Outcomes of percutaneous endoscopic gastrostomy in dementia patients.
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Biomedical subjects
Publications and source records attributed to T Nikolaus.
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The type III secretion system encoded by Salmonella pathogenicity island 2 (SPI2) is required for systemic infections and intracellular accumulation of Salmonella enterica. This system is induced by intracellular Salmonella and subsequently transfers effector proteins into the host cell. Growth conditions either inducing expression of the type III secretion system or the secretion of substrate proteins were defined. Here we report the identification of a set of substrate proteins consisting of SseB, SseC, and SseD that are secreted by the SPI2 system in vitro. Secretion was observed if bacterial cells were exposed to acidic pH after growth in minimal medium with limitation of Mg(2+) or phosphate. SseB, -C, and -D were isolated in a fraction detached from the bacterial cell surface by mechanical shearing, indicating that these proteins are predominantly assembled into complexes on the bacterial cell surface. The three proteins were required for the translocation of SPI2 effector proteins SspH1 and SspH2 into infected host cells. Thus, SseB, SseC, and SseD function as the translocon for effector proteins by intracellular Salmonella.
Some 25-50% of all elderly persons living at home suffer from chronic pain. Among nursing home residents, the figures are appreciably higher, ranging between 45% and 80%. The major causes of pain in old age are degenerative joint disease, lower back pain, cancer, osteoporosis and herpes zoster, polymyalgia rheumatica, and arterial occlusive disease. In many cases, chronic pain goes undiagnosed and is not properly treated. When a correct diagnosis is established, however, it is almost always possible to achieve adequate pain relief by a combination of non-drug treatment and analgesics, and thus to improve the patient's quality of life.
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Preventive home visits with multidimensional geriatric assessment have been shown to delay or prevent the onset of disability and reduce nursing home admissions in older people. The purpose of the present study was to develop and test a multidimensional instrument for in-home preventive assessments in older persons. In developing the instrument, we conducted a systematic literature review of risk factors for functional status decline and of appropriate instruments for measuring these risk factors. Based on an Expert Panel using a modified Delphi process [1] the risk factor domains for functional status decline were chosen, [2] the instruments for evaluating each of the included risk factor domains were selected, and [3] the individual instruments were combined into one comprehensive assessment instrument. A German language version of the original English version of the instrument was developed based on translation, backtranslation, and cultural adaptation. The feasibility of use of the new instrument was evaluated in a field test in 150 people aged 75 years and older in Hamburg, Ulm, Germany, and Bern, Switzerland. The instrument was well accepted by the older persons. The prevalence of risk factors for functional status decline in these populations (e.g., physical inactivity, urinary incontinence, vision impairment) was high. There was also a high prevalence of underuse of preventive care measures (e.g., no pneumococcal vaccination in over 95 percent of persons). These preliminary results support the possible usefulness of this instrument for conducting preventive home visits or for epidemiological purposes (e.g., prevention surveillance). In a next phase, the test-retest reliability of the instrument, and the feasibility and reliability of self-administration as compared to interviewer administration will be described in a separate paper.
BACKGROUND: In Germany the implementation of specialized wards for the care of stroke patients is proposed. However, which type of organized inpatient stroke unit care is most effective and which group of patients will benefit most remains unclear. METHODS: Based on the analyses of the Stroke Unit Trialists' Collaboration this paper reports results of randomized and quasi-randomized trials that compared organized inpatient (stroke unit) care with contemporary conventional care. The primary analyses examined death, dependency and institutionalization. Secondary outcome measures included patient quality of life, patient and carer satisfaction and length of stay in hospital and/or institution. RESULTS: The analysis of twenty trails with 3864 patients showed a reduction in the rate of deaths in the stroke unit group as compared with the control group (OR 0.83, 95% CI 0.71-0.97). The odds of death or institutionalized care were lower (OR 0.76, 95% CI 0.65-0.90) as were death or dependency (OR 0.75, 95% CI 0.65-0.87). The results were independent of patient age, sex, stroke severity, and type of stroke unit organization. CONCLUSION: Organized care in stroke units resulted in benefits for stroke patients with regard to survival, independence, and probability of living at home. However, these results refer exclusively to Anglo-American and Scandinavian trials. German stroke unit services are organized in a different way. No data about the effectiveness of the German model is yet available.
