Cutaneous leishmaniasis treated with itraconazole.

Leishmaniasis is a human disease produced by a parasite of the Leishmania genus transmitted by prick of an infected female sandfly. The disease occurs clinically with either cutaneous, mucocutaneous or visceral form, depending on the infective species and the immune status of the patient. Antimonial drugs are the current treatment of choice for all clinical forms. We report a case of cutaneous Leishmaniasis in a young girl successfully treated with itraconazole.

Tinea capitis mimicking tufted hair folliculitis.

We report a case of tinea capitis mimicking tufted hair folliculitis in a 56-year-old European man, who presented with a 4-year history of pain and erythema in an area of scarring alopecia of the occipital scalp, with scales and tufts of hair emerging from individual follicles. Histological examination showed hair plugging, and a dense perifollicular infiltrate of plasma cells, lymphocytes, and neutrophils. There was widespread scarring and fibrosis. Bacterial cultures were negative for Staphylococcus aureus, but fungal cultures and periodic-acid-Schiff stain were positive for Trichophyton tonsurans. Videodermatoscopy of the lesion showed a pattern consistent with folliculitis decalvans. Diagnosis was made on the basis of the clinical, histological, microbiological and videodermatoscopy data. After 30 days of systemic antifungal treatment, there were a substantial clinical improvement and disappearance of pain. After 5 months, a residual cicatricial area was seen with some hair tufts emerging from a single orifice.

Cefuroxime-induced pemphigus erythematosus in a young boy.

Pemphigus erythematosus (Senear-Usher syndrome) is a variant of superficial pemphigus with features of both lupus erythematosus and pemphigus. It affects mainly middle-aged adults, and is rarely observed before the age of 20 years. The case of a 14-year-old boy who showed cutaneous lesions suggestive for pemphigus erythematosus is described. Not all laboratory and histopathological investigations confirmed the hypothesis, so a diagnosis of clinical pemphigus erythematosus was made. Systemic steroid therapy was effective in controlling the disease. This case is interesting because of the rare occurrence of pemphigus erythematosus in adolescence and the possibility of another drug being added to the list of pemphigus inducers.

Non-invasive vascular detection of early signs of atherosclerosis in hypercholesterolemic children: why and how.

Atherosclerosis is a lifelong disease process that begins in childhood and may lead to cardiovascular disease in middle age or later. Non-invasive methods for vascular diagnosis help identify hypercholesterolemic children to treat with dietary or pharmacological intervention on the basis of anatomical or functional markers of arterial pathology. It would be unethical to assess these markers using angiographic or other invasive procedures (such as intravascular ultrasound), but the measurement of intermediate vascular end-points using non-invasive techniques is feasible. We here review the methods and procedures of non-invasive vascular examination that have been demonstrated to be feasible and informative with regard to arterial pathology in hypercholesterolemic children. These include measuring carotid intima-media thickness (IMT) by means of B-mode imaging, Doppler evaluation of the transvalvular aortic pressure gradient, measuring coronary calcium by means of computed tomography, studying the elastic properties of arteries, detecting impaired vasodilation, and measuring arterial remodelling. Suggested operative guidelines could be to measure carotid IMT in all hypercholesterolemic children aged > 10 years. The measurement should be repeated each year if the IMT is in the upper tertile of distribution for that age. A progression in IMT or the development of new lesions during the study could be an indication for more aggressive treatment.

Correction of erythrocyte shape abnormalities in familial hypercholesterolemia after LDL-apheresis: does it influence cerebral hemodynamics?

