Niemann-Pick disease

Results of the investigation carried out during this decade brought unambigous evidence of biochemical heterogeneity inside the complex of Niemann-Pick disease according to which two entirely different metabolic disorders can be recognized. 1. Niemann-Pick sphingomyelinosis, a clear-cut enzymopathy, the pivotal lesion of which is the deficiency of lysosomal spingomyelinase leading to widespread lysosomal deposition of sphingomyelin liquid crystals. Two main allelic variants are known. The first one, neuronopathic (former type A) known as infantile with rapid course, may also manifest considerably prolonged course or an atypical course with predominantly visceral symptomatology. Patients with the second, visceral, variant (former type B), display mainly slow clinical course and often reach adulthood. With rare exceptions the neuronopathic variant can be biochemically recognized from the visceral one by much lower values of the in vivo sphingomyelin degradation test in the former. 2. The rest of the complex comprising types C-D differs substantially from the sphingomyelinase deficiency group by the remarkable heterogeneity in the lysosomal stored lipid pattern given by differences among the affected cell populations. Sphingomyelin storage could be proved histochemically solely in the histiocytic population together with cholesterol, neutral glycosphingolipids and lysobisphosphatidic acid, whereas the brain neurons displayed only neutral glycosphingolipid storage. There is an increasing evidence of the crucial biochemical lesion in this group being an altered intracellular traffic of exogenously derived cholesterol caused probably by its deficient translocation from lysosomes to other intracellular membrane sites. This leads to decreased cholesterol esterification rate which is the basis of the newly developed diagnostic test. Inconstant depression of sphingomyelinase activity is considered to be a secondary phenomenon. The so-called lactosylceramidosis is a rare variant pertinent to this group. The biochemical nature of type E still awaits clarification. Both groups of Niemann-Pick disease display clinical and especially histochemical features which allows to establish diagnosis in a highly efficient way already at the clinicopathological level.     

Electron microscopic immunocytochemical evidence for the existence of bidirectional synaptic connections between growth hormone-releasing hormone- and somatostatin-containing neurons in the hypothalamus of the rat

Synaptic contacts between growth hormone-releasing hormone (GHRH)- and somatostatin-containing neurons were demonstrated in the rat hypothalamus by a double-staining immunocytochemical method at the electron microscopic level. Somatostatin-immunoreactive nerve terminals synapse on GHRH-positive dendrites and cell bodies in the arcuate nucleus. A fine network of GHRH-immunopositive nerve terminals was observed at the light microscopic level in the rostral part of the periventricular nucleus and in the dorsal part of the arcuate nucleus around somatostatin-containing neuronal elements. With the electron microscope synaptic contact between GHRH-containing nerve terminals and somatostatin-containing dendrites are demonstrated. The reciprocal innervation between GHRH- and somatostatin-containing neurons that project to the median eminence and regulate growth hormone secretion must allow them to coordinate their activities.     

Cerebrovascular and metabolic perturbations in delayed heavy charged particle radiation injury

Focal heavy charged particle irradiation of the rabbit brain created defined lesions which were observable by nuclear magnetic resonance (NMR) and positron emission tomography (PET) imaging techniques. The lesions appeared approximately 9-11 months after left partial hemibrain irradiation with 30 Gy (230 MeV/u helium ions), and were restricted to the white matter tracts and deep perithalamic and thalamic regions. 82Rubidium PET and Gadolinium DTPA enhanced NMR imaging were used to detect blood-brain barrier perturbations. 18Fluordeoxyglucose PET studies demonstrated widespread decreases in cerebral glucose uptake in the cortex and thalamus of the irradiated hemisphere. NMR and PET imaging results correlated well with histological findings. Rabbits irradiated with 15 Gy did not demonstrate any abnormalities in the brain with sequential NMR scans through 14 months post-irradiation.     

Administration of kainic acid and colchicine alters mu and lambda opiate binding in rat hippocampus

