Rapid measurement of S-100B serum protein levels by Elecsys S100 immunoassay in patients undergoing carotid artery stenting or endarterectomy

OBJECTIVES:: This study was designed to apply the rapid Elecsys(R) S100 immunoassay for real-time measurement of S100 protein serum levels indicating acute brain damage in patients undergoing carotid artery stenting (CAS) or endarterectomy (CEA). DESIGN AND METHODS:: Data of 14 CAS patients were compared to those of 43 CEA and 14 control patients undergoing coronary angiography (CA). S100 serum levels were measured by the full-automatic Elecsys(R) S100 immunoassay and compared to those obtained by the well-established LIA-mat(R) S100 system. RESULTS:: In contrast to CAS and CA patients, median S100 serum levels of CEA patients significantly increased to 0.24 ng/mL before declamping, but subsequently returned to baseline. Three CEA patients with neurological deficits showed sustained elevated S100 levels 6 h after extubation. Absolute S100 values were not significantly different between the two methods. Bland-Altman plot analyses displayed a good agreement, mostly indicating slightly smaller values applying the Elecsys(R) S100 system. CONCLUSIONS:: The Elecsys(R) S100 system appears to be suitable for rapid real-time detection of neurological deficits in patients undergoing CAS and CEA. Persistent elevations of Elecsys(R) S100 levels during CEA were associated with prolonged neurological disorders, whereas transient increases seem to represent impaired blood-brain barrier integrity without neurological deficits.

[The "globulomaxillary cyst" a specific entity or a myth?]

The following review investigates the term and concept of the globulomaxillary cyst as a correct clinico-pathological diagnosis to describe a so-called fissural cyst said to be caused by epithelial entrapment between the nasal and maxillary process. After analyzing the available literature it has to be concluded that neither from an embryologic nor from a clinical or pathohistological standpoint the term globulomaxillary cyst represents a real entity by itself. Therefore, globulomaxillary cysts have to be diagnosed alternatively after a thorough clinical, radiological and histological examination as other odontogenic cysts like dentigerous cysts or odontogenic keratocysts, odontogenic tumors like ameloblastoma, central giant cell tumors, solitary bone cysts, etc.

Substitutions due to antiretroviral toxicity or contraindication in the first 3 years of antiretroviral therapy in a large South African cohort

INTRODUCTION: The patterns and reasons for antiretroviral therapy (ART) drug substitutions are poorly described in resource-limited settings. METHODS: Time to and reason for drug substitution were recorded in treatment-naive adults receiving ART in two primary care treatment programmes in Cape Town. The cumulative proportion of patients having therapy changed because of toxicity was described for each drug, and associations with these changes were explored in multivariate models. RESULTS: Analysis included 2,679 individuals followed for a median of 11 months. Median CD4+ T-cell count at baseline was 85 cells/microl. Mean weight was 59 kg, mean age was 32 years and 71% were women. All started non-nucleoside reverse transcriptase inhibitor-based ART (60% on efavrienz) and 75% started on stavudine (d4T). After 3 years, 75% remained in care on-site, of whom 72% remained on their initial regimen. Substitutions due to toxicity of nevirapine (8% by 3 years), efavirenz (2%) and zidovudine (8%) occurred early. Substitutions on d4T occurred in 21% of patients by 3 years, due to symptomatic hyperlactataemia (5%), lipodystrophy (9%) or peripheral neuropathy (6%), and continued to accumulate over time. Those at greatest risk of hyperlactataemia or lipodystrophy were women on ART > or =6 months, weighing > or =75 kg at baseline. DISCUSSION: A high proportion of adult patients are able to tolerate their initial ART regimen for up to 3 years. In most instances treatment-limiting toxicities occur early, but continue to accumulate over time in patients on d4T. Whilst awaiting other treatment options, the risks of known toxicities could be minimized through early identification of patients at the highest risk.

