Hypertonic saline lowers raised intracranial pressure in children after head trauma

Eighteen pediatric patients who sustained traumatic brain injury were enrolled in a double-blind, crossover study comparing the effects of 3% saline and 0.9% saline infusions on raised intracranial pressure (ICP). After resuscitation, each patient received a bolus of each saline concentration, and ICP was monitored for 2 h. Initial mean ICP before 0.9% saline infusions equaled 19.3 mm Hg and averaged 20.0 mm Hg during the subsequent 2-h trials (p = 0.32). Baseline mean ICP before 3% saline administration equaled 19.9 mm Hg and averaged 15.8 mm Hg for 2 h postinfusion (p = 0.003). Central venous pressure did not change significantly in either group, nor did measurements of renal function. Serum sodium concentrations increased in all 18 trials of 3% saline. Maximal concentrations of serum sodium occurred 30 min after bolus administration of 3% saline. Three percent saline significantly reduces raised ICP after traumatic brain injury when compared with normal saline. Intravascular dehydration, as measured by central venous pressure, did not occur during the study period.     

A variant of guided exposure to mourning for use with treatment resistant patients.

We report a variant of "guided exposure to mourning," designed for use with patients who have proved resistant to other treatments for unresolved, morbid grief. The work provides some indication as to when such behavioral techniques for resolution of morbid grief are likely to prove successful, and when not.     

Dolichol-bound oligosaccharides and the transfer of distal monosaccharides in the synthesis of glycoproteins by normal and tumor mammary epithelial cells

Summary The main dolichol diphosphate-bound oligosaccharides present in primary cultures of both normal and tumor mouse mammary epithelial cells had the same size, yielded the same pattern after acetolysis and paper chromatography, had the same number of mannose residues susceptible to-mannosidase degradation, and were composed of the same monosaccharide residues. This is the first demonstration that normal and tumor mammary cells have dolichol diphosphate-bound oligosaccharides with very similar, if not identical, structures. These compounds are intermediates in the synthesis of asparagine-linked oligosaccharides. On the other hand, normal and tumor cells showed differences in the specific activities of the enzymes involved in the transfer of the distal monosaccharides from the sugar nucleotides to glycoproteins. Sialyl- and fucosyl-transferases were elevated and galactosyl- and N-acetylglucosaminyltransferases were diminished in mammary tumor cells. The intact tumor cells showed an increased fucosylation of glycoproteins of the asparagine-linkage type. Address for reprints: Roberto L. Ceriani, M.D., Ph.D., Bruce Lyon Memorial Research Laboratory, Children's Hospital Medical Center, 51st and Grove Streets, Oakland, CA 94609, USA.     

Uptake of the daunorubicin-DNA complex in cultured fibroblasts

Summary The uptake and fate of the daunorubicin-DNA complex have been studied in cultured rat embryo fibroblasts. ¹²⁵I-DNA was digested by the cells and appeared as low molecular weight fragments in the incubation medium. Subcellular fractionation of fibroblasts, previously incubated with the complex, showed that daunorubicin was localized to nuclei and lysosomes. At a high incubation concentration (17.5 M), the accumulation of the free drug exceeded that of the complex. However, at a lower concentration (1.75 M), the accumulation of the complex was as high as that of the free drug.The results are consistent with an uptake of the complex into cultured rat embryo fibroblasts by endocytosis. However, it cannot be excluded that the complex partly dissociates in the incubation medium, and that daunorubicin and DNA thereafter enter the cells separately.     

Hypoxia and glucose metabolism in malignant tumors: evaluation by [18F]fluoromisonidazole and [18F]fluorodeoxyglucose positron emission tomography imaging.

PURPOSE: The aim of this study is to compare glucose metabolism and hypoxia in four different tumor types using positron emission tomography (PET). (18)F-labeled fluorodeoxyglucose (FDG) evaluates energy metabolism, whereas the uptake of (18)F-labeled fluoromisonidazole (FMISO) is proportional to tissue hypoxia. Although acute hypoxia results in accelerated glycolysis, cellular metabolism is slowed in chronic hypoxia, prompting us to look for discordance between FMISO and FDG uptake. EXPERIMENTAL DESIGN: Forty-nine patients (26 with head and neck cancer, 11 with soft tissue sarcoma, 7 with breast cancer, and 5 with glioblastoma multiforme) who had both FMISO and FDG PET scans as part of research protocols through February 2003 were included in this study. The maximum standardized uptake value was used to depict FDG uptake, and hypoxic volume and maximum tissue:blood ratio were used to quantify hypoxia. Pixel-by-pixel correlation of radiotracer uptake was performed on coregistered images for each corresponding tumor plane. RESULTS: Hypoxia was detected in all four patient groups. The mean correlation coefficients between FMISO and FDG uptake were 0.62 for head and neck cancer, 0.47 for breast cancer, 0.38 for glioblastoma multiforme, and 0.32 for soft tissue sarcoma. The correlation between the overall tumor maximum standardized uptake value for FDG and hypoxic volume was small (Spearman r = 0.24), with highly significant differences among the different tumor types (P < 0.005). CONCLUSIONS: Hypoxia is a general factor affecting glucose metabolism; however, some hypoxic tumors can have modest glucose metabolism, whereas some highly metabolic tumors are not hypoxic, showing discordance in tracer uptake that can be tumor type specific.     

