Migraine and Tension-Type Headache Reduction Through Pericranial Muscular Suppression: A Preliminary Report

Migraine and tension-type headaches have always plagued mankind. In spite of all the research dollars spent trying to determine the etiologies of these headaches, the neurology community still has not established a known cause of migraine and tension type headaches. This paper describes a study that was conducted for the U.S. Food and Drug Administration in which the efficacy of the Nociceptive Trigeminal Inhibition Tension Suppression System was evaluated and proved safe and efficacious in the reduction of medically diagnosed migraine and tension-type headache.     

Medullary and Odontogenic Disease in the Painful Jaw: Clinicopathologic Review of 500 Consecutive Lesions

Jaw-deviation dystonia is characterized by the lateral shift of the mandible due to involuntary masticatory muscle contraction, causing difficulties in speech or mastication. We evaluated a patient with jaw-deviation dystonia by recording movement-related cortical potentials (MRCPs) and treated with muscle afferent block (MAB). MRCP associated with mandibular movements (mouth opening, closing, and left and right lateral movements) was recorded in the patient and ten age-matched healthy subjects. In the control subjects, the amplitude of Bereitschaftspotential (BP)/negative slope (NS') was significantly higher for left lateral movements than for the mouth closing. The cortical map of BP/NS' prior to mouth opening and closing showed symmetric distribution, whereas those of lateral movements showed a slight predominance in the ipsilateral hemisphere. The patient showed lower amplitude as compared with control subjects. The right lateral movement (homonymous task) showed task-specific markedly reduced potentials. After MAB by intramuscular injection of lidocaine and ethanol to the inferior head of the left lateral pterygoid muscle, the deviation abolished and severity in speech and mastication was significantly improved. This study suggests that jaw-deviation dystonia might have the same etiology as other focal dystonias.     

Skeletal effects of zoledronic acid in an animal model of chronic kidney disease

Summary

Bisphosphonates reduce skeletal loss and fracture risk, but their use has been limited in patients with chronic kidney disease. This study shows skeletal benefits of zoledronic acid in an animal model of chronic kidney disease.

Introduction

Bisphosphonates are routinely used to reduce fractures but limited data exists concerning their efficacy in non-dialysis chronic kidney disease. The goal of this study was to test the hypothesis that zoledronic acid produces similar skeletal effects in normal animals and those with kidney disease.

Methods

At 25 weeks of age, normal rats were treated with a single dose of saline vehicle or 100 μg/kg of zoledronic acid while animals with kidney disease (approximately 30 % of normal kidney function) were treated with vehicle, low dose (20 μg/kg), or high dose (100 μg/kg) zoledronic acid, or calcium gluconate (3 % in the drinking water). Skeletal properties were assessed 5 weeks later using micro-computed tomography, dynamic histomorphometry, and mechanical testing.

Results

Animals with kidney disease had significantly higher trabecular bone remodeling compared to normal animals. Zoledronic acid significantly suppressed remodeling in both normal and diseased animals yet the remodeling response to zoledronic acid was no different in normal and animals with kidney disease. Animals with kidney disease had significantly lower cortical bone biomechanical properties; these were partially normalized by treatment.

Conclusions

Based on these results, we conclude that zoledronic acid produces similar amounts of remodeling suppression in animals with high turnover kidney disease as it does in normal animals, and has positive effects on select biomechanical properties that are similar in normal animals and those with chronic kidney disease.     

Practice patterns in high-risk bariatric venous thromboembolism prophylaxis

Background

In the morbidly obese population that undergoes bariatric surgery, venous thromboembolism (VTE) is the leading cause of morbidity and mortality. Certain factors place a patient at higher risk for VTE. No consensus exists on VTE screening or prophylaxis for the high-risk patient. This report describes the results of a survey on VTE screening and prophylaxis patterns in high-risk bariatric surgery.

Methods

Members of the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) were queried on factors that identified bariatric patients as high risk for VTE and on routine screening and prophylaxis practices. This included mechanical and chemical prophylaxis, duration of therapy, and use of inferior vena cava (IVC) filters.

Results

Of the 385 surgeons who responded to the survey, 81 % were bariatric surgeons, and the majority managed more than 50 cases annually. One or more of the following risk factors qualified patients as high risk: history of VTE, hypercoagulable status, body mass index (BMI) exceeding 55 kg/m², partial pressure of arterial oxygen (PaO₂) lower than 60 mmHg, and severe immobility. Preoperative screening of patients for VTE was practiced routinely by 56 % of the surgeons, and 92.4 % used preoperative chemoprophylaxis. The most common agent used preoperatively was heparin (48 %), and Lovenox was most commonly used postoperatively (49 %). Whereas 48 % of the patients discontinued chemoprophylaxis at discharge, 43 % continued chemoprophylaxis as outpatients, and 47 % routinely screened for VTE postoperatively. Use of IVC filters was routine for 28 % of the patients, who most commonly removed them after 1–3 months.

Conclusions

This study describes current practice patterns of VTE screening and prophylaxis in high-risk bariatric surgery. Nearly all surgeons agree on risk factors that qualify patients as high risk, but only half routinely screen patients preoperatively. Preoperative VTE chemoprophylaxis is used by nearly all surgeons, but the duration of therapy varies. Use of IVC filters is not routine, and postoperative screening was performed by less than half of the respondents. An understanding of current practice patterns yields insight into the rates of VTE and shows variability in the need for evidence-based prophylaxis and standardized screening.     

