Preoperative esophageal manometry and outcome of laparoscopic adjustable silicone gastric banding.

BACKGROUND: Laparoscopic adjustable silicone gastric banding (LASGB) for morbid obesity has been reported to provide long-term weight loss with a low risk of operative complications. Nevertheless, esophageal dilation leading to achalasia-like and reflux symptoms is a feared complication of LASGB. This study evaluates the clinical benefit of routine preoperative esophageal manometry in predicting outcome after LASGB in morbidly obese patients. METHOD: A review of prospectively collected data on 77 patients who underwent routine esophageal manometry prior to LASGB for morbid obesity from February 2001 to September 2003 was performed. Aberrant motility, abnormal lower esophageal sphincter (LES) pressures, and other nonspecific esophageal motility disorders noted on preoperative esophageal manometry defined patients of the abnormal manometry group. Outcome differences in weight loss, emesis, band complications, and gastroesophageal reflux disease (GERD) resolution or improvement were compared between patients of the abnormal and normal manometry groups after LASGB. Analysis of variance (ANOVA) and chi-square tests were performed to determine the significance of these outcomes. RESULTS: Of the patients tested, 14 had abnormal esophageal manometry results, whereas 63 had normal manometry results before LASGB. There was no significant difference in percent excess weight loss (%EWL) at 6 and 12 months between the groups after gastric banding. Severe postoperative emesis occurred more frequently in patients with abnormal manometry results than in those with normal manometry results. There were two band-related complications, both of which occurred in patients of the normal manometry group. CONCLUSIONS: Preoperative esophageal manometry does not predict weight loss or GERD outcomes after LASGB in morbidly obese patients. Postoperative emesis was more common in patients with abnormal manometry findings, but such symptoms were manageable and did not lead to poor weight loss or to band removal or increased band-related complications.

Memory complaints in nondemented men predict future pathologic diagnosis of Alzheimer disease.

The validity of memory complaints as a predictor of Alzheimer disease (AD) was assessed in 237 Japanese-American men autopsied at ages 74 to 97 years. These men were free of dementia at the time memory complaints were assessed 1 to 11 years earlier. Memory complaints were found to predict the neuropathologic diagnosis of AD after adjusting for age, time to death, education, depression, and cognitive functioning.

3-Nitrotyrosine immunoreactivity in olfactory receptor neurons of patients with Alzheimer's disease: implications for impaired odor sensitivity.

Olfactory sensory function is impaired in patients with the diagnosis of probable Alzheimer's disease (AD) compared to elderly controls, and the olfactory epithelium (OE) of AD patients exhibits several pathological changes characteristic of the AD brain. To confirm that the populations from whom our postmortem tissues are obtained exhibit similar decrements in sensory function, threshold testing was performed; probable AD patients had significantly higher olfactory thresholds than controls. To determine if oxidative stress contributes to decreased olfactory function in AD, we localized 3-nitrotyrosine (3-NT) immunoreactivity in OE obtained postmortem from patients with neuropathologically confirmed AD and age-matched controls with brains free of significant neurodegenerative pathology. In AD patients, immunoreactivity was localized in olfactory receptor neurons (ORNs), including dendritic knobs where ion channels that participate in sensory transduction are located, suggesting a direct mechanism for olfactory impairment. In controls, immunoreactivity occurred in blood vessel endothelium, suggesting age-related vascular dysfunction. Immunohistochemistry for CD68, a macrophage scavenger receptor, demonstrated activated macrophages, a source of free radicals contributing to 3-NT formation, in the OE of AD patients but not controls. These results demonstrate increased oxidative stress and modification of ORN proteins that may contribute directly to olfactory impairment in AD patients.

Comparison of objective outcomes following laparoscopic Nissen fundoplication versus laparoscopic gastric bypass in the morbidly obese with heartburn.

