Translational Biomedicine

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Translational Biomedicine (TBM)
Published by IMedPub publishing house.
ISSN: 2172-0479
Frequency: Bimonthly
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An unusual case of Winkler’s disease of Pinna

Dr. Nagaraj.B.T, Dr. Ravi.G.C, Dr. Somasundar Reddy
MVJ Medical College and research Hospital, Bangalore.

Abstract:

Chondrodermatitis nodularis chronica helicis is a painful nodule of the external ear.These uncommon lesions are most often encountered on the helix in white men older than 40 years, although they also rarely occur on the antihelix in women.The lesions frequently present with exquisite tenderness that interferes with sleep.While the cause of this dermal inflammatory process is not known, long-term trauma or sun damage may play a role. Recurrences often complicate treatment if all sites of inflammation are not eradicated. Surgical treatment is generally recommended,either by wide excision or by deep shave and treatment of the underlying cartilage. Winkler’s disease usually presents as 3 to 10 mm nodule in the helix or anti helix. We are reporting an unusual presentation of Winkler’s disease as a large nodular mass arising from the tragus, nearly occluding the external auditory canal (size about 1.5x2.0 cms).

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Global translational medicine initiatives and programs

Aamir Shahzad*, Craig S McLachlan, Judith Gault, Randall J Cohrs, Xiangdong Wang & Gottfried Köhler.

1Department for Biomolecular Structural Chemistry, Max F. Perutz Laboratories, University of Vienna,Austria.

2Rural Clinical School, Faculty of Medicine, University of New South Wales, Sydney, Australia.

3Department of Psychiatry & Neurosurgery, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA.

4Department of Neurology, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA.

5Biomedical Research Center and Department of Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.

Abstract:

Translational medicine results from collaborations between clinics, research hospitals, governments, academics, and small to large scale industry where diseases (infectious, acquired, or genetic) are identified, candidate therapeutics optimized and tested in cell culture, humanized small animal models, and in clinical trial. The goal of translational medicine is to bring to market safe and effective therapeutics in a timely and cost efficient manner. However, clinician/scientists critically trained in translational research are few and more programs to foster their development are required. Herein the state of translational medicine in leading countries (UK,Netherlands, Austria, Singapore, China, Australia, Japan, India, Malaysia, South Korea and the United States) as well as joint EU efforts is described. A summary of programs, research projects, funding agencies, national support levels and unique opportunities within each nation are presented. The future of translational medicine and interagency collaborations is promising, provided highly trained translational medicine experts can be trained. That is to produce translational leaders that engage the patient, the laboratory, industry and government.

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Cloacal anomaly and cleft palate following Phenobarbital usage during pregnancy: The first report

Seyed Abdollah Mousavi, Ebrahim Salehifar*
Department of Pediatric Surgery, Mazandaran University of Medical Sciences, Sari, Iran.
Department of Clinical Pharmacy, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.

Abstract:

Background: Several congenital malformations such as craniofacial and digital abnormalities, and less commonly, cleft lip and palate have been reported with phenobarbital. According to our knowledge, it is the first report of cloacal anomaly and cleft palate following prenatal phenobarbital exposure. Case: A 20-year-old gravid 1, Para 1 woman at 40 weeks of gestation was admitted for a normal vaginal delivery. She had a history of convulsion one month before pregnancy. The described dosage of Phenobarbital by her physician was 100mg every night but she had increased the dosage to 100mg q8h incidentally. Other medication was folic acid in usual dosage and continued until delivery. There was no familial history of birth defects, any antenatal infection or exposure to any other medications, alcohol, smoking, or exposure to X-rays. Pregnancy was uncomplicated and a baby girl weighing 2600g was born. APGAR scores were 8 and 9 at 1 and 5 minutes, respectively. By clinical picture, diagnosis of cloacal anomaly was confirmed. The other anomalies were cleft palate, a small patent ductus arteriosus in echocardiography and a short sacrum. A nuclear renal scan, which was performed after two months, suggested severe decrease perfusion and function of right kidney. The patient was treated with multiple operations on oral, urogenital and anorectal system. Conclusion: In addition to previously recognized risks associated with phenobarbital during pregnancy, cloacal anomaly should be considered as a possible adverse outcome.

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Neurophysiological involvement in hypervolemic hyponatremia - evoked by hypersecretion of vasopressin

Yu-Feng Wang1*, Li-Xiao Liu*, and Hai-Peng Yang
1 Department of Cellular Biology and Anatomy, LSU Health Sciences Center, Shreveport,
LA,USA;
2 Department of Pediatrics, the Fourth Affiliated Hospital, Harbin Medical University, Harbin,
Heilongjiang, China.

Abstract:

Arginine vasopressin (AVP) is a neuropeptide mainly synthesized in the supraoptic and paraventricular nuclei in the hypothalamus and released from the posterior pituitary when physiological demands are increased.The major function of circulating AVP is to promote water retention and vasoconstriction, thereby maintaining hydromineral homeostasis and blood volume and pressure. Physiological regulation of AVP secretion includes osmotic and nonosmotic neurohumoral reflexes, actions of bloodborne factors, interactions between glia and AVP neurons, autoregulation, and other cellular events. These modulatory processes, ultimately integrated in AVP neurons,determine their firing rate and pattern and the amount of AVP secretion. In water retaining diseases such as congestive heart failure and hepatic cirrhosis, efficient arterial volume is relatively low despite water retention in the body; high levels of AVP cannot correct insufficiency of efficient arterial volume and/or high levels of circulating renin-angiotensin-aldosterone. These nonosmotic factors can counterbalance and even override the inhibitory effect of AVP-elicited hyponatremia on AVP secretion.Under this condition, a facilitatory feature of local neural circuits controlling AVP secretion becomes active, leading to further secretion of AVP. This inherent feature in the local circuit mainly includes: 1) adaptive reduction of osmosensory threshold, 2) removal of astrocytic restriction of AVP neuronal activity, and 3) damaging effects of protein tyrosine nitration on enzymes for glutamate conversion and on other functional molecules. These factors will be discussed in this review.
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Efficacy of oral DMSA and intravenous EDTA in chelation of toxic metals and improvement of the number of stem/ progenitor cells in circulation