It is well known that red blood cells incubated in low-density lipoprotein (LDL)-rich medium show shape abnormalities that revert to normal after reincubation in normal plasma. Patients with homozygous familial hypercholesterolemia (HFH) have an increased percentage of abnormally-shaped erythrocytes (mostly stomatocytes, knisocytes, and crenated cells) compared to normocholesterolemic controls: 7.73+/-0.96 versus 3.52+/-0.52 (mean+/-SEM; P = 0.001). To confirm the role of high LDL concentration in inducing red cell shape abnormalities we determined the percentage of abnormally shaped erythrocytes in seven HFH patients 1 day after the procedure of LDL-apheresis with a 40% cholesterol decrease. A reduction in kniscocytes, stomatocytes, and crenated cells was observed in the patients treated by LDL-apheresis (P < 0.01). To investigate the possible benefit of a reduction in erythrocyte shape abnormality on cerebral hemodynamics, cerebral flow velocity, as evaluated by transcranial Doppler, was evaluated concomitantly and found to be remarkably increased after apheresis (P < 0.01). No significant change in hematocrit, plasma viscosity, blood viscosity, mean pressure, or cardiac output was detected, 1 day after apheresis. An inverse correlation was demonstrated (r = 0.55; P = 0.04) between changes in the percentage of knisocytes+stomatocytes +crenated cells and percent changes in middle cerebral artery peak systolic velocity. The correction of erythrocyte shape abnormalities after LDL-apheresis might be related to dramatic changes in plasma phospholipid concentration and proportion occurring after this procedure in HFH patients. The reduction of erythrocyte shape abnormalities could contribute, together with other hemorheological factors, to the improvement of cerebral hemodynamics after LDL-apheresis.

Premature carotid atherosclerosis: does it occur in both familial hypercholesterolemia and homocystinuria? Ultrasound assessment of arterial intima-media thickness and blood flow velocity.

BACKGROUND AND PURPOSE: Homocystinuria due to cystathionine beta-synthase deficiency and familial hypercholesterolemia are inherited disorders of metabolism that are associated with premature development of cardiovascular disease. This study addresses the possibility that different patterns of carotid wall damage and cerebral blood flow hemodynamics are present in these two metabolic diseases. METHODS: Twelve patients with homocystinuria due to cystathionine beta-synthase deficiency (mean age, 24 years), 10 patients with homozygous familial hypercholesterolemia (mean age, 26 years), and 11 healthy control subjects (mean age, 26 years) underwent a vascular examination by noninvasive methods. B-mode ultrasound imaging was used to obtain measurements of intima-media thickness of common carotid, bifurcation, and internal carotid arteries as an index of atherosclerosis. Cerebral blood flow velocity was estimated from vascular examination of the middle cerebral artery by transcranial Doppler. Systolic, diastolic, and mean velocities were measured. Pulsatility index, a possible indicator of vascular resistance in the cerebral circulation, was also calculated. RESULTS: Mean maximum intima-media thickness was 1.4 mm in patients with familial hypercholesterolemia, 0.6 mm in patients with homocystinuria, and 0.6 mm in control subjects. The difference between hypercholesterolemic and homocystinuric patients or control subjects was statistically significant (P < .001). Diastolic blood flow velocities were significantly reduced in the middle cerebral arteries of hypercholesterolemic patients compared with homocystinuric patients or control subjects (P < .05), whereas systolic or mean velocities did not differ. The pulsatility index, a possible indicator of vascular resistance in the cerebral circulation, was significantly higher in hypercholesterolemic patients compared with homocystinuric patients or healthy control subjects (P < .01). A direct relation was demonstrated between pulsatility index of the middle cerebral artery and mean maximum intima-media thickness of carotid arteries on the same side (P < .001). CONCLUSIONS: Familial hypercholesterolemia is responsible for diffuse and focal thickening of carotid arteries and possibly also for hyperlipidemic endothelial dysfunction extending to small resistance arteries and leading to a disturbed cerebral blood flow. Patients with homocystinuria due to homozygosis for cystathionine beta-synthase deficiency seldom have plaques in their carotid arteries. They are similar to healthy control subjects with regard to both intima-media thickness and blood flow velocity in the middle cerebral artery. Therefore, it is unlikely that typical atherosclerotic lesions precede thrombotic events in homocystinuria. However, it is possible that arterial dilatations caused by medial damage lead to thrombosis in homocystinuric patients.

Noninvasive ultrasound techniques versus angiography for monitoring drug-induced changes of the arterial walls.

