Stereotactic brain biopsy: An audit of sampling reliability in a clinical case series.

Stereotactic brain biopsy is the current gold standard procedure to obtain a neuropathological diagnosis. An audit of 207 stereotactic cases, between January 1997 and December 2000 was carried out. The aim was to determine the optimum number of target sites required to make the final diagnosis and thereby set up recommendations for future practice. The overall diagnostic success rate was 89.3%. A significant positive correlation between the number of targets taken and the probability of achieving the final diagnosis was seen. In a subset of glioblastoma cases 96.1% of the tumours could have been confidently diagnosed on the basis of any two of the targets chosen, although often more targets were taken than this. The recommendations made by the audit were: (i) in cases where it is suspected the lesion does not require grading, one target site should be taken and further sites should only be taken if the first proves to be non diagnostic; (ii) in suspected glial series tumours, two targets should be routinely taken, with further sites taken only if these prove inconclusive on intraoperative smear.

In vitro model of infectious crystalline keratopathy: tissue architecture determines pattern of microbial spread.

PURPOSE: To develop an in vitro model of infectious crystalline keratopathy using human corneal buttons and to test the hypothesis that the compactness of the corneal stroma determines the pattern of microbial spread. METHODS: Twenty human corneal buttons obtained after penetrating keratoplasty for keratoconus (KC) and eight human corneal buttons obtained from eye bank (EB) donor eyes were maintained in organ culture. Fourteen buttons (10 KC and 4 EB donors) were maintained in a turgid state (swollen, edematous) and 14 in a nonturgid state (compact, normal state of deturgescence) by the omission or addition of 5% dextran to the culture medium. Eight KC and four EB nonturgid buttons and eight KC and four EB turgid buttons were inoculated with Streptococcus viridans (Lancefield group G, gram-positive) organisms. Two KC nonturgid and two KC turgid buttons were inoculated with Klebsiella oxytoca (gram-negative) organisms. Bacterial migration and spread in the tissue were observed by light and electron microscopy. RESULTS: Of the nonturgid buttons, six KC buttons and all four EB buttons inoculated with S. viridans and both KC buttons inoculated with K. oxytoca demonstrated an arborizing, crystallike pattern of bacterial spread. In the turgid buttons, five KC and all four EB buttons inoculated with S. viridans and both KC buttons inoculated with K. oxytoca demonstrated globular, amorphous colonies. This was in complete contrast to the needlelike branching appearance seen in nonturgid corneal buttons. Electron microscopy confirmed an interlamellar spread of the bacterial colonies. CONCLUSIONS: This is the first in vitro model of bacterial keratitis. It demonstrates that the pattern of spread of bacteria within corneal tissue is largely determined by the compactness of the corneal stroma. Altering tissue architecture changed the pattern of bacterial migration and spread. This model has considerable potential in further understanding host-microbe interactions and microbial spread that occurs during infection.

Dementia with Lewy bodies.

Dementia with Lewy bodies (DLB) is the recommended term for a common cause of dementia characterized by the histological presence of distinctive inclusions within neurons, Lewy bodies (McKeith et al, 1996). Following increasing pathological recognition, core clinical diagnostic features have been identified to allow diagnosis in life. Insights into the biology of this type of neurodegeneration suggest that the regional patterns of involvement might allow therapeutic intervention. Although Lewy bodies had long been recognized in the substantia nigra and other subcortical nuclei in patients with Parkinson's disease (PD), it was only in the 1970s that a significant number of reports began to be published from Japan describing patients with dementia and parkinsonism associated with the presence of Lewy bodies in cortical neurons (reviewed by Kosaka, 1990). Since these reports, different workers have used a variety of terms to describe this disease process, including diffuse Lewy body disease (Yoshimura, 1983), Lewy body dementia (Gibb et al, 1987), senile dementia of Lewy body type (Perry et al, 1990a) and the Lewy body variant of Alzheimer's disease (Hansen et al, 1990).

Primary causes of medical instability of Medicare patients at discharge 1990-1991.

BACKGROUND: HCFA-sponsored Peer Review Organizations nationwide have been criticized by organized medicine, Medicare beneficiaries and interested Congressional parties for being punitive without exploiting educational opportunities garnered through their massive data collection capabilities. Until now this data has been poorly analyzed and has not been adequately utilized as a positive motivational tool. METHODS: HCFA has developed, with the cooperation of the medical community, six generic screens for Peer Review Organizations to utilize when evaluating quality care provided Medicare beneficiaries in an acute care setting. Through the sheer volume of cases seen, significant inpatient information can be obtained that cannot be duplicated in any other epidemiological endeavor. Line item discrepancies can be further studied through small-area-analysis to determine "who" as well as "what" may be the problem. RESULTS: By compiling and reviewing data in a systematic manner over two years (1990-1991), the Alabama Quality Assurance Foundation (AQAF) has singled out problems with patient medical stability at discharge as the predominant concern for care providers and reviewers alike. CONCLUSIONS: Having determined the primary problem in rendering quality care in a Prospective Payment System to Medicare beneficiaries lies in premature discharges, subsequent small-area-analysis further narrows the focus of concerned individuals. Hopefully, practitioners and providers alike will act on their own initiative in correcting this problem. Follow-up review will be utilized to assure this self-corrective action.

