Efficacy of a combination of diluted calcium hydroxylapatite-based filler and an energy-based device for the treatment of facial atrophic acne scars.

BACKGROUND: Treatment options for atrophic acne scars include the use of various energy-based devices (EBDs) and dermal fillers. AIM: To evaluate the level of improvement and safety of four treatments for atrophic acne scars used in our centre. METHODS: We reviewed the medical records of all patients with acne scars treated between 2013 and 2016 with one of four treatments: ablative fractional CO2 laser (FACL), a radiofrequency (RF) bipolar device, a 1540 nm nonablative fractional laser (NAFL) and injection of diluted calcium hydroxylapatite (CaHA). The EBDs were used either as monotherapy or in combination with diluted CaHA. The aesthetic improvement achieved following the various treatments was evaluated by the patients and by two independent dermatologists who were not involved in the treatments. The patients also rated their satisfaction with the treatment, recorded the number of days of downtime (including time to full recovery and time for resolution of redness) and reported any adverse effects (AEs). RESULTS: In total, 352 patients (mean ± SD age 28.7 ± 8.7 years; 65.6% women, 34.4% men) were treated for acne scars. The integrated mean Global Assessment Scale by both dermatologists and patients were highest for the combined CaHA-FACL treatment at separate sessions (injection in one session; laser treatment in another) (P < 0.001). However, patients treated with FACL reported more AEs and longer downtime and duration of erythema. CONCLUSION: The combination of a diluted CaHA-based filler injection followed by FACL in separate treatment sessions yielded better aesthetic improvement compared with the other tested treatments.

Quantitative, Absolute Count-Based T-Cell Analysis of CD69 Upregulation as a New Methodology for In Vitro Diagnosis of Delayed-Type Hypersensitivity Reaction to Nickel.

BACKGROUND: T cells play a major role in delayed-type hypersensitivity reactions. Their reactivity can be assessed by measuring the upregulation of the activation marker CD69, followed by assessment of proliferation and cytokine production. The aim of our study was to develop a novel, whole blood-based, quantitative, absolute count activation index (AI) for analysis of CD69 upregulation in various subsets of T cells in nickel-hypersensitive patients and compare it with previously reported approaches. METHODS: The study population comprised 10 patients with nickel allergy and 9 healthy controls. CD69 expression of CD3+, CD3+CD4+, and CD3+CD8+ T cells in heparinized blood was determined with flow cytometry after incubation with nickel sulfate for 48 hours. The absolute count of CD69+ cells was determined using microbeads. Production of the cytokines IL-2, IL-5, IL-13, and IFN-γ was determined after stimulation of peripheral blood mononuclear cells with nickel sulfate for 48 hours. RESULTS: We showed absolute AI to be the most sensitive approach. The index was calculated as the ratio of the absolute count of nickel-stimulated CD69-positive T cells to the absolute count of CD69-positive T cells in nonstimulated blood. This novel quantitative approach was more discriminative than previously reported approaches in which the T-cell CD69 percentage AI and cytokine production are measured. CONCLUSIONS: Our results demonstrated that measuring the absolute CD69 AI is a novel and accurate approach for quantification of antigen-specific T cells in the blood of patients with hypersensitivity reactions to nickel. This approach may be useful for better in vitro assessment of patients with delayed-type hypersensitivity reactions.

Deleterious mutation in the FYB gene is associated with congenital autosomal recessive small-platelet thrombocytopenia.

