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Aims.: Anxiety is debilitating and associated with numerous mental and physical comorbidities. There is a need to identify and investigate low-risk prevention and treatment strategies. Therefore, the purpose of this study was to investigate cross-sectional and longitudinal associations between different volumes of moderate-to-vigorous physical activity (PA) and anxiety symptoms and status among older adults in Ireland. Methods.: Participants (n = 4175; 56.8% female) aged ⩾50 years completed the International PA Questionnaire (IPAQ) at baseline, and the anxiety subscale of the Hospital Anxiety and Depression Scale at baseline and follow-up (2009–2013). Participants were classified according to meeting World Health Organisation PA guidelines, and divided into IPAQ categories. Respondents without anxiety at baseline (n = 3165) were included in prospective analyses. Data were analysed in 2017. Results.: Anxiety symptoms were significantly higher among females than males (p < 0.001). Models were adjusted for age, sex, waist circumference, social class, smoking status and pain. In cross-sectional analyses, meeting PA guidelines was associated with 9.3% (OR = 0.91, 95% confidence interval 0.78–1.06) lower odds of anxiety. Compared with the inactive group, the minimally- and very-active groups were associated with 8.4% (OR = 0.92, 0.76–1.10) and 18.8% (OR = 0.81, 0.67–0.98) lower odds of anxiety, respectively. In prospective analyses, meeting guidelines was associated with 6.3% (OR = 0.94, 0.63–1.40) reduced odds of anxiety. Compared with the inactive group, the minimally and very-active groups were associated with 43.5% (OR = 1.44, 0.89–2.32) increased, and 4.3% (OR = 0.96, 0.56–1.63) reduced odds of anxiety. The presence of pain, included in models as a covariate, was associated with a 108.7% (OR = 2.09, 1.80–2.42) increase in odds of prevalent anxiety, and a 109.7% (OR = 2.10, 1.41–3.11) increase in odds of incident anxiety. Conclusion.: High volumes of PA are cross-sectionally associated with lower anxiety symptoms and status, with a potential dose–response apparent. However, significant associations were not observed in prospective analyses. The low absolute number of incident anxiety cases (n = 109) potentially influenced these findings. Further, as older adults may tend to experience and/or report more somatic anxiety symptoms, and the HADS focuses primarily on cognitive symptoms, it is plausible that the HADS was not an optimal measure of anxiety symptoms in the current population. [ABSTRACT FROM AUTHOR]

Objectives: To determine the rate of successful prosthetic fitting in geriatric vascular amputees in the community and to determine predictors of successful fit., Design: Epidemiologic survey., Setting: General community, Olmsted County, Minnesota., Patients: All Olmsted County residents more than 65 years old who had a major lower extremity amputation (below knee amputation [BKA] or higher) for peripheral vascular disease between 1974-1995, of whom 199 were identified. Median age at amputation was 79.7 years with a median survival of 1.5 years., Intervention: A retrospective chart review., Main Outcome Measure: Successful prosthetic fit., Results: Amputation levels were: 64% BKA, 4.5% knee disarticulation, 31% above knee amputation (AKA), and 0.5% hip disarticulation. Only 36% of the population was successfully fitted, compared with 74% of patients referred to the Amputee Clinic. Major reasons for not being fitted included death, reamputation, cerebrovascular disease, and cognitive deficits. Increased age (p < .001), cerebrovascular disease (p < .001), dementia (p = .002), and AKA (p < .001) were associated with failure to fit., Conclusion: The high probability of successful prosthetic fitting reported among referral practices cannot be generalized to unselected elderly individuals. However, selected individuals can successfully be fitted with a prosthesis; knowledge of predictors of prosthetic fitting may facilitate setting of realistic goals during presurgical counseling in this age group.

The care of patients at risk for amputation includes the identification of at-risk patients, appropriate follow-up and treatment, and the anticipation of possible complications. Education and long-term follow-up are vital for management of the patient at risk for amputation.

Matrix metalloproteinases are matrix degrading enzymes implicated in many biological processes, including development and inflammation. Gelatinase B (gelB; also known as MMP-9) is expressed in the kidney and is hypothesized to be involved in basement membrane remodeling and in preventing pathogenic accumulation of extracellular matrix in the kidney. Inhibition of gelB activity in metanephric organ culture disrupts branching morphogenesis of the ureteric bud, suggesting that gelB plays a role in kidney development in vivo. We studied kidneys of gelB-deficient mice to search for developmental, histological, molecular, ultrastructural, and functional defects. Surprisingly, no differences between gelB-/- and control kidneys were detected, and renal function was normal in gelB mutants. In addition, gelB-/- embryonic kidneys developed normally in organ culture. Gelatinase B-deficient mice were bred with Col4a3-/- mice, a model for Alport syndrome, to determine whether gelB influences the progression of glomerulonephritis. This is an important question, as it has been hypothesized that proteases are involved in damaging Alport glomerular basement membrane. However, the presence or absence of gelB did not affect the rate of progression of renal disease. Thus, gelB does not have a discernible role in the normal kidney and gelB is not involved in the progression of glomerulonephritis in a mouse model of Alport syndrome.