Minority recruitment in hereditary breast cancer research.

Although recruitment of ethnic and racial minorities in medical research has been evaluated in several studies, much less is known about the methods used to recruit these populations to participate in cancer genetics research. This report reviews the resources that have been used to identify and recruit ethnic and racial minorities to participate in hereditary breast cancer research. Overall, hospital-based resources were used most often to identify potential subjects, and active recruitment methods were used most frequently to enroll eligible subjects. This review suggests that there appears to be a finite number of resources and strategies to identify and recruit potential subjects to participate in cancer genetics research; however, options for improving awareness about cancer genetics research among ethnic and racial minorities have not been extensively evaluated. To study ethnic and racial minority participation in cancer genetics research, stronger evaluation components will need to be integrated into research methods. Both observational and experimental studies are needed to determine resources that are most effective for identifying potential subjects who are ethnic and racial minorities and to evaluate the effects of different recruitment strategies on enrollment decisions among these populations.     

Peripheral blood mononuclear cell responses from type 1 diabetic patients and subjects at-risk for type 1 diabetes to human fetal pancreatic tissue proteins

BACKGROUND: Fetal pancreatic tissue has been suggested to be less immunogenic than adult islets. Thus, transplantation of human fetal pancreatic tissue as treatment for type 1 diabetes has been gaining interest. To investigate this question, we tested the peripheral blood mononuclear cell (PBMC) responses from different subject populations to human adult islet proteins (AIP) versus human fetal pancreatic proteins (FPP). METHODS: PBMC responses to FPP and AIP from normal controls (n=14), newly diagnosed type 1 diabetes patients (n=5), long-term type 1 diabetes patients (n=9), and subjects at-risk for development of type 1 diabetes (n=3) were studied. RESULTS: We observed that normal controls demonstrated PBMC reactivity to 0-3 molecular weight regions (mwr) for both the AIP (mean+/-SD, 0.8+/-1.1) and the FPP (0.6+/-0.7). In contrast, newly diagnosed type 1 diabetic patients (<1 year) demonstrated PBMC responses to 9-16 mwr for the AIP (12.8+/-2.5) and 0-14 mwr for the FPP (6.8+/-5.0). The PBMCs from long-term type 1 diabetes patients (> 3 years) were responsive to 2-11 mwr for AIP (6.0+/-2.8) and 0-11 mwr for FPP (4.9+/-4.0). Three nondiabetic ICA positive subjects at-risk for development of type 1 diabetes demonstrated positive PBMC reactivity to 9-18 mwr for the AIP (12.7+/-3.9) and 4-18 mwr for the FPP (10.0+/-5.9). CONCLUSIONS: We conclude that human fetal pancreatic proteins are not significantly less stimulatory than human adult islet proteins to PBMCs of subjects with or at risk for type 1 diabetes.     

Induction of apoptosis in multi-drug resistant (MDR) human glioblastoma cells by SN-38, a metabolite of the camptothecin derivative CPT-11

 The overexpression of the multidrug resistance (mdr1) gene and its product, P-glycoprotein (P-gp), is thought to limit the successful chemotherapy of human tumors. Recent studies demonstrate that SN-38, a metabolite of the camptothecin (CPT) derivative CPT-11, has antitumor effects on several tumors, but the mechanisms responsible for its cytotoxicity remain unclear. We therefore determined whether SN-38 has cytotoxic effects on MDR human glioblastoma GB-1 cells and non-MDR human glioblastoma U87-MG cells. Furthermore, we determined what role SN-38 plays in the induction of cytotoxicity in these tumor cells. In this study, we demonstrated that SN-38 had significantly stronger antitumor effects on GB-1 and U-87MG cells than did CPT (P<0.01 and P<0.05, respectively). In addition, findings obtained using a DNA fragmentation assay, Hoechst 33258 staining, in situ end-labeling and cell cycle analysis demonstrated that SN-38 induced apoptosis in these tumors. Our results suggest that SN-38 has a stronger antitumor effect on malignant glioma cells regardless of MDR expression than does CPT, and therefore can be considered a new chemotherapeutic agent potentially effective in the treatment of human primary or recurrent malignant gliomas resistant to chemotherapy. Received: 6 October 1995/Accepted 29 June 1996