Intralesional injection of triamcinolone hexacetonide as an alternative treatment for central giant-cell granuloma in 21 cases

Central giant-cell granulomas are benign, but occasionally aggressive, lesions that traditionally have been treated surgically. 21 cases of central giant-cell granuloma of the jaw were treated with intralesional injection of corticosteroids. The treatment protocol adopted was intralesional injection of 20 mg/ml triamcinolone hexacetonide diluted in an anaesthetic solution of 2% lidocaine/epinephrine 1:200,000 in the proportion 1:1; 1.0 ml of the solution was infiltrated for every 1 cm(3) of radiolucid area of the lesion, totalling 6 biweekly applications. Ten patients had aggressive lesions and 11 nonaggressive. Two patients showed a negative response to the treatment and underwent surgical resection, 4 showed a moderate response and 15 a good response. 8 of the 19 who had a moderate-to-good response to the drug treatment underwent osteoplasty to reestablish facial aesthetics. In these cases, only mature or dysplastic bone was observed, with the presence or absence of rare giant multinucleated cells. The advantages of this therapy are its less-invasive nature, the probable lower cost to the patient, lower risk and the ability to treat the lesion surgically in the future, if necessary.

Pyrrolidine dithiocarbamate down-regulates vascular matrix metalloproteinases and ameliorates vascular dysfunction and remodelling in renovascular hypertension

BACKGROUND AND PURPOSE Mounting evidence implicates matrix metalloproteinase (MMP) in the vascular dysfunction and remodelling associated with hypertension. We tested the hypothesis that treatment with pyrrolidine dithiocarbamate (PDTC), which interferes with NF-kappa B-induced MMPs gene transcription, could exert antihypertensive effects, prevent MMP-2 and MMP-9 up-regulation, and protect against the functional alterations and vascular remodelling of two-kidney, one clip (2K1C) hypertension. EXPERIMENTAL APPROACH Sham-operated or hypertensive rats were treated with vehicle or PDTC (100 mg.Kg(-1).day(-1)) by gavage for 8 weeks. Systolic blood pressure (SBP) was monitored weekly. Aortic rings were isolated to assess endothelium-dependent relaxations. Quantitative morphometry of structural alterations of the aortic wall was carried out in haematoxylin/eosin sections. Formation of vascular reactive oxygen species (ROS), and inducible (i) NOS and phosphorylated-p65 NF-kappa B subunit expression were measured in the aortas. MMP-2 and MMP-9 aortic levels and gelatinolytic activity were determined by gelatin and in situ zymography and by immunofluorescence. KEY RESULTS Treatment with PDTC attenuated the increases in SBP and prevented the endothelial dysfunction associated with 2K1C hypertension. Moreover, PDTC reversed the vascular aortic remodelling, the increases in aortic ROS levels and in iNOS and phosphorylated-p65 NF-kappa B expression found in 2K1C rats. These effects were associated with attenuation of 2K1C up-regulation of aortic MMP-2 and MMP-9 levels and gelatinolytic activity. CONCLUSION AND IMPLICATIONS These findings suggest that PDTC down-regulates vascular MMPs and ameliorates vascular dysfunction and remodelling in renovascular hypertension, thus providing evidence supporting the suggestion that PDTC is probably a good candidate to be used to treat hypertension.

NITRIC OXIDE SYNTHASE INHIBITION ATTENUATES L-DOPA-INDUCED DYSKINESIAS IN A RODENT MODEL OF PARKINSON`S DISEASE

Chronic L-DOPA pharmacotherapy in Parkinson`s disease is often, accompanied by the development of abnormal and excessive movements known as L-DOPA-induced dyskinesia. Rats with 6-hydroxydopamine lesion of dopaminergic neurons chronically treated with L-DOPA develop a rodent analog of this dyskinesia characterized by severe axial, limb, locomotor and orofacial abnormal involuntary movements. While the mechanisms by which these effects occur are not clear, they may involve the nitric oxide system. In the present study we investigate if nitric oxide synthase inhibitors can prevent dyskinesias induced by repeated administration Of L-DOPA in rats with unilateral 6-hydroxydopamine lesion. Chronic L-DOPA (high fixed dose, 100 mg/kg; low escalating dose, 10-30 mg/kg) treatment induced progressive dyskinesia changes. Two nitric oxide synthase inhibitors, 7-nitroindazole (1-30 mg/kg) and NG-nitro-L-arginine (50 mg/kg), given 30 min before L-DOPA, attenuate dyskinesia. 7-Nitroindazolee also improved motor performance of these animals in the rota-rod test. These results suggest the possibility that nitric oxide synthase inhibitors may be useful to treat L-DOPA.-Induced dyskinesia. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.

