bluuebunny/crossref_metadata_2025 huggingface dataset:
The Heat Strain of Various Athletic Surfaces: A Comparison Between Observed and Modeled Wet-Bulb Globe Temperatures
Authors: Pryor J. Luke , Pryor Riana R. , Grundstein Andrew , Casa Douglas J.
Published: November 2017

Context: 

The National Athletic Trainers' Association recommends using onsite wet-bulb globe temperature (WBGT) measurement to determine whether to modify or cancel physical activity. However, not all practitioners do so and instead they may rely on the National Weather Service (NWS) to monitor weather conditions.

Objective: 

To compare regional NWS WBGT estimates with local athletic-surface readings and compare WBGT measurements among various local athletic surfaces.

Design: 

Observational study.

Setting: 

Athletic fields.

Main Outcome Measure(s): 

Measurements from 2 identical WBGT devices were averaged on 10 athletic surfaces within an NWS station reporting radius. Athletic surfaces consisted of red and black all-weather tracks (track), blue and black hard tennis courts (tennis), nylon-knit artificial green turf, green synthetic turfgrass, volleyball sand, softball clay, natural grass (grass), and a natural lake (water). Measurements (n = 143 data pairs) were taken over 18 days (May through September) between 1 pm and 4:30 pm in direct sunlight 1.2 m above ground. The starting location was counterbalanced across surfaces. The NWS weather data were entered into an algorithm to model NWS WBGT.

Results: 

Black tennis, black track, red track, and volleyball sand WBGT recordings were greater than NWS estimates (P ≤ .05). When all athletic-surface measurements were combined, NWS (26.85°C ± 2.93°C) underestimated athletic-surface WBGT measurements (27.52°C ± 3.13°C; P < .001). The range of difference scores (−4.42°C to 6.14°C) and the absolute mean difference (1.71°C ± 1.32°C) were large. The difference between the onsite and NWS WBGT measurements resulted in misclassification of the heat-safety activity category 45% (65/143) of the time (= 3.857, P = .05). The WBGT of water was 1.4°C to 2.7°C lower than that of all other athletic surfaces (P = .04). We observed no other differences among athletic surfaces but noted large WBGT measurement variability among athletic playing surfaces.

Conclusions: 

Clinicians should use an onsite WBGT device to determine environmental conditions and the need for modification of athletic events, especially as environmental conditions worsen. Given the large WBGT variability among athletic surfaces, WBGT measurements should be obtained from each athletic surface.
#FeesMustFall as social movement and emancipatory politics? Moving towards an apocalyptic theological praxis outside the limits of party politics
Authors: Buttelli Felipe G.K. , Le Bruyns Clint
Published: November 2017

This article proposes three reflexive movements. The first one offers an introduction to Fees Must Fall, pointing to some aspects that allow us to understand it as a social movement and some of its basic features. The second movement is a theoretical one, constructing the notion of emancipatory politics. It is based on the distinctions suggested by Jacques Rancière between ‘police and politics’ and by Michael Neocosmos between ‘excessive and expressive’ politics. It will also present the Freirean notion of ‘conscientisation and dialogicity’, emphasising the learning experience from the political praxis within emancipatory social movements. The third movement offers, as conclusion, an apocalyptic politics as suggested by Žižek, envisioned through the lens of Christian eschatology, as a critical approach to social movements towards the radical transformation of society.
Computerised tomography findings in HIV-associated cryptococcal meningoencephalitis at a tertiary hospital in Pretoria
Authors: Khan Nausheen , Hiesgen Juliane
Published: November 2017

Objective: Computerised tomography (CT) scans of 30 patients, admitted with HIV-associated cryptococcal meningoencephalitis (CM), were retrospectively reviewed and the different neuroradiological findings categorised. In addition to the characterisation of the cohort, we looked at whether positive CT scans can indicate negative outcomes when compared with normal imaging.Methods: We identified all patients admitted with CM to Kalafong Hospital in Pretoria, South Africa, over a 2-year period and selected those who underwent brain CT. Abnormal findings were divided into cryptococcal-related lesions and other pathological findings. Clinical data, as well as laboratory data and information about the outcomes were collected.Results: Thirty-nine (44.8%) out of 87 patients had a CT done during the hospital admission, of which 30 were reviewed and independently reported by the authors. The majority of CT scans were non-contrasted (n = 21). Four patients (13.3%) had normal imaging. Amongst the 26 patients with abnormal CTs, we found 16 brain scans (53.3%) with changes most likely attributed to CM. Dilated Virchow–Robin (VR) spaces, found on eight scans (26.7%), were the most common CT finding related to neurocryptococcosis. Global cerebral atrophy, present in 17 patients (56.7%), was the prevailing generalised abnormality. The mortality of all patients who underwent imaging was similar (33.3%) to the mortality in the total cohort of patients with cryptococcal meningitis (31%). In the group with cryptococcal-related changes on imaging, the mortality was higher (53.3%) than in both groups and a subgroup of five patients with hydrocephalus showed 100% mortality.Conclusion: Computerised tomography brain imaging was performed in 44.8% of all patients admitted with CM into our hospital. More than half of the images showed cryptococcal-related pathological findings, of which dilated VR spaces were the most common. Only 13.3% of scans were normal. Mortality was higher in the patients with cryptococcal-related pathology (53.3% vs. 31%), with hydrocephalus being associated with a 100% mortality. No scan in our cohort showed any pathology requiring neurosurgical intervention or contraindicating the procedure of a lumbar puncture.
Unusual complication and successful high-dose chemotherapy treatment of advanced Burkitt’s lymphoma in an adult HIV-positive patient
Authors: McGrath Henrietta W.H. , Fitzhugh Alexander , Javed Maria , Rockwood Neesha , Kazmi Farhat
Published: November 2017

