Adult medulloblastoma: an analysis of survival and prognostic factors

PURPOSE: This analysis aimed to review the experience in the management of adult medulloblastoma at the University of California, San Francisco, and to identify important prognostic factors for survival and posterior fossa control. PATIENTS AND METHODS: We performed a retrospective review of 34 adult patients, age > or = 15, with cerebellar medulloblastoma treated with radiotherapy at the University of California, San Francisco from 1970 to 1994. All patients underwent a surgical procedure (complete resection in 17, subtotal resection in 10, and biopsy alone in seven), followed by craniospinal irradiation. Most patients treated after 1979 also received chemotherapy. Twenty were classified as poor-risk due to either incomplete resection or evidence of disease outside of the posterior fossa at diagnosis. RESULTS: The 5-year posterior fossa control and overall survival rates were 61% and 58%, respectively. The majority of relapses occurred in the posterior fossa (14 of 17). Multivariate analysis revealed that age (favoring older patients), gender (favoring female patients), and extent of disease at diagnosis (favoring localized disease) were important prognostic factors for posterior fossa control. There was a trend toward improved posterior fossa control with higher radiation dose to the posterior fossa in patients with a complete resection. Gender and extent of disease at presentation were significant prognostic factors for survival. The 5-year survival rates were 92% for female patients versus 40% for male patients, and 67% for patients with localized disease versus 25% for those with disseminated disease. The prognosis following recurrence was poor; all died of the disease. DISCUSSION: Survival for adult medulloblastoma was comparable to its pediatric counterpart. In patients with localized disease at presentation, gender (favoring female patients) and age (favoring older patients) were important prognostic factors for posterior fossa control and survival. In patients with disseminated disease at presentation, the prognosis is poor, and innovative therapy is needed to improve survival.     

Cell adhesion properties of hemolin, an insect immune protein in the Ig superfamily

The isolation of antibacterial peptides from the giant silkmoth Hyalophora cecropia has opened the area of animal antibiotics [Boman, H. G. (1991) Cell 65, 205-207] and the study of insect immune genes has revealed striking similarities to many immune response genes in mammals [Hultmark, D. (1994) Nature 267, 116-117]. However, the molecules and mechanisms behind primordial immune recognition are not understood. One candidate for one such recognition molecule is hemolin, a 48-kDa immunoglobulin-related protein first isolated from H. cecropia, where it is up-regulated upon infection and secreted into the hemolymph. Hemolin was shown to bind to bacteria and to hemocytes, giving rise to changes in hemocyte adhesiveness and intracellular phosphorylation patterns [Faye, I. & Kanost, M. (1997) in Molecular mechanisms of immune responses in insects (Brey, P. T. & Hultmark, D., eds) Chapman and Hall, London]. In the present publication, we give evidence for the presence of a 52-kDa membrane form of hemolin on hemocytes, based on flow-activated cell sorting and membrane protein extractions. In addition we reveal calcium-dependent homophilic binding properties of hemolin, using hemolin-coated microspheres. When biotinylated recombinant hemolin was allowed to bind to hemocyte membranes, higher molecular-mass complexes were formed. Furthermore, we used immunological methods and Northern-blot analysis to demonstrate the presence of hemolin in embryos and retinal discs, suggesting that hemolin is expressed in several tissues at different developmental stages. These results show novel cell adhesion features of hemolin, corroborating its multifunctional character with putative roles in cellular and humoral immunity and in development.     

Prognostic value of treadmill exercise testing: a population-based study in Olmsted County, Minnesota

BACKGROUND: The prognostic value of treadmill exercise testing (TMET) has been studied in selected populations. The generalizability of these data to different populations and to women is uncertain. METHODS AND RESULTS: A retrospective, population-based cohort study of all persons (1452 men and 741 women) who underwent TMET in years 1987 to 1989 in Olmsted County, Minnesota, was undertaken. Individuals were followed up for all-cause mortality and cardiac events (cardiac deaths, nonfatal myocardial infarction, or congestive heart failure). Sex-specific analyses were performed to determine whether the predictors of outcome and the magnitude of the associations were similar in both sexes. In men, 77 deaths and 106 cardiac events occurred during 8956 person-years of observation; in women, 46 deaths and 54 cardiac events occurred during 4801 person-years of follow-up. Exercise-induced angina, ECG changes, and workload achieved on the TMET were strongly associated with all-cause mortality and cardiac events in both sexes, and the strength of the association was similar. After adjustment, workload was the only TMET variable associated with outcome. A higher workload was associated with a reduction in the risk of cardiac events and of all-cause mortality; the protective effect of exercise capacity was strong and was similar in both sexes. CONCLUSIONS: In this population-based cohort, exercise capacity was the TMET variable that exhibited the strongest association with all-cause mortality and cardiac events. This protective effect of exercise capacity was observed in both sexes.     

