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Biomedical subjects

S Schreiber

Publications and source records attributed to S Schreiber.

At least 109 records · Page 6Linked to original sources
PubMed2001

Antivascular treatment of solid melanoma tumors with bacteriochlorophyll-serine-based photodynamic therapy.

We describe here a strategy for photodynamic eradication of solid melanoma tumors that is based on photo-induced vascular destruction. The suggested protocol relies on synchronizing illumination with maximal circulating drug concentration in the tumor vasculature attained within the first minute after administrating the sensitizer. This differs from conventional photodynamic therapy (PDT) of tumors where illumination coincides with a maximal concentration differential of sensitizer in favor of the tumor, relative to the normal surrounding tissue. This time window is often achieved after a delay (3-48 h) following sensitizer administration. We used a novel photosensitizer, bacteriochlorophyll-serine (Bchl-Ser), which is water soluble, highly toxic upon illumination in the near-infrared (lambda max 765-780 nm) and clears from the circulation in less than 24 h. Nude CD1 mice bearing malignant M2R melanotic melanoma xenografts (76-212 mm3) received a single complete treatment session. Massive vascular damage was already apparent 1 h after treatment. Changes in vascular permeability were observed in vivo using contrast-enhanced magnetic resonance imaging (MRI), with the contrast reagent Gd-DTPA, by shortening spin-spin relaxation time because of hemorrhage formation and by determination of vascular macromolecular leakage. Twenty-four hours after treatment a complete arrest of vascular perfusion was observed by Gd-DTPA-enhanced MRI. Histopathology performed at the same time confirmed primary vascular damage with occlusive thrombi, hemorrhage and tumor necrosis. The success rate of cure of over 80% with Bchl-Ser indicates the benefits of the short and effective treatment protocol. Combining the sensitizer administration and illumination steps into one treatment session (30 min) suggests a clear advantage for future PDT of solid tumors.

Animals↗
PubMed2001

A randomized trial of fluoxetine versus amitriptyline in musculo-skeletal pain.

In a preclinical study we found fluoxetine alone to induce a serotonin-mediated, dose-dependent antinociceptive effect in the mouse hot plate assay. In the present study we evaluated the clinical implication of these findings, comparing the efficacy of fluoxetine with that of amitriptyline for musculo-skeletal pain. Forty non-depressed patients, suffering from low back pain and whiplash associated cervical pain were enrolled in a randomized, six-week, "blind-rater" study, comparing the analgesic effect of amitriptyline (50-75 mgs/day) with that of fluoxetine (20 mgs/day). Twenty patients were randomly assigned to the amitriptyline group, and twenty to the fluoxetine group. Visual analogue and verbal rating scales were used for the assessment of pain intensity and pain relief. Thirty-five patients concluded the study. Moderate or good relief of pain was reported by 14 of the 17 patients (82%) in the amitriptyline group, and by 14 of the 18 patients (77%) in the fluoxetine group. The difference in responses between amitriptyline and fluoxetine was not statistically significant. In our study, fluoxetine relieved low back pain and whiplash associated cervical pain with efficacy similar to that of amitriptyline, offering an alternative for patients unable to tolerate the tricyclic antidepressants' side effects.

Adolescent↗
PubMed2001

[Anti-TNF alpha in rheumatoid arthritis].

Thanks to the better understanding of the physiopathological mechanisms in action in rheumatoid arthritis (RA), new therapeutic weapons have appeared, which have dramatically modified our approach of the disease. These so-called "biological" therapies antagonize the action of the cytokine at the top of the cascade which maintains the synovial inflammation, and leads to the joint destruction, i.e. the Tissue Necrosis Factor alpha (TNF alpha). Several controlled clinical studies have clearly demonstrated their short and middle term efficacy and safety profile, and they will soon become at the Belgian clinicians disposal. They have a rapid and dramatic effect on the signs and symptoms of RA and they slow down the radiologic progression. Some questions remain unresolved concerning their place in the general therapeutic strategy against RA, due to the uncertainties of their use in the long run, and to their cost.

Antibodies, Monoclonal↗
PubMed2000

First observation of self-amplified spontaneous emission in a free-electron laser at 109 nm wavelength

We present the first observation of self-amplified spontaneous emission (SASE) in a free-electron laser (FEL) in the vacuum ultraviolet regime at 109 nm wavelength (11 eV). The observed free-electron laser gain (approximately 3000) and the radiation characteristics, such as dependency on bunch charge, angular distribution, spectral width, and intensity fluctuations, are all consistent with the present models for SASE FELs.