Nina Mikirova*, Joseph Casciari,Ronald Hunninghake.
Riordan Clinic, Wichita, KS, 3100 N. Hillside,USA.

Abstract:

Metal toxicity represents a significant public health concern and contributes to many toxic metal-exposure related diseases. In particular, toxic metals promote the oxidative stress in stem cells and endothelial progenitor cells (EPCs). EPCs that are presented in peripheral blood function to replenish aging damaged endothelial cells and play important role in the maintenance of vasculature and neovascularization. Given the links between oxidative injury, endothelial cell dysfunction and vascular disease, we focused our investigation on the response of CD34-positive cells to chelation by DMSA.In addition, we compared the effectiveness of DMSA and EDTA in the chelation of toxic metals and the excretion of essential metals.The data were compared for 160 subjects after oral DMSA (500mg) chelation and 250 subjects after intravenous EDTA (1g-3g) chelation. Our in vitro experiments were designed to compare the intrinsic toxicity of two antidotes and their effectiveness in lead chelation. One of the important results of our study shows that the removal of toxic metals improves the number of stem/progenitor cells in circulation. After a series of five DMSA treatments, the number of CD34+ cells in circulation was increased on 50%-160% (p<0.05).Our in vitro experiments demonstrated that toxic metals (lead and mercury) inhibit mesenchymal stem cell metabolism and proliferation, and that stem cells are more sensitive to these metals than differentiated cells. In comparison with EDTA, DMSA was more effective in the extraction of lead, but treatment by this antidote resulted in a very high excretion of copper (55 folds). Clearance of essential metals during chelation by 1g-3g of EDTA was increased over twenty-fold for zinc and manganese.In summary, we suggest that chelation therapy shows promise in repairing metal toxicity damage and restoring circulating stem cells.

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Recommendations for comprehensive translational medicine education and training

Aamir Shahzad*, Randall J Cohrs, Roland Andersson, Xiangdong Wang & Gottfried Köhler.

1 Department for Biomolecular Structural Chemistry, Max F. Perutz Laboratories, University of Vienna, Austria.
2 Departments of Neurology, University of Colorado Health Sciences Center, Denver, Colorado, USA.
3 Department of Clinical Sciences, BMC F10,Lund University Hospital, Lund, Sweden.
4 Biomedical Research Center and Department of Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.

Abstract:

The gap between basic research and its practical application is ever widening.Translational research promises to bridge this gap with the added potential to accelerate product R&D in both pharma and biotech industries by supplying the field with well-qualified ‘Medical Translators.’ To ensure proper training, both comprehensive educational and corporate mentorship is needed. This training program should cover all aspects of translational medicine. Herein, we propose recommendations for a comprehensive translational medicine educational and training program to meet industry requirements. Both the curricula and practical aspects of this program are also discussed.
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Malarial infection among patients attending a Nigerian semi-urban based hospital and performance of HRP-2 pf Rapid diagnostic Test (RDT) in screening clinical cases of Plasmodium falciparum malaria

*R S Houmsou, E. U. Amuta, Sar, T.T, A. H. Adagba.

1* Department of Biological Sciences, Faculty of Science, Taraba State University, P.M.B 1167 Jalingo, Nigeria.
2 Department of Biological Sciences, College of Science, University of Agriculture Makurdi, Benue State, Nigeria.
3 Department of Biological Sciences, College of Natural and Applied Sciences, University of Mkar, Mkar, Benue State, Nigeria.

Background: Malaria is a life threatening disease caused by Plasmodium spp that are transmitted to people through the bite of infected mosquitoes. This study was undertaken to determine malarial infection among patients attending General Hospital Gboko, Benue State, Nigeria and evaluate the performance of the Histidine Rich Protein (HRP-2) pf Rapid Diagnosis Test (RDT) in screening clinical cases of Plasmodium falciparum malaria in a field setting. Methods and Findings: The study was conducted between June and October 2010. Thick blood smears were prepared using standard parasitological procedures,other information concerning the patients were obtained using a well structured questionnaire. Prevalence rate of malaria irrespective of Plasmodium species among the patients examined was 39.5% (102/258). Prevalence rate of malarial infection was not significantly different between sexes (χ2 = 0.01, p>0.05), age groups (χ2 = 6.44,p>0.05), educational status (χ2= 6.1, p>0.05) and occupation of the patients examined (χ2= 8.4, P>0.05). The study also revealed predominance of Plasmodium falciparum malaria (59.1%) among all the positive cases of malaria. Performance of the HRP-2 pf RDTs showed a sensitivity of 89.5% and specificity of 100% in the area. Conclusion:The results obtained suggested that microscopy remains the gold standard method for diagnosis of malarial infection, although the HRP-2 pf RDTs can be used where microscopy is not available and in cases where urgent malaria diagnosis is needed.

