Foot pain in later life: some psychosocial correlates

What we have just described is a collection of problems that mark our aged of today and clearly indicate that primary foot care should be provided as a primary health service for the elderly, the mentally ill, the emotionally ill, the retarded, the blind, and others with chronic diseases. For if any of the primary problems were present on any other part of the body, except the foot, they would be provided as a covered service under the current Medicare regulations. One might ask if the foot is not a part of the anatomy and if perhaps we have forgotten the words of the classic song, which proclaims that the foot bone is connected to the head bone. The author might add a "footnote" ... in so many ways. To achieve the desired outcome of having podiatric services available to all aging patients, foot care must be integrated into all comprehensive forms of health care delivery, so that podiatric care becomes a primary service, thus permitting patients to maintain an optimal level of foot health and general health. The ability to walk requires a catalyst--foot health. Keeping patients walking is a goal that has been a part of the podiatric profession since its inception over a century ago. With the high prevalence of foot problems in the elderly, and especially in those with chronic disease and mental impairment, the needs for the future are significant. It has been projected that we as a nation and society cannot afford to deliver a maximum level of health care for the elderly. In truth, we cannot afford not to provide these basic and needed services. For it is our society that has prolonged life. It is now our responsibility to provide life for these precious given years and to assure dignity for those who have made life better for all of us.     

Assessing onychial disorders in the older patient

Disorders and diseases of the toenails (onychial) in the older patient are often the focus of the primary foot complaints. They may be a result of the aging process, the end result of repetitive microtrauma or historical major trauma, a complication or related clinical change associated with a multiple system disease or condition, or a localized foot problem. This article details the symptoms of and problems associated with onychial disorders in the elderly.     

Beta-lactamases: a survey of protein diversity

Bacterial resistance to beta-lactam antibiotics and beta-lactamase inhibitors is an ever increasing problem that threatens the clinical utility of drugs that form the cornerstone of the antibiotic armamentarium. Especially among Gram-negative pathogens, elaboration of structurally and mechanistically novel beta-lactamase enzymes is the most important means by which resistance occurs. An appreciation of the tremendous diversity of these drug-modifying enzymes will assist in understanding why so few generally effective inhibitory agents exist for these unique drug targets. This review will give a general background on the reaction mechanisms and classification schemes of the more than 340 beta-lactamase enzymes described to date. A discussion will follow highlighting the emerging Class A SHV and TEM-derived extended-spectrum (ESBLs), and inhibitor-resistant enzymes, non-TEM, non-SHV Class A ESBLs, and carbapenemases, Class B metallo-beta-lactamases and some of their novel inhibitors, plasmid and chromosomally encoded Class C enzymes, and finally, the OXA-type oxacillinases, ESBLs, and carbapenemases of Class D. The clinical importance of multiple resistance mechanisms in conjunction with the production of beta-lactamase enzymes is emphasized.     

Spontaneous canine mast cell tumors express tandem duplications in the proto-oncogene c-kit

Spontaneous mast cell tumors (MCT) are the most common malignant neoplasm in the dog, representing between 7% and 21% of all canine tumors, an incidence much higher than that found in humans. These tumors often behave in an aggressive manner, metastasizing to local lymph nodes, liver, spleen, and bone marrow. The proto-oncogene c-kit is known to play a critical role in the development and function of mast cells. Point mutations in the kinase domain of c-kit leading to tyrosine phosphorylation in the absence of ligand binding have been identified in three mastocytoma lines, (P815, RBL, and HMC-1), and some human patients with various forms of mastocytosis. We now demonstrate that although c-kit derived from canine MCT did not contain the previously described activating point mutations, 5 of the 11 tumors analyzed possessed novel mutations consisting of tandem duplications involving exons 11 and 12. We also show that one such duplication, detected in a canine mastocytoma cell line, was associated with constitutive phosphorylation of c-kit protein (KIT), suggesting that these mutations may contribute to the development or progression of canine MCT.     

Dietary fat, body weight, and cancer: contributions of studies in rodents to understanding these cancer risk factors in humans

Understanding diet and energy balance as risk factors for breast, colon, and other cancers requires information on the contribution of each factor and of interactions among factors to cancer risk. Rodent models for breast cancer provide extensive data on effects of dietary fat and calories, energy balance, body weight gain, and physical activity on tumor development. Analyses of the combined data from many studies have shown clearly that quality and quantity of dietary fat and energy balance contribute independently to increased mammary gland tumorigenesis. These findings were seen in female rats fed diets high in fat (35-40% of calories) compared to rats fed control diets, with approximately 10% of calories as fat (Fay and Freedman, 1997, Breast Cancer Res. Treat. 46, 215-223). The methods used permit comparison of experimental and epidemiological data, and they may be useful in extrapolating between species and developing public health recommendations. In addition to the contributions of lifetime-diet composition, intake, energy balance, and physical activity to cancer risk, there are questions about the timing and duration of alterations in these factors and about the "dose-response" characteristics of cancer risk to the factors. Endocrine mechanisms may be significant in mammary gland tumor risk, but experimental and epidemiological data indicate that cancers at other sites, such as colon and liver, also are influenced by the factors listed. Other diet and lifestyle factors that influence energy, or specifically fat, metabolism may also affect risk for cancers that are promoted by increased intake of fat and calories. Studies of separate and interactive effects of dietary fat, black tea, weight gain, and mammary gland tumorigenesis (Rogers, et al, 1998, Carcinogenesis 19, 1269-1273) have been analyzed. Using adjustment of carcinogenesis endpoints for body weight, tumor burden, and latency, they were found to be related to weight gain within treatment groups in 2 of 3 experiments.