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Biomedical subjects

R Schumacher

Publications and source records attributed to R Schumacher.

At least 19 recordsLinked to original sources
PubMed2006

Colchicine for acute gout.

BACKGROUND: Gout is one of the most common rheumatic diseases worldwide. Colchicine is regarded as beneficial in the treatment of acute gout, but has a high frequency of gastrointestinal adverse events. OBJECTIVES: To evaluate the efficacy and safety of colchicine for relief of the signs and symptoms of acute gouty arthritis, compared to placebo and other treatment interventions. SEARCH STRATEGY: We searched the following electronic databases to March 2006: Cochrane Central Register of Controlled Trials (CENTRAL, Issue 1, 2006), MEDLINE (from 1966), EMBASE (from 1980), CINAHL (from 1982), AMED (from 1985), Web of Science (from 1945) and Current Controlled Trials. SELECTION CRITERIA: Published randomised controlled trials (RCTs) and controlled clinical trials evaluating symptom relief and adverse outcomes of colchicine therapy in acute gout were considered for this review. DATA COLLECTION AND ANALYSIS: Two reviewers independently screened search results for inclusion, collected the data in a standardized form and assessed the methodological quality of the trial using validated criteria. Results for continuous outcome measures were expressed as weighted mean differences. Dichotomous outcome measures were pooled using relative risk. The number needed to treat was calculated for significant outcomes. MAIN RESULTS: One RCT (N=43) comparing colchicine to placebo for the treatment of acute gout was included in this review. The results favour the use of colchicine over placebo with an absolute reduction of 34% for pain and a 30% reduction in clinical symptoms such as tenderness on palpation, swelling, redness, and pain. The number needed to treat (NNT) with colchicine versus placebo to reduce pain was 3 and the NNT to reduce clinical symptoms was 2. All participants treated with colchicine experienced gastrointestinal side effects (diarrhea and/or vomiting) and the number needed to harm (NNH) with colchicine versus placebo was 1. No studies comparing colchicine to NSAIDs or other treatments such as corticosteroids or ACTH were identified. AUTHORS' CONCLUSIONS: Colchicine is an effective treatment for the reduction of pain and clinical symptoms in patients experiencing acute attacks of gout, although in the regimen studied its low benefit to toxicity ratio limits its usefulness. It should be used as a second line therapy when NSAIDs or corticosteroids are contraindicated or ineffective. More evidence is needed to compare the efficacy of colchicine to that of NSAIDs or corticosteroids, the current first line therapy for acute gout.

Colchicine↗
PubMed2004

Encapsulation into sterically stabilised liposomes enhances the immunogenicity of melanoma-associated Melan-A/MART-1 epitopes.

Tumour-associated antigens (TAA)-specific vaccination requires highly immunogenic reagents capable of inducing cytotoxic T cells (CTL). Soluble peptides are currently used in clinical applications despite an acknowledged poor immunogenicity. Encapsulation into liposomes has been suggested to improve the immunogenicity of discrete antigen formulations. We comparatively evaluated the capacity of HLA-A2.1 restricted Melan-A/MART-1 epitopes in soluble form (S) or following inclusion into sterically stabilised liposomes (SSL) to be recognised by specific CTL, to stimulate their proliferation and to induce them in healthy donors' peripheral blood mononuclear cells (PBMC), as well as in melanoma-derived tumour-infiltrating lymphocytes (TIL). HLA-A2.1(+), Melan-A/MART-1-NA-8 melanoma cells served as targets of specific CTL in 51Cr release assays upon pulsing by untreated or human plasma-treated soluble or SSL-encapsulated Melan-A/MART-1 27-35 (M27-35) or 26-35 (M26-35) epitopes. These reagents were also used to stimulate CTL proliferation, measured as 3H-thymidine incorporation, in the presence of immature dendritic cells (iDC), as antigen-presenting cells (APC). Induction of specific CTL upon stimulation with soluble or SSL-encapsulated peptides was attempted in healthy donors' PBMC or melanoma-derived TIL, and monitored by 51Cr release assays and tetramer staining. Na-8 cells pulsing with SSL M27-35 resulted in a five-fold more effective killing by specific CTL as compared with equal amounts of S M27-35. Encapsulation into SSL also provided a partial (50%) protection of M27-35 from plasma hydrolysis. No specific advantages regarding M26-35 were detectable in these assays. However, at low epitope concentrations (</=100 ng ml(-1)), SSL M26-35 was significantly more effective in inducing CTL proliferation than S M26-35, in the presence of iDC, as APC. Preincubation with iDC for 6 h virtually abolished the capacity of S M26-35 to stimulate specific CTL proliferation, but only partially affected that of SSL M26-35. Most importantly, SSL M26-35 was able to enhance the induction of specific CTL in healthy donors PBMC and in melanoma-derived TIL as compared to S M26-35. Taken together, our data indicate that encapsulation of TAA epitopes into SSL results in effective immunogenic formulations suitable for clinical use in active specific tumour immunotherapy.

