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Biomedical subjects

S Rapp

Publications and source records attributed to S Rapp.

At least 19 recordsLinked to original sources

Analysis and cryopreservation of hematopoietic stem and progenitor cells from umbilical cord blood.

BACKGROUND: Umbilical cord blood (UCB) is an important source of hematopoietic stem and progenitor cells (HSC/HPC) for the reconstitution of the hematopoietic system after clinical transplantation. Cryopreservation of these cells is critical for UCB banking and transplantation as well as for research applications by providing readily available specimens. The objective of this study was to optimize cryopreservation conditions for CD34+ HSC/HPC from UCB. METHODS: Cryopreservation of CD34+ HSC/HPC from UCB after mononuclear cell (MNC) preparation was tested in a research-scale setup. Experimental variations were concentration of the cryoprotectant, the protein additive and cell concentration. In addition, protocols involving slow, serial addition and removal of DMSO were compared with standard protocols (fast addition and removal of DMSO) in order to avoid osmotic stress for the cryopreserved cells. Viability and recoveries of MNC, CD34+ cells and total colony-forming units (CFU) were calculated as read-outs. In addition, sterility testing of the collected UCB units before further processing was performed. RESULTS: The optimal conditions for cryopreservation of CD34+ HPC in MNC preparations were 10% DMSO and 2% human albumin at high cell concentrations (5 x 10(7) MNC/mL) with fast addition and removal of DMSO. After cryopreservation using a computer-controlled freezer, high viabilities (89%) and recoveries for CD34+ cells (89%) as well as for CFU (88%) were observed. Microbial contamination of the collected UCB samples was reduced to a rate of 6.4%. DISCUSSION: Optimized cryopreservation conditions were developed for UCB MNC in respect of the composition of the cryosolution. In addition, our results showed that fast addition of DMSO is essential for improved cryopreservation and post-thaw quality assessment results, whereas the speed of DMSO removal after thawing has little influence on the recoveries of CD34+ cells and CFU.

Antigens, CD34↗

Filter Buffy Coats (FBC): a source of peripheral blood leukocytes recovered from leukocyte depletion filters.

In compliance with federal regulations, blood banks routinely use leukocyte depletion filters to eliminate contaminating leukocytes from blood products such as red blood cell and platelet concentrates. We developed and optimized conditions to elute leukocytes adsorbed to these filters; resulting in leukocyte suspensions which we termed Filter Buffy Coats (FBCs). These Filter Buffy Coats can replace standard buffy coats for various research applications. After optimizing both the filter elution medium as well as elution protocols, we compared commonly used leukocyte depletion filters from four different manufacturers. Relative fractions as well as total recoveries of leukocyte subsets, such as lymphocytes, monocytes and granulocytes, found in Filter Buffy Coats were identified and compared among the filters as well as to standard buffy coats and whole blood. Flow cytometric analysis of Filter Buffy Coats confirmed the presence of T- and B-lymphocytes, NK cells and monocytes. Furthermore, a significant quantity of CD34(+) hematopoietic stem or progenitor cells (HSC/HPC) was detected in Filter Buffy Coats prepared from different filters, thus making FBCs a valuable source for research on HSC/HPC. Colony assays revealed that most of these CD34(+) cells are functional. Using immunomagnetic cell sorting (MACS), we isolated a variety of leukocyte populations from FBC mononuclear cells (Filter-PBMCs) including T lymphocytes (CD4(+), CD8(+), CD3(+)), B lymphocytes (CD19(+)), NK cells (CD56(+)), HSC/HPC (CD34(+), CD133(+)) or dendritic cells (BDCA-4(+)). Functional properties of Filter-PBMCs, as well as of some of these isolated leukocyte populations, were confirmed using standard assays. In summary, Filter Buffy Coats are a valuable and convenient source of different peripheral leukocyte populations and can replace standard buffy coat preparations for research applications.

Antigens, CD↗

Statins and cognitive function in the elderly: the Cardiovascular Health Study.

