Effect of a passive jaw motion device on pain and range of motion in TMD patients not responding to flat plane intraoral appliances

This study was designed to compare the effectiveness of a passive jaw motion device, the Therabite, and wooden tongue depressors (WTD), in patients with temporomandibular joint and muscle disorders, who did not improve after manual manipulation of the mandible and flat bite plane therapy. Forty-three patients were enrolled in the study and were classified as joint or muscle groups according to the Research Diagnostic Criteria for TMD. Twenty-four were assigned to the joint group, and 19 patients were assigned to the muscle group. The patients were assigned at random to three treatment subgroups: 1. passive jaw motion device therapy (Therabite); 2. wooden tongue depressors therapy (WTD); and 3. control group. All subjects received flat bite plane appliance therapy throughout the treatment period. Mandibular range of motion was measured for maximum opening (MO), right and left lateral (Rt. Lateral, Lt. Lateral) and protrusive (Pr) movements. Pain level was also assessed at the beginning and at the end of the treatment. The results suggested that a passive jaw motion device is effective in increasing range of motion in both groups of temporomandibular disorder patients, joint (intracapsular) and muscle (extracapsular). It also appears to decrease pain in patients with temporomandibular disorders. Pain was relieved to a greater degree in the muscle group than the joint group.     

Corticobasal degeneration: structural and functional MRI and single-photon emission computed tomography

We studied seven patients with corticobasal degeneration (CBD) from a clinical and imaging perspective. We describe the main morphological features of CBD and, using functional MRI, try to define the possible role of the parietal lobe in simple and complex learned motor sequences. We showed decreased activation of the parietal lobe contralateral to the more affected arm, when movements, simple or complex, are performed with that hand. Moreover we found that functional imaging can demonstrate parietal and motor cortex dysfunction before structural, and even single-photon emission computed tomography changes become evident.     

A new in vitro model of venous hypertension: the effect of pressure on dermal fibroblasts

PURPOSE: Venous hypertension leads to venous stasis ulcers. White cell activation, protein leakage from pressurized capillaries, and cytokine imbalances have all been implicated as indirect effects of venous hypertension that contribute to dermal changes seen in chronic venous insufficiency. The direct effect of increased tissue pressures on dermal elements has not been investigated. Prior studies have shown that fibroblasts isolated from venous ulcers have altered growth rates, morphologies, and protein production similar to senescent or aged fibroblasts. We hypothesize that neonatal fibroblasts (NNFs) cultured in conditions of increased atmospheric pressure will demonstrate altered cell function when compared with those grown at normal atmospheric pressure (ATM). METHODS: A pressure incubator was used to culture populations of NNFs at ATM, 60 mm Hg over ATM (ATM + 60 mm Hg), and 120 mm Hg over ATM (ATM + 120 mm Hg). NNF population growth rates were determined by periodic flow cytometry analysis over a 2-week period. Light microscopy and digital imaging were used to evaluate cell morphology. Senescence-associated B-galactosidase (SA-beta-Gal) activity was determined using the X-Gal stain. Fibronectin production was assessed by exposing cells sequentially to anti-fibronectin antibodies and Oregon Green-conjugated goat anti-mouse secondary antibodies. Flow cytometry then was used to determine relative proportions of cells staining positively for fibronectin. Statistical analysis was accomplished with analysis of variance. RESULTS: Populations of cells grown under increased pressures (both ATM + 60 and ATM + 120) showed reduced growth rates (P <.001). Similarly, morphologies of cells grown under pressure had increased cytoplasm to nuclear ratios with abnormal nuclear shapes. Populations of cells grown under pressure had higher percentages of cells staining positive for fibronectin (ATM = 45%, ATM + 60 = 59%, ATM + 120 = 79%). After 14 days of growth under pressure, fibroblast populations did not demonstrate augmented productions of the senescence marker SA-beta-Gal (ATM =.5%, ATM + 60 =.25%, ATM + 120 =.75%). CONCLUSIONS: This study demonstrated that NNFs grown in culture under increased pressures undergo a transformation not seen in cells grown at atmospheric pressure. Cells grown under pressure demonstrated reduced growth rates, increased fibronectin production, and abnormal morphologies similar to fibroblasts isolated from venous ulcers. This study suggests that pressure elevations (like venous hypertension) can directly result in altered cell function and morphology that may contribute to the delayed wound healing seen in patients with venous ulcers. This model uses a pressurized incubator that may prove to be a valuable adjunct in studying the effects of venous hypertension.     

