Search PubMed⌕ Search

Biomedical subjects

C Brandt

Publications and source records attributed to C Brandt.

At least 37 records · Page 2Linked to original sources
PubMed2001

Repeated low-dose treatment of rats with pilocarpine: low mortality but high proportion of rats developing epilepsy.

Systemic administration of pilocarpine in rats can result in a chronic behavioral state that is similar to human temporal lobe epilepsy. The pilocarpine model of epilepsy is widely used for studying the factors that contribute to the development of epilepsy as a consequence of status epilepticus (SE). For this purpose, pilocarpine is either administered alone at a high systemic dose or in combination with lithium, which markedly potentiates the convulsant effect of pilocarpine. Both experimental protocols, however, are associated with high mortality rates. In the present study, we evaluated whether mortality rate in rats can be decreased by repeated administration of low doses of pilocarpine. The time the rats spent in SE was limited by diazepam. Preliminary experiments in lithium-free rats indicated that repeated low-dose administration of pilocarpine is too time-consuming to produce SE compared to single high-dose administration. All subsequent experiments were performed in lithium-pretreated rats. Single-dose injection of 30 mg/kg pilocarpine produced SE in approximately 70% of the animals, but 45% of the rats died although SE was interrupted by diazepam after 90 min. Repeated i.p. administration of 10 mg/kg pilocarpine at 30-min intervals resulted in SE after 2-4 injections; the mean dose of pilocarpine needed to induce SE was 26 mg/kg. When SE was interrupted after 90 min, mortality rate was below 10%, which was significantly lower compared to the protocol with one single administration of 30 mg/kg pilocarpine. In contrast to mortality rate, the development of spontaneous recurrent seizures did not differ between experimental protocols. Almost all rats which had experienced a SE of at least 60 min developed chronic epilepsy. Average latency to the first spontaneous seizure was approximately 40 days. The frequency and severity of spontaneous seizures was not significantly different between protocols, although animal groups with repeated low-dose treatment tended to have higher frequencies of spontaneous seizures compared to single-dose administration. The present study demonstrates that systemic treatment of lithium-pretreated rats with several low doses of pilocarpine efficiently produces SE and chronic epilepsy with much lower mortality rates than single-dose pilocarpine.

Animals↗
PubMed2001

Horizontal gene transfer and host specificity of beta-haemolytic streptococci: the role of a putative composite transposon containing scpB and lmb.

Beta-haemolytic streptococci are important human and animal pathogens: their genetic traits that are associated with the ability to infect human hosts remain, however, unclear. The surface protein, Lmb, mediates the adherence of Streptococcus agalactiae to human laminin. For further analysis of the corresponding gene, the adjacent genomic regions were sequenced. Lmb is localized on a putative composite transposon of 16 kb and is flanked by two copies of a novel insertion sequence element (ISSag2). It harbours the genes scpB and lmb, which are 98% identical with the respective genes of Streptococcus pyogenes. Analysis of the distribution of these genes and ISSag2 among 131 streptococcal strains revealed that all of the human isolates, but only 20% (12 of 61) of the animal isolates, contained scpB and lmb or their homologues. To investigate if the putative transposon can be mobilized, an erythromycin resistance marker was incorporated into the lmb gene of S. agalactiae. Screening for mutant strains with a regained susceptibility for erythromycin identified strains with a deletion of scpB, lmb, and one copy of ISSag2. We hypothesize that a horizontal gene transfer caused the exchange of scpB and lmb and that the ability of S. pyogenes, S. agalactiae and group C and G streptococcal strains to colonize or infect human hosts is dependent on their presence.

Adhesins, Bacterial↗
PubMed2001

Exercise tolerance and quality of life in elderly patients with chronic atrial fibrillation.

BACKGROUND: Atrial fibrillation is the most common arrhythmia affecting the elderly. Although the risk of cardioembolic stroke is well defined, the effects of chronic atrial fibrillation on exercise tolerance and quality of life have been less well quantified. METHODS: We compared a group of 52 elderly patients with chronic atrial fibrillation to a group of 48 control patients in sinus rhythm. Each patient underwent an interview that incorporated the Short Form-36 Health Survey (SF-36) to quantify individual perceptions on quality of life. In addition each person underwent physiologic testing that included a Modified Bruce Protocol exercise tolerance test, 24-hour ambulatory monitor test, and an echocardiogram. RESULTS: Both groups were elderly, 77 vs 76 years of age (P=0.35). The two groups had similar ejection fractions, 55.4% vs 58.4% (P=0.10). The atrial fibrillation patients demonstrated a higher level of comorbidity based on the Charlson Comorbidity Index, 2.46 vs 1.57 (P=0.03). On formal exercise testing there was no statistical difference in exercise duration between the two groups 9.0 vs 10.1 minutes (P=0.24). Similarly the Physical Summary Score (PCS) and the Mental Summary Score (MCS) of the SF-36 quality of life survey did not demonstrate a statistical difference between the two groups. PCS: 43.0 vs 45.9 (P=0.24); MCS: 52.5 vs 55.7 (P=0.07). CONCLUSIONS: Despite a higher level of comorbidity, elderly, ambulatory patients with chronic atrial fibrillation demonstrate similar exercise tolerance and report similar quality of life to a group of age-matched control patients in sinus rhythm. There is a cohort of patients in chronic atrial fibrillation in whom a strategy of rate control and anticoagulation may be appropriate.