Adult Burkitt’s lymphoma emerged as an AIDS-defining condition in the 1980s. We describe a case of HIV-associated adult Burkitt’s lymphoma diagnosed and treated with high-dose chemotherapy in our institution, complicated by unusual bilateral renal vein tumour thrombi and tumour lysis syndrome. We believe this unique case highlights the need for early recognition of current and potential complications on staging computed tomography imaging, as well as successful use of a high-dose chemotherapy regimen.
Disseminated Kaposi sarcoma presenting in unusual locations: A case report
Authors: Mudau Adziambei , Makhanya Nonjabulo Z. , Suleman Farhana E.
Published: November 2017

Kaposi sarcoma (KS) is the most common malignancy associated with HIV infection. It usually affects the skin, the gastrointestinal tract and the lungs. It is generally described in the setting of CD4 counts < 150 cells/mm3 – 200 cells/mm3. We describe a case of recurrence of KS with a rare presentation of breast and musculoskeletal involvement in the setting of a CD4 count of 374 cell/mm3 and an undetectable viral load. The patient was on highly active antiretroviral therapy for 5 years at the time of the second presentation.
Attitudes, barriers, and practices toward research and publication among medical students at the University of Damascus, Syria
Authors: Turk Tarek , Al Saadi Tareq , Alkhatib Mahmoud , Hanafi Ibrahem , Alahdab Fares , Firwana Belal , Koudsi Maysoun , Al-Moujahed Ahmad
Published: November 2017

Introduction: Research is crucial for health-care delivery. However, medical students may not participate in research during their training, which might negatively affect their understanding of the importance of research and their future ability to conduct research projects. This is more prominent in developing countries. We aim to assess the attitudes of a sample of Syrian medical students toward research and suggest plausible solutions to reduce their self-reported barriers. Methods: A cross-sectional study was conducted using a self-administered, pretested questionnaire. Results: Three hundred and twenty-three responses were included. Most students demonstrated positive attitudes toward research. However, most of the responses indicated that they did not receive any training in academic writing or research and therefore did not have the opportunity to participate in formal research projects or scholarly writing. Students reported various types of barriers that challenged their progress in the field of research. Students who reported being encouraged by their professors to participate in research and writing/publishing scientific papers or reported receiving training about these activities were more likely to participate in research projects or writing scientific articles. Conclusion: Students have positive attitudes toward research and publication while they reported poor education, limited participation, and presence of many barriers that impede their participation in such activities.
The Influence of Free 3-Nitrotyrosine and Saliva on the Quantitative Analysis of Protein-Bound 3-Nitrotyrosine in Sputum
Authors: Ueshima Kazuhito , Minakata Yoshiaki , Sugiura Hisatoshi , Yanagisawa Satoru , Ichikawa Tomohiro , Akamatsu Keiichirou , Hirano Tsunahiko , Nakanishi Masanori , Matsunaga Kazuto , Yamagata Toshiyuki , Ichinose Masakazu
Published: November 2017

Background

We have recently developed a new technique for quantitatively measuring protein-bound 3-nitrotyrosine (3-NT), a footprint of nitrosative stress, utilizing high-performance liquid chromatography with an electrochemical detection (HPLC-ECD) system. Using this system, we showed that 3-NT formation was upregulated in the sputum of both COPD and asthmatic patients. However, in order to improve the accuracy of the measurement system, We have to resolve some problems which were the influence of free amino acid form of 3-NT and of salivary contamination.

Objectives

We initially investigated the amount of the free amino acid form of 3-NT in induced sputum and compared with that of protein-bound 3-NT. Next, we evaluated the concentration of protein-bound 3-NT in saliva and compared with that in induced sputum by means of HPLC-ECD.

Methods

Five male COPD patients were enrolled. Induced sputum and saliva were obtained from the patients. The free amino acid form of 3-NT in sputum and saliva was measured by HPLC-ECD, and the protein-bound 3-NT and tyrosine in sputum and saliva were enzymatically hydrolyzed by Streptomyces griseus Pronase and measured for the protein hydrolysate by HPLC-ECD.

Results

The mean value of the amount of protein-bound 3-NT was 65.0 fmol (31.2 to 106.4 fmol). On the other hand, the amount of the free amino acid form of 3-NT was under the detection limit (<10 fmol). The levels of both 3-NT (sputum: 0.55 ± 0.15 pmol/ml, saliva: 0.02 ± 0.01 pmol/ml, p < 0.01) and tyrosine (sputum: 0.81 ± 0.43 μmol/ml, saliva: 0.07 ± 0.04 μmol/ml, p < 0.01) in saliva were significantly lower than in sputum. The percentage of 3-NT in saliva to that in sputum was about 3.1%, and that of tyrosine was about 9.0%.

