Anti-Yo antibody-mediated paraneoplastic cerebellar degeneration associated with cognitive affective syndrome in a patient with breast cancer: a case report and literature review.

Breast cancer is the most common cancer in women, with 15%-25% of those tumours overexpressing the human epidermal growth factor receptor 2 (her2), which is associated with more aggressive disease. On rare occasions, patients present with a paraneoplastic syndrome months to years before their cancer diagnosis. Paraneoplastic cerebellar degeneration (pcd) is associated with fewer than 1% of cancers and is strongly associated with breast and gynecologic malignancies. Anti-Yo antibody is the antibody most frequently identified with the syndrome, and it is associated with a very poor prognosis. Recent studies have implicated a relationship between overexpression of her2 and anti-Yo-mediated pcd. Current pcd treatments include tumour removal, chemotherapy, targeted therapy, and immune-suppressive treatments. Outcomes of pcd are typically poor, and no guidelines for treatment currently exist. Early recognition followed by rapid initiation of treatment remains the cornerstone of therapy. Here, we present a case of anti-Yo-antibody pcd secondary to estrogen and progesterone receptor-negative, her2-positive breast cancer. Despite treatment with mastectomy, chemotherapy, and her2-targeted therapy, no significant neurologic improvement was achieved, and cerebellar cognitive affective syndrome subsequently developed.

A prospective randomized evaluation of a pharmacogenomic approach to antiplatelet therapy among patients with ST-elevation myocardial infarction: the RAPID STEMI study.

Treatment of carriers of the CYP2C19*2 allele and ABCB1 TT genotype with clopidogrel is associated with increased ischemic complications after percutaneous coronary intervention (PCI). We sought to evaluate a pharmacogenomic strategy among patients undergoing PCI for ST-elevation myocardial infarction (STEMI), by performing a randomized trial, enrolling 102 patients. Point-of-care genetic testing for CYP2C19*2, ABCB1 TT and CYP2C19*17 was performed with carriers of either the CYP2C19*2 allele or ABCB1 TT genotype randomly assigned to a strategy of prasugrel 10 mg daily or an augmented dosing strategy of clopidogrel (150 mg daily for 6 days then 75 mg daily). The primary end point was the proportion of at-risk carriers exhibiting high on-treatment platelet reactivity (HPR), a marker associated with increased adverse cardiovascular events, after 1 month. Fifty-nine subjects (57.8%) were identified as carriers of at least one at-risk variant. Treatment with prasugrel significantly reduced HPR compared with clopidogrel by P2Y12 reaction unit (PRU) thresholds of >234 (0 vs 24.1%, P=0.0046) and PRU>208 (3.3 vs 34.5%, P=0.0025). The sensitivity of point-of-care testing was 100% (95% CI 88.0-100), 100% (86.3-100) and 96.9% (82.0-99.8) and specificity was 97.0% (88.5-99.5), 97.1% (89.0-99.5) and 98.5% (90.9-99.9) for identifying CYP2C19*2, ABCB1 TT and CYP2C19*17, respectively. Logistic regression confirmed carriers as a strong predictor of HPR (OR=6.58, 95% CI 1.24-34.92; P=0.03). We confirmed that concurrent identification of three separate genetic variants in patients with STEMI receiving PCI is feasible at the bedside. Among carriers of at-risk genotypes, treatment with prasugrel was superior to an augmented dosing strategy of clopidogrel in reducing HPR.

ST segment resolution in patients with tenecteplase-facilitated percutaneous coronary intervention versus tenecteplase alone: Insights from the Combined Angioplasty and Pharmacological Intervention versus Thrombolysis ALone in Acute Myocardial Infarction (CAPITAL AMI) trial.

BACKGROUND: Compared with fibrinolysis alone, fibrinolysis followed by immediate percutaneous coronary intervention (PCI) reduced clinical events in the Combined Angioplasty and Pharmacological Intervention versus Thrombolysis ALone in Acute Myocardial Infarction (CAPITAL AMI) study. It is unclear whether the benefits go beyond achieving epicardial reperfusion. OBJECTIVES: To determine the differences in ST segment resolution (STR) among patients treated with tenecteplase (TNK)-facilitated PCI compared with patients treated with TNK alone. METHODS AND RESULTS: A formal ST segment analysis was conducted on the 170 patients with ST elevation myocardial infarction in the CAPITAL AMI trial: 86 patients treated with TNK-facilitated PCI were compared with 84 patients who were treated with TNK alone. Epicardial flow measured by percentage with Thrombolysis In Myocardial Infarction (TIMI) 3 flow improved from 52% (pre-PCI) to 89% (post-PCI) in those assigned to facilitated PCI. ST segment resolution was stratified by complete (70% or greater), partial (less than 70% to 30%) or no (less than 30% to 0%) resolution. The baseline mean ST segment elevation was 11.3+/-7.5 mm in the facilitated PCI patients and 11.8+/-7.1 mm in patients with TNK alone (P=0.66). Complete STR in the facilitated PCI patients versus the TNK-alone patients was present in 55.6% versus 54.6%, respectively (P=0.58) at 180 min and 62.0% versus 55.3% (P=0.64), respectively at day 1. The mean STR at 180 min and day 1 were similar in patients who experienced death, reinfarction, recurrent unstable ischemia or stroke at six months compared with patients who remained event free: 56.3% versus 64.6% at 180 min (P=0.40); and 67.7% versus 67.6% at day 1 (P=0.99), respectively. CONCLUSIONS: TNK-facilitated PCI did not demonstrate differences in ST segment resolution compared with TNK alone, despite improvement in epicardial flow after PCI. Further studies are required to clarify these findings.

