Citations

Denosumab is a monoclonal antibody used for prevention of skeletal-related events (SREs) in patients with bone metastases from solid tumors. Hypocalcemia is a rare and dangerous side effect of the drug Denosumab. We present a case of a patient with metastatic prostate cancer who developed severe hypocalcemia after the administration of the drug. The patient’s vitamin D levels were low when checked after administration of the drug, which likely predisposed him to the development of hypocalcemia. He was placed on high doses of oral and intravenous (IV) calcium and vitamin D without any appreciable response in the serum calcium level. His ionized calcium remained below 0.71 mmol/L despite very high doses of oral and IV calcium supplements. During the hospital course, he developed hydronephrosis from the spread of a tumor and did not want to undergo percutaneous nephrostomy tube placement; therefore, it was decided to dialyse him for acute renal failure and to correct his hypocalcemia. Checking calcium and vitamin D levels prior to the administration of Denosumab is vital in preventing hypocalcemia. If hypocalcemia is severe and not responsive to high doses of vitamin D, oral and IV calcium, then hemodialysis with a high calcium bath can correct this electrolyte abnormality.

Deletion of 15q11.2‐q13 results in either Prader–Willi syndrome (PWS) or Angelman syndrome (AS) depending on the parent of origin. Duplication of the PWS/AS critical region (PWASCR) has also been reported in association with developmental delay and autism, and it has been shown that they also show a parent‐of‐origin effect. It is generally accepted that maternal duplications are pathogenic. However, there is conflicting evidence as to the pathogenicity of paternal duplications. We have identified 35 patients with gain of the PWASCR using array comparative genomic hybridization. Methylation testing was performed to determine parent of origin of the extra copies. Of the 35 cases, 22 had a supernumerary marker chromosome 15 (SMC15), 12 had a tandem duplication, and 1 had a tandem triplication. Only one patient had a paternal duplication; this patient does not have features typical of patients with maternal duplication of the PWASCR. Three of the mothers had a tandem duplication (two were paternal and one was maternal origin). While one of the two mothers with paternal duplication was noted not to have autism, the other was noted to have learning disability and depression. Based on our data, we conclude that SMC15 are almost exclusively maternal in origin and result in an abnormal phenotype. Tandem duplications/triplications are generally of maternal origin when ascertained on the basis of abnormal phenotype; however, tandem duplications of paternal origin have also been identified. Therefore, we suggest that methylation testing be performed for cases of tandem duplications/triplications since the pathogenicity of paternal gains is uncertain. © 2014 Wiley Periodicals, Inc.

Standard cutaneous innervation maps show strict midline demarcation. Although authors of these maps accept variability of peripheral nerve distribution or occasionally even the midline overlap of cutaneous nerves, this concept seems to be neglected by many other anatomists. To support the statement that such transmedian overlap exists, we performed an extensive literature search and found ample evidence for all regions (head/neck, thorax/abdomen, back, perineum, and genitalia) that peripheral nerves cross the midline or communicate across the midline. This concept has substantial clinical implications, most notably in anesthesia and perineural tumor spread. This article serves as a springboard for future anatomical, clinical, and experimental research. Clin. Anat. 28:96–100, 2015. © 2014 Wiley Periodicals, Inc.

See article, page 900

Objective: This study was conducted to determine whether installation of sit-stand desks (SSDs) could lead to decreased sitting time during the workday among sedentary office workers. Methods: A randomized cross-over trial was conducted from January to April, 2012 at a business in Minneapolis. 28 (nine men, 26 full-time) sedentary office workers took part in a 4 week intervention period which included the use of SSDs to gradually replace 50% of sitting time with standing during the workday. Physical activity was the primary outcome. Mood, energy level, fatigue, appetite, dietary intake, and productivity were explored as secondary outcomes. Results: The intervention reduced sitting time at work by 21% (95% CI 18%–25%) and sedentary time by 4.8 min/work-hr (95% CI 4.1–5.4 min/work-hr). For a 40 h work-week, this translates into replacement of 8 h of sitting time with standing and sedentary time being reduced by 3.2 h. Activity level during non-work hours did not change. The intervention also increased overall sense of well-being, energy, decreased fatigue, had no impact on productivity, and reduced appetite and dietary intake. The workstations were popular with the participants. Conclusion: The SSD intervention was successful in increasing work-time activity level, without changing activity level during non-work hours.

The kidney of marine teleosts is the major site of Mg2+excretion and produces urine with a high Mg2+concentration. However, the transporters involved in Mg2+excretion are poorly understood. The cyclin M (Cnnm; also known as ancient conserved domain protein) family comprises membrane proteins homologous to the bacterial Mg2+and Co2+efflux protein, CorC. To understand the molecular mechanism of Mg2+homeostasis in marine teleosts, we analyzed the expression of the C nnm family genes in the seawater (SW) pufferfish, torafugu ( Takifugu rubripes), and the closely related euryhaline species, mefugu ( Takifugu obscurus). Database mining and phylogenetic analysis indicated that the Takifugu genome contains six members of the Cnnm family: two orthologs of Cnnm1, one of Cnnm2, one of Cnnm3, and two of Cnnm4. RT-PCR analyses indicated that Cnnm2, Cnnm3, and Cnnm4a are expressed in the kidney, whereas other members are mainly expressed in the brain. Renal expression of Cnnm3 was upregulated in SW mefugu, whereas renal expression of Cnnm2 was upregulated in freshwater (FW) mefugu. No significant difference was observed in renal expression of Cnnm4a between SW and FW mefugu. In situ hybridization and immunohistochemical analyses of the SW mefugu kidney revealed that Cnnm3 is expressed in the proximal tubule, and its product localizes to the lateral membrane. When Cnnm3 was expressed in Xenopus laevis oocytes, whole cellular Mg2+content and free intracellular Mg2+activity significantly decreased. These results suggest that Cnnm3 is involved in body fluid Mg2+homeostasis in marine teleosts.

Background Atrial fibrillation ( AF ) is a common sequela of hypertrophic cardiomyopathy ( HCM ), but evidence on its prevalence, risk factors, and effect on mortality is sparse. We sought to evaluate the prevalence of AF , identify clinical and echocardiographic correlates, and assess its effect on mortality in a large high‐risk HCM population. Methods and Results We identified HCM patients who underwent evaluation at our institution from 1975 to 2012. AF was defined by known history (either chronic or paroxysmal), electrocardiogram, or Holter monitoring at index visit. We examined clinical and echocardiographic variables in association with AF . The effect of AF on overall and cause‐specific mortality was evaluated with multivariate Cox proportional hazards models. Of 3673 patients with HCM , 650 (18%) had AF. Patients with AF were older and more symptomatic ( P <0.001). AF was less common among patients with obstructive HCM phenotype and was associated with larger left atria, higher E/e’ ratios, and worse cardiopulmonary exercise tolerance (all P values<0.001). During median (interquartile range) follow‐up of 4.1 (0.2 to 10) years, 1069 (29%) patients died. Patients with AF had worse survival compared to those without AF ( P <0.001). In multivariate analysis adjusted for established risk factors of mortality in HCM , the hazard ratio (95% confidence interval) for the effect of AF on overall mortality was 1.48 (1.27 to 1.71). AF did not have an effect on sudden or nonsudden cardiac death. Conclusions In this large referral HCM population, approximately 1 in 5 patients had AF . AF was a strong predictor of mortality, even after adjustment for established risk factors.