The spectral signature method for the analysis of PET brain images

We introduce the concept of the metabolic centroid spectrum as the feature space to characterize the distribution of metabolic activity in three-dimensional brains. The method computes the metabolic centroid of a brain subvolume for each increment of metabolic activity occurring in the whole brain. The result is the metabolic spectral signature, a continuous three-dimensional curve whose shape reflects the distribution of metabolic rates in the brain. The method's sensitivity to metabolic distribution asymmetries is greatly increased over that of the metabolic centroid method, while retaining its advantages; it is almost invariant to head size, head positioning, photon scatter, and the positron emission tomography (PET) camera's full width at half-maximum. It does not require magnetic resonance, computed tomography, or x-ray images. To test the method we analyzed the metabolic PET images of 40 normal subjects and 20 schizophrenics. The results show a unification of several metabolic characteristics of schizophrenic brains, such as laterality, hypofrontality, cortical/subcortical abnormalities, and overall brain hypometabolism, which were identified by different laboratories in separate studies using differing methodologies. Here they are presented by a single automatic objective method.     

Ganglioside or sialic acid attenuates ethanol-induced decrements in locomotion, nose-poke exploration, and anxiety, but not body temperature.

1. This laboratory has previously reported that pretreatment with ganglioside, or even with its constituent, sialic acid (SA), can attenuate certain intoxicating effects of ethanol. It was important to see if these findings could be replicated, particularly by using other measures of ethanol effects. Herein we report that pretreatment with either gangliosides or SA attenuated ethanol-induced decrements in locomotion, nose-poke exploration, and anxiety, but not body temperature. 2. An ethanol dose of 4 gm/kg caused a temperature drop of about 3 degrees C, which was unaffected by any pretreatment. The onset to sleep, however, was delayed an average of 18 or 36 secs in mice pretreated with ganglioside or SA, respectively. Ethanol-only (4 gm/kg) depressed mean cumulative locomotor activity to 31% of normal, whereas the depression was 83% of normal with beef brain ganglioside pretreatment. At 2 gm/kg ethanol alone decreased nose poking in a hole-board test to 29% of normal, but the depression was only 55-63% of normal with SA or ganglioside pretreatment. In a staircase climbing anxiety test, this dose of ethanol had no effect by itself, but both ganglioside and SA pre-treatment increased climbing by 22%. Ethanol did depress rearing to only 11% of normal, whereas rearing was 51 and 99% of normal with SA and ganglioside pretreatment, respectively. In a dark-preference test, ethanol-only caused mice to spend 64% of the time in the light, compared to 31% for controls. Time in the light was only 39 and 46% with ganglioside and SA pretreatment, respectively. 3. Blood levels of ethanol were not significantly affected by pretreatment. 4. When given alone, gangliosides significantly stimulated locomotion and staircase climbing. SA significantly decreased rearing in the staircase test. Both gangliosides and SA tended to increase nose poking, number of crossings in the dark-preference test, and time in a lighted compartment. Thus, it is possible that some of the attenuation of intoxication is attributable to non-specific stimulant properties of gangliosides and SA.     

Serotonergic interhemispheric asymmetry: Neurochemical and pharmaco-EEG evidence

1. Postmortem neurochemical investigations revealed interhemispheric asymmetry in the mediofrontal region of human brain. Significantly higher right hemisphere serotonin metabolite (5HIAA) content as well as increased maximal imipramine binding (IB) were found in the right hemisphere than in the left side.

2. IB did not show a gender difference in the mediofrontal area. However, women had higher IB in the right orbital frontal cortex than did men.

3. In vivo pharmaco-EEG results tend to support the postmortem neurochemical data. Intravenous chlorimipramine resulted in an asymmetric topographic distribution of the P300 auditory evoked potential, peak amplitudes were shifted to the right hemisphere.     