Whole-body MRI of multiple myeloma: comparison of different MRI sequences in assessment of different growth patterns

PURPOSE: To determine sensitivity, specificity and inter-observer variability of different whole-body MRI (WB-MRI) sequences in patients with multiple myeloma (MM). METHODS AND MATERIALS: WB-MRI using a 1.5T MRI scanner was performed in 23 consecutive patients (13 males, 10 females; mean age 63+/-12 years) with histologically proven MM. All patients were clinically classified according to infiltration (low-grade, n=7; intermediate-grade, n=7; high-grade, n=9) and to the staging system of Durie and Salmon PLUS (stage I, n=12; stage II, n=4; stage III, n=7). The control group consisted of 36 individuals without malignancy (25 males, 11 females; mean age 57+/-13 years). Two observers independently evaluated the following WB-MRI sequences: T1w-TSE (T1), T2w-TIRM (T2), and the combination of both sequences, including a contrast-enhanced T1w-TSE with fat-saturation (T1+/-CE/T2). They had to determine growth patterns (focal and/or diffuse) and the MRI sequence that provided the highest confidence level in depicting the MM lesions. Results were calculated on a per-patient basis. RESULTS: Visual detection of MM was as follows: T1, 65% (sensitivity)/85% (specificity); T2, 76%/81%; T1+/-CE/T2, 67%/88%. Inter-observer variability was as follows: T1, 0.3; T2, 0.55; T1+/-CE/T2, 0.55. Sensitivity improved depending on infiltration grade (T1: 1=60%; 2=36%; 3=83%; T2: 1=70%; 2=71%; 3=89%; T1+/-CE/T2: 1=50%; 2=50%; 3=89%) and clinical stage (T1: 1=58%; 2=63%; 3=79%; T2: 1=58%; 2=88%; 3=100%; T1+/-CE/T2: 1=50%; 2=63%; 3=100%). T2w-TIRM sequences achieved the best reliability in depicting the MM lesions (65% in the mean of both readers). CONCLUSIONS: T2w-TIRM sequences achieved the highest level of sensitivity and best reliability, and thus might be valuable for initial assessment of MM. For an exact staging and grading the examination protocol should encompass unenhanced and enhanced T1w-MRI sequences, in addition to T2w-TIRM.

Rapid determination of gemcitabine in plasma and serum using reversed-phase HPLC

Gemcitabine (2'2'-difluorodeoxycytidine) is a pyrimidine analog used in the treatment of a variety of solid tumors. After intravenous (i.v.) administration, it is rapidly inactivated to 2'-deoxy-2',2'-difluorouridine (dFdU). A sensitive analytical method for the quantitation of gemcitabine is required for the assessment of alternative dosage and treatment schemes. A rapid and robust RP-HPLC assay for analysis of gemcitabine in human and animal plasma and serum was developed and validated using 2'-deoxyuridine (dU) and 5-fluoro-2'-deoxyuridine (5FdU) as internal standards. It is based on protein precipitation, the use of an Atlantis dC18 column of 100 mm length (inner diameter, 4.6 mm; particle size, 3 microm) and isocratic elution using a 10 mM phosphate buffer, pH 3.0, followed by isocratic elution with the same buffer containing 3% of ACN. For gemcitabine, RSD values for intraday and interday precision were < 4.4 and 5.3%, respectively, the LOQ was 20 ng/mL, and the assay was linear in the range of 0.020-20 microg/mL with an accuracy of > or =89%. The recovery for gemcitabine, dU and 5FdU was 86-98%. The assay was applied to determine gemcitabine levels in plasma samples of patients collected during and shortly after conventional infusion of 25-30 mg/kg body mass (levels: 2.0-18.9 microg/mL) and rats that received lower doses (1.5 mg/kg) via i.v., subcutaneous and oral drug administration (levels: 0.20-2.60 microg/mL). It could also be applied to estimate dFdU levels in human plasma.

Pathomorphologic alterations predict presence or absence of hip osteoarthrosis

Abnormal morphology of the hip has been associated with primary osteoarthrosis. We evaluated the morphology of 464 consecutive hips contralateral to hips treated by THA. We excluded all hips with known diagnoses leading to secondary osteoarthritis and all hips with advanced arthrosis to eliminate the effect of arthritic remodeling on the morphologic measurements. Of the remaining 119 hips, 25 were in patients aged 60 years or older who had no or mild arthrosis (Tönnis Grade 0 or 1) and 94 hips had Tönnis Grade 2 osteoarthrosis. We quantified morphologic parameters on plain radiographs and CT images and simulated range of motion using virtual bone models from the CT data. The nonarthritic hips had fewer pathomorphologic findings. High alpha angles and high lateral center edge angles were strongly associated with the presence of arthritis; decreased internal and external rotation in 90 degrees flexion showed lesser correlation. The data confirm previous observations that abnormal hip morphology predates arthrosis and is not secondary to the osteoarthritic process. Hips at risk for developing arthrosis resulting from pathomorphologic changes may potentially be identified at the cessation of growth, long before the development of osteoarthrosis.

