Giant cell arteritis: a new association with benign paroxysmal positional vertigo

OBJECTIVE: To assess the incidence and characteristics of both benign paroxysmal positional vertigo (BPPV) and positional nystagmus in a series of patients with giant cell arteritis (GCA). STUDY DESIGN: Patients diagnosed with GCA between June 1999 and May 2001 at the single hospital for a defined population were examined prospectively. METHOD: Patients included in this study fulfilled the 1990 American College of Rheumatology classification criteria for GCA. Otologic and oculographic studies were performed. Type, frequency, and outcome of positional oculographic findings was assessed. Patients were required to have been examined within 1 week after the onset of corticosteroid therapy. Data found in GCA patients were compared with those observed in an age, sex, and ethnically matched control population. Further studies in patients and controls were performed 3 and 6 months later. RESULTS: Forty-four patients and 44 matched controls were included in this study. Nine (20.5%) GCA patients fulfilled diagnostic criteria of BPPV compared with only 1 (2.3%) of the controls (P =.007). In seven of these nine GCA patients, BPPV was related to the posterior and two to the horizontal semicircular canals, respectively. Horizontal nystagmus was found in seven GCA patients who developed nystagmus in the head hanging position test compared with none in the controls (P =.006). CONCLUSIONS: The present study shows a higher frequency of BPPV in GCA than in matched controls. Because most clinical manifestations in GCA are caused by ischemic complications, our results suggest an ischemic etiology as responsible for BPPV in these elderly patients. According to these results, GCA may constitute a new association with BPPV.     

Lung cancer audit in an Irish teaching hospital

Background Lung cancer is the most common cause of cancer-related death in Ireland. There are few complete data sets available as to the stage and cell type of lung cancers at time of presentation in Ireland. Aim To audit the lung cancers presenting to a large Dublin teaching hospital over a 12-month period. Method Prospective evaluation of all lung tumours presenting to our institution over a consecutive 12-month period. Results One hundred and ninety-eight lung cancers presented over the study period. There were 34 cases of small cell carcinoma and 150 cases of non-small cell carcinoma (NSCC). Fourteen patients were too ill or compromised at time of presentation for tissue confirmation. The most common cell type was squamous carcinoma. Eighty-four per cent of the NSCCs were either stage 3 or 4 at presentation. Conclusion Most lung cancers present late in the time course of the disease. Distribution of cell type and location are similar in Ireland and other developed countries.     

Genetic association of CYP46 and risk for Alzheimer's disease

An increasing number of studies suggest that cholesterol plays an important role in regulating beta-amyloid (Abeta) metabolism in Alzheimer's disease (AD). One of the most important mechanisms for the elimination of excess brain cholesterol is its conversion into the 24S-hydroxycholesterol catalyzed by cholesterol 24S-hydroxylase (CYP46). Preliminary evidence indicates that an intron 2 CYP46 T/C gene polymorphismis associated with increased brain Abeta load and higher risk of AD. A case-control study utilizing a clinically well-defined group of 321 sporadic AD patients and 315 control subjects was performed to test this association. Our results indicate that the intron 2 CYP46 C/C genotype may predispose to AD, and this association is independent of the apolipoprotein E genotype.     

Escitalopram is more effective than citalopram for the treatment of severe major depressive disorder

