Dandruff: a condition characterized by decreased levels of intercellular lipids in scalp stratum corneum and impaired barrier function.

Dandruff is a major problem, yet little is known about the underlying mechanism and subsequent biochemical changes occurring in the scalp skin that lead to its manifestation. The characteristic flaking and scaling of the scalp experienced by dandruff sufferers suggests, similar to the changes classically seen in xerosis, that the desquamation process is impaired. We initiated studies to quantify the biochemical nature of the stratum corneum in the scalp of healthy individuals and dandruff sufferers. Total amounts and relative ratios of stratum corneum lipids species were analysed in scalp stratum corneum samples collected during studies conducted in the UK and Thailand in order to examine ethnic differences. In both populations, dandruff was associated with a dramatic decrease in free lipid levels, with significant decreases in ceramides, fatty acids, and cholesterol. Detailed sub-analysis of the major ceramide species within the total ceramide fraction revealed a decrease in ceramide 1 and increased proportions of ceramide 6i and 6ii. In a separate study, we demonstrated that dandruff sufferers show both an elevated blood flow and an increased reported incidence of itch in response to histamine topically applied to the scalp compared with no-dandruff controls. Taken together these two studies indicate that the quality and resilience of the epidermal water barrier is impaired in the scalp of dandruff sufferers. We propose that the perturbed barrier leaves dandruff sufferers more prone to the adverse effects of microbial and fungal toxins, and environmental pollutants, thus perpetuating their impaired barrier.

Prognosis after transient monocular blindness associated with carotid-artery stenosis.

BACKGROUND: Transient monocular blindness associated with internal-carotid-artery stenosis is a risk factor for stroke. The effect of carotid endarterectomy in patients who present with transient monocular blindness has not been determined. METHODS: We compared the risk of stroke among patients presenting with transient monocular blindness with the risk among patients presenting with hemispheric transient ischemic attack. The effect of endarterectomy was assessed in patients with transient monocular blindness. The analyses were based on data from the North American Symptomatic Carotid Endarterectomy Trial. RESULTS: A total of 198 medically treated patients with transient monocular blindness had a three-year risk of ipsilateral stroke that was approximately half of that among 417 medically treated patients with hemispheric transient ischemic attack (adjusted hazard ratio, 0.53; 95 percent confidence interval, 0.30 to 0.94). Six factors were associated with a higher risk of stroke in patients with monocular blindness--an age of 75 years or more, male sex, a history of hemispheric transient ischemic attack or stroke, a history of intermittent claudication, stenosis of 80 to 94 percent of the luminal diameter, and the absence of collateral circulation. The three-year risk of stroke with medical treatment for patients with zero or one risk factor was 1.8 percent, with two risk factors 12.3 percent, and with three or more risk factors 24.2 percent (P=0.003). The three-year absolute reduction in the risk of stroke associated with endarterectomy was -2.2 percent (i.e., a 2.2 percent increase in risk) among patients with zero or one risk factor, 4.9 percent among those with two risk factors, and 14.3 percent among those with three or more risk factors (P=0.23 by a test for interaction). CONCLUSIONS: Among patients with internal-carotidartery stenosis, the prognosis was better for those presenting with transient monocular blindness than for those presenting with hemispheric transient ischemic attack. Among patients with transient monocular blindness, carotid endarterectomy may be beneficial when other risk factors for stroke are also present.

Risk, causes, and prevention of ischaemic stroke in elderly patients with symptomatic internal-carotid-artery stenosis.

BACKGROUND: Carotid endarterectomy benefits patients with symptomatic stenosis of 70-99% in the internal carotid artery, with smaller benefit for 50-69% stenosis. The benefit of carotid endarterectomy in patients of 75 years and older remains unclear. METHODS: Patients aged 75 years or older from the North American Symptomatic Carotid Endarterectomy Trial were compared with those aged 65-74 years and less than 65 years for baseline characteristics and risk of ipsilateral ischaemic stroke at 2 years by degree of stenosis and treatment group. FINDINGS: Among patients with 70-99% stenosis, the absolute risk reduction of ipsilateral ischaemic stroke with carotid endarterectomy was 28.9% (95% CI 12.9-44.9) for patients aged 75 years or older (n=71), 15.1% (7.2-23.0) for those aged 65-74 years (n=285), and 9.7% (1.5-17.9) for the youngest group (n=303). Among patients with 50-69% stenosis, the absolute risk reduction was significant only in those of 75 years and older (n=145; 17.3% [6.6-28.0]). The perioperative risk of stroke and death at any degree of stenosis was 5.2% for the oldest group, 5.5% for 65-74 years, and 7.9% for less than 65 years. The number of patients aged 75 years or older needed to treat to prevent one ipsilateral stroke within 2 years was three with 70-99% stenosis and six with 50-69% stenosis. INTERPRETATION: In the prevention of ipsilateral ischaemic stroke, elderly patients with 50-99% symptomatic carotid stenosis benefited more from carotid endarterectomy than younger patients did. To achieve this treatment benefit, surgeons must be skilled and patients with other life-threatening illnesses must be excluded.

