Development and evaluation of the clinimetric properties of the Medication-Related Osteonecrosis of the Jaw Quality of Life Questionnaire (MRONJ-QoL).

The purpose of this study was to develop a self-administered questionnaire (MRONJ-QoL) to assess the quality of life (QoL) of patients with medication-related osteonecrosis of the jaw (MRONJ). A prospective study was performed to develop and evaluate the questionnaire. The MRONJ-QoL was formulated through a review of the literature and interviews of experts and patients. Following development, it was administered to 60 patients with a diagnosis of MRONJ. The sensibility of the questionnaire was assessed by evaluating feasibility (via interviews of patients), face validity (via interviews of patients and experts), and content validity (via evaluation of internal consistency, floor/ceiling effects, and factor analysis). Reliability was evaluated by measuring intra-rater reliability. Construct validity of the questionnaire was evaluated by both cross-sectional and longitudinal comparisons, including comparing scores of the MRONJ-QoL to disease resolution at 6 months. The final MRONJ-QoL questionnaire consisted of 14 questions, demonstrating high internal consistency (Cronbach's alpha of 0.85) and good reliability (weighted kappa score of 0.65). At the 6-month follow-up, disease resolution was found to be significantly associated with improved MRONJ-QoL scores, suggesting validity of the questionnaire (P < 0.01). Therefore, this is a sensible, reliable, and valid questionnaire for evaluating the QoL of patients with MRONJ.

Metastatic epithelioid angiosarcoma to the mandible: report of a case and review of the literature.

Angiosarcoma and its epithelioid variant are vascular malignancies that rarely affect the facial skeleton. Epithelioid angiosarcoma resembles carcinoma and can be difficult to diagnose. A case is presented of metastatic epithelioid angiosarcoma to the mandible from an angiosarcomatoid portion of renal carcinoma. The diagnostic challenge is outlined and the literature is reviewed.

Serine proteases and protease-activated receptor 2-dependent allodynia: a novel cancer pain pathway.

Mediators involved in the generation of pain in patients with cancer are poorly understood. Using a combined molecular, pharmacologic, behavioral, and genetic approach, we have identified a novel mechanism of cancer-dependent allodynia induced by protease-activated receptor 2 (PAR2). Here we show that human head and neck carcinoma cells have increased levels of proteolytic activity compared to normal human cell controls. Supernatant from human carcinoma cells, but not controls, caused marked and prolonged mechanical allodynia in mice, when administered into the hindpaw. This nociceptive effect was abolished by serine protease inhibition, diminished by mast cell depletion and absent in PAR2-deficient mice. In addition, non-contact co-culture of trigeminal ganglion neurons with human head and neck carcinoma cells increased the proportion of neurons that exhibited PAR2-immunoreactivity. Our results point to a direct role for serine proteases and their receptor in the pathogenesis of cancer pain. This previously unrecognized cancer pain pathway has important therapeutic implications wherein serine protease inhibitors and PAR2 antagonists may be useful for the treatment of cancer pain.

Surgical incision can alter capsaicin-induced central sensitization in rat brainstem nociceptive neurons.

Surgical trauma can affect spinal neuronal excitability, but there have been no studies of the effects of surgical cutaneous injury on central nociceptive processing of deep afferent inputs evoked by noxious stimuli such as capsaicin. Thus our aim was to test the effect of surgical cutaneous incision in influencing central sensitization induced by capsaicin injection into the temporomandibular joint (TMJ). The activity of single nociceptive neurons activated by noxious mechanical stimulation of the TMJ was recorded in the trigeminal subnucleus caudalis/upper cervical cord of halothane-anesthetized rats. The cutaneous mechanoreceptive field (RF), cutaneous mechanical activation threshold (MAT) and TMJ MAT of neurons before and after both surgical cutaneous incision alone and capsaicin injection were compared with results of incision and lidocaine pretreatment of the facial skin overlying the TMJ and capsaicin injection into the TMJ. Incision itself induced a barrage of neuronal spikes and excitability increases reflecting central sensitization (cutaneous RF expansion, cutaneous MAT reduction) in most neurons tested whereas lidocaine pretreatment significantly attenuated the barrage and central sensitization. Capsaicin injection into the TMJ induced cutaneous RF expansion, cutaneous MAT reduction and TMJ MAT reduction following lidocaine pretreatment of the cutaneous incision site whereas capsaicin injection following incision alone not only failed to induce further central sensitization but also decreased the existing incision-induced central sensitization (no cutaneous RF expansion, increased cutaneous MAT and TMJ MAT) in most neurons tested. These findings suggest that central sensitization induced by capsaicin alone or by cutaneous incision alone can readily occur in TMJ-responsive nociceptive neurons and that following incision-induced excitability increases, capsaicin may result in a temporary suppression of nociceptive neuronal changes reflecting central sensitization.

