Clinical Study Research Papers - Academia.edu (original) (raw)

This is a literature review about large granular lymphocyte leukemia (LGLL), a rare and misdiagnosed oncohematological disease, characterized by a clonal expansion of T-cells (T-LGLL) or NK-cells (NK-LGLL) in the bone marrow and/or... more

This is a literature review about large granular lymphocyte leukemia (LGLL), a rare and misdiagnosed oncohematological disease, characterized by a clonal expansion of T-cells (T-LGLL) or NK-cells (NK-LGLL) in the bone marrow and/or peripheral blood. The clinical features of LGLL include cytopenias (anemia, neutropenia and thrombocytopenia), lymphocytosis (usually discrete), lymphadenopathy, hepatomegaly, splenomegaly, immune abnormalities and constitutional symptoms (fever, night sweats and weight loss). The diagnosis is based on the confirmation of the clonality of T-cells or NK-cells (polymerase chain reaction and Southern blot are the two methods most commonly used) and typical findings of the immunophenotypic analysis of peripheral blood lymphocytes (flow cytometry analyses for specific surface antigens). In contrast to the chronic and indolent course of T-LGLL, NK-LGLL has an acute presentation and poor clinical outcome. There are different current treatment options, depending on clinical presentation.

Tissue hypoxia results from an inadequate supply of oxygen (O2) that compromises biological functions. Structural and functional abnormalities of the tumour vasculature together with altered diffusion conditions inside the tumour seem to... more

Tissue hypoxia results from an inadequate supply of oxygen (O2) that compromises biological functions. Structural and functional abnormalities of the tumour vasculature together with altered diffusion conditions inside the tumour seem to be the main causes of tumour hypoxia. Evidence from experimental and clinical studies points to a role for tumour hypoxia in tumour propagation, resistance to therapy and malignant

Quantitative ultrasound has attracted significant interest in the evaluation of bone fracture healing. Animal and clinical studies have demonstrated that the propagation velocity across fractured bones can be used as an indicator of... more

Quantitative ultrasound has attracted significant interest in the evaluation of bone fracture healing. Animal and clinical studies have demonstrated that the propagation velocity across fractured bones can be used as an indicator of healing. Researchers have recently employed computational methods for modeling wave propagation in bones, aiming to gain insight into the underlying mechanisms of wave propagation and to further enhance the monitoring capabilities of ultrasound. In this paper, we review the relevant literature and present the current status of knowledge.

Chronic low back pain (LBP) is an extremely common problem in practice, where it is often labeled idiopathic. No sufficient studies have been conducted to analyze the contribution of hypovitaminosis D to the etiology of chronic LBP in... more

Chronic low back pain (LBP) is an extremely common problem in practice, where it is often labeled idiopathic. No sufficient studies have been conducted to analyze the contribution of hypovitaminosis D to the etiology of chronic LBP in populations wherein vitamin D deficiency is endemic. The present study was, therefore, carried out to examine hypovitaminosis D and its determinants in female patients with chronic LBP during the childbearing period. Sixty female patients complaining of LBP lasting more than 3 months were clinically studied rheumatologically and neurologically. Questionnaires and indices quantifying risk factors associated with vitamin D deficiency were utilized. Biochemical assays of serum calcium, phosphorus, alkaline phosphatase (ALP), parathormone (PTH), and 25-hydroxyvitamin D (25 OHD) were performed and compared to those of 20 matched healthy controls. The determinants of vitamin D levels in patients were examined by stepwise regression. Patients with LBP had significantly lower 25 OHD levels (p<0.05) and significantly higher PTH (p<0.05) and ALP (p<0.001) than controls, although there were no significant group differences in calcium and phosphorus. Hypovitaminosis D (25 OHD < 40 ng/ml) was found in 49/60 patients (81%) and 12/20 (60%) of controls, with an odds ratio of 2.97. Although many risk factors related to sun exposure, clothing, diet, and pregnancy were significantly correlated with vitamin D levels in patients, only limited duration of sun exposure, contributing 55% to the variance of 25 OHD, limited areas of skin exposed (13%), and increased number of pregnancies (2%), were significant determinants of vitamin D levels in patients. Despite the sunny climate, hypovitaminosis D is prevalent among Egyptian women in the childbearing period, especially those presenting with chronic LBP, where it is associated with hyperphosphatasia and hyperparathyroidism, without alterations in serum calcium. The major determinant of hypovitaminosis D in our patients is limited sun exposure.

We aimed to evaluate the effectiveness of balneotherapy in fibromyalgia management. Fifty women with fibromyalgia under pharmacological treatment were randomly assigned to either the balneotherapy (25) or the control (25) group. Four... more

We aimed to evaluate the effectiveness of balneotherapy in fibromyalgia management. Fifty women with fibromyalgia under pharmacological treatment were randomly assigned to either the balneotherapy (25) or the control (25) group. Four patients from the balneotherapy group and one patient from the control group left the study after randomization. The patients in the balneotherapy group (21) had 2 thermomineral water baths daily for 2 weeks in Tuzla Spa Center. The patients in the control group (24) continued to have their medical treatment and routine daily life. An investigator who was blinded to the study arms assessed the patients. All patients were assessed four times; at the beginning of the study, at the end of the 2nd week, the 1st month, and the 3rd month after balneotherapy. Outcome measures of the study were pain intensity, Fibromyalgia Impact Questionnaire (FIQ), Beck Depression Inventory (BDI), patient's global assessment, investigator's global assessment, SF-36 scores, and tender point count. Balneotherapy was found to be superior at the end of the cure period in terms of pain intensity, FIQ, Beck Depression Inventory, patient's global assessment, investigator's global assessment scores, and tender point count as compared to the control group. The superiority of balneotherapy lasted up to the end of the 3rd month, except for the Beck Depression Inventory score and the investigator's global assessment score. Significant improvements were observed in PF, GH, and MH subscales of SF-36 during the study period in the balneotherapy group; however, no such improvement was observed in the control group. Balneotherapy was superior only in VT subscale at the end of therapy and at the end of the third month after the therapy as compared to the controls. It was concluded that balneotherapy provides beneficial effects in patients with fibromyalgia.