Journal Article↗
PubMed2000

Mechanisms in failure of infliximab for Crohn's disease.

BACKGROUND: Expression of tumour necrosis factor-alpha (TNF-alpha) is increased in patients with Crohn's disease. Nuclear factor kappa B (NFkappaB) controls transcription of inflammation genes. Treatment with monoclonal antibodies to TNF (infliximab) in refractory Crohn's disease results in a remission rate of 30-50% after 4 weeks. We aimed to assess the clinical and immunological mechanism of failure to respond to infliximab. METHODS: 24 patients with steroid refractory, chronic active Crohn's disease (Crohn's disease activity index [CDAI]>200), who showed an inflammatory manifestation in the sigmoid colon, had a single infusion of infliximab (5 mg/kg bodyweight) and were followed up for 16 weeks. Secretion capacity for TNF-alpha was assessed in whole-blood cytokine assays and nuclear concentrations of NFkappaB p65 were determined in colonic mucosal biopsy samples. FINDINGS: 21 (88%) of 24 patients were in remission (CDAI<150) after 1 week, ten (42%) at 4 weeks, five (21%) at 8 weeks, and two (8%) of 24 at 12 and 16 weeks. Six (29%) of 21 patients who reached remission in week 1 relapsed at week 4, 13 (62%) at week 8, 17 (81%) at week 12, and 19 (90%) at week 16. Infliximab downregulated secretion of TNF-alpha in all patients to undetectable concentrations (day 1 after infusion). Relapsers were characterised by a rise in TNF-alpha secretion capacity and by increase of mucosal nuclear NFkappaB p65 before reactivation of clinical symptoms. INTERPRETATION: Infliximab greatly improved clinical symptoms in 88% of patients with Crohn's disease after 1 week. Response in some patients was of short duration. Reactivation of the mucosal and the systemic immune system preceded clinical relapse.

Antibodies, Monoclonal↗
PubMed2000

A hybrid between Na+,K+-ATPase and H+,K+-ATPase is sensitive to palytoxin, ouabain, and SCH 28080.

Na(+),K(+)-ATPase is inhibited by cardiac glycosides such as ouabain, and palytoxin, which do not inhibit gastric H(+),K(+)-ATPase. Gastric H(+),K(+)-ATPase is inhibited by SCH28080, which has no effect on Na(+),K(+)-ATPase. The goal of the current study was to identify amino acid sequences of the gastric proton-potassium pump that are involved in recognition of the pump-specific inhibitor SCH 28080. A chimeric polypeptide consisting of the rat sodium pump alpha3 subunit with the peptide Gln(905)-Val(930) of the gastric proton pump alpha subunit substituted in place of the original Asn(886)-Ala(911) sequence was expressed together with the gastric beta subunit in the yeast Saccharomyces cerevisiae. Yeast cells that express this subunit combination are sensitive to palytoxin, which interacts specifically with the sodium pump, and lose intracellular K(+) ions. The palytoxin-induced K(+) efflux is inhibited by the sodium pump-specific inhibitor ouabain and also by the gastric proton pump-specific inhibitor SCH 28080. The IC(50) for SCH 28080 inhibition of palytoxin-induced K(+) efflux is 14.3 +/- 2.4 microm, which is similar to the K(i) for SCH 28080 inhibition of ATP hydrolysis by the gastric H(+),K(+)-ATPase. In contrast, palytoxin-induced K(+) efflux from cells expressing either the native alpha3 and beta1 subunits of the sodium pump or the alpha3 subunit of the sodium pump together with the beta subunit of the gastric proton pump is inhibited by ouabain but not by SCH 28080. The acquisition of SCH 28080 sensitivity by the chimera indicates that the Gln(905)-Val(930) peptide of the gastric proton pump is likely to be involved in the interactions of the gastric proton-potassium pump with SCH 28080.

Acrylamides↗
PubMed2000

A possible role for caveolin as a signaling organizer in olfactory sensory membranes.

Fast kinetics and sensitivity of olfactory signaling raise the question of whether the participating proteins may be associated in supramolecular transduction complexes. We found evidence that caveolin proteins could play an important role in organizing signaling elements in olfactory sensory neurons. Western blot analysis indicated that caveolins are highly enriched in olfactory sensory membranes, where they co-localize in detergent-insoluble complexes with key components of the signaling pathways. Furthermore, the results of immunoprecipitation experiments suggest that G proteins and effector enzyme form preassembled subcellular complexes with caveolins. Since anti-caveolin antibodies and synthetic peptides derived from the scaffolding domains of caveolin-1 and caveolin-2 effectively attenuated second messenger responses in sensory cilia preparations in a characteristic manner, the data led to the suggestion that caveolins could mediate the assembly of signaling complexes within specialized membrane microdomains of olfactory sensory neurons.