Conclusion

The free amino acid form of 3-NT does not affect the measurement of protein-bound 3-NT. Furthermore, the influence of salivary contamination on the measurement of protein-bound 3-NT in induced sputum by means of HPLC-ECD was very small and could be negligible.
Database Analysis of Adults with Bipolar Disorder Consuming a Micronutrient Formula
Authors: Gately Dermot , Kaplan Bonnie J.
Published: November 2017

Background

Bipolar disorder is a lifelong problem with imperfect available treatments. Recent research has shown potential benefit of nutritional treatment for mood symptoms. The goal of the current study was to determine whether adults with bipolar disorder reported treatment benefit from consuming a micronutrient formula.

Methods

Self-report data were available from 682 adults who reported a diagnosis of bipolar disorder; 81% were taking psychiatric medications. Those reporting additional diagnoses were excluded, as well as those who provided data <60 times during 180 days of using the micronutrients, leaving 358 for analysis.

Results

Mean symptom severity was 41% lower than baseline after 3 months (effect size = 0.78), and 45% lower after 6 months (effect size = 0.76) (both paired t-tests significant, p < 0.001). In terms of responder status, 53% experienced ≥50% improvement at 6 months. Half the sample were taking medications approved for bipolar disorder (lithium, anticonvulsants, atypical antipsychotics), and half were either medication-free or taking other medications: the magnitude of treatment benefit did not differ between these two groups. Regression analyses indicated that decreased symptom severity over the 6 months was associated with increasing micronutrient dosage and with reducing medication. Symptom improvements were significant and sustained at 6 months, suggesting that benefits were not attributable to placebo/expectancy effects.

Conclusions

Further research on this micronutrient formula is warranted.
Hopelessness and Low Social and Occupational Functioning are Associated with Non-Recovery from Depression—Results of a 6-Year Follow-Up Study
Authors: Viinamäki Heimo , Koivumaa-Honkanen Heli , Honkalampi Kirsi , Haatainen Kaisa , Tolmunen Tommi , Antikainen Risto , Hintikka Jukka
Published: November 2017

Objective

The aim of this study was to explore variables associated with poor recovery from depression.

Method

A sample of depressive patients (n = 121) referred to treatment was followed prospectively for 6 years. Clinical evaluations were done at baseline and at 6 month, 1, 2 and 6 years study visits. A diagnosis of major depression based on SCID interview at 6 year and high BDI score along follow-up indicated poor recovery. A diagnosis of full remission at 6 year and low BDI score during follow-up indicated good recovery.

Results

Chronic depression was found in 15% of patients. A repeated measures analysis of variance of HDRS-, SCL-90, hopelessness (HS) and Social and Occupational Functioning Assessment Scale (SOFAS) scores showed that those with poor recovery had recovered poorly also according these scales during the whole follow-up. Treatment factors did not associate with recovery. Logistic regression analyses revealed an independent association between poor recovery at 6 year and both high HS- and low SOFAS scores at 12 months, 24 months and 6 year assessments.

Conclusions

Assessment of hopelessness and social and occupational functioning help to early identify high-risk patients who would be in need for more individually tailored treatments.
Hormone Refractory Prostate Cancer: Focus on Sipuleucel-T
Authors: Doehn Christian , Sommerauer Martin , Guo Xiyuan , Kausch Ingo , Jocham Dieter
Published: November 2017

Sipuleucel-T is a vaccine based on autologous antigen presenting cells that are loaded with an antigen-cytokine (prostatic acid phosphatase and granulocyte-macrophage colony-stimulating factor) fusion product. Sipuleucel-T is given intravenous in weeks 0, 2, and 4. Within phase I–III trials, patients with metastatic hormone-refractory prostate cancer have been treated. In these trials an activation of the immune system could be demonstrated. Also, some clinical responses could be documented. Moreover, in a placebo-controlled phase III trial including 127 patients a statistical significantly prolongation of survival was achieved. Side effects from the vaccine are rather mild and included fever, myalgia, fatigue and others. The Food and Drug Administration in the United States requested further data before possible approval of sipuleucel-T.
Safety and Efficacy of Ivabradine in the Management of Stable Angina Pectoris
Authors: Tardif Jean-Claude
Published: November 2017

The first selective If current inhibitor, ivabradine, lowers heart rate (HR) at rest and during exercise with no vasomotor, negative inotropic, or negative lusitropic effects. Given that elevated resting HR is a key factor in the onset of myocardial ischemia and a strong independent predictor of cardiovascular outcomes, ivabradine provides new therapeutic prospects in coronary artery disease (CAD). Its selective HR-lowering action has proven anti-ischemic and anti-anginal efficacy, and ivabradine is currently indicated for the symptomatic treatment of stable angina pectoris. Ivabradine can also be safely combined with other anti-anginal agents, and addition of ivabradine to beta-blocker therapy further improves anti-ischemic efficacy and exercise capacity of patients with stable angina. The recent BEAUTIFUL trial demonstrated that although the primary endpoint was not met in the overall population, addition of ivabradine on top of standard preventive treatments significantly reduced the risk of coronary events in stable CAD patients with left ventricular systolic dysfunction among the subgroup of patients with a resting HR ≥ 70 bpm. This is in accordance with pre-clinical data showing that long-term HR reduction improves endothelial function and reduces the progression of atherosclerosis. A significant proportion of patients with stable angina have elevated resting HR and ivabradine should therefore be considered as an important therapy in these cases. In combination with other standard treatments, ivabradine can improve angina and could potentially improve coronary outcomes. Ongoing and future clinical studies will evaluate the presence and magnitude of the cardioprotective benefits of HR lowering with ivabradine in patients with cardiovascular diseases.
Pregabalin and Fibromyalgia Syndrome: A Treatment Option
Authors: Lawson Kim
Published: November 2017