Widespread serum amyloid P immunoreactivity in cortical amyloid deposits and the neurofibrillary pathology of Alzheimer's disease and other degenerative disorders

Amyloid P (AP) component is present in all types of systemic amyloid deposits. Recently, it has been shown to be also present in cerebral amyloid lesions of Alzheimer's disease (AD). In this study, we used immunocytochemical methods to extend these findings at the electron microscope level and characterize the spectrum of AP immunoreactivity in neurofibrillary pathology (NFP) of AD and other neurodegenerative disorders including Down's syndrome (DS), Creutzfeldt-Jakob, Parkinson's, Pick's and diffuse Lewy body diseases and progressive supranuclear palsy. In AD and DS, AP immunoreaction product was evident in all the classical amyloid lesions and NFP in a large sample of all cortical areas examined. The distribution and relative intensity of immunostaining was similar to that of thioflavin S staining in serial sections. In many cases, however, plaques and vessels stained by anti-AP serum were not apparent with thioflavin S. Serial sections immunostained with antiserum to amyloid A, C-reactive protein or to other proteins involved in systemic amyloidoses and the acute phase response showed no evidence of staining in any of the cerebral lesions. Electron microscopy confirmed that AP immunoreactivity was associated with the abnormal filaments characteristic of NFP as well as amyloid fibrils found in plaques and vessels showing congophilic amyloid angiopathy. Plaques of Creutzfeldt-Jakob disease, Pick bodies of Pick's disease, tangles and Lewy bodies in Parkinson's disease and a subpopulation of Lewy bodies in the diffuse Lewy body disease coexistent with AD were also stained. With the exception of vessels in two of the five cases, AP was not detected in age-matched controls. Our observations indicate AP to be a consistent feature of cerebral NFP and amyloid deposits.     

Development of rostrocaudal dendritic bundles in rat thoracic spinal cord: analysis of cholinergic sympathetic preganglionic neurons.

Using monoclonal antibodies to choline acetyltransferase (ChAT) and glial fibrillary acidic protein (GFAP), we have analyzed the development of the dendritic bundles formed by cholinergic sympathetic preganglionic neurons (SPNs) in relationship to changes in the organization of glial fibers. In adult rat thoracic spinal cord, SPNs in the intermediolateral (IML) and central autonomic (CA) regions extend dendrites in both the mediolateral and rostrocaudal directions, forming a ladder-like pattern in horizontal sections of thoracic spinal cord. We report that, while the mediolateral dendrites form prenatally, the rostrocaudal dendritic bundles are not detected until at least a week later, during early postnatal life. The rostrocaudal dendrites develop rapidly during the first postnatal week, and achieve an adult-like pattern by postnatal day 14. The observed ontogenetic arrangements of dendritic bundles were correlated with the developing organization of astroglial processes with which they are intimately associated. While the appearance of mediolateral dendrites is consistent with the radial organization of glial in the embryonic spinal cord, the developmental time course of the rostrocaudal dendritic bundles coincides with the transformation of glial cells from this predominantly radial or transverse orientation to the randomly-oriented, stellate pattern of mature astrocytes. This temporal association suggests that ontogenetic changes in the organization of glial cells may contribute to the differential development of mediolateral and rostrocaudal dendritic patterns in the spinal cord.     

Differential ontogenesis of type I and II benzodiazepine receptors in mouse cerebellum

The ontogeny of type I and type II benzodiazepine binding sites was studied in mouse cerebellum by displacement of [3H]flunitrazepam binding by zolpidem, a ligand specific for the type I sites. Type I binding sites predominate throughout development and in the adult while type II sites account for 25% of total cerebellar benzodiazepine binding sites at birth and, during development, decrease to 10% or less in the adult. On a per cerebellum basis type II sites increase during the first postnatal week and then remain at a steady level while type I sites increase until adulthood. These results may indicate a specific localization of the type II sites (and of the corresponding alpha-protein subunits in the GABA/benzodiazepine receptor complex) in structures already present at birth and developing during a short early postnatal period. The affinity of zolpidem for its high affinity (type I) binding sites increases during cerebellar ontogeny, this increase possibly indicates an epigenetic (post-translational) 'maturation' process of the corresponding receptor molecule. Hill numbers indicate the existence of an additional binding site heterogeneity greater during development but still present in the adult; probably this is to be related to the simultaneous presence of different 'maturation' stages during development and with a certain variety of the final products.     

