Incidence, event rates, and early outcome of stroke in Dublin, Ireland: the North Dublin population stroke study.

BACKGROUND AND PURPOSE: The World Health Organization has emphasized the importance of international population-based data for unbiased surveillance of stroke incidence and outcome. To date, few such studies have been conducted using recommended gold-standard ascertainment methods. We conducted a large, population-based stroke study in Dublin, Ireland. METHODS: Using gold-standard ascertainment methods, individuals with stroke and transient ischemic attack occurring over a 12-month period (December 1, 2005-November 30, 2006) in North Dublin were identified. Disability was assessed using the modified Rankin score and stroke severity (<72 hours) by the National Institutes of Health Stroke Scale. Stroke-related deaths were confirmed by review of medical files, death certificates, pathology, and coroner's records. Crude and standardized (to European and World Health Organization standard populations) rates of incidence, risk factors, severity, and early outcome (mortality, case-fatality, disability) were calculated, assuming a Poisson distribution for the number of events. RESULTS: Seven hundred one patients with new stroke or transient ischemic attack were ascertained (485 first-ever stroke patients, 83 recurrent stroke patients, 133 first-ever transient ischemic attack patients). Crude frequency rates (all rates per 1000 person-years) were: 1.65 (95% CI, 1.5-1.79; first-ever stroke), 0.28 (95% CI, 0.22-0.35; recurrent stroke), and 0.45 (95% CI, 0.37-0.53; first-ever transient ischemic attack). Age-adjusted stroke rates were higher than those in 9 other recent population-based samples from high-income countries. High rates of subtype-specific risk factors were observed (atrial fibrillation, 31.3% and smoking, 29.1% in ischemic stroke; warfarin use, 21.2% in primary intracerebral hemorrhage; smoking, 53.9% in subarachnoid hemorrhage; P<0.01 for all compared with other subtypes). Compared with recent studies, 28-day case-fatality rates for primary intracerebral hemorrhage (41%; 95% CI, 29.2%-54.1%) and subarachnoid hemorrhage (46%; 95% CI, 28.8%-64.5%) were greater in Dublin. CONCLUSIONS: Using gold-standard methods for case ascertainment, we found high incidence rates of stroke in Dublin compared with those in similar high-income countries; this is likely explained in part by high rates of subtype-specific risk factors.

Association between acute statin therapy, survival, and improved functional outcome after ischemic stroke: the North Dublin Population Stroke Study.

BACKGROUND AND PURPOSE: Statins improve infarct volume and neurological outcome in animal stroke models. We investigated the relationship between statin therapy and ischemic stroke outcome in the North Dublin Population Stroke Study. METHODS: A population-based prospective cohort study was performed using rigorous ascertainment methods. Prestroke and acute (≤72 hours) poststroke medications were recorded. Modified Rankin score and fatality were assessed at 7, 28, and 90 days and 1 year. RESULTS: Of 448 ischemic stroke patients, statins were prescribed before stroke onset in 30.1% (134/445) and were begun acutely (≤72 hours) in an additional 42.5% (189/445). On logistic regression analysis, adjusting for age, prestroke disability (modified Rankin scale), NIHSS score, hypertension, and aspirin, new poststroke statin therapy was independently associated with improved early and late survival (compared with statin untreated patients: OR for death, 0.12; CI, 0.03-0.54 at 7 days; OR, 0.19; CI, 0.07-0.48 at 90 days; OR, 0.26; CI, 0.12-0.55 at 1 year; P≤0.006 for all). Similar findings were observed for statin therapy before stroke onset (adjusted OR for death compared with statin-untreated-patients, 0.04; CI, 0.00-0.33; P=0.003 at 7 days; OR, 0.23; CI, 0.09-0.58; P=0.002 at 90 days; OR, 0.48; CI, 0.23-1.01; P=0.05 at 1 year). CONCLUSIONS: Statin therapy at stroke onset and newly begun statins were associated with improved early and late outcomes, supporting data from experimental studies. Randomized trials of statin therapy for treatment of acute stroke are needed.