BACKGROUND: The FYB gene encodes adhesion and degranulation-promoting adaptor protein (ADAP), a hematopoietic-specific protein involved in platelet activation, cell motility and proliferation, and integrin-mediated cell adhesion. No ADAP-related diseases have been described in humans, but ADAP-deficient mice have mild thrombocytopenia and increased rebleeding from tail wounds. PATIENTS AND METHODS: We studied a previously reported family of five children from two consanguineous sibships of Arab Christian descent affected with a novel autosomal recessive bleeding disorder with small-platelet thrombocytopenia. Homozygosity mapping and exome sequencing were used to identify the genetic lesion causing the disease phenotype on chromosome 5. Bone-marrow morphology and platelet function were analyzed. Platelets were characterized by scanning electron microscopy. RESULTS: We identified a homozygous deleterious nonsense mutation, c.393G>A, in FYB. A reduced percentage of mature megakaryocytes was found in the bone marrow. Patients' platelets showed increased basal expression of P-selectin and PAC-1, and reduced increments of activation markers after stimulation with ADP, as detected by flow cytometry; they also showed reduced pseudopodium formation and the presence of trapped platelets between the fibrin fibers after thrombin addition, as observed on scanning electron microscopy. CONCLUSIONS: This is the first report of a disease caused by an FYB defect in humans, manifested by remarkable small-platelet thrombocytopenia and a significant bleeding tendency. The described phenotype shows ADAP to be important for normal platelet production, morphologic changes, and function. It is suggested that mutation analysis of this gene be included in the diagnosis of inherited thrombocytopenia.

Urinary tract infection: is there a need for routine renal ultrasonography?

AIMS: To assess the yield of routine renal ultrasound (RUS) in the management of young children hospitalised with first uncomplicated febrile urinary tract infection (UTI). METHODS: All children aged 0-5 years who had been hospitalised over a two year period with first uncomplicated febrile UTI in a medium size institutional regional medical centre were included. Children with known urinary abnormalities and/or who had been treated with antibacterial agents within seven days before admission were excluded. All included children underwent renal ultrasonography during hospitalisation and voiding cystouretrography (VCUG) within 2-6 months. The yield of RUS was measured by its ability to detect renal abnormalities, its sensitivity, specificity, and positive and negative predictive values for detecting vesicoureteral reflux (VUR), and by its impact on UTI management. RESULTS: Of 255 children that were included in the study, 33 children had mild to moderate renal pelvis dilatation on RUS suggesting VUR, of whom only nine had VUR on VCUG. On the other hand, in 36 children with VUR on VCUG the RUS was normal. The sensitivity, specificity, positive predictive value, and negative predictive value of abnormal RUS for detecting VUR were 17.7%, 87.6%, 23.5%, and 83.2% respectively. In none of the patients with abnormal RUS was a change in the management at or following hospitalisation needed. CONCLUSION: Results show that the yield of RUS to the management of children with first uncomplicated UTI is questionable.

Severe lymphedema of the arm as a potential cause of shoulder trauma.

The aim of this study was to determine whether lymphedema of the arm is associated with traumatic injury to the shoulder and to assess the role of lymphatic physiotherapy in reducing disabling shoulder pain. The study group consisted of 10 women aged 58-81 years (mean 66.9) with arm lymphedema after surgery for breast cancer. The average interval between the operation and the appearance of lymphedema was 9.8 years. All patients complained of shoulder pain. Five patients had a tear in the supraspinatus muscle diagnosed by ultrasound examination, and 5 had chronic bursitis; the nonaffected arm showed no pathology. The mean volume of the affected arm was 568 ml greater. Treatment consisted of manual lymphatic drainage and intermittent sessions of pneumatic compression with the LymphaPress device. This led to an average decrease in arm volume of 170 ml, with improvement of arm mobility and a drastic reduction in shoulder pain. In conclusion, lymphedema of the arm can cause severe shoulder trauma, pain and disability. Proper physiotherapy can reduce these effects. Patients should be referred for early treatment and follow-up to avoid permanent damage to the shoulder muscles.

[Community acquired urinary tract infection among hospitalized children in northern Israel: pathogens, susceptibility patterns and urinary tract anomalies].