Aural symptoms in temporomandibular disorder patients attending a craniofacial pain unit.

AIMS: To determine (1) the prevalence of aural symptoms in orofacial pain patients and (2) a potential association between temporomandibular disorders (TMD) and aural health, while controlling for covariates known to be associated with TMD or auditory dysfunction. METHODS: In a retrospective study, health questionnaires, medical histories, clinical findings, diagnoses, and treatments were systematically retrieved from the charts of 776 patients. The dates of initial assessment ranged from May 1987 to June 1999. Of the included subjects, 39.7% were female; the median age was 39 years; 16.4% displayed only aural symptoms (otalgia, tinnitus, vertigo, or perceived hearing loss); 26.4% had both TMD and aural symptoms; 17.8% had TMD but no aural complaints; and 39.4% had neither TMD nor aural symptoms. RESULTS: Of the 344 subjects who had TMD, 59.9% complained of aural symptoms, versus 29.2% of the 432 patients without TMD. Of the subjects with otalgia, tinnitus, vertigo, or perceived hearing loss, 67%, 64.1%, 65.2%, and 62.2% had TMD, respectively. Subjects with aural symptoms were significantly more likely to be female; to consider themselves in poor health; to smoke; or to have TMD, orofacial pain, headaches (temporal, occipital, or frontal), neck and shoulder pain, altered vision and sensation, sleep disturbances, loss of appetite, memory loss, or low energy. Clinical findings indicated that pathognomonic signs of TMD were associated with an increased risk of aural complaints in this patient population. A significantly greater negative impact on normal life functions was found in subjects exhibiting aural symptoms versus those who only had TMD complaints. CONCLUSION: These findings indicate that TMD is significantly correlated to aural health, although no cause-and-effect relationship has yet been demonstrated. Aural symptoms were also found to have a measurable impact on the subjects' quality of life.

Hybrid optoelectronic integrated circuit.

The distribution of optical signals to a monolithic array of GaAs photoconductors by means of ion-exchanged glass optical waveguides is demonstrated. In this hybrid technique both optical and electronic interconnections of semiconductor elements are achieved through the use of a metallic interconnect layer deposited on the surface of a glass substrate which has a mating waveguide pattern. The low optical loss, ease of fabrication, and low material cost of diffused glass waveguides with such layers permit relatively large optoelectronic circuit boards to be made, in which numerous semiconductor active optoelectronic devices can be included. The device reported here serves as the signal distribution and cross-point switching section of an optoelectronic switch matrix.

The influx of ascorbic acid into the rat's brain.

The influx of [14C]ascorbic acid into the rat's brain through the cerebral capillaries was measured by the steady-state initial-rate technique. Ascorbic acid was found to pass through the capillaries by a carrier-mediated process and by simple diffusion. The carrier system was found to have an apparent Vmax of 1.2 nmol . min-1 . g-1 of cerebral tissue and a Kt of 125 microM. The apparent constant of transfer, Kd, of the diffusional component was 0.98 microliter. min-1 . g-1. The contribution of the cerebral capillaries to the movement of ascorbic acid into the brain is discussed and was found to be the major route of entry into the brain for this vitamin.

Atrophy of the thymus in rats rendered diabetic by streptozotocin.

The thymus atrophied rapidly in rats rendered diabetic by a single injection of streptozotocin. The weight of the gland was reduced to one-fifth of its original weight within three weeks. Histologically there was a great loss of cortical thymocytes and a marked increase in mast cells lying in the thickened fibrous tissue. These findings may have a bearing on the state of immune deficiency observed in animals with diabetes induced by streptozotocin.

Comparison of the vascular permeability of the brain and the spinal cord to mannitol and inulin in rats.