A one-year clinical study was performed on the efficacy of a bioactive dental cement (Ceramir C&B) with calcium aluminate and glass ionomer components. The study was performed on 38 crown and bridge abutments in 17 patients. Preparation... more

A one-year clinical study was performed on the efficacy of a bioactive dental cement (Ceramir C&B) with calcium aluminate and glass ionomer components. The study was performed on 38 crown and bridge abutments in 17 patients. Preparation parameters were recorded, as well as working-times, setting-times, and other handling characteristics. Baseline data were also recorded for gingival inflammation (GI) and pre-cementation sensitivity. Post-cementation parameters included sensitivity, gingival tissue reactions, marginal integrity and discolorations. All patients were seen for recall examinations at 30 days, and 6 months. For sixteen patients one-year recall data were collected on retention and subjective sensitivity. Fifteen subjects were available for one year clinical examinations. Three independent examiners found the working and setting time of the cement to be well within expected limits and that cement removal was easy. Four patients reported low-grades of immediate post-cementat...

BLAAKAND THE NUGENOB CONSORTIUM. Impaired fat-induced thermogenesis in obese subjects: the NUGENOB study. Obesity. 2007;15: 653-663. Objectives: To study energy expenditure before and 3 hours after a high-fat load in a large cohort of... more

BLAAKAND THE NUGENOB CONSORTIUM. Impaired fat-induced thermogenesis in obese subjects: the NUGENOB study. Obesity. 2007;15: 653-663. Objectives: To study energy expenditure before and 3 hours after a high-fat load in a large cohort of obese subjects (n ϭ 701) and a lean reference group (n ϭ 113). Research Methods and Procedures: Subjects from seven European countries underwent a 1-day clinical study with a liquid test meal challenge containing 95% fat (energy con-tent was 50% of estimated resting energy expenditure). Fasting and 3-hour postprandial energy expenditures, as well as metabolites and hormones, were determined. Results: Obese subjects had a reduced postprandial energy expenditure after the high-fat load, independent of body composition, age, sex, research center, and resting energy expenditure, whereas within the obese group, thermogenesis increased again with increasing BMI category. Additionally, insulin resistance, habitual physical activity, postprandial plasma triacylglycerols, and insulin were all independently positively related to the postprandial energy expenditure. Resting energy expenditure, adjusted for fat-free mass, increased with degree of obesity, a difference that disappeared after adjustment for fat mass. Furthermore, insulin resistance, fasting plasma free fatty acids, and cortisol were positively associated, whereas fasting plasma leptin and insulin-like growth factor-1 were negatively associated, with resting energy expenditure. Discussion: The 3-hour fat-induced thermogenic response is reduced in obesity. It remains to be determined whether this blunted thermogenic response is a contributory factor or an adaptive response to the obese state. REE, resting energy expenditure; HOMA IR , homeostasis model assessment of insulin resistance; AU, arbitrary units; EI, energy intake; FFA, free fatty acid; IGF-1, insulin-like growth factor-1. Model 1 includes the indicated variables in addition to FM, FFM, and center. Model 2 includes the indicated variables in addition to Model 1. p Values of the multiple regression analysis are indicated in the right column.

Objective: No outcome measures specific to pulmonary hypertension (PH) currently exist. The aim of the study was to develop health-related quality of life (symptoms and functioning) scales and a quality of life scale that would allow... more

Objective: No outcome measures specific to pulmonary hypertension (PH) currently exist. The aim of the study was to develop health-related quality of life (symptoms and functioning) scales and a quality of life scale that would allow comprehensive, accurate and valid patient-reported outcome assessment in clinical studies. Methods: The content of the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) was derived from qualitative interviews conducted with 35 patients. Item reduction was based on the analysis of responses to a postal survey (n=75) and patient interviews (n=15) designed to determine face and content validity. A final postal validation study (n=91) was performed to determine reproducibility and construct validity. Results: The questionnaire was well received by participants who found it to be relevant, comprehensible and quick and easy to complete. Rasch and factor analyses were conducted to ensure unidimensionality of the final CAMPHOR scales; Overall symptoms (made up of Energy, Breathlessness and Mood subscales), Functioning and Quality of life. The CAMPHOR scales had good internal consistency (a=0.90-0.92) and reproducibility (test-retest correlations=0.86-0.92). They also exhibited convergent, divergent and known groups validity. Conclusions: The CAMPHOR is a valuable new instrument for assessing patient-reported outcome in PH clinical trials and routine practice.

MSC (Avemar) is a medical nutriment of which preclinical and observational clinical studies suggested an antimetastatic activity with no toxicity. This open-label cohort trial has compared anticancer treatments plus MSC (9 g once daily)... more

MSC (Avemar) is a medical nutriment of which preclinical and observational clinical studies suggested an antimetastatic activity with no toxicity. This open-label cohort trial has compared anticancer treatments plus MSC (9 g once daily) vs anticancer treatments alone in colorectal patients, enrolled from three oncosurgical centres; cohort allocation was on the basis of patients' choice. Sixty-six colorectal cancer patients received MSC supplement for more than 6 months and 104 patients served as controls (anticancer therapies alone): no statistical difference was noted in the time from diagnosis to the last visit between the two groups. End-point analysis revealed that progression-related events were significantly less frequent in the MSC group (new recurrences: 3.0 vs 17.3%, P<0.01; new metastases: 7.6 vs 23.1%, P<0.01; deaths: 12.1 vs 31.7%, P<0.01). Survival analysis showed significant improvements in the MSC group regarding progression-free (P=0.0184) and overall su...

Achieving progress in understanding the cause, nature, and treatment of autism requires an integration of concepts, approaches, and empirical findings from genetic, cognitive neuroscience, animal, and clinical studies. The need for such... more

Achieving progress in understanding the cause, nature, and treatment of autism requires an integration of concepts, approaches, and empirical findings from genetic, cognitive neuroscience, animal, and clinical studies. The need for such integration has been a fundamental tenet of the discipline of developmental psychopathology from its inception. It is likely that the discovery of autism susceptibility genes will depend on the development of dimensional measures of broader phenotype autism traits. It is argued that knowledge of the cognitive neuroscience of social and language behavior will provide a useful framework for defining such measures. In this article, the current state of knowledge of the cognitive neuroscience of social and language impairments in autism is reviewed. Following from this, six candidate broader phenotype autism traits are proposed: (a) face processing, including structural encoding of facial features and face movements, such as eye gaze; (b) social affiliat...