BACKGROUND: Heartburn and gastroesophageal reflux disease (GERD) affects approximately 25-50% of morbidly obese patients. Although objective physiologic testing has been reported extensively in patients following Nissen fundoplication, there are no previous reports of such testing in morbidly obese patients. A life-saving surgical alternative for the morbidly obese patient is gastric bypass surgery, which usually improves heartburn symptoms in addition to many serious health conditions such as diabetes, hypertension, and sleep apnea. We hypothesized that, in morbidly obese patients, gastric bypass surgery would be as effective as Nissen fundoplication in reducing both heartburn symptoms and esophageal acid exposure, as reflected by the DeMeester score. METHODS: Between 1995 and 2000, all patients undergoing laparoscopic Nissen fundoplication (LN) and laparoscopic gastric bypass (LGB) in our practice underwent preoperative and postoperative esophageal physiologic testing. Patients were included in this study that were morbidly obese and had significant heartburn symptoms or objective evidence of acid reflux, and had repeat esophageal physiologic testing after either LN or LGB. Data were obtained through retrospective review of prospectively collected data. RESULTS: Twelve patients met the inclusion criteria: six patients who had LN and six who had LGB. The mean body mass index (BMI) was 55 kg/m2 in the LGB group and 39.8 in the LN group. After surgery, the mean DeMeester score decreased from 64.3 to 2.8 in the LN group ( p = 0.01) and from 34.7 to 5.7 in the LGB group ( p = 0.1). Both groups' mean postoperative DeMeester scores were normal after surgery, and there was no significant difference between the two groups ( p = 0.3). Both groups experienced a significant improvement in heartburn symptoms postoperatively. The mean preoperative symptom score improved from 3.5 to 0.5 in the LN group ( p = 0.01) and from 2.2 to 0.2 in the LGB group ( p = 0.003). There was no difference in the mean postoperative symptom scores between the groups ( p = 0.35). After surgery, mean LES resting pressures increased from 12.9 to 35.5 ( p = 0.003) in the LN group and from 23.6 to 29.7 ( p = 0.45) in the LGB group. There were no complications in either group. CONCLUSION: Results of this study show that laparoscopic gastric bypass and laparoscopic Nissen fundoplication are both effective in treating heartburn symptoms and objective acid reflux in morbidly obese patients. The health benefits of weight loss after laparoscopic gastric bypass should make this operation the procedure of choice in the morbidly obese patient with heartburn.

Cerebellar liponeurocytoma. Case report and review of the literature.

Cerebellar liponeurocytoma is a rare tumor of the posterior fossa that has many morphological similarities to medulloblastoma and neurocytoma. Recently the World Health Organization working group for classification of central nervous system neoplasms adopted the term "cerebellar liponeurocytoma" to provide a unified nomenclature for a tumor variously labeled in the literature as lipomatous medulloblastoma, lipidized medulloblastoma, medullocytoma. neurolipocytoma, lipomatous glioneurocytoma, and lipidized mature neuroectodermal tumor of the cerebellum. The rarity of this tumor and paucity of pertinent information regarding its biological potential and natural history have resulted in the application of various treatment modalities. It is suggested in the available literature that these lesions have a much more favorable prognosis than typical medulloblastomas, and that adjuvant therapy for liponeurocytoma need not be as extensive as that administered for medulloblastomas.

Congenital glioblastoma multiforme: a report of three cases and a review of the literature.

The clinical histories, histologic features, and immunohistochemical staining patterns for glial fibrillary acidic protein, vimentin, p53, and epidermal growth factor receptor (EGFR) of three cases of congenital glioblastoma multiforme are given and previous case reports are reviewed. Of the three cases reported in this series, two have had long-term survivals of greater than 2 1/2 and 5 1/2 years after surgery and surgery followed by chemotherapy, respectively. Both of these cases also demonstrated p53 protein accumulation, a finding in pediatric glioblastoma multiforme associated with poor prognosis. The third case occurred in an infant who died at birth and demonstrated a well-circumscribed tumor that did not invade adjacent brain parenchyma. Considering these three cases, the biological behavior in congenital glioblastoma multiforme may not be unfavorable as portrayed in the literature or as seen in its adult counterpart.

Accuracy of clinical criteria for AD in the Honolulu-Asia Aging Study, a population-based study.

OBJECTIVE: To determine diagnostic accuracy for AD in a population-based study of Japanese-American men. AD is neuropathologically confirmed for more than 80% of cases at major referral centers (primarily Caucasians); however, information on diagnostic accuracy in population-based studies and studies of different ethnic groups is limited. METHODS: There were 3,734 men who participated in the Honolulu-Asia Aging Study 1991 through 1993 dementia examination and 2,603 in the 1994 through 1996 examination. Diagnoses were based on published criteria. Neuropathologists blinded to clinical data quantified neurofibrillary tangles (NFT) and neuritic plaques (NP). RESULTS: Of 220 autopsied subjects, clinical evaluation revealed 68 with normal cognition, 73 intermediate, and 79 with dementia: 20 AD, 27 vascular dementia, 19 AD + other, and 13 other dementia. Among 20 cases with pure AD, the median value for maximum neocortical NFT density was 6.9/mm(2) and for neocortical NP density was 8.0/mm2. Corresponding densities for other groups were <3.0/mm2. Using established neuropathologic criteria, 25% (5/20) of clinical AD cases had enough NP to meet definite AD criteria, whereas 65% (13/20) had sufficient NP to meet neuropathologic definite or probable AD criteria. Among nine AD cases with moderately severe dementia, only two (22%) had NP densities great enough to meet definite neuropathologic criteria, whereas seven (78%) met neuropathologic criteria for probable AD. CONCLUSIONS: Neuropathologic confirmation and NP density among decedents with clinical AD in this population-based study were lower than reported by referral centers and similar to reports from two other community studies. Ethnic differences in propensity for amyloid deposition as well as differences in clinical severity and representativeness of cases might contribute to these findings.

