Immunohistological diagnosis of central nervous system tumours using a monoclonal antibody panel.

A panel of seven monoclonal antibodies has been used to characterise 164 cerebral and spinal tumours. These reagents have enabled rapid and accurate diagnosis of tumours to be made, particularly in cases where standard techniques have proved equivocal. On the basis of characteristic antigenic profiles of tumours, it has been possible to distinguish between gliomas, meningiomas, schwannomas, medulloblastomas, neuroblastomas, choroid plexus tumours, various metastatic deposits, and primary brain lymphomas. The reagents used in the study comprise antibodies binding to (a) most neuroectodermally derived tissues and tumours (UJ13A), (b) fetal brain and tumours of neuroblastic origin (UJ181.4), (c) schwannomas, normal and neoplastic neurones (UJ127.11), (d) glial cells (FD19), (e) epithelial cells (LE61), and (f) leucocytes (2D1). Some reagents, such as antibody A2B5, were less effective as diagnostic markers than originally suggested by previously described specificity. This monoclonal antibody reacted with both neuroectodermal and epithelial derived tumours. The panel of monoclonal antibodies was most useful in the diagnosis of tumours composed of small round cells, particularly lymphoma and neuroblastoma, but the pattern of reactivities allowed most of the central nervous system tumours to be accurately classified. This approach was a valuable adjunct to conventional histological techniques in about 20% of the cases examined.

Distribution of measles antigen and immunoglobulin-containing cells in the CNS in subacute sclerosing panencephalitis (SSPE) and atypical measles encephalitis.

The immunoperoxidase technique has been used to study the distribution of measles virus antigen and immunoglobulin (Ig)-containing cells within the CNS, in 5 cases of subacute sclerosing panencephalitis (SSPE) and 1 case of atypical measles encephalitis. Measles virus antigen was demonstrated within the brain in all cases, and in the spinal cord in 1 case of SSPE. Ig-containing cells were also demonstrated in all cases, the proportions of the different light and heavy chain types varying somewhat from case to case. In SSPE IgG constituted the major and IgA the principal minor heavy chain demonstrated. In all cases of SSPE there was significant excess of light-chain-containing over heavy-chain-containing cells. In the case of atypical measles encephalitis there was a paucity of Ig-containing cells and a relatively high proportion (39%) of these contained IgM. The case of atypical measles encephalitis differed from those of SSPE also in the presence of multinucleate giant cells, some of which contained measles virus antigen.

Subependymomas of the fourth ventricle. Surgical treatment in 12 cases.

Subependymomas of the fourth ventricle are generally considered incidental postmortem findings, and have received scant attention from neurosurgeons. The authors present a surgical series of 12 cases of this disorder diagnosed over a 13-year period. The clinical and radiological findings were reviewed and correlations made with pathological studies. The subependymoma is a histologically benign tumor that tends to be calcified. It has a predilection for the fourth ventricle and a peak incidence in the fifth decade of life. It is usually of considerable size with extensive attachment at the time of its detection, and is associated with significant surgical morbidity. The authors believe that magnetic resonance imaging may be the best method of investigation. Intraoperative disturbance of circulatory or respiratory control should suggest to the surgeon that the operation be abandoned. A laser or ultrasonic aspirator may be very helpful in removing these tumors. Postoperative care must include monitoring for apnea.

Trends in the in-hospital treatment of acute myocardial infarction between 1984 and 1993 - The Halifax County MONICA Project.