Stenting versus thrombolysis in acute myocardial infarction trial (STAT).

OBJECTIVES: We sought to directly compare primary stenting with accelerated tissue plasminogen activator (t-PA) in patients presenting with acute ST-elevation myocardial infarction (AMI). BACKGROUND: Thrombolysis remains the standard therapy for AMI. However, at some institutions primary angioplasty is favored. Randomized trials have shown that primary angioplasty is equal or superior to thrombolysis, while recent studies demonstrate that stent implantation improves the results of primary angioplasty. METHODS: Patients presenting with AMI were randomly assigned to primary stenting (n = 62) or accelerated t-PA (n = 61). The primary end point was the composite of death, reinfarction, stroke or repeat target vessel revascularization (TVR) for ischemia at six months. RESULTS: The primary end point was significantly reduced in the stent group compared with the accelerated t-PA group, 24.2% versus 55.7% (p < 0.001). The event rates for other outcomes in the stent group versus the t-PA group were as follows: mortality: 4.8% versus 3.3% (p = 1.00); reinfarction: 6.5% versus 16.4% (p = 0.096); stroke: 1.6% versus 4.9% (p = 0.36); recurrent unstable ischemia: 9.7% versus 26.2% (p = 0.03) and repeat TVR for ischemia: 14.5% versus 49.2% (p < 0.001). The median length of the initial hospitalization was four days in the stent group and seven days in the t-PA group (p < 0.001). CONCLUSIONS: Compared with accelerated t-PA, primary stenting reduces death, reinfarction, stroke or repeat TVR for ischemia. In centers where facilities and experienced interventionists are available, primary stenting offers an attractive alternative to thrombolysis.

Stenting of an unprotected left main coronary artery stenosis in a cardiac transplant patient.

Cardiac allograft vasculopathy is the leading cause of death in cardiac transplant patients who survive the first year. Retransplantation is limited by shortage of donors and reduced survival rates compared with the initial transplant. Recent reports of successful stenting in these patients may offer some hope, although randomized trials are lacking. Successful stenting of an 'unprotected' left main coronary artery stenosis under cardiopulmonary support is presented in a cardiac transplant patient. A 16-month follow-up angiogram demonstrated a patent stent without restenosis and no interim clinical events.

Predictors of long-term outcome after stent implantation in a saphenous vein graft.

Stenting of saphenous vein graft (SVG) lesions is associated with significant clinical events at late follow-up. We sought to determine predictors of clinical outcome after this procedure. One hundred twenty-eight balloon-expandable stents were implanted in the SVGs of 106 patients. Baseline clinical and angiographic characteristics were analyzed. All grafts, including those not stented, were scored for extent of disease involving the luminal surface of the graft, and for the presence of low profile lesions (< 50% graft stenosis) and/or high profile lesions (> or = 50% graft stenosis). The in-hospital success rate was 98.1%. Before discharge, no patient died, required bypass surgery, or had repeat angioplasty of the same graft. Follow-up was obtained on all the patients. At a median of 18 months, 15% had died, 17% had experienced myocardial infarction, 20% had required repeat bypass surgery, and 37% needed repeat angioplasty to either the same site or a different lesion. Event-free survival was recorded in only 44% of the patients. The cumulative Kaplan-Meier survival at 2.4 years was 78.7%. Using the Cox proportional hazards model, predictors of survival were the absence of a high profile lesion in any nonstented patent graft (p = 0.004), and the use of lipid-lowering agents at follow-up (p = 0.01). Stenting SVG lesions can be performed with a high degree of procedural success, but at long-term follow-up there is a high rate of cardiac events. The absence of a high profile lesion in any nonstented patent graft is the strongest predictor of survival.

Late clinical and angiographic follow-up after stenting in evolving and recent myocardial infarction.

