Search PubMed⌕ Search

Biomedical subjects

M Gross

Publications and source records attributed to M Gross.

At least 37 records · Page 2Linked to original sources
PubMed2005

[Interferon beta1-a IM once weekly does not modify general psychological function in the first months after therapy in patients with relapsing-remitting multiple sclerosis].

INTRODUCTION: Psychological troubles are common in multiple sclerosis but their underlying etiology is still controversial. METHODS: The objective of this open, non comparative, multicenter study was to assess changes in global psychological functioning in new multiple sclerosis patients during the first 3 months of treatment with intramuscular interferon beta-1a once weekly (Avonex). This functioning was rated every 4 weeks with the GAF (Global Assessment Functioning) scale. Depression measured on MADRS (Montgomery & Asberg Depression Rating Scale), clinical global impression (CGI) on patients'psychological status and clinical as well as biological tolerance were also assessed every 4 weeks. RESULTS: Five hundred and ninety-nine patients (71.4 percent women), aged 39.4 years were included. No clinically significant difference in mean GAF score between baseline and the end of the first 3 months of interferon beta-1a IM treatment (main evaluation outcome) was found. Similar results were obtained on MADRS scale. CONCLUSION: No clinically significant alteration of global psychological functioning, including symptoms of depression, was observed during the first 3 months of treatment with interferon beta-1a IM.

Adjuvants, Immunologic↗
PubMed2005

[Correlations between "questionnaire of auditory perception disorders" and "Heidelberger test of phonemic discrimination"].

BACKGROUND: A standardized anamnestic questionnaire of central auditory processing disorders ("Anamnestischer Erhebungs- und Beobachtungsbogen für auditive Verarbeitungs- und Wahrnehmungsstörungen") (FB-AVWS) was developed by German paedaudiologists. The present study examined the relations between this questionnaire and the results of selected auditory-perceptual tests to evaluate the validity of the FB-AVWS. SUBJECTS AND METHOD: As part of a multicentric study, 113 pupils in primary schools were examined by the "Heidelberger Lautdifferenzierungstest", a test of phonemic discrimination and identification (HLAD). Additionally, the parents answered the FB-AVWS. Sensitivity, specificity and correlations with the FB-AVWS were determined referred to the HLAD. RESULTS: We found significant, though moderate correlations, between the scale "auditory discrimination" of the FB-AVWS and the subtests "kinaesthetic/phonemic identification" and "phonemic analysis" of the HLAD. The other subscales of the FB-AVWS showed no significant correlations with the HLAD and its several subtests. The values for the sensitivity of the FB-AVWS were relatively high (93 and 100 %) as where the negatively predictive values for the HLAD as a whole and the subscale 1B (98 and 100 %), referred to HLAD. The specificity and the positive values were relatively low for the HLAD as a whole and for several of its subtests. CONCLUSION: The FB-AVWS is a useful supplementation for the complementary clinical evaluation of central auditory disorders. It allows an assessment of the child's auditory perception and processing skills compared to the general population of primary school children. However, it is not valid as a screening or diagnostic instrument.

Age Factors↗
PubMed2005

[Universal hearing screening in newborns -- recommendations for organizing and conducting universal hearing screening for congenital hearing loss in Germany].

The Interdisciplinary Consensus Conference for Newborn Hearing Screening (IKKNHS) has worked out joint recommendations for universal hearing screening of newborns. In the consensus paper, 11 professional associations and scientific societies in the fields of gynecology and obstetrics, ENT, pediatrics, and phoniatrics and pedaudiology came to an agreement how to implement newborn hearing screening in Germany. The paper deals with the following topics: goals of universal newborn hearing screening, target group of hearing screening, schedule for screening, personnel involved in the screening program, technologies and framework conditions of hearing screening, documentation, continuous quality control of screening, confirmation diagnostics for conspicuous test subjects, motivation to take part in screening, information on newborn hearing screening, tracking, various infrastructural situations in urban and rural regions, follow-up care, in-patient vs. out-patient screening, cost factors of screening, reporting children with permanent hearing loss to the German Central Registry for hearing loss in children.

Animals↗
PubMed2004

Increased intestinal permeability in patients with inflammatory bowel disease.