Even though angiographic studies contribute to understanding the process of atherosclerosis progression/regression in humans, they have several important limitations. The number of participants in all the studies is small and those who accept the invasive vascular investigation are highly selected patients, in most instances in an advanced stage of cardiovascular disease. Furthermore, arteriography provides the image of the vessel lumen but no information on the vessel wall. Noninvasive methods can describe the characteristics of the arteries with regard to morphology (intima-media thickness, surface irregularities, areas of calcification) and the hemodynamic correlates of vascular lesions. No single methodology describes all aspects of the disease process. However, B-mode ultrasound imaging gives information on the vessel wall, whereas Doppler mainly describes the hemodynamic consequences of arterial disease. Before any noninvasive methodology can be adopted for a clinical trial, extensive validation data (preferably using pathology rather than angiography as a "gold standard"), and accurate information on reproducibility and on inter-, intraobserver variability, should be available. Also, quantitative details on the natural history of the disease and on the potential of intervention, as evaluated by the specific methodology to be used, should be known.

Cerebral blood flow velocity and systemic vascular resistance after acute reduction of low-density lipoprotein in familial hypercholesterolemia.

BACKGROUND AND PURPOSE: Low-density lipoprotein apheresis is currently used for the treatment of familial hypercholesterolemia, an inherited disorder of metabolism associated with premature development of cardiovascular disease. We wanted to evaluate cerebral blood flow velocity, cardiac output, and systemic vascular resistance in patients with familial hypercholesterolemia before and after low-density lipoprotein apheresis. METHODS: Ten patients (age range, 14 to 46 years; 4 males, 6 females) with familial hypercholesterolemia (8 homozygotes, 2 heterozygotes) and 10 healthy control subjects of comparable age and sex distribution participated in the study. Low-density lipoprotein apheresis by dextran sulfate was performed in 8 patients (7 homozygotes, 1 heterozygote). Six patients (4 homozygotes, 2 heterozygotes) underwent a procedure of extracorporeal erythrocyte filtration with the same extracorporeal volume as for low-density lipoprotein apheresis, but with the exclusion of the passage of plasma through the dextran sulfate column. Cerebral blood flow velocity (transcranial Doppler), cardiac output, and systemic vascular resistance (electric bioimpedance cardiography) were determined by noninvasive techniques before and 1 day and 7 days after low-density lipoprotein apheresis or extracorporeal erythrocyte filtration. Plasma and blood viscosities were measured at the same time. RESULTS: Before apheresis, mean and diastolic cerebral flow velocities were abnormally low in hypercholesterolemic patients (P < .01 and P < .02 vs healthy control subjects, respectively). After apheresis, low-density lipoprotein cholesterol was lowered by 40% to 60% from baseline, and cerebral blood flow velocities (mean, systolic, and diastolic velocities) were increased (P < .01). Cardiac output, systemic vascular resistance, and viscosity values were not significantly modified. Extracorporeal erythrocyte filtration (without passage of plasma through the dextran sulfate column) did not modify serum lipids, hemodynamic parameters, or viscosity values. CONCLUSIONS: Low-density lipoprotein apheresis produces potentially useful hemodynamic effects. They are not adequately explained by changes in blood viscosity alone and might reflect a restoration of endothelium-mediated vasodilation, which is inhibited by high concentrations of low-density lipoprotein.

Sneddon's syndrome, anticardiolipin antibodies and anticardiolipin cofactor. A case report.

Sneddon's syndrome is a rare entity characterized by idiopathic livedo reticularis and cerebrovascular lesions. A case of a young woman with livedo reticularis and progressive cerebral arteriopathy is described. Abnormalities of sexual and gonadotropic hormones were present. Anticardiolipin and anticardiolipin-cofactor complex antibodies were not found.

Changes in middle cerebral artery blood velocity in uremic patients after hemodialysis.