Photodynamic therapy (PDT) is a binary treatment modality that has been used to treat malignant brain tumours for 25 years. The treatment involves the selective uptake of a photosensitizer (PS) by the tumour cells followed by irradiation... more

Photodynamic therapy (PDT) is a binary treatment modality that has been used to treat malignant brain tumours for 25 years. The treatment involves the selective uptake of a photosensitizer (PS) by the tumour cells followed by irradiation of the tumour with light of the appropriate wavelength to excite and activate the PS resulting in selective tumour destruction and is a potentially valuable adjunct to surgical excision and other conventional therapies. PDT has undergone extensive laboratory studies and clinical trials with a variety of PS and tumour models. These are discussed with reference mainly to clinical studies involving the PDT of brain tumours.

A multiinslitutiiinal Phase I study using i.v. melphalan was conducted in dogs with spontaneously occurring neoplasia. Melphalan was admin istered at 1.5, 10, 11.25, 12.5, and 20 mg/m2 of body surface area. Disproportionately greater... more

A multiinslitutiiinal Phase I study using i.v. melphalan was conducted in dogs with spontaneously occurring neoplasia. Melphalan was admin istered at 1.5, 10, 11.25, 12.5, and 20 mg/m2 of body surface area. Disproportionately greater toxicity was observed in small dogs. Seven of the eight dogs (88%) weighing less than 14 kg experienced severe myelosuppression (neutropenia, < 151M I/mm1; and/or thrombocytopenia,

Atopic dermatitis (eczema) is an immune-mediated dermatological condition characterized by severe and prolonged itching and rough, red patches of skin. Rash typically occurs on the face, neck, upper trunk, wrists, hands, knees, and... more

Atopic dermatitis (eczema) is an immune-mediated dermatological condition characterized by severe and prolonged itching and rough, red patches of skin. Rash typically occurs on the face, neck, upper trunk, wrists, hands, knees, and elbows. It may form weeping, crusting lesions, which can become infected. Patients with atopic dermatitis may have difficulty sleeping due to the discomfort caused by the rash

Background: Wasting, or cachexia, is a significant, debilitating, and potentially life-threatening complication of HIV infection. It is associated with reduced strength and functional ability, reduced ability to withstand opportunistic... more

Background: Wasting, or cachexia, is a significant, debilitating, and potentially life-threatening complication of HIV infection. It is associated with reduced strength and functional ability, reduced ability to withstand opportunistic infections, and increased risk of mortality. Although the incidence of HIV-associated wasting may have declined since the introduction of highly active antiretroviral therapy (HAART), it continues to be a concern in this patient population. Objective: This paper reviews available data on the etiology and clinical impact of HIV-associated wasting, the role of the growth hormone/insulin-like growth factor-I axis in the pathophysiology of this condition, and the rationale for its treatment with recombinant human growth hormone (rhGH). Methods: MEDLINE was searched for articles published in English through August 2007 using the terms HIV, wasting (and related terms), and growth hormone. Preference was given to clinical studies (including randomized clinical studies), meta-analyses, and guidelines. Review articles were evaluated and the bibliographies examined for additional relevant articles. The analysis was restricted to studies conducted in developed countries. Results: Alterations in the growth hormone/insulinlike growth factor-I axis have been observed in patients with HIV-associated wasting, including elevated levels of the former and reduced levels of insulin-like growth factor I. In randomized, placebo-controlled studies, rhGH significantly improved lean body mass by-3 kg compared with placebo (P < 0.001) and total body weight by-3 kg (P < 0.001), and was associated with significant improvements in physical endurance and quality of life (P < 0.001). Common adverse events with rhGH therapy include blood glucose elevations, arthralgia (36.4%), myalgia (30.4%), and peripheral edema (26.1%), but these usually respond to dose reduction or drug discontinuation. Conclusions: Physicians should be alert to the possibility of wasting in HIV-infected patients receiving HAART and should consider treatment to improve patients' stamina and quality of life. The evidence supports a role for rhGH in the treatment of patients with HIV-associated wasting. Regular blood glucose monitoring is advised when treating wasting with rhGH.

Advances in pacemaker technology in the 1980s have generated a wide variety of complex multiprogrammable pacemakers and pacing modes. The aim of the present review is to address the different rate responsive pacing modalities presently... more

Advances in pacemaker technology in the 1980s have generated a wide variety of complex multiprogrammable pacemakers and pacing modes. The aim of the present review is to address the different rate responsive pacing modalities presently available in respect to physiological situations and pathological conditions. Rate adaptive pacing has been shown to improve exercise capacity in patients with chronotropic incompetence. A number of activity and metabolic sensors have been proposed and used for rate control. However, all sensors used to optimize pacing rate metabolic demands show typical limitations. To overcome these weaknesses the use of two sensors has been proposed. Indeed an unspecific but fast reacting sensor is combined with a more specific but slower metabolic one. Clinical studies have demonstrated that this methodology is suitable to reproduce normal sinus behavior during different types and loads of exercise. Sensor combinations require adequate sensor blending and cross ch...

Cyproterone acetate is a powerful antiandrogen used in the treatment of the paraphilias for at least a decade. Studies have reported it effective in reducing the recidivism rates of sexual crimes perpetrated by men. It acts through... more

Cyproterone acetate is a powerful antiandrogen used in the treatment of the paraphilias for at least a decade. Studies have reported it effective in reducing the recidivism rates of sexual crimes perpetrated by men. It acts through competitive inhibition of the androgen receptors blocking the effects of testosterone and dihydrotestosterone. Systematic clinical study of its effectiveness and its clinical effects on sexual behavior is lacking, however. In the current study 19 paraphilic men who had also recidivated in a variety of sexual crimes were treated with cyproterone acetate and placebo in a double-blind crossover design. The use of active drug was associated with a significant reduction of some aspects of sexual behavior, particularly sexual fantasies. There were also significant effects on levels of circulating sex hormones and some effects on physiological measurements and self-reports of sexual arousal.