OBJECTIVE: To examine the association of statin drug use on cognitive and MRI change in older adults. METHODS: Participants in the Cardiovascular Health Study, a longitudinal study of people age 65 or older, were classified into three groups determined by whether they were taking statin drugs on a continuous basis, intermittently, or not at all. The untreated group was further divided into categories based on National Cholesterol Education Program recommendations for lipid-lowering treatment. Participants with prevalent or incident clinical TIA or stroke or with baseline Modified Mini-Mental State Examination (3MS) scores at or below 80 were excluded. Outcomes examined included rate of change on the 3MS over an average observational period of 7 years, along with changes in MRI white matter grade and measures of atrophy. RESULTS: Three thousand three hundred thirty-four participants had adequate data for analysis. At baseline, the untreated group in which lipid-lowering drug treatment was recommended were slightly older, less likely to be on estrogen replacement, and had higher serum cholesterol and lower 3MS scores than the statin-treated group. The rate of decline on the 3MS was 0.48 point/year less in those taking statins compared with the untreated group for which treatment was recommended (p = 0.069) and 0.49 point/year less in statin users compared with the group in which lipid-lowering treatment was not recommended (p = 0.009). This effect remained after controlling for serum cholesterol levels. One thousand seven hundred thirty participants with baseline 3MS scores of > 80 underwent cranial MRI scans on two occasions separated by 5 years. There was no significant difference in white matter grade change or atrophy measures between groups. CONCLUSION: Statin drug use was associated with a slight reduction in cognitive decline in an elderly population. This relationship could not be completely explained by the effect of statins on lowering of serum cholesterol.

Aged↗

[The STEMMAT-project as part of health initiative BayernAktiv: adult stem cells from umbilical cord and cord blood as alternative to embryonic stem cell research].

Adult stem cells from umbilical cord and cord blood are an interesting alternative to embryonic stem cells because such research is commonly recognized as ethical undisputed and many aspects are still insufficiently investigated. In the context of the STEMMAT research project (STEM = Stem Cell and MAT = Material) different aspects of stem cells from umbilical cord and cord blood are investigated, to improve basic science understanding and potentially leading someday to a clinical application.

Cord Blood Stem Cell Transplantation↗

[Synaptic vesicle proteins and psychiatric disorders].

Synaptic vesicle proteins modulate the release of neurotransmitters in the synaptic cleft via regulation of vesicle transport, membrane fusion and exocytosis. Due to their relevance for neural and synaptic plasticity, they represent an important object of molecular psychiatric research. There is increasing evidence that they play a significant role in the pathophysiology of several psychiatric disorders. Furthermore, psychotropic drugs differentially modify the expression of synaptic vesicle proteins; thus, this group of molecules is also of considerable interest from a therapeutic point of view.

Brain↗

Differential regulation of synaptic vesicle proteins by antidepressant drugs.

Synaptic vesicle proteins (SVP) play a critical role in neurotransmitter release and neural plasticity, and have been implicated in the pathophysiology of psychiatric disorders such as depression. Antidepressant drugs not only alter the level of neurotransmitters, but also modulate de novo gene transcription and synthesis of proteins involved in neural plasticity. In order to investigate the effects of antidepressant compounds on SVP-mRNA levels, the expressions of synaptophysin, synaptotagmin, VAMP, and synapsin-I were analysed by in situ hybridization in rats which had been treated with desipramine, fluoxetine, tranylcypromine, or saline. The results demonstrate that chronic treatment with fluoxetine and tranylcypromine leads to an increased expression of synaptophysin, but decreased expression of synaptotagmin and VAMP in the hippocampus and cerebral cortex. Additionally, synapsin I-mRNA levels in the hippocampus and cerebral cortex are significantly reduced in tranylcypromine-treated animals. This identifies SVP genes as target genes of antidepressant treatment.

Animals↗

Uncommon vascular naevi associated with focal acantholytic dyskeratosis.

Cutis marmorata telangiectatica congenita and vascular twin naevi are rare vascular anomalies in which focal acantholytic dyskeratosis is usually not observed. We describe a 44-year-old-man who presented for evaluation of skin lesions that had been present since birth. Physical examination revealed anaemic macules adjacent to a naevus telangiectaticus on the chest. Naevus anaemicus was also seen on the shoulders, arms, and left leg. There was bluish-reddish reticulate marking of the skin and cutaneous atrophy. Shortening and hypoplasia of the left leg was observed. Histologic examination of two biopsy specimens revealed focal acantholytic dyskeratosis. In vivo confocal laser scanning microscopy showed dilated capillaries and vessels of the upper dermal plexus in the telangiectatic and decreased capillary blood flow in the anaemic skin sites. The findings were consistent with a diagnosis of cutis marmorata telangiectatica congenita, vascular twin naevi, and incidental focal acantholytic dyskeratosis. The particularities of the present case are the following: firstly, the association of two rare vascular anomalies to which the genetic concept of mosaicism can be applied; secondly, the occurrence of incidental focal acantholytic dyskeratosis in sites of vascular naevi.