OBJECTIVES: This study sought to assess the late clinical and angiographic outcomes of patients who received stents within the first week of acute myocardial infarction (AMI). BACKGROUND: Recent studies have demonstrated that stenting of the infarct-related artery is a useful adjunct to balloon angioplasty in patients with AMI. However, there are limited data on the late clinical and angiographic outcomes of these patients. METHODS: Between January 1994 and September 1995, 32 patients at our institution underwent stenting of the infarct-related artery within 1 week of AMI: 13 within 14 hours (evolving group) and 19 between days 2 and 7 (recent AMI group). Late clinical follow-up was obtained on all survivors. Quantitative angiographic measurements were recorded on the stented segments before stenting, immediately after stenting, and on the follow-up angiograms. RESULTS: At 13.1+/-6.4 months from the time of stenting, three patients died and three required repeat angioplasty, but no patient had reinfarction or required bypass surgery. At follow-up 26 (81%) of 32 patients remained free of major cardiac events; of these, 24 (92%) were free of angina. Repeat angiography performed at 10.8+/-7.5 months in 26 (87%) of 30 discharged patients showed that all infarct-related arteries were patent and the restenosis rate was low: 22% in the 13 patients with evolving AMI (<14 hours) and 12% in the 19 patients with recent AMI (days 2 through 7). CONCLUSION: In this study stenting of the infarct-related artery in patients with evolving and recent AMI was associated with a favorable late clinical outcome. Patency of the infarct-related artery was well maintained, and the restenosis rate was low.

Three into one will go! Collaborative practice in practice.

This paper is concerned with three speech and language therapy services from neighbouring NHS trusts and the single education authority they all share. The authors have always been committed to working collaboratively with local services but found the competitive health care environment of the late 1980s and early 1990s often-made this difficult. It describes how the three services came together to identify common service issues for children of school-age with speech and language difficulties and how these were addressed.

What is the outcome of the outcomes? Evaluation of the therapy outcome measures.

In 1996, the Speech and Language Therapy Departments of First Community Health NHS Trust and Kidderminster Care NHS Trusts agreed to take part in a year's pilot study of the Therapy Outcome Measures developed by Enderby and John (1997). This paper will discuss the rationale for choosing to pilot these outcome measures and discuss the implementation of the project from a service manager's perspective. The discussion will focus upon what has been learnt from piloting the Therapy Outcome Measures.

Coronary stenting in acute myocardial infarction--patency demonstrated postmortem.

This report describes a patient with an acute anterior myocardial infarction treated by primary angioplasty and stenting of the infarct-related artery. The patient died 48 h later and at postmortem examination, patency of the stented artery was demonstrated, despite the adverse conditions which preceded death.

Usefulness of intracoronary stenting in acute myocardial infarction.

Data on the feasibility, safety, and clinical outcome of intracoronary stenting in acute myocardial infarction (AMI) are limited. This study examined the immediate angiographic results and the early and late outcomes in 32 patients who had stenting during AMI. Coronary angiograms recorded at the time of stenting were reviewed with quantitative measurements obtained on the "target" coronary lesion before and after stenting. Immediate angiographic success was achieved in 30 patients (94%). The minimal luminal diameter increased from 0.36 +/- 0.37 to 2.58 +/- 0.41 mm (p<0.0001). Two patients died in the hospital. Of the remainder, none had reinfarction or required bypass surgery, whereas 2 required repeat coronary angioplasty for recurrent ischemia. Although thrombus at the infarct-related coronary lesion was initially detected in 41% of the patients, its presence was not associated with adverse procedural outcome. Only 1 patient had persistent thrombus after stenting, which resolved with intracoronary urokinase. At a mean follow-up of 6.1 +/- 4.1 months, there was 1 additional cardiac death, and no patient had AMI or required repeat coronary angioplasty or bypass; among the 29 survivors, 86% were free of angina. Thus, intracoronary stenting of the infarct-related artery in the setting of AMI is associated with excellent immediate angiographic success and a favorable clinical outcome, and remains an option even in the presence of thrombus.

Refractory ventricular fibrillation complicating acute myocardial infarction terminated by intracoronary stenting.

We report on a case of intractable recurrent ventricular fibrillation that responded poorly to antiarrhythmic medication and balloon angioplasty, but resolved instantaneously following intracoronary stenting.

Effects of monotherapy with an HMG-CoA reductase inhibitor on the progression of coronary atherosclerosis as assessed by serial quantitative arteriography. The Canadian Coronary Atherosclerosis Intervention Trial.