Antigens, Neoplasm↗
PubMed2004

Computer aided designed neo-clavicle out of osteotomized free fibula: case report.

Total clavicle reconstruction is a challenging task. We performed a reconstruction of the ventral shoulder girdle by calculating a 3D DICOM representation of the left clavicle to create a right neo-clavicle. Two cuts in correct position and angle leads to a natural 3D shape of the new clavicle. The data were used with a thermo-jet procedure to form model slices of thermoplastic wax. Subsequently, the double titanium osteotomy template with correct cut-angulation was constructed. A 40-year old patient presented with symptoms of progressive pain and instability in the shoulder girdle resulting from complete right clavicle resection due to desmoid tumour 23 years earlier. During the operative procedure, dissection, guided double osteotomy, microvascular anastomoses and acromioclavicular-sternoclavicular fixation were performed. The computer-assisted planning resulted in the exact calculation of the two osteotomy cuts, hence, the 3D appearance of the neo-clavicle. Two years postoperatively, patient showed slightly improved elevation and complete recovery from pain. Our operative procedure demonstrates that the computer-assisted planning with construction of a wax model and an osteotomy template is a useful approach to plan the two precise cuts leading to a predictable shape of the clavicle.

Adult↗
PubMed2002

[Pre- and postnatal kidney screening compared: an analysis of 34,450 newborn infants of the Mainz model birth register].

UNLABELLED: Malformations of the internal urogenital system are common. The birth registry "Mainz Model" reflects population-based prevalence of renal malformations, calculates sensitivity rates of the prenatal ultrasonographic findings and demonstrates rates of surgery needed. METHOD AND MATERIAL: During the study period (1990-2001) all newborns of the area of Mainz were examined according to a standardized procedure including ultrasonography of the kidneys. Pathology reports were reviewed for stillbirth, abortions (> 15.SSW) and induced abortions. Beside these clinical findings, since 1996 (after implementation of a special ultrasonographic malformation screening according to the german maternity guidelines) the results of prenatal as well as postnatal ultrasonographic examinations of the kidney were recorded. All children with pathologic diagnoses of the kidneys were retrospectively analysed. Data about the follow up and surgery if needed, were collected. RESULTS: During the study period from 1990-2001 34.450 newborns were examined. 407 of the neonates (1.2%) had a malformation of the kidney. During the study period from 1996-2001 13.162 neonates were examined. 194 neonates (1.5%) had pathologic and 225 neonates (2.07%) had controllable findings. The most common diagnoses were supernumerary kidney, hydronephroses und megaureter. 22 neonates (12.8%) underwent surgery. The sensitivity of the prenatal ultrasonography was 36% and the specificity was 99%. CONCLUSION: Both, the prenatal as well as the postnatal ultrasonographic screening of the kidneys are ingenious examinations. The prenatal examination detects life threatening malformations of the kidneys. The postnatal examination completes early diagnosis of renal defects by uncovering the malformations, which have been missed prenatally. The prevalence of malformations of the kidney is comparable to the one of hip dislocation. We therefore conclude, that ultrasonographic screening of the kidneys is needed.