Acantholysis↗

Memory enhancement training for older adults with mild cognitive impairment: a preliminary study.

'Mild cognitive impairment' (MCI) in older adults refers to a significant decline in memory function but not other cognitive functions. Pharmacological and non-pharmacological treatments for MCI are needed. The present randomized clinical trial tests the efficacy of a cognitive and behavioral treatment to improve memory performance and participants' attitudes about their memory. A multi-faceted intervention that included education about memory loss, relaxation training, memory skills training, and cognitive restructuring for memory-related beliefs was compared to a no-treatment control condition. Outcomes included memory performance and appraisals of memory function and control. Results indicate that the treated group had significantly better memory appraisals than controls at the end of treatment and at a six-month follow-up. There were no differences between groups on memory performance at post-test but at follow-up the trained individuals showed a trend toward better word list recall than controls. Findings suggest that individuals with MCI can benefit from multi-component memory enhancement training. Further development of such training programs and tests of their efficacy alone and in combination with medications are needed.

Aged↗

Balneophototherapy of psoriasis: highly concentrated salt water versus tap water--a randomized, one-blind, right/left comparative study.

BACKGROUND/PURPOSE: Apart from climatotherapy and spa therapy, combined treatment with salt water baths and artificial UV radiation (balneophototherapy) has been advocated for the treatment of psoriasis. As there is a lack of controlled studies on balneophototherapy (BPT), we conducted a randomized, one-blind, right/left comparison with salt water versus tap water in order to investigate the significance of the salt concentration in the efficacy of BPT. METHODS: Ten psoriasis patients with chronic plaques on the elbows were included in the study. One elbow was soaked in 24% NaCl solution and the other in tap water. Subsequently, broadband UVB irradiation was administered. BPT was performed 4 times weekly with a total of 30 treatments. RESULTS: A highly significant (P<0.001) decrease of the clinical baseline score was observed after 30 treatments; however, there was no significant (P>0.5) difference in clearance of the psoriatic lesions between the sites soaked in salt water and tap water. CONCLUSION: Our results suggest that any additional benefit of soaking in salt water and tap water in BPT are unlikely to be due to the salinity of the liquids.

Adult↗

Self-efficacy and the progression of functional limitations and self-reported disability in older adults with knee pain.

OBJECTIVES: The prospective relationships between self-efficacy beliefs, in conjunction with measures of knee pain and knee strength, and subsequent decline in both physical performance and self-reported disability among older adults with knee pain were examined. METHODS: In this prospective epidemiological trial, 480 men and women aged 65 years and older who had knee pain on most days of the week and difficulty with daily activity were followed for 30 months. RESULTS: There was a significant interaction of baseline self-efficacy with baseline knee strength in predicting both self-reported disability and stair climb performance. Participants who had low self-efficacy and low strength at baseline had the largest 30-month decline in these outcomes. DISCUSSION: These data underscore the important role that self-efficacy beliefs play in understanding functional decline with chronic disease and aging. Self-efficacy beliefs appear to be most important to functional decline in older adults when they are challenged by muscular weakness in the lower extremities.

Activities of Daily Living↗

[Bilateral segmental neurofibromatosis simulating epidermal nevus].

Neurofibromatosis is a neuroectodermal systemic disease. A rare variant of this condition is bilateral segmental neurofibromatosis. A 29-year-old man presented with bilateral papillomatous plaques in the lumbar dermatomes. Clinically, the lesions were very similar to an epidermal nevus but histologic examination revealed superficial neurofibromas. Family history, ophthalmologic and neurologic investigations were unremarkable. The unusual morphologic presentation of bilateral segmental neurofibromas in this case points to the wide clinical spectrum of the disease and the significance of histologic examination in systematic nevoid lesions.

Adult↗

An examination of theory and behavior change in randomized clinical trials.