Aged↗
PubMed2001

Generation of pedigree diagrams for web display using scalable vector graphics from a clinical trials database.

The standard method of studying inherited disease is to observe its pattern of distribution in families, that is, its pattern in a pedigree. For clinical studies focused on inherited disease, a pedigree diagram is a valuable visual tool for the display of inheritance patterns. We describe the creation of a web-based pedigree display module for Trial/DB, a Web accessible database developed at the Yale Center for Medical Informatics (YCMI) to support clinical research studies. The pedigree diagram is generated dynamically from the database. The icons representing each subject in the pedigree are selectable hyperlinks that will display detailed clinical data collected on the subject. Microsoft Active Server Page and Scalable Vector Graphics (SVG) are used to create the interactive pedigree diagrams.

Clinical Trials as Topic↗
PubMed2000

Interleukin 21 and its receptor are involved in NK cell expansion and regulation of lymphocyte function.

Cytokines are important in the regulation of haematopoiesis and immune responses, and can influence lymphocyte development. Here we have identified a class I cytokine receptor that is selectively expressed in lymphoid tissues and is capable of signal transduction. The full-length receptor was expressed in BaF3 cells, which created a functional assay for ligand detection and cloning. Conditioned media from activated human CD3+ T cells supported proliferation of the assay cell line. We constructed a complementary DNA expression library from activated human CD3+ T cells, and identified a cytokine with a four-helix-bundle structure using functional cloning. This cytokine is most closely related to IL2 and IL15, and has been designated IL21 with the receptor designated IL21 R. In vitro assays suggest that IL21 has a role in the proliferation and maturation of natural killer (NK) cell populations from bone marrow, in the proliferation of mature B-cell populations co-stimulated with anti-CD40, and in the proliferation of T cells co-stimulated with anti-CD3.

Amino Acid Sequence↗
PubMed2000

The cyl genes of Streptococcus agalactiae are involved in the production of pigment.

The cyl genes of Streptococcus agalactiae are required for the production of hemolysin. Based on the observation that nonhemolytic S. agalactiae mutants do not produce pigment, a close genetic linkage between hemolysin and pigment has been postulated. To investigate this genetic linkage and to identify genes involved in the production of the S. agalactiae pigment, we screened mutant libraries for nonpigmented clones. Four distinct mutants were isolated with a nonpigmented and nonhemolytic phenotype. The mutations had occurred either in known cyl genes or in two open reading frames located immediately downstream. These novel genes are cotranscribed with the cyl gene cluster and were designated cylF and cylI. Our data indicate that identical genes participate in the production of S. agalactiae hemolysin and pigment.

Cloning, Molecular↗
PubMed2000

Potential of allospecific gene-engineered T cells in transplantation gene therapy: specific T cell activation determines transgene expression in vitro and in vivo.

T lymphocytes, regardless of their specificity, are considered key targets for genetic modification in the treatment of inherited or acquired human diseases. In this study, we generated Lewis T cell lines specific for Dark Agouti rat alloantigens and tested the potential of allospecific T lymphocytes as carriers of genes encoding therapeutic proteins in transplantation gene therapy. These allospecific T lymphocytes were successfully, stably transduced with enhanced green fluorescent protein (EGFP) by an Mo-MuLV-based retrovirus vector. A novel gene delivery protocol was utilized, resulting in nearly 100% EGFP-expressing T cells. This approach enabled tracking of allospecific transduced T cells in vivo and illustrates their transgene production by fluorometric determination after ex vivo isolation. Quantitation of EGFP transgene expression was used to determine the influence of T cell receptor-specific activation on transgene regulation. A strict positive correlation between activation state and expression level was detected in vitro and in vivo. The activation-induced increase in transgene expression could be blocked by interference with T cell activation signaling pathways by cyclosporin A, anti-CD4 MAb, or CTLA4-Ig. These data provide strong evidence that direct or indirect effects caused by activation-induced transcription factors are crucial in transgene upregulation. Allospecific activation in spleens, lymph nodes, and transplanted grafts can be considered as antigen-specific targeting strategy. This activation might be useful in expressing therapeutic proteins such as TGF-beta or IL-10 specific to these sites. T lymphocyte priming and activation might be prevented or altered by modification of the local microenvironments, thereby exerting a therapeutic influence on acute and chronic graft rejection processes.