Endarterectomy for carotid stenosis: new approaches in patient selection.

Results of randomized trials on carotid endarterectomy make it mandatory that therapeutic decisions for patients with carotid stenosis consider the degree of stenosis, presence of symptoms, skill of surgeon and time since the last ischemic event. Patients with severe (>70% by angiogram) stenosis should receive carotid endarterectomy, provided the operative risk is <6% and symptoms have recurred within 6 months. With moderate stenosis (50--69% by angiogram), and with similar low operative risk and time limit, males with hemispheric, nondisabling stroke and appropriate CT lesion will benefit from carotid endarterectomy. Patients with TIA only, retinal symptoms alone and who are women are not going to benefit in this range of stenosis. Particularly at risk with medical care alone are symptomatic patients with coexistent intracranial stenosis, widespread white-matter lesions, intraluminal thrombi, contralateral occlusion and absence of good collateral circulation. The same high-risk patients, enjoy good long-term results from endarterectomy. Lacunar syndromes at presentation respond to endarterectomy, but with less benefit. Symptomatic patients do as well, regardless of age, provided patients with serious cardiac disorders and with organ failure are avoided. Serious doubt exists about indications for endarterectomy in asymptomatic subjects. Even if the upper limit of 3% perioperative risk is exceeded (and in large institutional databases and other studies, it usually is), the risk of large-artery strokes from the asymptomatic lesion is only slightly above the risk facing these subjects from lacunar and cardioembolic stroke. To prevent 1 large-artery stroke in 5 years in asymptomatic subjects requires that 111 subjects be submitted to endarterectomy.

Appropriate use of carotid endarterectomy.

When stroke-threatening symptoms derive from the extracranial portion of a carotid artery, endarterectomy becomes a consideration. The available evidence indicates clear benefit for patients with a severe symptomatic stenosis. For asymptomatic carotid disease, the risk of a surgical complication may contraindicate the procedure.

Long-term clinical and angiographic outcomes in symptomatic patients with 70% to 99% carotid artery stenosis.

BACKGROUND AND PURPOSE: In 1991, the North American Symptomatic Carotid Endarterectomy Trial (NASCET) reported the benefit of carotid endarterectomy for 659 patients with 70% to 99% stenosis. Follow-up continued until 1997. METHODS: The present study examined the risks and causes of ipsilateral stroke in the randomized groups and in those who had delayed endarterectomy or continued on medical therapy and also examined the evolution of carotid disease on follow-up imaging. RESULTS: By on-treatment (efficacy) analysis, the risk of any ipsilateral stroke at 3 years was 28.3% for medically randomized and 8.9% for surgically randomized patients (19.4% absolute risk reduction, P:<0.001). For combined disabling or fatal ipsilateral stroke, the risks were 14.0% and 3.4%, respectively (10. 6% absolute risk reduction). In medical patients, >80% of the first strokes at 3 years were of large-artery origin. After February 1991, 116 suitable medical patients underwent endarterectomy within 6 months, and 115 continued on medical therapy. The 3-year risk of any ipsilateral stroke in the groups of 116 and 115 patients was 7.9% and 15.0%, respectively (7.1% absolute risk reduction). During follow-up, 81 patients had angiograms comparable to the baseline images. Progression by >/=10% occurred in 7 patients; regression, in 8; no change, in 39; and occlusion, in 27. By use of both angiography and ultrasound, 63 (25.5%) of the 247 medically treated patients progressed to occlusion, of whom 31.7% had an ipsilateral stroke before or on the day of occlusion. CONCLUSIONS: Endarterectomy for patients with 70% to 99% stenosis and recent symptoms was efficacious in the long term. Compared with patients who continued on medical therapy, medical patients with delayed endarterectomy experienced a moderate benefit. Medically treated patients experienced a high risk of occlusion.