Female↗
PubMed2002

[Diagnosis of elevated intracranial pressure in children with shunt under special consideration of transglobe sonography of the optic nerve].

OBJECTIVE: Transglobe B-mode sonography of the optic nerve and its sheets is evaluated in respect to its value in detecting increased intracranial pressure. METHODS AND PATIENTS: For a standardized procedure we used linear probes (7-13 MHz). We measured the total diameter of the optic nerve and evaluated the optic nerve papilla. 60 controls and 102 patients with internal hydrocephalus were studied; of these 50 had no signs and 52 showed signs of elevated intracranial pressure. RESULTS: The total diameter of the nerve with its sheets in the control group varied between 1.8 and 4.1 mm (mean 3.1mm). In 50 patients without signs of elevated intracranial pressure it measured between 2.6 and 4.1 mm (mean 3.5 mm), and in 52 patients with signs of elevated intracranial pressure between 3.9 and 6.9 mm (mean 5.4 mm). The diameter of the optic nerve in patients with elevated intracranial pressure was significantly wider compared to normal data (Wilcoxon's test p < 0.01). 24 patients with a history of elevated intracranial pressure of more than 48 hours' duration showed a papilloedema as an additional finding. The upper limit of the normal diameter of the optic nerve with its sheets is 4.1 mm. CONCLUSION: A standardized transglobe sonogram of the optic nerve in combination with transcranial and abdominal sonography is a reliable method for the detection of elevated intracranial pressure.

Brain Diseases↗
PubMed2001

A PDZ domain protein interacts with the C-terminal tail of the insulin-like growth factor-1 receptor but not with the insulin receptor.

In this study, we report on the isolation of a PDZ domain protein, here designated as IIP-1, insulin-like growth factor-1 (IGF-1) receptor-interacting protein-1, which binds to the IGF-1 receptor, but not to the related insulin receptor, and which is involved in the regulation of cell motility. The interaction between the IGF-1 receptor and IIP-1 as well as a splice variant IIP-1/p26 was demonstrated in the yeast two-hybrid system. Using co-precipitation experiments, we confirmed the interaction in transfected cells as well as in vitro. Analysis of deletion mutants indicates that the PDZ domain of IIP-1 mediates interaction with the C-terminal tail of the IGF-1 receptor (serine-threonine-cysteine). This finding demonstrates that the C terminus of the IGF-1 receptor acts as novel PDZ domain binding site. Immunofluorescence analysis revealed an overlapping localization of IIP-1 and the IGF-1 receptor in the breast cancer cell line MCF-7. A functional connection between IIP-1 and the IGF-1 receptor is further supported by the finding that the level of expression of IIP-1 and the IGF-1 receptor strongly correlates in different normal and cancer cells. Furthermore, overexpression of IIP-1 resulted in an attenuation of migration of MCF-7 cells, which is one of the biological activities mediated by the IGF-1 signaling system.

3T3 Cells↗
PubMed2001

Chalcone derivatives antagonize interactions between the human oncoprotein MDM2 and p53.

The oncoprotein MDM2 inhibits the tumor suppressor protein p53 by binding to the p53 transactivation domain. The p53 gene is inactivated in many human tumors either by mutations or by binding to oncogenic proteins. In some tumors, such as soft tissue sarcomas, overexpression of MDM2 inactivates an otherwise intact p53, disabling the genome integrity checkpoint and allowing cell cycle progression of defective cells. Disruption of the MDM2/p53 interaction leads to increased p53 levels and restored p53 transcriptional activity, indicating restoration of the genome integrity check and therapeutic potential for MDM2/p53 binding antagonists. Here, we show by multidimensional NMR spectroscopy that chalcones (1,3-diphenyl-2-propen-1-ones) are MDM2 inhibitors that bind to a subsite of the p53 binding cleft of human MDM2. Biochemical experiments showed that these compounds can disrupt the MDM2/p53 protein complex, releasing p53 from both the p53/MDM2 and DNA-bound p53/MDM2 complexes. These results thus offer a starting basis for structure-based drug design of cancer therapeutics.

