Biomedical subjects

J Gerber

Publications and source records attributed to J Gerber.

At least 19 recordsLinked to original sources

PubMed2001

Organotypic hippocampal cultures. A model of brain tissue damage in Streptococcus pneumoniae meningitis.

Hippocampal slices of newborn rats were exposed to either heat-inactivated Streptococcus pneumoniae R6 (hiR6) equivalent to 10(6) and 10(8) CFU/ml, lipoteichoic acid (LTA) (0.3 microg/ml and 30 microg/ml), peptidoglycans (PG) (0.3, 30, 50 and 100 microg/ml), pneumococcal DNA (pDNA) (0.3 and 30 microg/ml) or medium only (control). Cell injury was examined by Nissl staining, Annexin V and NeuN immunohistochemistry, and quantified by propidium iodide (PI) uptake and by determining neuron-specific enolase (NSE) concentration in the culture medium. Necrotic and apoptotic cell damage occurred in all treatment groups. Overall damage (Nissl and PI staining) was most prominent after hiR6 (10(8) CFU/ml), followed by LTA (30 microg/ml), pDNA (30 microg/ml), and not detectable after PG (30 microg/ml) exposure. PG (100 microg/ml) induced severe damage. Apoptotic cells were most frequent after exposure to LTA and hiR6. Damage in the neuronal cell layers (NeuN, NSE) was most severe after treatment with hiR6 (10(8) CFU/ml), followed by PG (100 microg/ml), pDNA (30 microg/ml), and LTA (30 microg/ml).

Animals↗

PubMed2000

Spatial memory and learning deficits after experimental pneumococcal meningitis in mice.

Survivors of bacterial meningitis frequently suffer from long-term sequelae, particularly from learning and memory deficits. For this reason, spatial memory and learning was studied in a mouse model of ceftriaxone-treated Streptococcus pneumoniae meningitis. Persistent deficits of spatial learning despite normal motor function were observed in mice infected with 10(4) colony-forming units (CFU) in 25 microl of saline into the right forebrain in comparison to mice treated with an equal amount of saline. Survivors of meningitis performed significantly worse in memorizing a hidden platform in a Morris water maze. After 2 weeks, the difference between post-meningitis and control mice diminished. Yet, when the platform was moved after 180 days, learning of the new location was still strongly impaired in mice surviving meningitis.

Animals↗

PubMed2000

Rifampin reduces production of reactive oxygen species of cerebrospinal fluid phagocytes and hippocampal neuronal apoptosis in experimental Streptococcus pneumoniae meningitis.

Bacterial compounds induce the production of reactive oxygen species (ROS) in meningitis. Rifampin releases smaller quantities of proinflammatory compounds from Streptococcus pneumoniae than do beta-lactam antibiotics. Therefore, rabbits infected intracisternally with S. pneumoniae were treated intravenously either with rifampin 5 mg/kg/h or ceftriaxone 10 mg/kg/h (n=9 each). Before initiation of antibiotic treatment, a strong positive correlation between ROS production of cerebrospinal fluid (CSF) phagocyte populations and bacterial CSF titers was observed (granulocytes: rs=.90, P<.0001; monocytes: rs=.81, P<.0001). CSF leukocytes from rifampin-treated rabbits produced less ROS (monocytes at 2 h after initiation of treatment: P=.045; at 5 h: P=.014; granulocytes at 5 h: P=.036) than did leukocytes from animals receiving ceftriaxone. The CSF malondialdehyde concentrations and the density of apoptotic neurons in the dentate gyrus were lower in rifampin- than in ceftriaxone-treated animals (P=.002 and.005). The use of rifampin to reduce the release of ROS and to decrease secondary brain injury appears promising.

Animals↗

PubMed2000

Stringent tests of shell model calculations in fp shell nuclei (46, 48)Ti and (50,52)Cr from measurements of g factors and B(E2) values

Measurements of magnetic moments and lifetimes of 2(+)(1) and 4(+)(1) states of (46,48)Ti and (50,52)Cr were performed with high accuracy via projectile Coulomb excitation and the technique of transient magnetic fields. The high quality of the data allows for the first time to establish stringent constraints on large scale shell model calculations. Whereas the global behavior of the data is well explained by full fp shell model calculations, distinct deviations in the g factors and B(E2) values of (46,48)Ti from theoretical predictions can be attributed to excitations of the 40Ca core. This suggestion is supported by recent Monte Carlo calculations which provide evidence that 48Ca is a better inert core.