Pure Erythroid Leukemia Mimicking Ewing Sarcoma/Primitive Neuroectodermal Tumor in an Infant

Pure erythroid leukemia (PEL) is a rare type of acute myeloid leukemia (AML) with a very aggressive clinical course. Presentation as a myeloid/erythroid sarcoma is exceedingly rare. We describe an infantile PEL presenting as a multifocal myeloid sarcoma, clinically and pathologically mimicking Ewing sarcoma/PNET family of tumors. The patient died 8 weeks after the initial presentation due to widespread disease. Our case shows that PEL needs to be considered in the differential diagnosis of small round blue cell tumors in infancy. A meticulous workup including immunohistochemistry, flow cytometry, molecular, and cytogenetic studies was required to reach the diagnosis.     

Phase 3 evaluation of HP802‐247 in the treatment of chronic venous leg ulcers

In 2012 we reported promising results from a phase 2 clinical trial of HP802‐247, a novel spray‐applied investigational treatment for chronic venous leg ulcers consisting of human, allogeneic fibroblasts and keratinocytes. We now describe phase 3 clinical testing of HP802‐247, its failure to detect efficacy, and subsequent investigation into the root causes of the failure. Two randomized, controlled trials enrolled a total of 673 adult outpatients at 96 centers in North America and Europe. The primary endpoint was the proportion of ulcers with confirmed closure at the end of 12 weeks of treatment. An investigation into the root cause for the failure of HP802‐247 to show efficacy in these two phase 3 trials was initiated immediately following the initial review of the North American trial results. Four hundred twenty‐one patients were enrolled in the North American (HP802‐247, 211; Vehicle 210) and 252 in the European (HP802‐247, 131; Vehicle 121) trials. No difference in proportion of closed ulcers at week 12 was observed between treatment groups for either the North American (HP802‐247, 61.1%; Vehicle 60.0%; p = 0.5896) or the European (HP802‐247, 47.0%; Vehicle 50.0%; p = 0.5348) trials. Thorough investigation found no likelihood that design or execution of the trials contributed to the failure. Variability over time during the trials in the clinical response implicated the quality of the cells comprising HP802‐247. Concordance between the two separate, randomized, controlled trials with distinct, nonoverlapping investigative sites and independent monitoring teams renders the possibility of a Type II error vanishingly small and provides strong credibility for the unexpected lack of efficacy observed. The most likely causative factors for the efficacy failure in phase 3 was phenotypic change in the cells (primarily keratinocytes) leading to batch to batch variability due to the age of the cell banks.     

Effects of Lung Cotransplantation on Cardiac Allograft Tolerance Across a Full Major Histocompatibility Complex Barrier in Miniature Swine

A 12‐day course of high‐dose tacrolimus induces tolerance of major histocompatibility complex–mismatched lung allografts in miniature swine but does not induce tolerance of heart allografts unless a kidney is cotransplanted. To determine whether lungs share with kidneys the ability to induce cardiac allograft tolerance, we investigated heart–lung cotransplantation using the same induction protocol. Hearts (n = 3), heart–kidneys (n = 3), lungs (n = 6), and hearts–lungs (n = 3) were transplanted into fully major histocompatibility complex–mismatched recipients treated with high‐dose tacrolimus for 12 days. Serial biopsy samples were used to evaluate rejection, and in vitro assays were used to detect donor responsiveness. All heart–kidney recipients and five of six lung recipients demonstrated long‐term graft survival for longer than 272 days, while all heart recipients rejected their allografts within 35 days. Tolerant recipients remained free of alloantibody and showed persistent donor‐specific unresponsiveness by cell‐mediated lympholysis/mixed‐lymphocyte reaction. In contrast, heart–lung recipients demonstrated rejection of both allografts (days 47, 55, and 202) and antidonor responsiveness in vitro. In contrast to kidneys, lung cotransplantation leads to rejection of both heart and lung allografts, indicating that lungs do not have the same tolerogenic capacity as kidneys. We conclude that cells or cell products present in kidney, but not heart or lung allografts, have a unique capacity to confer unresponsiveness on cotransplanted organs, most likely by amplifying host regulatory mechanisms.     

Antitubercular evaluation of root extract and isolated phytochemicals from Lophira lanceolata against two resistant strains of Mycobacterium tuberculosis

Context: The roots of Lophira lanceolata Van Tiegh. Ex Keay (Ochnaceae) have numerous medicinal values in the Central African region. Even though the MeOH extract of the roots has shown antimycobacterial activities, the constituents responsible for this inhibitory activity remain unknown.

Objective: Phytochemical investigation of the MeOH root extract of L. lanceolata and determination of the antimycobacterial activities of that extract and constituents against the growth of Mycobacterium tuberculosis.

Materials and methods: Column chromatography was used to provide bioactive phytoconstituents. Those compounds were elucidated using MS and NMR spectroscopic data. Antimycobacterial screening of the extract (4.882–5000 µg/mL in DMSO during 24?h at 37?°C) and isolated compounds (0.244–250 µg/mL in DMSO during 24?h at 37?°C) was performed by microplate alamar blue assay (MABA) against two mycobacterial strains.

Results: The investigation of L. lanceolata MeOH roots extract provided of mixture of unseparated biflavonoids with a newly described one, dihydrolophirone A (1a) associated to lophirone A (1b). The bioactive compounds that effectively inhibited the growth of M. tuberculosis AC45 were found to be compounds 1 and 2. They exhibited MIC values of 31.25 and 15.75 µg/mL, respectively, and their MIC was found to be 62.5 µg/mL against resistant strain AC83.

Discussion and conclusions: It is clearly evident from the results obtained that the mycobacterial activity of L. lanceolata could be related mainly to its steroid and flavonoid contents. Therefore, this study suggests the potential of the above-mentioned classes of compounds as promising candidate agents for developing new anti-tuberculosis drugs.