Antineoplastic Agents↗
PubMed2001

Cerebral spinal fluid flow, venous drainage and spinal cord compression in achondroplastic children: impact of magnetic resonance findings for decompressive surgery at the cranio-cervical junction.

UNLABELLED: In order to investigate the diagnostic properties of MRI of the brain and spine in achondroplastic children with regard to decompressive surgery, 25 patients were examined by conventional morphological and by "functional" imaging of CSF flow and magnetic resonance angiography (MRA) of the veins and sinuses at the cranial base following a special protocol. The results were compared to those from age-matched controls and were correlated with each other and retrospectively with the neurological findings. Measurements of distances and angulations at the cranio-cervical junction (CCJ) from MR scans showed similar values to those from conventional radiographs and CTs and thus can be used without correction for spatial distorsion. Signs of cervical medullary compression, myelomalacia and intramedullary cyst formation were found in six, seven and three children respectively. These alterations correlated significantly with each other (P < 0.05). Semiquantitative evaluation of CSF flow demonstrated interruption of CSF pathways at the CCJ, which correlated with CCJ narrowing (P < 0.05). MRA showed a significant narrowing of the jugular foramina with a variable compensatory enlargement of the emissary veins and a significant reduction of the total outflow area (P < 0.01). There were no significant correlations between these MR changes and neurological deficits. CONCLUSION: Due to this unexpectedly poor correlation between magnetic resonance and clinical findings in achondroplastic children, the present role of magnetic resonance in the clinical setting is limited to the demonstration of spinal cord compression in individual cases. In three of our patients with prominent neurological abnormalities, the severe changes demonstrated by magnetic resonance imaging strongly supported the indication for surgical decompression.

Achondroplasia↗
PubMed2001

The phenomenon of treatment failures in Human African Trypanosomiasis.

Treatment of Human African Trypanosomiasis (HAT or sleeping sickness) relies on a few drugs which are old, toxic and expensive. The most important drug for the treatment of second stage infection is melarsoprol. During the last 50 years treatment failures with melarsoprol were not a major problem in Trypanosoma brucei gambiense patients. Commonly a relapse rate of 5-8% was reported, but in recent years it has increased dramatically in some important foci of T. b. gambiense sleeping sickness. Treatment failures for T. b. rhodesiense are much less of a problem apart from some reports between 1960 and 1985 of refractoriness in T. b. rhodesiense patients in East Africa. Analysis of those isolates revealed that their in vitro sensitivity to melarsoprol was one-tenth that of sensitive isolates, and complete failure to cure the infection in the acute mouse model with melarsoprol levels comparable with those in human patients. There was very little indication of resistance in T. b. gambiense isolates from Côte d'Ivoire and NW Uganda. The in vitro melarsoprol sensitivities for populations from relapsing and from curable patients were in the same range. Melarsoprol concentrations in the plasma and cerebrospinal fluid of patients 24 h after treatment did not show any difference between patients who relapsed and those who could be cured. The reason for relapses in the recent T. b. gambiense epidemics are not known. Other parasite-related factors might be involved, e.g. affinity to extravascular sites other than the CNS which are less accessible to the drug. In conclusion, a combination of factors rather than a single one may be responsible for the phenomenon of melarsoprol treatment failures in T. b. gambiense patients.

Africa, Eastern↗
PubMed2001

[Head circumference in relation to sonographic morphometry of the cerebral ventricles in neonates and infants].