Journal Article↗

PubMed2000

Gemifloxacin is effective in experimental pneumococcal meningitis.

In a rabbit model of Streptococcus pneumoniae meningitis, 5 mg of gemifloxacin mesylate (SB-265805) per kg/h reduced the bacterial titers in cerebrospinal fluid (CSF) almost as rapidly as 10 mg of ceftriaxone per kg/h (Deltalog CFU/ml/h +/- standard deviation [SD], -0.25 +/- 0.09 versus -0.38 +/- 0.11; serum and CSF concentrations of gemifloxacin were 2.1 +/- 1.4 mg/liter and 0.59 +/- 0.38 mg/liter, respectively, at 24 h). Coadministration of 1 mg of dexamethasone per kg did not affect gemifloxacin serum and CSF levels (2.7 +/- 1.4 mg/liter and 0.75 +/- 0.34 mg/liter, respectively, at 24 h) or activity (Deltalog CFU/ml/h +/- SD, -0.26 +/- 0.11).

Animals↗

PubMed2000

CT and arteriography in the evaluation of indirect myocardial revascularization with a free-muscle transplant: initial experience.

PURPOSE: To examine patients with advanced cardiovascular disease with radiology after indirect myocardial revascularization with a free-skeletal-muscle transplant and to determine whether the attached vessel remains patent over the middle and long terms. MATERIALS AND METHODS: In 10 patients with advanced, inoperable cardiovascular disease treated with indirect myocardial revascularization with a free-muscle transplant, radiologic follow-up was performed postoperatively and every 6 months. All 10 patients underwent selective arteriography of the anastomosed vessel and contrast material-enhanced helical computed tomography (CT) (transverse sections and reconstructions). RESULTS: All patients showed adequate vascular conditions postoperatively, as did nine of 10 patients after 1 year. In one patient, the anastomosed artery was occluded. CT showed time-dependent muscle degeneration in all patients. Postoperative, contrast-enhanced, superselective CT showed an area of high-attenuating uptake in the muscle transplant in all patients. After 1 year, CT depicted perfusion defects of the skeletal muscle in two patients. In eight patients, however, small vascular bridges from the skeletal muscle to the myocardium were detected. Radiologic results correlated well with clinical outcome and stress electrocardiograms. CONCLUSION: Helical intraarterial CT and arteriography were sensitive in depicting enhancement and remaining vital function in nine of 10 patients after indirect myocardial revascularization with a free-muscle transplant. This combination seems promising for postoperative examination in such patients.

Aged↗

PubMed2000

Follistatin (FS) in human cerebrospinal fluid and regulation of FS expression in a mouse model of meningitis.

OBJECTIVE: Follistatin (FS) is the specific binding protein of activin and expression of both factors is regulated by inflammatory agents. Therefore, FS concentrations were determined in cerebrospinal fluid (CSF) of patients with bacterial and viral meningitis or multiple sclerosis (MS), as well as in the CSF of patients without meningial inflammation or autoimmune diseases. Furthermore, a mouse pneumococcal meningitis model was used to localise the cellular sources of FS in brains of normal and meningitic mice. METHODS: FS concentrations in CSF were determined by ELISA; FS in mice was localised by in situ hybridisation and immunohistochemistry. RESULTS: FS concentrations were > or =0.4 microg/l in 22 of 66 CSF samples of meningitis patients versus 2 of 27 CSF samples from patients with multiple sclerosis (P<0.05) and 2 of 41 CSF specimen from patients without neuroinflammatory diseases (P<0.01). In the CSF of patients with meningitis, the concentration of FS was correlated with total protein (P<0.005) and lactate concentrations (P<0.05), but not with leukocyte counts, interval between onset of disease and CSF analysis, or clinical outcome. The CSF-to-serum ratios of FS and albumin also correlated significantly (P<0.0005). In some patients with meningitis the CSF-to-serum ratios suggested that the elevated FS in CSF did not originate from serum alone. FS was localised in mice brains to neurones of the hippocampus, dentate gyrus, neocortex, and to the choroid plexus. Analyses of brains and other organs from uninfected and infected animals sacrificed 6-36 h after infection did not reveal any obvious differences in the distribution and intensity of FS mRNA and protein expression. CONCLUSIONS: The concentration of FS in humans is elevated during meningitis. In some patients the increase is caused by a release of FS from brain into CSF. Data from the mouse meningitis model suggest that increased CSF concentrations of FS in meningitis appear not to be accompanied by an elevated number of cells containing FS mRNA or protein in the brain.

