Brown-Séquard revisited: a lesson from history on the placebo effect of androgen treatment

BACKGROUND: In 1889, Brown-Séquard, aged 72, reported dramatic rejuvenating effects after self-administering testicular extracts of dogs and guinea-pigs. His report resulted in widespread use of testicular extracts throughout Europe and North America for several decades. More recently, the male ageing process has been attributed to partial androgen deficiency, or "andropause", and testosterone treatment is claimed to improve well-being in middle-aged and elderly men. DESIGN: We prepared extracts from five dog testes using Brown-Séquard's methods and assayed testosterone concentrations. RESULTS: Testosterone concentrations were four orders of magnitude less than that required for a biological effect. CONCLUSIONS: Our study illustrates the marked placebo response that can be evoked by androgen treatment. It cautions against the empirical use of testosterone treatment for older men, unless a diagnosis of hypogonadism has been substantiated.     

Synchronous granulocytic sarcoma of the breast and spine: a case report and review of the literature

Granulocytic sarcoma or chloroma is a rare tumour derived from myeloid cell precursors. It is generally seen before or after or together with the onset of myelocytic leukaemia. Immunohistochemical staining of myeloperoxidase is necessary for a definite diagnosis of granulocytic sarcoma. Recognition of this entity ensures an early aggressive chemotherapy that causes regression of the tumour.1-3 We present an unusual case of a 40-year-old woman who presented with back pain, numbness in the legs, and fatigue for 2 weeks. She was diagnosed as having synchronous granulocytic sarcomas of the breast and spine, confirmed surgically and histopathologically. After a subsequent systemic chemotherapy the patient was completely asymptomatic during a 20-month follow-up. We also reviewed the literature about the clinical manifestations, diagnosis, treatment, and prognosis of this condition.     

Wilms’ tumour in adults: a case report and review of the literature

Background  

Wilms’ tumour is a very rare adult malignancy representing 1% of adult renal tumours. It is however the most common renal tumour of childhood, and adult patients are treated in accordance with paediatric protocols.     

Uncommon features of pulmonary Langerhans’ cell histiocytosis: analysis of 11 cases and a review of the literature

Pulmonary Langerhans＇ cell histiocytosis （PLCH） is an isolated form of Langerhans＇ cell histiocytosis thatusually develops in cigarette smokers.1＇2^ PLCH usually has typical light microscopic morphology with a spectrum of progressive changes.2-4^ It is characterized by peribronchiolar Langerhans＇ cell infiltrates mixed with macrophages, lymphocytes and eosinophils, that form stellate nodules. The nodular lesions are frequently cavitated and form thick- and thin-walled cysts, which are thought to represent enlarged airway lumina. PLCH lesions display temporal microscopic heterogeneity, with a progression from dense cellular nodules to cavitary nodules with increasing degrees of fibrosis that may extend along alveolar walls. In advanced cases,     

Pituitary involvement in Wegener’s granulomatosis: a case report and review of the literature

Wegener's Granulomatosis (WG)is a multi-system disorder characterized by necrotizing granulomas in the upper and/or lower respiratory tract, with or without focal     

Whose ethics of knowledge? Taking the next step in evaluating knowledge in synthetic biology: a response to Douglas and Savulescu

The recent proposal by Douglas and Savulescu for an ethics of knowledge provokes a renewed consideration of an enduring issue. Yet, the concept raises significant challenges for procedural and substantive justice. Indeed, the operationalisation of 'an ethics of knowledge' could be as alarming as what it seeks to prevent. While we can acknowledge that there is, and surely always will be, potential for misuse of beneficial science and technology, a contemplated conception of what we ought to not know, devise or disseminate sets before us an enormously complex task. This essay challenges an ethics of knowledge to respond to concerns of procedural and substantive justice. While the concept has a certain appeal, it does not appear to adequately address certain fundamental issues as it is currently presented. Here, the author invites consideration of two primary points: (1) who should decide, based on whose interests? and (2) could such an exercise actually be effective in achieving its goal?     

An angiogenic factor from human bladder cancer: the investigation of purification and biological activities.