This paper underscores the important role played by theory-based mediating variables in randomized clinical trials. Indeed, it is essential that we know what mediating variables are relevant for particular outcomes in randomized clinical trials and that we design interventions to optimize change in the mediators of interest. Yet, knowledge of the pivotal mediating variables in behavior change does not imply that we know how to intervene effectively. This gap may be due to the fact that existing research typically has been designed to garner support for theory, as opposed to testing support for behavior change strategies that are based on theory. In addition, we argue that there are important mediating variables in behavior change that have not been given systematic attention in theory development. For example, behavior change must be viewed as a collaborative process, and participants' perceptions concerning the feasibility of change is important to motivational processes in randomized clinical trials. Control Clin Trials 2000;21:164S-170S

Aged↗

Hepatic artery embolization: factors predisposing to postembolization pain and nausea.

PURPOSE: Analysis of preprocedural factors that may be helpful in predicting the severity of pain and nausea after hepatic arterial embolization (HAE) for liver neoplasms. MATERIALS AND METHODS: During a 2-year period, 62 patients (33 men, 29 women) underwent 130 palliative lobar HAEs for unresectable liver neoplasms. The hepatic lobe was embolized with 150-250-microm polyvinyl alcohol particulates with or without lipiodol and/or chemotherapeutic agents. Postembolization pain was rated at rest and during movement with use of an 11-point verbal pain scale, and postembolization nausea was assessed with use of a four-point verbal scale, each at two separate time periods. Daily morphine use was also recorded. Primary analysis was made using the first embolization procedure. One-way analysis of variance and Spearman correlation coefficients were used to identify associated predictors. Plots of the outcomes versus the pre-embolization liver function tests and sensitivities and specificities were used to identify the strength of the associations for prediction purposes. A secondary analysis was performed in patients who underwent multiple embolizations. RESULTS: No strong categorical predictors were found from the ANOVA on the severity of postembolization pain or nausea. There were significant (P < .05) associations between the pre-embolization liver function tests and the pain outcomes only. However, while these laboratory values demonstrate strong associations with resultant pain, they are not strong predictors of pain and morphine requirements for any individual patient. The morphine requirements were highly associated (P < .0001) with the pain scores at rest and with movement. The authors did not find significant differences on any of the pain outcomes or morphine requirements between the first and second embolizations. CONCLUSION: Laboratory values and patient age are not predictors for the severity of postembolization pain and nausea. Postembolization pain is a significant complication and poses a continuing challenge to the physician with regards to patient management.

Adult↗

Deep shave excision of macular melanocytic nevi with the razor blade biopsy technique.

BACKGROUND: Shave excision is an established surgical method for removing benign skin lesions for cosmetic and functional reasons. Usually superficial shave excision is performed with a common scalpel blade for the removal of papular nevi. However, there is little known about deep shave excision of macular melanocytic nevi with the razor blade technique. OBJECTIVE: The present study was undertaken to evaluate the cosmetic outcome of deep shave excision of macular melanocytic nevi with the razor blade technique. Moreover, its potency for sufficient removal of these lesions was investigated. METHODS: Within routine skin cancer screening 45 outpatients with a total of 77 macular melanocytic nevi were prospectively recruited. Deep shave excisions of these lesions were performed with a double-edged razor blade followed by chemical hemostasis. Histologically all specimens were processed and evaluated in a routine manner. After 6 months the physician and patients evaluated the shave sites for cosmetic outcome with a score graded from 1 to 4 (1 = excellent; 2 = good; 3 = moderate; 4 = poor). RESULTS: Histologically 88% (68 of 77) of the melanocytic lesions were described as completely excised and 60% (46 of 77) were diagnosed as atypical melanocytic nevi; 12% (9 of 77) of the nevi were incompletely excised on the depth. On average, the deep margin of the specimens (n = 77) was 0.5 mm (range 0-1.8 mm) and the lateral margin was 2 mm (range 0.3-8.2 mm). After 6 months 56 shave sites could be reassessed. We observed mild hypopigmentation in 52% (29 of 56), hyperpigmentation in 32% (18 of 56), and erythema in 23% (13 of 56). Recurrent nevi occurred in 13% (7 of 56). The evaluation of the cosmetic outcome by the patients (mean score 1.7) achieved better results than the evaluation by the physician (mean score 2.5). The cosmetic results showed no significant (P >.05) differences in various anatomic sites. CONCLUSION: Our data confirm that deep razor blade excision presents a highly useful and inexpensive method for the removal of macular melanocytic nevi that yields adequate specimens for pathologic interpretation. We consider that shave excision with the razor blade technique is potentially much less scarring than full-thickness scalpel excisions of nevi. In particular, this is of great significance for patients with multiple nevi, such as dysplastic nevi syndrome.

