Polypharmacy in Older Adults: A Case Study.

Polypharmacy is defined as concurrent use of multiple drugs for one or more conditions. The occurrence of polypharmacy in vulnerable populations, particularly the elderly, is frequent. Increased incidents of adverse drug reactions and drug-drug interactions plus high costs are not offset by a noticeable improvement in outcome. The practice of polypharmacy persists despite frequent adverse outcomes and reduced effectiveness. We present a case in which an elderly woman presented with falls and delirium. She was taking multiple medications for anxiety and depression in addition to several psychoactive medications for pain, restless leg syndrome, muscle spasms, blood pressure and many nonpsychoactive medications for other conditions. In total, she was taking 24 medications, many of which were likely contributing to her presenting problems.

Anti-Oxidative Therapy in Diabetic Nephropathy.

Chronic kidney disease is generally progressive and currently has no reliable treatment to reverse a decline in kidney function or to slow the progression of the disease. Diabetic nephropathy is one of the leading causes of end-stage kidney failure. Kidney damage in diabetic nephropathy is largely attributed to the increased oxidative stress, affecting its metabolic activity, metabolic pathways, and hemodynamic pathways. In diabetic patients, hyperglycemia causes an increase in the production of reactive oxygen species that further increase oxidative stress. These reactive oxygen species are created through a variety of pathways, providing the opportunity for treatment using anti-oxidative defense mechanisms to prevent vascular injury. This review will give an overview of oxidative stress, along with the current treatments and limitations of diabetic nephropathy. We will also discuss the potential of antioxidative therapies, with an emphasis on the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway.

Dysregulation of ß-Cell Proliferation in Diabetes: Possibilities of Combination Therapy in the Development of a Comprehensive Treatment.

Diabetes mellitus (DM) is a metabolic disorder characterized by chronic hyperglycemia as a result of insufficient insulin levels and/or impaired function as a result of autoimmune destruction or insulin resistance. While Type 1 DM (T1DM) and Type 2 DM (T2DM) occur through different pathological processes, both result in ß-cell destruction and/or dysfunction, which ultimately lead to insufficient ß-cell mass to maintain normoglycemia. Therefore, therapeutic agents capable of inducing ß-cell proliferation is crucial in treating and reversing diabetes; unfortunately, adult human ß-cell proliferation has been shown to be very limited (~0.2% of ß-cells/24 h) and poorly responsive to many mitogens. Furthermore, diabetogenic insults result in damage to ß cells, making it ever more difficult to induce proliferation. In this review, we discuss ß-cell mass/proliferation pathways dysregulated in diabetes and current therapeutic agents studied to induce ß-cell proliferation. Furthermore, we discuss possible combination therapies of proliferation agents with immunosuppressants and antioxidative therapy to improve overall long-term outcomes of diabetes.

A Threat to Military Combat Power: Dietary Supplements.

BACKGROUND: The use of dietary supplements by young warfighters is pervasive and comes with a readiness cost, especially in the deployed setting. Predatory targeting and marketing by various unscrupulous companies put this population at risk for a higher than baseline risk for adverse events. METHODS: We report on 6 serious adverse events experienced by warfighters while deployed in Kuwait and Afghanistan. Presented is a discussion of current practice gaps and solutions, as well as details regarding how polypharmacy contributes to the seriousness of the threat posed by problematic supplements. RESULTS: The morbidity associated with the 6 cases of dietary supplement adverse events compromised mission readiness and was costly in terms of health and health care expenditures. CONCLUSION: The military dietary supplement issue needs exposure, review, and action at the highest levels of government.

An overview of current advancements in pancreatic islet transplantation into the omentum.

Pancreatic islet transplantation to restore insulin production in Type 1 Diabetes Mellitus patients is commonly performed by infusion of islets into the hepatic portal system. However, the risk of portal vein thrombosis or elevation of portal pressure after transplantation introduces challenges to this procedure. Thus, alternative sites have been investigated, among which the omentum represents an ideal candidate. The surgical site is easily accessible, and the tissue is highly vascularized with a large surface area for metabolic exchange. Furthermore, the ability of the omentum to host large volumes of islets represents an intriguing if not ideal site for encapsulated islet transplantation. Research on the safety and efficacy of the omentum as a transplant site focuses on the utilization of biologic scaffolds or encapsulation of islets in a biocompatible semi-permeable membrane. Currently, more clinical trials are required to better characterize the safety and efficacy of islet transplantation into the omentum.