"Preclinical" AD revisited: neuropathology of cognitively normal older adults.

OBJECTIVE: To classify neuropathologic alterations in the brains of nondemented older adults using current sets of criteria for AD. BACKGROUND: AD neuropathologic alterations are found in the brains of some nondemented elderly subjects and suggest the possibility of presymptomatic AD. Three sets of guidelines have been developed to classify AD using senile plaques, neuritic plaques, and neurofibrillary tangles (NFT). METHODS: Neuropathologic changes in 59 older adults followed longitudinally with a standard battery of mental status measures were investigated using Khachaturian, Consortium to Establish a Registry for Alzheimer's Disease (CERAD), and National Institute on Aging-Reagan Institute (NIA-RI) guidelines. AD neuropathologic markers were evaluated in neocortical and allocortical regions. Cases were categorized as neuropathologically "normal" or "AD-like" and compared for possible mental status differences. RESULTS: Between 11 and 49% of cases met one or more of the three classifications of AD. With adjustments for multiple comparisons, only NFT in hippocampal CA1 region were associated with autopsy age, suggesting that this may represent a pathologic process associated with normal brain aging. Using the NIA-RI guidelines, subjects in the AD-like group performed less well on the immediate paragraph recall and word-list delayed recall than their counterparts who did not meet these guidelines. CONCLUSIONS: These data indicate that the prevalence of "preclinical" AD in our population is relatively low based on the NIA-RI classification. Although many subjects had AD-like changes based on CERAD and Khachaturian guidelines, they exhibited no differences in mental performance, suggesting that the aging brain may be able to withstand such structural changes without meaningful impact on mental functioning.

Midlife blood pressure and neuritic plaques, neurofibrillary tangles, and brain weight at death: the HAAS. Honolulu-Asia aging Study.

Midlife hypertension is associated with later development of cognitive impairment, vascular dementia (VsD), and possibly Alzheimer's disease (AD). Neuropathic cerebrovascular lesions and brain atrophy have been associated with elevated blood pressure (BP), however, to our knowledge there have been no prospective investigations of an association of blood pressure levels measured in midlife with the microscopic lesions of AD. We investigated the relationship of BP level in midlife to development of neurofibrillary tangles (NFT), neuritic plaques (NP), and low brain weight at autopsy among Japanese-American men who were members of the Honolulu Heart Program/Honolulu-Asia aging Study (HHP/HAAS) cohort. The HHP/HAAS is a population-based, longitudinal study of cognitive function and dementia with 36 years of follow-up. Neocortical and hippocampal NFT and NP were counted per mm(2), and fixed brain weight was measured for 243 decedents. Elevated systolic BP, (> or =160 mm Hg) in midlife was associated with low brain weight and greater numbers of NP in both neocortex and hippocampus. Diastolic BP elevation, (> or =95 mm Hg) was associated with greater numbers of NFT in hippocampus. Results indicate that in addition to the accepted association of high BP with neuropathic cerebrovascular lesions, there is a direct relationship with brain atrophy, NP and NFT.

Intracavernous teratoma in a school-aged child.

An eight-year-old boy presented with left eye pain, photophobia, proptosis, third nerve paresis and decreased visual acuity. Magnetic resonance imaging revealed a nonenhancing mass filling the cavernous sinus. Using an extradural fronto-orbitozygomatic approach, the cavernous sinus was approached laterally, and a teratoma was removed from within the cavernous sinus. This is the first case of a truly intracavernous teratoma in a child and the fourth case of a teratoma reported in the cavernous sinus region overall. This report outlines the diagnosis and treatment of this unusual cavernous sinus tumor.

Alzheimer neuropathologic alterations in aged cognitively normal subjects.

The histopathologic changes distinguishing early Alzheimer disease (AD) from normal or pathologic aging are not clearly defined. This report describes the autopsy findings of 59 elderly, well-educated, volunteers. They were examined longitudinally with mental status testing, some for up to 8 years, as part of our normal aging study. This study reveals that (1) the brains of many subjects who did not show cognitive impairment on neuropsychologic testing contain abundant senile plaques (SP) and/or neurofibrillary tangles (NFT); (2) 29 subjects met Khachaturian criteria for AD, 15 met CERAD and 7 met National Institute on Aging-Reagan Institute guidelines; (3) Braak and Braak staging method included 9 in stage IV subjects, 4 in stage V, and 1 in stage VI; (4) there was a progression of NFT from entorhinal cortex to hippocampus and amygdala as a function of age; (5) 2 subjects met criteria for a diagnosis of dementia with Lewy bodies but were not demented; (6) cerebral amyloid angiopathy was present in leptomeningeal vessels in 75% of subjects and in parenchymal vessels in 62% of subjects; (7) only 10 of 59 subjects (17%) had no or few degenerative brain changes. Our study demonstrates that the brains of a large percentage of cognitively normal, relatively well-educated individuals contain numerous degenerative changes and only a small percentage are relatively free of these changes.