BACKGROUND: Urinary tract infection (UTI) is one of the most common diseases in children. Vesicoureteral reflux (VUR) has been demonstrated in a substantial number of young children with UTI. Empiric antibacterial therapy is recommended before results of the urine culture are available in order to shorten the duration of the disease and prevent renal complications. OBJECTIVES: The aims of this study were to assess the prevalence and susceptibility patterns of UTI pathogens, and urinary anomalies in children admitted with UTI. METHODS: The study population included 151 children younger than 14 years admitted with first UTI. Renal ultrasound was performed in all the patients and voiding cystourethrography (VCUG) in children younger than 5 years. Dimercaptosuccinic acid (DMSA) scan was performed in children with vesicoureteral reflux. The data included age, sex, symptoms and signs, urinalysis, the pathogen and its sensitivity and the results of the imaging studies. RESULTS: A total of 119 patients (79%) were females. Gram negative rods caused 98% of the infections, of which Escherichia coli (87%) was the most prevalent pathogen, followed by Klebsiella pneumoniae (4%), and Proteus mirabilis (4%). The sensitivities to antibacterial agents were: Amikacin 100%, ceftazidime 97%, gentamicin 96%, ceftriaxone 96%, cefuroxime 95%, amoxicillin-clavulanate 84%, trimethoprim-sulfamethoxazole 63%, cephalexin 58%, and ampicillin 28%. Renal US showed minor abnormalities in 24/149 (16%) and VCUG demonstrated vesicoureteral reflux in 38/127 (30%) patients. DMSA revealed renal scars in 7/28 (25%) children with vesicoureteral reflux. CONCLUSIONS: Overall Gram negative rods cause 98% of the UTI in hospitalized children in our area. E. coli is the leading pathogen and aminoglycosides and second or third generation cephalosporins are the most suitable agents for empiric therapy in UTI. A high incidence of renal scars in young children with vesicoureteral reflux was found.

Comparison of the complete mtDNA genome sequences of human cell lines--HL-60 and GM10742A--from individuals with pro-myelocytic leukemia and leber hereditary optic neuropathy, respectively, and the inclusion of HL-60 in the NIST human mitochondrial DNA standard reference material--SRM 2392-I.

Forensic and clinical laboratories benefit from DNA standard reference materials (SRMs) that provide the quality control and assurance that their results from sequencing unknown samples are correct. Therefore, the mitochondrial DNA (mtDNA) genome of HL-60, a promyelocytic leukemia cell line, has been completely sequenced by four laboratories and will be available to the forensic and medical communities in the spring of 2003; it will be called National Institute of Standards and Technology (NIST) SRM 2392-I. NIST human mtDNA SRM 2392 will continue to be available and includes the DNA from two apparently healthy individuals. Both SRM 2392 and 2392-I contain all the information (e.g. the sequences of 58 unique primer sets) needed to use these SRMs as positive controls for the amplification and sequencing any DNA. Compared to the templates in SRM 2392, the HL-60 mtDNA in SRM 2392-I has two tRNA differences and more polymorphisms resulting in amino acid changes. Four of these HL-60 mtDNA polymorphisms have been associated with Leber Hereditary Optic Neuropathy (LHON), one as an intermediate mutation and three as secondary mutations. The mtDNA from a cell line (GM10742A) from an individual with LHON was also completely sequenced for comparison and contained some of the same LHON mutations. The combination of these particular LHON associated mutations is also found in phylogenetic haplogroup J and its subset, J2, and may only be indicative that HL-60 belongs to haplogroup J, one of nine haplogroups that characterize Caucasian individuals of European descent or may mean that haplogroup J is more prone to LHON. Both these mtDNA SRMs will provide enhanced quality control in forensic identification, medical diagnosis, and single nucleotide polymorphism detection.

[Treatment of traumatic false aneurysm of the thoracic aorta with stent graft].

UNLABELLED: The treatment of traumatic false aneurysm of the thoracic aorta by endovascular stent graft may have advantages over conventional surgery. This is a case study of two women suffering from false aneurysm of the thoracic aorta caused in one by a knife injury and in the other by a car accident. After the patients became hemodynamically stable, a commercially available endothelial stent graft (Talent, Gor) was deployed. Recovery was rapid in the first patient. The second patient required emergency laparotomy for venous bleeding one day after stent placement; she died two weeks later, mainly from organ failure. CONCLUSIONS: Endovascular techniques can be used in selected cases to treat thoracic false aneurysms thereby avoiding the complexity and morbidity of conventional surgery.

Steroid responsive nephrotic syndrome associated with bilateral renal dysplasia.