Fibromyalgia (FM) is a chronic complex pain disorder that is multidimensional and exhibits heterogeneity requiring a long-term multidisciplinary approach to management. Many of the drugs used in the treatment of FM have been focused to the management of single symptoms; often such drugs fail to demonstrate acceptable efficacy in the majority of the patient population. Pregabalin is an α2-δ ligand that regulates the release and postsynaptic actions of neurotransmitters related to analgesic, anticonvulsant and anxiolytic properties. In randomized, double-blind, placebo-controlled studies, pregabalin has demonstrated an improvement in pain, sleep and fatigue symptoms associated with FM, as well as offering an improvement in parameters related to quality of life. Although the positive outcomes obtained with pregabalin support its use as an option for the management of FM, the efficacy was restricted to a selected patient population outside of the usual care setting. Current data do not allow an explanation where there are any limitations of pregabalin as a treatment of patients with FM, as to whether this is a deficiency of the drug or the process of assessment (e.g. assessment tools of FM, clinical trial design).
Pharmacotherapy of Hematologic Malignancies with Tipifarnib
Authors: Kotsianidis Ioannis , Nakou Evangelia , Bouchliou Irene
Published: November 2017

The illumination of cellular processes in cancer has revolutionized oncology drug development leading to a shift from non-specific chemotherapy to the selective targeting of tumorigenic signal transduction pathways. Farnesyltransferase inhibitors (FTIs) target proteins needing prenylation for functioning, thus inhibiting a wide variety of molecular targets crucial for cell proliferation and survival. Tipifarnib (R115777, Zarnestra®), a potent and specific inhibitor of Farnesyltransferase, can attain strong inhibition of tumor growth in preclinical models. As a single agent, tipifarnib has demonstrated activity in several hematologic malignancies, namely acute myeloid leukemia, myelodysplastic syndrome, chronic myeloid leukemia and multiple myeloma. However, considering the complexity of the molecular aberrations implicated in the pathogenesis of hematologic neoplasms, it is rather unlikely that monotherapy with tipifarnib will serve as a stand-alone treatment approach. Indeed, improved results have been achieved by combining tipifarnib with other anticancer agents, whereas the first efforts for the identification of molecular predictors of response are reporting intriguing results. Ongoing trials are anticipated to define the exact role of tipifarnib in the treatment of hematologic malignancies.
A Review of the Management of Chronic Myeloid Leukemia with Dasatinib
Authors: Gora-Tybor Joanna , Robak Tadeusz
Published: November 2017

Dasatinib is a multitargeted tyrosine kinase inhibitor (TKI), recommended for chronic myeloid leukemia (CML) in chronic, accelerated and blastic phases that are resistant or intolerant to imatinib. The recognition of BCR-ABL gene and corresponding protein with deregulated tyrosine kinase (TK) activity as crucial for malignant transformation in CML, led to synthesis of the small-molecule drugs designed to interfere with Bcr-Abl TK activation. The first TKI introduced into clinical practice in 1998, was imatinib mesylate, which became the first choice drug in chronic phase CML. However, approximately 20%-25% of patients initially successfully treated with imatinib, develop resistance to this drug, mainly because of selection of clones expressing mutant forms of BCR-ABL with impairing imatinib binding. Dasatinib is 325-fold more potent than imatinib against cell expressing wild-type BCR-ABL and showing activity against most imatinib-resistant Bcr-Abl mutants. Several clinical trials demonstrated that dasatinib is effective and generally well tolerated in imatinib resistant or intolerant CML and represents a promising therapeutic option for these patients.
A Review of Nelarabine in the Treatment of T-cell Lymphoblastic Leukemia/Lymphoma
Authors: Hernandez-Ilizaliturri Francisco J. , Czuczman Myron S.
Published: November 2017

Patients with relapsed/refractory T-cell acute lymphocytic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL) have a dismal prognosis. Prior to the development of novel purine analogs, salvage chemotherapy was of limited efficacy. Nelarabine, and more recently, clofarabine and forodesine have demonstrated significant anti-tumor activity in relapsed/refractory T-ALL and T-LBL. As a single agent, nelarabine induces response rates in between 33% to 50% of adult or pediatric patients with T-ALL/T-LBL, respectively. On the other hand, limited activity was observed in mature T-cell neoplasms. Significant neurotoxicity has been the major obstacle for the further clinical development of nelarabine. Alternative dose-schedules for administration have been evaluated with some degree of success. Ongoing clinical studies are integrating nelarabine in the front-line chemotherapy regimens for patients with T-ALL/T-LBL in pediatric and young adult patients. The current work summarizes the pre-clinical and clinical evaluation of nelarabine, a chemotherapy agent whose development demonstrates that industry, government agencies, and academia can effectively collaborate together to improve the patient outcomes with highly resistant/refractory rare hematological malignancies.
First-line Treatment of Metastatic Breast Cancer: Focus on Bevacizumab
Authors: Fujii Teruhiko , Takahashi Hiroki , Matsubayashi Roka Namoto , Inoue Yuka , Takenaka Miki , Toh Uhi , Kage Masayoshi , Yamana Hideaki , Shirouzu Kazuo
Published: November 2017

