Hypothesis: Thyroid Hormone Abnormalities and Frailty in Elderly Patients with Chronic Kidney Disease: A Hypothesis

Thyroid hormones play a crucial role in the metabolic activities of adults, affecting almost every organ system. All types of thyroid diseases are encountered in the elderly. As symptoms and signs of thyroid diseases may overlap with what is considered to be “normal aging,” the presence of a thyroid disorder may go undiagnosed in the elderly. This potential problem is further compounded in elderly patients with chronic kidney disease (CKD), where the presence of an underlying hormonal problem such as hypothyroidism may be erroneously attributed to multiple comorbidities, the aging process, or the kidney disease. Frailty is being recognized as a contributing factor to the poor outcomes (hospitalization and high mortality) in elderly patients with CKD. Predisposing factors leading to frailty in elderly with CKD such as increased inflammatory markers, anemia, low testosterone, sarcopenia, and depression are associated with thyroid hormonal abnormalities. These associations are remarkable and raise the question of whether routine monitoring and screening for thyroid hormone changes in elderly CKD patients might be helpful in identifying reversible causes of frailty. In this review, we will focus on the associations between thyroid hormone abnormalities and the predisposing factors of frailty in elderly patients with CKD. If a cause–effect relationship of thyroid hormone abnormalities and factors predisposing to frailty in CKD patients is established, identification and treatment of thyroid abnormalities in this population would assume increased importance.     

Effect of training on upper-extremity prosthetic performance and motor learning: a single-case study

Dromerick AW, Schabowsky CN, Holley RJ, Monroe B, Markotic A, Lum P. Effect of training on upper-extremity prosthetic performance and motor learning: a single-case study.

Objectives

To examine the impact of a new prosthesis on an experienced and highly motivated prosthetic limb user, to evaluate the effects of training and the ability of clinical measures to detect change, and to gain insight into the mechanisms by which improvement occurs.

Design

A single-case study.

Setting

An outpatient clinic.

Participant

A bilateral high-arm amputee (right shoulder disarticulation, left above elbow).

Interventions

Provision of new prosthesis and occupational therapy.

Main Outcome Measures

Action Research Arm Test, box and block test of manual dexterity, Jebsen-Taylor Hand Function Test, and speed and accuracy of reaching movements with and without visual guidance.

Results

In this experienced prosthesis user, provision of a new prosthesis led to an immediate worsening in functional limitation. With training, the subject recovered his baseline status and then exceeded it in both proximal and distal function. All study clinical measures detected change, but the change detected varied as much as 300-fold depending on the measure chosen. The clinical improvements were associated with modest improvements in the speed of reaching but not the accuracy of reaching under visual guidance. Improvements in reaching accuracy without visual guidance were seen after 10 trials, suggesting that some motor learning had occurred.

Conclusions

Provision of a new prosthesis can cause functional decline even in an experienced user; this decline can be reversed with training. There is wide variability in sensitivity to change among functional limitation measures. Although some training-related improvements may have been due to increased speed and accuracy of reaching without visual guidance, skill in prosthesis use also plays a role.     

Obesity increases the incidence of 7,12-dimethylbenz(a)anthracene-induced mammary tumors in an ovariectomized Zucker rat model

Obesity is associated with increased risk for postmenopausal, but not premenopausal breast cancer. Recently, we reported that intact obese Zucker rats had increased susceptibility to DMBA-induced mammary tumors compared to lean Zucker rats. In the present study, we investigated whether excessive adipose tissue would promote mammary tumor induction in the absence of ovarian estrogen. Lean and obese rats were sham-operated or ovariectomized at 40 days old and were gavaged at 50 days old with 65 mg/kg DMBA. Rats were weighed and palpated twice weekly for detection of mammary tumors and sacrificed 135 days post-DMBA treatment. Obese sham-operated (O/S) rats had a shorter latency period (102 days) compared to lean sham-operated (L/S) (134 days) and obese ovariectomized (O/O) rats (123 days). At the end of the experiment, 36% of the O/O rats developed mammary tumors while lean ovariectomized (L/O) rats developed no mammary tumors (P<0.001), and 59% of the O/S rats developed mammary tumors compared to 30% of the L/S rats (P<0.05). In summary, obesity increases the susceptibility of ovariectomized Zucker rats to DMBA-induced mammary tumors, suggesting that adipose tissue-derived estrogen in obese animals may be sufficient to promote DMBA-induced tumors in this model. These results suggest that obesity in postmenopausal women may increase breast cancer risk due to increased breast tissue exposure to adipose tissue-derived estrogen. In conclusion, we have developed an animal model to further investigate the role of obesity in breast cancer development in postmenopausal women.     