Depression, the metabolic syndrome and cardiovascular risk

BACKGROUND: The relationship between depression and the metabolic syndrome is unclear, and whether metabolic syndrome explains the association between depression and cardiovascular disease (CVD) risk is unknown. METHODS: We studied 652 women who received coronary angiography as part of the Women's Ischemia Syndrome Evaluation (WISE) study and completed the Beck Depression Inventory (BDI). Women who had both elevated depressive symptoms (BDI > or =10) and a previous diagnosis of depression were considered at highest risk, whereas those with one of the two conditions represented an intermediate group. The metabolic syndrome was defined according to the ATP-III criteria. The main outcome was incidence of adverse CVD events (hospitalizations for myocardial infarction, stroke, congestive heart failure, and CVD-related mortality) over a median follow-up of 5.9 years. RESULTS: After adjusting for demographic factors, lifestyle and functional status, both depression categories were associated with about 60% increased odds for metabolic syndrome compared with no depression (p = .03). The number of metabolic syndrome risk factors increased gradually across the three depression categories (p = .003). During follow-up, 104 women (15.9%) experienced CVD events. In multivariable analysis, women with both elevated symptoms and a previous diagnosis of depression had 2.6 times higher risk of CVD. When metabolic syndrome was added to the model, the risk associated with depression only decreased by 7%, and both depression and metabolic syndrome remained significant predictors of CVD. CONCLUSIONS: In women with suspected coronary artery disease, the metabolic syndrome is independently associated with depression but explains only a small portion of the association between depression and incident CVD.

Intra-arterial thrombolysis of acute iatrogenic intracranial arterial occlusion attributable to neuroendovascular procedures or coronary angiography

BACKGROUND AND PURPOSE: For selected stroke patients, intra-arterial thrombolysis (IAT) has been shown to be an effective treatment option. However, knowledge of safety and efficacy of IAT in patients with acute stroke as a complication of arterial catheter interventions is limited. METHODS: We analyzed clinical radiological findings and functional outcomes in consecutive patients 3 months after treatment with IAT for peri-procedural strokes occurring during neuroendovascular or cardiac catheter interventions. To measure outcome, the modified Rankin scale score was used. RESULTS: Of a total of 432 patients treated with IAT, 12 (4 women and 8 men; mean age, 60 years) were treated because of an ischemic stroke after a neuro-endovascular procedure (n=6) or coronary angiography (n=6). The median baseline National Institutes of Health Stroke Scale score was 15. Recanalization was complete (thrombolysis in myocardial infarction grade 3) in 6, partial (thrombolysis in myocardial infarction 2) in 5, and minimal (thrombolysis in myocardial infarction 1) in 1. Nine patients (75%) had a favorable outcome (modified Rankin scale score, 0 to 2), and 3 had a poor outcome (modified Rankin scale score, 3 or 4). All patients with complete recanalization had a favorable outcome, whereas only 3 of 6 patients with partial or minimal recanalization (P=0.18) had a favorable outcome. Follow-up brain imaging was normal in 2 and showed new ischemic lesions in 10 patients. Two patients (17%) had a symptomatic intracerebral hemorrhage. CONCLUSIONS: In acute stroke attributable to arterial catheter interventions, IAT is feasible and has the potential to improve outcome in these patients. A high recanalization rate could be achieved.

Takotsubo cardiomyopathy or transient left ventricular apical ballooning syndrome: A systematic review

BACKGROUND: Transient left ventricular apical ballooning syndrome (TLVABS) is an acute cardiac syndrome mimicking ST-segment elevation myocardial infarction characterized by transient wall-motion abnormalities involving apical and mid-portions of the left ventricle in the absence of significant obstructive coronary disease. METHODS: Searching the MEDLINE database 28 case series met the eligibility criteria and were summarized in a narrative synthesis of the demographic characteristics, clinical features and pathophysiological mechanisms. RESULTS: TLVABS is observed in 0.7-2.5% of patients with suspected ACS, affects women in 90.7% (95% CI: 88.2-93.2%) with a mean age ranging from 62 to 76 years and most commonly presents with chest pain (83.4%, 95% CI: 80.0-86.7%) and dyspnea (20.4%, 95% CI: 16.3-24.5%) following an emotionally or physically stressful event. ECG on admission shows ST-segment elevations in 71.1% (95% CI: 67.2-75.1%) and is accompanied by usually mild elevations of Troponins in 85.0% (95% CI: 80.8-89.1%). Despite dramatic clinical presentation and substantial risk of heart failure, cardiogenic shock and arrhythmias, LVEF improved from 20-49.9% to 59-76% within a mean time of 7-37 days with an in-hospital mortality rate of 1.7% (95% CI: 0.5-2.8%), complete recovery in 95.9% (95% CI: 93.8-98.1%) and rare recurrence. The underlying etiology is thought to be based on an exaggerated sympathetic stimulation. CONCLUSION: TLVABS is a considerable differential diagnosis in ACS, especially in postmenopausal women with a preceding stressful event. Data on longterm follow-up is pending and further studies will be necessary to clarify the etiology and reach consensus in acute and longterm management of TLVABS.

