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Biomedical subjects

S Brem

Publications and source records attributed to S Brem.

At least 19 recordsLinked to original sources

[Detection of leptospira in the vitreous body of horses without ocular diseases and of horses with equine recurrent uveitis (ERU) using transmission-electron microscopy].

Equine recurrent uveitis (ERU) is caused by persistent intraocular leptospira, which appear to use the vitreous body as a refuge. The detection of leptospira in the vitreous body of horses with spontaneous ERU by histological methods has not yet been described. Thirty eight vitreous body samples from 36 horses with ERU (collected during vitrectomy), and 10 vitreous body samples obtained from 5 horses without ocular disease (control group) were examined by transmission electron microscopy. Prior to sample collection, 2 ml of a leptospira culture suspension were injected into the vitreous body of 2 eyes enucleated from horses of the control group. The detection of leptospira in samples, experimentally inoculated with these bacteria was uncomplicated; in vitreous body samples from horses with spontaneous ERU the detection was successful in only a few cases (3/38). The morphologically varying envelope of leptospira in vitreous body samples of horses which developed ERU spontaneously suggests the existence of a bacterial masquerade in vivo.

Animals↗

Microbiological and serological study of leptospirosis in horses at slaughter: first isolations.

A bacteriological survey of kidneys from 145 abattoir horses was performed, which resulted in the isolation of two Leptospira strains. The isolates were serologically typed as belonging to serogroups Australis and Pomona, and REA identified them as L. interrogans serovar Bratislava and L. kirschneri serovar Tsaratsovo, respectively. These are the first Leptospira isolates obtained from horses in Portugal and the Bratislava strain is the first serogroup Australis strain to be isolated in this country. The 145 horses were also serologically tested for leptospiral antibodies, and 37% had MAT titres #10878;1:10.

Agglutination Tests↗

Method for determining novolac glycidyl ether (NOGE) and its chlorohydrins in oily canned foods.

In order to be analysed, NOGE components with epoxy groups must be separated from polar food material to prevent losses through uncontrolled reactions. Samples are homogenized minimally and extracted into a phase of minimized polarity. The NOGE components are then separated from the oil by extraction into acetonitrile and analysed by RPLC with fluorescence detection. Hydrolysis of the epoxy, and chlorohydroxy functions to diols may help the analysis. Application and limitations of the method are illustrated by examples. Detection limits vary widely, depending on interfering food components, but legal limits below 1 mg/kg can hardly be reliably enforced.

Animals↗

Clinical, microbiological and pathological observations in laboratory beagle dogs infected with leptospires of the serogroup Sejroe.

In beagle dogs infections with two different serovars of serogroup Sejroe are described. Saxkoebing titres of 27 beagle dogs were controlled for 7 to 9 months. Dogs serologically positive for saxkoebing showed no clinical symptoms. From the urine, an isolation of the microorganisms was possible. At necropsy, there was no evidence of any changes related to the proven infection. Histopathologically, in animals with persistent titres a mild interstitial nephritis was found. No changes were observed in the liver. Another three beagle dogs died after about two days of acute clinical illness with febrile temperature, exsiccosis and hematuria. Histopathologically, incipient inflammation was seen in the liver and kidneys. Besides, hepatic cholestasis, renal hemoglobin casts and degeneration of renal tubular epithelia were observed. In concurrent animals, an infection with another serovar of serogroup Sejroe was proven serologically. This serovar was also isolated. Transmission and spreading of leptospirosis within animals shelters or laboratories from clinically healthy carriers and its prevention as well as the protection of animal caretakers are discussed. Since leptospires are sensitive to physical and chemical methods of disinfection, this is easily feasible. However, the optimal prevention appears to be a stock- or population-specific vaccination.

Animals↗

Angiogenesis and Cancer Control: From Concept to Therapeutic Trial.

