Non-Alzheimer-type pattern of brain cholineacetyltransferase reduction in dominantly inherited olivopontocerebellar atrophy

We recently reported reduced activity of the cholinergic marker enzyme cholineacetyltransferase (ChAT) in several brain regions of patients with dominantly inherited olivopontocerebellar atrophy (OPCA). To document the regional extent of these changes we performed a comprehensive examination of the behavior of ChAT throughout both cerebral cortical and subcortical brain areas in 5 patients from one large OPCA pedigree. As compared with the controls, mean ChAT activities in OPCA were reduced by 39 to 72% in all (n = 27) cerebral cortical areas examined and in several thalamic subdivisions, caudate head, globus pallidus, red nucleus, and medial olfactory area. In contradistinction to findings in Alzheimer's disease (AD), mean ChAT levels in OPCA amygdala and hippocampal subdivisions were either normal or only mildly reduced. The lack of severe disabling dementia in our OPCA patients compared with AD patients having a similar cortical cholinergic reduction could be explained by an absence of either a marked cholinergic loss in amygdala or hippocampus or significant loss of noncholinergic cerebral cortical and limbic neurons as occurs in AD brain. We suggest that this and other OPCA pedigrees having a cortical cholinergic reduction represent a unique model for the study of behavioral consequences of a more selective cerebral cortical cholinergic lesion rather than a limbic cholinergic lesion.     

Clonidine treatment of schizophrenia. Double-blind comparison to placebo and neuroleptic drugs

Antipsychotic effects of clonidine were evaluated in one schizoaffective and seven schizophrenic patients, using a double-blind, cross-over design to compare placebo, clonidine, and standard neuroleptic drugs. Mean improvement on clonidine and neuroleptics was equal, and improvement scores on the two treatments were closely correlated for individual patients. Clonidine was selected because it blocks noradrenergic but not dopaminergic neurotransmission. Patients were selected because of co-existing psychosis and tardive dyskinesia, a movement disorder thought to be caused by the antidopaminergic properties of the neuroleptics. For all patients, dyskinesia improved when neuroleptics were discontinued during clonidine and placebo periods of the study. The data provide preliminary evidence that clonidine may be an effective alternative to neuroleptics, particularly for patients for whom the dopaminergic blocking action of the neuroleptics is undesirable. The study also prompts re-evaluation of theories of a unique role for dopamine in schizophrenia.     

Malignant round-cell tumours of bone: an analytical histological study from the Cancer Research Campaign's bone tumour panel.

A study of 40 cases of malignant round-cell tumour of one was made from the files of the Cancer Research Campaign''s Bone Tumour Panel. Five pathologists made a careful study of observer error, involving repeated examination of routine paraffin sections, to determine whether the cases were a homogeneous group or a collection of differing sub-groups. Cell outline, nuclear staining, nuclear pleomorphism, conspicuous nucleoli, reticulin pattern and intracellular glycogen were the histological features selected for study. For each feature, the results were analysed to assess the importance of differences between tumours, between samples of tissue from the same tumour, and between observers. It is concluded that round-cell tumours of bone are a heterogeneous group, although completely distinct sub-groups could not be identified. Certain histological features tend to be associated, and it is reasonable to distinguish on histological grounds between Ewing''s sarcoma and reticulum-cell sarcoma, although some tumours are not typical of either group.     

Asthma induced by sulphur dioxide, benzoate and tartrazine contained in orange drinks.

Of 272 patients with asthma, thirty (11%) gave a history of exacerbations occurring after ingestion, solutions of orange orange drinks. Fourteen of these were given provocation tests by drinking, on separate occasions of sulphur dioxide, sodium benzoate and tartrazine, which are present in all orange drinks. Eight reacted to sulphur dioxide with a fall in FEV1, four to sodium benzoate and one to tartrazine, and four did not react to any of these agents. Three of the benzoate patients were also sensitive to sulphur dioxide. The sulphur dioxide sensitive patients were predominantly young, with extrinsic asthma. The benzoate sensitive patients were predominantly middle-aged and the proportion with intrinsic asthma was higher. Prior inhalation of sodium cromoglycate by four patients inhibited the reaction to these substances. Sulphur dioxide has not previously been reported to cause exacerbations of asthma when ingested as a food preservative. It is used as a preservative in a wide range of acidic beverages and foods, and should be considered as possibly causal in patients suffering from apparently cryptogenic asthma, and asthma seemingly due to food allergy.     