Intestinal permeability can be measured by the sugar absorption test. This test is based on determining the ratio of the urinary excretion of a large and a small carbohydrate after oral administration. The aim of this study was to determine which combination of carbohydrates used in the test gives the highest correlation with disease activity in inflammatory bowel disease. 26 patients with Crohn's disease, 21 patients with ulcerative colitis and 27 healthy control subjects were included in the study. The patients with inflammatory bowel disease had either minimal or highly active disease or were in remission. Two disaccharides (lactulose: L, and cellobiose: C) and two smaller carbohydrates (rhamnose:R, and mannitol:M) were given orally and the urinary excretion was measured by high pressure liquid chromatography followed by pulsed amperometric electrochemical detection on a gold electrode. The ratios C/R, L/R, C/M and L/M were used as indicators for intestinal permeability. - There were no side effects of oral sugar administration. All patients tolerated the test well. Lactulose, rhamnose and cellobiose concentrations are easily be measured in the urine whereas mannitol measurement requires the use of an anion exchanger. This produced inconsistent results. Patients with Crohn's disease or with ulcerative colitis had increased permeability indices in comparison to healthy controls, even in remission. The L/R ratio gave a better differentiation between the healthy controls and patients with active disease than the other agents. Changes in disease activity are best reflected by use of cellobiose/rhamnose excretion quotient.

Adolescent↗
PubMed2004

Extended microsatellite analysis in microsatellite stable, MSH2 and MLH1 mutation-negative HNPCC patients: genetic reclassification and correlation with clinical features.

BACKGROUND: Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant disorder predisposing to predominantly colorectal cancer (CRC) and endometrial cancer frequently due to germline mutations in DNA mismatch repair (MMR) genes, mainly MLH1, MSH2 and also MSH6 in families seen to demonstrate an excess of endometrial cancer. As a consequence, tumors in HNPCC reveal alterations in the length of simple repetitive genomic sequences like poly-A, poly-T, CA or GT repeats (microsatellites) in at least 90% of the cases. AIM OF THE STUDY: The study cohort consisted of 25 HNPCC index patients (19 Amsterdam positive, 6 Bethesda positive) who revealed a microsatellite stable (MSS)--or low instable (MSI-L)--tumor phenotype with negative mutation analysis for the MMR genes MLH1 and MSH2. An extended marker panel (BAT40, D10S197, D13S153, D18S58, MYCL1) was analyzed for the tumors of these patients with regard to three aspects. First, to reconfirm the MSI-L phenotype found by the standard panel; second, to find minor MSIs which might point towards an MSH6 mutation, and third, to reconfirm the MSS status of hereditary tumors. The reconfirmation of the MSS status of tumors not caused by mutations in the MMR genes should allow one to define another entity of hereditary CRC. Their clinical features were compared with those of 150 patients with sporadic CRCs. RESULTS: In this way, 17 MSS and 8 MSI-L tumors were reclassified as 5 MSS, 18 MSI-L and even 2 MSI-H (high instability) tumors, the last being seen to demonstrate at least 4 instable markers out of 10. Among all family members, 87 malignancies were documented. The mean age of onset for CRCs was the lowest in the MSI-H-phenotyped patients with 40.5 +/- 4.9 years (vs. 47.0 +/- 14.6 and 49.8 +/- 11.9 years in MSI-L- and MSS-phenotyped patients, respectively). The percentage of CRC was the highest in families with MSS-phenotyped tumors (88%), followed by MSI-L-phenotyped (78%) and then by MSI-H-phenotyped (67%) tumors. MSS tumors were preferentially localized in the distal colon supposing a similar biologic behavior like sporadic CRC. MSH6 mutation analysis for the MSI-L and MSI-H patients revealed one truncating mutation for a patient initially with an MSS tumor, which was reclassified as MSI-L by analyzing the extended marker panel. CONCLUSION: Extended microsatellite analysis serves to evaluate the sensitivity of the reference panel for HNPCC detection and permits phenotype confirmation or upgrading. Additionally, it confirms the MSS status of hereditary CRCs not caused by the common mutations in the MMR genes and provides hints to another entity of hereditary CRC.

Adaptor Proteins, Signal Transducing↗
PubMed2004

Oral anti-pneumococcal activity and pharmacokinetic profiling of a novel peptide deformylase inhibitor.