Prospective, randomized study of external jugular vein patch versus polytetrafluoroethylene patch during carotid endarterectomy: perioperative and long-term results

OBJECTIVES: The purpose of this study was to evaluate the relative risks and advantages of using external jugular vein (EJV) patch, compared with polytetrafluoroethylene (PTFE) patch, during carotid endarterectomy. The primary end point was the relevant neurologic complication rate (RNCR; fatal or disabling stroke) at any time during follow-up. Secondary end points included stroke-free survival, 30-day and long-term mortality, recurrent stenosis rate (> or =50%), occlusion, patch infection, aneurysm formation, and other local complications. METHODS: The study, a prospective randomized clinical trial carried out at a single center, was divided into two 3-year phases: December 1996 to March 1999, when patients were enrolled, and March 1999 to March 2002, which was the follow-up period. Inclusion criteria included an external jugular vein suitable for patching, defined as vein diameter 3 mm or larger and absence of collateral vessels noted on preoperative color duplex ultrasound scans. Patients were prospectively randomized 1:1 to receive either the EJV (n = 80; group A) or synthetic (n = 80; group B) patch. RESULTS: Carotid endarterectomy and patching was performed by one surgeon. At 30 months the RNCR-free rate, analyzed with the Kaplan-Meier method, was 98.7% for group A (1 ipsilateral lethal stroke) and 94.6% for group B (4 ipsilateral disabling strokes), and remained stable to 60 months. No statistical difference was observed with the log-rank test. Stroke-free survival rate was 100% for group A and 98.7% for group B at 1 year, 98.7% for group A and 93.6% for group B (1 ipsilateral minor stroke) at 30 months, and was unchanged at 60 months. Life table analysis demonstrated freedom from significant recurrent stenosis (> or =50%) of 97.5% for both groups at 6 months, 93.6% for group A and 92.2% for group B at 30 months, and 90.2% for group A and 86.7% for group B at 60 months. No statistical difference was observed with the log-rank test. In no patients was recurrent stenosis greater than 70%. No aneurysm formation was noted during follow-up. CONCLUSIONS: We can conclude, with the power limitation of the study, that carotid endarterectomy can be safely performed with either the EJV or PTFE patch. Advantages of the EJV for carotid angioplasty include no cost for material, low risk for graft infection, and preservation of the saphenous vein.     

Gabapentin for the treatment of behavioural alterations in dementia: preliminary 15-month investigation

BACKGROUND: Although the core feature of dementia is progressive cognitive disruption, non-cognitive behavioural problems are expressed in most patients with dementia during the course of their illness. While psychotropic drugs are frequently used to control behavioural symptoms, comorbidities, which are very common in the geriatric population, could often limit their use. Gabapentin may be a potential treatment in such situations. METHODS: In this open, baseline comparison study 20 patients with probable Alzheimer's disease with behavioural alterations and serious comorbidities (paralytic ileus, open-angle glaucoma, ischaemic cardiopathy, hepatic failure or severe prostatic hyperplasia) received gabapentin for 15 months. Patients were allowed to continue any previous therapy for concurrent diseases. However, concomitant antipsychotic or benzodiazepine intake was not permitted. RESULTS: Gabapentin appeared to be efficacious and well tolerated in this patient population, and did not appear to interact with other drugs. General benefit is reflected by a reduction of caregiver stress. No patients withdrew before the end of the study and no serious adverse events were reported. CONCLUSION: The results of this study in patients with probable Alzheimer's disease with behavioural alterations and serious comorbidities indicate that gabapentin provides significant and sustained efficacy in terms of behaviour, with associated reductions in caregiver burden. The results of an ongoing larger, randomised, double-blind study of gabapentin are keenly awaited and may help to provide a safer and more efficacious treatment option for this group of patients.     

Iron-induced oxidant stress in alcoholic liver fibrogenesis.