BACKGROUND: There is extraordinary interest in developing angiosuppressive agents for cancer treatment. Several new agents appear promising for the treatment of a variety of human cancers. Current concepts and new agents in clinical trials are the focus of this article. In particular, the introduction of a new treatment for human brain tumors is presented in detail, using an antiangiogenic agent, penicillamine, and depletion of an obligatory cofactor of angiogenesis, copper. METHODS: The explosive increase in literature on antiangiogenesis is reviewed using computerized search, findings presented at the recent national cancer and angiogenesis meetings. A specific protocol, NABTT 97-04, "Penicillamine and Copper Reduction for Newly Diagnosed Glioblastoma," is presented as an example of angiotherapeutic drug discovery. RESULTS: A number of promising molecular approaches are being introduced to suppress tumor angiogenesis. Major categories of angiogenesis antagonists include protease inhibitors, direct inhibitors of endothelial cell proliferation and migration, suppression of angiogenic growth factors, inhibition of endothelial-specific integrin/ survival signaling, chelators of copper, and inhibitors with specific other mechanisms. The preliminary results of early trials offer a glimpse into how antiangiogenesis therapy will be integrated into future care of the patient with cancer. CONCLUSIONS: Thirty-five antiangiogenesis therapies are currently being evaluated in clinical trials. As we learn more about the fundamental mechanisms of angiogenesis, eg, the role of copper in growth factor activation, effective methods of cancer control will be implemented.

Journal Article↗

MRI measurement of brain tumor response: comparison of visual metric and automatic segmentation.

An automatic magnetic resonance imaging (MRI) multispectral segmentation method and a visual metric are compared for their effectiveness to measure tumor response to therapy. Automatic response measurements are important for multicenter clinical trials. A visual metric such as the product of the largest diameter and the largest perpendicular diameter of the tumor is a standard approach, and is currently used in the Radiation Treatment Oncology Group (RTOG) and the Eastern Cooperative Oncology Group (EGOG) clinical trials. In the standard approach, the tumor response is based on the percentage change in the visual metric and is categorized into cure, partial response, stable disease, or progression. Both visual and automatic methods are applied to six brain tumor cases (gliomas) of varying levels of segmentation difficulty. The analyzed data were serial multispectral MR images, collected using MR contrast enhancement. A fully automatic knowledge guided method (KG) was applied to the MRI multispectral data, while the visual metric was taken from the MRI films using the T1 gadolinium enhanced image, with repeat measurements done by two radiologists and two residents. Tumor measurements from both visual and automatic methods are compared to "ground truth," (GT) i.e., manually segmented tumor. The KG method was found to slightly overestimate tumor volume, but in a consistent manner, and the estimated tumor response compared very well to hand-drawn ground truth with a correlation coefficient of 0.96. In contrast, the visually estimated metric had a large variation between observers, particularly for difficult cases, where the tumor margins are not well delineated. The inter-observer variation for the measurement of the visual metric was only 16%, i.e., observers generally agreed on the lengths of the diameters. However, in 30% of the studied cases no consensus was found for the categorical tumor response measurement, indicating that the categories are very sensitive to variations in the diameter measurements. Moreover, the method failed to correctly identify the response in half of the cases. The data demonstrate that automatic 3D methods are clearly necessary for objective and clinically meaningful assessment of tumor volume in single or multicenter clinical trials.

Adult↗

Survival rates in patients with primary malignant brain tumors stratified by patient age and tumor histological type: an analysis based on Surveillance, Epidemiology, and End Results (SEER) data, 1973-1991.

OBJECT: The authors present population-based survival rate estimates for patients with malignant primary brain tumors based on an analysis of 18 years of data obtained from the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute. METHODS: Estimates of survival rates at 2 and 5 years after diagnosis for patients with specific histological tumor types were categorized by patient's age at diagnosis (< or = 20 years, 21-64 years, and 65 years or older) and by the time period in which the patients were diagnosed (1973-1980, 1981-1985, 1986-1991). Where appropriate, survival estimates were adjusted for changing patterns in the mean age at diagnosis. CONCLUSIONS: The authors observed a pattern of declining survival rates in patients with increasing age of the patient at diagnosis for most histological groups and overall improvements in survival rates of patients across these time periods adjusting for age at diagnosis. There were improvements in 2- and 5-year survival rates over the three time periods for children and adults with medulloblastoma and for adults with astrocytoma and oligodendroglioma. Improvements in survival rates for pediatric patients with medulloblastoma have leveled off in the most recent time period, and gender differences in survival rates for patients with this tumor, which were present in the 1970s, have disappeared. Clinically significant improvements in survival rates were not apparent in patients aged 65 years and older. Changes in diagnostic and treatment procedures since the mid-1970s have resulted in improved survival rates for patients diagnosed as having medulloblastoma, oligodendroglioma, and astrocytoma, controlling for age at diagnosis. Glioblastoma multiforme continues to be the most intractable brain tumor.

Adult↗

[Intraocular and serum antibody titers to Leptospira in 150 horses with equine recurrent uveitis (ERU) subjected to vitrectomy].