A comparison of glycoprotein biosynthesis in benign and malignant squamous epithelioma and normal epidermis.

Protein and N-linked glycoprotein biosynthesis was studied in histologically verified normal epidermis, actinic keratoses, keratoacanthoma, intra-epidermal carcinoma and squamous-cell carcinoma using polyacrylamide gel electrophoresis (PAGE). The PAGE profiles of 3[H]-leucine-labelled proteins and 3[H]-mannose-labelled glycoprotein from all disease states studied differed from each other and from normal epidermis. A large 3[H]-mannose-labelled glycoprotein region (band A) with a peak at 97-92 kDa appeared to indicate the presence of a relatively large proportion of basaloid cells in the tissue. An associated peak in the region of 78-74 kDa also appeared in normal epidermis and what appeared to be non-invasive lesions. The main region of change in all lesions corresponded to the 66-34-kDa region (bands B and C). The absence of a group of glycoproteins and proteins in the 62-58-kDa region appeared to be specific for invasive squamous-cell carcinoma. All tumours showed a peak at 38-34 kDa which was not present in normal epidermis. Actinic keratosis had a pattern similar to normal epidermis except that the peaks of band B tended towards the higher-molecular-weight end of the band than those in normal epidermis and peaks at 28-22 kDa were seen. The latter seemed to correspond to the presence of a high proportion of spinous cells in the tissue sample.

Statistical modelling in analysis of prognosis in glioblastoma multiforme: a study of clinical variables and Ki-67 index.

Statistical modelling was used to analyse clinical features and the Ki-67 proliferation index in a study of 77 cases of glioblastoma multiforme. Relative youth, frontal tumour site and treatment with external beam radiation had an important positive influence on survival. The pre-operative Karnovsky score and the presence of necrosis were not related to outcome. Despite the attractive hypothesis that rapidly proliferating tumours might be associated with a worse prognosis compared with slowly proliferating lesions, the Ki-67 index in this study offered no prognostic information even when individual sites were considered separately. The use of this form of computer modelling and its role in analysis of prognostic data is discussed.

Paraganglioma of the cauda equina. Report of three cases.

The authors report the clinical, radiological, and pathological findings in three cases of paraganglioma of the cauda equina. In one case, magnetic resonance imaging and neurochemical study results are described. No specific identifying features were encountered either clinically or radiologically that were helpful in making a distinction between this and other more common tumors at this site such as ependymoma or neurofibroma. At surgery, these neoplasms were well-circumscribed red fleshy tumors. Histological examination of one paraganglioma showed a superficial resemblance to ependymoma, and this may be particularly true on initial assessment by frozen section or smear. The use of electron microscopy and immunohistochemical demonstration of synaptophysin in these tumors allowed a confident diagnosis to be made. Neurochemical assessment in one case showed very high levels of serotonin and a turnover of dopamine similar to that of human cerebral cortex. Paraganglioma of the cauda equina is an uncommon tumor with just over 50 cases reported in the world literature. The clinical course of these tumors is benign and they should be completely removed at surgery to prevent later recurrence.

The clinical, radiological and histopathological features of cerebral primitive neuroectodermal tumours.

The clinical, radiological and pathological features of eight cases of supratentorial primitive neuroectodermal tumour are reviewed. These are tumours of children and young adults presenting with symptoms and signs of raised intracranial pressure. Radiologically they are characterized by a large enhancing mass lesion exciting little or modest surrounding oedema, with a propensity to develop in the frontal lobes. One tumour exhibited the pathological features of a primitive neuroectodermal tumour (PNET) with ependymal differentiation (ependymoblastoma). The rest showed no light microscopy patterns to indicate differentiation. Immunohistochemistry was helpful as it excluded other causes of a 'small blue cell' tumour but did not help in assessing differentiation. Ultrastructural examination of this group of apparently undifferentiated tumours showed focal markers of neuronal differentiation. Although features of neuronal differentiation can be found ultrastructurally in these tumours this is only evident after prolonged searching, often of several blocks, making assessment very prone to sampling errors. The term PNET thus remains appropriate and serves to group such tumours together to facilitate rational clinical management.

Diffuse Lewy body disease: an important differential diagnosis in dementia with extrapyramidal features.