Trastuzumab-associated cardiac adverse effects in the herceptin adjuvant trial

PURPOSE: The purpose of this analysis was to investigate trastuzumab-associated cardiac adverse effects in breast cancer patients after completion of (neo)adjuvant chemotherapy with or without radiotherapy. PATIENTS AND METHODS: The Herceptin Adjuvant (HERA) trial is a three-group, multicenter, open-label randomized trial that compared 1 or 2 years of trastuzumab given once every 3 weeks with observation in patients with HER-2-positive breast cancer. Only patients who after completion of (neo)adjuvant chemotherapy with or without radiotherapy had normal left ventricular ejection fraction (LVEF > or = 55%) were eligible. A repeat LVEF assessment was performed in case of cardiac dysfunction. RESULTS: Data were available for 1,693 patients randomly assigned to 1 year trastuzumab and 1,693 patients randomly assigned to observation. The incidence of trastuzumab discontinuation due to cardiac disorders was low (4.3%). The incidence of cardiac end points was higher in the trastuzumab group compared with observation (severe congestive heart failure [CHF], 0.60% v 0.00%; symptomatic CHF, 2.15% v 0.12%; confirmed significant LVEF drops, 3.04% v 0.53%). Most patients with cardiac dysfunction recovered in fewer than 6 months. Patients with trastuzumab-associated cardiac dysfunction were treated with higher cumulative doses of doxorubicin (287 mg/m(2) v 257 mg/m(2)) or epirubicin (480 mg/m(2) v 422 mg/m(2)) and had a lower screening LVEF and a higher body mass index. CONCLUSION: Given the clear benefit in disease-free survival, the low incidence of cardiac adverse events, and the suggestion that cardiac dysfunction might be reversible, adjuvant trastuzumab should be considered for treatment of breast cancer patients who fulfill the HERA trial eligibility criteria.

[Physical and psychological status of 60-70-year-old citizens of Bern with neurotic symptoms in childhood--a study over more than 50 years (Emmental cohort)]

The present study was undertaken to assess the influence of childhood variables (physical and emotional) to later well-being in a group of rural Swiss (Emmental Cohort). Our study is the first prospective cohort over a time period of more than 50 years. It includes 1537 children who were listed and assessed in 1942 (T1) because they had difficulties in school or were otherwise behaviorally disturbed. In 1995 (T2) more than 60% of the initial population could be reassessed by our study group. We found more subjects at T2 who had been rated as intelligent at T1. More subjects responding to T2 belonged to a higher social class, were more anxious, and had more psychosocial problems at T1. Social income at T2 is correlated to the social class at T1. More subjects have died since who were rated at T1 as being less intelligent, less neurotical, and having higher psychosocial problems. Twice as many men died than women. The emotional situation at T2 is significantly correlated to psychological well-being at T1. The somatic complaints at T2 correlate significantly to neurotic symptoms in childhood (T1). The more intelligent the children were rated at T1, the less emotional and somatic complaints were voiced at T2 and the better the psychic well-being was rated (T2). In addition, the former social milieu (T1) significantly determined somatic and psychological complaints at T2. Our data discern a significant correlation between actual status and former childhood variables more than 50 years later in a rural Swiss cohort (Emmental Cohort).