DOI to the publisher's website. • The final author version and the galley proof are versions of the publication after peer review. • The final published version features the final layout of the paper including the volume, issue and page... more

DOI to the publisher's website. • The final author version and the galley proof are versions of the publication after peer review. • The final published version features the final layout of the paper including the volume, issue and page numbers. Link to publication General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. • Users may download and print one copy of any publication from the public portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal. If the publication is distributed under the terms of Article 25fa of the Dutch Copyright Act, indicated by the "Taverne" license above, please follow below link for the End User Agreement:

Aim Numerous materials have been used to replace defects in the dura mater as result of neurosurgical and spinal procedures. Tissudura is a biomatrix made of cross-linked equine collagen fibrils, mainly of the interstitial type I. The... more

Aim Numerous materials have been used to replace defects in the dura mater as result of neurosurgical and spinal procedures. Tissudura is a biomatrix made of cross-linked equine collagen fibrils, mainly of the interstitial type I. The specially engineered dura-like layered structure provides a non porous primary water tight structure, is transparent and allows verification of the efficacy of cerebral hemostasis. Methods A consecutive series of patients between 18 years and 75 years of age were prospectively enrolled from three separate European institutions between May 2007 and February 2008. All patients underwent elective cranial or spinal surgery and required implantation of a dural substitute. We assessed the efficacy and safety of the collagen biomatrix as a dural substitute, intraoperatively and postoperatively, with a median follow-up 4.3 months. Results Fifty-six patients had cranial surgery, four patients underwent a spinal operation. Surgical cranial approaches included supratentorial procedures in 45 patients and posterior cranial fossa exploration in 11.

Conjugated linoleic acid (CLA) is a mixture of positional and geometric isomers of octadecadienoic acid [linoleic acid (LA), 18:2n-6] commonly found in beef, lamb and dairy products. The most abundant isomer of CLA in nature is the cis-9,... more

Conjugated linoleic acid (CLA) is a mixture of positional and geometric isomers of octadecadienoic acid [linoleic acid (LA), 18:2n-6] commonly found in beef, lamb and dairy products. The most abundant isomer of CLA in nature is the cis-9, trans-11 (c9t11) isomer. Commercially available CLA is usually a 1:1 mixture of c9t11 and trans-10, cis-12 (t10c12) isomers with other isomers as minor components. Conjugated LA isomer mixture and c9t11 and t10c12 isomers alone have been attributed to provide several health benefits that are largely based on animal and in vitro studies. Conjugated LA has been attributed many beneficial effects in prevention of atherosclerosis, different types of cancer, hypertension and also known to improve immune function. More recent literature with availability of purified c9t11 and t10c12 isomers suggests that t10c12 is the sole isomer involved in antiadipogenic role of CLA. Other studies in animals and cell lines suggest that the two isomers may act similarly or antagonistically to alter cellular function and metabolism, and may also act through different signaling pathways. The effect of CLA and individual isomers shows considerable variation between different strains (BALB/C mice vs. C57BL/6 mice) and species (e.g., rats vs. mice). The dramatic effects seen in animal studies have not been reflected in some clinical studies. This review comprehensively discusses the recent studies on the effects of CLA and individual isomers on body composition, cardiovascular disease, bone health, insulin resistance, mediators of inflammatory response and different types of cancer, obtained from both in vitro and animal studies. This review also discusses the latest available information from clinical studies in these areas of research. D

Cytomics aims to determine the molecular phenotype of single cells. Within the context of the -omics, cytomics allows the investigation of multiple biochemical features of the heterogeneous cellular systems known as the cytomes. Cytomics... more

Cytomics aims to determine the molecular phenotype of single cells. Within the context of the -omics, cytomics allows the investigation of multiple biochemical features of the heterogeneous cellular systems known as the cytomes. Cytomics can be considered as the science of single cell-based analyses that links genomics and proteomics with the dynamics of cell and tissue function, as modulated by external inXuences. Inherent to cytomics are the use of sensitive, scarcely invasive, Xuorescence-based multiparametric methods and the event-integrating concept of individual cells to understand the complexity and behaviour of tissues and organisms. Among cytomic technologies, Xow cytometry, confocal laser scanning microscopy and laser capture microdissection are of great relevance. Other recent technologies based on single cell bioimaging and bioinformatic tools become important in drug discovery and toxicity testing, because of both highcontent and high-troughput. The multiparametric capacity of cytomics is very useful for the identiWcation, characterization and isolation of stem cell populations. In our experience, Xow cytometry is a powerful and versatile tool that allows quantitative analysis of single molecules, prokaryotic and eukaryotic cells for basic, biotechnological, environmental and clinical studies. The dynamic nature of cytomic assays leads to a real-time kinetic approach based on sequential examination of diVerent single cells from a population undergoing a dynamic process, the in Xuxo level. Finally, cytomic technologies may provide in vitro methods alternative to laboratory animals for toxicity assessment.

Objective: To evaluate rehabilitation results of electrostimulation especially on joint effusion, swelling and pain recovery after anterior cruciate ligament reconstruction. Design: A randomized controlled trial; the assessor was not... more

Objective: To evaluate rehabilitation results of electrostimulation especially on joint effusion, swelling and pain recovery after anterior cruciate ligament reconstruction. Design: A randomized controlled trial; the assessor was not blinded to the group allocation. Setting: Orthopaedics-traumatology and physical medicine-rehabilitation departments. Subjects: Twenty-nine consecutive patients underwent anterior cruciate ligament reconstruction. Interventions: Both groups began the voluntary exercise protocol one day post-surgery. The intervention group (n ¼ 15) also received 30 sessions electrostimulation treatment protocol started four days after the operation. Main measures: Numerical bulge-dancing patella signs for effusion assessment; differences in circumferences of the mid-centre of the patella between operated and non-operated knees for swelling assessment. A self-report of average daily resting pain assessed by visual analogue scale; Intenational Knee Documentation Committee scoring system and Tegner Activity Scale for subjective response assessment. Results: Twenty-six subjects including 13 patients from the intervention group completed the study. Significantly less effusion and swelling were determined in the intervention group after seven days (1.8 AE 1.3 versus 2.4 AE 1.7 for effusion and 1.7 AE 1.2 versus 3.4 AE 1.5 for swelling) to 12 weeks (0.2 AE 0.7 versus 0.6 AE 0.8 for effusion and 0.2 AE 0.8 versus 0.8 AE 0.9 for swelling) postoperative (P < 0.05). Patients treated with electrostimulation had significantly lower pain scores from seven days up to 12 weeks after the operation (P < 0.05).