Renal dysplasia is characterized by hypoplastic kidneys that contain elements of primitive tubules. Patients may develop end-stage renal failure early in life. Nephrotic syndrome is one of the most common renal diseases in childhood and may occur in association with renal dysplasia. We report a case of a child with bilateral dysplastic kidneys and steroid responsive nephrotic syndrome (SRNS). An association between renal dysplasia with chronic renal failure and SRNS has not previously been reported in the English literature.

Saphenous vein harvesting for coronary artery bypass grafting. Retrospective analysis of possible causes of major wound complications in patients with peripheral arterial disease.

OBJECTIVES: to retrospectively evaluate the possible reasons for major wound complications at the saphenous vein harvesting site in patients with peripheral arterial disease (PAD). DESIGN: retrospective study. MATERIALS AND METHOD: fifteen consecutive patients admitted to the vascular department for impaired healing at the saphenous vein harvesting site after successful coronary bypass artery grafting (CABG) (Group A) were evaluated for medical, perioperative, laboratory and pathological factors and outcome. Findings were compared with those in 15 matched controls followed in the outpatient clinic after CABG (Group B). RESULTS: absence of pedal pulses in the affected leg was noted in 13 patients in group A and 3 patients in group B. Ankle brachial index ranged from 0.4--0.7 in group A and 1.7--1.1 in group B; corresponding ankle pressures were 40--100 mmHg (mean 60 mmHg) and 80--160 mmHg (mean 110 mmHg). All patients in group A had PAD, whereas none did in group B, and all patients in group A required intervention to save the leg. Wound healing was noted in 11 group A patients; four patients underwent below-knee amputation. CONCLUSION: saphenous vein harvesting from limbs with severe PAD can lead to significant morbidity, including limb loss. In patients lacking a palpable pedal pulse, we recommend harvesting only the proximal saphenous vein.

Relation of nonobstructive aortic valve calcium to carotid arterial atherosclerosis.

Recently it was shown that subjects with aortic valve calcium (AVC) are at increased risk for future cardiovascular disease including stroke. We hypothesized that the increased risk of stroke may be due to an association with carotid artery atherosclerotic disease. Between 1995 and 1999 our laboratory made a diagnosis of AVC without significant stenosis in 3,949 patients. Of those, 279 patients without other cardiac structural exclusion criteria (148 men and 131 women; mean age 73 +/- 9 years, range 45 to 90) underwent carotid artery duplex ultrasound for various indications, and formed the study group. Age- and sex-matched patients without AVC (n = 277), who underwent carotid artery duplex ultrasound during the same period and for the same indications, served as the control group. Compared with the control group, the AVC group had a significantly higher prevalence of carotid stenosis (> 40% to 60%, 89% vs 78% [p < 0.001]; >60% to 80%, 43% vs 23% [p <0.001];and > 80% to 100%, 32%vs 14% [p < 0.001]). The AVC group had a similar, significantly higher prevalence of > or = 2-vessel disease and bilateral carotid stenosis (stenosis levels of > 20% to 40%, >40% to 60%, > 60% to 80%, and > 80% to 100%). In multivariate analysis, AVC, but not traditional risk factors, was the only independent predictor of severe carotid atherosclerotic disease (stenosis > 80% to 100%; p = 0.0001). Thus, there is a significant association between the presence of AVC and carotid atherosclerotic disease.

Association between mitral annulus calcification and peripheral arterial atherosclerotic disease.

