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Biomedical subjects

D Weber

Publications and source records attributed to D Weber.

At least 37 records · Page 2Linked to original sources

[Fundamentals of hygiene in old-age and nursing homes. Recommendations for nursing personnel and for hygiene control by German public health offices].

New German legislative ordinances prescribe hygiene control in nursing homes and homes for the aged, e. g. the Law for Protection against Infectious Diseases and in North-Rhine Westphalia the Public Health Law. However, there are as yet no clearly defined standards of hygiene because the special features of nursing homes must be considered when applying the "Guidelines for Hospital Hygiene and Prevention of Infections" issued by the Robert Koch Institute. Hence, specific recommendations are given for hygiene of the hands, disinfection, hygienic treatment care, protective and professional clothing, washing of textiles, central kitchen, disposal of waste, house cleaning and handling of drugs and medicines.

Aged↗

Pleiotrophin can be rate-limiting for pancreatic cancer cell growth.

Pancreatic cancer is one of the most aggressive malignant tumors, with an overall survival rate of 2%. The identification of growth factors that contribute to the malignant phenotype can help to identify new targets for therapy. In this study, we analyzed the growth factor pleiotrophin (PTN) that was originally described as a developmentally regulated cytokine during early embryogenesis. More recently, PTN was found to be overexpressed in a variety of neuroectodermal tumors and described as an essential angiogenic growth factor in choriocarcinoma and melanoma, promoting metastatic growth. Recently, we discovered high expression levels of PTN in patients with gastrointestinal malignancies, particularly in those patients with pancreatic cancer. However, it is not known whether PTN is a contributor to the growth of pancreatic cancer or is only a bystander. We used ribozymes to deplete PTN mRNA from Colo357 pancreatic cancer cells and studied the resulting phenotype. The reduction of PTN resulted in a decrease in the proliferation rate, soft agar colony formation, and tumor growth in animals. Supplementation of cells with PTN partially reversed the ribozyme effect. The autocrine function of PTN was confirmed by using PTN-binding antibodies that inhibited the proliferation rate by 50% in Colo357 cells but also in a different pancreatic cancer cell line, Panc89. Our study identifies PTN as a new and essential growth factor for pancreatic cancer. Due to the restricted expression pattern of PTN in adults, PTN is suggested as a target for pancreatic cancer therapy.

Adenocarcinoma↗

Optimizing radiotherapy of orbital and paraorbital tumors: intensity-modulated X-ray beams vs. intensity-modulated proton beams.

PURPOSE: This study presents a dosimetric optimization effort aiming to compare intensity-modulated (IM) X-rays and IM protons in 4 different orbital and paraorbital tumors. These are most challenging targets for standard radiotherapy due to their close relationship with the eyes and related structures. METHODS AND MATERIALS: A primary orbital lymphoma, an optic nerve meningioma, a sphenoidal ridge meningioma protruding into the orbit, and a pediatric parameningeal paraorbital rhabdomyosarcoma were selected for the purpose of this study. Planning target volumes (PTVs) and organs at risk (OAR) were defined in each patient CT data set for each tumor site. IM X-ray and IM proton three-dimensional treatment plans were implemented. The following total tumor doses were prescribed: 30 Gy for the orbital lymphoma, 54 Gy for both meningiomas, and 50.4 Gy for the rhabdomyosarcoma case. Dose-volume histograms (DVHs) were obtained for all targets and OAR with both treatment techniques. DVHs were used to predict normal tissue complication probabilities (NTCPs) for the OAR in the vicinity of the tumor. RESULTS: The PTV coverage was optimal and equally homogeneous with both IM X-rays and IM proton plans in the 4 tumor sites. DVHs for most OAR were better with IM proton beams especially in the low- to mid-dose range region. The integral nontarget dose was lower with IM protons in every case (factor ranging from 1.5 to 1.9). However, predicted NTCPs (for severe late effects) were equally low for both treatment techniques in every tumor site. CONCLUSION: Although IM proton plans optimally decreased the dose to the OAR in all tumor sites, both optimized X-ray and proton beams equally succeeded to reduce severe-toxicity prediction risks to less than 5% while optimally treating the PTV.

Humans↗

Peptide and peptide mimetic inhibitors of antigen presentation by HLA-DR class II MHC molecules. Design, structure-activity relationships, and X-ray crystal structures.

Molecular features of ligand binding to MHC class II HLA-DR molecules have been elucidated through a combination of peptide structure-activity studies and structure-based drug design, resulting in analogues with nanomolar affinity in binding assays. Stabilization of lead compounds against cathepsin B cleavage by N-methylation of noncritical backbone NH groups or by dipeptide mimetic substitutions has generated analogues that compete effectively against protein antigens in cellular assays, resulting in inhibition of T-cell proliferation. Crystal structures of four ternary complexes of different peptide mimetics with the rheumatoid arthritis-linked MHC DRB10401 and the bacterial superantigen SEB have been obtained. Peptide-sugar hybrids have also been identified using a structure-based design approach in which the sugar residue replaces a dipeptide. These studies illustrate the complementary roles played by phage display library methods, peptide analogue SAR, peptide mimetics substitutions, and structure-based drug design in the discovery of inhibitors of antigen presentation by MHC class II HLA-DR molecules.