Background. Lhermitte-Duclos Disease (LDD) is an infrequent cerebellar disorder characterized by focal or diffuse enlargement of cerebellar folia presenting as a slowly growing mass in the posterior fossa. Over the past decade its... more

Background. Lhermitte-Duclos Disease (LDD) is an infrequent cerebellar disorder characterized by focal or diffuse enlargement of cerebellar folia presenting as a slowly growing mass in the posterior fossa. Over the past decade its association with Cowden disease (CD) has been recognized with increasing frequency. This latter disease is a genetic condition leading to the presence of multiple hamartomas and neoplasias which affect mainly the skin, thyroid, breast and genito-urinary and gastrointestinal tracts. It has even been hypothesized that LDD and CD constitute a single entity. This work is aimed to analyse to what extent this association was present in patients treated for LDD at our institution.

We report the clinical and MRI findings of two patients with familial spinal arachnoiditis. Although their initial symptoms were various, they both showed spastic paraparesis and sensory disturbance below the thoracic level. Cytokines and... more

We report the clinical and MRI findings of two patients with familial spinal arachnoiditis. Although their initial symptoms were various, they both showed spastic paraparesis and sensory disturbance below the thoracic level. Cytokines and WBC in the CSF were studied, but they were not elevated at all. The spinal magnetic resonance images of each showed extensive arachnoiditis and a cystic structure. The other impressive features included: (i) an enhancement within the thickened arachnoid and an adhesion between the spinal cord and the dura mater, (ii) deformation of the thoracic cord where the arachnoid adhered, and (iii) secondary syrinx formation. Laminectomy may have an adverse outcome for such patients.

Pompe disease is a metabolic myopathy caused by deficiency of lysosomal acid alpha-glucosidase. In this report we review the first 36 weeks of a clinical study on the safety and efficacy of enzyme therapy aimed at correcting the... more

Pompe disease is a metabolic myopathy caused by deficiency of lysosomal acid alpha-glucosidase. In this report we review the first 36 weeks of a clinical study on the safety and efficacy of enzyme therapy aimed at correcting the deficiency. Four patients with infantile Pompe disease were enrolled. They received recombinant human alpha-glucosidase from transgenic rabbit milk. The product is generally well tolerated and reaches the primary target tissues. Normalization of alpha-glucosidase activity in skeletal muscle was obtained and degradation of PAS-positive material was seen in tissue sections. The clinical condition of all patients improved. The effect on heart was most significant, with an impressive reduction of the left ventricular mass index (LVMI). Motor function improved. The positive preliminary results stimulate continuation and extension of efforts towards the realization of enzyme therapy for Pompe disease.

Background Over the past decade, annual funding for biomedical research has more than doubled while new molecular entity approvals have declined by one third. Objective To assess the value of practices commonly employed in the conduct of... more

Background Over the past decade, annual funding for biomedical research has more than doubled while new molecular entity approvals have declined by one third. Objective To assess the value of practices commonly employed in the conduct of large-scale clinical trials, and to identify areas where costs could be reduced without compromising scientific validity. Methods In the qualitative phase of the study, an expert panel recommended potential modifications of mega-trial designs and operations in order to maximize their value (cost versus scientific benefit tradeoff). In the quantitative phase, a mega-trial economic model was used to assess the financial implications of these recommendations. Our initial chronic disease trial design included 20,000 patients randomized at 1000 sites. Each site was assigned 24 monitoring visits and a 10,000perpatientsitepayment.Thecasereportform(CRF)was60pageslong,andtrialdurationwasassumedtobe48months.ResultsThetotalcostsoftheinitialtrialdesignwere10,000 per patient site payment. The case report form (CRF) was 60 pages long, and trial duration was assumed to be 48 months. Results The total costs of the initial trial design were 10,000perpatientsitepayment.Thecasereportform(CRF)was60pageslong,andtrialdurationwasassumedtobe48months.ResultsThetotalcostsoftheinitialtrialdesignwere421 million ($US 2007). Following the expert panel's recommendations, we varied study duration, CRF length, number of sites, electronic data capture (EDC), and site management components to determine their individual and combined effects upon total trial costs. The use of EDC and modified site management practices were associated with significant reductions in total trial costs. When reductions in all five trial components were combined in a streamlined pharmaceutical industry design, a 59% reduction in total trial costs resulted. When we assumed an even more streamlined trial design than has typically been considered for regulatory submissions in the past, there was a 90% reduction in total trial costs. Conclusion Our results suggest that it is possible to reduce substantially the cost of large-scale clinical trials without compromising the scientific validity of their results. If implemented, our recommendations could free billions of dollars annually for additional clinical studies. Research in the setting of clinical trials should be conducted to refine these findings. Clinical Trials 2008; 5: 75-84. http://

Background: Treatment of diabetes mellitus (DM) is complex, requiring multifaceted lifestyle change or regulation and, for many, self-regulation of insulin levels in the blood. Historically, daily insulin treatment has been viewed as... more

Background: Treatment of diabetes mellitus (DM) is complex, requiring multifaceted lifestyle change or regulation and, for many, self-regulation of insulin levels in the blood. Historically, daily insulin treatment has been viewed as burdensome to patients, prompting newer formulations and improved delivery methods. Objective: This multicenter, clinical study was designed to develop a conceptually sound, clinically meaningful, and psychometrically valid measure of insulin treatment satisfaction, applicable to a wide range of insulin therapies. Methods: A 3-phase iterative process was employed to develop and validate the Insulin Treatment Satisfaction Questionnaire (ITSQ): (1) conceptual development of items, (2) preliminary validation among patients with DM, and (3) confirmatory validation among patients with DM. Results: The ITSQ was validated with 170 patients in phase 2 and 402 patients in phase 3. Confirmatory factor analysis produced a 5-factor, 22-item instrument assessing regimen inconvenience, lifestyle flexibility, glycemic control, hypoglycemic control, and satisfaction with the insulin delivery device. Results for reliability and construct validity of the final version were consistent in both samples of patients treated with insulin, with different data collection methods. Internal consistency (using Cronbach α coefficient) of the subscales ranged from 0.79 to 0.91. Test-retest reliability (using Spearman rank correlation coefficients) ranged from 0.63 to 0.94. ITSQ scores showed moderate to high correlation with related measures of treatment burden. The ITSQ differentiated among insulin delivery methods, glycosylated hemoglobin values, the number of times the patient required assistance administering insulin, and insulin adherence. Conclusion: In our study samples, the ITSQ appeared to be conceptually and psychometrically sound and applicable to a wide range of insulin therapies.