Performance of dental implants after staged sinus floor elevation procedures: 5-year results of a prospective study in partially edentulous patients

OBJECTIVES: The aim of this prospective study was to evaluate the 5-year performance and success rate of titanium screw-type implants with the titanium plasma spray (TPS) or the sand-blasted, large grit, acid-etched (SLA) surface inserted in a two-stage sinus floor elevation (SFE) procedure in the posterior maxilla. MATERIAL AND METHODS: A total of 59 delayed SFEs were performed in 56 patients between January 1997 and December 2001, using a composite graft with autogenous bone chips combined with deproteinized bovine bone mineral (DBBM) or synthetic porous beta-tricalcium phosphate (beta-TCP). After a healing period averaging 7.75 months, 111 dental implants were inserted. After an additional 8-14-week healing period, all implants were functionally loaded with cemented crowns or fixed partial dentures. The patients were recalled at 12 and 60 months for clinical and radiographic examination. RESULTS: One patient developed an acute infection in the right maxillary sinus after SFE and did not undergo implant therapy. Two of the 111 inserted implants had to be removed because of a developing atypical facial pain, and 11 implants were lost to follow-up and were considered drop-outs. The remaining 98 implants showed favorable clinical and radiographic findings at the 5-year examination. The peri-implant soft tissues were stable over time; the mean probing depths and mean attachment levels did not change during the follow-up period. The measurement of the bone crest levels (DIB values) indicated stability as well. Based on strict success criteria, all 98 implants were considered successfully integrated, resulting in a 5-year success rate of 98% (for TPS implants 89%, for SLA implants 100%). CONCLUSION: This prospective study assessing the performance of dental implants inserted after SFE demonstrated that titanium implants can achieve and maintain successful tissue integration with high predictability for at least 5 years of follow-up in carefully selected patients.

The influence of non-matching implant and abutment diameters on radiographic crestal bone levels in dogs

BACKGROUND: It has been shown that different implant designs and different vertical implant positions have an influence on crestal bone levels. The aim of the present study was to evaluate radiographic crestal bone changes around experimental dental implants with non-matching implant-abutment diameters placed submucosally or transmucosally at three different levels relative to the alveolar crest. METHODS: Sixty two-piece dental implants with non-matching implant-abutment diameters were placed in edentulous spaces bilaterally in five foxhounds. The implants were placed submucosally or transmucosally in the left or the right side of the mandible. Within each side, six implants were randomly placed at three distinct levels relative to the alveolar crest. After 12 weeks, 60 crowns were cemented. Radiographs were obtained from all implant sites following implant placement, after crown insertion, and monthly for 6 months after loading. RESULTS: Radiographic analysis revealed very little bone loss and a slight increase in bone level for implants placed at the level of the crest or 1 mm above. The greatest bone loss occurred at implants placed 1 mm below the bone crest. No clinically significant differences regarding marginal bone loss and the level of the bone-to-implant contact were detected between implants with a submucosal or a transmucosal healing. CONCLUSIONS: Implants with non-matching implant-abutment diameters demonstrated some bone loss; however, it was a small amount. There was no clinically significant difference between submucosal and transmucosal approaches.

Controlled toothbrush abrasion of softened human enamel

The aim of this in vitro study was to compare toothbrush abrasion of softened enamel after brushing with two (soft and hard) toothbrushes. One hundred and fifty-six human enamel specimens were indented with a Knoop diamond. Salivary pellicle was formed in vitro over a period of 3 h. Erosive lesions were produced by means of 1% citric acid. A force-measuring device allowed a controlled toothbrushing force of 1.5 N. The specimens were brushed either in toothpaste slurry or with toothpaste in artificial saliva for 15 s. Enamel loss was calculated from the change in indentation depth of the same indent before and after abrasion. Mean surface losses (95% CI) were recorded in ten treatment groups: (1) soft toothbrush only [28 (17-39) nm]; (2) hard toothbrush only [25 (16-34) nm]; (3) soft toothbrush in Sensodyne MultiCare slurry [46 (27-65) nm]; (4) hard toothbrush in Sensodyne MultiCare slurry [45 (24-66) nm]; (5) soft toothbrush in Colgate sensation white slurry [71 (55-87) nm]; (6) hard toothbrush in Colgate sensation white slurry [85 (60-110) nm]; (7) soft toothbrush with Sensodyne MultiCare [48 (39-57) nm]; (8) hard toothbrush with Sensodyne MultiCare [40 (29-51) nm]; (9) soft toothbrush with Colgate sensation white [51 (37-65) nm]; (10) hard toothbrush with Colgate sensation white [52 (36-68) nm]. Neither soft nor hard toothbrushes produced significantly different toothbrush abrasion of softened human enamel in this model (p > 0.05).