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Yeast “contraceptives” also novel drugs

This lecture describes the translation of yeast "contraceptives" to new anti-mitochondrial drugs. Our nanotechnology research on yeast “contraceptives” suggests that “nanosurgery” and even “nanotransplantation” of cell parts on different viable cell types, should now be explored using Focused Ion Beam (FIB) technologies, References can be obtained from the authors.

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Elevated DISC1 transcript levels in PBMCs during acute psychosis in patients with schizophrenia

Ann Olincy, Robert House, Bifeng Gao, Peter Recksiek, Tzu Lip Phang, Bernadette Sullivan, Jeff P. Hollis, Janet Hopkins, Ted Shade, Michael G Edwards, Ruby Vianzon, Cory Griffiths, John Ceilley, Roger W. Helfrich, Jonathan Ritvo, Erica Weis,David Weiss, Judith Gault.*

1 Department of Psychiatry, University of Colorado, Anschutz Medical Campus, Aurora,CO, USA
2 Behavioral Health, Denver Health Medical Center, Denver, CO, USA.
3 Cancer Center, University of Colorado,Anschutz Medical Campus, Aurora, CO, USA.
4 Department of Neurosurgery, University of Colorado, Anschutz Medical Campus, Aurora,CO, USA.
5 Department of Pulmonary Sciences, University of Colorado, Anschutz Medical Campus,
Aurora,CO,USA.

Background: Severe mental disorders like schizophrenia are a leading cause of disability in people in the prime years of their lives (aged 15 to 44 years). Relapse is a primary contributor to schizophrenia disease burden and is frequently attributed to medication noncompliance and inadequate doses. Currently, a patient’s neuroleptic dose is titrated to clinical response within recommended dose ranges. Use of unbiased biomarkers of effective neuroleptic treatment-response would greatly facilitate the identification of a person’s lowest effective dose to minimize unsafe side effects and improve compliance. Biomarkers may allow precisely tailored adjustments of neuroleptic dose to reduce relapse due to variable disease course. Methods and Findings: Biomarkers of active psychosis were sought among persons with schizophrenia hospitalized with acute psychosis. The transcriptional response of peripheral blood mononuclear cells (PBMCs) to treatment of psychosis was measured using RNA expression profiling in 12-paired samples from patients with schizophrenia. The paired samples were collected early after treatment initiation and again just before patients were released from the hospital. Patients showed significant improvement in positive symptoms of psychosis assessed at each sample collection using a brief psychiatric rating scale (BPRS) (P<0.05). Preliminary evidence is presented indicating that decreased transcript levels of isoforms of disrupted in schizophrenia 1 (DISC1) measured in PBMCs were associated with treatment in 91% of samples (P=0.037). Conclusion: Further studies are warranted to identify neuroleptic-response biomarkers and to replicate this initial finding of association of DISC1 transcript levels with treatment of psychosis.

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Papillary cancer of the colon: A rare presentation with lower GI bleed and a review of the literature

*Viplove Senadhi, Deepika Arora, Dennis Emuron, Manish Arora, Andrew Ghaly, Franklin Marsh.
1 Johns Hopkins University/Sinai Hospital Program in Internal Medicine, Baltimore,Maryland, USA.
2 Elmhurst Hospital/ Mount Sinai School of Medicine, New York City, New York, USA.
3 Mbarara University of Science and Technology,Mbarara, Uganda.
4 Division of Gastroenterology, University of Maryland School of Medicine and National Institute of Health (NIH), Baltimore, Maryland,USA.
5 Saint Matthews University School of Medicine,Grand Caymen Islands, British West Indies.
6 Division of Gastroenterology, New York Hospital-Weill Cornell Medical Center, New York City, New York, USA.

Cancer is second only to Coronary Artery Disease in overall mortality in the United States. Amongst all the cancers, lung cancer is the most common and is associated with the highest cancer related mortality amongst both genders. Lung cancers present with metastasis about 50% of the time. The most common sites of lung metastases include the adrenal glands, brain, bone, liver, lymph nodes, and the contralateral lung. However, gastrointestinal (GI) metastasis and manifestations are rare.Most of the reported cases of lung cancer metastasis to the gastrointestinal tract involve the small bowel (2-5) and occur through lymphatic spread. We present a rare case of a primary papillary (subtype) adenocarcinoma of the lung recurring as lower GI bleeding due to colonic metastasis.

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A Balanced Trade Context for HIV Patent Pool

Daniele Dionisio, M.D.

Member, European Parliament Working Group on Innovation, Access to Medicines and Poverty-Related Diseases.
Reference Advisor for “Drugs for the developing countries”, SIMIT (Italian Society for Infectious and Tropical Diseases).
Former Director, Infectious Disease Division,Pistoia city Hospital (Italy).

Background: Reluctance of the multinational pharmaceutical companies to join the Medicines Patent Pool plan for HIV drugs (antiretrovirals-ARVs) might undermine its desirable objective of scaling up long-term, extended access to novel, affordable and appropriate ARV formulations in resource-limited settings. Methods: This paper makes an analysis of conflicting issues and calls for a trade context facilitating a reverse of multinational drug manufacturers’ reluctance to join patent pool. To this aim, partnerships between multinational companies are urged first to make cutting edge brand fixed-dose combination (FDC) ARVs promptly available, and secondly, to allow patent pool agreements to be negotiated immediately afterwards. This context rejects clauses that exclude middle-income countries from sharing in the patent pool. Expected Results: The suggested trade context can help speed up the participation of originator pharmaceutical companies in the Medicines Patent Pool, while allowing them to maintain competitiveness, take advantage of incoming joint venture opportunities and circumvent the need for additional incentives. This context potentially tackles in an appropriate way the directions of evolution in emerging markets, while bringing benefits to resource-limited populations, multinational drug corporations and manufacturers from middle-income countries. Conclusions: This study mixes analysis of health needs and of changing dimensions both in legislation and the pharmaceutical industry, with a political economy focus that considers the interests and capacities of key participants in global HIV treatment. So compounded, this study offers practical suggestions to stimulate the current debate.

