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Biomedical subjects

H Brem

Publications and source records attributed to H Brem.

At least 127 records · Page 7Linked to original sources

In vivo 31P nuclear magnetic resonance spectroscopy of rat 9L gliosarcoma treated with BCNU: dose response of spectral changes.

The 9L gliosarcoma, grown subcutaneously in juvenile Fischer 344 rats, was studied by in vivo 31P NMR spectroscopy following treatment with 1,3-bis(2-chloroethyl)-1-nitrosourea. Dose-dependent increases in the proportion of high-energy phosphates were observed for doses between 10 and 36 mg/kg (from 80% of the LD10 to greater than the LD50). These doses reduced clonogenic cell survival in a dose-dependent fashion by as much as 3 log orders and resulted in up to 16 days of growth delay (to pretreatment tumor volume). Increases in high-energy phosphates (relative to Pi) in the tumor were greater at higher doses despite the higher levels of clonogenic cell killing and the substantial host systemic toxicity.

Animals↗

Neonatal diagnosis of a presacral mass in the presence of congenital anal stenosis and partial sacral agenesis.

The simultaneous presentation of clinically symptomatic anal anomalies and roentgenographically demonstrated sacral dysgenesis should alert the pediatric surgeon to investigate for the presence of a presacral malformation. We report on such a case to illustrate a new radiographic technique that facilitates diagnosis and management of complex congenital malformations. A 1-day-old white boy presented with anal stenosis, a scimitar-shaped sacrum, and large anterior and posterior meningoceles. In addition, a distinct presacral tumor--a teratoma--was identified. These malformations were identified utilizing metrizamide myelography and three-dimensional reconstruction computed tomography (CT) scanning. The meningoceles and a tethered cord were successfully corrected utilizing a posterior approach. A diverting colostomy was performed and subsequently taken down. Two years postoperatively, the patient continues to do well. This case demonstrates that this triad of anomalies (presacral mass, sacral dysgenesis, and anorectal malformation), once considered, can be safely detected with modern radiologic techniques and can be expeditiously corrected during infancy before further deterioration occurs.

Abnormalities, Multiple↗

Congenital anal fistula with normal anus.

Three patients with a congenital anovestibular/perineal fistula were treated at the Montreal Children's Hospital. Two females (one of East Indian and the other of Japanese origin) had anovestibular fistulae that became symptomatic in the first few months of life. The third patient, a boy of Korean descent, presented at 9 months of age with a chronically draining perineal fistula. During surgery, a small fistula tract was easily dissected out and excised. Microscopic examination showed a well-preserved rectal mucosa throughout the tract. Most male patients described to date had anourethral fistulae, often accompanied by other major anomalies such as esophageal atresia or renal malformations. We believe our patient is the first male to be described with a congenital perineal fistula; this suggests that some fistula-in-ano in male infants may be due to a congenital sinus that secondarily becomes infected and drains to the skin.

Anus Diseases↗

Biocompatibility of a biodegradable, controlled-release polymer in the rabbit brain.

The biodegradable polyanhydrides are a new class of controlled release polymers developed for the interstitial delivery of drugs to their target site in the brain or other organs over periods ranging from days to years. These polymers can release molecules of any size in a predictable fashion. Their degradation products are non-cytotoxic and biocompatible. The biocompatibility of a biodegradable polyanhydride, the copolymer of poly[bis(p-carboxyphenoxy)propane] anhydride and sebacic acid (PCPP-SA) in a 50:50 formulation, was studied in the rabbit brain. Twenty adult New Zealand White male rabbits underwent implantation of PCPP-SA in a frontal lobe and absorbable gelatin sponge (Gelfoam) in the other frontal lobe. The animals were evaluated daily until the time of sacrifice. Groups of four animals were sacrificed sequentially on post-operative days 1, 3, 7, 21, and 60, and the brains processed for histological evaluation. None of the animals showed behavioral changes or neurological deficits suggestive of toxicity and all that received implants survived to their date of sacrifice. The histological examination showed no significant differences between the tissue reaction from PCPP-SA compared to Gelfoam. The polymers were also tested in the rabbit cornea bioassay and did not induce an inflammatory response. We conclude that PCPP-SA (50:50), a new biodegradable polymeric matrix that can be surgically implanted for the interstitial delivery of drugs in the brain, is biocompatible in the rabbit brain.

Animals↗

An endothelial cell growth factor from the mouse neuroblastoma cell line NB41.