The causes and risk of stroke in patients with asymptomatic internal-carotid-artery stenosis. North American Symptomatic Carotid Endarterectomy Trial Collaborators.

BACKGROUND: The causes of stroke in patients with asymptomatic carotid-artery stenosis have not been carefully studied. Information about causes might influence decisions about the use of carotid endarterectomy in such patients. METHODS: We studied patients with unilateral symptomatic carotid-artery stenosis and asymptomatic contralateral stenosis from 1988 to 1997. The causes, severity, risk, and predictors of stroke in the territory of the asymptomatic artery were examined and quantified. RESULTS: The risk of stroke at five years after study entry in a total of 1820 patients increased with the severity of stenosis. Among 1604 patients with stenosis of less than 60 percent of the luminal diameter, the risk of a first stroke was 8.0 percent (1.6 percent annually), as compared with 16.2 percent (3.2 percent annually) among 216 patients with 60 to 99 percent stenosis. In the group with 60 to 99 percent stenosis, the five-year risk of stroke in the territory of a large artery was 9.9 percent, that of lacunar stroke was 6.0 percent, and that of cardioembolic stroke 2.1 percent. Some patients had more than one stroke of more than one cause. In the territory of an asymptomatic occluded artery (as was identified in 86 patients), the annualized risk of stroke was 1.9 percent. Strokes with different causes had different risk factors. The risk factors for large-artery stroke were silent brain infarction, a history of diabetes, and a higher degree of stenosis; for cardioembolic stroke, a history of myocardial infarction or angina and hypertension; for lacunar stroke, age of 75 years or older, hypertension, diabetes, and a higher degree of stenosis. CONCLUSIONS: The risk of stroke among patients with asymptomatic carotid-artery stenosis is relatively low. Forty-five percent of strokes in patients with asymptomatic stenosis of 60 to 99 percent are attributable to lacunes or cardioembolism. These observations have implications for the use of endarterectomy in asymptomatic patients. Without analysis of the risk of stroke according to cause, the absolute benefit associated with endarterectomy may be overestimated.

Causes and severity of ischemic stroke in patients with internal carotid artery stenosis.

CONTEXT: Therapeutic trials generally have not distinguished outcomes of stroke according to cause. OBJECTIVE: To determine whether stroke and subsequent disability was of large-artery, lacunar, or cardioembolic origin in patients with different degrees of symptomatic and asymptomatic carotid stenosis. DESIGN: Observational study of prospective data collected from the North American Symptomatic Carotid Endarterectomy Trial between 1987 and 1997. SETTING AND PATIENTS: A total of 2885 patients from 106 sites in the United States and abroad (median age, 67 years; 70% male) who had symptomatic internal carotid artery stenosis. MAIN OUTCOME MEASURE: Risk of stroke from each of the 3 causes at 5 years by territory and degree of stenosis. RESULTS: During an average follow-up of 5 years, 749 patients had 1039 strokes, including 112 of cardioembolic, 211 of lacunar, 698 of large-artery, 17 of primary intracerebral hemorrhage, and 1 of subarachnoid hemorrhage origin. The 5-year risk of first stroke after entry into the trial in any territory was 2.6% of cardioembolic cause, 6.9% of lacunar cause, and 19.7% of large-artery cause. The proportion of cardioembolic strokes in the territory of the symptomatic artery was 12.0% and 6.9% in 60% to 69% and 70% to 99% arterial stenosis, respectively; large-artery strokes predominated (78.4%) at 70% to 99% arterial stenosis. With 70% to 99% arterial stenosis, the proportion of strokes of cardioembolic and lacunar origin was 43.5% and 21.6% in asymptomatic and symptomatic arteries, respectively. A total of 67.6% of cardioembolic, 16.7% of lacunar, and 33.0% of large-artery strokes in the territory of the asymptomatic artery were disabling or fatal. CONCLUSIONS: Our data suggest that approximately 20% and 45% of strokes in the territory of symptomatic and asymptomatic carotid arteries with 70% to 99% stenosis, respectively, are unrelated to carotid stenosis. The cause of subsequent strokes in similar types of patients should be considered when making treatment decisions involving carotid endarterectomy for patients with asymptomatic carotid stenosis, since lacunar and cardioembolic strokes cannot be prevented by endarterectomy.