Animals↗
PubMed2000

Anticipation in inflammatory bowel disease: a phenomenon caused by an accumulation of confounders.

Inflammatory bowel disease (IBD) has a definite genetic component as documented by epidemiological and linkage evidence. It shows an earlier onset of disease in children of affected patients than in their parents. This has lead to speculations about genetic anticipation in this disorder. 2,007 IBD patients with sporadic disease and 472 multiplex familial cases (including 103 affected parents and 99 children of affected patients) were evaluated with a multi-item questionnaire as part of a study of inflammatory bowel disease genetics. The Mann-Whitney U-test and the general linear model were used for analysis. Clinical characteristics such as presence of fistulae, stenoses, extraintestinal manifestations, and other parameters, which are related to the severity of the disease, were found to be similar between familial and sporadic cases of IBD (corrected P > or = 0.31 for all tests). The mean-age-of onset in children of affected patients was 19.4 years earlier than in their parents. However, the age of the parental cohort was significantly higher (27 years) and the diagnostic interval also longer (1.7 years). If these confounders are corrected in a general linear model, no significant difference is evident for the age-of-onset between the groups (P > or = 0.52). There is no evidence for genetic anticipation in inflammatory bowel disease. The absence of genetic anticipation is consistent with the clinical similarity of familial and sporadic inflammatory bowel disease. This finding justifies the primary genetic analysis of familial disease under the assumption that their genetic background will be representative for all presentations of IBD.

Adult↗
PubMed2000

Deletion of 13q14 remains an independent adverse prognostic variable in multiple myeloma despite its frequent detection by interphase fluorescence in situ hybridization.

Interphase fluorescence in situ hybridization (FISH) studies of chromosomal region 13q14 were performed to investigate the incidence and clinical importance of deletions in multiple myeloma (MM). Monoallelic deletions of the retinoblastoma-1 (rb-1) gene and the D13S319 locus were observed in 48 of 104 patients (46.2%) and in 28 of 72 (38.9%) patients, respectively, with newly diagnosed MM. FISH studies found that 13q14 was deleted in all 17 patients with karyotypic evidence of monosomy 13 or deletion of 13q but also in 9 of 19 patients with apparently normal karyotypes. Patients with a 13q14 deletion were more likely to have stage III disease (P =.022), higher serum levels of beta(2)-microglobulin (P =.059), and a higher percentage of bone marrow plasma cells (P =.085) than patients with a normal 13q14 status on FISH analysis. In patients with a deletion of 13q14, myeloma cell proliferation (Ki-67) was markedly increased (22.0% +/- 6.9% compared with 15.6% +/- 8.2% in patients without the deletion; P =.0008). Evaluation of bromodeoxyuridine incorporation in 5 patients revealed that both rb-1-deleted and rb-1-normal MM subpopulations were proliferative. The presence of a 13q14 deletion on FISH analysis was associated with a significantly lower rate of response to conventional-dose chemotherapy (40.8% compared with 78. 6%; P =.009) and a shorter overall survival (24.2 months compared with > 60 months; P <.005) than in patients without the deletion. Multivariate analysis of prognostic factors confirmed the independent predictive value of 13q14 deletions for shortened survival. In conclusion, deletions of 13q14 are frequently detected by interphase FISH in patients with newly diagnosed MM, correlate with increased proliferative activity, and represent an independent adverse prognostic feature in MM. (Blood. 2000;95:1925-1930)