Hypertension increases in prevalence with age. Population based studies suggest that more than 50% of people over the age of 65 years may have chronic hypertension. Hypertension, especially systolic hypertension, is the single most common, powerful, however, treatable risk factor for cardiovascular morbidity and mortality in the elderly. In order to assess the effectiveness of antihypertensive drug therapy among the elderly, with diuretics, beta-blockers and calcium channel blockers, a literature search was performed at the Cochrane Library, Medline and Excerpta medica. The Cochrane Hypertension Group identified 14 randomised controlled trials of at least one year duration with 21,785 elderly subjects where diuretics, beta-blockers or calcium channel blockers were used in the treatment group as first line drugs. In their meta-analysis (including one small trial with a central acting antiadrenergic drug) there was a decrease in total mortality (111 vs 129 deaths) and cardiovascular morbidity and mortality (126 vs 177 events) within the treatment group. The three trials restricted to persons with isolated systolic hypertension indicated beneficial effects in the treatment group with regard to cardiovascular morbidity and mortality (104 vs 157 events). Trial data on adverse effects is limited. In three studies, where adverse effects were reported, no substantial differences between treatment and control groups in measures of physical, cognitive and emotional function were found. Cardiovascular benefits of treatment with low dose diuretics or beta-blockers are cleared for elderly subjects with either diastolic or isolated systolic hypertension. Treatment with a long-acting dihydropyridine calcium channel blocker shows beneficial effects in reducing cardiovascular morbidity and mortality for elderly people with isolated systolic hypertension. Due to inconsistent findings in a subgroup meta-analysis of antihypertensive drug treatment in very old people, the efficacy of antihypertensive treatment in these subjects still remains unclear.
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Nursing homes are important, but often neglected, facilities for the care of frail older people. The demand for nursing home capacity in Germany will continue to increase over the next decade despite improvements in infrastructure of home care and day care centers. The leading medical reason for this is the growing number of elderly persons suffering from neurodegenerative diseases, depression, and stroke. Currently, more than 650,000 residents are in various forms of institutionalized care in Germany. To date, the medical profession has shown little interest in establishing an efficient medical care system for such patients, nor are care-providing physicians required to undergo special training in Germany. The article describes current practice and future principles of geriatric treatment.
The purpose of the study was to identify associations between drug prescriptions and the risk of falls in community-dwelling frail elderly people. 360 frail elderly patients underwent a comprehensive geriatric assessment during hospital stay. After discharge, the home falls were recorded by a questionnaire during the follow-up year and a home visit was carried out at the end of the year. Of 279 final patients with complete data, 141 subjects (50.5%) fell once; 62 subjects (22.2%) had a history of two or more falls during the follow-up period. Compared with subjects who did not fall or fell at the most once, those subjects with two or more falls showed a significantly higher prescription of tranquillizers/hypnotics, neuroleptics, diuretics, nitrates, and five or more different drugs. In multivariate analysis the prescription of tranquillizers/hypnotics with an adjusted odds ratio of 2.02 (95 percent confidence interval, 1.14 to 3.68) and the prescription of five or more different drugs with an adjusted odds ratio of 2.25 (95 percent confidence interval, 1.03 to 4.49) were found to be independent risk factors for multiple falls. In this prospective study in community-dwelling frail, elderly people the prescription of tranquillizers/hypnotics and five or more different medications could be identified as independent risk factors for multiple falls.
OBJECTIVE: to examine mortality, mobility, pain, institutionalization rates six month after hip fractures. DESIGN: observational study, non-selected consecutive patients, time-set protocol. SETTING: urban area (population n = 116,5000), five hospitals. PARTICIPANTS: hip fracture patients (n = 214), age 65 + years (mean 82.4 years). MEASUREMENTS: age, gender, prefracture status, operative procedures, complications, comorbidity, cognition (MMSE), depression (GDS), fear of falling, ADL (Barthel) and mobility and pain status (SAHFE protocol). RESULTS: the incidence for this age group was 636.9/100,000, 31.8% were institutionalized elderly. 84% of the patients were female. Pre-existing comorbidity showed a high prevalence of neurodegenerative (cognitive deficits 53. 6%, Parkinson's disease/syndrome 11.2%) and cerebrovascular diseases (16.8%). Six month postfracture, the mortality was 17.6%. From those surviving 76.2% did walk indoors, 58.5% did also walk outdoors. Independent to dress were 54.6%. Severe pain was reported by 10.2%, whereas 36.9% described no pain. The institutionalization rate at six month was 19.0%. CONCLUSIONS: the study showed considerable mortality, a significant loss in function and social disintegration. Considerable differences were observed for subgroups of patients. Future treatment should focus on risk stratification and include postdischarge training programs. Moreover, preventive strategies should be implemented for high risk groups, such as ambulating patients with a history of stroke. Parkinson's disease and syndrome, dementia and nursing home residents.