Acute otitis media

A 3-year-old girl is brought to your office by her mother because she has a fever and complains that her ear hurts. She has no significant medical history. The child is not pleased to be in the physician's office and has been crying. Her mother explains that she developed a cold about 3 days ago with sniffles. Her temperature is 37.8 degreesC (100 degreesF), and the rest of the physical examination is completed with some difficulty. The only abnormalities are slight redness of the throat. a nose full of thick green mucus, and injected tympanic membranes. You wonder what findings other than red tympanic membranes should lead you to diagnose otitis media and also consider the recent controversy about whether to treat acute otitis media (AOM) with antibiotics.

Quantum criticality

We investigate the theory of quantum fluctuations in non-equilibrium systems having large critical fluctuations. This allows us to treat the limits imposed by nonlinearities to quantum squeezing and noise reduction, and also to envisage future tests of quantum theory in regions of macroscopic quantum fluctuations. A long-term objective of this research is to identify suitable physical systems in which macroscopic 'Schrodinger cat'-like behaviour may be observed. We investigate two systems in particular of much current experimental interest, namely the degenerate parametric oscillator near threshold, and the evaporatively cooled (BEC). We compare the results obtained in the positive-P representation, as a fully quantum mechanical calculation, with the truncated Wigner phase space equation, also known as semi-classical theory. We show when these results agree and differ in calculations taken beyond the linearized approximation. In the region where the largest quantum fluctuations and Schrodinger cat-like behaviour might be expected, we find that the quantum predictions correspond very closely to the semi-classical theory. Nature abhors observing a Schrodinger car.

Effects of temporal association on recognition memory

The influence of temporal association on the representation and recognition of objects was investigated. Observers were shown sequences of novel faces in which the identity of the face changed as the head rotated. As a result, observers showed a tendency to treat the views as if they were of the same person. Additional experiments revealed that this was only true if the training sequences depicted head rotations rather than jumbled views: in other words, the sequence had to be spatially as well as temporally smooth. Results suggest that we are continuously associating views of objects to support later recognition, and that we do so not only on the basis of the physical similarity, but also the correlated appearance in time of the objects.

Quasimode theory of quantum optical processes in photonic band gap materials

This paper deals with atomic systems coupled to a structured reservoir of quantum EM field modes, with particular relevance to atoms interacting with the field in photonic band gap materials. The case of high Q cavities has been treated elsewhere using Fano diagonalization based on a quasimode approach, showing that the cavity quasimodes are responsible for pseudomodes introduced to treat non-Markovian behaviour. The paper considers a simple model of a photonic band gap case, where the spatially dependent permittivity consists of a constant term plus a small spatially periodic term that leads to a narrow band gap in the spectrum of mode frequencies. Most treatments of photonic band gap materials are based on the true modes, obtained numerically by solving the Helmholtz equation for the actual spatially periodic permittivity. Here the field modes are first treated in terms of a simpler quasimode approach, in which the quasimodes are plane waves associated with the constant permittivity term. Couplings between the quasimodes occur owing to the small periodic term in the permittivity, with selection rules for the coupled modes being related to the reciprocal lattice vectors. This produces a field Hamiltonian in quasimode form. A matrix diagonalization method may be applied to relate true mode annihilation operators to those for quasimodes. The atomic transitions are coupled to all the quasimodes, and the true mode atom-EM field coupling constants (one-photon Rabi frequencies) are related to those for the quasimodes and also expressions are obtained for the true mode density. The results for the one-photon Rabi frequencies differ from those assumed in other work. Expressions for atomic decay rates are obtained using the Fermi Golden rule, although these are valid only well away from the band gaps.

History and nomenclature of the theropod dinosaur tracks Bueckeburgichnus and Megalosauripus

The most recent account of Bueckeburgichnus maximus Kuhn 1958, a distinctive theropod dinosaur track from the Lower Cretaceous of Germany, is shown to be based on a referred specimen mistakenly identified as the holotype and the correct name of this taxon is deemed to be Megalosauripus maximus (Kuhn 1958). This minor revision has important consequences for nomenclature of the many European, Asian, North American and Australian dinosaur tracks attributed to megalosaurian theropods. Many of those tracks were named Megalosauripus, but that name has a confusing multiplicity of meanings and it should be restricted to the highly characteristic dinosaur track formerly identified as Bueckeburgichnus. Other tracks named "Megalosauripus”; (in its several other senses) will require new nomenclature, despite their extensive and repeated revision since 1996. It is recommended that future revision should adopt conventions of the International Code of Zoological Nomenclature. Although previous revisions expressed an intention to adhere to those conventions, these were not put into practice, with the unfortunate result of multiplying the problems that surround the nomenclature of megalosaur tracks. Introduction of the name Megalosauripus maximus (Kuhn 1958) eliminates those burgeoning problems and permits the introduction of new and objective nomenclature for presumed megalosaur tracks.