Between February 1993 and July 1997, 150 horses suffering from recurrent uveitis were subjected to parsplana vitrectomy. In these horses, antibody titers to Leptospira serovars were determined in serum samples and in samples from diluted vitreous collected during vitrectomy. Although the vitreous samples were diluted with 250 ml of balanced salt solution, in 86 of the 150 vitreous samples (= 57%) the antibody titers were higher than in the serum samples. Additionally, serum samples from 77 horses suffering from ERU, but which were not subjected to vitrectomy, and serum samples from 97 horses with clinically normal eyes were analyzed for antibodies to Leptospira serovars. Among the 227 horses with ERU (150 treated surgically, 77 treated conservatively) 50 horses (50 of 227 = 22%) had serum antibody titers to Leptospira serovars of > or = 1:800. Among the 97 horses with clinically normal eyes, 24 horses (24 of 97 = 25%) had serum antibody titers to Leptospira serovars of > or = 1:800. In undiluted vitreous samples from 20 horses with clinically normal eyes, no antibody titers to Leptospira serovars could be detected. Among the 150 horses with ERU, 90 animals (90 of 150 = 60%) had antibody titers of > or = 1:100 in the diluted vitreous samples, the difference being highly significant (p < 0.001). The findings are discussed in relation to the etiology of recurrent uveitis in horses.

Animals↗

Malignant brain tumors in the elderly.

The increase in the incidence of primary brain tumors in the elderly over the last decade represents a serious problem because of the severe disability and risk of death associated with this disease. Surgery remains the mainstay of the management of malignant gliomas, and the magnitude of the resection correlates with the length of survival. The additional standard treatment modalities are reviewed. This article also discusses novel approaches being evaluated to treat both newly diagnosed and recurrent brain tumors.

Aged↗

[Appearance of antibodies against Borrelia burgdorferi in different populations of pigeons (Columba livia var. domestica vel urbana].

Borrelia burgdorferi, the causative agent of Lyme borreliosis, can infect both mammals and birds. The purpose of the present survey was to determine the presence of antibodies against B. burgdorferi in different populations of pigeons. 1043 sera from pigeons (carrier-, urban-, show-pigeons) were examined by standard serological methods. B.burgdorferi shows crossreaction with B. anserina. Therefore all sera were evaluated by IFAT and ELISA for both Borrelia species. The results demonstrate no evidence for the pigeons (Columba livia var. domestica vel urbana) to be reservoir for Borrelia burgdorferi.

Animals↗

What is the etiology of human brain tumors? A report on the first Lebow conference.

Although the conference could not provide a definitive etiologic explanation for the observed increase in incidence of human brain tumors, particularly among the elderly, nevertheless, this interdisciplinary gathering of prominent scientists and clinicians proved invaluable in identifying new avenues of research. Clearly, the puzzle of what causes brain tumors is highly complex, involving links to ionizing/electromagnetic radiation, familial, and dietary factors. The Lebow Conference provided an important scientific framework upon which to build further research studies, and its influence will be felt for years to come.

Brain Neoplasms↗

Placebo-controlled trial of safety and efficacy of intraoperative controlled delivery by biodegradable polymers of chemotherapy for recurrent gliomas. The Polymer-brain Tumor Treatment Group.

Chemotherapy for brain tumours has been limited because of difficulty in achieving adequate exposure to the tumour without systemic toxicity. We have developed a method for local sustained release of chemotherapeutic agents by their incorporation into biodegradable polymers. Implantation of the drug-impregnated polymer at the tumour site allows prolonged local exposure with minimal systemic exposure. We conducted a randomised, placebo-controlled, prospective study to evaluate the effectiveness of biodegradable polymers impregnated with carmustine to treat recurrent malignant gliomas. In 27 medical centres, 222 patients with recurrent malignant brain tumours requiring re-operation were randomly assigned to receive surgically implanted biodegradable polymer discs with or without 3.85% carmustine. Randomisation balanced the treatment groups for all of the prognostic factors examined. Median survival of the 110 patients who received carmustine polymers was 31 weeks compared with 23 weeks for the 112 patients who received only placebo polymers (hazard ratio = 0.67, p = 0.006, after accounting for the effects of prognostic factors). Among patients with glioblastoma, 6-month survival in those treated with carmustine-polymer discs was 50% greater than in those treated with placebo (mortality = 32 of 72 [44%] vs 47 of 73 [64%], p = 0.02). There were no clinically important adverse reactions related to the carmustine polymer, either in the brain or systemically. Interstitial chemotherapy delivered with polymers directly to brain tumours at the time of surgery seems to be a safe and effective treatment for recurrent malignant gliomas.