As vascular endothelial growth factor (VEGF) plays a central role in tumor growth, invasion and metastasis, inhibiting tumor angiogenesis by blocking the actions of VEGF is a rational therapeutic strategy. Drugs targeting the VEGF system are currently in development and at the most advanced stage of development is bevacizumab. The effect of bevacizumab on breast cancer has been examined in many clinical trials, and promising results have been reported. The clinical effect of bevacizumab monotherapy for breast cancer is not clear; however, the ECOG-E2100 study showed that first-line anti-angiogenic therapy using bevacizumab combined with paclitaxel clearly improved the response for earlier stage metastatic breast cancer (MBC). As a stronger anti-tumor effect is expected when prescribing bevacizumab for patients at an early stage of MBC, many first-line clinical trials using bevacizumab with other combination regimens are currently ongoing. Although the common side effects of bevacizumab are hypertension, proteinuria, wound-healing complications, and thromboembolism, it is a comparatively safe agent. It is expected that the many ongoing clinical trials will establish bevacizumab as a standard first-line therapy for MBC.
A Re-assessment of the Safety and Efficacy of Interleukin-2 for the Treatment of Renal Cell Carcinoma
Authors: Jarkowski Anthony , Wong Michael K.K.
Published: November 2017

Interleukin-2 (IL-2) can provide long term durable remissions for patients with advanced or metastatic renal cell carcinoma. The perceived morbidity and the difficulties in delivering this treatment hampered its widespread use in these patients. This review aims to place IL-2 in the modern milieu by reviewing the pharmacology, efficacy and toxicity of this drug. These will be contrasted and compared with the new targeted-agents. The methodology of providing high dose IL-2 treatment, follow-up care and its impact on patient quality of life will be discussed. Importantly, the ability of these agents to provide durable, complete remissions for RCC patients will be placed in context. The goal is to provide the perspective and framework for the reader to balance the important attributes of each of these drugs during the clinical decision making process.
A Review of the Pharmacokinetics, Pharmacodynamics and Efficacy of Zolmitriptan in the Acute Abortive Treatment of Migraine
Authors: Kalanuria A.A. , Peterlin B.L.
Published: November 2017

Migraine is a common and often disabling neurovascular disorder. Changes in the metabolism and the central processing of serotonin, as well as abnormalities in the modulation of the central and peripheral trigeminal nociceptive pathways, have been shown to play significant roles in migraine pathophysiology. Recent evidence suggests that a low serotonin state facilitates activation of the trigeminal nociceptive pathways. In addition, several pharmacological agents that modulate serotonin are used in the treatment of migraine. Specifically there are seven FDA approved, 5-hydroxytryptamine (5-HT) 1B/1D receptor agonists, used for the acute abortive therapy of migraine. Zolmitriptan is one such triptan. Zolmitriptan is available as a tablet, orally disintegrating tablet and as a nasal spray. It is rapidly absorbed and detectable within the plasma, within 2 to 5 minutes for the nasal spray and within 15 minutes for the tablet. Zolmitriptan reaches peak plasma levels in 2-4 hours, with good levels maintained for up to 6 hours. Although the metabolism of zolmitriptan is predominantly hepatic, only 25% of zolmitriptan is bound to plasma proteins. Thus it is unlikely for drug interactions involving the displacement of highly protein-bound drugs. Zolmitriptan is very well tolerated with less than half of participants in clinical trials reporting adverse events, most of which were mild and transient. Although rare, serious cardiovascular events have been reported with all triptans. However, when patients are appropriately selected, zolmitriptan is both, a safe and effective acute migraine abortive agent. In this article, we will first briefly review the biological role of serotonin and the literature linking serotonin to migraine pathophysiology. This will be followed by a comprehensive review of the pharmacodynamics, pharmacokinetics and efficacy of zolmitriptan. Finally, the clinical application of the use of zolmitriptan in migraine therapy will be discussed.
Safety and Efficacy of Lamotrigine in Older Adults with Epilepsy and Co-Morbid Depressive Symptoms
Authors: Schiller Yitzhak , Krivoy Norberto
Published: November 2017

Lamotrigine is an oral well absorbed antiepileptic medication (AED) from the phenyltriazine class approved by the FDA in 1994 for the treatment of epilepsy and in 2003 for the treatment of bipolar disorder. For epilepsy it is used to treat partial seizures, primary and secondary tonic–clonic seizures, and seizures associated with Lennox-Gastaut syndrome. Lamotrigine is the only AED that treats the depressive as well as the maniac phases of bipolar disorders. It is important to consider lamotrigine adverse reactions and drug-drug interactions such as with other AED's, psychiatric medications, estrogens, and complementary-alternative medicines. Lamotrigine induces skin reactions as part of the hypersensitivity response (HSR), the actual incidence of skin rash is low (1.8%) providing slow escalation regimens are used when introducing this medication. An especially appealing indication for lamotrigine treatment is elderly epilepsy with depression. The main advantage of lamotrigine for the treatment of this indication in the elderly lies in its favorable and predictive adverse event profile and drug-drug interactions in comparison to other AEDs. Lamotrigine can serve in the elderly as both an antiepileptic and an antidepressant drug with a relatively favorable profile.
Pharmacotherapy with Pamidronate Disodium of Osteolytic Bone Metastases of Breast Cancer, Osteolytic Lesions of Multiple Myeloma, and Paget's Disease
Authors: Hoff Ana O. , Novis Yana
Published: November 2017