Abatacept↗
PubMed2000

The use of water-jetting technology in prostheses revision surgery-first results of parameter studies on bone and bone cement.

Water-jet cutting techniques have been used in industrial applications for many different materials. Recently these techniques have been developed into a revolutionary cutting tool for soft tissues in visceral surgery. The present study investigates the usage of this cutting technology for the revision surgery of endoprostheses. In the first part of the study, samples of bovine bone and acrylic bone cement (PMMA) were cut using an industrial jet cutting device with pure water. Below 400 bar, only PMMA was cut; above 400 bar, bone was also cut, but only pressures above 800 bar resulted in clinically useful rates of material removal (cut depth 2. 4 mm at 10 mm/min traverse speed). In the second part of the study, the effect of adding biocompatible abrasives to the water in order to reduce the required pressure was investigated, resulting in a significantly higher removal of material. At 600 bar, PMMA was cut 5. 2 mm deep with plain water and 15.2 mm deep with added abrasives. The quality of the cuts was increased by the abrasive. Though there was no clear selectivity between bone and PMMA any more, the rate of material removal at similar pressures was significantly higher for PMMA than for bone (600 bar: 1.6 mm cut depth for bone samples, 15.2 mm for PMMA). The measured cut depths with either method were not influenced by a change of the cutting direction with respect to the main direction of the osteons in the bone. However, a reduction of the jet surface angle (90 degrees to 23 degrees ) resulted for bone in a significantly lower cut depth at 600 bar (plain water: 0.62 mm vs. 0.06 mm; abrasive: 1.61 mm vs. 0.60 mm). The laboratory experiments indicate that abrasive water jets may be suitable for cutting biomaterials like bone and bone cement.

Analysis of Variance↗
PubMed2000

Stimulatory and inhibitory action of cytokines on the regulation of hCMV-IE promoter activity in human endothelial cells.

Viral promoters are commonly used as regulatory elements in gene therapy vectors due to their strong activity in various cell lines in vitro. However, transgene expression under the control of viral promoters in vivo has been shown to be limited to a short period of time. Several mechanisms for the transient expression of the delivered transgene may be important including deletion of transduced cells or promoter downregulation. Recently we reported that cytokines may either decrease or increase the activity of the human cytomegalovirus (hCMV) promoter in monocytes depending on the differentiation status of the transduced cells. For many applications, the gene of interest has to be delivered into an inflammatory milieu (tumour, ischaemia/reperfusion, vector-induced inflammation etc.). In this report we investigated the influence of various inflammatory cytokines on the hCMV-IE promoter activity in transduced human primary endothelial cells (Huvec) in vitro, which may be the first target cells after gene transfer into different organs. Cultured cells were infected with an E1-deleted adenoviral vector encoding for E. colibeta-galactosidase (Adbeta-gal) driven by the hCMV-IE promoter and incubated either with or without various cytokines. Our results indicate that interferon-gamma (IFN-gamma) and interleukin-10 (IL-10) downregulate promoter activity in endothelial cells whereas, in contrast, tumour necrosis factor (TNF-alpha), interleukin 1beta (IL-1beta) and interleukin 4 (IL-4) increased the promoter activity. These results suggest that inflammatory processes influence the in vivo expression of transferred viral promoter controlled genes of interest.

Cells, Cultured↗
PubMed2000

Effect of a subanesthetic dose of ketamine on memory and conscious awareness in healthy volunteers.

