New xenograft model for assessing experimental therapy of central nervous system tumors: human glioblastoma in the intrathecal compartment of the nude mouse

Ten congenitally athymic "nude" mice and 10 immunocompetent mice underwent intrathecal inoculation with a human glioblastoma cell line (U87MG) via percutaneous lumbar puncture (5 x 10(5) cells/animal). All of the nude mice developed paraplegia with or without incontinence at 2 weeks and routinely died of inanition 3 weeks postimplantation. Histological examination confirmed extensive proliferation of neoplastic cells within the intrathecal space. A second group of animals was inoculated with 5 x 10(4) cells/animal: 20 nude mice, 10 cyclosporine A-immunosuppressed animals, and 10 immunocompetent control mice. The 20 mice were further divided into four subsets. Subset A did not receive chemotherapy, Subset B received 200 mg of carmustine (BCNU) per m2 by intraperitoneal injection, Subset C received a single dose of 4 mg of methotrexate (MTX) per m2 by intrathecal injection 4 hours after tumor inoculation, and Subset D received 12 mg of intrathecal MTX per m2. Decreasing the concentration of cells per animal by 1 log doubled the time interval required for the development of paralysis and incontinence to 4 weeks. Treatment with intrathecal MTX at a dose of 4 mg/m2 extended the symptom-free period by an additional week (to 5 weeks postinoculation), and a dose of 12 mg/m2 allowed an average of 6 weeks before the onset of neurological impairment. The xenografts did not grow in the immunocompetent control mice, the BCNU-treated group, or the cyclosporine A-immunosuppressed animals. An intrathecal xenograft model of central nervous system malignancies allows a novel approach to the evaluation of experimental chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Activation of second-messenger pathways reactivates latent herpes simplex virus in neuronal cultures.

Herpes simplex virus type 1 (HSV-1) establishes latent infections in neurons of sympathetic and sensory ganglia in humans, and reactivation of latent virus results in recurrent disease. Previously, we reported establishment of latent HSV-1 infections in neuronal cultures derived from rats, monkeys, and humans; reactivation occurs following nerve growth factor (NGF) deprivation. The processes controlling HSV latency are not understood. Using the in vitro neuronal latency system, we have shown that latent HSV-1 reactivated in response to stimulation of at least two second-messenger pathways. Stimulation of cAMP-dependent pathways by several mechanisms or activation of protein kinase C by phorbol myristate acetate (PMA) resulted in reactivation of latent HSV-1. The reactivation kinetics following treatment with activators of protein kinase A and C were accelerated compared with those following NGF deprivation. 2-Aminopurine, which inhibits NGF-stimulated protein kinases and other classes of protein kinases, but does not effect protein kinase A or C, blocked reactivation produced by NGF deprivation or treatment with a cAMP analog, but not reactivation by PMA treatment. These results demonstrate that latent HSV-1 reactivates in neurons in vitro in response to activation of second-messenger pathways.     

Misidentification of toxigenic Corynebacterium diphtheriae as a Corynebacterium species with low virulence in a child with endocarditis.

A 6-year-old boy presented to a university hospital in Malaysia with infective endocarditis complicating cyanotic congenital heart disease. Blood cultures showed a gram-positive, aerobic, coryneform-like bacillus identified by the hospital laboratory as Corynebacterium xerosis, but a reference laboratory identified the organism as a toxigenic strain of Corynebacterium diphtheriae. The two laboratories concurred on all biochemical test results except for sucrose fermentation.     

