Citations

ABSTRACT A retrospective review of colloid cysts diagnosed from 1974 to 1986 emphasizes the presenting symptoms of these lesions, their surgical management, and the contribution of modern imaging techniques to their diagnosis and therapy. In this 12-year period, 84 patients (45 men and 39 women) had a colloid cyst diagnosed. The patients' mean age was 46 years (range, 7-82 years). Surgery was performed in 55 patients, 7 of whom had undergone prior surgery elsewhere. The surgical approaches used were transfrontal-transventricular, transcallosal, computer-assisted stereotactic aspiration and resection by stereotactic craniotomy, and shunting of cerebrospinal fluid without removal of the lesion. There was no operative mortality, but complications occurred in 15 patients (27%). Preoperative imaging showed hydrocephalus in 93% of the patients: severe in 43%, moderate in 36%, and mild in 14%. In the surgically treated group, the most common presenting symptoms were headache, change in mental status, ataxia, nausea and vomiting, visual disturbance, emotional lability/inappropriate affect, depersonalization, and hypersomnolence. Twenty-four patients for whom surgery was not recommended are being followed up closely. Most of these patients had normal ventricles. The symptoms in this group included headache, anxiety/nervousness, ataxia, memory impairment, visual disturbance, and seizures. Five autopsy cases of patients with colloid cysts were available during this period and were reviewed. Direct removal of colloid cysts can be accomplished with low morbidity and mortality, avoiding the frequent revisions and complications related to shunt procedures. There is a subgroup of colloid cysts that can be operated upon electively or followed up closely with serial imaging studies.

Abstract Six patients with juvenile pilocytic astrocytomas of the thalamus or basal ganglia underwent seven computer-assisted stereotactic laser craniotomies with complete or nearly complete removal of the tumor in all cases. The tumor was located in the right basal ganglia in one patient, the left basal ganglia in one patient, and the left thalamus in four patients. Postoperative assessment of the completeness of tumor removal was confirmed by contrast-enhanced computed tomographic scanning within the first 2 weeks after operation. None of the patients was neurologically worse after the procedure, and five were improved. The duration of follow-up ranged from 6 months to 3.5 years. In this group of patients, the computer-assisted, stereotactically guided resection of these deeply located, benign tumors was accomplished with no morbidity or mortality.

Abstract This report describes a computed tomography-based computer-assisted stereotactic technique for performing 3rd ventriculostomy. The procedure has been performed on seven patients with acquired obstructive hydrocephalus of various etiologies. None of these patients have yet required shunting. (18:791–794, 1986)

Abstract We have developed a computer-resident stereotactic atlas of the human brain that quantitatively defines subcortical structures within anatomical landmarks detected on obliquely reconstructed computed tomography (CT) slices. Horizontal stereotactic atlas sections can be stretched and contracted by polar transformation and labeled by a computer to fit within these CT scan-defined landmarks. The stereotactic coordinates of any substructure on the atlas-labeled CT slice may then be calculated by the computer and expressed in mechanical adjustments on a stereotactic surgical frame located in the operating room. We demonsrate the use of this method in the stereotactic treatment of movement disorders as an augmentation to conventional ventriculography and microelectrode recording.

A recently identified variant within the fat mass and obesity-associated ( FTO ) gene is carried by 46% of Western Europeans and is associated with an ~1.2 kg higher weight, on average, in adults and an ~1 cm greater waist circumference. With >1 billion overweight and 300 million obese persons worldwide, it is crucial to understand the implications of carrying this very common allele for the health of our aging population. FTO is highly expressed in the brain and elevated body mass index (BMI) is associated with brain atrophy, but it is unknown how the obesity-associated risk allele affects human brain structure. We therefore generated 3D maps of regional brain volume differences in 206 healthy elderly subjects scanned with MRI and genotyped as part of the Alzheimer's Disease Neuroimaging Initiative. We found a pattern of systematic brain volume deficits in carriers of the obesity-associated risk allele versus noncarriers. Relative to structure volumes in the mean template, FTO risk allele carriers versus noncarriers had an average brain volume difference of ~8% in the frontal lobes and 12% in the occipital lobes—these regions also showed significant volume deficits in subjects with higher BMI. These brain differences were not attributable to differences in cholesterol levels, hypertension, or the volume of white matter hyperintensities; which were not detectably higher in FTO risk allele carriers versus noncarriers. These brain maps reveal that a commonly carried susceptibility allele for obesity is associated with structural brain atrophy, with implications for the health of the elderly.