BACKGROUND: The Halifax County MONItoring of trends and determinants in CArdiovascular disease (MONICA) Project found that between 1984 and 1988, the proportion of myocardial infarctions (MIs) that were fatal within 28 days remained constant, but declined between 1989 and 1993. The objective was to investigate association among case fatality, treatment and case severity of MI in hospitalized patients. PATIENTS AND METHODS: The MONICA MI register contains data on demographics, health history, in-hospital investigations, interventions and treatment, and vital status at 28 days after onset of symptoms for all MIs occurring in residents of Halifax County, aged 25 to 74 years. Logistic regression analysis was used to estimate trends in the use of cardioactive drugs and revascularization procedures. A case severity score was developed from patient characteristics at time of admission. Case fatality was calculated as the proportion of MIs that were fatal within 28 days. RESULTS: Between 1984 and 1988, a large increase (OR 1.3) occurred in the use of angiotensin-converting enzyme (ACE) inhibitors, acetylsalicylic acid (ASA), thrombolysis and percutaneous transluminal coronary angioplasty (PTCA); a minor increase occurred in use of calcium channel blockers (OR=1.29, 99% CI 1.19 to 1.40); beta-blocker use decreased; case fatality remained constant and case severity score increased. From 1989 to 1993, ACE inhibitor use increased (OR=1.4, 99% CI 1.27 to 1.55); minor increases occurred in use of ASA and beta-blockers, and in PTCA and coronary artery bypass grafting; case severity did not change and case fatality decreased. CONCLUSIONS: While use of beneficial treatment increased between 1984 and 1988, MI case fatality did not decrease, probably because case severity increased. Between 1989 and 1993, case severity remained constant, and the further increase in the use of beneficial therapy was associated with a decline in case fatality.

Differences between perspectives of physicians and patients on anticoagulation in patients with atrial fibrillation: observational study.

OBJECTIVE: To determine and compare physicians' and patients' thresholds for how much reduction in risk of stroke is necessary and how much risk of excess bleeding is acceptable with antithrombotic treatment in people with atrial fibrillation. DESIGN: Prospective observational study. SETTING: Tertiary and peripheral referral centres in Nova Scotia, Canada. PARTICIPANTS: 63 physicians who were treating patients with atrial fibrillation and 61 patients at high risk for atrial fibrillation. MAIN OUTCOME MEASURES: Participants underwent a face to face interview with a probability trade-off tool. Thresholds were determined for the minimum reduction in risk of stroke necessary and the maximum increase in risk of excess bleeding acceptable for treatment with aspirin and warfarin in people with atrial fibrillation. RESULTS: The minimum number of strokes that needed to be prevented in 100 patients over two years for warfarin to be justified was significantly lower for patients than for physicians (1.8 (SD 1.9) v 2.5 (1.6), P=0.009), whereas for aspirin there was no difference between patients and physicians (1.3 (1.3) v 1.6 (1.5), P=0.29). The maximum number of excess bleeds acceptable in 100 patients over two years for use of warfarin and aspirin was significantly higher for patients than for physicians (warfarin 17.4 (7.1) v 10.3 (6.1); aspirin 14.7 (8.5) v 6.7 (6.2); P<0.001 for both comparisons). CONCLUSIONS: Patients at high risk for atrial fibrillation placed more value on the avoidance of stroke and less value on the avoidance of bleeding than did physicians who treat patients with atrial fibrillation. The views of the individual patient should be considered when decisions are being made about antithrombotic treatment for people with atrial fibrillation.

Degeneration of muscle in association with carcinoma of the bronchus.

The clinical features and necropsy findings are described in three cases in which severe and rapidly progressive muscle weakness developed in association with carcinoma of the bronchus. In all three cases, muscular weakness was directly responsible for death. Histological and ultramicroscopical examination in all cases showed an unusual type of degeneration of muscle fibres accompanied by degeneration of intramuscular nerve fibres, but without involvement of the central nervous system, or of the peripheral nerve trunks. The findings are compared with those of previously reported cases, and possible mechanisms for the muscle degeneration are discussed.

Granulomatous myopathy: its relationship to sarcoidosis and polymyositis.

In three cases of generalized muscle weakness, muscle biopsy revealed well-defined, non-caseating epithelioid granulomata with giant cells. In one of these patients there was, in addition, a high serum CPK and histological evidence of widespread muscle cell degeneration and regeneration, apparently unrelated to the granulomatous process. In a re-examination of the histopathology of these cases, using biopsy material from a fourth case of proven sarcoidosis as a standard, it was concluded that there are no special features of the granulomatous/giant cell process which permit the separation of the case of presumed polymyositis. However, it appeared that granulomata per se do not exert a significant ill effect on surrounding muscle cells, and that evidence of widespread degeneration of muscle cells is the important point of distinction.

