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Brainstem gliomas comprise 10-20% of all pediatric central nervous system (CNS) tumors and diffuse intrinsic pontine gliomas (DIPGs) account for the majority of these lesions. DIPG is a rapidly progressive disease with almost universally fatal outcomes and a median survival less than 12 months. Current standard-of-care treatment for DIPG includes radiation therapy, but its long-term survival effects are still under debate. Clinical trials investigating the efficacy of systemic administration of various therapeutic agents have been associated with disappointing outcomes. Recent efforts have focused on improvements in chemotherapeutic agents employed and in methods of localized and targeted drug delivery. This review provides an update on current preclinical and clinical studies investigating treatment options for brainstem gliomas.

Colony collapse disorder (CCD), a syndrome whose defining trait is the rapid loss of adult worker honey bees, Apis mellifera L., is thought to be responsible for a minority of the large overwintering losses experienced by U.S. beekeepers since the winter 2006-2007. Using the same data set developed to perform a monofactorial analysis (PloS ONE 4: e6481, 2009), we conducted a classification and regression tree (CART) analysis in an attempt to better understand the relative importance and interrelations among different risk variables in explaining CCD. Fifty-five exploratory variables were used to construct two CART models: one model with and one model without a cost of misclassifying a CCD-diagnosed colony as a non-CCD colony. The resulting model tree that permitted for misclassification had a sensitivity and specificity of 85 and 74%, respectively. Although factors measuring colony stress (e.g., adult bee physiological measures, such as fluctuating asymmetry or mass of head) were important discriminating values, six of the 19 variables having the greatest discriminatory value were pesticide levels in different hive matrices. Notably, coumaphos levels in brood (a miticide commonly used by beekeepers) had the highest discriminatory value and were highest in control (healthy) colonies. Our CART analysis provides evidence that CCD is probably the result of several factors acting in concert, making afflicted colonies more susceptible to disease. This analysis highlights several areas that warrant further attention, including the effect of sublethal pesticide exposure on pathogen prevalence and the role of variability in bee tolerance to pesticides on colony survivorship.

Fractionated radiotherapy (FRT) and gamma knife stereotactic radiosurgery (GKSRS) are used as adjuvant therapies to surgical resection for functional and non-functional pituitary adenomas, although their optimum role in the treatment algorithm, as well as long-term safety and efficacy, still awaits further study. We report a single center experience with 33 patients with non-functional (16 patients), ACTH- (five patients), GH- (four patients), or prolactin-secreting (eight patients) tumors treated with FRT or SRS. The median tumor diameter was 1.9 cm, and the median follow-up was 36 months. For GKSRS, the median dosage was 16 Gy for non-functional adenomas and 23 Gy for hormone-secreting tumors. The median total dose for FRT was 50.4 Gy over 28 fractions (median). Two patients (6%) demonstrated radiographic evidence of tumor progression, three patients (9%) demonstrated radiation-induced visual field deficits on neuro-ophthalmic evaluation, and two patients (6%) suffered from radiation-induced hypopituitarism. Biochemical control, defined as normalized hormone values in the absence of medical therapy, was achieved in five out of eight prolactinoma patients and two out of five patients with Cushing's disease, but none of the four patients with acromegaly. These results are presented with a review of the relevant literature on the differential characteristics of FRT versus SRS in the treatment of functional and non-functional pituitary adenomas and validate postoperative irradiation as a potentially safe and effective means for tumor control.

Disseminated intravascular coagulation (DIC) as a complication of surgery for ventriculoperitoneal (VP) shunts is extremely rare, and only one case has been documented in the literature. The authors present the case of a 9-year-old girl with shunted hydrocephalus who presented with a 3-day history of headaches and vomiting. A head CT showed enlarged ventricles compared with baseline. An emergent VP shunt revision was performed, during which an obstructed proximal catheter was found. Immediately after extubation, the patient became apneic and progressed to cardiopulmonary arrest. A breathing tube was reinserted followed by resuscitation attempts that led to extracorporeal membrane oxygenation. Soon after reintubation, bloody drainage was noted in the endotracheal tube, and subsequent laboratory studies were consistent with DIC. The patient died on postoperative Day 1, and autopsy findings confirmed DIC. Note that DIC is a recognized complication of trauma, particularly with brain injury, but it is rare with neurosurgical procedures. Disseminated intravascular coagulation should be considered if excessive bleeding occurs after any brain insult.