Abstract When cells encounter substantial DNA damage, critical cell cycle events are halted while DNA repair mechanisms are activated to restore genome integrity. Genomic integrity also depends on proper assembly and function of the bipolar mitotic spindle, which is required for equal chromosome segregation. Failure to execute either of these processes leads to genomic instability, aging, and cancer. Here, we show that following DNA damage in the breast cancer cell line MCF-7, the centrosome protein centrin2 moves from the cytoplasm and accumulates in the nucleus in a xeroderma pigmentosum complementation group C protein (XPC)–dependent manner, reducing the available cytoplasmic pool of this key centriole protein and preventing centrosome amplification. MDA-MB 231 cells do not express XPC and fail to move centrin into the nucleus following DNA damage. Reintroduction of XPC expression in MDA-MB 231 cells rescues nuclear centrin2 sequestration and reestablishes control against centrosome amplification, regardless of mutant p53 status. Importantly, the capacity to repair DNA damage was also dependent on the availability of centrin2 in the nucleus. These observations show that centrin and XPC cooperate in a reciprocal mechanism to coordinate centrosome homeostasis and DNA repair and suggest that this process may provide a tractable target to develop treatments to slow progression of cancer and aging. Cancer Res; 70(8); 3320–8. ©2010 AACR.

Abstract Bone mass and its mineral content are under genetic control. The vitamin D receptor (VDR) gene has been shown to be a major locus for genetic effects on bone mineral density (BMD), and polymorphisms in this gene accounted for a large proportion of genetic variance in BMD in an Australian population. In this study, we investigated whether similar associations are present in a North American population. We studied 139 normal healthy women (age 53.2 ± 14.5, mean ± SD) and 43 severely osteoporotic postmenopausal women (age 65.8 ± 5.9). In the 127 of them with complete genetic studies, the distribution of genotypes, determined by polymerase chain reaction on leukocyte DNA samples, agreed closely with that in the Australian population. BMD was strongly related to age and weight, and, thus was adjusted for these parameters prior to genetic analysis. We found that age modulated the effect of VDR genotypes on femoral neck BMD (FN-BMD) (TaqI, p = 0.036;BsmI, p = 0.118; ApaI, p = 0.041) such that the effect of genotype was greatest among younger (premenopausal) women and declined with age so that there was no discernible difference by age 70. Among the younger women, a high FN-BMD was associated with the TT (or aa or bb) genotype while low FN-BMD was associated with the tt (or AA or BB) genotype. In osteoporotic women, although the difference in FN-BMD between alternate TaqI homozygotes (TT vs. tt) was 0.13 g/cm2 (or about 18%), the overall difference among the genotype groups was not significant (TaqI, p = 0.13; BsmI, p = 0.21; ApaI, p = 0.09), possibly due to the small sample of osteoporotic women. There was no relationship of VDR genotype to lumbar spine BMD. We conclude that the VDR gene modulates differences in BMD in premenopausal women. Subsequent interaction of the gene and environmental factors and the role of VDR genotypes in predisposing to osteoporosis needs further study.

AbstractIn the past decade, interest in surgery as a means to improve public health and engage in international service has increased significantly. International organizations, academic institutions, professional associations, and humanitarian aid organizations recognize that disparate access to surgical care affects global health and they have recently joined forces to address access to surgical care. Current initiatives focus on quantitatively defining surgical disparity, prioritizing a surgical agenda, and developing economically sustainable models for health care assistance, training, and delivery. The Global Burden of Surgical Disease Working Group (GBoSD WG) strives to (1) quantitatively define global disparity in surgical care; (2) assess unmet surgical need; (3) identify priorities; (4) develop sustainable models for improved health care delivery; and (5) advocate for a surgical presence within the global public health agenda. This article formally introduces the GBoSD Working Group and papers presented during the 2009 Symposium at the American College of Surgeons in Chicago.

ABSTRACT Vesicular stomatitis virus (VSV) has long been regarded as a promising recombinant vaccine platform and oncolytic agent but has not yet been tested in humans because it causes encephalomyelitis in rodents and primates. Recent studies have shown that specific tropisms of several viruses could be eliminated by engineering microRNA target sequences into their genomes, thereby inhibiting spread in tissues expressing cognate microRNAs. We therefore sought to determine whether microRNA targets could be engineered into VSV to ameliorate its neuropathogenicity. Using a panel of recombinant VSVs incorporating microRNA target sequences corresponding to neuron-specific or control microRNAs (in forward and reverse orientations), we tested viral replication kinetics in cell lines treated with microRNA mimics, neurotoxicity after direct intracerebral inoculation in mice, and antitumor efficacy. Compared to picornaviruses and adenoviruses, the engineered VSVs were relatively resistant to microRNA-mediated inhibition, but neurotoxicity could nevertheless be ameliorated significantly using this approach, without compromise to antitumor efficacy. Neurotoxicity was most profoundly reduced in a virus carrying four tandem copies of a neuronal mir125 target sequence inserted in the 3′-untranslated region of the viral polymerase (L) gene.