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Effect of Pinus koraiensis seed oil on satiety hormones CCK and GLP-1 and appetite suppression

Zamola Frantisek M.D. Krewel Meuselbach,
Nam. Gen. Kutlvasra 6,Prague,Czech Republic.

Obesity is a serious public health challenge. In recent years various strategies for treatment of obesity are researched. Because of limitations of drugs currently available, new preparations for treatment are searched (especially safe natural products). PinnoThin™,Korean pine nut oil with high content of pinolenic acid, was subjected to two studies, which evaluated its influence on satiety hormones cholecystokinin and glucagon like peptide 1. The results of the studies confirmed, that pine nut oil is capable of increase of satiety hormones release and therefore it suppresses appetite. It does not have any effect on hunger inducing factor ghrelin. The study of toxicity showed that pine nut oil is not toxic and so it is safe for obesity treatment.

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Abstracts : First French-Argentine Immunology Congress, 2010 Buenos Aires, Argentina, 2nd-5th November, 2010

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Micronutrient optimization storage trial using customized vitamin & mineral replacement therapy (Most 2010)

Darrin L. Frye, MD, MPH ABAARM
Dr. Darrin L. Frye, MD, 8409 N. Military Trail, Suite 126, Palm Beach Gardens,FL,USA.

Background: Ultimate health and maximal life span require metabolic harmony and nutrient abundance. Evidence suggests that metabolic damage occurs at intake levels between the level causing micronutrient deficiency diseases and the recommended dietary allowances (RDA). This may result in an increase in DNA damage, neuronal or mitochondrial decay that could lead to accelerated aging, cancers, and degenerative diseases. The optimum amount of vitamins and minerals that are truly required is the amount that minimizes DNA damage and maximizes a healthy life span, which is higher than the amount to prevent acute disease. Maintaining healthy vitamin and mineral stores prevent disease and limit morbidity from them. Methods: We examined prospectively a cohort of active adults aged 34 to 73 (median 53.5) years of age who were seen at a preventive medicine center in 2009 - 2010. These 10 adult men and women had a comprehensive medical history and baseline and 6 month cellular blood testing utilizing SpectraCell Laboratory’s comprehensive micronutrient method. They were treated therapeutically using IVitaminScience’s (IVS) custom formulation supplementation therapy for six months. Individual nutrient values at six months were compared against their baseline values. Thirteen individual vitamin and ten mineral components that were supplemented based on a proprietary IVitaminScience algorithm. Findings: Both men and women showed substantial overall improvement in their vitamins and mineral cellular storage balance. Results of the testing revealed mean deviation from ideal of 15, that decreased from 7.18 (standard deviation 1.12) to 5.73 (standard deviation 2.09) a 20.55% improvement in just six months. Conclusions: In a society of nutrient depleted food sources, and poor dietary selection practices, determination of individual nutrient deficiencies and repletion with specific therapeutic doses of vitamins and minerals appears to have promise in restoring and maintaining health. Further studies on vitamin and mineral supplementation targeting disease specific states should be conducted using this model since treatment can be initiated precisely, and objective follow up data can be combined and correlated with clinical findings.

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Bone marrow derived mononuclear stem cell implantation in patients with Buerger’s disease

Shapour Shahgasempour, Habibullah Peirovi, and Afshin Fathi, M.D
Tissue Engineering and Nanomedicine Research Center, Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: Patients suffering from Thromboangiitis obliterans (TAO) have endothelial cell dysfunction and the severity of the disease lies in the need for amputation in more than a quarter of all sufferers. Methods and Findings: We report the safety and feasibility of autologous implantation of circulating mononuclear cells for patients suffering from Buerger’s disease following bone-marrow mobilization with granulocyte colony stimulating factor (5m g/kg/day for 5-7 days). Six patients participated in this study. Mononuclear cells were separated by Cobas Spectra cell separator. MNCs, CD34+ and CD133+ cells were enumerated prior to intramuscular injection into the affected foot/limb muscles at multiple sites on the collection day. Stem cell injection prevented disease progression in all six patients. In this small cohort of patients with critical limb ischemia, quality of life improved significantly over a two year period. Also, pain-free walking distance in all patients showed significant improvement. Conclusions: Autologous mononuclear cell containing CD34+/CD133+ stem cells collected from peripheral blood following G-CSF mobilization is effective, safe and results in sustained clinical results for patients with severe peripheral occlusive arterial disease.

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Targeted weight reduction using Sibutramine

Stritecka Hana, Hlubik Pavel, Hlubik Jan
University of Defence, Faculty of Military Health Science, Department of Military Hygiene, Group of Nutrition Hygiene, Trebeska 1575, 500 01 Hradec Kralove, Czech Republic.
Faculty of Electrical Engineering CTU, Karlovo namesti 13, 121 35 Praha 2, Czech Republic.