High bone turnover disorders are characterized by excessive osteoclastic activity resulting in loss of bone mass and quality, fractures, deformities, debilitating pain, loss of mobility and hypercalcemia. These complications have a major impact in quality of life, and control of osteoclast activity is critical to reduce or prevent these skeletal events. Over the last 2 decades bisphosphonates became an integral part of the management of these disorders. Bisphosphonates, analogues of pyrophosphate, bind to hydroxyapatite crystals and have a very high affinity for bone mineral. Their retention in bone and rapid clearance from the circulation make them safe and effective agents for inhibition of osteoclast activity. Pamidronate is one such bisphosphonate that has been effective in treating Paget's disease, myeloma bone disease and osteolytic bone metastases from breast cancer. This review will focus on the effects of pamidronate in these disorders.
Efficacy and Safety of Sitagliptin in the Treatment of Type 2 Diabetes
Authors: Gadsby Roger
Published: November 2017

Background

Sitagliptin was launched into the UK Market in 2007, as the first member of a new class of oral glucose lowering medications, the Dipetidyl Peptidase 4 inhibitors.

Aim

To review the efficacy and safety of sitagliptin and discuss its place in therapy.

Method

Expert review using published reviews and papers published on sitagliptin, information on guideline recommendations for sitagliptin and DPP4 inhibitors, and discussion of the author's use of the agent.

Results

Evidence from a Cochrane review and meta-analysis of 14 trials or study arms suggests that sitagliptin lowers HBA1c by 0.7% in sitagliptin versus placebo trials. Evidence from a pooled safety database of 3415 people taking sitagliptin, and the Cochrane review show that the drug is well tolerated, causes no hypoglycaemia and is weight neutral. No specific signals of concern for the safety of sitagliptin have so far arisen in the pooled database. Guidelines recommend its use in triple therapy with metformin and sulphonylurea in dual therapy with metformin or sulphonylurea or thiazolidinedione in certain circumstances.

Conclusion

Sitagliptin from this initial data appears to be a safe, weight neutral and effective anti-diabetic agent.
Sorafenib in Hepatocellular Carcinoma
Authors: Bajetta Emilio , Procopio Giuseppe , Colombo Andrea , Guadalupi Valentina , Verzoni Elena , Pietrantonio Filippo , Pusceddu Sara , Manzoni Mariangela , Gevorgyan Arpine , Buzzoni Roberto
Published: November 2017

Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide with approximately 500,000 new cases per year, ranking as the third cause of cancer deaths. Until the very recent past no systemic therapy was available for patients with advanced HCC. However, advances achieved in the understanding of the molecular cancer biology and the subsequent introduction of molecularly targeted agents have disclosed promising and interesting possibilities for the treatment of this highly vascularized tumor in which the inhibition of angiogenesis is likely to represent the main potential therapeutic target. In this regard, sorafenib, an oral multikinase inhibitor endowed with significant activity against several tyrosine-kinase receptors involved in blood vessel development, has shown to be very active in the treatment of advanced HCC. This review makes a survey of pharmacology, mode of action, pharmacokinetics, clinical value and safety of sorafenib when employed in the treatment of advanced HCC.
The Rise and Fall of Rosiglitazone
Authors: Tatti P.
Published: November 2017

Rosiglitazone is a member of the Thiazolidinedione class of drugs with a potent insulin sensitizing action. The drug has been extensively used and many early warnings on its potential risks were ignored mostly due to an aggressive commercial strategy. In 2007 some papers raised doubts on the cardiovascular safety of the drug and started a serious dispute. Irrespective of the real existence of this risk the story of Rosiglitazone led to the unveiling of many other side effects and emphasizes the need for a more accurate evaluation of any drug before is approved by the regulatory authority.
Tipranavir: A Review of its Use in Therapy of HIV Infection
Authors: Winzer R. , Langmann P.
Published: November 2017

Tipranavir (TPV) is a selective nonpeptidic HIV-1 protease inhibitor (PI) which is used in the treatment of treatment-experienced adults with HIV-1 infection. Tipranavir is administered orally twice daily in combination with low-dose ritonavir. The durable efficacy of tipranavir, in combination with low-dose ritonavir (tipranavir/ritonavir 500 mg/200 mg twice daily), has been demonstrated in well designed trials in treatment-experienced adults infected with multidrug-resistant strains of HIV-1. In treatment-experienced adults with HIV-1 infection receiving an optimized background regimen, viral suppression was greater and immunological responses were better with regimens containing tipranavir/ritonavir than with comparator ritonavir-boosted PI-containing regimens. The efficacy appeared to be more marked in patients receiving two fully active drugs in the regimen, with the combination of tipranavir/ritonavir and enfuvirtide (for the first time) appearing to be the most successful. Although tipranavir is generally well tolerated, clinical hepatitis and hepatic decompensation, and intracranial hemorrhage have been associated with the drug. Tipranavir also has a complex drug interaction profile. Thus, tipranavir, administered with ritonavir, is an effective treatment option for use in the combination therapy of adults with HIV-1 infection who have been previously treated with other antiretroviral drugs.
Safety and Efficacy of the bi-Sulfydryl ACE-Inhibitor Zofenopril in the Management of Cardiovascular Disease
Authors: Napoli Claudio
Published: November 2017

