Brain tumors in children under 2 years: treatment, survival and long-term prognosis

Survival for children with brain tumors less than 2 years of age at diagnosis is dismal, and the quality of life of long-term survivors poor. Between 1975 and 1987, 78 (13%) of 579 patients with brain tumors treated at Children's Hospital of Philadelphia were under 2 years of age. Tumor site was posterior fossa in 31 (40%) and supratentorial in 47 (60%). Nine of 37 patients (24%) with malignant tumors, and 30 of 41 (73%) patients with benign tumors are alive with a mean follow-up of 116 months. Long-term survival after treatment with chemotherapy alone occurred in 10 patients, including 3 with malignant tumors. In 5 additional patients, chemotherapy delayed the need for irradiation a mean of 30 months. Of the 29 patients who relapsed after initial therapy, 12 are alive without progressive disease (2 patients with malignant tumors and 10 with benign tumors) a mean of 80 months after relapse, 2 children are alive with progressive disease, and 14 died a median of 48 months (range 9-115 months) after relapse. Twenty-one of the 39 survivors have minimal or no neurological or intellectual dysfunction. Surviving patients treated with surgery and chemotherapy have better intellectual function than patients treated with surgery and radiation (with or without chemotherapy) in that 8 of 10 children treated with surgery and chemotherapy have normal or above normal intelligence compared with 5 of 12 children receiving irradiation before their second birthday.     

Expression of the c-erbB-3 gene product in gastric cancer

The pattern of c-erbB-3 gene product was studied in 91 advanced gastric carcinomas, adjacent hyperplastic mucosa, intestinal metaplasia and dysplasia and in normal controls, using immunohistochemistry in archival material. All tumours showed positive c-erbB-3 staining in both cytoplasm and membrane. No significant differences of expression were observed between intestinal and diffuse-type carcinomas or any other clinical parameters. Of interest is the expression in the adjacent mucosa, which is extensive, cytoplasmic, and of lower intensity than in the tumours. Further studies are currently being carried out to clarify the role of this protein in tumour behaviour and gastric carcinogenesis.     

Teaching severely self-abusive and aggressive autistic residents to exit to fire alarms

Fifty-two case-hardened, severely self-abusive and aggressive autistic and retarded students, living in six different community residences, were trained to exit their residences, without the presence or assistance of staff, when a fire alarm sounded at night. On a pretest, prior to an 11-week period of intensive environmental and behavioral interventions, only 25% of the students exited within 2 1/2 minutes and independent of staff assistance. At posttest, 100% exited successfully, in a mean evacuation time of 60 seconds. The study was conducted at the Behavior Research Institute (BRI).     

Effects of the glucocorticoid agonist, RU28362, and the antagonist RU486 on lung phosphatidylcholine and antioxidant enzyme development in the genetically obese Zucker rat

The biochemical maturation of the lung in late gestation and in the young animal is regulated by glucocorticoids. The present study was aimed at dissociating the different glucocorticoid receptor sites involved in these regulatory functions. The obese Zucker rat was selected as a model for this study as it exhibits hypersensitivity to glucocorticoid hormone action by virtue of its elevated receptor numbers and activity. Two synthetic steroid analogues were administered to obese animals; RU28362, a specific type II receptor agonist, and the type II antagonist RU486. RU28362 promoted a strong catabolic effect, which was associated with reduced food intake and the abolition of growth in the rats. The agonist, RU28362, attenuated developmental increases in antioxidant enzyme activities, and altered the growth of the tissue. At the age studied, development of the lung phosphatidylcholine (PC) system was almost complete, but RU28362 increased disaturated PC 16:0/16:0 concentrations by almost 2-fold, and altered the molecular composition of total pulmonary PC. RU486 attenuated the growth of the rats and reduced their food intake. Treatment with the type II antagonist attenuated lung growth and increased the activities of pulmonary copper zinc (Cu/Zn) and manganese (Mn) superoxide dismutases. RU486 had no effect on lung PC concentrations and molecular composition. The data suggest a role for type I glucocorticoid receptors in the regulation of the antioxidant enzyme system in the lung, as type II antagonism will channel endogenous glucocorticoid binding to the type I site. Type II receptor binding would appear to play a role in regulating the lung PC content.     