An angiogenic factor from human transitional cell cancer of bladder has been purified by protein extraction, cation exchange chromatography, gel filtration high-performance liquid chromatography (GE-HPLC) and reversed-phase high-performance liquid chromatography (RP-HPLC). The purified substance was named bladder cancer angiogenic factor (BCAF). Biological activity of the BCAF was assessed by the method of chick embryo chorioallantoic membrane (CAM) assay and 3H-TdR incorporation into DNA in Balb/C 3T3 cells. The BCAF displayed the potent activities of neovascularization in CAM and DNA synthesis in Balb/C 3T3 cells. The ultrastructural features of blood vessels induced by the BCAF were similar to the blood vessels in tumors. The BCAF contained a protein with an approximate molecular weight of 15,000 D which was identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and silver staining. Amino acid compositions of the BCAF were also analysed by acid hydrolysis.

     

The performance and problems of the Turkish pharmaceutical industry: is there a need to develop a national drug policy?

Turkey has a big pharmaceutical industry—of the drugs consumed there, 90% are manufactured domestically. Eighty percent of this manufacturing is run by foreign companies. In this study, the performance of the Turkish pharmaceutical industry in terms of the technology and production is examined and compared with that of some other countries, and the importance of the essential drugs list and national drug policy is discussed. At the end of the study, strategies are suggested toward meeting the main current challenges in the Turkish pharmaceutical industry.     

Understanding patients’ perspective of statin therapy: can we design a better approach to the management of dyslipidaemia? A literature review

INTRODUCTION

Dyslipidaemia leads to atherosclerosis and is a major risk factor for cardiovascular diseases. In clinical trials, 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, or statins, have been shown to effectively reduce dyslipidaemia. Despite the availability and accessibility of statins, myocardial infarctions and cerebrovascular accidents remain among the top causes of mortality in developed countries, including Singapore. This enigma could be attributed to suboptimal adherence to statin therapy. The present literature review aimed to evaluate patients’ perceptions of statin therapy.

METHODS

We searched PubMed and other databases for articles published in English from October 1991 to May 2012 containing keywords such as ‘patient’, ‘views’, ‘perceptions’, ‘adherence’, ‘statin’ and ‘dyslipidaemia’. Of the 122 eligible studies retrieved, 58 were reviewed. The findings were categorised and framed in accordance with the Health Belief Model.

RESULTS

Patients with dyslipidaemia appeared to underestimate their susceptibility to dyslipidaemia-related complications, partly due to their demographic profiles. Failure to appreciate the severity of potential complications was a major hindrance toward adherence to statin therapy. Other factors that affected a patient’s adherence included lack of perceived benefits, perceived side effects, the cost of statins, poor physician-patient relationship, and overestimation of the effectiveness of diet control as a treatment modality.

CONCLUSION

Existing evidence suggests that the cause of poor adherence to statin therapy is multifactorial. The use of the Health Belief Model to present the results of our literature review provides a systematic framework that could be used to design a patient-centric approach for enhancing adherence to statin therapy.     

Atypical femoral shaft fracture in a patient with non-metastatic prostate cancer on zoledronic acid therapy: effect of therapy or coincidence?

There have been recent concerns of atypical non-spinal fractures in patients with osteoporosis who are on long-term bisphosphonate therapy. These fractures are less commonly reported in cancer patients on zoledronic acid therapy, where it is used in higher doses as compared to patients with osteoporosis. We report the case of a 70-year-old man with non-metastatic prostate cancer who was on androgen deprivation therapy following bilateral orchiectomy. He was on bone protection with intravenous zoledronic acid 4 mg monthly for a period of two years. He presented with spontaneous acute right mid-thigh pain. Radiograph of the right femur showed an atypical femoral shaft fracture, which was treated with intramedullary nailing and teriparatide. This case report raises concerns of atypical fractures in cancer patients who receive high doses of zoledronic acid. Patients receiving bisphosphonates who present with thigh or groin pain must undergo radiographic examination of the femur to rule out atypical femoral fractures.     