Improved late survival and disability after stroke with therapeutic anticoagulation for atrial fibrillation: a population study.

BACKGROUND AND PURPOSE: Although therapeutic anticoagulation improves early (within 1 month) outcomes after ischemic stroke in hospital-admitted patients with atrial fibrillation, no information exists on late outcomes in unselected population-based studies, including patients with all stroke (ischemic and hemorrhagic). METHODS: We identified patients with atrial fibrillation and stroke in a prospective, population-based study in North Dublin. Clinical characteristics, stroke subtype, stroke severity (National Institutes of Health Stroke Scale), prestroke antithrombotic medication, and International Normalized Ratio (INR) at onset were documented. Modified Rankin Scale (mRS) score was measured before stroke and at 7, 28, and 90 days; 1 year; and 2 years after stroke. RESULTS: One hundred seventy-five patients had atrial fibrillation-associated stroke and medication data at stroke onset (159 ischemic, 16 hemorrhagic); 17% of those with ischemic stroke were anticoagulated before stroke (27 of 159.) On multivariable analysis, therapeutic INR was associated with improved late survival after ischemic stroke (adjusted 2-year odds ratio for death=0.08; 95% CI, 0.01 to 0.78; P=0.03). This survival benefit persisted when patients with hemorrhagic stroke were included (2-year survival; 70.5% therapeutic INR, 14.3% nontherapeutic INR; log-rank P<0.001; odds ratio for death=0.27; 95% CI, 0.09 to 0.88; P=0.03). Admission INR was inversely correlated with early and late modified Rankin Scale score (2-year Spearman ρ=-0.65; P<0.0003). An INR of 2 to 3 at ischemic stroke onset was associated with greater early (72 hours to 28 days) modified Rankin Scale score improvement (P=0.04) and good functional outcome (modified Rankin Scale score=0 to 2) at 1 year (adjusted odds ratio=4.8; 95% CI, 1.45 to 23.8; P=0.04). CONCLUSIONS: In addition to improving short-term outcome in selected hospital-treated patient groups, therapeutic anticoagulation may provide important benefits for long-term stroke outcomes in unselected populations.

Population-based study of ABCD2 score, carotid stenosis, and atrial fibrillation for early stroke prediction after transient ischemic attack: the North Dublin TIA study.

BACKGROUND AND PURPOSE: Transient ischemic attack (TIA) etiologic data and the ABCD(2) score may improve early stroke risk prediction, but studies are required in population-based cohorts. We investigated the external validity of the ABCD(2) score, carotid stenosis, and atrial fibrillation for prediction of early recurrent stroke after TIA. METHODS: Patients with TIA in the North Dublin city population (N=294 529) were ascertained by using overlapping hospital and community sources. The relations between individual ABCD(2) items, carotid stenosis, atrial fibrillation, and early stroke were examined. RESULTS: In confirmed TIA cases (n=443), carotid stenosis predicted 90-day stroke (hazard ratio=2.56; 95% CI, 1.27 to 5.15, P=0.003). Stroke risk rose with increasing grade of carotid stenosis, ranging from 5.4% (95% CI, 3.3% to 8.7%) with <50% stenosis to 17.2% (95% CI, 9.7% to 29.7%) with severe stenosis/occlusion (hazard ratio=3.3; 95% CI, 1.5 to 7.4, P=0.002). In confirmed TIA cases (n=443), the ABCD(2) score performed no better than chance for prediction of 90-day stroke (c-statistic=0.55; 95% CI, 0.45 to 0.64), largely related to the 24.2% (8/33) of patients who experienced a recurrence and had low ABCD(2) scores (0-3). However, in nonspecialist-suspected TIA cases (n=700), the predictive utility improved for stroke at 28 (c-statistic=0.61; 95% CI, 0.50 to 0.72) and 90 (c-statistic=0.61; 95% CI, 0.52 to 0.71) days. CONCLUSIONS: In a population-based TIA cohort, significant predictive information was provided by carotid stenosis. The ABCD(2) score had predictive utility in patients with TIA suspected by nonspecialists. Low scores occurred in several patients with stroke recurrences, suggesting that caution is needed before using the score in isolation.