Expression and distribution of leptospiral outer membrane components during renal infection of hamsters

The outer membrane of pathogenic Leptospira species grown in culture media contains lipopolysaccharide (LPS), a porin (OmpL1), and several lipoproteins, including LipL36 and LipL41. The purpose of this study was to characterize the expression and distribution of these outer membrane antigens during renal infection. Hamsters were challenged with host-derived Leptospira kirschneri to generate sera which contained antibodies to antigens expressed in vivo. Immunoblotting performed with sera from animals challenged with these host-derived organisms demonstrated reactivity with OmpL1, LipL41, and several other proteins but not with LipL36. Although LipL36 is a prominent outer membrane antigen of cultivated L. kirschneri, its expression also could not be detected in infected hamster kidney tissue by immunohistochemistry, indicating that expression of this protein is down-regulated in vivo. In contrast, LPS, OmpL1, and LipL41 were demonstrated on organisms colonizing the lumen of proximal convoluted renal tubules at both 10 and 28 days postinfection. Tubular epithelial cells around the luminal colonies had fine granular cytoplasmic LPS. When the cellular inflammatory response was present in the renal interstitium at 28 days postinfection, LPS and OmpL1 were also detectable within interstitial phagocytes. These data establish that outer membrane components expressed during infection have roles in the induction and persistence of leptospiral interstitial nephritis.     

Reversal of fortune: commercial HMOs in the Medicaid market

Between 1992 and 1996 the number of health maintenance organizations (HMOs) entering the Medicaid market grew at an average annual rate of approximately 22 percent. Participation among all ownership segments grew, resulting in a broad distribution of beneficiaries across the HMO industry. However, recent declines in financial performance within the industry appear to be more dramatic for plans with many Medicaid members. In addition, growing concerns about rate adequacy and volatility as well as expanding administrative demands raise questions about the long-term commitment of commercial HMOs to Medicaid participation. This paper analyzes operating characteristics and financial performance of licensed commercial HMOs from 1992 through 1996, drawing on indepth interviews with health plan executives and managed care stock analysts.     

Increased dietary oxalate does not increase urinary calcium oxalate saturation in hypercalciuric rats

BACKGROUND: Human calcium oxalate (CaOx) nephrolithiasis may occur if urine is supersaturated with respect to the solid-phase CaOx. In these patients, dietary oxalate is often restricted to reduce its absorption and subsequent excretion in an effort to lower supersaturation and to decrease stone formation. However, dietary oxalate also binds intestinal calcium which lowers calcium absorption and excretion. The effect of increasing dietary oxalate on urinary CaOx supersaturation is difficult to predict. METHODS: To determine the effect of dietary oxalate intake on urinary supersaturation with respect to CaOx and brushite (CaHPO4), we fed 36th and 37th generation genetic hypercalciuric rats a normal Ca diet (1.2% Ca) alone or with sodium oxalate added at 0.5%, 1.0%, or 2.0% for a total of 18 weeks. We measured urinary ion excretion and calculated supersaturation with respect to the CaOx and CaHPO4 solid phases and determined the type of stones formed. RESULTS: Increasing dietary oxalate from 0% to 2.0% significantly increased urinary oxalate and decreased urinary calcium excretion, the latter presumably due to increased dietary oxalate-binding intestinal calcium. Increasing dietary oxalate from 0% to 2.0% decreased CaOx supersaturation due to the decrease in urinary calcium offsetting the increase in urinary oxalate and the decreased CaHPO4 supersaturation. Each rat in each group formed stones. Scanning electron microscopy revealed discrete stones and not nephrocalcinosis. X-ray and electron diffraction and x-ray microanalysis revealed that the stones were composed of calcium and phosphate; there were no CaOx stones. CONCLUSION: Thus, increasing dietary oxalate led to a decrease in CaOx and CaHPO4 supersaturation and did not alter the universal stone formation found in these rats, nor the type of stones formed. These results suggest the necessity for human studies aimed at determining the role, if any, of limiting oxalate intake to prevent recurrence of CaOx nephrolithiasis.