Animals↗

PubMed2000

Contrast-enhanced transcranial color-coded duplexsonography in stroke patients with limited bone windows.

BACKGROUND AND PURPOSE: Thickening of the temporal bone in stroke-age patients may obviate sonographic evaluation of the circle of Willis in 20% to 30% of patients. We assessed the diagnostic efficacy of contrast-enhanced transcranial color-coded duplexsonography (TCCD) for noninvasive evaluation of the circle of Willis in stroke patients with limited bone windows. METHODS: Of 171 consecutive patients who presented with ischemic symptoms in the middle cerebral artery (MCA) territory, 49 patients (32 female, 17 male; age range, 70.5+/-10.6 years) had no detectable colorflow signals from the circle of Willis by TCCD because of limited acoustic windows. These 49 patients received an IV injection of a sonographic contrast-enhancing agent, Levovist (Schering; Berlin, Germany), and were re-examined. Correlative imaging studies of the circle of Willis were obtained in 42 of 49 of these patients. RESULTS: In 38 of 49 patients, contrast-enhanced TCCD enabled full visualization of the circle of Willis bilaterally; in an additional five patients, contrast-enhanced TCCD revealed only the portion of the circle of Willis ipsilateral to the probe through one temporal bone. In six of these 43 patients, contrast-enhanced TCCD showed MCA stenosis and MCA occlusion in three; three of the six cases of MCA stenosis and all three cases of the MCA occlusion were found on the symptomatic side. In six of 49 patients, no colorflow signals were obtained after contrast enhancement. All contrast-enhanced TCCD findings were confirmed by CT angiography, transfemoral digital subtraction angiography, MR angiography, or a combination of all three correlative studies. Levovist produced no serious adverse events. CONCLUSION: In stroke-age patients with limited acoustic windows, contrast-enhancement with Levovist can markedly increase the sensitivity of TCCD and increase the detection of clinically relevant intracranial arterial disease.

Aged↗

PubMed2000

[Comparison of cathepsin-B-like activity and CA 125 assays use in ovarian cancer diagnosis].

BACKGROUND: Determination of serum cathepsin B-like activity was used as a diagnostic marker of ovarian cancer. The aim of this study was to compare its diagnostic utility with CA 125 assay. METHODS: In 50 patients with epithelial ovarian cancer and 20 with ovarian cyst cathepsin B-like activity by fluorimety and CA 125 concentration by luminiscence immunoassay, were determined. The obtained results were compared by two cut-off values computed from the data obtained in healthy controls and ovarian cysts (cathepsin B: 11 and 108 mU/ml; CA 125: 35 and 135 U/ml), respectively. RESULTS: In differential diagnosis between ovarian carcinomas and ovarian cysts cathepsin B shows similar specificity (95%) as CA 125 but higher sensitivity (63.5% vs 50%). Both cathepsin B and CA 125 are good predictors of tumour response and recurrence CONCLUSIONS: Adding CA 125 determination to cathepsin B-like activity in the laboratory diagnostics of ovarian cancer increased the sensitivity and positive predictive values as compared to the use of cathepsin B alone.

Adolescent↗

PubMed2000

The effect of changing stimulus intensities on median nerve somatosensory-evoked potentials.

We investigated median nerve somatosensory-evoked potentials (SEP) in 31 healthy volunteers to test the hypothesis that 1) increasing stimulus intensity influences SEP components in both amplitude and latency 2) SEP components respond differently to changing intensities. Cluster analysis and analysis of variance were used for statistical testing. Three groups of components could be found according to latency changes in response to increasing stimulus intensities: N13, and P15, the primary cortical response (N19, P22) and the components over 30 ms. In general, SEP components below 30 ms significantly shortened in latency and increased in amplitude with subsequent saturation. In contrast, in components over 30 ms latencies decreased linearly and amplitudes changed inhomogeneously. The clear effect of stimulus intensity on most median nerve SEP components makes it necessary to maintain comparable stimulus intensities when comparing intra- and interindividual registrations.

Adolescent↗

PubMed1999

Rifampin reduces early mortality in experimental Streptococcus pneumoniae meningitis.