Diffuse intrinsic pontine gliomas constitute ~ 60–75% of tumors found within the pediatric brainstem. These malignant lesions present with rapidly progressive symptoms such as cranial nerve, long tract, or cerebellar dysfunctions. Magnetic resonance imaging is usually sufficient to establish the diagnosis and obviates the need for surgical biopsy in most cases. The prognosis of the disease is dismal, and the median survival is < 12 months. Resection is not a viable option. Standard therapy involves radiotherapy, which produces transient neurological improvement with a progression-free survival benefit, but provides no improvement in overall survival. Clinical trials have been conducted to assess the efficacy of chemotherapeutic and biological agents in the treatment of diffuse pontine gliomas. In this review, the authors discuss recent studies in which systemic therapy was administered prior to, concomitantly with, or after radiotherapy. For future perspective, the discussion includes a rationale for stereotactic biopsies as well as possible therapeutic options of local chemotherapy in these lesions.

Hypothalamic hamartomas are rare congenital malformations located in the region of the tuber cinereum and third ventricle. Patients may be asymptomatic, but the usual presentation is gelastic seizures, precocious puberty, and/or developmental delay. Without surgical intervention, the gelastic seizures, which are typically present in childhood, may progress to other seizure types, including generalized epilepsy, and are generally refractory to antiepileptic drugs. This review will discuss the clinical and electrophysiologic aspects of these lesions, as well as treatment options, including surgery, endoscopy, and radiosurgery.

Sellar and parasellar lesions in the pediatric population have traditionally been approached through either a transsphenoidal hypophysectomy or craniotomy or a combination of the two, with the surgical approach being dictated by the anatomical location and extent of the pathology. The introduction and evolution of the endonasal endoscopic technique has provided a minimally invasive method alone or in combination with the operative microscope for removal of these lesions in the pediatric population. The authors have implemented in their practice the use of endonasal endoscopic-assisted microsurgery in the pediatric population harboring sellar and/or lesions extending to the suprasellar space and report our experience in nine patients. Five craniopharyngiomas, one Rathke’s cleft cyst, and two pituitary tumors were treated via endonasal endoscopic-assisted microsurgery. Histopathologic examination revealed lymphocytic hypophysitis in one patient with an enhancing lesion in the pituitary stalk. The approach utilized by the authors is performed through one nostril without any resection of the nasal turbinates or nasal septum. The middle turbinate is displaced laterally, while the nasal septum is moved medially. Gross total, near-total, and subtotal resections and a diagnostic biopsy were obtained in six, one, one, and one patients, respectively. The authors were able to safely perform this procedure in nine pediatric patients, and the lack of turbinate or septum resection minimized postoperative discomfort.