BACKGROUND AND PURPOSE: Strokes are a frequent complication in uremic patients on dialysis. We wanted to evaluate the effect of this treatment on cerebral hemodynamic parameters, particularly those of patients with carotid stenosis, who are at higher risk for atherothrombotic ischemic events. METHODS: We used transcranial Doppler ultrasonography to evaluate blood velocity of the middle cerebral artery in 18 uremic patients before and after hemodialysis. Carotid stenosis was evaluated by echo-Doppler investigation. Six patients were also studied before and after recombinant human erythropoietin treatment. RESULTS: Dialysis treatment decreased mean blood velocity in all patients (p less than 0.001). Eight of 18 patients (44%) with mild (16-50%), moderate (51-80%), or severe (greater than 80%) carotid stenosis had lower velocity than patients with normal carotid arteries (p less than 0.01), and they experienced a further decrease to even lower levels after hemodialysis (p less than 0.05). In patients treated with recombinant human erythropoietin, hematocrit increased from 28 +/- 8% to 37 +/- 5% (p less than 0.001), and blood velocity had a further decrease by 11%. All changes were associated with modifications toward normality of pH, PaCO2, and hematocrit. CONCLUSIONS: Transcranial Doppler ultrasonography represents a useful method for monitoring cerebral circulation of uremic patients, especially of those at possible risk for ischemia.

Diabetes mellitus and localizations of obliterating arterial disease of the lower limbs.

Thirty patients with intermittent claudication (IC) and treated diabetes mellitus and 30 age- and gender-matched nondiabetic claudicants underwent a vascular examination by noninvasive ultrasound methods (continuous-wave Doppler, duplex scanner). The ankle/arm systolic pressure index did not differ in the two groups. Diabetic patients with IC had more (p less than .001) non-flow-reducing stenoses (lumen reduction less than 50%) and fewer (p less than .002) flow-reducing obstructions (lumen reduction greater than 50%) of the iliac arteries than nondiabetics had. These data are consistent with a preferentially distal (below the inguinal ligament) localization of arterial stenoses in diabetic patients, whereas iliac artery diseases are relatively more severe in nondiabetics.

Early signs of vascular disease in homocystinuria: a noninvasive study by ultrasound methods in eight families with cystathionine-beta-synthase deficiency.

Fourteen patients (six males, eight females; mean age, 20 years) with homocystinuria due to homozygous cystathionine-beta-synthase (CBS) deficiency, underwent a vascular examination. Fourteen heterozygotes (seven males, seven females; mean age, 46 years), including 12 parents and one daughter of homozygotes (obligate heterozygotes), and one sister of a homozygote (with low enzyme activity as evaluated in vitro), were also examined. Homozygotes and heterozygotes were compared with two separate control groups of different age (mean age, 20 and 43 years, respectively). Ankle/arm systolic pressure index (by continuous-wave Doppler) was, on average, lower in homozygotes (P less than .01) and heterozygotes (P less than .05) as compared with the controls. An ankle/arm index less than 0.97 and suggesting flow-reducing arterial lesions was found in six (21%) lower limbs of homozygotes versus zero in controls (P less than .05). Echo Doppler (Duplex Scanner) abnormalities, indicating early, non-flow-reducing lesions of iliac arteries were more frequent in homozygotes (seven wall abnormalities or stenoses less than 15%) than in young controls (P less than .05). The corresponding figures for heterozygotes were seven wall abnormalities or stenoses (1% to 15% and one stenosis 16% to 50%) (P less than .01 v middle-aged controls). Early lesions (three wall abnormalities or stenoses less than 15%, three stenoses 16% to 50%) were detected in six (23%) internal carotids of heterozygotes versus three (3%) of corresponding controls (P less than .05). Technical limitations precluded the accurate detection of early lesions in the internal carotid arteries of young homozygotes and controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Noninvasive ultrasound evaluation of pressure gradients in aortic root of homozygotes for familial hypercholesterolemia.