Compared with beta-lactam antibiotics, rifampin releases smaller quantities of proinflammatory cell wall products from Streptococcus pneumoniae in vitro. Mice infected intracerebrally with S. pneumoniae were treated subcutaneously with 2-mg doses of rifampin or ceftriaxone (n=43 each) every 12 h for 3 days and then observed for another 3 days. Rifampin reduced overall mortality from 49% to 26% (P=.04). Kaplan-Meyer analysis revealed a substantial reduction of mortality during the first 24 h in mice receiving rifampin (difference in survival time: P=.007). Eight h after receiving a single 2-mg dose of rifampin or ceftriaxone, rifampin-treated mice had lower serum and cerebrospinal fluid concentrations of lipoteichoic and teichoic acids than did ceftriaxone-treated mice (median serum level: <0.5 vs. 27.0 ng/mL, P=.02; median cerebrospinal fluid level of pooled specimens: 97.5 vs. 206.0 ng/mL). Thus, the use of rifampin appears promising for reducing the release of proinflammatory bacterial components and decreasing early mortality in bacterial meningitis.

Animals↗

PubMed1999

Serum haptoglobin, CA 125 and interleukin 6 levels in malignant and non-malignant tumors of the ovary.

In sera of women with malignant and non-malignant ovarian tumors, concentrations of the following proteins were determined: haptoglobin, measured by the reactions either with hemoglobin (Hp-Hb) or with concanavalin A (Hp-Con A), CA 125 antigen and interleukin 6 (IL-6). Besides preoperative data, obtained from all the patients and the group of healthy women, in the patients with ovarian cancer (III/IV FIGO stages) effects of administration of cytostatics were measured by monitoring changes in the levels of the examined parameters through the course of the therapy. All the results were submitted to statistical evaluation which showed differences and correlations among definite groups (normal/non-malignant, normal/cancers, non-malignant/cancers). Similar results were obtained for Hp-Hb and CA 125 determination. Moreover, a correlation between haptoglobin level and age was found. Patterns of monitoring revealed a surprising absence of Hp-Con A interaction in some cases.

Adolescent↗

PubMed1998

Contributions of pathway and neuron to preferential motor reinnervation.

Motor axons regenerating after transection of mixed nerve preferentially reinnervate distal muscle branches, a process termed preferential motor reinnervation (PMR). Motor axon collaterals appear to enter both cutaneous and muscle Schwann cell tubes on a random basis. Double-labeling studies suggest that PMR is generated by pruning collaterals from cutaneous pathways while maintaining those in motor pathways (the "pruning hypothesis"). If all collaterals projecting to muscle are saved, then stimulation of regenerative sprouting should increase specificity by increasing the number of motoneurons with at least one collateral in a muscle pathway. In the current experiments, collateral sprouting is stimulated by crushing the nerve proximal to the repair site before suture, a maneuver that also conditions the neuron and predegenerates the distal pathway. Control experiments are performed to separate these effects from those of collateral generation. Experiments were performed on the rat femoral nerve and evaluated by exposing its terminal cutaneous and muscle branches to HRP or Fluoro-Gold. Crush proximal to the repair site increased motor axon collaterals at least fivefold and significantly increased the percentage of correctly projecting motoneurons, consistent with the pruning hypothesis. Conditioning the nerve with distal crushes before repair had no effect on specificity. A graft model was used to separate the effects of collateral generation and distal stump predegeneration. Previous crush of the proximal femoral nerve significantly increased the specificity of fresh graft reinnervation. Stimulation of regenerative collateral sprouting thus increased PMR, confirming the pruning hypothesis. However, this effect was overshadowed by the dramatic specificity with which predegenerated grafts were reinnervated by fresh uncrushed proximal axons. These unexpected effects of predegeneration on specificity could involve a variety of possible mechanisms and warrant further study because of their mechanistic and clinical implications.

Animals↗

PubMed1998

Granulocytes in the subarachnoid space of humans and rabbits with bacterial meningitis undergo apoptosis and are eliminated by macrophages.

The contribution of leukocyte apoptosis to the resolution of meningeal inflammation in bacterial meningitis was studied in the cerebrospinal fluid (CSF) and in meningeal infiltrates of humans and rabbits by in situ tailing, flow cytometry, agarose gel electrophoresis, and electron microscopy. In humans, the rate of apoptotic granulocytes was 21.0+/-20.8% (n=11) in cytocentrifuge preparations and 3.3+/-3.4 (n=14) in putrid infiltrates of autopsy cases (P=0.02). In rabbits, CSF pleocytosis peaked 8 h after the initiation of antibiotic treatment (5311+/-3122/microl). At this time, the rate of apoptotic granulocytes was 15.2+/-7.3% in CSF and 1.8+/-1.4% in the meningeal infiltrates (each group n=6, P=0.007). Thereafter, the rate of apoptotic granulocytes in CSF declined below 10%. In humans and rabbits, bands representing internucleosomal fragments of approximately 180 base pairs and multiples thereof were documented on agarose gels. Phagocytosis of apoptotic granulocytes by macrophages was visualized by light and electron microscopy. In conclusion, during resolution of subarachnoid space inflammation in bacterial meningitis, a substantial fraction of granulocytes undergoes apoptosis. These granulocytes are removed by phagocytosis by macrophages. Apoptosis is more frequent in granulocytes floating in the CSF than in adherent cells.