In the 1970s, pharmacological therapy interrupting the renin-angiotensin system was considered beneficial for patients with high-renin hypertension. Angiotensin-converting enzyme (ACE) inhibitors proved to be effective not only in patients with high renin and elevated blood pressure, but also in many hypertensive patients with normal levels of plasma renin activity. ACE inhibitors are used in a wide range of chronic illnesses such as atherosclerosis, hypertension, myocardial infarction, heart failure, diabetic complications, and stroke. To date, more than ninety controlled clinical trials evaluating the beneficial effects of 14 different ACE inhibitors were conducted. Moreover, data from experimental studies showed that ACE inhibitors can attenuate the development of atherosclerosis, oxidative stress, and vascular inflammation in a wide range of species indicating that ACE inhibition also favourably affects the vasculature. More than fifteen years ago, the bi-sulfydryl ACE-inhibitor zofenopril has shown an excellent clinical safety and efficacy in patients with hypertension and in those with myocardial infarction. More recently, this compound exhibited a potent antioxidant and antiatherosclerotic effect indicating a clinical useful vasoprotective action.
A Review of Levofloxacin for the Treatment of Bacterial Infections
Authors: Noel Gary J.
Published: November 2017

Completing its initial phases of drug development in the mid 1990s as the one of the first fluoroquinolones that could be used with confidence to treat respiratory tract infections, levofloxacin went on to become one of the most widely prescribed antibiotics in the world. Available in both oral (po) and intravenous (IV) formulations and with characteristics of over 90% bioavailability, distribution into both extracellular and intracellular pulmonary compartments, highly predictable pharmacokinetics with over 90% of the drug being excreted unchanged in urine, and reliable activity against a broad spectrum of clinically important pathogens, levofloxacin has been used successfully to treat patients with a variety of serious infectious diseases as well as common infections most often treated outside of the hospital setting. Results of clinical trials involving patients with respiratory tract, urinary tract, and skin infections have consistently shown rates of clinical success and bacteriological eradication that were comparable to other widely used broad-spectrum agents. Regimens of levofloxacin, initially involving total daily doses of 250 mg to 500 mg, but more recently regimens involving 750 mg doses, have been shown to be safe and effective. Nearly a decade and a half of clinical experience has defined a safety and tolerability profile that permits data-driven assessment of the risks and benefits of using levofloxacin. As resistance to currently available fluoroquinolones has emerged, the clinical value of levofloxacin deserves continued evaluation. However, consistently high rates of susceptibility of clinically important bacteria, especially among those bacteria that commonly cause respiratory tract infections, such as Streptococcus pneumoniae and Haemophilus influenzae, suggest that this agent will continue to be a widely used well past the 20-year anniversary of its introduction into the antibacterial armamentarium.
Experience with Cinacalcet for Secondary Hyperparathyroidism in Patients with Chronic Kidney Disease Stage III and IV
Authors: Forslund Terje , Koistinen Arvo , Miettinen Marja
Published: November 2017

Dysequilibrium in calcium and phosphate metabolism with development of secondary hyperparathyroidism (SHPT) is common in patients with chronic kidney disease (CKD) stage III and IV. Dietary phosphate restrictions and calcium based oral phosphate binders have not been effective in all subjects with SHPT, and soft tissue and vascular calcifications with an increased risk of cardiovascular death related are known consequences. Treatment with the calcimimetic Cinacalcet (Cc) has contributed to a better calcium and phosphate control in patients given hemodialysis treatment. In this retrospective study we present our experience with Cc given to ten (one year) or five (two years) patients with CKD stage III and IV and SHPT not suitable for surgery. With conventional therapy target levels of intact parathyroid hormon (iPTH) are seldomly reached the reason why an iPTH value < 300 ng/l was considered acceptable. Levels of iPTH decreased significantly after 3 months of Cc treatment and remained at the lower level. Plasma ionized-Ca (Ca) concentrations decreased initially but remained above 1.00 mmol/l in all but one patient. Phophate (P) levels increased to 1.41 ± 0.09 mmol/l (mean ± SE) leaving the Ca × P product unchanged. While patients with high iPTH needed high Cc doses up to 90 mg/day, some of the patients required very low doses 4.5-20 mg/day in order to achieve a decrease in iPTH levels. Only one patient reported gastric pain needing dose reduction and other adverse effects were not found. No changes in QT-time were observed. We experienced that Cc treatment was promising to control SHPT and stabilized the Ca-P balance in patients with CKD stage III and IV. Dosing may be challenging and laboratory values should be controlled often (monthly) as these patients may have variable response to Cc treatment. Due to the minimal knowledge about its effect on morbidity and mortality in the predialytic population further controlled studies are needed to confirm its efficacy and safety.
Cardiotoxicity of Oral Methadone as an Analgesic–-Recommendations for Safe Use
Authors: Guay David R.P.
Published: November 2017