Stroke subtype classification to mechanism-specific and undetermined categories by TOAST, A-S-C-O, and causative classification system: direct comparison in the North Dublin population stroke study.

BACKGROUND AND PURPOSE: Reliable etiologic classification of ischemic stroke may enhance clinical trial design and identification of subtype-specific environmental and genetic risk factors. Although new classification systems (Causative Classification System [CCS] and ASCO [A for atherosclerosis, S for small vessel disease, C for cardiac source, O for other cause]) have been developed to improve subtype assignment, few comparative data exist from large studies. We hypothesized that both CCS and ASCO would reduce the proportion of patients classified as cause undetermined compared with the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) scheme in a large population-based stroke study. METHODS: A single rater classified all first-ever ischemic strokes in the North Dublin Population Stroke Study, a population-based study of 294 529 North Dublin residents. Published algorithms for TOAST, CCS, and ASCO were applied. RESULTS: In 381 first-ever ischemic stroke patients, CCS assigned fewer patients as cause undetermined (26.2% versus 39.4%; P<0.000001), with increased assignment of cardio-aortic embolism (relative increase 6.9%; P=0.004), large artery atherosclerosis (relative increase 44.1%; P=0.00006), small artery occlusion (relative increase 27.3%; P=0.00006), and other causes (relative increase 91.7%; P=0.001) compared with TOAST. When ASCO grade 1 evidence was applied, fewer patients were classified as small artery disease (relative decrease 29.1%; P=0.007) and more as large artery/atherothrombotic (relative increase 17.6%; P=0.03). ASCO grade 1 did not reduce the proportion of cause undetermined cases compared with TOAST (42.3% versus 39.4%; P=0.2). Agreement between systems ranged from good (kappa=0.61 for TOAST/ASCO grade 1 small artery category) to excellent (kappa=0.95 for TOAST/CCS and ASCO grade 1/CCS cardio/aorto-embolism category). Application of ASCO grades 1 to 3 indicated evidence of large artery/atherosclerosis (73.3%), cardio-embolism (31.3%), small artery (64.7%), and other cause (12%) in TOAST-undetermined cases. CONCLUSIONS: Both CCS and ASCO schemes showed good-to-excellent agreement with TOAST, but each had specific characteristics compared with TOAST for subtype assignment and data retention. The feasibility of a single combined classification system should be considered.

Stroke associated with atrial fibrillation--incidence and early outcomes in the north Dublin population stroke study.

BACKGROUND: Prospective population-based studies are important to accurately determine the incidence and characteristics of stroke associated with atrial fibrillation (AF), while avoiding selection bias which may complicate hospital-based studies. METHODS: We investigated AF-associated stroke within the North Dublin Population Stroke Study, a prospective cohort study of stroke/transient ischaemic attack in 294,592 individuals, according to recommended criteria for rigorous stroke epidemiological studies. RESULTS: Of 568 stroke patients ascertained in the first year, 31.2% (177/568) were associated with AF (90.4%, i.e. 160/177 ischaemic infarcts). The crude incidence rate of all AF-associated stroke was 60/100,000 person-years (95% CI = 52-70). Prior stroke was almost twice as common in AF compared to non-AF groups (21.9 vs. 12.8%, p = 0.01). The frequency of AF progressively increased across ischaemic stroke patients stratified by increasing stroke severity (NIHSS 0-4, 29.7%; 5-9, 38.1%; 10-14, 43.8%; >or=15, 53.3%, p < 0.0001). The 90-day trajectory of recovery of AF-associated stroke was identical to that of non-AF stroke, but Rankin scores in AF stroke remained higher at 7, 28 and 90 days (p < 0.001 for all). DISCUSSION: AF-associated stroke occurred in one third of all patients and was associated with a distinct profile of recurrent, severe and disabling stroke. Targeted strategies to increase anticoagulation rates may provide a substantial benefit to prevent severe disabling stroke at a population level.