Combined physiotherapy and education is efficacious for chronic low back pain

Manual therapy, exercise and education target distinct aspects of chronic low back pain and probably have distinct effects, This study aimed to determine the efficacy of a combined physiotherapy treatment that comprised all of these strategies. By concealed randomisation, 57 chronic low back pain patients were allocated to either the four-week physiotherapy program or management as directed by their general practitioners, The dependent variables of interest were pain and disability. Assessors were blind to treatment group. Outcome data from 49 subjects (86%) showed a significant treatment effect. The physiotherapy program reduced pain and disability by a mean of 1.5/10 points on a numerical rating scale (95% CI 0.7 to 2.3) and 3.9 points on the 18-point Roland Morris Disability Questionnaire (95% CI 2 to 5.8), respectively. The number needed to treat in order to gain a clinically meaningful change was 3 (95% CI 3 to 8) for pain, and 2 (95% CI 2 to 5) for disability. A treatment effect was maintained at one-year follow-up. The findings support the efficacy of combined physiotherapy treatment in producing symptomatic and functional change in moderately disabled chronic low back pain patients.

Current concepts in central nervous system regeneration

A dictum long-held has stated that the adult mammalian brain and spinal cord are not capable of regeneration after injury. Recent discoveries have, however, challenged this dogma. In particular, a more complete understanding of developmental neurobiology has provided an insight into possible ways in which neuronal regeneration in the central nervous system may be encouraged. Knowledge of the role of neurotrophic factors has provided one set of strategies which may be useful in enhancing CNS regeneration. These factors can now even be delivered to injury sites by transplantation of genetically modified cells. Another strategy showing great promise is the discovery and isolation of neural stem cells from adult CNS tissue. It may become possible to grow such cells in the laboratory and use these to replace injured or dead neurons. The biological and cellular basis of neural injury is of special importance to neurosurgery, particularly as therapeutic options to treat a variety of CNS diseases becomes greater. (C) 2002 Published by Elsevier Science Ltd.

Impact numbers in health policy decisions

Objective: To outline the major methodological issues appropriate to the use of the population impact number (PIN) and the disease impact number (DIN) in health policy decision making. Design: Review of literature and calculation of PIN and DIN statistics in different settings. Setting: Previously proposed extensions to the number needed to treat (NNT): the DIN and the PIN, which give a population perspective to this measure. Main results: The PIN and DIN allow us to compare the population impact of different interventions either within the same disease or in different diseases or conditions. The primary studies used for relative risk estimates should have outcomes, time periods and comparison groups that are congruent and relevant to the local setting. These need to be combined with local data on disease rates and population size. Depending on the particular problem, the target may be disease incidence or prevalence and the effects of interest may be either the incremental impact or the total impact of each intervention. For practical application, it will be important to use sensitivity analyses to determine plausible intervals for the impact numbers. Conclusions: Attention to various methodological issues will permit the DIN and PIN to be used to assist health policy makers assign a population perspective to measures of risk.

Short report: Molecular genetic characterization of an unusually severe case of hydatid disease in Alaska caused by the cervid strain of Echinococcus granulosusi

Distinct Echinococcus granulosus life cycle patterns have been described in North America: domestic and sylvatic. Gene sequences of the sylvatic E. granulosus indicate that it represents a separate variant. Case-based data have suggested that the course of sylvatic disease is less severe than that of domestic disease. which led to the recommendation to treat cystic echinococcosis patients in the Arctic by careful medical management rather than by aggressive surgery. We recently reported the first two documented E. granalosus human cases in Alaska with accompanying severe sequelae. Here we describe the results of molecular genetic analysis of the cyst material of one of the subjects that supported identification of the parasite as the sylvatic (cervid) strain and not the domestic (common sheep strain), which was initially thought to be implicated in these unusually severe Alaskan cases.

