Denosumab is a potent novel antiresorptive agent for treatment of osteoporosis with unique mechanism of action . It is a fully human monoclonal antibody to the receptor activator of nuclear factor-κB ligand (RANKL) that blocks its binding to RANK, inhibiting the development and activity of osteoclasts, decreasing bone resorption, and increasing bone density. Initially denosumab appeared particularly promising for patients with advanced stages of renal failure but over the past two years several publications questioned that, reporting adverse effects and especially severe hypocalcaemia. Aim of the Study: to investigate further the effect of the osteoporosis dose of denosumab on serum calcium levels in patients with CKD 4 and CKD 5. Methods: This retrospective outpatient study included 17 females with CKD 4 and 5 who received a single or a multiple (at 6 months intervals) 60-mg subcutaneous dose of denosumab. Adjusted serum Calcium was measured prior to the dose and at various points of time after that. Results: Only two of the subjects developed clinically significant hypocalcaemia. Both of them were clearly inadequately supplemented with calcium and vitamin D. Conclusion: The results from the current study along with a critical analysis of the previous publications reveal that the vast majority of the previous reports were based on inadequately supplemented with calcium and vitamin D patients and that severe hypocalcaemia is unlikely in appropriately supplemented subjects, especially in the CKD 4 subgroup. However, due to the scarcity of data further research is warranted, especially in the CKD 5 subgroup. In the mean time more cautious approach rather than a blanket ban on denosumab appears to be the most appropriate policy in these two populations.
Aims: The aim of this study was to investigate of the roles of CD5+ and CD19+ on lymphocytes, CD5+ on B lymphocytes, CD41a+ on platelets and CD55+ and CD59+ on erythrocytes in platelet destruction; and evaluate them according to the patient response status to steroid therapy and platelet counts in chronic immune thrombocytopenic purpura (ITP). Study Design: This study included 20 chronic ITP patients and 20 healthy controls. We investigated the roles of CD5+ and CD19+ expression on lymphocytes, CD5+ expression on B lymphocytes, CD41a+expression on platelets, and CD55+ and CD59+ expression on erythrocytes, as well as the platelet counts in healthy and chronic ITP patients. Additionally, these markers were evaluated according to the patient response status to steroid therapy and platelet counts. Place and Duration of Study: This study took place at the Department of Internal Medicine and Haematology, Meram Medical Faculty at Selçuk University in Turkey, between November, 2008 and July, 2009. Methodology: A total of 40 patients (26 women, 14 men, age range: 19-79 years) were studied. The study group included 20 chronic ITP patients (12 women and 8 men, age range: 19-78 years) and the control group included 20 healthy volunteers (14 women and 6 men, age range: 22-79 years). The platelet counts and expressions of CD5+ and CD19+ on lymphocytes, CD5+ on B lymphocytes, CD41a+ on platelets, and CD55+ and CD59+ on erythrocytes were analysed in the patients and control subjects. The chronic ITP patients were evaluated according to their requirements of treatment. Five patients whose platelet counts were above 50,000 mm–3 were observed without treatment. The other 15 patients whose platelet counts were under 50.000 mm–3 and had bleeding, or whose platelet counts were under 20,000 mm–3, were given methylprednisolone treatments (1 mg/kg/day orally). Three of the 15 patients discontinued treatment for various reasons. The twelve patients who continued the methylprednisolone treatment were divided into two subgroups according to their responder status of steroid treatment. The patients whose platelet counts slowly increased above 30,000 mm–3 within three months included the steroid treatment responder subgroups. The chronic ITP patients were also divided into two subgroups according to the severity of their thrombocytopenia. The limit of the platelet count was 30,000 mm–3 for severe thrombocytopenia. These parameters were analysed according to the response status of the steroid treatment and platelet counts. The platelet counts, and the expressions of these markers, were compared between the subgroups. Results: The level of CD5+ on B lymphocyte expression (2.19 ± 1.65) in peripheral blood lymphocytes was significantly higher in the immune thrombocytopenic purpura patients than in the controls (P = .05). The CD55+ + CD59+ expression on erythrocytes (98.03 ± 1.77) was significantly higher in the ITP patients than in the controls (P = .05). There was no significant relationship between the expression of CD5+, CD19+ or CD5+on B lymphocytes, CD41a+ expression on platelets or CD55+ and CD59+ expression on erythrocytes, according to the response status to steroid therapy in the patient group (P > 0.05). Additionally, the patients were evaluated according to platelet counts, and there was a significantly positive correlation between the level of CD41a+ expression on the platelets and the platelet count (P = .05). Conclusion: The level of CD5+ on B lymphocytes was significantly higher in the ITP patients than in the controls. A relationship between CD55+ plus CD59+ expression on erythrocytes and immune destruction of platelets was not observed in the chronic ITP patients.