Once used only as third-line therapy in the management of chronic pain states, methadone is now being used as first- and second-line therapy. Most risks and the stigma associated with methadone use have been known for years. Only over the past decade or so have the unique pharmacokinetic-pharmacodynamic properties and methods for conversion from other opioids to methadone been established. Pertinent English-language literature was obtained from MEDLINE/PUBMED and EMBASE searches (1966-June 2009). This paper provides an overview of the cardiotoxicity of oral methadone, with an emphasis on its use as an analgesic. Cardiotoxicity during its use in the maintenance of opioid addiction has also been reviewed due to the wealth of epidemiologic, risk factor, and correlative analytic data contained therein. A series of recommendations are provided to improve the cardiac safety profile of oral methadone used for analgesia. In addition, there is a discussion of settings and patient types which may impact upon these recommendations.
Proteasome Inhibition: Thinking outside the Box
Authors: Armstrong Michael B.
Published: November 2017

A new era in cancer therapy is emerging with the development of tumor-specific agents exhibiting less toxicity. Since the advent of imatinib, several tumor-directed treatment options have been developed. However, therapies not directed specifically at a tumor target also have potential benefits. The 26S proteasome is a critical regulator of cell homeostasis through the degradation of key signaling molecules including p21, p27, and p53. Additionally, the proteasome degrades I-κB which inhibits the activity of NF-κB, an important promoter of cell proliferation. Blocking function of the proteasome disrupts tumor growth by shifting the balance of the cell from proliferation to apoptosis. In vitro, the proteasome inhibitor, bortezomib, inhibits NF-κB activity and prevents growth of several malignant cell types including multiple myeloma. Given the central role of NF-κB in the pathogenesis of multiple myeloma, bortezomib was a good candidate for use in therapy. Treatment of heavily pre-treated patients with bortezomib led to response rates of 30%-40%. More importantly, bortezomib led to improvements in bone metabolism, a major cause of morbidity in multiple myeloma. This effect was seen independent of the response of the myeloma. This finding correlates with in vitro studies which demonstrate increased BMP2 expression and osteoblast number after exposure to bortezomib. Moreover, bortezomib blocks NF-κB-mediated angiogenesis and tumor cell metastasis. While tumor-targeted treatments have an important role in the future of cancer therapy, these examples show that it is important not to lose sight of the benefits of less-specific agents in the treatment of malignant neoplasms.
Pamidronate and Zoledronic Acid in the Treatment of Paget's Disease of Bone
Authors: Colina Matteo , Ciancio Giovanni , Trotta Francesco
Published: November 2017

Paget's disease of bone (PDB) is a condition characterized by excessive and abnormal bone remodelling. Due to a high rate of bone remodelling, bisphosphonates, and especially pamidronate and the newer zolendronate, are indicated in the treatment of PDB. The presence of asymptomatic, but active PDB represents an indication for treatment aimed at preventing later complications. An additional indication for treatment is the involvement of skeletal segments that may give rise to severe complications. Pamidronate has a long history in the treatment of PDB. The more utilised regimen is 3 to 6 i.v. infusion of 60 mg of pamidronate at an infusion rate of 1 mg/min within 3-21 days. Zolendronate (5 mg once yearly) is the most powerful amino-bisphosphonate currently used. This primacy recognizes both the ability to inhibit the farnesyl-pyrophosphate synthetase and the higher affinity to hydroxyapatite crystals as a cause. Both pamidronate and zolendronate are effective in PDB, with an evidence-based superiority of the latter.
A Review of Trastuzumab-Based Therapy in Patients with HER2-positive Metastatic Breast Cancer
Authors: Church David N. , Price Chris G.A.
Published: November 2017

The ERBB2 or HER2 receptor is overexpressed in 25% of breast cancers and is associated with poor prognosis. Trastuzumab, a monoclonal antibody targeting HER2 has been demonstrated to improve survival when combined with chemotherapy for the treatment of HER2 overexpressing metastatic breast cancer (MBC). Further studies have endeavoured to clarify the optimum chemotherapy regimen in combination with trastuzumab for MBC and its use together with novel biological agents. This review summarises these data together with preclinical studies exploring the mechanism of trastuzumab action and causes of drug resistance. The frequent incidence of brain metastases in patients on trastuzumab is highlighted, and data on the continuation of trastuzumab following CNS and non-CNS progression reviewed.
Radiographic Outcome of Unstable Distal Radial Fracture Treated by Closed Reduction and Pin in Plaster
Authors: Hasankhani Ebrahim Ghaiem , Pivandi Mohamad Taghi , Nejad Ali Birjandi
Published: November 2017

Background

There is controversy about the appropriate treatment for severely displaced and unstable comminuted fracture of distal radius (type C of AO or OTA classification). Recently, there has been an increase in the number of predilection for surgical management of this fracture.

Aim

To determine the radiographic outcome in type C fractures of the distal radius treated with closed reduction and pin in plaster.

Materials and Methods

Eighty consecutive patients 60 male and 20 female, average age 40 years (22–60 years), with type C fractures of the distal radius seen between February 2001 and July 2003 in Shahid Kamiab Hospital of Mashad University, were treated by closed reduction and pin in plaster, followed up by anteroposterior and lateral radiographs to evaluate radial height, inclination and volar tilt.

Results

There was significant improvement in the measurements of radial height, inclination and volar tilt after closed reduction and pin in plaster, and at the time the pins and plaster were removed. (P = 0.00).

Conclusion

Closed reduction and pin in plaster is an effective, simple and low cost method in type C fractures of distal radius with satisfactory outcome.