Using differential display, we have identified a novel gene, KPL1, induced in rat tracheal epithelial (RTE) cells grown under conditions which stimulate ciliogenesis. The KPL1 protein is predicted to contain a pleckstrin homology (PH) domain, which has been found in numerous signal transduction and cytoskeletal proteins. These domains are thought to function by recruiting proteins to cellular membranes, and they have been shown to bind phosphoinositols and the beta/gamma subunit of G proteins. We have cloned rat and human KPL1; the predicted protein translations are 94% identical. Alternate transcripts exist in rat and human tracheal cells that predict a protein which contains a 35-amino acid insert. KPL1 was upregulated in RTE cultures undergoing mucociliary but not squamous differentiation; and in cultures undergoing mucociliary differentiation, KPL1 expression most closely paralleled that of a marker of ciliated cell differentiation (axonemal dynein heavy chain) and not a marker of mucous cell differentiation (mucin 5AC). As a new member of the family of PH domain-containing proteins, KPL1 may have a unique role in ciliated cell differentiation or function.

Repeated doses of beta-radiation in the mouse skin model have been reported to produce carcinomas and sarcomas with equal frequency. Among sarcomas, fibrosarcomas and osteosarcomas have been the predominant reported histologies. In this report we describe the beta-radiation induction of rhabdomyosarcoma (RMS), a histology previously undescribed with tumor induction protocols using ionizing radiation in an animal model. Radiation-induced RMS is often seen as a secondary tumor following therapeutic irradiation for retinoblastoma in children. In our experiment the backs of 50 CD-1 mice were irradiated 3 times weekly for 35 weeks using a 90Sr source. The initial dose was 5.5 Gy/application, which was later reduced to 3 Gy after 15 weeks due to severe skin reactions. In all, 27 skin and subcutaneous tumors were seen and collected. Of 12 sarcomas seen, 9 had a rhabdoid histology; cell lines from 3 such tumors as well as a squamous-cell carcinoma (SCC) and a malignant fibrous histiocytoma (MFH) were established. Immunohistochemical analysis of their parent tumors showed that the rhabdoid tumors expressed desmin, which established the diagnosis of RMS. Two-dimensional gel electrophoresis and Western analysis of insoluble protein extracts confirmed that the cell lines from RMS tumors expressed desmin. A screen for molecular alterations identified a mutant p53 phenotype for RMS and MFH cell lines. These radiation-induced RMS cell lines provide a unique opportunity to study the molecular biology of this tumor in an animal model and will help provide insight into the mechanisms of radiation-induced RMS in humans.

Symptomatic bladder dysfunction occurs at some time in most patients with multiple sclerosis. The relapsing-remitting course and progressive loss of mobility associated with multiple sclerosis make management of urinary urgency and incontinence difficult. Urodynamic evaluation serves as a guideline for appropriate treatment. After accurate diagnosis of bladder dysfunction, a management program is developed with use of fluid schedules, voiding techniques, neuropharmacologic manipulation, intermittent catheterization, surgical treatment, and other adjunctive measures as indicated. The goals of treatment are to protect and preserve renal function, relieve symptomatic voiding dysfunction, and avoid subsequent urinary complications. A management program should be individualized, dynamic, and monitored with periodic, systematic urologic review to maintain these goals.

Glutathione plays an essential role in protecting the pulmonary system from toxic insults. gamma-Glutamyl transpeptidase-related enzyme (GGT-rel) is a novel protein capable of cleaving the gamma-glutamyl peptide bond of glutathione and of converting leukotriene C4 to leukotriene D4. A rat homologue of GGT-rel was identified and was found to be highly expressed in cultures of differentiating rat tracheal epithelial (RTE) cells. The 2.6-kb cDNA predicts a 572-amino acid protein with 79% identity to human GGT-rel. GGT-rel was weakly expressed in normal trachea but was strongly induced by epidermal growth factor in cultures of RTE cells. GGT-rel was also highly expressed in lung tumors induced by inhalation of isobutyl nitrite. These results demonstrate that GGT-rel 1) is expressed in normal tracheal cells, 2) can be induced by epidermal growth factor, and 3) is elevated after chemical exposure. The induction of high levels of GGT-rel may play an important role in protecting the lung from oxidative stress or other toxic insults.

This self-directed learning module highlights advances in the evaluation and management of the geriatric amputee. It is part of the chapter on rehabilitation in limb deficiency in the Self-Directed Physiatric Education Program for practitioners and trainees in physical medicine and rehabilitation. This article discusses the impact of aging and comorbid factors on the function of the geriatric amputee. Specific clinical examples are provided to illustrate management issues. Advances that are covered include prosthetic management and modifications for the elderly.