Antigen Presentation↗

[Traumatic perforation of the small intestine--a rare complication of inguinal hernia].

Groin hernias are among the most common surgical diseases. Traumatic rupture of the intestine is a rare complication compared to incarceration. We report on a 90-year old male with a left-sided hernia and a traumatic rupture of the small bowel. The treatment consisted of an emergency laparoscopy with simple closure of the perforation, repair of the hernia by herniorrhaphy and drainage of the abdomen.

Aged↗

Updating working memory for words: a PET activation study.

A PET study of 10 normal individuals was carried out to investigate the cerebral regions involved in the controlled updating of verbal working memory. Subjects viewed single concrete words on a computer monitor and detected occasional target words in an attended color. In the activating condition, a target was defined as a word that was identical to the previous word presented in the attended color. In the control condition, the target was a predesignated word. The same word lists, target probabilities, and target response demands were used for both conditions, with interword intervals constrained to ensure equivalence in the demand for target rehearsal. A comparison of the conditions found bilateral activation of dorsolateral prefrontal (middle frontal gyrus; MFG) and inferior parietal (supramarginal gyrus; SMG) cortical regions. Activation of the MFG is taken to reflect executive control by prefrontal regions over the working memory updating process linking posterior representations of the anticipated target stimulus to anterior representations of the planned response. It is proposed that the updating of the stimulus link is mediated via connections between the MFG and SMG. The role of the SMG as an amodal region binding the various modal representations in posterior association cortex of the word being retained in working memory is considered and reviewed. It is suggested that the combined activation of these regions is related to the executive control of goal-setting in planned behavior.

Blood Flow Velocity↗

Randomized trial of alpha-interferon or dexamethasone as maintenance treatment for multiple myeloma.

In order to assess the role of alpha-interferon or dexamethasone as maintenance therapy for multiple myeloma, 172 consecutive, previously untreated patients with disease of low or intermediate tumor mass received primary therapy with oral melphalan and intermittent, high-dose dexamethasone (MD), repeated monthly. Within 5 months, 84 responding patients were assigned at random to maintenance treatment with alpha-interferon (3 mU s.c. 3 x weekly) or dexamethasone (20 mg/m2 p.o. each morning for 4 days) repeated monthly until relapse. Upon relapse, MD was resumed for 2 cycles and second responses were maintained with 4-day courses of melphalan-dexamethasone until second relapse. Initial response was achieved in 88 patients (51%) after a median 0.7 month and no more than 3 courses of MD, a frequency of response similar to that observed previously with dexamethasone alone. There were identical median remissions of 10 months with interferon or dexamethasone, both maintenance regimens being associated with infrequent, mild, and reversible side effects. Significantly more patients responded again to resumption of MD after disease relapse to interferon (82%) than to dexamethasone (44%) (P = 0.001). The median remission from randomization to melphalan-resistant second relapse was 32 months for patients maintained initially on interferon compared to 19 months for those on dexamethasone (P = 0.01). These findings supported an advantage for interferon in remission maintenance by increasing the frequency of tumor recontrol with later treatment that included dexamethasone.

Adult↗

Proximally porous coated femoral stem in total hip replacement--5- to 13-year follow-up report.

A series of total hip replacements was performed using a proximally porous coated, tapered femoral stem system. At a mean follow-up of 8.1 (5-13) years, 80 out of 107 hips were available for clinical and radiological examination. The mean age at the index procedure was 58.6 years. The mean Harris Hip Score at final follow-up was 91.7. Radiological ingrowth was observed in 77 femoral stems, 2 stems were fibrous stable and 1 stem was loose.

Female↗

Cementless hemispheric acetabular component in total hip replacement.

A series of 198 total hip arthroplasties was performed using a porous-coated, hemispheric press-fit cup. One hundred and twenty-seven cups were available for clinical and radiological examination at mean follow-up of 10.6 years. The mean age at the index procedure was 61.2 years. The mean Harris hip score at final follow-up was 89.8. Three cups were revised for aseptic loosening and two liners were changed for eccentric wear and pelvic osteolysis. Nine additional patients showed mild or suspected osteolysis. Two cups were rated "fibrous" stable. There was no correlation between additional screw fixation of the press-fit cup and osteolysis or revision.

Adult↗

Supracondylar nailing of distal periprosthetic femoral fractures.

Seven patients who sustained complex distal femoral fractures above total knee arthroplasties all treated by supracondylar (retrograde) femoral nailing were retrospectively evaluated. All the patients demonstrated uncomplicated postoperative follow-ups and returned to weight bearing between 2 and 3 months after surgery. No delayed healing occurred and alignment of the femur was satisfactory.

Aged↗

Investigation on the possible formation of N-nitroso-N-methylurea by nitrosation of creatinine in model systems and in cured meats at gastric pH.