Adolescent↗

Perceived importance and satisfaction with physical function in patients with knee osteoarthritis.

This investigation examined the determinants of satisfaction with physical function for participants in an Observational Arthritis Study in Seniors (OASIS). The sample consisted of 480 men (51%) and women (49%) over the age of 65 years who had difficulty performing activities of daily living due to knee pain. As part of baseline testing for OASIS, participants completed a measure that assessed satisfaction with function for six physical activities. After controlling for relevant covariates, scores on the satisfaction index were regressed on seven conceptually relevant predictor variables. The results revealed that satisfaction with physical function is a distinct construct from level of function, irrespective of whether the latter variable is measured objectively or subjectively. When entered into a hierarchical regression model, 6-minute walk test data accounted for 11% of the variance in satisfaction scores, whereas perceived difficulty accounted for an additional 22%. Moreover, a significant interaction term between importance and perceived difficulty revealed that patients who rated the activities as important and who had high levels of perceived difficulty had the lowest satisfaction scores. Discussion focuses on the determinants of satisfaction with physical function with emphasis on the interaction between perceived difficulty and importance.

Activities of Daily Living↗

Adaptation and evaluation of the Liverpool Seizure Severity Scale and Liverpool Quality of Life battery for American epilepsy patients.

The Liverpool Seizure Severity Scale (LSSS) and the Liverpool Quality of Life (LQOL) battery were developed in Great Britain to assess the severity of seizure symptoms and the impact of epilepsy on patients' quality of life. The scales have been validated on British patients, but have not been validated for use with American patients. The objectives of this study were to adapt the scales to the American population and to evaluate their reliability and validity. After modifications recommended by focus groups with patients and epilepsy specialists, the scales were administered to a sample of 90 epilepsy patients who had experienced seizures within the previous 4 weeks. Comparisons of patients with generalized tonic-clonic seizures (n = 58) and partial seizures (n = 32) revealed significant differences on 9 of the 20 items on the LSSS as well as the total score. None of the six LQOL subscales (negative drug effects, positive drug effects, affect balance, sense of mastery, life fulfilment and impact of epilepsy) distinguished patients with different seizure types but five of the six subscales were significantly correlated with seizure severity. The internal consistency and test-retest reliability were adequate for both the LSSS and LQOL. Finally, five of the six LQOL scales were significantly correlated with independent measures of mental health, physical health and role functioning.

Adult↗

Adaptation and evaluation of the Liverpool Seizure Severity Scale and Liverpool Quality of Life battery for American epilepsy patients.

The Liverpool Seizure Severity Scale (LSSS) and the Liverpool Quality of Life (LQOL) battery were developed in Great Britain to assess the severity of seizure symptoms and the impact of epilepsy on patients' quality of life. The scales have been validated on British patients, but have not been validated for use with American patients. The objectives of this study were to adapt the scales to the American population and to evaluate their reliability and validity. After modifications recommended by focus groups with patients and epilepsy specialists, the scales were administered to a sample of 90 epilepsy patients who had experienced seizures within the previous 4 weeks. Comparisons of patients with generalized tonic-clonic seizures (n = 58) and partial seizures (n = 32) revealed significant differences on 12 of the 20 items on the LSSS as well as the total score. None of the six LQOL subscales (negative drug effects, positive drug effects, affect balance, sense of mastery, life fulfillment and impact of epilepsy) distinguished patients with different seizure types but five of the six subscales were significantly correlated with seizure severity. The internal consistency and test-retest reliability were adequate for both the LSSS and LQOL. Finally, five of the six LQOL scales were significantly correlated with independent measures of mental health, physical health and role functioning.

Adult↗

Pain and the choice to hasten death in patients with painful metastatic cancer.

Unrelieved pain has been cited as an important reason why cancer patients may seek to hasten their deaths. We interviewed 48 patients with painful metastatic cancer to ascertain their interest in various active and passive modes of hastening death. Ninety percent of these patients supported the general right of terminally ill patients to passive modes of hastening death and 80% supported the right to active modes such as assisted suicide and euthanasia. If they developed severe pain that could not be relieved, 80% would instruct their physician write a "do not attempt resuscitation" order, 40%-50% would want to receive suicide information or a lethal prescription from their physician, and 34% would request a lethal injection from their physician. Current pain and depression levels were not associated with interest in hastening death, but current somatic symptom burden was significantly associated with this interest.

Adult↗