Apolipoprotein D is down-regulated during malignant transformation of neurofibromas

Apolipoprotein D (apoD) expression was studied in nonneoplastic peripheral nerve, neurofibromas (NFs), and malignant peripheral nerve sheath tumors (MPNSTs) by quantitative polymerase chain reaction, in situ hybridization, and immunohistochemistry. Multiplex quantitative polymerase chain reaction for messenger RNA was performed on a series of formalin-fixed and paraffin-embedded specimens that included 9 MPNSTs, 12 NFs, and 4 normal peripheral nerves. The average apoD expression was 108-fold decreased (DeltaCt = -7.3) in the MPNSTs compared with the NFs (P < .05). ApoD expression levels were 3.0-fold elevated (DeltaCt = 1.7) in the NFs compared with nonneoplastic peripheral nerve (P < .05). In situ hybridization for apoD RNA was performed on a separate series of 10 cases in which each microscopic section included both MPNST and the NF from which it arose. These studies confirmed elevated apoD expression in NFs compared with MPNSTs and demonstrated that this expression was variable among individual cells within the NFs. Differential expression by immunohistochemistry could only be demonstrated in selected areas, most likely because apoD protein is a small molecule that is secreted out of the cell into the extracellular space and plasma. ApoD expression initially increases a small amount with the formation of NFs from nonneoplastic peripheral nerve and subsequently decreases markedly as NFs transform into MPNSTs. This expression pattern may serve as a marker for cell cycle inhibition during peripheral nerve tumorigenesis.     

The Akron midtarsal dome osteotomy in the treatment of rigid pes cavus: a preliminary review

This study reviews the preliminary results of a previously unreported midtarsal "dome" osteotomy, all operations being performed by a single surgeon. The procedure is centered at the apex of the deformity and allows for extensive angular and rotational correction of the midfoot. The initial review has demonstrated 67% satisfactory results in 22 patients representing 35 feet. Satisfactory results were obtained in 15 of 16 feet (94%) in patients greater than 8 years of age. Careful short-term analysis suggests that the midtarsal "dome" osteotomy is best indicated for the child greater than 8 years of age with a rigid cavus or cavovarus foot.     

The incidence of deep venous thrombosis after arthroscopic knee surgery

We retrospectively reviewed the records of 2050 arthroscopic knee surgeries performed at The Orthopedic Specialty Hospital from January 1993 to December 1994. The number of clinically detected deep venous thromboses, with confirmation by duplex ultrasonography, was determined. Prospectively, preoperative and postoperative duplex ultrasonographic images were completed on 239 patients divided into 2 groups: those undergoing nonligament, intraarticular arthroscopic surgery (N = 131) and those undergoing arthroscopically assisted ligament surgery and extraarticular or osteotomy surgery (N = 108). For the retrospective study, the incidence of deep venous thrombosis was 0.24%. Prospectively, seven total deep venous thromboses were identified (rate, 2.9%), with five being identified within 8 days of surgery in asymptomatic patients (rate, 2.1%). There were no statistically significant associations or correlations between the development of deep venous thrombosis and patient personal data or surgical variables, respectively. The difference in the rate of deep venous thrombosis between the two prospective groups was not statistically significant; however, patients who had more invasive surgery tended to be at higher risk for developing deep venous thrombosis. A cost-benefit analysis did not support the routine use of duplex ultrasonography to detect deep venous thrombosis in patients undergoing arthroscopic knee surgery.     

T lymphocytes in patients with Down's syndrome.

Individuals with Down's syndrome (DS) are thought to have abnormalities in their immune system, and a tendency to infection and malignancy. Studies to quantify the number of T lymphocytes in the peripheral blood of 82 unselected institutionalized patients (50 DS, 27 controls matched for sex and age, 2 chronic lymphocytic leukemic, 2 acute leukemic, and 1 Hodgkin's disease) were conducted. The numbers of circulating T cells in DS patients did not differ significantly from the control group, and were in the upper limits of normality. Number of "avid" T cells, however, were significantly higher in the DS than in the control group. The blastogenic response of the T cells to mitogen was significantly depressed. The data did not exclude the existence of qualitative abnormalities. Except for DS patients with congenital heart disease, those older than 15 years were not more prone to upper respiratory infections than other institutionalized mentally retarded patients.