To lay the groundwork for devising, improving and implementing strategies to prevent or delay the onset of disability in the elderly, we conducted a systematic literature review of longitudinal studies published between 1985 and 1997 that reported statistical associations between individual base-line risk factors and subsequent functional status in community-living older persons. Functional status decline was defined as disability or physical function limitation. We used MEDLINE, PSYCINFO, SOCA, EMBASE, bibliographies and expert consultation to select the articles, 78 of which met the selection criteria. Risk factors were categorized into 14 domains and coded by two independent abstractors. Based on the methodological quality of the statistical analyses between risk factors and functional outcomes (e.g. control for base-line functional status, control for confounding, attrition rate), the strength of evidence was derived for each risk factor. The association of functional decline with medical findings was also analyzed. The highest strength of evidence for an increased risk in functional status decline was found for (alphabetical order) cognitive impairment, depression, disease burden (comorbidity), increased and decreased body mass index, lower extremity functional limitation, low frequency of social contacts, low level of physical activity, no alcohol use compared to moderate use, poor self-perceived health, smoking and vision impairment. The review revealed that some risk factors (e.g. nutrition, physical environment) have been neglected in past research. This review will help investigators set priorities for future research of the Disablement Process, plan health and social services for elderly persons and develop more cost-effective programs for preventing disability among them.
Two large virulence loci encoding type III secretion systems are present on the chromosome of Salmonella typhimurium. Salmonella pathogenicity island 2 (SPI2) is important for the survival of S. typhimurium in host organs and forms an insertion of about 40 kb at the tRNA(Val) gene. However, several indications suggested that SPI2 was not the result of a single event of horizontal gene transfer. We characterized the portion of SPI2 towards the 30 cs boundary and performed mutational analysis to investigate the contribution of this region to S. enterica virulence. This analysis indicates that SPI2 may be composed of at least two different genetic elements. About 15 kb of the 40 kb of SPI2 contain genes without a significant contribution to systemic infections in the model of murine salmonellosis. Our study allowed us to define genes in SPI2 important for virulence further and indicated that this locus has a complex mosaic structure.
The enteric pathogen Salmonella typhimurium co-ordinates the expression of virulence determinants in response to environmental cues from the host organism. S. typhimurium possesses Salmonella pathogenicity island 2 (SPI2), a large virulence locus encoding a type III secretion system for virulence determinants required for systemic infections and accumulation inside host cells. We have generated transcriptional fusions to SPI2 genes to analyse expression and used antibodies against recombinant SPI2 proteins to monitor levels of SPI2 proteins under various conditions. Here, we demonstrate that SPI2 gene expression is induced by Mg2+ deprivation and phosphate starvation. These conditions are likely to represent the environmental cues encountered by S. typhimurium inside the phagosome of infected host cells. The induction of SPI2 gene expression is modulated by the global regulatory system PhoPQ and is dependent on SsrAB, a two-component regulatory system encoded by SPI2.
A range of bacteria are able to use tetrathionate as a terminal respiratory electron acceptor. Here we report the identification and characterization of the ttrRSBCA locus required for tetrathionate respiration in Salmonella typhimurium LT2a. The ttr genes are located within Salmonella pathogenicity island 2 at centisome 30.5. ttrA, ttrB and ttrC are the tetrathionate reductase structural genes. Sequence analysis suggests that TtrA contains a molybdopterin guanine dinucleotide cofactor and a [4Fe-4S] cluster, that TtrB binds four [4Fe-4S] clusters, and that TtrC is an integral membrane protein containing a quinol oxidation site. TtrA and TtrB are predicted to be anchored by TtrC to the periplasmic face of the cytoplasmic membrane implying a periplasmic site for tetrathionate reduction. It is inferred that the tetrathionate reductase, together with thiosulphate and polysulphide reductases, make up a previously unrecognized class of molybdopterin-dependent enzymes that carry out the reductive cleavage of sulphur-sulphur bonds. Cys-256 in TtrA is proposed to be the amino acid ligand to the molybdopterin cofactor. TtrS and TtrR are the sensor and response regulator components of a two-component regulatory system that is absolutely required for transcription of the ttrBCA operon. Expression of an active tetrathionate reduction system also requires the anoxia-responsive global transcriptional regulator Fnr. The ttrRSBCA gene cluster confers on Escherichia coli the ability to respire with tetrathionate as electron acceptor.