Various chemical agents have been evaluated over the years with respect to their antimicrobial effects in the oral cavity; however, all are associated with side effects that prohibit regular long-term use. Therefore, the effectiveness of... more

Various chemical agents have been evaluated over the years with respect to their antimicrobial effects in the oral cavity; however, all are associated with side effects that prohibit regular long-term use. Therefore, the effectiveness of neem (Azadirachta indica A. Juss) leaf extract against plaque formation was assessed in males between the age group of 20-30 years over a period of 6 weeks. Present study includes formulation of mucoadhesive dental gel containing Azadirachta indica leaf extract (25 mg/g). A 6-week clinical study was conducted to evaluate the efficacy of neem extract dental gel with commercially available chlorhexidine gluconate (0.2% w/v) mouthwash as positive control. Microbial evaluation of Streptococcus mutans and Lactobacilli species was carried out to determine the total decrease in the salivary bacterial count over a period of treatment using a semi-quantitative four quadrant streaking method. The results of the study suggested that the dental gel containing neem extract has significantly (P < 0.05) reduced the plaque index and bacterial count than that of the control group.

Purpose: The goal of this study was to evaluate arthroscopic partial resection of discoid lateral meniscus tears with an emphasis on radiographic evidence of degenerative changes after this procedure. Type of Study: Retrospective clinical... more

Purpose: The goal of this study was to evaluate arthroscopic partial resection of discoid lateral meniscus tears with an emphasis on radiographic evidence of degenerative changes after this procedure. Type of Study: Retrospective clinical study. Methods: Of 41 patients with an arthroscopic diagnosis of discoid meniscus over an 8-year period, 34 symptomatic lateral discoid meniscus tears in 33 patients were analyzed at an average follow-up of 5.6 years. The average age at operation was 19.8 years and most patients had vague and intermittent symptoms that caused delay in clinical diagnosis. Results: Eight patients were lost to follow-up and were excluded from the study. Magnetic resonance imaging, performed in 12 cases, and arthroscopy in all of these patients provided the precise diagnosis. All of the knees with symptomatic torn discoid menisci underwent arthroscopic partial meniscectomy. Only 1 Watanabe Wrisberg ligament type of discoid meniscus with posterior instability was totally meniscected. Based on Ikeuchi's grading, 39% of the knees had an excellent result, 46% had a good result, and 15% had a fair result; none of the results was poor. Conclusions: At an average 5-year follow-up, partial meniscectomy in patients with a Watanabe complete or incomplete discoid meniscus showed 85% good or excellent clinical results. However, a significant percentage of patients show femoral condyle flattening on radiography.

Clinical studies have shown that the antioxidant vitamin E can slow the progression of Alzheimer's disease (AD). Other antioxidants reported to affect cognitive function include ginkgo biloba, vitamin C, and lipoic acid. To examine the... more

Clinical studies have shown that the antioxidant vitamin E can slow the progression of Alzheimer's disease (AD). Other antioxidants reported to affect cognitive function include ginkgo biloba, vitamin C, and lipoic acid. To examine the effects of combination antioxidant therapy (CAT) on longevity and neuropathology in mice, we supplemented the diet of ApoE-deficient mice with vitamin E, ginkgo biloba, pycnogenol, and ascorbyl palmitate. ApoEdeficient mice normally exhibit increased numbers of PAS-positive inclusion bodies with aging. However, supplementation with CAT resulted in a significant increase in life span and a marked reduction of inclusion body histopathology in the hippocampus. In addition, while untreated apoE-deficient mice exhibited increased levels of TUNEL staining, a marker of DNA fragmentation, supplementation with CAT resulted in a significant reduction in the levels of TUNEL staining. These findings suggest that oxidative mechanisms, perhaps related to neuronal apoptosis, are integral to inclusion body formation in aging mice. The association between the reduced number of apoptotic cells and the reduction in inclusion bodies may explain in part the increased longevity of mice fed CAT, and supports the contention that the combined actions of selected antioxidants may be therapeutically effective against neurodegenerative diseases.

During the past two decades, many pharmacological strategies have been investigated for the management of painful neuropathies. However, neuropathic pain still remains a clinical challenge. A combination of therapies is often required,... more

During the past two decades, many pharmacological strategies have been investigated for the management of painful neuropathies. However, neuropathic pain still remains a clinical challenge. A combination of therapies is often required, but unfortunately in most cases adequate pain relief is not achieved. Recently, attention has been focused on the physiological and pharmacological effects of L-acetylcarnitine in neurological disorders. There are a number of reports indicating that L-acetylcarnitine can be considered as a therapeutic agent in neuropathic disorders including painful peripheral neuropathies. In this review article, we will examine the antinociceptive and the neuroprotective effects of Lacetylcarnitine as tested in clinical studies and in animal models of nerve injury.