Pathology of peroneal muscular atrophy (Charcot-Marie-Tooth disease).

Four cases of peroneal muscular atrophy (Charcot-Marie-Tooth disease) are described in which observations were made from the necropsy examination of the central nervous system, the peripheral nervous system, and the skeletal muscles. The pattern of nerve degeneration in these various locations is described and the conclusion is drawn that the basis of the disease is a very chronic progressive neuropathy. To the pathological descriptions of previous observers is added the finding of fibrosis affecting the muscle spindles which was present in all four of the cases. The literature of the case reports with necropsy examination is reviewed.

Computed tomographic appearances in microgliomatosis.

The computed tomography (CT) appearances of 11 patients with microgliomatosis have been reviewed, and as a result it is possible to suggest that there may be typical features for the recognition of such tumours. In this series three fairly distinctive patterns were encountered. In view of their reputed response to radiotherapy, there is a strong case for making the diagnosis of such lesions, and CT has given the opportunity of alerting the surgeon and the pathologist to the likelihood of their presence at an early stage.

Malignant spread of haemangioblastoma: report on two cases.

Two cases are described in which, after successful removal of a cerebellar haemangioblastoma followed by several years of freedom from symptoms, there developed a progressive spinal cord compression, leading to death. At necropsy the spinal cords in both cases and the brainstem in one case, were irregularly plastered with haemangioblastoma. Although there was no doubt that malignant spread had occurred from one or more primary tumours, the histology of the tumour tissue was in no way different from that of conventional haemangioblastoma.

Effects of the oral administration of Cannabis sativa (dagga) on chacma baboons (Papio ursinus).

Eighteen adult chacma baboons were fed Cannabis sativa, the plant material being incorporated into their food. They were divided into three equal groups. Group 1 animals were fed on 2% cannabis in food for 4 months, after which 2 animals remained on 2%, 2 were given 4% and 2 6% cannabis in food for the next 4 months. They became mildy apathetic. Five gained weight. Serum glucose, potassium and CO2 values decreased. Neuropathological examination of their brains did not show any significant abnormality. Group 2 animals were fed 10% cannabis for several weeks. They ate less and lost weight, and later became very apathetic. Right temporal biopsies were done in all and in 3 the tissue was analysed for glutamine, glutamate, tryptophan, ammonia and cyclic AMP. No significant change was found. Serum glucose and CO2 levels rose and potassium levels fell. Blood cholesterol values decreased in 3 of the 9 males. Group 3 animals were fed 6% cannabis for 2--4 months. Radio-immunoassay of sera and urine showed the presence of cannabinoids. They became apathetic, and 5 lost weight. Serum glucose and potassium levels (measured in the males) decreased. No neuropathological lesions were found in the brains, apart from an incidental leptomeningitis in 1 animal which died suddenly. The question of cannabis encephalopathy is discussed.

Neurogenic muscle atrophy in myasthenia gravis.

Two cases of severe myasthenia gravis are described, with histological findings. Both cases showed severe neurogenic atrophy of the muscles of the tongue, with fatty pseudohypertrophy and a remarkable proliferation of terminal nerve fibres. Similar, but less severe, changes were present in other bulbar muscles. The findings are in keeping with the view that functional interruption at the neuromuscular junctions results first in failure to transmit the contractile impulse, and at a later stage in denervation atrophy. Terminal proliferation of axons is regarded as an attempt, on the part of motor fibres, to compensate for the breakdown of normal neuromuscular interaction.

The central nervous system in motor neurone disease.

Forty-five necropsied cases with primary degeneration of lower motor neurones are described and discussed. Of these, 36 are considered to be `typical' cases of motor neurone disease, eight of which showed no upper motor neurone lesions. The relation of the nine `atypical' cases to the remainder is discussed. It is concluded that motor neurone disease constitutes an ill-defined band in a broad spectrum of multiple system atrophies. The authors have found no evidence suggesting a causal relation between motor neurone disease and either vascular or malignant diseases. They point out suggestive analogies with various subacute encephalomyelopathies in man and other animals.