Rhodoaggregin:a novel multimeric platelet agonist from the venom of Calloselasma rhodostoma (Malayan Pit Viper)

By means of Superdex 75 gel filtration and Mono Q ion exchange chromatography, we have isolated a novel platelet aggregation inducer, termed rhodoaggregin, from the crude venom of Calloselasma rhodostoma (Malayan pit viper). The native molecular mass of rhodoaggregin (as estimated by gel filtration chromatography) was 66 kDa while its isoelectric point (pI) was determined to be 3.45. Under reducing conditions of SDS-PAGE, rhodoaggregin exhibited two distinctive bands with molecular masses of 18 kDa (α subunit) and 15 kDa (β subunit). In the absence of reducing agents, however, two bands were also observed, but with apparent molecular masses of 28 (major) and 52 (minor) kDa, respectively. Furthermore, mass spectrometric analysis also showed that rhodoaggregin had a molecular mass of 30155.39±3.25. These molecular weight data suggest that rhodoaggregin probably exists as a tetrameric structure consisting of two disulfide-linked heterodimers. N-terminal amino acid sequence analysis showed that the two subunits of rhodoaggregin exhibit a high degree of homology with each other and with those of the C-type lectin related proteins (CLPs) from other snake venoms. Functional platelet assays showed that rhodoaggregin induced platelet aggregation in rabbit and human whole blood, platelet-rich-plasma (PRP) and washed platelets with a lag period and in an all-or-none manner. The concentration of rhodoaggregin that induced maximal aggregation is estimated at about 0.04 μg/ml (or 0.7 nM).     

Associations of cholecystectomy with the risk of colorectal cancer: a Mendelian randomization study

Background: Cholecystectomy is a standard surgery for patients suffering from gallbladder diseases, while the causal effects of cholecystectomy on colorectal cancer (CRC) and other complications are still unknown.Methods: We obtained genetic variants associated with cholecystectomy at a genome-wide significant level (P value <5 × 10-8) as instrumental variables (IVs) and performed Mendelian randomization (MR) to identify the complications of cholecystectomy. Furthermore, the cholelithiasis wa...     

Evaluation of the effect of intra-operative intravenous fluid on post-operative pain and pulmonary function: a randomized trial comparing 10 and 30 ml kg−1 of crystalloid

Background

Existing evidence suggests that administration of intravenous fluids has been shown to improve outcomes including pain in gynecological laparoscopic surgery but the optimum fluid dose has not been determined.

Aims

To determine the effect of administration of intravenous fluids on post-operative pain and pulmonary function after gynecological laparoscopy.

Methods

In a prospective randomized double-blinded study 100 ASA 1 and 2 elective patients undergoing gynecological laparoscopy were randomized to receive intravenous compound sodium lactate 10 ml kg^?1 (CSL10-restrictive) or 30 ml kg^?1 (CSL30-liberal) administered intra-operatively. The primary outcome measure was the post-operative pain score at 24, 48 and 72 h, assessed by 0–10 verbal rating scale (VRS). Pulmonary function (FEV1, FVC, PEFR) and oxygen saturation were also measured.

Results

Patients who received CSL 30 had lower post-operative pain scores than CSL 10 (ANCOVA—mean difference = 0.47, 95 % CI 0.11–0.83, P = 0.01). Post-operative pain VRS was lower in CSL30 than CSL10 at 48 h (mean difference 0.56, 95 % CI 0.04–1.09, P = 0.036). Patients in CSL30 reported shoulder tip pain less frequently than those in CSL10 (30.4 vs. 43.9 % of assessments, P = 0.03, OR 0.58) but reported wound pain more frequently 39.0 vs. 24.2 %, P = 0.01, OR 2.0). Indices of pulmonary function did not differ between groups at any time.

Conclusions

Liberal compared to restrictive administration of i.v. crystalloid is associated with a clinical modest reduction in pain. Pulmonary dysfunction was not increased with liberal fluid administration.     

Studying the progression of chronic infection with the hepatitis B virus has a bearing on diagnosis and therapy: A more personal look at research that benefited from the communication with colleagues in China

Theinfectionanditsmanagement　AhighproportionofhepatitisBvirus (HBV )infections ,whichleadtochronicityratherthanbeingresolved ,areinfectionsoccuringatbirthorearlychildhood[1] .Despitesuc cessfulvaccination programs ,thenumberofchroniccarriersincreasesworldwide .Hepatocellularcarcinoma(HCC)developslateinthecourseofachronicinfec tion ,withitsconcomitantoveralldecreaseinviralreplication .However ,stagesassociatedwithaparticu larlyhighrisktodevelopcancerarenotdescribedtothisdate .Astillattract…