A Pilot Randomized Trial Comparing CD-34Selected Versus Unmanipulated Hemopoietic Stem Cell Transplantation for Severe, Refractory Rheumatoid Arthritis

Objective. Evidence from animal studies, case reports, and phase I studies suggests that hemopoietic stem cell transplantation (HSCT) can be effective in the treatment of rheumatoid arthritis (RA). It is unclear, however, if depletion of T cells in the stem cell product infused after high-dose chemotherapy is beneficial in prolonging responses by reducing the number of infused autoreactive T cells. This pilot multicenter, randomized trial was undertaken to obtain feasibility data on whether CD34 selection (as a form of T cell depletion) of an autologous stem cell graft is of benefit in the HSCT procedure in patients with severe, refractory RA. Methods. Thirty-three patients with severe RA who had been treated unsuccessfully with methotrexate and at least 1 other disease-modifying agent were enrolled in the trial. The patients received high-dose immunosuppressive treatment with 200 mg/kg cyclophosphamide followed by an infusion of autologous stem cells that were CD34 selected or unmanipulated. Safety, efficacy (based on American College of Rheumatology [ACR] response criteria), and time to recurrence of disease were assessed on a monthly basis for up to 12 months. Results. All patients were living at the end of the study, with no major unexpected toxicities. Overall, on an intent-to-treat basis, ACR 20% response (ACR20) was achieved in 70% of the patients. An ACR70 response was attained in 27.7% of the 18 patients who had received CD34-selected cells and 53.3% of the 15 who had received unmanipulated cells (P = 0.20). The median time to disease recurrence was 147 days in the CD34-selected cell group and 201 days in the unmanipulated cell group (P = 0.28). There was no relationship between CD4 lymphopenia and response, but 72% of rheumatoid factor (RF)-positive patients had an increase in RF titer prior to recurrence of disease. Conclusion. HSCT can be performed safely in patients with RA, and initial results indicate significant responses in patients with severe, treatment-resistant disease. Similar outcomes were observed in patients undergoing HSCT with unmanipulated cells and those receiving CD34-selected cells. Larger studies are needed to confirm these findings.

Lateral epicondylalgia: a musculoskeletal physiotherapy perspective

Tennis elbow or lateral epicondylalgia (LE) is a challenging musculoskeletal condition to treat. This is largely due to the lack of research-based evidence of the clinical efficacy of the myriad of treatment approaches espoused in the literature. In view of this, successful rehabilitation of LE is based on choosing treatments that address the physical impairments found during clinical examination. The primary physical impairment in LE is a deficit in grip strength predominately due to pain and its consequences on motor function. Hence the mainstay of successful management of this condition is therapeutic exercise, providing it is not pain provocative. Adjunctive procedures such as manipulative therapy and sports taping techniques have recently been shown to provide substantial initial pain relief. Early relief of pain in the rehabilitation program helps accelerate recovery and most importantly motivates the client to persist with the therapeutic exercise program. The manipulative therapy and taping treatments presented in this masterclass warrant consideration in the clinical best practice management of LE, and serve as a model for other similar musculoskeletal conditions. (C) 2003 Elsevier Science Ltd. All rights reserved.

Drug resistance in the sexually transmitted protozoan Trichomonas vaginalis

Trichomoniasis is the most common, sexually transmitted infection. It is caused by the flagellated protozoan parasite Trichomonas vaginalis. Symptoms include vaginitis and infections have been associated with preterm delivery, low birth weight and increased infant mortality, as well as predisposing to HIV/AIDS and cervical cancer. Trichomoniasis has the highest prevalence and incidence of any sexually transmitted infection. The 5-nitroimidazole drugs, of which metronidazole is the most prescribed, are the only approved, effective drugs to treat trichomoniasis. Resistance against metronidazole is frequently reported and cross-resistance among the family of 5-nitroimidazole drugs is common, leaving no alternative for treatment, with some cases remaining unresolved. The mechanism of metronidazole resistance in T. vaginalis from treatment failures is not well understood, unlike resistance which is developed in the laboratory under increasing metronidazole pressure. In the latter situation, hydrogenosomal function which is involved in activation of the prodrug, metronidazole, is down-regulated. Reversion to sensitivity is incomplete after removal of drug pressure in the highly resistant parasites while clinically resistant strains, so far analysed, maintain their resistance levels in the absence of drug pressure. Although anaerobic resistance has been regarded as a laboratory induced phenomenon, it clearly has been demonstrated in clinical isolates. Pursuit of both approaches will allow dissection of the underlying mechanisms. Many alternative drugs and treatments have been tested in vivo in cases of refractory trichomoniasis, as well as in vitro with some successes including the broad spectrum anti-parasitic drug nitazoxanide. Drug resistance incidence in T. vaginalis appears to be on the increase and improved surveillance of treatment failures is urged.