The authors previously demonstrated a significant association between the presence of mitral annulus calcification (MAC) and aortic atheroma, carotid atherosclerotic disease, and coronary artery disease. The present study was designed to determine whether an association exists between MAC and peripheral arterial atherosclerotic disease. Of the 805 patients in whom the diagnosis of MAC was made by transthoracic echocardiography between 1995 and 1997, 77 patients (40 men and 37 women; mean age, 73.1 +/- 11.4 years; range, 44-90 years) underwent peripheral arterial testing for various indications, and comprised the study group. They were compared with 58 age-matched and sex-matched patients without MAC (30 men and 28 women; mean age, 73.2 +/- 11.8 years; range, 31-93 years) who underwent peripheral arterial testing during the same period for the same indications (control group). MAC was defined as a dense, localized, highly reflective area at the base of the posterior mitral leaflet detected by transthoracic echocardiography. An ankle/brachial systolic pressure index (ABI) was calculated by dividing the higher dorsalis pedis or posterior tibial Doppler-derived pressures by the higher of the 2 upper extremity systolic pressures. ABI was graded as follows: normal > or = 1, abnormal < 1, mild 0.71 to 0.99, moderate 0.41 to 0.7, and severe < or = 0.4. No differences were found between the groups in indications for referral for peripheral arterial testing and in risk factors for atherosclerosis except for hypertension, which was found to be significantly more prevalent in the study group (66% vs 41%, p = 0.004). The study group included 151 limbs, and the control group included 113 limbs. The mean ABI was significantly lower for all limbs in the MAC group (0.56 +/- 0.27 vs 0.87 +/- 0.24, p = 0.0001), abnormal ABI < 1 (94% vs 68%, p = 0.001), moderate peripheral arterial disease (44% vs 25%, p = 0.001), and a severe disease (27% vs 1%, p = 0.001). Of the 77 patients with MAC, 73 (95%) had a disease (right and/or left limbs) compared with 40 of 58 (69%) in the control group (p = 0.001). Bilateral disease (Doppler index < 1 for both right and left limbs), and severe bilateral disease (Doppler index < or = 0.4 for both right and left limb) were also found to be significantly more prevalent in the MAC group (87% vs 60%, p = 0.001; and 12% vs 0%, p = 0.007, respectively). There is a significant association between the presence of MAC and peripheral arterial disease. This information strengthens our hypothesis that MAC may be an important marker for generalized vascular atherosclerotic disease.

Development of ligands for in vivo imaging of cerebral nicotinic receptors.

Nicotinic acetylcholine receptors (nAChRs) mediate a variety of brain functions. Findings from postmortem studies and clinical investigations have implicated them in the pathophysiology and treatment of Alzheimer's and Parkinson's diseases and other CNS disorders (e.g. Tourette's syndrome, epilepsy, nicotine dependence). Therefore, it ultimately might be useful to image nAChRs noninvasively for diagnosis, for studies on how changes in nAChRs might contribute to cerebral disorders, for development of therapies targeted at nAChRs, and to monitor the effects of such treatments. To date, only (S)-(-)-nicotine, radiolabeled with 11C, has been used for external imaging of nAChRs in human subjects. Since this radiotracer presents drawbacks, new ligands, with more favorable properties, have been synthesized and tested. Three general classes of compounds, namely, nicotine and its analogs, epibatidine and related compounds, and 3-pyridyl ether compounds, including A-85380, have been evaluated. Analogs of A-85380 appear to be the most promising candidates because of their low toxicity and high selectivity for the alpha4beta2 subtype of nAChRs.

5-Iodo-A-85380, an alpha4beta2 subtype-selective ligand for nicotinic acetylcholine receptors.

In an effort to develop selective radioligands for in vivo imaging of neuronal nicotinic acetylcholine receptors (nAChRs), we synthesized 5-iodo-3-(2(S)-azetidinylmethoxy)pyridine (5-iodo-A-85380) and labeled it with (125)I and (123)I. Here we present the results of experiments characterizing this radioiodinated ligand in vitro. The affinity of 5-[(125)I]iodo-A-85380 for alpha4beta2 nAChRs in rat and human brain is defined by K(d) values of 10 and 12 pM, respectively, similar to that of epibatidine (8 pM). In contrast to epibatidine, however, 5-iodo-A-85380 is more selective in binding to the alpha4beta2 subtype than to other nAChR subtypes. In rat adrenal glands, 5-iodo-A-85380 binds to nAChRs containing alpha3 and beta4 subunits with 1/1000th the affinity of epibatidine, and exhibits 1/60th and 1/190th the affinity of epibatidine at alpha7 and muscle-type nAChRs, respectively. Moreover, unlike epibatidine and cytisine, 5-[(125)I]iodo-A-85380 shows no binding in any brain regions in mice homozygous for a mutation in the beta2 subunit of nAChRs. Binding of 5-[(125)I]iodo-A-85380 in rat brain is reversible, and is characterized by high specificity and a slow rate of dissociation of the receptor-ligand complex (t(1/2) for dissociation approximately 2 h). These properties, along with other features observed previously in in vivo experiments (low toxicity, rapid penetration of the blood-brain barrier, and a high ratio of specific to nonspecific binding), suggest that this compound, labeled with (125)I or (123)I, is superior to other radioligands available for in vitro and in vivo studies of alpha4beta2 nAChRs, respectively.