OBJECTIVE: BB-81384, a novel peptide deformylase (PDF) inhibitor, was characterized in terms of enzyme inhibition profile, antibacterial activity, rodent pharmacokinetics and oral efficacy in murine infection models. METHODS: MICs were determined by standard NCCLS broth microdilution. Selectivity of metalloenzyme inhibition was determined with a limited panel of enzymes via standard biochemical assays. Profiling of the pharmacokinetics and select tissue disposition in mice was determined and compared with that of the macrolide, azithromycin. In vivo murine efficacy studies using Streptococcus pneumoniae were conducted using a peritonitis model, as well as lung and thigh burden models of infection. RESULTS: BB-81384 selectively inhibited PDF with an IC(50) approximately 10 nM and with MICs < 0.5 mg/L against most S. pneumoniae pathogens. Pharmacokinetic analysis revealed good oral bioavailability and moderate clearance and volume of distribution. BB-81384 partitioning to lung tissue was similar in terms of magnitude and kinetics to that of the plasma compartment. Single-administration oral efficacy in a mouse peritonitis model was evident with an ED(50) of 30 mg/kg. BB-81384 reduced the bacterial load by approximately 5 and 3 log units in organ-burden models of lung and thigh infection, respectively. CONCLUSION: BB-81384, a novel PDF inhibitor with good activity against S. pneumoniae in vitro, was the first compound of this class to be profiled for oral pharmacokinetics and tissue disposition and to demonstrate oral anti-pneumococcal efficacy in mice.

Amidohydrolases↗
PubMed2004

Proton MR spectroscopy detected glutamate/glutamine is increased in children with traumatic brain injury.

Adults with traumatic brain injury (TBI) have been shown by invasive methods to have increased levels of the excitatory neurotransmitter glutamate. It is unclear whether glutamate release contributes to primary or secondary injury and whether its protracted elevation is predictive of a poor outcome. Preliminary studies at our institution in adults found that early increases in magnetic resonance spectroscopy (MRS)-detected glutamate/glutamine (Glx) were associated with poor outcomes. We therefore studied 38 children (mean age, 11 years; range, 1.6-17 years) who had TBI with quantitative short-echo time (STEAM, TE = 20 msec) proton MRS, a mean of 7 +/- 4 (range, 1-17) days after injury in order to determine if their occipital or parietal Glx levels correlated with the severity of injury or outcome. Occipital Glx was significantly increased in children with TBI compared to controls (13.5 +/- 2.4 vs. 10.7 +/- 1.8; p = 0.002), but there was no difference between children with good compared to poor outcomes as determined by the Pediatric Cerebral Performance Category Scale score at 6-12 months after injury. We also did not find a correlation between the amount of Glx and the initial Glasgow Coma Scale score, duration of coma, nor with changes in spectral metabolites, including N-acetyl aspartate, choline, and myoinositol. In part, this may have occurred because, in this study, most patients with poor outcomes were studied later than patients with good outcomes, potentially beyond the time frame for peak elevation of Glx after injury. Additional early and late studies of patients with varying degrees of injury are required to assess the importance to the pathophysiology of TBI of this excitatory neurotransmitter.

Adolescent↗
PubMed2003

Shot-noise detection of ultrasound-tagged photons in ultrasound-modulated optical imaging.

We propose a new detection method for ultrasound-modulated optical tomography that allows us to perform parallel speckle detection with optimum shot-noise sensitivity, using a CCD camera. Moreover, we show that making use of a spatial filter system allows us to fully filter out speckle decorrelation noise. This method is confirmed by a test experiment.

Journal Article↗
PubMed2003

Complete dynamic repopulation of decellularized heart valves by application of defined physical signals-an in vitro study.

OBJECTIVE: Cardiovascular tissue engineering is a novel concept to develop ideal heart valve substitutes. The objective of this study was to use decellularized porcine pulmonary valves, ovine cells and dynamic tissue culture to obtain viable and biomechanically stable constructs, resembling native aortic heart valves. METHODS: Endothelial cells and myofibroblasts were obtained from ovine carotid arteries. Porcine pulmonary valves were decellularized enzymatically, reseeded and cultured using a hydrodynamic bioreactor system over a time period of 9 or 16 days. Controls were grown over an equivalent time period under static conditions. Specimens of each valve were examined biochemically (cell proliferation, DNA, collagen, 4-hydroxyproline, elastin and glycosaminoglycans), histologically (hematoxylin-eosin, Movat-pentachrome and immunostains) and mechanically (radial and circumferential strength). RESULTS: Histology and biochemical assays demonstrated the removal of almost all cells after decellularization with preservation of the extracellular matrix. Recellularization under pulsatile conditions was significantly improved after 9 and 16 days compared to static conditions. Biochemical and mechanical analysis revealed a continuous increase of cell mass, collagen and elastin contents and strength under pulsatile culture conditions compared to significantly lower values in the static controls. CONCLUSION: This study demonstrated the superiority of the hydrodynamic approach of cellular reseeding to replace decellularized porcine heart valves with ovine cells with almost complete preservation of extracellular matrix integrity.