Quantitative in vitro autoradiography was used to assess the effects of kainic acid (KA) and colchicine (COL) on mu and lambda opiate binding in the rat hippocampus. Rats were treated with either systemic KA, a neurotoxin that damages CA3 pyramidal cells and causes seizures and wet-dog shakes, or intrahippocampal COL to destroy dentate granule cells and their mossy fibers, or both toxins. Moderate levels of mu binding were detected in the pyramidal layer and in the stratum lacunosum-moleculare; binding was greater in the ventral hippocampus. Levels of mu binding were markedly increased in all regions 48 h after treatment with KA. Two weeks after COL treatment, there was a modest decrease in mu binding; COL plus KA gave results similar to COL alone. Dense lambda binding was present over the mossy fibers in the stratum lucidum, but was absent over the pyramidal layer. In contrast to mu binding, lambda binding was greater in the dorsal hippocampus. KA alone had little effect on lambda binding, whereas COL alone caused large decreases. KA plus COL caused even larger decreases in lambda binding, to as much as 85% below control. These results demonstrate that mu and lambda binding are localized to different parts of the hippocampus, respond differently to neurotoxin lesions, and likely serve different roles in this brain region. The number of mu sites is responsive to the release of enkephalin; these receptors appear to be linked to opiate-induced hippocampal seizure activity, especially wet-dog shakes. Lambda sites may serve as autoreceptors on mossy fibers.     

The factor of magnification in mammography

The last generation of mammographic equipment allows mammography to be performed with direct magnification techniques, thanks to such technical features as microfocus, high focus-film distance, high-power generators. The authors compared the diagnostic yield of two different equipment sets, with 1.4x and 2x magnification respectively, and verified the utility of magnification radiography. A significant reduction was obtained in questionable diagnoses (42 to 18) in a group of 63 patients, with no evidence of substantial differences in the diagnostic yield of the images obtained with different magnification ratios. An objective analysis of the system resolution power privileges 2x magnification ratio, which however implies an increase in the average dose to the breast. The use of faster recording systems reduces the dose by 50%, though maintaining good image quality.     

Behavioral treatment of angina-like chest pain in patients with hyperventilation syndrome

The hyperventilation syndrome is present in as many as 50% of patients with non-cardiac chest pain. This study evaluated a behavioral treatment of this disorder in three adult females. They had long histories of chest pain and were documented to be free of coronary artery disease. Each subject met the DSM-III-R diagnostic criteria for an anxiety disorder. Following treatment, all subjects showed a marked decrease in the frequency and intensity of chest pain episodes and in the frequency of shortness of breath episodes. Two subjects maintained their progress at one-year follow-up. The results lend support to the efficacy of controlled breathing and relaxation training for the treatment of hyperventilation-related chest pain and to the inclusion of a hyperventilation provocation test in the diagnosis of the syndrome as well as its role in changing cognitions regarding cardiac status. Also discussed is the rationale for treating hyperventilation related chest pain in a medical care setting.     

Blood alcohol level among emergency room patients: a multivariate analysis

This article examines the distribution of positive blood alcohol levels (BALs) among emergency room patients and the relationship between intoxication and other variables. Approximately one-quarter of the 640 subjects had positive blood alcohol levels and 16.3% had BAL readings above 0.10%, the legal limit for operating a motor vehicle in most states. Chi-square tests and logistic regression analysis indicated a significant relationship between employment status, gender, educational attainment, age and BAL. There were no significant racial differences. Analysis of the role of the presenting problem with BAL revealed that being involved in an accident was significantly predictive of a high BAL in a multivariate context. However, patients presenting with psychiatric problems had overall higher levels of intoxication than other patients. These findings have major implications for public policy formulation vis-à-vis public health delivery.     

Cranial nasal bone grafts

Reconstitution of the nasal scaffolding with maintainence of soft tissue proportions either following severe facial trauma or as a sequela to aesthetic rhinoplasty misadventures frequently is best achieved using the stability afforded by bone grafts. Split cranial bone grafts offer many advantages and may be the donor site of choice, and may even allow such surgery to be performed on an outpatient basis in some cases. The use of miniplate or screw osteosynthesis, now commonly accepted as a superior technique in craniomaxillofacial procedures, may simplify fixation of these calvarial nasal bone grafts with an apparent decrease in the risk of resorption.     

Outflow of aqueous humor following cyclodialysis or ciliochoroidal detachment in rabbit

Cyclodialysis and ciliochoroidal detachment were performed in three eyes of three rabbits and in three eyes of another three rabbits, respectively. After aspiration of the aqueous humor, 0.1 ml of 10% sodium fluorescein was injected intracamerally, and the eyeball was enucleated between 30 minutes and one hour after injection and prepared for fluorescence microscopy. Sodium fluorescein concentrations in the supraciliary space were much greater in the group with cyclodialysis or ciliochoroidal detachment than in the normal control group. These results suggest that (1) in the eye with cyclodialysis, the aqueous humor may freely gain access to the supraciliary space through the cleft between the anterior chamber and the supraciliary space and then be removed rapidly and (2) in the eye with ciliochoroidal detachment, the aqueous humor may pass through the uveoscleral outflow pathway.