A growth factor that stimulates the proliferation of endothelial cells from human umbilical vein but is not mitogenic for fibroblastic cells is present in medium conditioned by the mouse neuroblastoma cell line NB41. In a partially purified preparation, factor activity coeluted from a reverse-phase high-pressure liquid chromatography (HPLC) column with a reduced protein of about 24 kd. Activity recovered following electrophoresis of HPLC fractions corresponded to protein of 43-51 kd in the absence of reducing agent and to protein of 23-29 kd after reduction. Antiserum raised against a peptide corresponding to the putative N-terminal amino acid sequence of the 24-kd protein reacted with the 24-kd protein and with a protein of about 47 kd in the nonreduced preparation. After N-glycanase treatment, the immunoreactive 24-kd protein had a mobility corresponding to 19 kd. We infer that the native NB41 factor is a glycosylated dimer whose biochemical and biological properties distinguish if from other endothelial cell growth factors.

Animals↗

Neonatal model of heterotopic heart transplantation in pigs.

To investigate the long-term success of heart transplantation in newborn infants who have complex congenital heart disease, we have developed a model of heterotopic heart transplantation in immature pigs. We chose the heterotopic technique because it is simple, does not require cardiopulmonary bypass or heparin, allows for significant size disparity between the recipient and donor hearts, and allows for experimental comparisons between the two hearts. Small newborn piglet hearts are harvested, prepared, and then transplanted into the left chest of larger weanling pigs to augment or substitute for the native left ventricle. Preliminary data from transplants into 49 pigs suggest that the technique is technically possible, the pigs can be immunosuppressed over the long term, and the donor heart can contribute hemodynamically. Experimentally, the model is well designed for the investigation of issues critical for the long-term success of heart transplantation in infants and children, including growth and development, optimal long-term immunosuppression, differences in immunotolerance, and the study of coronary obliterative disease. Clinically, the model has potential applicability in congenital heart anomalies if one native functioning atrium and ventricle are present.

Animals↗

Lipomeningioma: report of three cases and review of the literature.

Lipomeningioma is a benign tumor of the meninges that contains mature adipose tissue. It demonstrates fat density on computed tomographic scan and mixed signal intensities on magnetic resonance imaging scan. Although the pluripotential nature of the mesenchymal cell has long been recognized, only a single case with this diagnosis has been documented in the literature to date. Three patients with this diagnosis seen at the Johns Hopkins Hospital during the last two years are presented, and the literature is reviewed.

Aged↗

In vivo 31P nuclear magnetic resonance spectroscopy of subcutaneous 9L gliosarcoma: effects of tumor growth and treatment with 1,3-bis(2-chloroethyl)-1-nitrosourea on tumor bioenergetics and histology.

In vivo 31P nuclear magnetic resonance spectroscopy was used to examine the bioenergetics of the rat 9L gliosarcoma during untreated growth and in response to chemotherapy with 1,3-bis(2-chloroethyl)-1-nitrosourea. Tumor growth was associated with a decline in the phosphocreatine and nucleoside triphosphate resonances, consistent with an increase in tumor hypoxia during untreated growth. Following chemotherapy with 1,3-bis(2-chloroethyl)-1-nitrosourea (10 mg/kg), tumor levels of phosphocreatine and nucleoside triphosphate rebounded while the level of inorganic phosphate in the tumor declined. Histological comparison of treated and untreated tumor sections 4 days posttreatment showed that the treated tumor had a lower proportion of necrotic cells, a higher proportion of viable cells, and a 5-fold higher level of interstitial space than the control tumor.

Animals↗

Posterior fossa neuroblastoma occurring in an elderly man.

A case of a neuroblastoma occurring in the cerebellum of a 73-year-old man is reported. The patient presented with progressive truncal ataxia and was found to have an enhancing tumor mass in the cerebellar vermis. By light microscopy, the tumor was a small cell neoplasm and was similar to medulloblastoma, with areas showing structures suggestive of Homer-Wright pseudorosettes. By electron microscopy and immunoperoxidase techniques, however, the tumor showed convincing evidence of neuronal differentiation. The absence of previous reports of this tumor in the posterior fossa of adults suggests that immunoperoxidase techniques and/or electron microscopy of such small cell tumors may be required for accurate diagnosis.

Aged↗

Heterotransplantation of malignant human gliomas in neonatal rats.

Three human glioma cell lines (TE-671 medulloblastoma, U-87 MG glioblastoma, and U-373 MG glioblastoma) were transplanted to the quadrigeminal cistern of the brain in 37 newborn Sprague-Dawley rats and to the subcutaneous space in 30 of their siblings. Two of the three gliomas (the TE-671 medulloblastoma and the U-87 MG glioblastoma) grew both intracranially and subcutaneously. The U-373 MG glioblastoma did not grow in either site. The resulting tumors expressed unique morphological features characteristic of their tissue of origin. The newborn rat represents a model for the heterologous transplantation of human gliomas, providing a biological window for the study of these lesions.

Animals↗

Carotid bifurcation imaging model for more accurately comparing imaging techniques.