Animals↗
PubMed2003

Heat-shock protein HSP70-2 genotypes in patients with Crohn's disease: a more severe clinical course with intestinal complications in presence of the PstI-polymorphism.

BACKGROUND: 70 kDa Heat shock proteins are involved in mucosal protecting reactions in the gut of patients with inflammatory bowel disease. Recently, a single nucleotide polymorphism (PstI, nucleotide 1267) was associated with intestinal perforations and formation of abscesses and fistulas in Japanese patients with Crohn's disease. Our purpose was to evaluate this phenomenon in Caucasian patients with Crohn's disease and to verify the clinical importance of this polymorphism. PATIENTS AND METHODS: 61 consecutive patients with Crohn's disease and 61 healthy control persons were examined. After DNA extraction and PCR amplification spanning the PstI-site, restriction fragment length polymorphism analyses (RFLP) were performed. Homozygous and heterozygous genotypes (AA, AB, BB) were then correlated with the clinical characteristics of the patients, especially with their intestinal complications. RESULTS: Intestinal perforations and formation of fistulas, abscesses and conglomerate tumors were significantly associated with allele B (p = 0.04). Patients with genotype BB showed the highest prevalence for surgical interventions (82%), whereas patients with genotype AA had the lowest prevalence (56%). Onset of disease, the need for immunosuppressive therapy and the occurrence of extraintestinal manifestations did not differ between the three genotypes. Allele A was significantly associated with combined involvement of ileum and colon. CONCLUSION: Caucasian patients carrying the HSP70-2 PstI-polymorphism seem to have a more severe form of Crohn's disease (perforations, abscesses, fistulas, conglomerate tumors). Especially, the homozygous genotype (BB) predisposes for a clinical course with high risk of surgical intervention.

Adolescent↗
PubMed2003

Pharmacology of novel heteroaromatic polycycle antibacterials.

Heteroaromatic polycycle (HARP) compounds are a novel class of small (M(w), 600 to 650) DNA-binding antibacterials. HARP compounds exhibit a novel mechanism of action by preferentially binding to AT-rich sites commonly found in bacterial promoters and replication origins. Noncovalent binding in the minor groove of DNA results in inhibition of DNA replication and DNA-dependent RNA transcription and subsequent bacterial growth. HARP compounds have previously been shown to have potent in vitro activities against a broad spectrum of gram-positive organisms. The present report describes the extensive profiling of the in vitro and in vivo pharmacology of HARP antibacterials. The efficacies of representative compounds (GSQ-2287, GSQ-10547, and GSQ-11203), which exhibited good MIC activity, were tested in murine lethal peritonitis and neutropenic thigh infection models following intravenous (i.v.) administration. All compounds were efficacious in vivo, with potencies generally correlating with MICs. GSQ-10547 was the most potent compound in vitro and in vivo, with a 50% effective dose in the murine lethal peritonitis model of 7 mg/kg of body weight against methicillin-sensitive Staphylococcus aureus (MSSA) and 13 mg/kg against methicillin-resistant S. aureus (MRSA). In the neutropenic mouse thigh infection model, GSQ-11203 reduced the bacterial load (MRSA and MSSA) 2 log units following administration of a 25-mg/kg i.v. dose. In a murine lung infection model, treatment with GSQ-10547 at a dose of 50 mg/kg resulted in 100% survival. In addition to determination of efficacy in animals, the pharmacokinetic and tissue disposition profiles in animals following administration of an i.v. dose were determined. The compounds were advanced into broad safety screening studies, including screening for safety pharmacology, genotoxicity, and rodent toxicity. The results support further development of this novel class of antibiotics.

Acetamides↗
PubMed2003

Randomised controlled trial of site specific advice on school travel patterns.