Purpose: To test a new multiple endpoint analysis (MEA) including occludin gene expression for screening the ocular irritation potential of tear substitutes on human corneal epithelium (HCE), an in vitro model proposed to limit the use of... more

Purpose: To test a new multiple endpoint analysis (MEA) including occludin gene expression for screening the ocular irritation potential of tear substitutes on human corneal epithelium (HCE), an in vitro model proposed to limit the use of animal testing in pre-clinical studies. Methods: Four chemically-preserved and two non chemically-preserved tear substitutes were tested after acute (24 h, 24 h + 24 h post incubation) and repeated applications (for 72 h) and compared to the positive control, benzalkonium chloride (BAK) at 0.1% and 0.01%, by assessing complementary parameters. Cellular viability was evaluated using MTT, histomorphologic analysis was performed on H&E stained vertical sections, IL-8 release was measured by ELISA, and occludin gene expression was quantified using qRT-PCR. Results: Cellular viability was moderately reduced by Perborate and Polyquad-preserved tear substitutes and dramatically reduced by BAK and by Thiomersal Ò and Oxyd Ò preserved tear substitutes. Thiomersal Ò also increased IL-8 release. Occludin expression profiles were modified by the four chemically-preserved tear substitutes and by the mechanically-preserved Comod Ò , but not by the mechanically-preserved Abak Ò . The behavior of BAK and tear substitutes led us to propose a prediction model for the classification of different levels of irritants, mainly based on the occludin transcriptional study. Conclusion: The versatility and sensitivity of the HCE model allowed the modeling of cumulative effects that may approach conditions obtained after long term application of tear substitutes. Thus, the modified MEA proposed in this study represents a valuable tool for in vitro eye irritation assessment with the power to detect mild irritants and subclinical eye irritant potential.

Abstract Turner syndrome is a common genetic disorder associated with abnormalities of the X chromosome and occurs in about 50 per 100,000 liveborn girls. It is associated with reduced adult height, gonadal dysgenesis and thus insuffi... more

Abstract Turner syndrome is a common genetic disorder associated with abnormalities of the X chromosome and occurs in about 50 per 100,000 liveborn girls. It is associated with reduced adult height, gonadal dysgenesis and thus insuffi cient circulating levels of female sex steroids and infertility. Morbidity and mortality are increased throughout the lifespan. The average intellectual performance is within the normal range. A number of recent clinical studies have given new insight particularly into the adult phase of Turner syndrome. Treatment with growth hormone during childhood and adolescence enables a considerable gain in adult height. In most cases puberty has to be induced and female sex hormone replacement therapy is given during adulthood. Type 2 diabetes is often seen, and hypertension and associated cardiovascular disorders are frequent. The proper treatments of these disorders have not been fi rmly established. Since the risk of cardiovascular and endocrinological disease is clearly elevated, proper care during adulthood is crucial. Cognition and social functioning are altered in Turner syndrome.

acid (diammonium salt); Tiron, 4,5dihydroxy-1,3-benzenedisulfonic acid disodium salt; EDTA, ethylenediaminetetraacetic acid dihydrate disodium salt; PBS, phosphate-buffered saline; SD, standard deviation; ANOVA, analysis of variance; LOD,... more

acid (diammonium salt); Tiron, 4,5dihydroxy-1,3-benzenedisulfonic acid disodium salt; EDTA, ethylenediaminetetraacetic acid dihydrate disodium salt; PBS, phosphate-buffered saline; SD, standard deviation; ANOVA, analysis of variance; LOD, limit of detection; LOQ, limit of quantitation.

Da us Sadaf is an accumulation of Ghair Tab'ee Sauda (abnormal atrabilious humour) in the skin causes impaired function. When the saudavi maaddah (atrabilious matter) collected in the body, the Tabi'at (physis) tries to expel it through... more

Da us Sadaf is an accumulation of Ghair Tab'ee Sauda (abnormal atrabilious humour) in the skin causes impaired function. When the saudavi maaddah (atrabilious matter) collected in the body, the Tabi'at (physis) tries to expel it through the skin, due to the acrid nature of the ghair tab'ee sauda and it produces burning sensation, irritation and scaling on the site of the skin. In modern medicine, this condition can be correlated with Psoriasis vulgaris, which is an immunologically mediated, common chronic inflammatory condition. Usually the skin lesions are symmetrical well-defined red plaques with silvery scale, located on extensor aspects of elbow and knees, the scalp and sacrum. It can arise at any age but peak around the 2 nd-3 rd decades and affecting the sexes equally. The prevalence is 2-3% of the general population worldwide. The aim of the study was to evaluate the therapeutic effect of a herbal paste in the treatment of skin lesions in Da us Sadaf patient. It was conducted in the outpatient department of National Teaching Hospital of Ayurveda, Borella. This study describes a case of clinically and histopathologically diagnosed 25year-old male patient. He was treated by an external application of a herbal paste over the lesion daily for 3 months. The results suggested that, the drugs under the trial had shown considerable improvement in the signs and symptoms of Da us Sadaf from 3 rd week onwards. Hence, it can be concluded that further trials should be done in large samples to evaluate the efficacy and safety of particular medicines in the treatment of Da us Sadaf.

Wheel-running and treadmill running physical exercise have been shown to alleviate parkinsonism in both laboratory and clinical studies. MPTP was administered to C57/BL6 mice using two different procedures: (a) administration of a... more

Wheel-running and treadmill running physical exercise have been shown to alleviate parkinsonism in both laboratory and clinical studies. MPTP was administered to C57/BL6 mice using two different procedures: (a) administration of a double-dose regime (MPTP 2 × 20 or 2 × 40 mg/kg, separated by a 24-h interval), vehicle (saline 5 ml/kg) or saline (vehicle 2 × 5 ml/kg), and (b) administration of a single-dose weekly regime (MPTP 1 × 40 mg/kg) or saline (vehicle 1 × 5 ml/kg) repeated over 4 consecutive weeks. For each procedure, two different physical exercise regimes were followed: (a) after the double-dose MPTP regime, mice were given daily 30-min periods of wheel-running exercise over 5 consecutive days/week or placed in a cage in close proximity to the running wheels for 3 weeks. (b) Mice were either given wheel-running activity on 4 consecutive days (30-min periods) or placed in a cage nearby for 14 weeks. Behavioral testing was as follows: (a) after 3 weeks of exercise/no exercise,...