Comparison of neuropathologic criteria for the diagnosis of Alzheimer's disease.

The National Institute on Aging and Reagan Institute (NIA-RI) criteria, and other neuropathologic criteria for Alzheimer's disease (AD), were compared with the clinical diagnosis of dementia in a well defined population of Catholic sisters. The 47-participant subset examined in this study were college educated and lacked complicating conditions such as brain infarcts or diffuse Lewy body disease. Sixteen participants had a clinical diagnosis of dementia. The NIA-RI criteria imply a perfect correlation between neuritic plaque (NP) density and neurofibrillary tangle distribution. However, NP density often did not coincide with tangle distribution. As a result, it was not possible to categorize many of the participants using the NIA-RI guidelines. The 'high likelihood' category of the NIA-RI criteria for AD research settings (neocortical Braak stage and frequent neocortical NP) had relatively high specificity (90% of nondemented participants did not meet this criteria). However, only half of the demented participants were in this category. Neuropathologic criteria requiring the presence of neocortical tangles (rather than neocortical Braak stage) had relatively high sensitivity, accounting for 87-94% of participants with dementia, but also included 32-35% of nondemented participants. Criteria based on neocortical NP or senile plaques had 100% sensitivity, but a majority of nondemented participants also met these criteria. The results support consideration of both tangles and NP for the neuropathologic diagnosis of AD, but indicate that refinement of the NIA-RI criteria is necessary. A possible refinement is suggested for further consideration.

A phase I trial of neutron brachytherapy for the treatment of malignant gliomas.

We performed a phase I trial to test the feasibility of neutron brachytherapy using californium-252 (252Cf) as the sole source of radiation, and to determine the maximum tolerable dose (MTD), for the treatment of malignant gliomas. Previous studies using external beam neutron radiation have shown that neutrons are capable of totally eradicating malignant gliomas. However, in most cases, fatal widespread radiation necrosis resulted. Radioactive implants are a logical method of increasing the dose to the tumour and decreasing the dose to normal brain. 252Cf is a relatively stable neutron-emitting isotope suitable for implant therapy. The study was an open ended dose-escalation study. All radiation was delivered by using only 252Cf implants, without external beam therapy of any type. The first dose step was 900 neutron cGy (ncGy); each subsequent step was increased by 100 ncGy. Three patients with newly diagnosed malignant gliomas were entered at each dose step, and the number was increased to six patients in dose steps at which necrosis of brain occurred. The study ended when two patients at any dose step developed radiation necrosis of brain outside the prescribed radiation field. 33 patients were entered into the study. 10 patients developed scalp necrosis associated with scalp doses above 900 ncGy. The study ended when two patients at the 1300 ncGy dose step developed radiation necrosis of brain. We conclude: (1) neutron brachytherapy using 252Cf as the sole source of radiation is a feasible treatment for malignant gliomas; (2) the scalp tolerates less neutron radiation than the brain; (3) the MTD (and the recommended dose for a phase II trial) of interstitial neutron brachytherapy is 1200 ncGy.

Increased ALZ-50 immunoreactivity in sudden infant death syndrome.

Neuronal expression of the ALZ-50 epitope was investigated in hippocampus and medulla from infants dying of sudden infant death syndrome or known causes (controls). Hippocampal studies include data from 31 infants dying of known causes between 32 weeks' gestation and 16 months postpartum and 46 infants who died of sudden infant death syndrome. The medulla at the level of the mid olivary protuberance was investigated in 22 infants with sudden infant death syndrome and 11 controls matched for age and postmortem interval. Medullary sections were also examined using immunohistochemical methods to demonstrate reactivity to glial fibrillary acidic protein antibody. The density of ALZ-50-immunodecorated neurons in control hippocampus rises from the level observable in utero to a maximum between 1 and 4 months of age and declines thereafter. The density of ALZ-50-immunoreactive neurons in hippocampus is significantly increased in infants with sudden infant death syndrome at all ages. Significant regionally specific increases in the number of ALZ-50-immunoreactive neurons, and glial fibrillary acidic protein-reactive cells were found in sudden infant death syndrome medulla; coincidental increases were observed in only the solitary nucleus. Neurons exhibiting the ALZ-50 epitope may reflect apoptotic neuron death of normal development, and increased numbers of immunoreactive neurons may suggest enhanced neurodegeneration in sudden infant death syndrome.