AIMS: To evaluate the effect of site specific advice from a school travel coordinator on school travel patterns. METHODS: Cluster randomised controlled trial of children attending 21 primary schools in the London boroughs of Camden and Islington. A post-intervention survey measured the proportion of children walking, cycling, or using public transport for travel to school, and the proportion of parents/carers very or quite worried about traffic and abduction. The proportion of schools that developed and implemented travel plans was assessed. RESULTS: One year post-intervention, nine of 11 intervention schools and none of 10 control schools had travel plans. Proportions of children walking, cycling, or using public transport on the school journey were similar in intervention and control schools. The proportion of parents who were very or quite worried about traffic danger was similar in the intervention (85%) and control groups (87%). However, after adjusting for baseline and other potential confounding factors we could not exclude the possibility of a modest reduction in parental concern about traffic danger as a result of the intervention. CONCLUSIONS: Having a school travel coordinator increased the production of school travel plans but there was no evidence that this changed travel patterns or reduced parental fears. Given the uncertainty about effectiveness, the policy of providing school travel coordinators should only be implemented within the context of a randomised controlled trial.

Bicycling↗
PubMed2003

Image guided navigation system-a new technology for complex endoscopic endonasal surgery.

PURPOSE: Endoscopic endonasal surgery (EES) has become the standard practice in sinonasal and anterior skull base surgery. The purpose of this manuscript is to describe experience using a new technology-the image guided navigation system (IGNS)-in complex cases undergoing EES. The advantages and disadvantages of computer aided surgery are discussed. PATIENTS AND METHODS: A total of 165 endoscopic endonasal procedures were performed between April 2001 and January 2003. IGNS was used in 34 patients in whom it was assumed that the ability to identify surgical sites accurately could be compromised by previous surgery, massive recurrent polyposis, or abnormal anatomy, or when biopsies had to be taken from specific anatomic locations (for example, clivus, wall of sphenoid sinus, orbital apex). The precision of the navigation system, total operating room time, surgeon's satisfaction and confidence, and intraoperative and postoperative complications were recorded. RESULTS: In 33 out of 34 patients the surgical procedure was uneventful. One patient with an atelectatic maxillary sinus developed a minor complication of preseptal orbital haematoma. In 94% the IGNS provided accurate anatomical localisation with less than 2 mm localisation error (1.1-2.0 mm, mean 1.6 mm). In all cases the surgical team felt that the system increased the intraoperative safety factor for the patient. The overall operating room time at the end of the study was 15 minutes longer than when regular EES was used. CONCLUSIONS: IGNS enables a new level of efficiency and safety in EES. Nevertheless, it is not advised for surgeons who are not familiar with regular EES. For the experienced endoscopist, however, IGNS is a valuable new tool in complex procedures.

Adult↗
PubMed2002

Thyroid hypoechogenicity in patients with chronic hepatitis receiving interferon-alpha therapy: evaluation by standardized grey scale ultrasonography.

BACKGROUND: Recombinant human interferon-a therapy of chronic hepatitis B and C is associated with the induction of thyroid dysfunction in up to 15%. Little is known about morphological changes of the thyroid gland, especially about its tissue echogenicity under this immunomodulative drug treatment. METHODS: 116 patients with chronic hepatitis B or C were consecutively investigated. 53 patients qualified for treatment with interferon-a alone or in combination with ribavirin. Patients with normal serum aminotransferase levels, advanced liver cirrhosis, hepatocellular carcinoma, active intravenous drug or alcohol abusus and with focal thyroid lesions (nodes, cysts, calcifications) were excluded. Thyroid function was determined by measurements of FT4, TSH and thyroidal autoantibodies. Ultrasonography was performed before, during and after interferon-a therapy including volumetry and standardized grey scale analysis. The data were compared with values of 100 euthyroid volunteers as control group. RESULTS: After six months of therapy patients differed from controls by significant TSH elevation (12.8 +/- 9.34 vs. 2.8 +/- 1.1 microU/ml, p<0.02). Six patients (11%) developed overt hypothyroidism with detectable thyroidal autoantibodies. Thyroid volume in patients was similar (13.0 +/- 4.1 ml) to that in the control group (12.6 +/- 4.7 ml). However, thyroid echogenicity of the patients was significantly lower after 6 months of therapy (21.9 +/- 2.5 grey scales) compared to the status before (25.6 +/- 2.3 grey scales) and compared to the values of controls (25.4 +/- 2.1 grey scales, p <0.002). CONCLUSION: Beside of functional disorders interferon-alpha leads to thyroid hypoechogenicity suggesting relevant morphological changes of the organ.

Adult↗