BACKGROUND: 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors are widely prescribed for hyperlipidemia, yet their effect on the evolution of coronary atherosclerosis has not been defined. METHODS AND RESULTS: To address this issue, 331 patients with diffuse but not necessarily severe coronary atherosclerosis documented on a recent arteriogram and with fasting serum cholesterol between 220 and 300 mg/dL were enrolled in a randomized, double-blind, placebo-controlled trial. All patients received intensive dietary counseling. Lovastatin or placebo was begun at 20 mg/d and was titrated to 40 and 80 mg during the first 16 weeks to attain a fasting low-density lipoprotein (LDL) cholesterol < or = 130 mg/dL. The mean lovastatin dose was 36 mg/d. Coronary arteriography was repeated after 2 years. In 299 patients (90%), 3858 coronary segments containing 2309 stenoses were measured blindly on pairs of films with an automated computerized quantitative system. Total and LDL cholesterol decreased by 21 +/- 11% and 29 +/- 11%, respectively, in the lovastatin-treated group but changed by < 2% in placebo patients. The primary end point, coronary change score, defined as the per-patient mean of the minimum lumen diameter changes (follow-up minus baseline angiogram) for all lesions measured, excluding those < 25% on both films, worsened by 0.09 +/- 0.16 mm in the placebo group and by 0.05 +/- 0.13 mm in the lovastatin group (P = .01). Progression (a worsening in minimum diameter of one or more stenoses by > or = 0.4 mm) with no regression at other sites occurred in 48 of 146 lovastatin and 76 of 153 placebo patients (33% versus 50%, P = .003). New coronary lesions developed in 23 lovastatin and 49 placebo patients (P = .001). The beneficial effect of treatment was most pronounced in the more numerous, milder lesions and in patients whose baseline total or LDL cholesterol levels were above the group median. CONCLUSIONS: Lovastatin slows the progression of coronary atherosclerosis and inhibits the development of new coronary lesions.

A survey of aphasia services in the United Kingdom.

A survey of the service available, in speech and language therapy departments, to adults with aphasia revealed that many districts in the United Kingdom are unable to fulfil the professional recommendations for the care of aphasic clients. Although individual 'good practice' criteria could be satisfied, only a minority of districts were able to provide a comprehensive service. Levels of staffing for the adult neurological caseload are variable and even, at best, hinder therapists in delivering the recommended standard of management to aphasic clients and their carers.

A comparative study of virus isolation, polymerase chain reaction, and antigen detection in children of mothers infected with human immunodeficiency virus.

We report on an investigation designed to compare the polymerase chain reaction (PCR) with culture and p24 measurement for the diagnosis of human immunodeficiency virus (HIV) infection in infants and children. Forty-five children born of mothers with antibodies to HIV type 1 were studied; P24 antigen was measured in plasma, and HIV-1 proviral DNA was sought in peripheral blood mononuclear cells after amplification by PCR. In 26 cases, blood specimens were cultured for HIV; in all but two instances cultures were established at the same time that the PCR test was performed. Primer pairs in three regions of the proviral genome were used for the PCR test. There was good agreement between the results obtained from PCR tests and from cultures; of 24 children in whom both tests were done at the same time, 10 had positive results on both the culture and the PCR test, 1 had positive results on the PCR test but negative culture results, and 13 had negative results on both tests (concordance 96%). Measurement of p24 antigen in plasma was, in contrast, an insensitive marker of infection: 6 of 12 infants with positive cultures had positive p24 test results, and 8 of 18 infants had positive PCR test results. Sixteen children with subsequent seronegativity for HIV-1 had negative PCR results. This study provides further evidence that the PCR test is a valid alternative to viral culture for the diagnosis of pediatric HIV infection.

Computerized tomography and B-scan ultrasonography in the diagnosis of fractures of the medial orbital wall.

Ultrasound and CT scans have been used to examine 12 patients with suspected medial orbital wall fractures. A good correlation between ultrasound and CT scanning was demonstrated, and the authors believe that either investigation is a suitable alternative to conventional radiology when this type of injury is suspected.

Investigation and management of orbital trauma.

Clinical examination and conventional radiography of the orbit following recent orbital trauma often gives an incomplete picture of the damage present. In many infra-orbital blowout injuries, damage to the medial orbital wall occurs with prolapse and sometimes incarceration of orbital contents into both the maxillary and ethmoidal air sinuses. Late enophthalmos is thought to be caused by both atrophy of orbital fat and its loss into the paranasal sinuses. Hypocycloidal tomography in an antero-posterior plane is helpful in the recognition of those defects, but it does not distinguish between the presence of blood clot and soft tissue. Computerised axial tomography (C.A.T.) and ultrasonography are currently available investigative techniques which do distinguish between the presence of air, blood clot, soft tissue and bone and, in addition, there is a significant reduction in radiation dosage when compared with tomography. A comparison of these techniques and the clinical findings is described. These investigations should indicate the necessity for surgical intervention and prevent some of the late complications, such as enophthalmos.

Diagnosis of cranial asymmetries in cerebral arteriovenous malformations.

Nine of 29 patients with cerebral arteriovenous malformations exhibited abnormal cranial asymmetries on computed tomography (CT). Two of these patients showed no other abnormalities on their precontrast CT scans. Assessment of cranial asymmetry is recommended in all patients suspected of having an arteriovenous malformation.