Obesity is a serious chronic disease resulting from positive energy balance. Obesity is also an independent risk factor for the development of non-communicable widespread disorders. The endpoint of the trial was a targeted reduction of excessive body weight in 99 individuals with BMI over 30 or 27 kg/m2 respectively. Three-month weight reduction therapy was based on the restriction of energy intake and pharmacotherapy by Sibutramine hydrochloride monohydrate (Sibutramine) 10mg/person/day. Results: Three-month targeted therapy resulted in statistically significant decrease of BMI, body weight, body fat and waist circumference. The reduction improved lipid profile and resulted in the decrease of systolic and diastolic blood pressure. Heart rate increased only insignificantly. Targeted reduction of excessive body weight using Sibutramine pharmacotherapy had a positive effect on anthropometric and biochemical characteristics without any adverse effect of nutrition in participating individuals.

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CXCR4 inhibitor plerixafor and G-CSF allow for an effective peripheral blood stem cell collection in patients who failed previous mobilization attempt

Grzegorz Wladyslaw Basak, Elzbieta Urbanowska, Magdalena Witkowska, Dorota Zdunczyk, Anna Waszczuk-Gajda, Kamila Skwierawska, Joanna Drozd-Sokolowska, Monika Skibinska, Magdalena Glazer, Krzysztof Madry, Tigran Torosian, Kazimierz Halaburda, Maria Krol, Karolina Serzysko, Patrycja Rusicka, Maciej Gontarewicz, Wieslaw Wiktor- Jedrzejczak.
Department of Hematology, Oncology and Internal Diseases, The Medical University of Warsaw, Poland.

Background: Plerixafor is a CXCR4 receptor inhibitor, which was recently introduced for stem cell mobilization in myeloma and lymphoma patients prior to their transplantation. Since March 2009, we performed 16 mobilizations using plerixafor in combination with G-CSF in 10 patients with multiple myeloma, 3 Non-Hodgkin’s lymphoma and 3 Hodgkin’s lymphoma, who failed previous mobilization attempts with G-CSF in combination with chemotherapy. Methods and Findings: Our protocol consisted of daily s.c. injections of G-CSF (2 x 5 µg/kg) on days 1 through 7 and plerixafor (240 µg/kg) on day 4, 5 and 6. In three patients, plerixafor was added to chemotherapy-based mobilization regimen, in case when No. of CD34+ cell was too low to start cell collections. The median No. of circulating CD34+ cells after first administration of plerixafor was 23/µL (range 11-62) and in 13/16 patients it exceeded minimum of 15 cells/µL required to begin leukapheresis on that day. However, due to high peripheral blood leukocytosis (median 36.5 G/L; range, 11.4-72.5) the frequency of CD34+ cells was low (median 0.067%, range 0.030-0.215) that affected low collection efficiency of CD34+ cells. Moreover, this required collection and freezing of abundant No. of nucleated cells (median 9.3 x 108 NCs/kg, range 6.15-24.05). In our setting, high nucleated cell count translated into high volume of stem cell product (median 1260 mL; range 500-2050). Nevertheless, the final stem cell products contained median of 2.8 x 106 CD34+ cells/kg b.w. (range, 0.57-4.5 x 106) and in 12/16 patients (75%) it exceeded 2.0 x 106 CD34+ cells/kg b.w., which is required for stem cell transplantation. Eight patients have already been transplanted and median time to neutrophil (>0.5 G/L) recovery was 12 days (11-14) and platelet (>20 G/L) recovery was 14 days (10-25) that is satisfactory. Conclusions: Stem cell mobilization with plerixafor and G-CSF provides solution for majority of patients requiring autologous hematopoietic stem cell transplantation and failing mobilization with G-CSF in combination with chemotherapy. However, due to high leukocytosis, this protocol requires modification of stem cell collection and freezing procedures in order to avoid large volumes of stem cell product.

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Knowledge of female genital cutting among parents in south west Nigeria

Olukunmi ‘Lanre OLAITAN, Ph.D.
Department of Human Kinetics and Health Education, University of llorin, Nigeria.

Objective: To find out the knowledge of FGC among parents in south west Nigeria. Study design: Descriptive cross-sectional survey method was used to conduct the study. Study period: March 2009 to December 2009. Sample size: 536 parents from 3 selected state capitals in south west Nigeria. Study variables: Age, gender and educational status. Statistical analysis: Descriptive and inferential statistics (mean, standard deviation, t-test, Analysis of Variance (ANOVA) and Duncan Multiple Range Test (DMRT). Results : The study revealed that there is no significant difference in the knowledge of parents on FGC based on gender. The null hypotheses were not rejected, because the calculated value t=1.91 obtained, was less than the table value of 1.96 at 534 degrees of freedom at 5% level of significance. This shows respondents did not differ in their knowledge about FGC based on gender whereas, other null hypotheses were rejected, be- cause there existed significant differences in the parents’ knowledge of FGC based on age and educational status with calculated F-values 7.62 and 7.62, while the table values were 2.08 and 2.12 respectively. Duncan Multiple Range Test was employed to determine the significant differences existed between and within the group of means where ANOVA was used. Conclusion: On the basis of the findings, it was recommended that parents, community leaders, religious leaders as well as traditional rulers should be educated on the hazards of FGC and should inculcate in their people on how to stop harmful traditional practices. Government should enact a law to prohibit FGC; there should be public enlightenment campaign to the general public about consequences and health hazards of FGC on the victim. Also community health education should be organized for traditional circumcisers to stop this harmful to stop this harmful practice among girls and women.