Iron is an essential micronutrient. However, because human beings have no means to control iron excretion, excess iron, regardless of the route of entry, accumulates in parenchymal organs and threatens cell viability. Indeed, when iron-buffering capability is overwhelmed, oxidative stress-induced cell damage and fibrogenesis may arise, mainly in the liver, the main storage site for iron in the body. Results of recent studies have clearly shown that these pathologic events are induced by iron-generated reactive oxygen species and lipid peroxidation by-products. Hepatic fibrosis, characterized by excessive accumulation of extracellular matrix components in the liver, is a dynamic process, from chronic liver damage to end-stage liver cirrhosis. Iron-induced oxidant stress is involved in this process (1) as the primary cause of parenchymal cell necrosis or (2) as activator of cells that are effectors [e.g., hepatic stellate cells, (myo)fibroblasts] or key mediators (e.g., Kupffer cells) of hepatic fibrogenesis (or through both mechanisms). Beyond their effect as direct cytotoxic agents, iron and free radicals may trigger increased synthesis of collagen in myofibroblast-like cells as well as activate granulocytes and Kupffer cells, resulting in an increased formation of cytokines and eicosanoids and further reactive oxygen species. This may constitute a cascade of amplifying loops, which perpetuate the fibrogenic process. The fibrogenic potential of iron is even more dramatic when iron acts in concert with other hepatotoxins such as alcohol. In this instance, even if tissue iron levels are only slightly elevated, the toxic effect of alcohol or its metabolites may be amplified and propagated with rapid acceleration of the liver disease. At the molecular level, the presence of catalytically active "free iron" may (1) contribute directly to the hepatotoxicity of alcohol or (2) enhance the generation of cytokine and fibrogenic mediators from resident Kupffer cells (or be involved in both ways). A challenge for future research is to develop therapeutic tools able to block "redox-active" free iron in the cell.     

Nonlethal conditioning for the induction of allogeneic chimerism and tolerance to islet allografts

BACKGROUND: We reported that tolerance to skin grafts can be achieved by chimerism induction by way of nonlethal conditioning. In the present study, we evaluated the outcome of islet allografts implanted either simultaneously or after donor bone marrow cell (BMC) infusion when nonlethal conditioning was used. METHODS AND RESULTS: B10 (H-2b) mice were conditioned with antilymphocyte serum (ALS), 100 cGy total body irradiation (TBI), and given 30 x 10(6) allogeneic (B10.BR, H-2k) BMC on day 0. On day 2, cyclophosphamide was given intraperitoneally (IP), followed by a second BMC infusion on day 3. After chimeras were typed for allogeneic BMC engraftment on day 28, animals were rendered diabetic chemically and transplanted under the kidney capsule with islet allografts genetically matched or disparate to the BM. Donor-specific islet grafts were accepted (median survival time [MST] > 180 days, n=6), whereas all major histocompatibility complex (MHC)-disparate third-party BALB/c (H-2d) islet grafts were rejected (MST=13.8 days, n=4). When B10.BR BMC and islets were given simultaneously, graft acceptance (MST >140 days, n=4) was observed. Surprisingly, when MHC-disparate third-party islets (BALB/c) were given together with B10.BR BMC, long-term survival was also observed (MST >100 days, n=3). These findings suggested that conditioning alone at the time of islet implant might induce long-term engraftment without further treatment. However, only chimeric animals accepted a second-set donor-specific graft, whereas all other groups rejected it. CONCLUSION: Our data indicates that stable allogeneic chimerism and islet indefinite survival can be achieved by the use of a nonmyeloablative protocol. The results of the conditioning-only experiments are consistent with the possibility of graft accommodation.     

Design,synthesis and biological evaluation of ambenonium derivatives as AChE inhibitors

Ambenonium (1), an old AChE inhibitor, is endowed with an outstanding affinity and a peculiar mechanism of action that, taken together, make it a very promising pharmacological tool for the treatment of Alzheimer's disease (AD). Unfortunately, the bisquaternary structure of 1 prevents its passage through the blood brain barrier. In a search of centrally active ambenonium derivatives, we planned to synthesize tertiary amines of 1, such as 2 and 3. In addition, to add new insights into the binding mechanism of the inhibitor, we designed constrained analogues of ambenonium by incorporating the diamine functions into cyclic moieties (4-12). The biological evaluation of the new compounds has been assessed in vitro against human AChE and BChE. All tertiary amine derivatives resulted more than 1000-fold less potent than 1 and, unlike prototype, did not show any selectivity between the two enzymes. This result, because of recent findings concerning the role of BChE in AD, makes our compounds, endowed with a well-balanced profile of AChE/BChE inhibition, valuable candidates for further development. To better clarify the interactions that account for the high affinity of 1, docking simulations and molecular dynamics studies on the AChE-1 complex were also carried out.