Large medical image datasets form a rich source of anatomical descriptions for research into pathology and clinical biomarkers. Many features may be extracted from data such as MR images to provide, through manifold learning methods, new... more

Large medical image datasets form a rich source of anatomical descriptions for research into pathology and clinical biomarkers. Many features may be extracted from data such as MR images to provide, through manifold learning methods, new representations of the population's anatomy. However, the ability of any individual feature to fully capture all aspects morphology is limited. We propose a framework for deriving a representation from multiple features or measures which can be chosen to suit the application and are processed using separate manifold-learning steps. The results are then combined to give a single set of embedding coordinates for the data. We illustrate the framework in a population study of neonatal brain MR images and show how consistent representations, correlating well with clinical data, are given by measures of shape and of appearance. These particular measures were chosen as the developing neonatal brain undergoes rapid changes in shape and MR appearance and were derived from extracted cortical surfaces, non-rigid deformations and image similarities. Combined single embeddings show improved correlations demonstrating their benefit for further studies such as identifying patterns in the trajectories of brain development. The results also suggest a lasting effect of age at birth on brain morphology, coinciding with previous clinical studies.

Objective: Anti-aromatase therapy is important in the treatment of breast cancer in postmenopausal women but they have effects on the bone mineral density (BMD) and osteoporosis. Cyclooxygenase-2 (COX-2) inhibitors have been shown to be... more

Objective: Anti-aromatase therapy is important in the treatment of breast cancer in postmenopausal women but they have effects on the bone mineral density (BMD) and osteoporosis. Cyclooxygenase-2 (COX-2) inhibitors have been shown to be effective in chemoprevention in animal and clinical studies. A proof of principle study was performed to investigate the efficacy of combing anti-aromatase therapy (exemestane) and COX-2 inhibitors neoadjuvantly. The changes in the BMD, bone turnover proteins and quality-of-life (QoL) were analyzed and presented here. Method: 82 postmenopausal patients with histologically confirmed invasive hormone-sensitive breast cancers were included for the neoadjuvant therapy (NHT). 30 patients received exemestane (EXE) 25 mg daily and celecoxib (CXB) 400 mg twice daily (group A), 24 patients received EXE 25 mg daily (group B) and 28 patients received letrozole (LET) 2.5 mg daily (group C). The same assigned treatment was intended to continue for 2 years to study the changes in the bone metabolism. BMD of 48 patients were analyzed; 23 belongs to group A, 10 to group B and 15 to group C. The serum bone turnover proteins bone-specific alkaline phosphatase (BAP) and carboxyterminal crosslinked telopeptide of type I collagen (ICTP), were measured with commercially available test kits before treatment, 3 months and 15 months after treatment. Functional Assessment of Cancer Therapy core questionnaire (FACT-G) with its additional breast cancer subscale were performed at baseline, 4, 8, and 12 weeks after NHT. Result: Difference between groups (p = 0.007) for BMD at femur was significant. The changes of BMD in group B patients were significantly greater than patients in group A (p = 0.011, CI = 0.063-0.437), and group C (p = 0.003, CI = 0.146-0.620). The mean BAP increased from baseline in group B patients but decreased from baseline in group C patients at 3 months and 15 months. No statistical significance was found in the FACT-G scores and FACT-B scores among different groups at baseline, week 4, week 8 and week 12 after NHT. The Breast Cancer Subscale scores in group A patients were significantly higher than that of group C patients (p = 0.021). After 4 weeks of NHT, negative changes of FACT-B and FACT-G scores were found in group B and C patients, but there were positive changes in group A patients. Significant differences of FACT-B score (p = 0.008) and FACT-G score (p = 0.019) were observed at that time point.

The perceived association between dietary cholesterol (DC) and risk for coronary heart disease (CHD) has resulted in recommendations of no more than 300 mg/d for healthy persons in the United States. These dietary recommendations proposed... more

The perceived association between dietary cholesterol (DC) and risk for coronary heart disease (CHD) has resulted in recommendations of no more than 300 mg/d for healthy persons in the United States. These dietary recommendations proposed in the 1960s had little scientific evidence other than the known association between saturated fat and cholesterol and animal studies where cholesterol was fed in amounts

Purpose Analgesic regimes to avoid opioid-related adverse effects have been recommended in gastrointestinal surgery. Non-steroidal anti-inflammatory drugs (NSAIDs) are an important component of opioid sparing regimes in that these drugs... more

Purpose Analgesic regimes to avoid opioid-related adverse effects have been recommended in gastrointestinal surgery. Non-steroidal anti-inflammatory drugs (NSAIDs) are an important component of opioid sparing regimes in that these drugs indirectly reduce pain by inhibiting inflammation. Although beneficial for most surgical patients, animal studies and recent clinical studies suggest a harmful effect on new intestinal anastomoses by increasing the rate of leakage. NSAIDs may indirectly disturb anastomotic healing by inhibiting inflammation as an integrated part of the wound healing process in an early, critical phase after surgery. Methods A literature review based on a structured search in PubMed of clinical and experimental studies investigating the effects of NSAIDs on anastomotic healing and leakage rates after intestinal surgery, as well as proposed mechanisms and effects studied in animal models.

Many lines of independent research have provided convergent evidence regarding oxidative stress, cerebrovascular disease, dementia, and Alzheimer's disease (AD). Clinical studies spurred by these findings engage basic and clinical... more

Many lines of independent research have provided convergent evidence regarding oxidative stress, cerebrovascular disease, dementia, and Alzheimer's disease (AD). Clinical studies spurred by these findings engage basic and clinical communities with tangible results regarding molecular targets and patient outcomes. Focusing on recent progress in characterizing age-related diseases specifically highlights oxidative stress and mechanisms for therapeutic action in AD. Oxidative stress has been investigated independently for its relationship with aging and cardiovascular and neurodegenerative diseases and provides evidence of shared pathophysiology across these conditions. The mechanisms by which oxidative stress impacts the cerebrovasculature and bloodbrain barrier are of critical importance for evaluating antioxidant therapies. Clinical research has identified homocysteine as a relevant risk factor for AD and dementia; basic research into molecular mechanisms associated with homocysteine metabolism has revealed important findings. Oxidative stress has direct implications in the pathogenesis of age-related neurodegenerative diseases and careful scrutiny of oxidative stress in the CNS has therapeutic implications for future clinical trials. These mechanisms of dysfunction, acting independently or in concert, through oxidative stress may provide the research community with concise working concepts and promising new directions to yield new methods for evaluation and treatment of dementia and AD.