Objective: To describe the causes, evaluation, and management of urinary incontinence in the elderly population., Design: We reviewed pertinent articles in the medical literature and summarized the types of incontinence and contributing factors., Results: Urinary incontinence is common in elderly patients and often has a major role in determining whether a person can remain independent in the community or requires nursing home placement. Urinary incontinence is not a single entity but rather several different conditions, each with specific symptoms, findings on examination, and recommended treatment. Thus, accurate classification is important for appropriate management. Because of the complexity of urinary incontinence, many physicians are uncomfortable with undertaking assessment and treatment. Hence, many patients are not asked about incontinence, and the condition remains untreated and often considered a natural consequence of the aging process. Urinary incontinence can be treated and either cured or alleviated with treatment., Conclusion: Elderly patients should be asked about symptoms of urinary incontinence because appropriate assessment and treatment can usually provide relief.

Objective: To describe important aspects of pressure ulcer prevention and management, especially in elderly patients., Design: We reviewed pertinent published material in the medical literature and summarized effective strategies in the overall management of the elderly population with pressure ulcers., Results: Pressure ulcers are commonly encountered in geriatric patients. The development of a pressure ulcer is associated with an increased risk of death. Certain well-recognized risk factors, such as immobility and incontinence, may predispose to the development of pressure ulcers; consequently, risk factor modification is an important aspect of prevention and treatment. For existing lesions, various innovative patient support surfaces and wound care products have been developed to alleviate pressure and to facilitate wound healing. The use of a particular product should be based on the clinical setting and the limited scientific evidence available. With treatment, most pressure ulcers eventually heal., Conclusion: Pressure ulcers are often, but not always, preventable. The occurrence of such an ulcer signals the possible presence of chronic comorbid disease and should prompt a search for underlying risk factors in patients for whom ulcer treatment is considered appropriate.

Many studies have tested the insulin absorption rate and mechanical reliability of jet injectors. However, no published papers have dealt exclusively with patient preference for this method of administering insulin over a period of years. This paper reports the results of a survey done to determine if use of a jet injector for delivering insulin has an effect on acceptance of and adherence to a regimen of multiple doses of insulin. Over the past 15 years, the authors have instructed approximately 70 patients to use various jet injectors. A questionnaire was developed and sent to 75 patients. Of these, 42 completed and returned the questionnaire. Survey results indicate that even though some problems with the injectors were identified, 70% of those responding still preferred to take insulin by jet injector.

We have generated milligram quantities of human monoclonal antibodies (Hu-MAbs) in the ascites of pristane-primed nude mice injected with human-mouse heterohybridomas. After contaminating mouse immunoglobulins were removed by affinity chromatography, an enzyme immunosorbent assay (EIA) was used to measure the concentrations of human immunoglobulins. Ten different partially purified preparations were tested. The titration curves with all 5 IgG Hu-MAbs were unusual, reaching a plateau at a very low apparent maximum concentration of antibody. In contrast, the EIA yielded more usual titration curves and thus apparently more reliable estimates of the concentrations of 4 IgM and 1 IgA monoclonal antibodies. An analogous EIA for the quantitation of mouse IgG monoclonal antibodies also gave accurate estimates. To understand the nature of the discrepancy with human IgG, 5 Hu-MAbs of the 3 classes (2 IgG, 2 pentameric IgM and 1 IgA) were purified to homogeneity for a more detailed analysis. The inability to quantitate the human IgG monoclonal antibodies by EIA was not due to defective molecules, as shown by SDS polyacrylamide gel electrophoresis. The human IgG monoclonal antibodies were found to consist of intact heavy and light chains, as were the IgM and IgA antibodies. The possibility that the human IgG monoclonal antibodies differed antigenically from polyclonal IgG was explored by comparing the concentrations by EIA with the protein concentrations determined by absorbance at 280 nm. This analysis permitted a comparison of the detectability of antigenic determinants on Hu-MAbs with those on polyclonal Ig with goat antibodies to Ig or Ig subclass. The IgG monoclonal antibodies differed from polyclonal IgG in both their heavy and light chains. Goat antiserum monospecific for the gamma chain in fact underestimated the concentration by as much as one hundred-fold. IgM and IgA monoclonal antibodies were less antigenically distinct from their polyclonal counterparts even though their light chains were also underestimated, because goat monospecific antibodies were more efficient at recognizing their heavy chains. The molecular basis for the observed difference in antigenicity is not yet known. These findings have important implications for the analysis of the binding of IgG Hu-MAbs. A direct binding assay with the label directly conjugated to the Hu-MAb should be used in preference to an indirect assay with a labeled detecting antibody to maximize the sensitivity of the assay. The altered antigenicity of IgG Hu-MAbs may also imply decreased immunogenicity when they are given in vivo as carriers for radionuclides or cytotoxic antitumor materials.