RATIONALE: Ketamine is an NMDA receptor antagonist with psychotogenic and cognitive effects in healthy volunteers and schizophrenic patients which has been proposed to be a useful tool to investigate neurobiological basis of schizophrenia. OBJECTIVE: The present study characterized the effects of a subanesthetic dose of ketamine on memory and related subjective states of awareness in healthy volunteers. METHODS: Twenty-six subjects were given either a 60-min ketamine (0.5 mg/kg per hour) or a placebo infusion. To obtain constant plasma ketamine throughout the experiment, ketamine was administered using a computer-controlled infusion system. Subjects carried out episodic memory tasks involving words presented before and during infusion. Memory performance was assessed with recognition and free recall tasks. Subjective states of awareness were assessed using an experiential approach. Levels of psychopathology were evaluated with BPRS. RESULTS: Ketamine impaired performance in free recall and recognition of words presented during, but not before, infusion. There were no differences between groups concerning states of awareness associated with recognition memory. Subjects under ketamine had higher BPRS total scores as well as BPRS negative and positive cluster scores than control subjects. CONCLUSIONS: Ketamine decreases episodic memory performance by impairing encoding, but not retrieval processes. It does not selectively impair subjective states of awareness associated with recognition memory as it has been seen in patients with schizophrenia. Ketamine might mimic the memory impairment associated with acute, but not chronic, forms of schizophrenia.

Adult↗
PubMed2000

[Functional MR-pancreatography with secretin. A comparison of imaging quality and diagnostic value].

PURPOSE: The aim of the present study was to assess imaging improvement and diagnostic value of secretin stimulated MR-pancreatography (MRP) compared to conventional MRP. MATERIALS AND METHODS: 50 patients were studied with a 1.0 T system using a single-shot-TSE sequence (RARE). Imaging quality and diameter of the different parts of the pancreatic tract and diagnoses were monitored before and after secretin. RESULTS: The visualization of the normal main pancreatic duct (MPD) was improved significantly in head, body and tail. Side branches were not depicted at all. Even in chronic pancreatitis a significant improvement of imaging quality could be observed, but only in patients without duct dilation before secretin. In advanced disease with duct dilation, secretin stimulation provided no further diagnostic improvement. CONCLUSIONS: In conclusion, secretin increases the diagnostic value of MRP especially in patients with normal or non-dilated native MPD and may help to avoid unnecessary invasive procedures such as ERCP.

Adolescent↗
PubMed2000

CD4(+) T-cell-mediated antiviral protection of the upper respiratory tract in BALB/c mice following parenteral immunization with a recombinant respiratory syncytial virus G protein fragment.

We analyzed the protective mechanisms induced against respiratory syncytial virus subgroup A (RSV-A) infection in the lower and upper respiratory tracts (LRT and URT) of BALB/c mice after intraperitoneal immunization with a recombinant fusion protein incorporating residues 130 to 230 of RSV-A G protein (BBG2Na). Mother-to-offspring antibody (Ab) transfer and adoptive transfer of BBG2Na-primed B cells into SCID mice demonstrated that Abs are important for LRT protection but have no effect on URT infection. In contrast, RSV-A clearance in the URT was achieved in a dose-dependent fashion after adoptive transfer of BBG2Na-primed T cells, while it was abolished in BBG2Na-immunized mice upon in vivo depletion of CD4(+), but not CD8(+), T cells. Furthermore, the conserved RSV-A G protein cysteines and residues 193 and 194, overlapping the recently identified T helper cell epitope on the G protein (P. W. Tebbey et al., J. Exp. Med. 188:1967-1972, 1998), were found to be essential for URT but not LRT protection. Taken together, these results demonstrate for the first time that CD4(+) T cells induced upon parenteral immunization with an RSV G protein fragment play a critical role in URT protection of normal mice against RSV infection.

Adoptive Transfer↗
PubMed2000

[Agoraphobia with panic disorder or epilepsy? Differential diagnostic considerations in a case].

This paper describes a patient suffering from agoraphobia with panic disorder and with a history of self-induced epileptic seizures. The anxiety syndrome causing the admission to hospital could be diagnosed as non epileptic. He was treated successfully with a behaviour therapy. We discuss the possible interactions between anxiety disorders and epileptic seizures and some diagnostic demarcations. We conclude that even people with mild forms of epilepsy may develop an anxiety disorder arising from the fear of again getting epileptic seizures. To work out the different syndromes of epileptic seizures and of panic attacks should be part of the therapy.

Adult↗
PubMed2000

Building a vision for the future: strategic planning in a shared governance nursing organization.

Today's health care delivery environment is marked by extreme turbulence and ever-increasing complexity. Now, more than ever, an organization's strategic plan must do more than outline a business plan. Rather, the strategic plan is a fundamental tool for building and sustaining an organizational vision for the future. The strong, dynamic strategic plan (1) represents a long-range vision for improving organizational performance, (2) provides a model for planning and implementing structures and processes for the management of outcomes, (3) reflects and shapes the organizational culture and customer focus, (4) provides decision support for difficult operational choices made day to day, and (5) integrates and aligns the work of the organization. This article describes the development, implementation, and evaluation of a methodology for strategic planning within a shared governance nursing organization. Built upon the strategic plan of the hospital, the process undertaken by the nursing organization reflects the following commitments: (1) to develop a strategic plan that is meaningful and part of daily work life at all levels of the nursing organization, (2) to make the plan practical and realistic through incremental building, (3) to locate and articulate accountability for each step, and (4) to build in a process for checking progress toward goal achievement and readjusting the plan as necessary.

