fibrosis is an insidious, chronic disease affecting the oral cavity, sometimes the pharynx and rarely the tongue. 15 patients with Oral Submucous Fibrosis presenting with severe trismus were treated with lysis of the fibrotic bands with a KTP-532 Laser and adjunctive treatment with excellent results over a 12 month follow-up period.     

Induction of thioguanine-resistant mutations in human uroepithelial cells by 4-aminobiphenyl and its N-hydroxy derivatives.

The mutagenic potentials of the human bladder carcinogen 4-amino-biphenyl (ABP) and three of its proximate carcinogenic metabolites, N-hydroxy-4-aminobiphenyl (N-OH-ABP), N-hydroxy-4-acetylaminobiphenyl (N-OH-AABP) and N-acetoxy-4-acetylaminobiphenyl (N-OAc-AABP) were tested on a prime human target cell type for carcinogenesis, human uroepithelial cells (HUC). SV-HUC (PC), a near diploid, clonally derived, nontumorigenic SV40-immortalized human uroepithelial cell line that is transformable to tumorigenicity after exposure to ABP and its metabolites, was used for quantitative mutation assays. The end point used was the induction of mutations in the hypoxanthine-guanine phosphoribosyltransferase (HGPRT) locus, selected using 6-thioguanine resistance (TGr). A single, 24-h exposure of SV-HUC to ABP, N-OH-ABP, N-OH-AABP, or N-OAc-AABP caused a statistically significant, dose-dependent increase in mutation frequency resulting in a 2-30-fold increase in the number of TGr mutants in carcinogen-exposed groups compared to untreated controls. These chemicals were similarly mutagenic towards MC-T11, an SV-HUC-derived low grade tumor cell line that was also shown to be responsive to transformation (in a separate study) by ABP, N-OH-ABP, or N-OH-AABP as judged by the generation of higher grade tumors. In contrast, the mutagenic potencies of ABP and N-OH-ABP were lower when tested on a subclone of SV-HUC (BC) that is refractory to transformation by these chemicals. Thus, these data support a model of transformation in which ABP as well as its metabolites contribute to tumorigenic transformation and neoplastic progression of HUC by inducing mutations in susceptible target cell genes.     

Competitive dissociation of encephalitogenic complexes between antigen presenting cells and myelin basic protein

Splenic T cells from myelin basic protein (MBP)-immunised Lewis rats were activated to transfer experimental autoimmune encephalomyelitis (EAE) by co-culture with MBP-pulsed lymphoid dendritic cells (DC). MBP-pulsed DC could be kept for at least 24 h at 37 degrees C in antigen-free medium without affecting their ability subsequently to activate encephalitogenic T cells. However, MBP-pulsed DC were rendered much less stimulatory after a 6 h, but not 2 h, secondary incubation with ovalbumin. Thus, although encephalitogenic complexes between MBP and DC appear very stable in the absence of competing antigens, in their presence, antigen exchange can take place over a period of a few hours; this has positive implications for therapy of EAE by antigen competition.     

A comparison of presenting characteristics of patients with intracapsular and extracapsular proximal femoral fractures.

The presenting characteristics of 1423 consecutive admissions with proximal femoral fractures were prospectively studied, to determine any differences that may exist between patients, dependent on the radiological site of the fracture. Patients with intracapsular fractures were of a lower average age, more mobile, less likely to use walking aids or live in residential accommodation, they also had a considerably shorter length of hospital stay than for those patients with extracapsular fractures. Comparison against previous series shows that the average age of hip fracture patients and the proportion of trochanteric fractures is increasing.