Improving outcomes in geriatric surgery: Is there more to the equation?

The era of geriatric surgery has arrived with increased global life expectancy. The need to optimize outcomes in this group of patients goes beyond traditional outcomes such as postoperative morbidity and mortality indicators. Recognizing risk factors that impact adverse surgical outcomes such as frailty and sarcopenia, individualizing optimization strategies such as prehabilitation and a multidisciplinary geriatric surgical service have been shown to improve postoperative outcomes and help the older surgical patient regain premorbid function and maintain quality of life. There needs to be a concerted effort to increase awareness of this increasingly important topic in practicing surgeons around the world to meet the challenges of the aging population.     

Asymmetric segregation of mitochondria and mortalin correlates with the multi-lineage potential of inner ear sensory cell progenitors in vitro

The sensory epithelia of the inner ear include hair cells and supporting cells that share a common precursor. One possible mechanism involved in the genesis of these cell types is through asymmetric cell division. In this work we have studied asymmetric division of inner ear sensory cell progenitors in vitro in an attempt to understand how the different cell phenotypes are generated. In the search for molecules that will segregate asymmetrically we have found that mitochondria in general, and a mitochondrial protein named mortalin in particular, are asymmetrically segregated during certain cell divisions. In one conditionally immortal cell line (UB/OC-1), which represents a population of committed hair cell precursors, mortalin is uniformly distributed in the cytoplasm and shared equally between sibling cells during division. In another cell line (UB/UE-1), which represents a bipotent, vestibular supporting cell that can produce both neonatal hair cells as well as supporting cells, mortalin segregates asymmetrically. In UB/UE-1, approximately 12% of the cells display an asymmetric distribution of mortalin and mitochondria. The proportion of asymmetric cells increases immediately after the release of the immortalizing gene and before the onset of differentiation. The asymmetric segregation of mortalin in the bipotent cell line and its uniform distribution in a committed, lineage-restricted cell line raises the possibility that it may play a role in cell fate determination.     

Acute respiratory distress in a bleomycin primed patient: a new use for nitric oxide

We describe the use of nitric oxide as an oxygen-sparing strategy in the context of prior bleomycin exposure. A 27-year-old male, previously treated with bleomycin for a testicular germ cell tumour presented with severe acute respiratory distress syndrome on the second postoperative day following an extensive retroperitoneal dissection. The mechanism of bleomycin toxicity and potential benefits of nitric oxide in this situation are considered.     

Overexpression of H- and L-ferritin subunits in lens epithelial cells: Fe metabolism and cellular response to UVB irradiation.

PURPOSE. To determine the effect of changes in ferritin subunit makeup on Fe metabolism and the resistance of lens epithelial cells (LEC) to photo-oxidative stress. METHODS. Cultured canine LEC were transiently transfected with pTargeT mammalian expression vector containing the whole coding sequence of H- or L-chain cDNA. The subunit composition of newly synthesized ferritin was analyzed by metabolic labeling and SDS-PAGE electrophoresis. Total ferritin concentration was measured by ELISA. Fe uptake and incorporation into ferritin was determined by incubating transfected cells with (59)Fe-labeled transferrin followed by native PAGE electrophoresis. The effect of UV irradiation was assessed by cell count after exposure of transfected cells to UVB radiation. RESULTS. Transfected cells differentially expressed H- and L-ferritin chains from cDNA under the control of CMV promoter; overexpression of L-chain was much greater than that of H-chain. The expressed chains assembled into ferritin molecules under in vitro and in vivo condition. The ferritin of H-transfectants incorporated significantly more Fe than those of L-transfectants. The UVB irradiation reduced cell number of L-transfectants by half, whereas H-chain transfectants were protected. CONCLUSIONS. Post-transfectional expression of ferritin H- and L-chains in LEC appears to be regulated differentially. Overexpression of L-chain ferritin did not have a major effect on cellular Fe distribution and did not protect LEC against UV irradiation, whereas overexpression of H-chain resulted in increased storage of Fe in ferritin and protected cells from UV damage.