Decision Making, Organizational↗
PubMed1999

[Problem-based learning (POL) in environmental medicine].

"Environmental medicine" is a new sub-discipline in the spectrum of medical specialization in Germany. The Berlin Academy of Occupational Medicine and Health Protection, now a branch of the Berlin Chamber of Physicians, developed a 200-lesson curriculum for physicians who want to specialize in this field. Coincidentally during the initial courses, the attendants were already highly qualified ("Facharzt"-level) and experts in various occupational fields, and hence the composition of the classes was highly heterogeneous on the levels of practical experience as well as theoretical knowledge. The Academy therefore decided to change the teaching method to Problem-Oriented Learning (POL). This required training tutors for small learning groups, supervision for these tutors and supplying adequate teaching materials and a stimulating environment for the student. The "Arbeitsgruppe Reformstudiengang Medizin" (Medicine Curriculum Reform Project) at the Berlin Humboldt University as well as the Dutch Rijksuniversiteit Limburg in Maastricht helped in the process of conceptualization. Participants worked in groups of up to 8 persons under non-directive tutors. A new "case" was presented every day, and the students developed individual learning goals according to the Seven Steps-method, which were then researched individually and with the help of outside experts. The findings were reported back and discussed in the group. Initially there was irritation, but after two or three days participants got used to not being lectured. Instead of being passive recipients of expert knowledge they felt that the POL method of learning enhanced their competence to act independently.

Curriculum↗
PubMed1998

Influence of maternal antibodies on vaccine responses: inhibition of antibody but not T cell responses allows successful early prime-boost strategies in mice.

The transfer of maternal antibodies to the offspring and their inhibitory effects on active infant immunization is an important factor hampering the use of certain vaccines, such as measles or respiratory syncytial virus vaccine, in early infancy. The resulting delay in protection by conventional or novel vaccines may have significant public health consequences. To define immunization approaches which may circumvent this phenomenon, experiments were set up to further elucidate its immunological bases. The influence of maternal antibodies on antibody and T cell responses to measles hemagglutinin (MV-HA) were analyzed following MV-HA immunization of pups born to immune or control BALB/c mothers using four different antigen delivery systems: live or inactivated conventional measles vaccine, a live recombinant canarypox vector and a DNA vaccine. High levels (> 5 log10) of maternal anti-HA antibodies totally inhibited antibody responses to each of the vaccine constructs, whereas normal antibody responses were elicited in presence of lower titers of maternal antibodies. However, even high titers of maternal antibodies affected neither the induction of vaccine-specific Th1/Th2 responses, as assessed by proliferation and levels of IFN-gamma and IL-5 production, nor CTL responses in infant mice. On the basis of these unaltered T cell responses, very early priming and boosting (at 1 and 3 weeks of age, respectively) with live measles vaccine allowed to circumvent maternal antibody inhibition of antibody responses in pups of immune mothers. This was confirmed in another immunization model (tetanus toxoid). It suggests that effective vaccine responses may be obtained earlier in presence of maternal antibodies through the use of appropriate immunization strategies using conventional or novel vaccines for early priming.

Animals↗
PubMed1998

Tools for immunization guideline knowledge maintenance. II. Automated Web-based generation of user-customized test cases.

IMM/Test is a prototype software tool built to generate test cases that can be used to help test and verify the internal logic of an immunization forecasting program. A forecasting program takes as input a child's immunization history and produces recommendations as to which vaccinations are due and which should be scheduled next. IMM/Test was developed to test a specific immunization forecasting program, IMM/Serve. In addition, IMM/Test has been incorporated into a broader Web-based tool, IMM/Web, which allows the user (e.g., a member of an immunization registry staff) to customize the parameters used for immunization forecasting (e.g., the minimum ages for each dose and the minimum wait intervals between doses) to reflect local practice. IMM/Web then generates a customized set of test cases that may be used to test the user's immunization forecasting program. The user may also request that the test cases be automatically passed to IMM/Serve to analyze using the newly defined parameters. The paper describes the internal design of IMM/Test and IMM/Web and discusses certain lessons learned in the implementation of the two programs.

Adolescent↗