Cryopreservation: An Overview of Principles and Cell-Specific Considerations.

The origins of low-temperature tissue storage research date back to the late 1800s. Over half a century later, osmotic stress was revealed to be a main contributor to cell death during cryopreservation. Consequently, the addition of cryoprotective agents (CPAs) such as dimethyl sulfoxide (DMSO), glycerol (GLY), ethylene glycol (EG), or propylene glycol (PG), although toxic to cells at high concentrations, was identified as a necessary step to protect against rampant cell death during cryopreservation. In addition to osmotic stress, cooling and thawing rates were also shown to have significant influence on cell survival during low temperature storage. In general, successful low-temperature cell preservation consists of the addition of a CPA (commonly 10% DMSO), alone or in combination with additional permeating or non-permeating agents, cooling rates of approximately 1ºC/min, and storage in either liquid or vapor phase nitrogen. In addition to general considerations, cell-specific recommendations for hepatocytes, pancreatic islets, sperm, oocytes, and stem cells should be observed to maximize yields. For example, rapid cooling is associated with better cryopreservation outcomes for oocytes, pancreatic islets, and embryonic stem cells while slow cooling is recommended for cryopreservation of hepatocytes, hematopoietic stem cells, and mesenchymal stem cells. Yields can be further maximized by implementing additional pre-cryo steps such as: pre-incubation with glucose and anti-oxidants, alginate encapsulation, and selecting cells within an optimal age range and functional ability. Finally, viability and functional assays are critical steps in determining the quality of the cells post-thaw and improving the efficiency of the current cryopreservation methods.

Improved cryopreservation yield of pancreatic islets using combination of lower dose permeable cryoprotective agents.

Islet transplantation has been shown to restore normoglycemia in animal models and for type 1 diabetic patients in clinical trials. One method of storing islets intended for transplantation is via cryobanking at very low temperatures (-196 °C). Cryobanking islets without the use of cryoprotecting agents (CPAs) contributes to cellular shear stress and cell death. Although current CPA protocols vary, high concentrations of these agents are toxic to islets cells. This study tested the effects of the permeating CPA dimethyl sulfoxide (Me2SO) with the addition of ethylene glycol (EG), both at reduced concentrations, on rat and human islet cell yield, viability, and glucose stimulated insulin release (GSIR). To test this, islets were treated using three combinations of CPAs (2M ME2SO, 1M ME2SO + 1M EG, and 1M ME2SO + 0.5M EG). Next, fresh islets, 2M ME2SO islets, and 1M ME2SO + 0.5M EG isolated rat islets were transplanted into streptozotocin-induced (STZ) diabetic mice. Our data showed that cryopreservation with a reduced concentration of ME2SO (1M ME2SO + multimolar EG) achieved a higher percent yield and viability when compared to the current standard 2M ME2SO treatment for both rat and human islets. Furthermore, STZ-induced diabetic mice achieved normoglycemia after transplantation with 1000 islet equivalents (IE), an average 12 days sooner, with islets cryopreserved with reduced-concentration (ME2SO + 0.5M EG), compared to islets preserved with 2M ME2SO. In conclusion, reduced concentration of penetrating CPAs during islet cryopreservation increases islet yield and viability in vitro and reduces delay before normoglycemia in diabetic mice.

Reprising the taxonomy of Cyprus Scops Owl Otus (scops) cyprius, a neglected island endemic.

The endemic Cyprus Scops Owl Otus (scops) cyprius has been treated as a subspecies of the widespread Eurasian Scops Owl O. scops since at least the 1940s. However, its song is distinct from that of all other subspecies of O. scops in being double-noted, rather than single-noted. Its plumage also differs, most obviously in being consistently darker than other subspecies and in lacking a rufous morph. However, it shows no biometric differences from O. s. cycladum and southern populations of O. s. scops. It is also unusual among scops (s. l.) populations in being at least partially resident, although two specimens showing characters of this taxon were collected in Israel in early spring, and the numbers of birds that are resident on Cyprus appear to vary, with few recent winter records. It differs from O. s. scops by one synapomorphic nucleotide exchange in the analysed mitochondrial marker, indicating a recent separation. Given that large numbers of O. s. scops and O. s. cycladum pass through Cyprus on spring migration, and that the latter breeds in adjacent countries, it seems probable that cycladum would colonize the island, but for the presence of cyprius. That it does not do so, and that cyprius retains its distinctive song and plumage, suggests that isolating mechanisms exist. We recommend that cyprius be considered specifically distinct, as are other distinctively voiced insular Otus populations.