Nutritional and metabolic bone disease in a zoological population

The radiologic survey technique used at the National Zoological Park has disclosed many cases of nutritional and metabolic bone disease of various types. This communication discusses calcium deficiency states seen in lion cubs associated with a meat diet, the increased need for calcium noted in egg-laying lizards, problems found in New World monkeys, antelopes (due to selenium and/or vitamin E deficiency), hypervitaminosis D, and lead poisoning noted in young primates. In all of these diagnoses, the use of routine radiographic studies has been extremely helpful, first in detecting that a bone or soft tissue abnormality is present, and then in the differential diagnosis of the etiology of this abnormality. As more is learned of the necessary nutriments for exotic species kept in captivity, it is expected that the nutritional disturbances described in this article will be seen with decreasing frequency.     

Chronic mesangiolytic glomerulopathy in a patient with SC hemoglobinopathy

Numerous cases of glomerular disease in sickle cell patients have been reported. Glomerular disease in SC double heterozygotes has not been reported despite its equal prevalence in adults. We herein report a case of mesangiolytic glomerulopathy in a patient with SC disease.     

Characterization of lymphoid cells isolated from human gliomas

To analyze the phenotypic profile of lymphoid cells freshly isolated from surgically resected human gliomas, a double-immunostaining technique was developed which permitted the investigators simultaneously to distinguish between hematogenous and tumor cell populations and to detect expression of lymphocyte-monocyte subset-specific antigens on hematogenous cells. With this technique, the profiles of tumor-infiltrating lymphocytes (TIL's) derived from high- and low-grade gliomas were compared with phenotypes of lymphocytes concurrently isolated from peripheral blood. The total leukocyte cell yield from high-grade glioma cases exceeded that of low-grade cases. In nine high-grade glioma cases the proportion of CD8-positive cells was increased within the TIL population (41.2% +/- 1.9%, mean +/- standard error of the mean) as compared to the corresponding peripheral blood lymphocyte (PBL) population (30.8% +/- 4.1%, p less than 0.05). The proportion of natural killer HNK-positive cells, some of which bear the CD8 antigen (although not necessarily the pan T cell antigens CD2 and CD3), was also increased in the TIL's (41.9% +/- 4.2%) compared to that found in PBL's (32.1 +/- 5.6%, p less than 0.05) of high-grade glioma cases. The observed phenotypic pattern of high-grade glioma TIL's is similar to that reported based on immunohistochemical analysis of tumor tissue sections, suggesting that the techniques described here resulted in isolation of lymphoid cells representative of TIL's.     

Relation of triglyceride levels to coronary artery disease: the Milwaukee Cardiovascular Data Registry

Although levels of triglycerides have consistently shown a strong association with cardiovascular disease in both case-control and cohort studies, it remains controversial whether this relation exists independently of levels of cholesterol and other risk factors. The association of arteriographically documented coronary artery disease with plasma levels of triglycerides, total cholesterol, and high density lipoprotein (HDL) cholesterol was therefore examined in 5,216 white adults (81% were male) referred to two Milwaukee hospitals between 1972 and 1986. Elevated levels of triglycerides were related to the extent of coronary artery disease (estimated using the total number and severity of stenoses) in both sexes; this association existed independently of total cholesterol, age, obesity, hypertension, smoking, and alcohol consumption. In addition, the association between triglycerides and coronary artery occlusion was strongest at total cholesterol levels less than or equal to 250 mg/dl. However, both stratified and regression analyses indicated there was no residual association between triglyceride levels and occlusion after controlling for HDL cholesterol. (Levels of HDL cholesterol and triglycerides showed a moderate inverse association: r = -0.39 to -0.51.) These results indicate that the association between coronary artery occlusion and levels of triglycerides is indirect, and that the disparate findings of earlier studies may have resulted from not controlling for HDL cholesterol.