Venous thromboembolism, factor V Leiden, and methylenetetrahydrofolate reductase in a sickle cell anemia patient.

Vaso-occlusive crisis is the most common cause of morbidity in patients with sickle cell anemia (SCA). Central nervous system involvement that leads to hemiplegia is the most frequent neurological complication in those patients. Peripheral deep venous thromboembolism was not reported in SCA patients. Activated protein C resistance is associated with an increased risk of thrombophilia. The authors report an SCA patient with recurrent cerebrovascular accident and deep venous thrombosis. Activated protein C resistance due to factor V Leiden heterozygous and heterozygocity for the methylenetetrahydrofolate reductase were diagnosed and suspected to be the risk factors that contribute to the development of the deep vein thrombosis in this SCA patient.

Effect of hydroxyurea in sickle cell anemia: a clinical trial in children and teenagers with severe sickle cell anemia and sickle cell beta-thalassemia.

This study evaluated the efficacy of hydroxyurea treatment in the prevention of vaso-occlusive crises among children and teenagers with severe sickle cell anemia and sickle cell beta-thalassemia. Nineteen children and young adults with severe sickle cell disease were enrolled to the hydroxyurea treatment trial. The incidence of vaso-occlusive crises, acute chest syndrome, hemolytic crises, splenic sequestration episodes, blood transfusions, and hospital days in the 2 years before hydroxyurea (HU) treatment were compared with the same parameters in the first 2 years of treatment. The patients received a mean dose of 21.3 mg/kg/day daily and were treated during a mean period of 40.3 +/- 14 months (range 20 to 68 months). Significant increases were observed after 1 month in the Hgb, MCV, MCH, and MCHC levels and were more notable after 3 months. The increase in the Hgb F level became important after 3 months of HU therapy and was highly significant (p < .001) beyond 6 months. No differences were observed in the RDW, reticulocyte count, Hgb S, and Hgb A2. Severe neutropenia was observed in one case. A decrease in the frequency of vaso-occlusive crises, acute chest syndrome, hemolytic crises, blood transfusions, and days spent in the hospital was demonstrated during the HU treatment period compared to the same period before. The clinical and laboratory response to HU was dramatic in severely affected sickle cell anemia (SCA) patients. The response to HU in children and teenagers with severe sickle cell anemia is similar to the response in adults, and no severe adverse effects were observed.

Radiosynthesis and preliminary evaluation of 5-[123/125I]iodo-3-(2(S)-azetidinylmethoxy)pyridine: a radioligand for nicotinic acetylcholine receptors.

The radiochemical syntheses of 5-[125I]iodo-3-(2(S)-azetidinylmethoxy)pyridine (5-[125I]-iodo-A-85380, [125I]1) and 5-[123I]-iodo-A-85380, [123I]1, were accomplished by radioiodination of 5-trimethylstannyl-3-((1-tert-butoxycarbonyl-2(S)-azetidinyl)metho xy)pyridine, 2, followed by acidic deprotection. Average radiochemical yields of [125I]1 and [123I]1 were 40-55%; and the average specific radioactivities were 1,700 and 7,000 mCi/mumol, respectively. Binding affinities of [125I]1 and [123I]1 in vitro (rat brain membranes) were each characterized by a Kd value of 11 pM. Preliminary in vivo assay and ex vivo autoradiography of mouse brain indicated that [125I]1 selectively labels nicotinic acetylcholine receptors (nAChRs) with very high affinity and specificity. These studies suggest that [123I]1 may be useful as a radioligand for single photon emission computed tomography (SPECT) imaging of nAChRs.