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Kaposi Sarcoma Pathogenesis: A Triad of Viral Infection, Oncogenesis and Chronic Infammation

Janet L. Douglas, Jean K. Gustin, Ashlee V. Moses,Bruce J. Dezube and Liron Pantanowitz
Vaccine and Gene Therapy Institute, Oregon Health Sciences University, Beaverton, OR.
Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA.

Kaposi sarcoma (KS) is a complex cancer that arises from the initial infection of an appropriate endothelial or progenitor cell by Kaposi Sarcoma Herpesvirus/Human Herpesvirus-8 (KSHV/HHV8). However, the majority of KS cases occur when infected patients also suffer from some coincident form of immune deregulation, providing a favorable microenvironment for tumor development. Cellular hallmarks of KS progression include both the hyper-proliferation of KSHV-infected cells and the infiltration of immune modulatory cells into KS lesions, which together result in chronic inflammation,the induction of angiogenesis and tumor growth.This review describes the current understanding of the interactions between KSHV and host responses that result in this unusual cancer, along with existing treatments and prospects for

future therapeutic approaches.

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Rho Kinase-mediated Coronary Arteriolar Constriction to Endothelin-1: Mechanistic Implications for Cardiac Syndrome X

Guangrong Lu, Travis W. Hein, Lih Kuo
Department of Systems Biology and Translational Medicine, and Department of Surgery, College of Medicine, Texas A&M Health Science Center, Temple, Texas 76504, USA.
Correspondence: Lih Kuo, Ph.D., Department of Systems Biology and Translational Medicine, Cardiovascular Research Institute, Texas A&M Health Science Center, Temple, Texas 76504, USA.

Rho kinase (ROCK) has been implicated in mediating diverse biological functions of various cells. Accumulating evidence has suggested that abnormal activation of ROCK contributes to the development of cardiovascular disease. The elevation of endothelin-1, the most potent endogenous vasoconstrictor, is also known to be associated with numerous cardiovascular disorders. Recent reports suggest that the constriction of the coronary microvasculature to endothelin-1 is mediated by the activation of ROCK signaling. In this article, we provide an overview on the ROCK and endothelin-1 vascular biology in relation to the control of vasomotor activity and speculate on their contributions to local myocardial ischemia and cardiac syndrome X. Although the underlying cellular and molecular mechanisms involved in exerting endothelin-1/ROCK regulation of coronary microvascular function remain elusive, the development of specific and selective ROCK inhibitors appears to have therapeutic potential in cardiovascular disease treatment.

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Possible correlation of plica-limbal distance with the presence of primary medial pterygium

Herman Christiaan Izaak Themen, Dennis Ricardo August Mans, Robbert Bipat ,Denise Judith Doelwijt, Dineshpersad Jiawan, Annemarie Thelma Bueno de Mesquita-Voigt

Department of Ophthalmology, Academic Hospital Paramaribo, Paramaribo, Suriname;
Department of Ophthalmology, Faculty of Medical Sciences, Anton de Kom University of Suriname;
Department of Pharmacology, Faculty of Medical Sciences, Anton de Kom University of Suriname;
Department of Physiology, Faculty of Medical Sciences, Anton de Kom University of Suriname.

Background: Loss of elastic properties, the introduction of tractional forces, and shortening of the plica-limbal distance (the distance between the nasal limbus and the semilunar plica bottom in full abduction) are common anatomical abnormalities in eyes of patients with primary medial pterygium. In this study, we assessed whether, and to which degree the latter phenomenon correlated with the presence of pterygium. Methods and findings: Plica-limbal distance was measured using a slit lamp in individuals who came for routine eye examination, and was related to pterygium size, as well as to patients’ gender and age. Data were expressed as means (95% CI). Eighty-three males and 118 females were enrolled in the study. There were 49 eyes from patients with uni-lateral pterygium, 84 from patients with bilateral pterygium, and 220 from individuals who did not surfer from either uni-or bilateral pterygium. The mean plica-limbal distance in eyes with pterygium (7.3 mm, 95% CI: 6.9–7.7 mm) was significantly shorter than that in eyes without pterygium (9.9 mm, 95% CI: 9.7–10.1 mm). Plica-limbal distance correlated inversely with pterygium size (r2 = 0.32, p< 0.0001) was not related to gender, but decreased with increasing age in both individuals with and without pterygium. Conclusion: Our results suggest that plica-limbal distance correlated inversely with the presence of pterygium. This finding may have important consequences for the identification of individuals at risk, as well as for improvement of the treatment of this condition.

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A Rare Presentation of Community - acquired Pneumonia Caused by Corynebacterium pseudodiptheriticum: A Case Report

Addison Parris, Jane S. Tang and Ganesh D. Kini
Departments of Infectious Diseases and Internal Medicine; The Rockingham Memorial Hospital. 2010 Health Campus Drive, Harrisonburg, VA 22801, USA.2 Noblis. Falls Church, VA 22042, USA.

Background:As a normal flora in the upper respiratory tract,Corynebacterium (C.) pseudo diptheriticum is not often considered as the causative bacterium for community-acquired pneumonia. Findings: In this case report, a patient with bronchiectasis was initially suspected as being infected with Mycobacterium avium. When antibiotic treatment was not successful, bronchial alveolar lavage was obtained for microbiological culturing. Once C.pseudodiptheriticum was recovered from this less-frequently requested respiratory sample, its antibiotic susceptibility profile was obtained to allow appropriate antimicrobial intervention to arrest the infection. The patient experienced full recovery. Conclusion: This report shows the importance of considering non-routine, sometimes invasive clinical specimens to make a diagnosis. Furthermore, commensal microbes should not be dismissed as possible etiological agents in pulmonary infections.