Animals↗

PubMed1998

Lumbar and ventricular CSF protein, leukocytes, and lactate in suspected bacterial CNS infections.

Protein concentration, leukocyte density, and lactate concentration were studied in 41 pairs of ventricular and lumbar CSF drawn at an interval of less than 24 hours from patients with suspected bacterial CNS infections. The ventriculo-lumbar ratios ranged from 0.003 to 10.2 (median=0.42) for protein and from 0.002 to 53.5 (median=0.17) for leukocytes. The uneven distribution of leukocytes and proteins in the CSF space may produce findings that fail to indicate bacterial CNS infections. Lactate was distributed more homogeneously in the CSF space than protein and leukocytes (ventriculo-lumbar ratio 0.52 to 1.66 [median=0.811).

Adult↗

PubMed1998

Training environment for inferior vena caval filter placement.

This paper describes a Virtual Environment system designed to aid in training interventional radiologists in inferior vena cava filter placement. It is being developed as part of a VE simulator for a number of surgical and interventional radiology procedures at the Laboratory for Advanced Computer Applications in Medicine at the George Washington University. In this procedure a filter is placed in the inferior vena cava to prevent blood clots from the lower portion of the body from reaching the lungs and causing a pulmonary embolus. The simulation is designed to provide both tutorial and testing modes for the filter placement procedure.

Algorithms↗

PubMed1998

[Dependence of serous activity of cathepsin B on histological types of ovarian carcinomas].

The preoperative activity of cathepsin B was determined in the serum of 110 patients with primary ovarian carcinomas and in 35 women with benign ovarian tumor. The significant increase of cathepsin B activity in ovarian carcinomas is independent of its types in comparison to benign ovarian tumor. The percentage of the results with value above the cut-off values was the highest for serous types of ovarian carcinomas. The dependence between the increase of cathepsin B activity and the FIGO stage of the disease was observed only for serous and endometrioid type of ovarian carcinomas.

Adolescent↗

PubMed1997

Implementing quality assurance programs in multigroup practices for treating hypercholesterolemia in patients with coronary artery disease.

Healthcare reform is driving the development of specialty physician practices into larger regional and national physician networks. These networks arise from the federation of > or =2 practices that negotiate with managed-care organizations for contracts. Developing cardiovascular networks and establishing and implementing lipid management quality assurance programs into the network are presented in this article. Goals of the lipid management program include enhancing the identification, diagnosis, education, and comprehensive treatment of patients with cardiovascular disease. Utilizing an integrated, coordinated, multidisciplinary approach to lipid management allows the cardiology network to improve patients' quality of life, reduce long-term costs, and gain a competitive advantage for successful contracting. A network lipid management program involves targeting eligible patients and treating them to a targeted level for low-density lipoprotein (LDL) cholesterol where possible. Among cardiologists, there is a consensus that achieving an LDL cholesterol of < 100 mg/dL for patients with pre-existing cardiovascular disease is desirable. Secondary lipid management program goals include: (1) collecting, storing, and analyzing patient demographics; (2) implementing programs involving lifestyle modification, smoking cessation, weight control; and (3) measuring clinical and economic outcomes. Convergence of several driving forces in managing hypercholesterolemia provides cardiologists with the ability to improve the process. These forces include: market-consolidated delivery systems, established lipid management guidelines, and employer-initiated policies requiring higher quality care within managed-care organizations. Methods to achieve enhanced treatment effectiveness, patient satisfaction, and control costs are discussed. Utilizing multidisciplinary teams including nurse case managers, clinical pharmacists, dietitians, and physician assistants to achieve lipid level goals and for nutritional counseling is desirable. Developing disease state management programs, treatment algorithms, databases with analytic reports, and process improvement across the network is of paramount importance for future progress and success.

Cardiology↗