AIM: To determine normal values of sonographic measurements of the brain in neonates and infants. METHOD: Cerebral ultrasonographic examinations were performed in 143 healthy newborns and infants. The size of the ventricles was determined by ascertaining distances as well as performing planimetric measurements of the ventricular area and circumference in standardized planes. RESULTS: Throughout the course of the study we observed a continous increase in size and a strong correlation with head circumference. The middle coronary plane used for the measurements allows the accurate representation of the ventricles and a more objective assessment of size. CONCLUSION: Based on the morphometric data, charts for the determination of ventricular size were developed.

Body Height↗
PubMed2000

[Sociodemographic characteristics and use of health services by the immigrant population residing in a district of the Community of Madrid].

OBJECTIVE: To describe the social and demographic characteristics of the immigrant population residing in a health district and their use of health services. PARTICIPANTS: Immigrant population with papers or otherwise living in the area under study. SETTING: Health District 6 in the Community of Madrid. MEASUREMENTS AND MAIN RESULTS: Individual interviews with 300 immigrants chosen by two-stage conglomerate sampling. Average age was 32.6 (95% CI, 31.6-33.7) with 6.6 years living in Spain. 30.9% (CI, 24.3-35.9) lived in a situation of administrative and health-coverage irregularity. One of every five people had neither running water nor rubbish collection. The main health problems arising were muscular pains (69%; CI, 63.9-74.1), upper respiratory path ailments (40.3%; CI, 33.9-46.7) and accidents (27.3%; CI, 16.9-37.7). Health centres (64.5%; CI, 56.7-72.3) were used in preference to other services, with emergency being almost the only path into hospital admission. CONCLUSIONS: The immigrant population has lived in this area for a long time, despite living in adverse conditions in administrative and health terms. The public health service through INSALUD is the principal provider of health services to immigrants.

Adult↗
PubMed2000

Kinetics and mechanism of complex formation of nickel(II) with tetra-N-alkylated cyclam in N,N-dimethylformamide (DMF): comparative study on the reactivity and solvent exchange of the species Ni(DMF)6(2+) and Ni(DMF)5Cl+.

13C NMR was used to study the rate of DMF exchange in the nickel(II) cation Ni(DMF)6(2+) and in the monochloro species Ni(DMF)5Cl+ with 13C-labeled DMF in the temperature range of 193-395 K in DMF (DMF = N,N-dimethylformamide). The kinetic parameters for solvent exchange are kex = (3.7 +/- 0.4) x 10(3) s-1, delta H++ = 59.3 +/- 5 kJ mol-1, and delta S++ = +22.3 +/- 14 J mol-1 K-1 for Ni(DMF)6(2+) and kex = (5.3 +/- 1) x 10(5) s-1, delta H++ = 42.4 +/- 4 kJ mol-1, and delta S++ = +6.7 +/- 15 J mol-1 K-1 for Ni(DMF)5Cl+. Multiwavelength stopped-flow spectrophotometry was used to study the kinetics of complex formation of the cation Ni(DMF)6(2+) and of the 100-fold more labile cation Ni(DMF)5Cl+ with TMC (1,4,8,11-tetramethyl-1,4,8,11-tetraazacyclotetradecane) and TEC (1,4,8,11-tetraethyl-1,4,8,11-tetraazacyclotetradecane) in DMF at 298 K and I = 0.6 M (tetra-n-butylammoniumperchlorate). Equilibrium constants K for the addition of the nucleophiles DMF, Cl-, and Br- to the complexes Ni(TMC)2+ and Ni(TEC)2+ were determined by spectrophotometric titration. Formation of the complexes Ni(TMC)2+ and Ni(TEC)2+ was found to occur in two stages. In the initial stage, fast, second-order nickel incorporation with rate constants k1(TMC) = 99 +/- 5 M-1 s-1 and k1 (TEC) = 235 +/- 12 M-1 s-1 leads to the intermediates Ni(TMC)int2+ and Ni(TEC)int2+, which have N4-coordinated nickel. In the second stage, these intermediates rearrange slowly to form the stereochemically most stable configuration. First-order rate constants for the one-step rearrangement of Ni(TMC)int2+ and the two-step rearrangment of Ni(TEC)int2+ are presented. Because of the rapid formation of Ni(DMF)5Cl+, the reactions of Ni(DMF)6(2+) with TMC and TEC are accelerated upon the addition of tetra-n-butylammoniumchloride (TBACl) and lead to the complexes Ni(TMC)Cl+ and Ni(TEC)Cl+, respectively. For initial concentrations such that [TBACl]o/[nickel]o > or = 20, intermediate formation is 230 times (TMC) and 47 times (TEC) faster than in the absence of chloride. The mechanism of complex formation is discussed.