Diagnostic usefulness of the ABCD2 score to distinguish transient ischemic attack and minor ischemic stroke from noncerebrovascular events: the North Dublin TIA Study.

BACKGROUND AND PURPOSE: Transient ischemic attack (TIA) diagnosis is frequently difficult in clinical practice. Noncerebrovascular symptoms are often misclassified as TIA by nonspecialist physicians. Clinical prediction rules such as ABCD(2) improve the identification of patients with TIA at high risk of early stroke. We hypothesized that the ABCD(2) score may partly improve risk stratification due to improved discrimination of true TIA and minor ischemic stroke (MIS) from noncerebrovascular events. METHODS: Consecutive patients with TIA were identified within a prospective population-based cohort study of stroke and TIA. The cohort was expanded by inclusion of patients with MIS and noncerebrovascular events referred to a daily TIA clinic serving the population. Diagnosis was assigned by a trained stroke physician independent of ABCD(2) score. RESULTS: Five hundred ninety-four patients were included (292 [49.2%] TIA, 45 [7.6%] MIS, and 257 [43.3%] noncerebrovascular). The mean ABCD(2) score showed a graded increase across diagnostic groups (MIS mean 4.8 [SD 1.4] versus TIA mean 3.9 [SD 1.5] versus noncerebrovascular mean 2.9 [SD 1.5]; P<0.00001). The ABCD(2) score discriminated well between noncerebrovascular and cerebrovascular events-TIA (c-statistic 0.68; 95% CI, 0.64 to 0.72), any vascular event (TIA+MIS; c-statistic 0.7; 95% CI, 0.66 to 0.74), and MIS (c-statistic 0.81; 95% CI, 0.75 to 0.87)-from noncerebrovascular events. Of ABCD(2) items, unilateral weakness (OR, 4.5; 95% CI, 3.1 to 6.6) and speech disturbance (OR, 2.5; 95% CI, 1.6, 4.1) were most likely overrepresented in TIA compared with noncerebrovascular groups. CONCLUSIONS: The ABCD(2) score had significant diagnostic usefulness for discrimination of true TIA and MIS from noncerebrovascular events, which may contribute to its predictive usefulness.

The value of ambulatory blood pressure in older adults: the Dublin outcome study.

BACKGROUND: ambulatory blood pressure (ABPM) appears to be a more accurate predictor of cardiovascular outcome than blood pressure (BP) measured in the clinic setting in younger adults. OBJECTIVES: the purpose of this study was to determine if ABPM predicted total and cardiovascular mortality independently of clinic BP and other cardiovascular risk factors in those aged 65 years and over. METHODS: one thousand one hundred and forty-four individuals aged 65 and over referred to a single BP clinic had 24-h ABP measurement and clinic measurement at baseline off treatment. There were 385 deaths (of which 246 were cardiovascular) during a mean follow-up period of 6.7 years. RESULTS: with adjustment for gender, age, risk indices and also for clinic BP, a higher mean value of ABPM was an independent predictor of cardiovascular mortality. The relative hazard ratio for each 10-mmHg rise in systolic blood pressure (SBP) was 1.10 (1.06-1.18, P < 0.001) for daytime and 1.18 (1.11-1.25, P < 0.001) for night-time SBP. The hazard ratios for each 5-mmHg rise in diastolic blood pressure (DBP) were 1.05 (1.00-1.10, P = NS) for daytime and 1.09 (1.04-1.14, P < 0.001) for night-time diastolic pressure. The hazard ratios for night-time ABPM remained significant after adjustment for daytime ABPM. CONCLUSIONS: ambulatory measurement of BP is superior to clinic measurement in predicting cardiovascular mortality in elderly subjects. Night-time BP is the strongest predictor of outcome in this age group.