Physiological responses of typical versus heavy weight triathletes to treadmill and bicycle exercise.

A physiological comparison of the responses of typical weight (less than 90 kg) versus heavy weight (greater than 90 kg) male triathletes to maximal treadmill and maximal bicycle exercise was performed to better understand the effects of weight on endurance performance. The heavy triathlete group (90.9 +/- 3.2 kg, mean +/- SD) had significantly (p less than .01) greater percent body fat (11.9 +/- 3.6 vs 7.4 +/- 1.8%) while having significantly (p +/- .01) lower VO2max values expressed in ml.kg-1.min-1 on both the treadmill (55.6 +/- 4.1 vs 69.9 +/- 5.5) and bicycle ergometer (51.9 +/- 3.9 vs 60.5 +/- 6.2) than the typical triathlete group (66.6 +/- 5.9 kg). Analysis of covariance using body fat as the covariate resulted in persistent significant (p less than .02) VO2max (ml.kg-1.min-1) differences between the groups. Statistically significant (p less than .05) differences in running economy existed between the groups (33.7 +/- 2.7 vs 37.1 +/- 1.5 ml.kg-1.min-1; typical vs heavy). The heavy triathletes also had a significantly (p less than .01) shorter treadmill performance time (9.6 +/- 2.3 vs 13.2 +/- 1.7 min) and significantly (p less than .01) lower power per weight ratio on the bicycle ergometer (5.37 +/- 0.48 vs 6.47 +/- 0.59 watts/kg). These findings indicate that the heavy triathlete is at a physiological disadvantage when competing in endurance events and supports the inclusion of a weight category in these events. The reported triathlon results support these physiological findings.     

Temporomandibular joint eminence augmentation by down-fracture and inter-positional cartilage graft. A new surgical technique.

A new surgical technique for the treatment of recurrent temporomandibular joint subluxation or dislocation is described. Following a horizontal osteotomy and down-fracture of the articular eminence an inter-positional bovine cartilage xenograft is inserted in order to augment the vertical height of the eminence. The procedure combines simplicity with minimal post-operative morbidity. The increase in eminence height is both predictable and stable.     

Microscopic endonasal surgery of the paranasal sinuses and the parasellar region

The anatomic principles and operative techniques currently applied to functional endoscopic endonasal surgery have allowed for significant refinements in another approach to regional pathology that uses the operating microscope, newly designed sinus instruments, and a self-retaining nasal speculum system. The main benefits of this method are the superb widefield stereoscopic vision and the distinct freedom to work bimanually. Additionally, direct bipolar cautery of bleeders is afforded while use of the observer tube or video allows for excellent teaching. The precise nature of this surgery affords less fear of serious complications in the treatment of periorbital, paranasal sinus, and parasellar diseases. We describe technical aspects of the surgery and associated complications in 219 patients treated from 1984 to 1987.     

Manifestation of malignant lymphoma of the head and neck with special reference to the salivary glands

We found that thirteen per cent of all head and neck malignomas are malignant lymphomas. In 75% of these cases the Non-Hodgkin type could be found. The major salivary glands were involved by the lymphoma in 55% out of 104 patients. Paraglandular lymph nodes of the parotid gland were affected as well as intraglandular lymph nodes and the lymphoid tissue within the gland proper. The submandibular gland normally shows an involvement only with its paraglandular lymph nodes. Two thirds of the Non-Hodgkin lymphomas located in the salivary glands were low-grade. In case of clinical suspicion of a malignant lymphoma, fine needle biopsy is required for cytological diagnosis. However, surgery is mandatory for histological diagnosis, not as a therapeutic measure.