Journal Article↗
PubMed2000

Syndrome of autosomal recessive polycystic kidneys with skeletal and facial anomalies is not linked to the ARPKD gene locus on chromosome 6p.

We report on two sibs, both males, one born at 37 the other at 24 weeks of gestation, both with a syndrome similar to that seen in three sets of sibs by Gillessen-Kaesbach et al. [1993: Am J Med Genet 45:511-518]. Both propositi had polycystic kidneys and hepatic fibrosis indistinguishable from that seen in autosomal recessive polycystic kidney disease (ARPKD), and skeletal and facial anomalies. Skeletal abnormalities included "butterfly" vertebrae, square shape of pelvis, and brachymelia. The facial anomalies included hypertelorism, epicanthic folds, and anteverted nares. Additional external findings were apparently low-set ears and a short neck. Histopathological examination of the kidneys showed radial orientation and cystic dilatation of the cortical and medullar tubules. The liver showed "congenital hepatic fibrosis." The hepatic findings in the second infant were less severe. Renal abnormalities were limited to focal tubular cystic changes. Linkage analysis with polymorphic markers of the region 6p21.1-p12, flanking the gene locus of ARPKD, showed different haplotypes in the sibs, thus excluding the ARPKD gene locus in this family and indicating genetic heterogeneity.

Abortion, Induced↗
PubMed1999

Neonatal body composition: dual-energy X-ray absorptiometry, magnetic resonance imaging, and three-dimensional chemical shift imaging versus chemical analysis in piglets.

An animal study to evaluate dual-energy x-ray absorptiometry (DXA) and magnetic resonance (MR) imaging and spectroscopy for measurement of neonatal body composition was performed. Twenty-three piglets with body weights ranging from 848 to 7550 g were used. After measuring total body water, animals were killed and body composition was assessed using DXA and MR (1.5 T; MR imaging, T1-weighted sagittal spin-echo sequence; MR spectroscopy, three-dimensional chemical shift imaging) as well as chemical carcass analysis (standard methods) after homogenization. Body composition by chemical analysis (percent of body weight, mean +/- SD) was as follows: body water, 75.3 +/- 3.9%; total protein, 13.9 +/- 8.8%; and total fat, 6.5 +/- 3.7%. Absolute content of fat and total ash was 7-674 and 35-237 g, respectively. Mean hydration of fat-free mass was 0.804 +/- 0.011 g/kg and decreased with increasing body weight (r2 = 0.419) independent of age. Using DXA, bone mineral content was highly correlated with calcium content (r2 = 0.992), and calcium per bone mineral content was 44.1 +/- 4.2%. DXA fat mass correlated with total fat (r2 = 0.961). Using MR, spectroscopy and chemical analysis were highly correlated with fat-to-water ratio (r2 = 0.984) and absolute fat content (r2 = 0.988). Total fat by MR imaging volumetry showed a lower correlation (r2 = 0.913) and overestimated total fat by a factor of 2.46. Conversion equations for DXA were developed (total fat = 1.31 x fat mass measured by DXA--68.8; calcium = 0.402 x bone mineral content + 1.7), which improved precision and accuracy of DXA measurements. In conclusion, both DXA and MR spectroscopy give accurate and precise estimates of neonatal body composition and may become valuable tools for the noninvasive assessment of neonatal growth and nutritional status.

Absorptiometry, Photon↗