HDL cholesterol and bone mineral density: is there a genetic link?

Overwhelming evidence has linked cardiovascular disease and osteoporosis, but the shared root cause of these two diseases of the elderly remains unknown. Low levels of high density lipoprotein cholesterol (HDL) and bone mineral density (BMD) are risk factors for cardiovascular disease and osteoporosis respectively. A number of correlation studies have attempted to determine if there is a relationship between serum HDL and BMD but these studies are confounded by a number of variables including age, diet, genetic background, gender and hormonal status. Collectively, these data suggest that there is a relationship between these two phenotypes, but that the nature of this relationship is context specific. Studies in mice plainly demonstrate that genetic loci for BMD and HDL co-map and transgenic mouse models have been used to show that a single gene can affect both serum HDL and BMD. Work completed to date has demonstrated that HDL can interact directly with both osteoblasts and osteoclasts, but no direct evidence links bone back to the regulation of HDL levels. Understanding the genetic relationship between BMD and HDL has huge implications for understanding the clinical relationship between CVD and osteoporosis and for the development of safe treatment options for both diseases.     

Postoperative wound blistering: is there a link with dressing usage?

Practitioners on an orthopaedic ward used three different types of dressing on two groups of 100 patients who had undergone hip or knee operations, and compared the number of blisters that resulted. They describe their findings.     

SATB1 and bladder cancer: Is there a functional link?

Purpose

SATB1, a global genome organizer, has been shown to play a role in the development and progression of some solid tumors, but its role in bladder cancer is undetermined. Moreover, there is conflicting data about the role of SATB1 in other tumors. This study was initiated to assess a potential role for SATB1 with the hypothesis that SATB1 acts as a tumor promoter in bladder cancer.

Dementia and osteoporosis in a geriatric population: Is there a common link?

AIM To determine the existence of a common pathological link between dementia and osteoporosis through reviewing the current evidence base. METHODS This paper reviews the current literature on osteoporosis and dementia in order to ascertain evidence of a common predisposing aetiology. A literature search of Ovid MEDLINE(1950 to June 2016) was conducted. The keywords osteoporosis, osteoporotic fracture, dementia and Alzheimer's disease(AD) were used to determine the theoretical links with the most significant evidence base behind them. The key links were found to be vitamins D and K, calcium, thyroid disease, statins, alcohol and sex steroids. These subjects were then searched in combination with the previous terms and the resulting papers manually examined. Theoretical, in vitro and in vivo research were all used to inform this review which focuses on the most well developed theoretical common causes for dementia(predominantly Alzheimer's type) and osteoporosis.RESULTS Dementia and osteoporosis are multifaceted disease processes with similar epidemiology and a marked increase in prevalence in elderly populations. The existence of a common link between the two has been suggested despite a lack of clear pathological overlap in our current understanding. Research to date has tended to be fragmented and relatively weak in nature with multiple confounding factors reflecting the difficulties of in vivo experimentation in the population of interest. Despite exploration of various possible mechanisms in search for a link between the two pathologies, this paper found that it is possible that these associations are coincidental due to the nature of the evidence available. One finding in this review is that prior investigation into common aetiologies has found raised amyloid beta peptide levels in osteoporotic bone tissue, with a hypothesis that amyloid beta disorders are systemic disorders resulting in differing tissue manifestations. However, our findings were that the most compelling evidence of a common yet independent aetiology lies in the APOE4 allele, which is a well-established risk for AD but also carries an independent association with fracture risk. The mechanism behind this is thought to be the reduced plasma vitamin K levels in individuals exhibiting the APOE4 allele which may be amplified by the nutritional deficiencies associated with dementia, which are known to include vitamins K and D. The vitamin theory postulates that malnutrition and reduced exposure to sunlight in patients with AD leads to vitamin deficiencies. CONCLUSION Robust evidence remains to be produced regarding potential links and regarding the exact aetiology of these diseases and remains relevant given the burden of dementia and osteoporosis in our ageing population. Future research into amyloid beta, APOE4 and vitamins K and D as the most promising aetiological links should be welcomed.     

Inflammatory bowel disease and diabetes: Is there a link between them?

Patients with inflammatory bowel disease (IBD) are reported to have an increased risk of diabetes. IBD therapies may also modulate blood glucose substantially. These observations are indicative of mechanistic connection(s) between IBD and diabetes.     

Fibrosis, regeneration and cancer: what is the link?

