Abnormal liver function tests associated with severe rhabdomyolysis

Rhabdomyolysis is a syndrome of skeletal muscle injury with release of cellular constituents such as potassium,phosphate,urate and intracellular proteins such as myoglobin into the circulation,which may cause complications including acute kidney injury,electrolyte disturbance and cardiac instability.Abnormal liver function tests are frequently observed in cases of severe rhabdomyolysis.Typically,there is an increase in serum aminotransferases,namely aspartate aminotransferase and alanine aminotransferase.This raises the question of liver injury and often triggers a pathway of investigation which may lead to a liver biopsy.However,muscle can also be a source of the increased aminotransferase activity.This review discusses the dilemma of finding abnormal liver function tests in the setting of muscle injury and the potential implications of such an association.It delves into some of the clinical and experimental evidence for correlating muscle injury to raised aminotransferases,and discusses pathophysiological mechanisms such as oxidative stress which may cause actual liver injury.Serum aminotransferases lack tissue specificity to allow clinicians to distinguish primary liver injury from muscle injury.This review also explores potential approaches to improve the accuracy of our diagnostic tools,so that excessive or unnecessary liver investigations can be avoided.     

Bone Microarchitecture Phenotypes Identified in Older Adults Are Associated With Different Levels of Osteoporotic Fracture Risk

Prevalence of osteoporosis is more than 50% in older adults, yet current clinical methods for diagnosis that rely on areal bone mineral density (aBMD) fail to detect most individuals who have a fragility fracture. Bone fragility can manifest in different forms, and a “one-size-fits-all” approach to diagnosis and management of osteoporosis may not be suitable. High-resolution peripheral quantitative computed tomography (HR-pQCT) provides additive information by capturing information about volumetric density and microarchitecture, but interpretation is challenging because of the complex interactions between the numerous properties measured. In this study, we propose that there are common combinations of bone properties, referred to as phenotypes, that are predisposed to different levels of fracture risk. Using HR-pQCT data from a multinational cohort (n = 5873, 71% female) between 40 and 96 years of age, we employed fuzzy c-means clustering, an unsupervised machine-learning method, to identify phenotypes of bone microarchitecture. Three clusters were identified, and using partial correlation analysis of HR-pQCT parameters, we characterized the clusters as low density, low volume, and healthy bone phenotypes. Most males were associated with the healthy bone phenotype, whereas females were more often associated with the low volume or low density bone phenotypes. Each phenotype had a significantly different cumulative hazard of major osteoporotic fracture (MOF) and of any incident osteoporotic fracture (p < 0.05). After adjustment for covariates (cohort, sex, and age), the low density followed by the low volume phenotype had the highest association with MOF (hazard ratio = 2.96 and 2.35, respectively), and significant associations were maintained when additionally adjusted for femoral neck aBMD (hazard ratio = 1.69 and 1.90, respectively). Further, within each phenotype, different imaging biomarkers of fracture were identified. These findings suggest that osteoporotic fracture risk is associated with bone phenotypes that capture key features of bone deterioration that are not distinguishable by aBMD. © 2021 American Society for Bone and Mineral Research (ASBMR).     

A Simple Dressing Technique Following Dermofasciectomy and Full Thickness Skin Grafting of the Fingers in the Treatment of Severe Dupuytren’s Contracture

Dupuytren’s disease with severe finger contractures and recurrent contractures following previous surgery often have extensive skin involvement. In these severe cases, excision of the diseased chord along with the involved skin is a good option to reduce the risk of recurrance. The resulting skin defect can be covered with a full thickness skin graft (FTSG) or a cross finger flap. Cross finger flaps have donor finger morbidity and hence a full thickness graft is usually preferred. The FTSG extending to the midlateral margins on both sides of the finger reduces the risk of joint contracture due to graft shrinkage. Once the FTSG is sutured in place, the standard practice is to compress and secure the graft to its recipient bed with a tie-over dressing and this can be time consuming. We present a simple dressing technique to secure the FTSG without the need for a tie-over dressing.     