BACKGROUND: Escitalopram is a highly selective serotonin reuptake inhibitor (SSRI). It is the therapeutically active S-enantiomer of citalopram. It has been shown, compared with placebo, to be an effective and well-tolerated treatment for major depressive disorders (MDD) in both primary and specialist care settings. A recent meta-analysis has found that escitalopram-treated patients showed significant higher response rates and increased mean change from baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) total scores at weeks 1 and 8 compared with citalopram-treated patients. Each of these active drugs shares similar safety profiles. Although the efficacy of newer antidepressants has been well established for the treatment of mild-to-moderate depression, there are very few studies concerning severe depression. OBJECTIVE: To determine if escitalopram is more effective than citalopram in patients with severe depression. METHODS: Data were pooled from three different clinical trials, each similar in design and inclusion/exclusion criteria, primary endpoints and assessment schedules. This analysis was exhaustive because it included all trials in which the maximum dose for escitalopram (20 mg) could be administered. According to the cut-off point taken to define severe depression based on the MADRS total score ( 30), 506 patients were considered as severely depressed patients and so included in this analysis. Among them, 169 received escitalopram, 171 received citalopram and 166 received the placebo. The primary efficacy parameter was the mean change from baseline to end of treatment in MADRS total score between escitalopram and citalopram groups, based on last-observation-carried-forward method. The change from baseline to endpoint of the Hamilton rating scale for Depression (HAM-D) and the Clinical Global Impression of Improvement and Severity (CGI-I and CGI-S) were also analysed as secondary criteria. Clinical response was defined by at least a 50% reduction in baseline MADRS total score or by at least a 60% reduction in baseline HAM-D score or by a score of 1 (very much improved) on the CGI scale, and remission by a MADRS total score pound 12. RESULTS: Results showed that the mean change from baseline in the MADRS total score was significantly higher in the escitalopram group compared with the citalopram group (- 17.3 vs - 13.8 respectively, p=0.003). This significant difference was observed as early as week 1 (p=0.01). Response rates were significantly higher for escitalopram than for citalopram (56% vs 41% respectively, p=0.007). A borderline significant difference was found for remission rate in the observed-cases analysis (43% vs 33% respectively, p=0.07). Analyses of the HAM-D, CGI-I and CGI-S scores revealed consistent results. DISCUSSION: This study shows that the new SSRI escitalopram has better efficacy in the treatment of severe depression than citalopram, its racemic parent. Mean differences between treatments groups were in favour of escitalopram for all scales. The benefits of escitalopram compared with citalopram, as demonstrated by both magnitude of effect and time of onset, are superior to the benefits of citalopram, an antidepressant drug with proven efficacy. This evidence clearly supports the use of escitalopram as a legitimate first-line treatment for MDD.     

Relapsing upper bleeding in non-Hodgkin's oesophageal lymphoma associated with achalasia

Achalasia is a disease of unknown origin in which there is a denervation of the myenteric plexus on the smooth muscle of the lower oesophageal sphincter, causing a cardial stenosis and a loss of efficacy of oesophageal peristalsis. The predominant symptoms are dysphagia for solids and liquids and regurgitation of the retained food. Occasionally, there may be oesophageal haemorrhage as a consequence of oesophagitis and stasis ulcers. An important but uncommon complication is the development of oesophageal cancer, which is typically squamous cell carcinoma. We report an exceptional case of a 77-year-old woman with a long-term achalasia and mega-oesophagus who presented four episodes of upper gastrointestinal bleeding in a 2 month period. The patient underwent surgical resection of the 10 cm of distal oesophagus, performing a partial fundoplication, and the pathological study revealed an oesophageal infiltration by a low-grade non-Hodgkin's lymphoma. After an insidious outcome, she died on the 47th day after admission.     

Polymorphism at codon 174 of the prion-like protein gene is not associated with sporadic Alzheimer's disease

Dyslexic subjects show a variety of mild sensory and motor deficits that have been assumed to reflect dysfunction of the large-diameter 'magnocells' in different parts of the brain. Hearing as a warning sense relies on rapidly-conducting fibers, and on the basis of the magnocellular deficit theory, we wondered whether auditory alerting would be weakened in dyslexic adults. We quantified the strength of sound-induced spinal facilitation in seven dyslexic and eight normal-reading adults by measuring the amplitudes of H-reflex, a monosynaptic spinal reflex, after loud binaural sounds. The audiospinal facilitation was of similar strength in dyslexic and control adults, indicating normal auditory alerting via cerebrospinal pathways. The slightly prolonged facilitation in dyslexics agrees with the dyslexics' general sluggishness of sensorimotor processing.     

Interaction of the H63D mutation in the hemochromatosis gene with the apolipoprotein E epsilon 4 allele modulates age at onset of Alzheimer's disease

The H63D mutation in the hemochromatosis gene (HFE) has recently been considered as a risk factor in Alzheimer's disease (AD) with advancing age at onset of the disease, independently of the apolipoprotein E (ApoE) epsilon4 allele effect. We examined the distribution of the H63D mutation and ApoE genotypes as a function of age at AD onset in 328 patients with sporadic AD. Our data show that the mutant H63D allele potentially interacts with the ApoE epsilon4 allele to significantly reduce age at onset of AD compared to ApoE epsilon4 carriers alone, but has no effect on age at onset in ApoE epsilon4 non-carriers.