Tubulo-interstitial fibrosis constitutes the final common pathway for all pathological conditions that evolve towards chronic kidney disease, and transforming growth factor-β1 plays a key role in this process. Furthermore, neutrophil gelatinase-associated lipocalin appears not only to be a simple marker of renal injury but also an active player in disease progression. We are not yet able to control and modulate this phenomenon. Therefore, a better understanding of fibrogenic molecular mechanisms is necessary to detect possible therapeutic strategies that interfere with fibrosis and then stop the progression of renal disease. The line of research called 'regenerative medicine' works toward this. According to many authors, the formation of a fibrotic extracellular matrix disrupts the cells' polarity and stimulates their proliferation, creating conditions for cancer development. However, there is another plausible hypothesis: is it possible that fibrosis provides a sort of 'protection' from the development of a cancer as a consequence of the intense proliferation that characterizes any inflammatory process? In superior organisms, and also in humans, regeneration may have been selected negatively and replaced by fibrosis in the course of evolution, to warrant species survival: in fact, unchecked pluripotent cell production and proliferation can lead to tumour development and the potential death of a single individual. Hence, tumours might be the outcome of the failure of fibrotic processes, most likely due to some mediators predominating over others. So, valid experimental models are necessary to understand the interactions that exist between fibrosis and tumours and to evaluate the real advantage of therapies that aim to inhibit the fibrotic process at the renal level or that of other organs. The ideal approach would be to limit fibrosis and then organ function loss but without exposing the patient to risks of developing a tumour, starting from as early as the drugs prescribed.     

Severe atherosclerosis in rheumatoid arthritis and hyperhomocysteinemia: Is there a link?

Rheumatoid arthritis (RA) is a chronic inflammatory joint disease whose main complication is accelerated atheroma responsible for high rates of cardiovascular morbidity and mortality. Hyperhomocysteinemia is among the factors incriminated in RA-associated atheroma. We managed a 46-year-old patient with RA who required admission to evaluate severe arterial and venous disease with involvement of the coronary, renal, and peripheral arteries. She had no laboratory evidence of rheumatoid vasculitis or conventional cardiovascular risk factors (diabetes and hypercholesterolemia) and had never smoked. Her serum homocysteine level was elevated to 20.9 micromol/L as a result of a homozygous C667T mutation in the methylenetetrahydrofolate (MTHFR) gene. Folate and vitamin B12 levels were normal. A circulating anticoagulant was identified. Hyperhomocysteinemia, which is defined as a homocysteine level greater than 15 micromol/L, is a risk factor for arterial and venous disease. Hyperhomocysteinemia is found in 20%-42% of patients with RA. Methotrexate therapy is the most common causative factor. Other causes include MTHFR deficiency, vitamin B12 deficiency, renal failure, old age, and smoking. Whatever the underlying cause, folic acid supplementation returns the homocysteine level to normal.     

Topical agents and erectile dysfunction: is there a place?

Despite the proven efficacy of oral therapy for erectile dysfunction (ED), some patients are unable to take these medications because of drug interactions (ie, sildenafil and nitroglycerin) or a lack of response. Topical agents represent another minimally invasive option for the treatment of ED. This review discusses the impediments to effective topical therapy and examines the developmental status of several candidate drugs. Although still in the investigative stage, topical medications can be another tool in the urologist’s armamentarium against ED.     

Peripheral arterial disease,type 2 diabetes and postprandial lipidaemia: Is there a link?

Peripheral arterial disease, manifested as intermittent claudication or critical ischaemia, or identified by an ankle/brachial index 0.9, is present in at least one in every four patients with type 2 diabetes mellitus.Several reasons exist for peripheral arterial disease indiabetes. In addition to hyperglycaemia, smoking and hypertension, the dyslipidaemia that accompanies type2 diabetes and is characterised by increased triglyceride levels and reduced high-density lipoprotein cholesterol concentrations also seems to contribute to this association. Recent years have witnessed an increased interest in postprandial lipidaemia, as a result of various prospective studies showing that non-fasting triglycerides predict the onset of arteriosclerotic cardiovascular disease better than fasting measurements do. Additionally,the use of certain specific postprandial particle markers,such as apolipoprotein B-48, makes it easier and more simple to approach the postprandial phenomenon. Despite this, only a few studies have evaluated the role of postprandial triglycerides in the development of peripheral arterial disease and type 2 diabetes. The purpose of this review is to examine the epidemiology and risk factors of peripheral arterial disease in type 2 diabetes, focusing on the role of postprandial triglycerides and particles.     

Pacemaker placement and shoulder surgery: is there a risk?

INTRODUCTION

Surgery to the anterior aspect of the shoulder is performed by many surgical specialties but the techniques used by our cardiology colleagues for insertion of cardiac pacemaker wires are often not appreciated by the surgical community. The deltopectoral approach has been used for open pacemaker wire insertion for many years by cardiologists. METHODS We surveyed a group of subspecialty shoulder surgeons as well as orthopaedic trainees to see if this approach for pacemakers is well recognised. We tried to assess what level of knowledge exists regarding pacemaker placement in general as well as specific risks.

RESULTS

There appears to be a paucity of knowledge regarding pacemaker placement and related patient safety issues in both surveyed groups. There was no difference between the two groups, suggesting that the level of knowledge does not increase with experience and specialisation.

CONCLUSIONS

There is the potential to cause harm to patients if the insertion site and type of device is not identified before commencing surgery in this region and steps must be taken to minimise any intra-operative risk. There is a risk from direct injury to the pacemaker and/or leads as well as the hazards of using diathermy in close proximity to a pacemaker. There must be more widespread dissemination of this information in order to minimise risks to patients with pacemakers in situ.