Biodegradation, Environmental↗

Expression of plasminogen activator inhibitor type 1 by human prostate carcinoma cells inhibits primary tumor growth, tumor-associated angiogenesis, and metastasis to lung and liver in an athymic mouse model.

Expression of urokinase-type plasminogen activator (uPA) by malignant cells correlates with an aggressive phenotype, including increased invasiveness, tumor-associated angiogenesis, and metastases. Plasminogen activator inhibitor type 1 (PAI-1) is undetectable in cells of some aggressive malignancies, but present in the stroma of tumor-associated microvasculature. This analysis of an athymic mouse model of prostate carcinoma further defines the role of the uPA/PAI-1/plasmin system in primary growth and metastasis. A marked increase in PAI-1 expression was induced in clones of the aggressive human prostate carcinoma line, PC-3, by stable transfection. Primary PC-3 tumors, in mice, were significantly smaller when derived from PAI-1 expressing versus control cells. PAI-1 expression reduced the density of tumor-associated microvasculature by 22-38%. Microscopic metastases were quantitated using stable expression of the chromogenic label (beta-galactosidase) in control and PAI-1 expressing cells. PAI-1 expression resulted in a significant inhibition of lung metastases, and liver metastases. Expression of PAI-1 by malignant prostate cells resulted in a less aggressive phenotype, presumably by inhibition of uPA activity, suggesting pharmacologic or molecular inhibition of uPA activity as a potential therapeutic target.

Animals↗

Cells transfected with the basic fibroblast growth factor gene fused to a signal sequence are invasive in vitro and in situ in the brain.

Invasiveness is a critical event in the development of malignancy in brain tumors. A potential molecular mediator is basic fibroblast growth factor (bFGF). NIH-3T3 cells transfected with the bFGF gene fused with a signal peptide sequence (signal peptide bFGF) acquire an invasive phenotype as measured by in vitro assays of invasion including: 1) the formation of branching networks on Matrigel; 2) invasiveness in a chemoinvasion assay; 3) migration in a cell spreading assay; 4) detection of an Mr 92,000 gelatinase; and 5) local invasion into the surrounding neuropil after injection in the athymic mouse brain. By contrast, cells transfected with only the native bFGF gene (wild-type bFGF): 1) formed discrete cell clusters on Matrigel; 2) were less invasive and migratory in vitro; 3) released minimal Mr 92,000 collagenase; and 4) in vivo formed a pseudocapsule that separated the tumor cells from the neuropil. Quantitation of bFGF in the conditioned serum-free medium of the cell lines by enzyme-linked immunosorbent assay demonstrated that the signal peptide-bFGF cell clone secreted bFGF. These findings suggest a role for bFGF-mediated pathways and collagenase as molecular determinants of invasiveness in the brain.

3T3 Cells↗

The potential role of basic fibroblast growth factor in the transformation of cultured primary human fetal astrocytes and the proliferation of human glioma (U-87) cells.

Basic fibroblast growth factor (bFGF) is a potent stimulator of angiogenesis, proliferation, and invasion in human gliomas. To test the hypothesis that bFGF is important in the development of the malignant phenotype of human gliomas, bFGF expression was prospectively modulated in primary human fetal astrocytes and in an established human glioma cell line. Fetal astrocytes were transfected with a vector expressing bFGF modified by the addition of a secretory signal peptide sequence. Two of these bFGF astrocyte clones examined in vitro demonstrated anchorage-independent growth, loss of contact inhibition, and decreased glial fibrillary acidic protein immunoreactivity, changes consistent with cellular transformation. To analyze the inhibition of bFGF expression, phosphorothioated bFGF antisense oligodeoxynucleotides were added to cultures of the U-87 human glioma cell line. The U-87 cell proliferation was inhibited to 70.6 +/- 0.4% of control at 10 mumol/L and to 53.2 +/- 5.6% of control at 20 mumol/L (P < 0.05). Both the 7.0- and 4.0-kilobase bFGF messenger ribonucleic acid transcripts were reduced after exposure to the antisense oligodeoxynucleotide, and cell-associated bFGF protein was reduced by 44%. The sense oligodeoxynucleotide, a negative control, failed to inhibit U-87 proliferation. These data support the concept that bFGF expression could be a key event in glial tumorigenesis that may be necessary for the sustained growth of human gliomas.

Astrocytes↗