MONOCLONAL ANTIBODY TREATMENT IN RHEUMATOID ARTHRITIS: THE CLINICAL AND IMMUNOLOGICAL EFFECTS OF A CD7 MONOCLONAL ANTIBODY

Six patients with rheumatoid arthritis were treated with a CD7mouse monoclonal antibody, RFT2, daily for 14 days. Only twopatients had a significant improvement in clinical disease activitywhich lasted 7–14 days. No serious adverse effects occurredalthough all patients developed antibodies against mouse immunoglobulin.During treatment T-lymphocyte numbers decreased and T-lymphocyteCD7 expression was absent in all but one patient. KEY WORDS: Immunotherapy, Antigen modulation, RA     

Gold in the dermis following chrysotherapy: histopathology and microanalysis

Novel antibodies have been generated by immunizing with bacterially expressed fragments of the repetitive motif of the Ki-67 gene. One such antibody, MIB1, recognizes a fixation and embedding resistant epitope on the Ki-67 protein if sections are previously microwaved in a citrate buffer. We have investigated the utility of this antibody as a marker of cell proliferation in archival material. The microwave technique is simple but requires careful monitoring since different tissues and fixatives require different irradiation times. Strong nuclear immunoreactivity was detected with all fixatives studied. Cytoplasmic staining was not identified. In a wide range of normal tissues the distribution and number of MIB1 immunoreactive cells matched that of cryostat sections stained with Ki-67. In nude mouse xenografts in which the growth fraction had been defined using a fraction of labelled mitosis method, the labelling index with MIB1 matched that previously determined for Ki-67 and correlated well with the growth fraction. Other markers of proliferation (e.g. proliferating cell nulcear antigen) have been shown to be expressed in DNA repair, thus we investigated expression of MIB1 immunoreactivity in situations of DNA repair in vivo —ultraviolet irradiated human skin. MIB1 staining correlated with semi-conservative DNA synthesis rather than excision repair DNA synthesis. Finally, the morphological and cell cycle distribution of MIB1 expression is identical to that of Ki-67. Thus, MIB1 represents a new anti-Ki-67 antibody which appears to be a robust marker of cell proliferation easily applicable to archival material.     

Merkel cell carcinoma: a report of three cases with neurone-specific enolase activity

Three cases are described of a primary cutaneous neoplasm occurring in elderly patients, histological and immunohistochemical features of which support an origin from Merkel cells. Microscopically sheets of uniform small cells filled the dermis, often with a prominent trabecular pattern. Ultrastructurally the cells showed neurosecretory granules, tangles of microfilaments, scattered mitochondria and occasional intranuclear rodlets. Immunohistochemical staining for neurone-specific enolase was positive and for prekeratin was negative in each case. The definitive diagnosis of Merkel cell tumour can be made with a combination of electron microscopy and immunohistochemistry.     

USE OF SEQUENTIAL DTPA CLEARANCE AND HIGH RESOLUTION COMPUTERIZED TOMOGRAPHY EN MONITORING INTERSTITIAL LUNG DISEASE IN DERMATOMYOSITTS

Interstitial lung disease complicating polymyositis—dermatomyositishas a grave prognosis. We report the case of a 50-yr-old womanwith dermatomyositis and interstitial lung disease monitoredby sequential high-resolution computerized tomography (HRCT)of lung and aerosol clearance times of the radionuclide ⁹⁹Technetium-diethylenetriamine pentacctate (DTPA). She was treated with oral cyclophosphamideand prednisolone with good outcome. Pulmonary response to therapywas followed with sequential HRCT and DTPA scanning. DTPA clearance,a measure of lung inflammation, and HRCT paralleled clinicalcourse during the treatment of interstitial lung disease. SequentialHRCT and DTPA were useful adjuncts in the initial assessmentand monitoring of interstitial lung disease in association withdermatomyositis. KEY WORDS: Interstitial lung disease, Dermatomyositis, ⁹⁹Technetium-diethylene triamine pentacetate scan, High-resolution computerized tomography      

INTRAMUSCULAR DEPOT METHYLPREDNISOLONE INDUCTION OF CHRYSOTHERAPY IN RHEUMATOID ARTHRITIS: A 24-WEEK RANDOMIZED CONTROLLED TRIAL

Fifty-nine patients commencing intramuscular sodium aurothiomalatetherapy were randomized to receive three doses of 120 mg intramusculardepot methylprednisolone acetate or matching placebo at weeks0, 4, and 8 in addition to chrysotherapy. The group receivingmethylprednisolone had more rapid disease improvement. Thisadvantage persisted for up to 12 weeks, although by 24 weeksboth groups exhibited similar benefits due to continued improvementin the group treated with gold alone. Withdrawals secondaryto gold-induced side-effects occurred later in the steroid group(median time to withdrawal: 15 weeks steroid; 4.5 weeks placebo,P<0.05), and there were fewer withdrawals due to a lack ofeffect in the steroid group (one steroid versus three placebo,PNS). We conclude that glucocorticoids given as intermittent,intramuscular depot injections have a significant short termbenefit which can be maintained by concomitant administrationof intramuscular gold. KEY WORDS: Glucocorticoids, Gold therapy, Sodium aurothiomalate, Therapy     

Outcome following decompressive craniectomy for malignant middle cerebral artery infarction in children

Aim Mortality from malignant middle cerebral artery infarction (MMCAI) approaches 80% in adult series. Although decompressive craniectomy decreases mortality and leads to an acceptable outcome in selected adult patients, there are few data on MMCAI in children with stroke. This study evaluated the frequency of MMCAI and the use of decompressive craniectomy in children. Method We retrospectively reviewed cases of MMCAI from five pediatric tertiary care centers. Results Ten children (two females, eight males; median age 9y 10mo, range 22mo–14y) had MMCAI, with a median Glasgow Coma Scale score of 6 (range 3–9). MMCAI represented fewer than 2% of cases of pediatric arterial ischemic stroke. Three patients who did not undergo decompression, all of whom had monitoring of intracranial pressure, developed intractable intracranial hypertension, and fulfilled criteria for brain death. In contrast, seven patients underwent decompressive craniectomy and survived, with rapid improvement in their level of consciousness postoperatively. All seven survivors now walk independently with mild to moderate residual hemiparesis and speak fluently, even though four had left‐sided infarcts. Interpretation Decompressive craniectomy can lead to a moderately good outcome for children with MMCAI and should be considered, even with symptomatic stroke and deep coma. Monitoring of intracranial pressure may delay life‐saving treatment.