Dr. Fumio Matsumura's legacy embraced a passion for exploring environmental impacts of agrochemicals on non-target species such as bees. Why most formulations are more toxic to bees than respective active ingredients and how pesticides interact to cause pollinator decline cannot be answered without understanding the prevailing environmental chemical background to which bees are exposed. Modern pesticide formulations and seed treatments, particularly when multiple active ingredients are blended, require proprietary adjuvants and inert ingredients to achieve high efficacy for targeted pests. Although we have found over 130 different pesticides and metabolites in beehive samples, no individual pesticide or amount correlates with recent bee declines. Recently we have shown that honey bees are sensitive to organosilicone surfactants, nonylphenol polyethoxylates and the solvent N-methyl-2-pyrrolidone (NMP), widespread co-formulants used in agrochemicals and frequent pollutants within the beehive. Effects include learning impairment for adult bees and chronic toxicity in larval feeding bioassays. Multi-billion pounds of formulation ingredients like NMP are used and released into US environments. These synthetic organic chemicals are generally recognized as safe, have no mandated tolerances, and residues remain largely unmonitored. In contrast to finding about 70% of the pesticide active ingredients searched for in our pesticide analysis of beehive samples, we have found 100% of the other formulation ingredients targeted for analysis. These ‘inerts’ overwhelm the chemical burden from active pesticide, drug and personal care ingredients with which they are formulated. Honey bees serve as an optimal terrestrial bioindicator to determine if ‘the formulation and not just the dose makes the poison’.

This article provides a broad overview of the data, including laboratory and clinical studies, currently available on the combination of immunotherapy and chemotherapy for treating cancer. The various forms of immunotherapy combined with chemotherapy include monoclonal antibodies, adoptive lymphocyte transfer, or active specific immunotherapy, such as tumor proteins, irradiated tumor cells, tumor cell lysates, dendritic cells pulsed with peptides or lysates, or tumor antigens expressed in plasmids or viral vectors. This discussion is not limited to malignant brain tumors, because many of the studies have been conducted on various cancer types, thereby providing a comprehensive perspective that may encourage further studies that combine chemotherapy and immunotherapy for treating brain tumors.

✓ Brain abscesses occur infrequently but continue to be problematic for the pediatric neurosurgical community. The incidence of brain abscesses in children has not changed much, although individual reports may show an increase or decrease in the number of reported cases depending on the patient population studied. An increase could be attributed to earlier detection due to advancements in imaging modalities and/or to an increase in the number of children with immunodeficient states caused by AIDS, chemotherapy for malignant lesions, and immunosuppressive therapy for organ transplantation. A decrease in the incidence of brain abscesses could be attributed to practices such as antibiotic treatment for otitis media, sinusitis, and/or prophylactic antimicrobial treatment for congenital heart disease in children. The morbidity and mortality rates associated with brain abscesses have not changed dramatically in the antibiotic and imaging era, and their preferred management can vary among healthcare providers. These lesions have been successfully treated by neurosurgeons. The causes of brain abscesses are highly variable in children, which is also the case in adults, but the predisposing factors in the pediatric population differ in prevalence. Cyanotic congenital heart disease, hematogenous dissemination, contiguous infection, and penetrating traumatic injuries are the most common causes of brain abscesses in children. In this review, the authors discuss the causes and medical and surgical management of brain abscesses in children.

1. 1. Whole-body homogenate and hemolymph enzyme profiles of normal and γ-irradiated boll weevils were compared. 2. 2. The specific activity of homogenate lactic dehydrogenase (LDH) in treated males was significantly lower than that in normal males ( 73 ± 3 vs 104 ± 3 mU/mg protein ). 3. 3. The specific activity of homogenate acid phosphatase (AP) in treated females was significantly lower than that observed in normal females ( 89 ± 5 vs 109 ± 5 mU/mg protein ). 4. 4. Hemolymph LDH and AP showed a comparable activity pattern to homogenate LDH and AP activities. 5. 5. The homogenate LDH activity in normal males correlated well with egg production and egg hatching by females after mating with normal males. 6. 6. Low LDH activity corresponded with very low egg production and no egg hatching in irradiated males. 7. 7. LDH and AP may be monitored to assess the sterility of the boll weevil after γ-irradiation.

1. 1. The specific activities of lactic dehydrogenase, α-hydroxybutyric dehydrogenase, glutamic oxalacetic transaminase, glutamic pyruvic transaminase, and acid phosphatase were monitored in adult male and female boll weevil homogenates for eleven days post emergence. 2. 2. The above enzymes, plus β-glucuronidase, were monitored in adult male and female boll weevil hemolymph for 10 days post emergence.