In vivo imaging of brain nicotinic acetylcholine receptors with 5-[123I]iodo-A-85380 using single photon emission computed tomography.

The distribution and kinetics of 5-[123I]iodo-A-85380, a novel ligand for brain nicotinic acetylcholine receptors (nAChRs), were evaluated in the Rhesus monkey using single photon emission computed tomography (SPECT). Peak levels of radioactivity were measured in brain at 90 min after injection of the tracer. Accumulation of radioactivity was highest in the thalamus, intermediate in the frontal cortex and basal ganglia, and lowest in the cerebellum. The ratio of specific to nonspecific binding (V3") in the thalamus, estimated from the (thalamic-cerebellar)/cerebellar radioactivity ratio, reached a value of 6 at 4 h post-injection. Specific binding was reduced by subcutaneous injection of 1 mg/kg cytisine at 2.25 h after injection of radiotracer. At 2.5 h after cytisine administration, radioactivity in the thalamus was reduced by 84%, in the frontal cortex, by 76%, and in the basal ganglia, by 57% of the level measured at the time of cytisine administration, demonstrating that the binding was reversible. On the basis of these findings, together with other data indicating high affinity, receptor subtype selectivity, low nonspecific binding and lack of toxicity in animals, 5-[123I]iodo-A-85380 appears to be a promising ligand for SPECT imaging of nAChRs in the human brain.

Association between mitral annulus calcification and carotid atherosclerotic disease.

BACKGROUND AND PURPOSE: It has been established that mitral annulus calcification (MAC) is an independent predictor of stroke, though a causative relationship was not proved, and that carotid artery atherosclerotic disease is also associated with stroke. The aim of this study was to determine whether there is an association between the presence of MAC and carotid artery atherosclerotic disease. METHODS: Of the 805 patients in whom the diagnosis of MAC was made by transthoracic echocardiography between 1995 and 1997, 133 patients (60 men and 73 women; mean age, 74.3+/-8 years; range, 47 to 89 years) underwent carotid artery duplex ultrasound for various indications; the study group comprised these patients. They were compared with 129 age- and sex-matched patients without MAC (57 men and 72 women; mean age, 73.6+/-7 years; range, 61 to 96 years) who underwent carotid artery duplex ultrasound during the same period for the same indications. MAC was defined as a dense, localized, highly reflective area at the base of the posterior mitral leaflet. MAC was considered severe when the thickness of the localized, highly reflective area was > or =5 mm on 2-dimensional echocardiography in the 4-chamber view. Carotid artery stenosis was graded as follows: 0%, 20%, 40%, 60%, 80%, and 100%. RESULTS: Compared with the control group, the MAC group showed a significantly higher prevalence of carotid stenosis of > or =40% (45% versus 29%, P=0.006), which was associated with > or =2-vessel disease (23% versus 10%, P=0.006) and bilateral carotid artery atherosclerotic disease (21% versus 10%, P=0.011). Severe MAC was found in 48 patients. More significant differences were found for the severe MAC subgroup (for carotid stenosis of > or =40%) in rates of carotid artery atherosclerotic disease (58% versus 29%, P=0.001), and > or =2-vessel disease (31% versus 10%, P=0.001), in addition to bilateral carotid artery stenosis (27% versus 10%, P=0.004) and even bilateral proximal internal carotid artery stenosis (21% versus 8%, P=0.015). Furthermore, significant carotid artery atherosclerotic disease (stenosis of > or =60%) was significantly more common in the severe MAC subgroup than in the controls (42% versus 26%, P<0.05) and was associated with higher rates of > or =2-vessel disease (19% versus 7%, P=0.02) and bilateral carotid artery stenosis (17% versus 7%, P=0.05). On multivariate analysis, MAC and age but not traditional risk factors were the only independent predictors of carotid atherosclerotic disease (P=0.007 and P=0.04, respectively). CONCLUSIONS: There is a significant association between the presence of MAC and carotid artery atherosclerotic disease. MAC may be an important marker for atherosclerotic disease of the carotid arteries. This association may explain the high prevalence of stroke in patients with MAC.