Ambulatory arterial stiffness index: rationale and methodology.

OBJECTIVES: Increased arterial stiffness is associated with the development of cardiovascular disease and may even predict its development at an early stage. Increased pulse pressure is seen as a marker of increased arterial stiffness and can be readily measured by ambulatory blood pressure monitoring. We propose another surrogate measure of arterial stiffness derived from ambulatory blood pressure monitoring that may predict cardiovascular mortality over and above pulse pressure, namely, the dynamic relationship between diastolic and systolic blood pressure over 24 h--the ambulatory arterial stiffness index. METHODS: Using all blood pressure readings over the 24-h period from 11 291 (5965 women; mean age 54.6 years) patients referred for ambulatory blood pressure monitoring to a blood pressure clinic, diastolic blood pressure was plotted against systolic blood pressure, and the regression slope was calculated; ambulatory arterial stiffness index was defined as one minus this regression slope. RESULTS: Both ambulatory arterial stiffness index and pulse pressure were higher in women (0.42 vs. 0.40 and 57.0 vs. 55.3 mmHg, respectively). For the entire group, the correlation between ambulatory arterial stiffness index and pulse pressure was 0.5. CONCLUSIONS: Ambulatory arterial stiffness index is a new measure that is readily available from ambulatory blood pressure monitoring and may provide added prognostic information for cardiovascular outcome.

Effects of immediate versus delayed antihypertensive therapy on outcome in the Systolic Hypertension in Europe Trial.

BACKGROUND: To assess the impact of immediate versus delayed antihypertensive treatment on the outcome of older patients with isolated systolic hypertension, we extended the double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) trial by an open-label follow-up study lasting 4 years. METHODS: The Syst-Eur trial included 4695 randomized patients with minimum age of 60 years and an untreated blood pressure of 160-219 mmHg systolic and below 95 mmHg diastolic. The double-blind trial ended after a median follow-up of 2.0 years (range 1-97 months). Of 4409 patients still alive, 3517 received open-label treatment consisting of nitrendipine (10-40 mg daily) with the possible addition of enalapril (5-20 mg daily), hydrochlorothiazide (12.5-25 mg daily), or both add-on drugs. Non-participants (n = 892) were also followed up. RESULTS: Median follow-up increased to 6.1 years. Systolic pressure decreased to below 150 mmHg (target level) in 2628 participants (75.0%). During the 4-year open-label follow-up, stroke and cardiovascular complications occurred at similar frequencies in patients formerly randomized to placebo and those continuing active treatment. These rates were similar to those previously observed in the active-treatment group during the double-blind trial. Considering the total follow-up of 4695 randomized patients, immediate compared with delayed antihypertensive treatment reduced the occurrence of stroke and cardiovascular complications by 28% (P = 0.01) and 15% (P = 0.03), respectively, with a similar tendency for total mortality (13%, P = 0.09). In 492 diabetic patients, the corresponding estimates of long-term benefit (P < 0.02) were 60, 51 and 38%, respectively. CONCLUSIONS: Antihypertensive treatment can achieve blood pressure control in most older patients with isolated systolic hypertension. Immediate compared with delayed treatment prevented 17 strokes or 25 major cardiovascular events per 1000 patients followed up for 6 years. These findings underscore the necessity of early treatment of isolated systolic hypertension.

Ambulatory blood pressure measurement as a predictor of outcome in an Irish population: methodology for ascertaining mortality outcome.