Adult↗
PubMed2000

Repetitive transcranial magnetic stimulation is as effective as electroconvulsive therapy in the treatment of nondelusional major depressive disorder: an open study.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS), a new method for the stimulation of the central nervous system, is being proposed as a potential new treatment in patients with major depressive disorder (MDD). We tested the hypothesis that rTMS would be as effective as electroconvulsive therapy (ECT) in patients with MDD. METHODS: Forty patients with MDD referred for ECT were randomly assigned to either ECT or rTMS. Repetitive transcranial magnetic stimulation was performed at 90% power of the motor threshold. The stimulation frequency was 10 Hz for either 2 sec (first eight patients) or 6 sec (final 12 patients) for 20 trains. Patients were treated for up to 20 treatment days. Electroconvulsive therapy was performed according to standard protocols. RESULTS: Overall patients responded best to ECT (chi(2) = 3.8, p <.05). Patients with MDD and psychosis responded significantly better to ECT (chi(2) = 9.2, p <. 01), whereas MDD patients without psychosis responded similarly to both treatments (chi(2) = 0.0, ns). The analysis of variance with repeated measures of clinical variables for the whole sample revealed significant treatment effects for both groups; however, interaction between group and treatment was seen only for the Global Assessment of Function and the Sleep assessment. When the psychosis-nonpsychosis grouping was considered, patients with psychosis responded dramatically better to ECT in all assessments, whereas those without psychosis responded similarly to both treatments. CONCLUSIONS: Overall ECT was a more potent treatment for patients with MDD, this being particularly evident in patients with MDD and psychosis; however, in patients with MDD without psychosis the effects of rTMS were similar to those of ECT. The results we report are encouraging and support an important role for rTMS in the treatment of severe MDD; however, additional blinded studies are needed to precisely define this role.

Administration, Cutaneous↗
PubMed2000

Postural dependency of the cerebral venous outflow.

We have shown that predominance of the jugular veins in cerebrovenous drainage is limited to the supine position. In the erect position, the vertebral venous system represents the major outflow pathway.

Adult↗
PubMed2000

[Computer-assisted implant positioning in knee endoprosthetics. Kinematic analysis for optimization of surgical technique].

Modern approaches in knee endoprosthetics using computer-assisted navigation systems are based on matching procedures which refer to osseous anatomical landmarks. However, surface replacement techniques require a correct position of the implants in relation to the bone, as well as an optimal postoperative interaction of the ligaments and the surface design of the endoprosthesis. Functional aspects are of elementary importance. Insufficient design of the prosthetic surface or incorrect implantation overstresses ligamentous structures and result in functional disturbance, increased wear, and early loosening of the components. The present computer model permits a quantitative analysis of different implant positions. Distal positioning of the femoral component or insufficient resection of the tibial plateau results in a lag of extension. Increased distal resection of the tibial plateau produces marked translatory instabilities in the sagital plane which exceed the absolute height of the resection in millimeters. Monocondylar replacements with preservation of the ACL react kinematically more sensitively than bicondylar endoprostheses sacrificing the ACL. The results of this study are systematically summarized in an algorithm and indicate correction steps in order to avoid functional impairment. The computer model delivers in addition some basic data for optimized navigation procedures in knee surgery and demonstrates the importance of further developments in custom-made endoprosthetics.

Algorithms↗
PubMed2000

Analysis of single-nucleotide polymorphisms in the interleukin-4 receptor gene for association with inflammatory bowel disease.

Genetic linkage analysis in families with multiple cases of inflammatory bowel disease (IBD) has mapped a gene which confers susceptibility to IBD to the pericentromeric region of chromosome 16 (IBD1). The linked region includes the interleukin(IL)-4 receptor gene (IL4R). Since IL-4 regulation and expression are abnormal in IBD, the IL4R gene is thus both a positional and functional candidate for IBD1. We screened the gene for single-nucleotide polymorphisms (SNPs) by fluorescent chemical cleavage analysis, and tested a subset of known and novel SNPs for allelic association with IBD in 355 families, which included 435 cases of Crohn's disease and 329 cases of ulcerative colitis. No association was observed between a haplotype of four SNPs (val50ile, gln576arg, A3044G, G3289A) and either the Crohn's disease or ulcerative colitis phenotypes using the transmission disequilibrium test. There was also no evidence for association when the four markers were analyzed individually. The results indicate that these variants are not significant genetic determinants of IBD, and that the IL4R gene is unlikely to be IBD1. Linkage disequilibrium analyses showed that the val50ile and gln576arg variants are in complete equilibrium with each other, although they are separated by only about 21 kilobases of genomic DNA. This suggests that a very dense SNP map may be required to exclude or detect disease associations with some candidate genes.

Alleles↗
PubMed2000

The effect of electroconvulsive therapy (ECT) on implicit memory: skill learning and perceptual priming in patients with major depression.