Aims: The objective of this research is to extract the aorta and to measure its diameter for preoperative planning of heart surgeries such as Endo Vascular Aortic Repair (EVAR) or Aortic Valvular Replacement (AVR). Study Design: Experimental Study. Place and Duration of Study: Department of Knowledge Engineering and Graduate School of Engineering in Tokyo City University, and Department of Cardiovascular Surgery in Sakakibara Heart Institute, between April 2009 and August 2012. Methodology: In order to extract the aorta correctly, the spine is removed first. Then, the diameter of the aorta is measured by considering the curvature of the aorta, especially the aortic arch. The novelty of the proposed method is as follows. 1) The spine that is almost parallel to the aorta is extracted and removed before the aorta extraction. 2) The aorta is traced by interpolating the image between the Computer Tomography (CT) sliced data to compensate the insufficient axial resolution. 3) The diameter of the aorta is measured by considering some planes, one of which is perpendicular to the center line of the aorta to lower the error due to the curvature. Results: The spine has been extracted and removed correctly and also the aorta has been extracted with the proposed method even if there is an aneurysm in the aorta. In addition, the diameter measured automatically is almost the same as that measured manually. Conclusion: It has become possible to extract the aorta even if the spine overlaps with the aorta. In addition, the measured diameter of the aorta ranges from 20 to 30 [mm], which is almost the same as the average of normal persons’ aorta. However, some parts of the heart were extracted as the aorta, and the diameter of the aortic arch was not correct. These are the issues for future works.
Aims: Neurotransmitter overflow into the extracellular space and activation of nitric oxide synthase were implicated in neuronal death after cerebral ischemia. A small temperature reduction induced after the insult crucially mitigated the neuronal death. To elucidate the mechanisms, dopamine and glutamate as marker of excitatory amino acid (EAA) overflow and the citrulline/arginine ratio (CAR) as marker of nitric oxide synthase were analysed. Study Design: Animal experiments in rats. Place and Duration of the Study: Laboratory of the Department of Pharmaceutical Chemistry and Drug Analysis, Vrije Universiteit Brussel, Brussels between 2001 and 2003. Methodology: Striatal Glutamate and dopamine and CAR were measured by using microdialysis under normothermic and hypothermic conditions before asphyxial cardiac arrest, during the insult and resuscitation as well as during the weaning process from mechanical ventilation. Results: After the insult, the EAA overflow increased significantly in the normothermic group. In the hypothermic group, however this overflow was not significantly different from the sham group. The CAR increased up to 5-fold compared to the basal value in the normothermic group and only 2.5-fold in the hypothermic group. The brain damage was mitigated in the hypothermic group, while this increased further up 7 days after the insult in the normothermic group. Conclusion: These results suggest that the neuroprotective effect of mild hypothermia resides in attenuation of the striatal EAA overflow and diminution of the CAR and were associated with a reduction of brain damage at 24 hours and 7 days post insult.
Aims: To investigate women’s perceptions of miscarriage and its complications. Study Design: A qualitative design was used with data collected through semi-structured interviews. Place and Duration of Study: Gynaecology ward of the Queen Elizabeth Central Hospital, Blantyre, Malawi, during February and March 2012. Methodology: Sample: We included 30 patients (aged between 18 and 39) admitted to the gynaecology ward for surgery following miscarriage. Inclusion criteria were: (a) diagnosis of miscarriage (b) aged over 18. Semi-structured interviews were conducted through a translator and lasted an average of 30 minutes (range 14 – 46minutes). Results: 14 of the women interviewed knew what a miscarriage was. Perceived causes included contraceptives, prohibited medicines, hard labour, stress, HIV, malaria, witchcraft, traditional medicines, lack of child spacing and abuse by their male partners. Women obtained knowledge from their own experience of miscarriage and through the shared experiences of female family members and friends. Women were found to have concerns about death from miscarriage; facing stigmatising attitudes of community and health workers; and the treatment they would receive in hospital, particularly the surgical procedure. Conclusions: The women had poor knowledge of the causes and symptoms of miscarriage. They were concerned about the treatment that they would receive in the hospital and how their miscarriage would be perceived by both the hospital staff and within their communities. Women who have miscarriages should be encouraged to discuss this with female friends and relatives to improve knowledge on miscarriage and help dispel the stigma surrounding it. Providing information on the treatment they would receive whilst in hospital may help to allay women’s concerns. Incorporating education about miscarriage into the school syllabus may help to improve women’s awareness and understanding.