BACKGROUND: Ambulatory blood pressure monitoring (ABPM) has proven to be a superior predictor of morbid events when compared to clinic or office blood pressure measurement (CBPM). The purpose of this study was to evaluate the predictive value of ABPM in a sample of 14 414 people referred for management of cardiovascular risk. METHODS: In this paper we describe the methodology required to examine mortality outcome in the absence of a national unique identifier. RESULTS: Using a computerized database of deaths we were able to establish that 1348 people had died by the end of the follow-up period (30 September 2002). Sixty-four percent of deaths were cardiovascular and in 207 subjects who had post-mortem examinations, 78% were cardiovascular. CONCLUSIONS: The accurate identification of the cause of death in a large population will allow comparison of the relative predictive power of APBM and CBPM in an Irish population.

Yellow nail pigmentation following Depakote therapy.

Two months after being started on Depakote (divalproex sodium: Abbott Laboratories Inc., Abbott Park, Illinois), a 57-year-old female noticed the development of a transverse yellow band on all 20 proximal nails that eventually led to complete nail plate discoloration. Six to eight weeks after discontinuation of Depakote, normalization of her proximal nail plates was noted. Other anticonvulsants such as phenytoin and lithium have been documented to lead to nail pigmentation. Although several dermatologic reactions to Depakote have been described, we are not aware of any reported cases of nail discoloration secondary to Depakote. While our patient did have a history of renal disease with azotemia, we find it highly unlikely to be a contributing factor secondary to the fact that our patient's abnormality did not present similar to the nail abnormalities of renal disease. In conclusion, we found the temporal relationship between Depakote initiation/discontinuation and the nail discoloration to be highly indicative of Depakote as the source. Other anticonvulsants such as phenytoin and lithium have been documented to lead to nail pigmentation. Although several dermatologic reactions to Depakote have been described, we are not aware of any reported cases of nail discoloration secondary to Depakote. While our patient did have a history of renal disease with azotemia, we find it highly unlikely to be a contributing factor secondary to the fact that our patient's abnormality did not present similar to the nail abnormalities of renal disease. In conclusion, we found the temporal relationship between Depakote initiation/discontinuation and the nail discoloration to be highly indicative of Depakote as the source.

Ambulatory arterial stiffness index as a predictor of cardiovascular mortality in the Dublin Outcome Study.

We hypothesized that the dynamic relation between diastolic and systolic blood pressure over 24 hours provides a measure of arterial stiffness and might, therefore, predict cardiovascular mortality over and above pulse pressure. At baseline, while not on antihypertensive medication, 11 291 patients (mean age, 54.6 years; 5965 women) underwent ambulatory blood pressure monitoring. Using all of the blood pressure readings, we plotted diastolic against systolic blood pressure from each individual and calculated the regression slope. The ambulatory arterial stiffness index (AASI) was defined as 1 minus this regression slope. Over a median follow-up of 5.3 years, 566 cardiovascular deaths occurred, including 151 from stroke and 358 from cardiac disorders. Before and after adjustment for other cardiovascular risk factors, AASI and pulse pressure significantly predicted total cardiovascular mortality. AASI was a stronger predictor than pulse pressure for stroke (mutually adjusted relative hazard ratios for 1 SD increase, 1.21 versus 1.04; P=0.02 versus 0.66) with the opposite trend for cardiac mortality (relative hazard ratios, 1.03 versus 1.21; P=0.63 versus 0.002). In subjects with normal daytime ambulatory blood pressure (<135/<85 mm Hg), AASI was more predictive than pulse pressure of cardiovascular mortality (1.26 versus 0.96; P=0.04 versus 0.70) and of stroke mortality (1.81 versus 1.12; P=0.007 versus 0.58), whereas neither independently predicted cardiac mortality (1.11 versus 0.89; P=0.47 versus 0.40). AASI is a novel measure of arterial stiffness, which can be readily determined from ambulatory blood pressure recordings and which independently predicts cardiovascular mortality, even in normotensive subjects.

Superiority of ambulatory over clinic blood pressure measurement in predicting mortality: the Dublin outcome study.