The kinetics of the movement of [14C]mannitol and [14C]inulin from the blood into the CNS of the rat were measured. The spinal cord was found to have a higher permeability to these two substances than the brain. It is likely that the channels through which the tracers diffused are larger in the capillaries of the spinal cord than those in the brain.

The effects of fasting on core temperature, blood glucose and body and organ weights in rats.

Male Wistar rats of about 300 g body weight were fasted from 1 to 7 d. They were weighed and had their temperature taken daily. At the end of the experimental period, they were anaesthetized and blood was taken for measurement of the glucose content. The animals were killed and various organs were taken and weighed. Over the first 24 h there were striking reductions in body weight, core temperature and level of blood glucose. Throughout the succeeding days of fasting, there was a gradual decrease in body weight and core temperature, while the level of the blood glucose was maintained at about 3 mmol X l-1. The decrease in body weight and core temperature was matched by the weight loss of the liver and skeletal muscles. The heart and the kidney and spleen were not affected over the first day, but thereafter their weight declined steadily. The brain, the testes and the lungs retained their mass throughout.

Relation between the increase in the diffusional permeability of the blood-central nervous system barrier and other changes during the development of experimental allergic encephalomyelitis in the Lewis rat.

The reduction in the effectiveness of the blood-brain and blood-spinal cord barriers, previously seen in rats at the height of the acute episode of experimental allergic encephalomyelitis, has now been measured at various stages in the development of the disease up to 60 days after inoculation with guinea pig spinal cord in complete Freund's adjuvants. The marker of extracellular space, radioactively labelled mannitol, only crosses the blood-central nervous system barriers very slowly by passive diffusion in normal rats. An abnormal penetration of this marker into the central nervous system began to develop during the second week after inoculation, appearing first in the lower spinal cord, where it also reaches the highest level during the acute phase of the attack. The leak begins before either the clinical signs become evident or cuffing is seen around blood vessels in stained sections. As the clinical signs are disappearing, from about 15 days onwards, the permeability of the barrier returns steadily to its normal low value, starting in the spinal cord, especially the caudal part. The timing of the reduction in the effectiveness of the blood-central nervous system barrier in relation to other clinical and histological changes suggests that it may play a part in the development of the lesion. The relation between the timing of these changes in EAE and that in the development of a new lesion in (exacerbation of) multiple sclerosis is discussed.

Dispersion cancellation using optical-fiber filters.

The anomalous dispersion characteristic of recently reported [Opt. Lett. 5, 476 (1980)] optical-fiber filters is proposed for use in equalization of material dispersion in optical-communication (OC) links employing single-mode fibers. Calculations show that, under appropriate circumstances, a fiber filter of length shorter than 2 cm can equalize dispersion from an OC link about 1 km long.

Changes in the effectiveness of the blood-brain and blood-spinal cord barriers in experimental allergic encephalomyelitis.

Experimental allergic encephalomyelitis (EAE) was induced In Lewis rats by the intradermal inoculation of an homogenate of guinea pig spinal cord in complete Freund's adjuvant. In these animals the effectiveness with which the capillary barrier excluded mannitol (a substance which normally only crosses this barrier very slowly) from the brain and spinal cord involvement were at their height, 14 days after the inoculation, the effectiveness of the barrier was reduced since the rate of diffusion of the mannitol out of the blood into the brain-stem and spinal cord was approximately doubled. Even as early as 7 days after inoculation, before any clinical signs had appeared, the rate of diffusion was significantly increased in the region of the lumbo-sacral cord. These changes roughly paralleled the histological changes seen in many of the small vessels. We believe that the changes are due to an increase in the permeability of the vessels to mannitol. The bearing of these findings on multiple sclerosis is discussed.

Characterization of single-mode optical fiber filters.

The fabrication of narrowband highly reflecting filters in single-mode step-index fibers was reported recently by Hill et al. [Appl. Phys. Lett. 32, 647 (1978)]. The underlying effect on which these filters are based is a photoinduced refractive-index change in the GeO(2) used as a core dopant in SiO(2) fibers. A study is reported aimed at the characterization of such optical fiber filters. A theoretical model is developed, and relevant fiber parameters are determined through intercomparison with experiment. In this way, both the magnitude of the photoinduced index change and its dependence on the writing power coupled into the fiber are determined.