Aims: Several scoring systems have been developed for diagnosis of appendicitis. This study aims to systematically explore how those scores were derived and validated, and to compare their performance. Study Design: Systematic review. Place and Duration of Study: We searched Medline from 1949 and EMBASE from 1974 to March 2012 to identify relevant articles published in English. Methodology: Information about model development and performance was extracted. The “risk of bias” assessment tool was developed based on a critical appraisal guide for clinical prediction rules. Calibration (O/E ratio) and discrimination (C-statistic) coefficients were estimated. A meta-analysis was applied to pool calibration coefficients and C-statistics. Results: Forty-four out of 468 studies were eligible. Of these, 14 developed or modified diagnostic scoring systems and 30 validated existing models. Four scores had been most frequently validated, i.e., Alvarado, modified Alvarado, Fenyo, and Eskelinen. Among them, only the Eskelinen model was derived based on a multivariate regression whereas the rest used univariate or non-statistical methodology. All studies reported very good but imprecise calibration. For discrimination, the pooled C-statistics for these corresponding scores were 0.77, 0.86, 0.81, and 0.84 respectively. In the external validation, the discriminative performance decreased about 25.3% and 10.1% for the Alvarado and Fenyo scores respectively. Conclusion: The research methods for scoring systems of appendicitis were inconsistent. More efficient scoring systems which have been internally and externally validated are required.
Background:Garcinia kola (bitter kola) is one of the most common masticatories in Nigeria having social and ethnomedicinal applications. G. kola seeds are believed to contain caffeine, one of the major constituent of coffee which is also believed to improve memory. Aim: This study was set to ascertain the caffeine content of G. kola and compare the effects of G. kola and coffee diets on learning and memory in mice. Methodology: Thirty male CD1 mice were randomly assigned into three groups, viz; control, Garcinia koladiet (30%w/w) and coffee diet (2%w/w) groups. Chemical content and LD50 of the Garcinia kola and coffee were determined using standard methods. Daily food intake, water intake and body weight changes were also measured for 31 days before testing for learning and memory. The Morris water maze was used to assess learning and memory. Results: The major constituents of Garcinia kola were alkaloids (high quantities), saponins, tannins, flavonoids, glycosides, sterols and phenols found in moderate quantities. The coffee contained high quantity caffeine (4.7%) whereas alkaloids, saponins, tannins, flavonoids, and phenols were present in slight quantities. Coffee diet decreased food intake, water intake body weight change in the mice when compared to G. kola and control diet groups (p<0.05). On the other hand, coffee diet fed mice showed better learning and memory when compared to G. kola diet-fed and control mice. Garcinia kola diet did not affect learning and memory. Conclusion: Coffee diet decreased food and water intake and body weight, but improved learning and memory in mice when compared to Garcinia kola.
Aims: To evaluate the pattern of skin prick test results of atopic dermatitis patients. Study: This was a retrospective study. Data were collected for the results of skin prick tests for atopic dermatitis patients who attended the King Abdul Aziz University Medical Services Dermatology clinic in Jeddah Saudi Arabia between October 2010 and November 2012 Results: A total of 63 cases were collected. The rate of sensitization was 85.7% (54 out of 63). Most of them had been sensitized to more than one allergen (77.8%). Most of the patients were sensitized to Dermatophagoides pteronyssinus and Dermatophagoides farina (80% and 74% respectively). Less commonly they were sensitized to cat fur (44%) and to cockroaches (37%). Conclusion: House dust mite, cats and cockroaches allergens appear to be the most prevalent sensitizers in atopic dermatitis patients in Jeddah region.