For comparing current and presubably forthcoming imaging modalities, a carotid bifurcation model was made from cadaveric specimens. Perfusing and pulsing the immersed common carotid artery and its proximal branches via a Harvard pump simulated clinical imaging conditions. Film-screen (F-S) and digital subtraction (DS) angiography, computed tomography (CT), ultrasound and magnetic resonance imaging (MRI) were compared. For CT and MRI, scanning parameters such as slice thickness, degree of overlapping, amount of contrast medium needed, scanning mode and multiplanar and three-dimensional techniques enabled enhancing the capacity for CT in the clinical setting. Direct axial CT proved to be most accurate for assessing the contours and magnitude of carotid narrowing. Nonetheless, these serial segments were not readily compared with F-S and DS angiographic full length images. The use of multiplanar reconstruction (MPR) and three-dimensional (3-D) CT achieved this and furthermore showed the external contour of the diseased segment. Concerning carotid ulceration, our carotid model study showed CT to be equally accurate with DS and superior to F-S angiography. However, in our clinical study of 34 carotid arteries in 17 patients ulcerations were equally well identified by CT and angiography but DS angiography proved superior in identifying ulcers not seen with CT. Perhaps this discrepancy is explained by the clinical routine of attaining multiple fluoroscopically positioned views of the common carotid bifurcations in DS catheter angiography unlike the complexity of attaining optimal views of tortuous vessels on CT.

Angiography↗

Biocompatibility of polymeric delivery systems for macromolecules.

We previously reported the use of polymeric delivery systems capable of sustained release of substances with molecular weights up to 2 X 10(6). The current study examined the tissue compatibilities of these slow-release agents and of other polymeric materials. To observe in vivo host responses to specific implants, tests were conducted in the rabbit cornea. The cornea as an implant site has several advantages compared to other organs including its clarity, avascularity, sensitivity, and convenient access to view. Corneas were examined using stereomicroscopy and histology. Two polymers suitable for sustained macromolecular release, poly(hydroxyethyl methacrylate), and alcohol-washed ethylene-vinyl acetate copolymer, were noninflammatory. Other polymers considered for sustained macromolecular release, such as polyacrylamide and poly(vinyl pyrrolidone), produced significant inflammation.

Animals↗

Inhibition of neovascularization by an extract derived from vitreous.

An extract of the vitreous body, inhibited the growth of new blood vessels induced by tumors in the rabbit cornea. This extract was delivered by an inert, continuously releasing polymer. The average vessel growth rate in the region surrounding the polymer was 32% less in corneas containing the inhibitory substance than in control corneas.

Animals↗

Isolations of a cartilage factor that inhibits tumor neovascularization.

A cartilage fraction isolated by guanidine extraction and purified by affinity chromatography inhibits tumor-induced vascular proliferation and consequently restricts tumor growth. This fraction contains several different proteins; the major one has a molecular weight of about 16,000. The fraction strongly inhibits protease activity.

Carcinoma↗

Prolonged tumor dormancy by prevention of neovascularization in the vitreous.

Tumors release a diffusible substance that stimulates neovascularization. To study the neovascularization that occurs in diabetic retinopathy, we implanted V2 carcinomas and mouse ependymoblastomas into the vitreous of experimental animals. In the vitreous, unlike previous sites, the tumors failed to stimulate neovascularization. They grew for weeks as small, unvascularized, three-dimensional aggregates of cells. Explosive growth into a large, vascularized mass occurred when the avascular tumors reached the retinal surface. The vitreous proved to be a valuable model for observing the in vivo growth of small, solid tumors. Xenografts survived for months without evidence of immune rejection. The consequence of the prolonged avascular state is the restriction of tumor size. The normal vitreous may act to inhibit capillary proliferation. An understanding of the mechanism for maintaining the avascular state may lead to therapeutic blockade of neovascularization. This would be important in the management of diabetic retinopathy and neoplasia.

Animals↗

Inhibition of tumor angiogenesis mediated by cartilage.

Capillary proliferation induced by tumor is shown to be inhibited by neonatal scapular cartilage. Using the rabbit cornea as an assay, the cartilage implant decreased the rate of capillary growth, induced by tumor, by an average of 75%. Vascularization was prevented completely in 28% of tumors. The inhibitory effect of small cartilage implants operates over distances of up to 2.0 mm and displays a gradient from the cartilage source. The experiments suggest that the cartilage inhibitor does not antagonize tumor angiogenesis factor, but appears to inhibit capillary proliferation directly. The inhibitory material does not elicit an inflammatory response in either the rabbit cornea or in the chick chorioallantoic membrane. Thus with further purification, it may prove useful as a means of maintining tumor dormancy by "antiangiogenesis."

Animals↗