OBJECTIVE: to prove the effectiveness of geriatric evaluation and management for elderly, hospitalized patients, combined with post-discharge home intervention by an interdisciplinary team. DESIGN: randomized controlled trial with outcome and costs assessed for 12 months after the date of admission. SETTING: university-affiliated geriatric hospital and the homes of elderly patients. SUBJECTS: 545 patients with acute illnesses admitted from home to the geriatric hospital. INTERVENTIONS: patients were randomly assigned to receive either comprehensive geriatric assessment and post-discharge home intervention (intervention), comprehensive geriatric assessment alone (assessment) or usual care. MAIN OUTCOME MEASURES: survival, functional status, rehospitalization, nursing home placement and direct costs over 12 months. RESULTS: the intervention group showed a significant reduction in length of hospital stay (33.49 days vs 40.7 days in the assessment group and 42.7 days in the control group; P < 0.05) and rate of immediate nursing home placement (4.4% vs 7.3% and 8.1%; P < 0.05). There was no difference in survival, acute care hospital readmissions or new admissions to nursing homes but the intervention group had significantly shorter hospital readmissions (22.2 days vs 34.2 days and 35.7 days; P < 0.05) and nursing home placements (114.7 days vs 161.6 days and 170.0 days; P < 0.05). Direct costs were lower in the intervention group [about DM 7000 (US $4000) per person per year]. Functional capacities were significantly better in the intervention group. CONCLUSIONS: comprehensive geriatric assessment in combination with post-discharge home intervention does not improve survival, but does improve functional status and can reduce the length of the initial hospital stay and of subsequent readmissions. It can reduce the rate of immediate nursing home admissions and delay permanent nursing home placement. It may also substantially reduce direct costs of hospitalized patients.
The potential use as vaccine delivery system of Salmonella typhimurium strains harboring defined mutations in the sseC (HH104) and sseD (MvP101) genes, which encode putative effector proteins of the type III secretion system of Salmonella pathogenicity island 2, was evaluated and compared with that of the well-characterized aroA mutant strain SL7207 by using beta-galactosidase (beta-Gal) as a model antigen. When orally administered to immune-competent or gamma interferon-deficient (IFN-gamma-/-) BALB/c mice, both mutants were found to be highly attenuated (50% lethal dose, >10(9) bacteria). Both strains were also able to efficiently colonize and persist in Peyer's patches. Immunization with HH104 and MvP101 triggered beta-Gal-specific serum and mucosal antibody responses equivalent to or stronger than those observed in SL7207-immunized mice. Although immunoglobulin G2 (IgG2) serum antibodies were dominant in all groups, IgG1 was also significantly increased in mice vaccinated with MvP101 and SL7207. Comparable beta-Gal-specific IgA and IgG antibodies were detected in intestinal lavages from mice immunized with the different strains. Antigen-specific CD4(+) T-helper cells were generated after vaccination with all vaccine prototypes; however, responses were significantly more efficient when HH104 and MvP101 were used (P < 0.05). Significantly higher levels of IFN-gamma were produced by restimulated spleen cells from mice immunized with HH104 than from those vaccinated with the MvP101 or SL7207 derivatives (P </= 0.05). Interestingly, the three strains induced major histocompatibility complex class I-restricted CD8(+) cytotoxic T cells against beta-Gal; however, cytotoxic T-lymphocyte responses were significantly stronger after immunization with HH104 (P < 0.05). These novel S. typhimurium attenuated strains constitute promising delivery systems for vaccine antigens. The qualitative differences observed in the obtained responses with different carriers may be useful for those applications in which a targeted immunomodulation is required.
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