Aims: As differences in promoter activity and CD30 surface expression between CD30+ lymphoid cell-lines and peripheral blood leukocytes have been shown previously to be independent of the size of the CD30 promoter microsatellite, in this study we investigate the instability within the region in a range of neoplasms including malignant lymphoma, breast and colon carcinoma and lung adenocarcinoma. Study Design: A representative sample of CD30+ and CD30- lymphomas and cell lines as well as non-haemopoietic malignancies and normal tissues were typed for CD30 microsatellite length and compared. Place and Duration of Study: Department of Anatomical Pathology, Pathwest Laboratory Medicine WA, Perth, Australia and School of Chemistry & Biochemistry, University of Western Australia, 2000-2012. Methodology: DNA was prepared from archived biopsy specimens and used to PCR ampify the CD30 microsatellite region prior to size determination using an Genescan instrument (Applied Biosystems). Results: This study has identified instability within the CD30 promoter microsatellite region in DNA from the tumour tissue of cases of malignant lymphoma, colon carcinoma and lung adenocarcinoma but not in DNA from benign lymphoid cells or normal tissues. Conclusion: These findings indicate that variability in the length of the CD30 microsatellite may be a general characteristic of the neoplastic phenotype and may reflect defects in the mismatch repair system in these malignancies rather than a specific feature of CD30-positive neoplasms. Our results suggest that the CD30-MS may be a useful marker to distinguish between normal lymphoid tissue and lymphoid malignancy.
The relationship between glycated haemoglobin, fasting plasma glucose, packed cell volume and albumin creatinine ratio in diabetic patients in south-south Nigeria was investigated in 118 diabetic patients (80 females and 38 males) and 36 apparently healthy controls (20 females and 16 males). The glycated haemoglobin (HbA1c), fasting blood glucose (FBG) and albumin creatinine ratio (ACR) of (6.5±0.65%, 113±7.9mgldL and 48.4±6.3 respectively) were significantly higher in the diabetic patients than in control subjects (3.7±0.13%, 86±2.6mgldL and 21.0±5.1 respectively), while the packed cell volume (PCV) was higher in the control subjects than in diabetic patients (46.3±1.13% vs 40.6±0.92%). There was a significant positive correlation between the HbA1c, and FBG in both the diabetic patients and control subjects (r=0.418 and 0.782 respectively, P<0.001) and there was also a significant positive correlation between the HbA1c and ACR in both the diabetic patients and control subjects (r= 0.244 and 0.618 respectively, P< 0.001). In conclusion, there is a strong relationship between HbA1c, FBG and ACR in diabetic patients and control subjects.
Aim: To know whether one of the commercially available immunochromatographic tuberculosis tests is comparable with the widely available method, direct sputum microscopy. Design: The study prospectively validated the pulmonary tuberculosis rapid test kit using the reference standard, Lowenstein Jensen culture and compared the outcome with the direct sputum microscopy. Place and Duration: The study was conducted in Zankli Medical Centre, Abuja, between November 2004 and July 2005. Methodology: 340 patients from direct observation therapy clinics located in six different government owned health facilities were referred to our facility. These patients; male (192) and female (148) were between the age of 10 and 64 years old. Three sputa samples were collected over two consecutive days and direct microscopy and culture were performed on these samples. Also, 4ml of blood were collected from the same patients for antibody detection using immunochromatographic technique. Results: The evaluated rapid diagnostic kit when compared with the reference standard has a sensitivity of 59.3% and 81.1% specificity. Sensitivity and specificity of direct microscopy, when compared with the rapid test is statistically significant (P=0.001); indicating diagnostic accuracy of the conventional method of pulmonary tuberculosis testing over the immunochromatographic test. Conclusions: The conventional test indicated high performance in this report and it is suggestive of the relevance and diagnostic accuracy of the widely available method in the diagnosis of pulmonary tuberculosis in developing countries. This assertion is also, supported by the 2008 WHO/TDR report on evaluation of nineteen tuberculosis rapid diagnostic kits
Aims: The aim of the study was to determine the extent of compliance and non-compliance with treatment of psychiatric patients and examine the factors affecting compliance and non-compliance with treatment. Study Design: Hospital based prospective descriptive study. Place and Duration of Study: The study was carried out from September 2010 to May 2011 in Qatari population aged above 16 years at the Psychiatry Department of the Hamad Medical Corporation, Qatar. Methodology: The study included 628 patients aged 16-77 years who were hospitalized with psychiatric disorders and treated in the outpatient clinics of the Psychiatry department. The diagnostic classification of definite psychotic disorders was according to the International Classification of Disease, Tenth revision (ICD-10). Results: Of the 628 patients studied, 62.4% of them were compliant with treatment and 37.6% were non-compliant. High compliance was significantly more in patients in the age group (16 - 20) years old (84.4%), retired (70.2%) and housewives (70%) (P<0.001). Social support (40.3%) was poor in non-compliant patients, whereas 50.3% of compliant patients had good social support (P<0.001). The major reasons for non-compliance were irregular attendance to clinic (55.5%; P<0.001), ignorance about side effects of medication (61.0%; P=0.001), and lack of education about medication (47.9%; P<0.001). Conclusion: Non-compliance is quite common in Qatari population like any other society. All efforts should be exerted to improve the compliance of psychiatric patients by eliminating the factors leading to non-compliance. High complaint patients were more satisfied with psychiatrist than non compliant patients. The main reasons found for compliance were lack of family support, irregular attendance to clinic, ignorance about side effects of medication, free medicine and lack of education about medication.