Biliary sludge formation during enteral nutrition: prevalence and natural history

BACKGROUND: Total parenteral nutrition is an etiologic factor in the formation of biliary sludge. We studied whether enteral nutrition is also a risk factor for sludge. METHODS: Fifty patients with a needle catheter jejunostomy (NCJ) placed during a major abdominal operation underwent preoperative and weekly postoperative ultrasonography until NCJ feedings were discontinued (1 to 6 weeks). RESULTS: All patients were men. The mean age was 63.2 +/- 1.6 years. Fourteen asymptomatic patients (28.0%) had biliary sludge within 2 weeks of beginning enteral feedings through a NCJ. Complete ultrasonographic resolution of sludge was observed in 13 of the 14 positive patients within 1 to 2 weeks of resuming an oral diet. One patient was lost to follow-up after 14 week; a positive sonogram had persisted but the patient remained asymptomatic. During the period of observation, no other patient had signs of biliary tract disease. CONCLUSIONS: (1) Biliary sludge may form in some patients during enteral feeding with NCJ. (2) Sludge is cleared by the gallbladder once an oral diet is resumed. (3) There appears to be little risk of complications during postoperative enteral feeding.     

Abnormalities of apolipoprotein E in the acquired immunodeficiency syndrome

Given the important role of apolipoprotein E (apoE) in triglyceride metabolism, we analyzed plasma levels and degree of sialylation of apoE in subjects with the acquired immunodeficiency syndrome (AIDS), a disorder accompanied by hypertriglyceridemia. Levels of apoE were significantly increased (1.84-fold) and correlated with plasma triglycerides (r = .663, P < .001) in AIDS. Subjects with AIDS and the apoE3/E2 phenotype showed the most prominent increases in both plasma triglyceride and apoE levels (3.4 and 2.2-fold over controls). Additionally, apoE from subjects with AIDS showed an increased amount of sialylation, compared with controls (34% increase in apoE3/E3 subjects). Increased sialylation correlated with the increase in apoE levels. In contrast, there was no increase in sialylation of apo C-III in AIDS. Thus, triglyceride levels in AIDS are influenced by apoE subtype and subjects with AIDS show changes in apoE structure.     

Influence of dietary restriction on ionotropic glutamate receptors during aging in C57B1 mice

The present study was designed to determine whether the memory sparing effects of dietary restriction during aging could be through an effect on ionotropic glutamate receptors. Quantitative autoradiography was performed on 3, 10, and 26 month old mice to examine the density changes of NMDA, AMPA and kainate binding sites in aging animals. Spatial memory performance was also tested in these mice with the use of the Morris water maze. The 10 and 26 month olds were either ad libitum-fed or diet-restricted (60% of ad libitum-fed calories). Ad libitum-fed, 26 month old mice had significant decreases in NMDA-displaceable [3H]glutamate in all ten cortical, two out of seven hippocampal, and two out of four subcortical regions, as compared to 3 month olds. Diet-restricted, 26 month old mice only differed significantly from young in three cortical and two subcortical regions. The aged ad libitum-fed mice exhibited significantly poorer performance in the spatial memory task than all other groups. The diet-restricted 26 month olds only performed significantly worse than 3 month olds and diet-restricted 10 month olds. These results suggest that some of the memory sparing effects of dietary restriction on aged animals may be due to an influence on NMDA receptors.     

Endovascular treatment of ruptured posterior circulation aneurysms using electrolytically detachable coils

The murine interleukin-7 (IL-7) gene was disrupted to examine the role of IL-7 in the lymphoid system. Expansion of lymphoid cells is sharply curtailed in IL-7-deficient mice. This is evident in a dramatic reduction but not elimination of lymphoid cells in the thymus, bone marrow and spleen. The few thymocytes present express CD4 and/or CD8 markers associated with T-cell maturation. Similarly, a limited number of B cells detected in the bone marrow rearrange and express immunoglobulin genes. Small but distinct populations of B and T cells are found in the spleens of IL-7-deficient mice. Thus the signal transmitted by IL-7 plays a central role in the expansion of lymphocytes while it is not absolutely required for their maturation. A transgene that directs expression of IL-7 to lymphoid cells was found to restore the numbers of thymocytes, bone marrow B-cell progenitors and splenic lymphocytes of IL-7-deficient mice to approximately normal levels. This genetic complementation confirms that the lymphoid defect is specifically due to the absence of IL-7 and demonstrates that the expansion of lymphoid cells in an organism is regulated by their exposure to IL-7.     

Cardiopulmonary function at rest and during exercise after resection for bronchial carcinoma

BACKGROUND: Measurements of postoperative spirometric values after pneumonectomy and lobectomy vary considerably, and few researchers have studied the changes in exercise capacity during maximal work after lung resection. The purpose of this study was to describe the postoperative alterations in cardiopulmonary function. METHODS: Ninety-seven consecutive patients with lung malignancy were prospectively examined with maximal exercise test, spirometry, and arterial gas tensions. Fifty-seven patients were reinvestigated 6 months postoperatively. RESULTS: In patients having lobectomy, forced expiratory volume in 1 second decreased 8%, and exercise capacity, expressed by maximal oxygen uptake and maximal work rate, significantly decreased 13%. In patients having pneumonectomy forced expiratory volume in 1 second significantly decreased 23%, but the loss in lung volume was partly compensated as measured by exercise capacity, which decreased only 16%. Generally patients with the smallest preoperative forced vital capacity had the smallest postoperative deterioration expressed in percentages. We found a weak correlation between alterations in maximal oxygen uptake and lung function after resection. CONCLUSIONS: Lobectomy is associated with only minor deterioration of lung function and exercise capacity. Pneumonectomy causes a decrease in pulmonary volumes to about 75% of the preoperative values, partly compensated in better oxygen uptake, which postoperatively was about 85% of the preoperative values. Alteration in forced expiratory volume in 1 second is a poor predictor of change in exercise capacity after pulmonary resection.