The purpose of this study was to determine if ambulatory blood pressure measurement predicted total and cardiovascular mortality over and beyond clinic blood pressure measurement and other cardiovascular risk factors; 5292 untreated hypertensive patients referred to a single blood pressure clinic who had clinic and ambulatory blood pressure measurement at baseline were followed up in a prospective study of mortality outcome. Multiple Cox regression was used to model time to total and cause-specific mortality for ambulatory blood pressure measurement while adjusting for clinic blood pressure measurement and other risk factors at baseline. There were 646 deaths (of which 389 were cardiovascular) during a median follow-up period of 8.4 years. With adjustment for gender, age, risk indices, and clinic blood pressure, higher mean values of ambulatory blood pressure were independent predictors for cardiovascular mortality. The relative hazard ratio for each 10-mm Hg increase in systolic blood pressure was 1.12 (1.06 to 1.18; P<0.001) for daytime and 1.21 (1.15 to 1.27; P<0.001) for nighttime systolic blood pressure. The hazard ratios for each 5-mm Hg increase in diastolic blood pressure were 1.02 (0.99 to 1.07; P=NS) for daytime and 1.09 (1.04 to 1.13; P<0.01) for nighttime diastolic pressures. The hazard ratios for nighttime ambulatory blood pressure remained significant after adjustment for daytime ambulatory blood pressure. These results have 2 important clinical messages: ambulatory measurement of blood pressure is superior to clinic measurement in predicting cardiovascular mortality, and nighttime blood pressure is the most potent predictor of outcome.

Gouty tophi: a squamous cell carcinoma mimicker?

BACKGROUND: Digital lesions can have a broad differential diagnosis. Squamous cell carcinoma (SCC), the most common digital malignant neoplasm, must be excluded as the cause of persistent digital lesions causing nail dystrophy. OBJECTIVE: To describe a patient with a periungual hyperkeratotic lesion on the left fifth digit which, upon initial dermatopathologic examination, appeared to be a malignancy. However, on further biopsy, the lesion proved to be a gouty tophus. METHODS: Case report and literature review. RESULTS: An 84-year-old white man presented with a hyperkeratotic papule on the lateral proximal nail fold of the left fifth digit, which resulted in nail dystrophy for 1 year. Similar lesions were present on several other digits which did not affect the nail plate. Initial biopsy was consistent with actinic keratosis and was treated with cryotherapy. When the lesion persisted, repeat biopsy was performed, demonstrating fragments of squamous epithelium with focal atypia and an infiltrative growth pattern. SCC could not be excluded and the patient was referred for Mohs micrographic surgery (MMS) consultation. An excisional biopsy was performed and a white chalky material was observed at the base of the defect. Histopathology confirmed a gouty tophus. The patient was referred to his primary care physician and was treated with allopurinol. CONCLUSION: This is the first report of gouty tophus of the periungual region presenting as a hyperkeratotic lesion. Initial clinical diagnosis favored SCC and histologic evidence suggested a possible early SCC. This lesion can be confused with digital squamous cell carcinoma. The presence of pseu- docarcinomatous hyperplasia may complicate accurate diagnosis.

Exposure to low infective doses of HCV induces cellular immune responses without consistently detectable viremia or seroconversion in chimpanzees.

In hepatitis C virus (HCV) infection, there is accumulating data suggesting the presence of cellular immune responses to HCV in exposed but seemingly uninfected populations. Some studies have suggested cross-reactive antigens rather than prior HCV exposure as the main reason for the immune responses. In this study we address this question by analyzing the immune response of chimpanzees that have been sequentially exposed to increasing doses of HCV virions. The level of viremia, as well as the immune responses to HCV at different times after virus inoculation, were examined. Our data indicate that HCV infective doses as low as 1-10 RNA (+) virions induce detectable cellular immune responses in chimpanzees without consistently detectable viremia or persistent seroconversion. However, increasing the infective doses of HCV to 100 RNA (+) virions overcame the low-inoculum-induced immune response and produced high-level viremia followed by seroconversion.