Clostridium infections associated with musculoskeletal-tissue allografts.

BACKGROUND: Allografts are commonly used in orthopedic reconstructive surgery. In 2001, approximately 875,000 musculoskeletal allografts were distributed by U.S. tissue banks. After the death from Clostridium sordellii sepsis of a 23-year-old man who had received a contaminated allograft from a tissue bank (Tissue Bank A), the Centers for Disease Control and Prevention initiated an investigation, including enhanced case finding, of the methods used for the recovery, processing, and testing of tissue. METHODS: A case of allograft-associated clostridium infection was defined as a culture-proven infection of a surgical site within one year after allograft implantation, from January 1998 to March 2002. We traced tissues to tissue banks that recovered and processed these tissues. We also estimated the rates of and risk ratios for clostridium infections for tissues processed by the implicated tissue bank and reviewed processing and testing methods used by various tissue banks. RESULTS: Fourteen patients were identified, all of whom had received allografts processed by Tissue Bank A. The rates of clostridium infection were 0.12 percent among patients who received sports-medicine tissues (i.e., tendons, femoral condyles, menisci) from Tissue Bank A and 0.36 percent among those who received femoral condyles in particular. The risk-ratio estimates for clostridium infections from tissues processed by Tissue Bank A, as compared with those from other tissue banks, were infinite (P<0.001) for musculoskeletal allografts, sports-medicine tissues, or tendons. Because Tissue Bank A cultured tissues only after treating them with a nonsporicidal antimicrobial solution, some test results were probably false negatives. Tissues from implicated donors were released despite the isolation of clostridium or bowel flora from other anatomical sites or reports of infections in other recipients. CONCLUSIONS: Clostridium infections were traced to allograft implantation. We provide interim recommendations to enhance tissue-transplantation safety. Tissue banks should validate processes and culture methods. Sterilization methods that do not adversely affect the functioning of transplanted tissue are needed to prevent allograft-related infections.

Pulmonary effects of welding fumes: review of worker and experimental animal studies.

BACKGROUND: Approximately one million workers worldwide perform welding as part of their work duties. Electric arc welding processes produce metal fumes and gases which may be harmful to exposed workers. METHODS: This review summarizes human and animals studies which have examined the effect of welding fume exposure on respiratory health. An extensive search of the scientific and occupational health literature was performed, acquiring published articles which examined the effects of welding on all aspects of worker and laboratory animal health. The databases accessed included PubMed, Ovid, NIOSHTIC, and TOXNET. RESULTS: Pulmonary effects observed in full-time welders have included metal fume fever, airway irritation, lung function changes, susceptibility to pulmonary infection, and a possible increase in the incidence of lung cancer. Although limited in most cases, animal studies have tended to support the findings from epidemiologic studies. CONCLUSIONS: Despite the numerous studies on welding fumes, incomplete information still exists regarding the causality and possible underlying mechanisms associated with welding fume inhalation and pulmonary disease. The use of animal models and the ability to control the welding fume exposure in toxicology studies could be utilized in an attempt to develop a better understanding of how welding fumes affect pulmonary health.

Surface sampling methods for Bacillus anthracis spore contamination.

During an investigation conducted December 17-20, 2001, we collected environmental samples from a U.S. postal facility in Washington, D.C., known to be extensively contaminated with Bacillus anthracis spores. Because methods for collecting and analyzing B. anthracis spores have not yet been validated, our objective was to compare the relative effectiveness of sampling methods used for collecting spores from contaminated surfaces. Comparison of wipe, wet and dry swab, and HEPA vacuum sock samples on nonporous surfaces indicated good agreement between results with HEPA vacuum and wipe samples. However, results from HEPA vacuum sock and wipe samples agreed poorly with the swab samples. Dry swabs failed to detect spores >75% of the time when they were detected by wipe and HEPA vacuum samples. Wipe samples collected after HEPA vacuum samples and HEPA vacuum samples collected after wipe samples indicated that neither method completely removed spores from the sampled surfaces.