N-Nitroso-N-methylurea (NMU) is a highly potent direct-acting carcinogen that has been shown to induce cancer in a number of animal species. Although previous research has indicated that nitrosation of creatinine (CRN), a common constituent of meats, dried fish, and seafoods, can form traces of NMU, there is uncertainty as to (1) the yield of NMU and (2) whether detectable amounts of NMU can be formed from cured meats following nitrosation under acidic conditions given the low residual levels of nitrite found in cured meats at the present time. Lack of sensitive and specific analytical methods most likely has hindered progress in research in these areas. An HPLC postcolumn denitrosation-thermal energy analyzer technique and a GC-MS confirmation technique were developed for the determination of NMU in cured meats. Both techniques are highly sensitive (0.5 and 0.03 ppb, respectively) and specific. The optimum pH for NMU formation from CRN ranged between pH 1 and pH 3, and the yields of NMU under variable reactant concentrations ranged between 0.00004 and 0.0046%. When 27 samples of various cured meats (10 g aliquots each) were acidified with HCl (final pH values of 0.8-2.5) and incubated at room temperature for 2 h, without any additional nitrite, 24 gave results below detectable levels but 3 formed 2-26 ng of NMU/10 g of meat. Incubation of the negative meats with additional nitrite (50-500 microg/g of meat) formed 0.6-176 ng of NMU/10 g of sample. Although the amounts of NMU formed were extremely small, this seems to be the first reported formation of NMU from cured meats with and without additional nitrite.

Creatinine↗

Imaging of myeloma bone disease--implications for staging, prognosis and follow-up.

Among all imaging modalities, magnetic resonance imaging provides the most useful information about the accurate staging of solitary bone plasmacytoma, the prediction of progression of asymptomatic multiple myeloma and the prognosis of symptomatic multiple myeloma. Furthermore, magnetic resonance imaging contributes to the differential diagnosis of compression fractures in patients with myeloma and can be used for assessment of response to treatment.

Diagnosis, Differential↗

Inclusion of HNEt3+ in an acyclic tetraphenolate

The acyclic tetraphenolic derivative 2, 2'-methylenebis[6-(3-tert-butyl-2-hydroxy-5-methylbenzyl)-4-methylphe nol] reacts with excess triethylamine in acetonitrile to form a molecular complex, i.e. triethylammonium 2-(3-tert-butyl-2-hydroxy-5-methylbenzyl)-6-[3-(3-tert-butyl-2-hydrox y-5-methylbenzyl)-2-hydroxy-5-methylbenzyl]-4-methylphenolate acetonitrile solvate, C(6)H(16)N(+).C(39)H(47)O(4)(-).C(2)H(3)N, where the organic HNEt(3)(+) cation is included in the partial cone defined by the aromatic faces of the acyclic polyphenolate.

Journal Article↗

Competency development in public health leadership.

The professional development of public health leaders requires competency-based instruction to increase their ability to address complex and changing demands for critical services. This article reviews the development of the Leadership Competency Framework by the National Public Health Leadership Development Network and discusses its significance. After reviewing pertinent literature and existing practice-based competency frameworks, network members developed the framework through sequential use of workgroup assignments and nominal group process. The framework is being used by network members to develop and refine program competency lists and content; to compare programs; to develop needs assessments, baseline measures, and performance standards; and to evaluate educational outcomes. It is a working document, to be continually refined and evaluated to ensure its continued relevance to performance in practice. Understanding both the applications and the limits of competency frameworks is important in individual, program, and organizational assessment. Benefits of using defined competencies in designing leadership programs include the integrated and sustained development of leadership capacity and the use of technology for increased access and quality control.

Curriculum↗

Experience with 9-cis retinoic acid in patients with relapsed and refractory non-Hodgkin's lymphoma.

We conducted a phase II study to determine the efficacy and toxicity of 9-cis-retinoic acid (9-cis RA), a pan-retinoid receptor agonist, in the treatment of patients with relapsed and refractory NHL. Patients were eligible if they had histologically documented relapsed or refractory T cell or indolent B cell NHL. The first three patients enrolled received 70 mg/m2 of 9-cis RA orally twice a day, but the remaining patients received a single oral daily dose of 100 mg/m2. After 6 weeks of therapy, tumor response was assessed objectively. Response rate and toxicity were determined in all 29 eligible patients based on an intent-to-treat analysis. Four patients (14%) responded (3 PRs and 1 CR; 95% CI 4%-33%). One patient had a minor response, and eight had stable disease. Responses were observed in two (11%) of 19 patients with B-cell lymphoma and in two (20%) of 10 patients with T-cell lymphoma. The median time-to-treatment failure for the 29 eligible patients was 8 weeks. The most frequent toxic effects were dry skin, headache, hypertriglyceridemia, and hypercalcemia. Five patients discontinued therapy due to toxic side effects, but no toxic deaths occurred during the study. We conclude that 9-cis RA has a modest activity in relapsed and refractory NHL. In this study, responses were observed in patients with B-cell lymphomas and those with T-cell lymphomas.

Adult↗