While explicit memory in amnesics is impaired, their implicit memory remains preserved. Memory impairment is one of the side effects of electroconvulsive therapy (ECT). ECT patients are expected to show impairment on explicit but not implicit tasks. The present study examined 17 normal controls and 17 patients with severe major depressive disorder who underwent right unilateral ECT. Patients were tested in three sessions: 24-48 hours prior to, 24-48 hours following the first ECT, and 24-48 hours following the eighth ECT. The controls were tested in three sessions, at time intervals that paralleled those of the patients. Implicit memory was tested by the perceptual priming task - Partial Picture-Identification (PPI). The skill learning task used entailed solving the Tower of Hanoi puzzle (TOHP). Explicit memory was tested by picture recall from the PPI task, verbal recall of information regarding the TOHP, and by the Visual Paired Association (VPA) test. Results showed that explicit questions about the implicit tasks were impaired following ECT treatment. Patients' learning ability, as measured by the VPA task, was only impaired in the first testing session, prior to ECT treatment, reflecting the effect of depression. In addition, groups only differed in the first session on the learning rate of the skill learning task. Perceptual priming was preserved in the patients' group in all sessions, indicating that it is resilient to the effect of depression and ECT. The results are interpreted in terms of the differential effect of depression and ECT on explicit and implicit memory.

Adult↗
PubMed2000

The antinociceptive effect of trazodone in mice is mediated through both mu-opioid and serotonergic mechanisms.

The antinociceptive effects of trazodone (a triazolopyridine derivative with antidepressant activity) and its interaction with various opioid, noradrenaline and serotonin receptor subtypes were evaluated. Mice were tested with a hotplate analgesia meter. Trazodone induced a dose-dependent antinociceptive effect following i.p. administration. The ED(50) for mice in the hotplate assay for trazodone was 24.8 mg/kg (9.8; 67.4; 95% CL). The effect of opioid, adrenergic and serotonergic receptor antagonists was examined as to their ability to block trazodone antinociception. Trazodone-induced antinociception was significantly inhibited by naloxone, beta-FNA and naloxonazine, but not by nor-BNI or naltrindole, implying involvement of mu1- and mu2-opioid mechanisms. When adrenergic and serotonergic antagonists were used, metergoline (p<0.05) but not phentolamine or yohimbine, decreased antinociception elicited by trazodone, implying a clear 5-HT mechanism of antinociception. When trazodone was administered together with various agonists of the opioid receptor subtypes, it significantly potentiated antinociception mediated by mu1- and mu2- opioid receptor subtypes. Summing up these results, we conclude that the antinociceptive effect of trazodone is mainly influenced by the mu1- +mu2-opioid receptor subtype combined with the serotonergic receptor. These results explain the diffuse clinical use of trazodone in the management of some pain syndromes, and in opioid- and alcohol-detoxification programs, but raise questions regarding a possible 'indirect' opioid-dependence induced by trazodone itself.

Analgesics↗
PubMed2000

Androgen receptor in pituitary adenomas of the gonadotroph cell complex.

Although androgen receptors have been identified in normal gonadotroph and somatotroph cells of the pituitary, immunohistochemical studies have failed to reveal these receptors in pituitary adenomas so far. Using a monoclonal antibody to androgen receptor in our series of 60 adenomas of the gonadotroph cell complex (20 FSH/LH cell adenomas, 20 null cell adenomas, 20 oncocytic adenomas), only one null cell adenoma showed strong nuclear immunostaining. All the other antibodies were completely negative. The significance of this finding in correlation with clinical data is still unclear, although it may be associated with more rapid tumor growth. In paraadenomous tissue, some normal gonadotrophs expressed the androgen receptor.

Adenoma, Oxyphilic↗
PubMed2000

Deletions of chromosome 13q in monoclonal gammopathy of undetermined significance.

Since deletion of chromosome 13q is a clinically relevant feature in multiple myeloma (MM), we analyzed bone marrow plasma cells from 29 patients with monoclonal gammopathy of undetermined significance (MGUS) to investigate the chromosome 13 status in MGUS. Studies were performed by interphase fluorescence in situ hybridization (FISH) with a panel of 13q14-specific probes (RB1, D13S319, D13S25, D13S31). Plasma cells with a deletion of at least one of the 13q14 loci were detected in 13 patients (44.8%) with MGUS. In five patients (17.2%), deletions of all four 13q14-specific probes were observed, and the additional deletion of a 13q telomeric region (D13S327) suggested loss of the entire 13q arm or monosomy 13. Loss of 13q14 was observed to be monoallelic and to occur in 11.0 to 35.0% of plasma cells (cut-off levels for a deletion <10% with all probes). Nine of 17 patients (52.9%) with MM progressing from a pre-existing MGUS had evidence for a deletion of 13q14 as determined by FISH with the RB1 probe. These results suggest that deletion of 13q14 is an early event in the development of monoclonal gammopathies, but its role for the eventual progression to MM remains to be determined prospectively.

Adult↗