Fifteen cases of diffuse Lewy body disease were identified in a systematic survey of all 216 brains referred to this hospital from a single health district in a single year. These cases presented with Parkinson's disease (40%), cognitive impairment (40%) and both (20%). Quantitative neuropathological studies using anti-ubiquitin immunocytochemistry revealed that dementia severity was related to cortical Lewy body density. The prevalence of diffuse Lewy body disease may have been underestimated in the past because of the neuropathological difficulties in making the diagnosis. Firstly, cortical Lewy bodies have a subtle appearance and are easy to overlook. Secondly, senile plaques are a common feature of diffuse Lewy body disease and may lead the unwary to make an erroneous diagnosis of Alzheimer's disease or "plaque-only Alzheimer's disease'. Diffuse Lewy body disease is a common and important cause of parkinsonian dementia, including the dementia of Parkinson's disease itself.

Achalasia like disorder of the oesophagus in von Recklinghausen's neurofibromatosis.

The association of achalasia like disorder of the oesophagus with von Recklinghausen's neurofibromatosis to our knowledge not previously reported is described in a 56 year old man who also had bladder dysfunction. At necropsy the oesophageal myenteric plexus showed ganglion cell depletion with nerve fibre hyperplasia probably the result of Schwann cell hyperplasia. We suggest that the disturbances of oesophageal and bladder function were a consequence of involvement of the autonomic nervous system by neurofibromatosis.

Popliteal artery perforation during low dose intra-arterial streptokinase infusion.

There has been a recent increase in the use of low dose intra-arterial streptokinase infusion for the management of patients with acute peripheral arterial occlusions. Though serious complications using this technique occur less frequently than when using systemic thrombolytic therapy, a case is reported where the catheter used to infuse streptokinase perforated the popliteal artery 36 hours after the infusion commenced. The use of softer arterial catheters and restriction of patient movement where possible may prevent the recurrence of this previously unreported hazard.

Morphology of physiologically identified bipolar cells in the retina of the tiger salamander, Ambystoma tigrinum.

Intracellular recordings of the light responses of bipolar cells were made in the isolated perfused retina of the larval tiger salamander by microelectrodes filled with a 1% solution of the enzyme horseradish peroxidase (HRP). Two classes of bipolar cell were identified in terms of their responses to luminous spots and annuli centered upon their receptive fields: on-center cells, which depolarized in response to a centered spot and hyperpolarized in response to a concentric annulus, and off-center cells, which responded with the opposite polarities. Physiologically identified cells were labelled with HRP by iontophoretic injection and prepared for light microscopy. Examples of each of the three classes of bipolar cell described in Cajal's study of the amphibian retina were found amongst the labelled cells. The only morphological feature found to correlate with the physiological classification was the stratum at which the axon of the cell arborized in the inner plexiform layer. The axons of on-center cells arborized in the more proximal sublamina b, while those of off-center cells arborized in the more distal sublamina a. This is consistent with earlier findings in the retinae of the cat and the carp.

Monoclonal antibodies raised against a subsequence of senile plaque core protein react with plaque cores, plaque periphery and cerebrovascular amyloid in Alzheimer's disease.

Four monoclonal antibodies (1D2/1/2, 1G10/2/3, 3B6/1/1, 4D12/2/6) were raised against a synthetic peptide consisting of residues 8-17 of a protein reported to be common to senile plaque cores, cerebrovascular amyloid and neurofibrillary tangles in Alzheimer's disease. In an immunoperoxidase study of Alzheimer brain tissue, these antibodies stained plaque and vascular amyloid but not tangles, suggesting that the polypeptide chain in the region of residues 8-17 is exposed in the former two but, if present, inaccessible in the latter. In addition, staining of granular material in the plaque periphery was observed. These antibodies will be useful tools for future work on the origin of this protein.

Type III glycogenosis presenting as liver disease in adults with atypical histological features.

Two cases of type III glycogen storage disease are reported in adults; the occurrence of cirrhosis in one case illustrates the potential development of chronic liver disease in this condition. The other was the oldest patient with this condition found in a review of published reports. Electron microscopy of peripheral blood leucocytes to demonstrate excess glycogen was found to be a quick and useful aid to diagnosis. Histology of these adult cases showed a distribution of hepatocyte vacuolation which has not been previously recorded.

Perforation of a suppurative solitary renal cyst.

A fatal case of rupture of a large infected renal cyst is presented. Antibiotic therapy is indicated after aspiration of a suppurative renal cyst, and recurrence, particularly if large, is an indication for prompt surgical intervention.

Collagenolytic cathepsin activity in rabbit peritoneal polymorphonuclear leucocyte granules.

Collagenolytic cathepsin activity was detected in lysed rabbit peritoneal polymorphonuclear leucocytes. The pH optimum was around 3, and activity was greatly enhanced by the presence of cysteine and EDTA. Digestion of polymeric collagen resulted in the release of alpha, beta, and gamma-chains. Collagenolytic cathepsin activity was associated mainly with the granule fraction isolated from homogenates by differential centrifugation. The granule fraction was further fractionated by isopycnic density-gradient centrifugation, and the collagenolytic cathepsin activity was shown to be associated with the azurophil and tertiary granules, both lysosome-like organelles.