Capturing the paradigm shift in HIV treatment: changing attitudes in the choice of combination antiretroviral drugs by high HIV caseload Australian GPs (1996-1997).

The use of combination antiretroviral therapy for HIV infection is a rapidly changing field. To assess the impact of recent studies on prescribing patterns, two surveys of 21 high HIV caseload Australian GPs were undertaken in June 1996 and June 1997 to plot changes in the choice of combination antiviral therapy. Of the 17 GPs who responded to the survey in each year, the number of HIV-infected patients seen at their practices were estimated to be 5,061 in 1996 and 5,912 in 1997. In 1996, 40% of their patients were estimated to be on antiretroviral therapy compared to 60% in 1997 (p < 0.05). In 1996, most GPs preferred using dual combination therapy (59%); whereas in 1997, triple combination therapy was preferred (82%). Between 1996 and 1997, there was a significant change by high caseload Australian GPs in the choice of antiretroviral drugs with many combinations being preferred prior to presentation of efficacy data for those combinations, or recommendation through national guidelines.

Benefit of carotid endarterectomy in patients with symptomatic moderate or severe stenosis. North American Symptomatic Carotid Endarterectomy Trial Collaborators.

BACKGROUND: Previous studies have shown that carotid endarterectomy in patients with symptomatic severe carotid stenosis (defined as stenosis of 70 to 99 percent of the luminal diameter) is beneficial up to two years after the procedure. In this clinical trial, we assessed the benefit of carotid endarterectomy in patients with symptomatic moderate stenosis, defined as stenosis of less than 70 percent. We also studied the durability of the benefit of endarterectomy in patients with severe stenosis over eight years of follow-up. METHODS: Patients who had moderate carotid stenosis and transient ischemic attacks or nondisabling strokes on the same side as the stenosis (ipsilateral) within 180 days before study entry were stratified according to the degree of stenosis (50 to 69 percent or <50 percent) and randomly assigned either to undergo carotid endarterectomy (1108 patients) or to receive medical care alone (1118 patients). The average follow-up was five years, and complete data on outcome events were available for 99.7 percent of the patients. The primary outcome event was any fatal or nonfatal stroke ipsilateral to the stenosis for which the patient underwent randomization. RESULTS: Among patients with stenosis of 50 to 69 percent, the five-year rate of any ipsilateral stroke (failure rate) was 15.7 percent among patients treated surgically and 22.2 percent among those treated medically (P=0.045); to prevent one ipsilateral stroke during the five-year period, 15 patients would have to be treated with carotid endarterectomy. Among patients with less than 50 percent stenosis, the failure rate was not significantly lower in the group treated with endarterectomy (14.9 percent) than in the medically treated group (18.7 percent, P=0.16). Among the patients with severe stenosis who underwent endarterectomy, the 30-day rate of death or disabling ipsilateral stroke persisting at 90 days was 2.1 percent; this rate increased to only 6.7 percent at 8 years. Benefit was greatest among men, patients with recent stroke as the qualifying event, and patients with hemispheric symptoms. CONCLUSIONS: Endarterectomy in patients with symptomatic moderate carotid stenosis of 50 to 69 percent yielded only a moderate reduction in the risk of stroke. Decisions about treatment for patients in this category must take into account recognized risk factors, and exceptional surgical skill is obligatory if carotid endarterectomy is to be performed. Patients with stenosis of less than 50 percent did not benefit from surgery. Patients with severe stenosis (> or =70 percent) had a durable benefit from endarterectomy at eight years of follow-up.

Do the facts and figures warrant a 10-fold increase in the performance of carotid endarterectomy on asymptomatic patients?

The detailed results of the Asymptomatic Carotid Atherosclerosis Study (ACAS) have been published. Electrifying reports in the media suggested that 53% fewer strokes would occur if individuals with 60% or greater stenosis were submitted to endarterectomy. The burning question is whether the evidence from this trial, and those preceding it, is sufficiently compelling to persuade any or all individuals with carotid stenosis, but free of any hemisphere and retinal symptoms, to have carotid endarterectomy. Based on a variety of population samplings, it is reasonable to estimate that approximately two million people are living in North America and Europe with asymptomatic lesions comparable with those studied in the ACAS.