Delivery of therapeutic doses of doxorubicin to the mouse lung using lung-accumulating liposomes proves unsuccessful

Cancer Chemotherapy and Pharmacology - Addition of solid doxorubicin or solutions to pre-formed liposomes proved to be the optimal method for incorporating the drug into liposomes whilst...     

Antidepressant and other centrally acting drugs regulate glucocorticoid receptor messenger RNA levels in rat brain

The effect of imipramine, desipramine, ketanserin and lithium on Type II glucocorticoid receptor (GR) mRNA levels was studied in rat brain regions involved in the control of the hypothalamo-pituitary-adrenal (HPA) axis, the dysregulation of which has been implicated in the pathophysiology of major depression. Northern blot analysis of Type II GR mRNA showed that treatment of male rats with either desipramine or imipramine increased hypothalamic and hippocampal GR mRNA levels. Upregulation of GR mRNA following administration of imipramine was found in brain regions of female rats, while desipramine had no effect. Ketanserin increased levels of GR mRNA in hippocampus of male, but not female, rats. Lithium also was able to induce important increases rat brain GR mRNA; this effect was particularly marked in females.

We conclude that desipramine, imipramine, ketanserin and lithium can modulate GR mRNA in regions of rat brain involved in the control of the HPA axis and may have a common mechanism of action at the level of the GR gene. Sexual dimorphism for drug regulation of brain GR mRNA content was shown and may be related to sex differences in the prevalence of certain affective disorders.     

Evaluation of a mass dispensing exercise in a Cities Readiness Initiative setting.

PURPOSE: The effectiveness of a point of dispensing (POD) used in a mass dispensing exercise was evaluated. METHODS: Public Health-Seattle & King County (PHSKC), in conjunction with the University of Washington, conducted a functional exercise of mass dispensing plans to test the effectiveness of a POD. Specifically, the organization and maintenance of patient flow, staffing model, signage, and dissemination of public information were evaluated. A data collection application using cellular telephones was used to record time and patient flow data to evaluate patient flow. Questionnaires distributed to staff and volunteer patients at the end of the exercise obtained feedback regarding the setup, organization, and operations of the POD. RESULTS: The POD was operational for approximately 68 minutes. The majority of POD staff reported feeling comfortable with their specific job tasks and duties within 15 minutes of opening the doors to the POD to the public. Staff questionnaires also revealed a high level of self-reported confidence in their ability and in the ability of their colleagues to perform the job-specific responsibilities required of them or respond to this hypothetical event. The majority of volunteer patients found the signs helpful and easy to follow and the check-in form easy to complete. Despite efforts to provide patients with oral and written information about the medications being dispensed, only 80% indicated that they knew how to take the medication, and only 73% reported understanding the medication instructions for all the individuals for whom they picked up medication. CONCLUSION: The majority of volunteer patients and staff who participated in a functional exercise of mass dispensing plans found the POD to be effective. Time-flow analysis provided preliminary estimates of the total amount of time needed to complete the dispensing process for each head of household.     

Youth Tobacco Access and Possession Policy Interventions: Effects on Observed and Perceived Tobacco Use

This study evaluated the effects of tobacco Purchase, Use and Possession (PUP) laws on student perceptions of adolescent tobacco use within towns and schools. Twenty‐four towns were randomly assigned into two conditions, the experimental condition (E PUP) involved efforts to increase both PUP law enforcement and reduce minors' access to commercial sources of tobacco, whereas the control condition (C) focused only on efforts to reduce minors' access to commercial sources of tobacco. A hierarchical linear modeling analytical approach was selected due to the multilevel data and nested design. The present study found that over time, youth in the experimental PUP condition observed less youth tobacco usage at school and in their town, and perceived lower rates of tobacco among their peers at school and among friends than youth in the control condition. The findings suggest that PUP law enforcement might be used to strengthen community norms against youth tobacco use.