Genome-wide association studies (GWAS) have identified variants associated with type 2 diabetes (T2D), but less than five percent of the genetic variance associated with T2D is accounted for in GWAS studies performed using T2D as endpoint. These findings suggest relevance of assessing preceding quantitative traits (QTs) or sub-phenotypes and their respective markers for contributing to the appearance of glycemic thresholds defining T2D. The QTs first appear in gestation and childhood when birth weight and childhood weight gain have an influence on T2D. Changes in fetal growth are associated with metabolic programming for T2D in adulthood. Subsequently gains in body fat leading to obesity, ectopic lipid deposition in liver and muscle, dyslipidemia and hypertension express in the β-cells, hypothalamus, adipocytes, myocytes, liver and kidney, and are associated with worsening insulin resistance and β-cell failure preceding overt T2D. Obesity, an increasingly common trait is associated with gene variants that regulate energy balance but have no association with T2D with few exceptions. For instance, FTO gene variants are associated with early onset of obesity and have also been associated with T2D and hypertension suggesting pleiotropism. Non-alcoholic fatty liver disease (NAFLD) has an independent genetic background and is considered as a new addition to the metabolic syndrome. Association of NAFLD with dyslipidemia, cardiovascular disease and hepatic insulin resistance contributes to progression to T2D. The classic dyslipidemia encountered in insulin resistant states consisting of increased triglyceride, low high-density lipoprotein cholesterol (HDL-C) and molding of triglyceride-containing lipoproteins to form atherogenic LDL particles and dysfunctional HDL particles, has strong environmental and genetic association. In addition evidence is accumulating to show that the abnormal lipoproteins have a direct effect on β-cells leading to failure and possible acceleration of diabetes onset. Consequently known variants affecting either the dyslipidemia or β-cell function have a compound effect on T2D. Like other preceding traits the genetic background for commonly encountered hypertension is independent of diabetes although it remains a predictive trait. However, increasing evidence supports a role for the renin-angiotensin system in causing oxidative stress and insulin resistance. Finally when glucose intolerance has progressed to overt T2D, reversibility is usually no longer possible; therefore recognition of preceding pre-diabetic glycemic thresholds and both their genetic and environmental associations may facilitate and serve as signals for prevention. Thus a better understanding of the sequential expression of the respective QTs and genetic variation affecting their metabolic effects leading to T2D could initiate more effective prevention strategies.
The majority of penile cancers develop from squamous cells within the skin resulting in a non-melanoma form of skin cancer, squamous cell carcinoma. Squamous cell carcinomas can develop anywhere on the penis, most appear on the foreskin in men who have not been circumcised or on the glans. Various types of squamous cell carcinomas ranging from Bowen’s disease, erythroplasia of Queyrat and Buschke-Lowenstein tumour have been identified on the penis. When detected early, these types of cancer can be successfully treated. However, the current treatment procedures have the potential for disfigurement and dysfunction of male genitalia, with associated psychological distress. A relatively new class of antineoplastic agents, consisting of the solasodine rhamnosides, solamargine and solasonine, are very effective and safe for the treatment of a variety of skin cancers and show promise for the treatment of internal cancers. Here, three cases of distinct squamous cell carcinomas on the penis, Bowen’s disease, erythroplasia of Queyrat and Buschke-Lowenstein tumour are reviewed which were successfully treated with a standard mixture of solasodine rhamnosides.
Posttraumatic stress disorder is a type of anxiety disorder that manifests after exposure to a traumatic event that was perceived as life threatening. Individuals with posttraumatic stress disorder have a deficiency in the extinction of fear memory. Moreover, environmental cues similar to the ones present during the trauma induced abnormal symptoms of fear and anxiety. Current therapies only help a small percentage of patients with this condition, thus pharmacological interventions to reduce the conditioned fear response are needed. Nicotine and its main metabolite, cotinine, have been shown to help in the extinction of fear memories in animal models. In this article we will discuss potential mechanisms and brain regions that may be underlying the effect of cotinine in enhancing the extinction of fear response after fear conditioning. The relevance of these mechanisms in posttraumatic stress disorder is discussed.