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Estimation of Familial Association of Blood Pressure with BMI and WHR among Type 2 Diabetic and Non-diabetic Punjabi Population in Punjab, India

Badaruddoza, Ramandeep Kaur and Basanti Barna
Department of Human Genetics, Guru Nanak Dev University, Amritsar-143005, Punjab, India

Background: There is a common opinion that Indians have more tendencies to develop greater waist circumference and waist to hip ratio, thus having a greater degree of central obesity. This total abdominal and visceral fat increases insulin resistance and the development of type 2 diabetes with elevated blood pressure. Objective: To describe the basic design for family correlation between blood pressure phenotypes, body mass index (BMI) and waist to hip ratio (WHR) among non-diabetic and type 2 diabetic individuals. Methods: A cross-sectional descriptive study of 449 (246 non-diabetic and 203 type 2 diabetic) individuals from 130 families were ascertained for the present study. The anthropometric measurements included height (cm), weight (kg), waist circumference (cm), hip circumference (cm), biceps skinfold (mm), triceps skinfold (mm), mid upper arm circumference (MUAC) (cm). The physiometric variables included systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial blood pressure (MBP) and pulse rate. All the measurements were taken on each individual using standard technique. Results: It is observed from the present investigation that type 2 diabetes predominately occur among male individuals. It has been observed that onset of type 2diabetes among female offspring is much lower (31.67 ± 5.58 years) as compared to male offspring (40.75 ± 5.98 years). The descriptive analysis suggests that most of the anthropometric variables are significantly (p<0.001)> Conclusion: The present study reveals a pronounced role of cohabitation and familial aggregation for the association of blood pressure with BMI and WHR among non-diabetic individuals as compared to diabetic individuals.

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Phosphate buffer-stabilized 0.1% chlorine dioxide-containing mouth wash facilitated sequestration of Bishphosphonate Related Osteonecrosis

Ehsan Soolari, Amin Soolari and Ahmad Soolari

College of Chemical and Life Sciences, University of Maryland, USA.
Churchill High School, Potomac, MD, USA.
Private periodontal practice in Silver Spring and Potomac, Maryland, USA.

Background: Inconclusive protocol and consensus exist at present time regarding treatment of patients who have developed Osteonecrosis of the Jaw (ONJ) following administration of intravenous Bisphosphonates. Most clinicians are avoiding treatment for patients presenting with BRONJ due to lack of predictable treatment outcome. Findings: In this case report, patient was suffering from a non healing lesion on anterior mandible, which was not responsive to any conventional treatment. Patient was recommended to rinse with the PBSCD for treatment of BRONJ (Bisphosphonate Related Osteonecrosis of the Jaw) lesion seen on some patients who were on intravenous Bisphosphonate medications for multiple myeloma. Patient was recommended to rinse three times a day with PBSCD. After 4 month use of the solution patient presented with soft tissue healing on previously exposed necrotic bone on mandibular anterior region. Conclusion: The benefit of Phosphate buffer-stabilized 0.1% chlorine dioxide-containing mouth wash (PBSCD) is discussed. This is a non invasive protocol that has proved to be effective in closing of an open wound.

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Translational Biomedicine: a clinician’s view

Lawrence Leung
Centre of Studies in Primary Care Queen’s University, Kingston Ontario, Canada.

We all know what translation is all about in language when you need to express ideas and concepts from one common set of symbols and semantics to another set. How about in science and medicine? Merriam-Webster Dictionary defines “translational research” as “medical research that is concerned with facilitating the practical application of scientific discoveries to the development and implementation of new ways to prevent, diagnose, and treat disease.” Professor Lee Nadler, senior vice president for Experimental Medicine at the Dana Farber Cancer Institute also epitomises a translational researcher as “someone who takes something from basic research to a patient and measures an endpoint in a patient”. That undoubtedly has been the a leading definition and scope for translational research in the last decade, a bench-to-bedside (N2B) mode as I would call it. But is that the whole picture for translational research? Or, should this be only direction that we use?

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A Review of Clinical Trials in Spain

Patrick Bohan and Ouadah Hadjebi

Harrison Clinical Research, Barcelona, Spain,
Biocompatibles International plc, Farnham, UK.

Background: The European Directive 2001/20/EC sought to harmonize conditions and regulatory requirements for the conduct of clinical research in Europe. This article describes the context and recent history of research in Spain,reviews how clinical trials have been affected and assesses both the challenges and benefits of conducting trials there. Methods and Findings: Descriptions, findings and opinions are based on field experience and literature review.Available literature was found to be limited to descriptive data compiled by stakeholders without a general overview of the entire process of conducting clinical trials in Spain. Conclusions: This review argues that Spain presents several advantages as the location for clinical research, among them: highly-qualified research professionals; medical excellence; and the embrace of regulatory harmonization processes, which are due to historical factors that have otherwise limited growth in the pharmaceutical, medical and basic research sectors. Commonly experienced challenges in the conduct of trials are discussed as well as how these issues can be addressed.

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Academic websites containing H1N1 swine flu information need to provide content on therapeutic options including vaccines and neuraminidase-inhibitors

Alison Jane Murray and Craig Steven McLachlan
Department of Medical and Molecular Biosciences, Pharmacology Division, University of Technology Sydney, Australia.
University of Sydney, Sydney School of Medicine, Kolling Institute, Australia.