The aim of this study was to measure noninvasively by Doppler ultrasound the blood flow velocity at the level of the aortic root in patients with homozygous familial hypercholesterolemia (FH) to detect abnormal pressure gradients. Seven patients with homozygous FH and seven healthy controls matched for age and sex were included in the study. Continuous-wave Doppler (2 MHz) was used to measure the highest detectable velocity from the aortic root; the probe was positioned in the suprasternal notch. When an abnormal velocity was detected, the corresponding pressure drop was calculated from the formula: Delta P = 4Vmax2. Each FH patient had an abnormal aortic velocity consistent with a pressure gradient across the valvular area. All the controls had normal aortic velocities (p less than 0.01). The measurement of the pressure drop across the aortic valvular area in FH patients gives an estimate of the lesions produced by cholesterol deposition in a crucial area of the cardiovascular system near the origin of coronary arteries. The noninvasivity of this method makes it an excellent method for obtaining parameters for follow-up and clinical trials.

Dissociation between vascular and metabolic effects of nicotinic acid in Gilbert's syndrome.

The relationship between the vasodilating and the hyperbilirubinaemic effect of low and high doses (50 and 300 mg i.v.) of nicotinic acid was studied in baseline conditions and after indomethacin pretreatment in healthy controls and patients with Gilbert's syndrome (a condition characterized by fluctuating, nonhaemolytic unconjugated hyperbilirubinaemia). The hyperbilirubinaemic effect of nicotinic acid was confirmed to be more pronounced in Gilbert's syndrome patients than in controls. The magnitude of hyperbilirubinaemia in the two groups was not dependent on the dose of nicotinic acid or indomethacin pretreatment. A dose-dependent vasodilation which was inhibited by indomethacin could be demonstrated in both controls and Gilbert's syndrome subjects. Vasodilating properties of nicotinic acid were therefore found to be dissociated from the effect on bilirubin.

Blood flow velocity in the middle cerebral artery during carotid cross-clamping: loss of regulatory response to carbon dioxide partial pressure. A transcranial Doppler intraoperative study.

The CO2 reactivity of blood flow velocity in the Middle Cerebral Artery (MCA) was explored by Doppler ultrasound, in nine patients, at the time of common carotid artery cross-clamping during vascular surgery, in order to detect if a regulatory response apply during operative occlusion of common carotid artery. Transcranial Doppler was used to monitor ipsilateral MCA blood velocity during carotid surgery. MCA velocity, arterial blood pressure and pCO2 (arterial or end-tidal) were measured, during carotid cross clamping, before and after an increase in pCO2 was induced by changing respiratory rate and volumes. No relevant changes in MCA flow velocities were detected in patients with stable arterial blood pressure. In those patients showing an increase in blood pressure during the surgical procedure the MCA velocity increased accordingly. It is suggested that the cross-clamping of common carotid artery is a critical condition in which no regulatory response can be elicited: blood flow velocity tends to parallel the perfusion pressure and also CO2 reactivity is lost.

Reproducibility of non-invasive vascular diagnosis in patients with diabetes mellitus.

Reproducibility of noninvasive ultrasound methods for vascular diagnosis was studied in 36 patients with Insulin Dependent Diabetes Mellitus. The vascular examination included a) the measurement of ankle systolic arterial pressure and ankle/arm pressure index (c.w. Doppler), b) Echo-Doppler examination of iliac arteries with measurement of maximum systolic frequency, systolic spectrum width and diastolic reverse flow component. A grading of iliac artery stenosis was also performed. The examination was repeated after one month according to a blind protocol. The coefficients of variation were as follows: 8% for ankle pressure; 8% for ankle/arm pressure index; 9% for the maximum systolic frequency; 18% for the spectrum width and 15% for the reverse flow component. The reproducibility of the grading of iliac artery stenosis based on the combined use of the three Echo-Doppler parametres was measured by the Kendall coefficient (W = 0.865). These results confirm that non invasive methods are suitable and reliable for investigating vascular disease in diabetic patients. Accurate estimates of reproducibility are essential pre-requisites for the planning of studies on the natural history of vascular disease and on progression-regression of arterial lesions.

Lipoprotein abnormalities and extracoronary atherosclerosis in patients with premature ischemic heart disease.