We retrospectively reviewed 21 National Australian University academic websites for swine flu guidelines for pregnancy and therapeutic measures. This study was conducted at the height of the swine flu epidemic in Australia, August 2009. No detailed information on the use and safety of neuraminidase-inhibitors, across population sub-groups were identified within the content pages of Australian University Websites. Further concern was an absence of information on which antiviral and vaccination treatments are appropriate for pregnant women and breast feeding mothers. Pregnant women are at high risk of developing severe illness and related complications with the onset of swine flu. It is thus important that pregnant women have access to adequate web site information and updated information advising on appropriate use of anti-viral neuraminidase-inhibiting drugs and treatment, vaccination and options for associated fever and information that they represent a high risk subgroup. This mini-commentary provides useful information and a relevant web link (http://www.rcog.org.uk/news/swine-flu-alerts) for inclusion on academic websites to inform pregnant women on effective therapeutic information that can be communicated via university and health web sites even after a swine flu pandemic.

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Needs - driven rather than market - driven rules to spread access to medicines in poor countries

Daniele Dionisio
Reference Advisor, “Drugs for the developing countries”, SIMIT (Italian Society for Infectious and Tropical Diseases).
Member, European Parliament Working Group on Innovation, Access to Medicines and Poverty-Related Diseases.
Former Director, Infectious Disease Division, Pistoia Hospital, Pistoia (Italy).

Background: Communicable diseases (including HIV/AIDS, malaria, tuberculosis, schistosomiasis, river blindness, Chagas,sleeping sickness, and leishmaniasis) disproportionately affect the people living in resource-limited countries.While current patent system does not work for poor end users in these countries, it adds to the stranglehold on accessto lifesaving medicines by the protectionist policies of wealthy countries. Nonetheless, increasing pressure is registered nowadays for strategies up to promoting pharmaceutical innovation, research and development (R&D) and equitable access to medicines in the sake of the worst-off. Method: Analysis here will compare some strategy models in their potential to fairly attune patents to innovation, R&D and access, in the light of new perspectives by governments and institutions aligning with the spirit and resolutions of just closed sixty-third WHO World Health Assembly. Conclusion: No single model is likely to be enough solution, and a combination of two or more may be needed to ensure that outputs of R&D, innovation and access are available without restrictions. To this aim, all models should complement current intellectual property regimens and channel open source schemes, sustainable financing mechanisms, and needs-driven rather than merely market-driven rules.

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The incidence of head and neck cancers in the Republic of Suriname between the years 1980 and 2004

Dennis Ricardo August Mans, Jerry R. Toelsie, Robbert Bipat, Rakesh Bansie, Martinus Albert Vrede

Department of Pharmacology, Faculty of Medical Sciences. Anton de Kom University of Suriname. Kernkampweg 5, Paramaribo, Suriname.
Department of Physiology, Faculty of Medical Sciences. Anton de Kom University of Suriname. Kernkampweg 5, Paramaribo, Suriname.
Department of Pathology, Faculty of Medical Sciences. Anton de Kom University of Suriname. Kernkampweg 5, Paramaribo, Suriname.

Background: The development of head and neck cancers is associated with extensive use of tobacco and/or tobacco-like products and alcohol; excessive consumption of processed meat and fish; exposure to certain occupational hazards; and infection with certain oncogenic viruses. At least some of these risk factors are operative in the Republic of Suriname. This suggests that the population may run a greater than average risk for head and neck cancers. In this study, the incidence of this group of cancers in Suriname has been determined for 1980 through 2004. The data obtained have been stratified according to anatomical location, gender, age, as well as ethnic background, and compared with global values. Methods and findings. Numbers of diagnoses and patient information were from the Pathologic Anatomy Laboratory. Relevant population data were provided by the General Bureau of Statistics. Crude and/or sex-specific incidence rates were calculated for head and neck cancers overall as well as for all anatomical sites (oral cavity; salivary glands; nasal cavity and paranasal sinuses; nasopharynx, oropharynx, as well as hypopharynx; and larynx), and were stratified according to gender, age strata 0-19, 20-49, and 50+ years, and the largest ethnic groups, viz. Hindustani, Creole, and Javanese. From these data, average incidence rates were calculated which were expressed as means ± SDs per year, per 100,000 population per year, or per 100,000 males or females per year. Average yearly crude rates for head and neck cancers overall were approximately 4, and average yearly sex-specific rates about 5 in men and 2 in women. The most common sites were oral cavity, nasopharyngeal, and laryngeal cancer, occurring at average frequencies of about 4, 3, and 3 cases, respectively, per year. Overall head and neck cancers as well as most anatomical sites were 2-3 times more common in men than in women, increased strongly with older age, and manifested about 2.5 times more often in Creole than in Hindustani or Javanese. The exceptions were laryngeal cancer that displayed a male-to-female ratio of almost 6 to 1, and nasopharyngeal cancer, the age-dependent rise in incidence of which was more gradual than that for oral cavity and laryngeal cancer, and that occurred more often in Javanese. Conclusions. The results from this study suggest that Suriname is a low-risk country for head and neck cancers. These tumors were in general more common in men than in women, occurred more often at older then at younger age, and manifested more frequently in Creole than in Hindustani and Javanese. Nasopharyngeal cancer, however, may have a predilection for Javanese. Detailed follow-up studies in Suriname’s cultural, religious, and ethnic diversity may help improve our understanding of head and neck cancer etiology.

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