A study of serum lipoprotein (VLDL, LDL, HDL) concentration has been performed on 36 males who had undergone an aorto-coronary bypass operation before age 50. They have been compared to 33 healthy men in the same age range. The presence and severity of coronary, carotid and peripheral atherosclerosis in these patients has been evaluated on the basis of coronary angiograms, continuous wave Doppler and Duplex scanning by echo-Doppler. Lipoprotein abnormalities have been related to the occurrence of extracoronary arterial lesions in association with myocardial ischemia. Total serum cholesterol and triglycerides, LDL cholesterol and triglycerides were higher in IHD patients (p less than 0.05), while HDL cholesterol was lower (p less than 0.01). No statistically significant difference was detected in VLDL lipids or apo B and in LDL apo B. Signs of extracoronary atherosclerosis were more frequent among IHD patients than in controls. Ankle/arm pressure ratio was abnormally low in 12 patients as compared to only one control (p less than 0.01). Echo-Doppler examinations of iliac arteries demonstrated a higher prevalence of lesions among IHD patients as compared to controls (20 versus 2; p less than 0.01). All patients (4 out of 36) with audible carotid bruits had stenoses in the internal carotid artery. In order to evaluate the relationships between lipoprotein concentration and occurrence of extracoronary atherosclerosis, analysis of variance and multiple comparisons were performed on values for lipoprotein concentration in three groups: controls, IHD patients without evidence of extracoronary atherosclerosis, IHD patients with detectable extracoronary lesions. Significant differences among the three groups were demonstrated as regard to LDL cholesterol or triglycerides and HDL cholesterol.(ABSTRACT TRUNCATED AT 250 WORDS)

Doppler measurement of the pressure drop caused by arterial stenosis: an experimental study: a case report.

A stenotic arterial lesion which reduces the cross-sectional area of the artery causes an increased velocity and, as a consequence, a loss in kinetic energy and a pressure drop. A simplified formula, derived from the Bernoulli principle, relates the pressure drop to the maximum velocity of the blood flow in the stenotic segment: delta P (mmHg) = 4 Vmax2 (m/sec). This formula has been validated for stenosis of cardiac valves. Aim of our study was to test the hypothesis that this formula applies in the major arteries using Doppler ultrasound with spectrum analysis. In our experiments we created artificial graded stenoses of varied geometry in the thoracic aorta of dogs. Invasive pressure measurements were obtained using intra-arterial needles on both sides of the stenosis. A Doppler signal was obtained with a 2.5 MHz CW probe, insonating the stenotic area from a distance, with an almost parallel approach. In these conditions the maximum Doppler frequency shift is an accurate estimate of the maximum flow velocity, according to the Doppler equation. We compared the Doppler derived (delta P = 0.36 Fmax2) and the invasive measurements of pressure drops. Our results show a highly significant correlation between the intra-arterial and the Doppler measurements of the pressure drops caused by arterial stenoses and encourage efforts in applying similar techniques in the noninvasive evaluation of vascular patients.

Improvement of the nicotinic acid test in the diagnosis of Gilbert's syndrome by pretreatment with indomethacin.

The hyperbilirubinemia induced by nicotinic acid (NA) is well correlated to 14C-bilirubin clearance, and is utilized to diagnose Gilbert's syndrome (GS). However, NA produces a number of vascular prostaglandin-mediated side effects. In an attempt to improve the NA test we evaluated the influence of pretreatment with Indomethacin, a PG-synthetase inhibitor, both on side effects and hyperbilirubinemia. NA (5.9 mumoles/kg of body weight i.v.) was administered on two separate occasions, before and one hour after i.m. injection of 100 mg Indomethacin in 11 GS males and 11 controls matched for sex and age (age range 18.34 years). The hyperbilirubinemic effect of NA was not modified by Indomethacin in any subject; the side effects were either significantly reduced or completely abolished. We suggest that patients undergoing the NA test for the diagnosis of GS be pretreated with Indomethacin.