Biomedical subjects

Achim Heinecke

Publications and source records attributed to Achim Heinecke.

At least 37 records · Page 2Linked to original sources

PubMed2004

Endoscopic retrograde cholangiopancreatography, intraductal ultrasonography, and magnetic resonance cholangiopancreatography in bile duct strictures: a prospective comparison of imaging diagnostics with histopathological correlation.

OBJECTIVES: A variety of imaging techniques are available to diagnose bile duct strictures; the most effective imaging technique, however, has not been established yet. In the present study, we compared the impact of endoscopic retrograde cholangiopancreatography (ERCP), intraductal ultrasonography (IDUS), and magnetic resonance cholangiopancreatography (MRCP) with regard to diagnosing bile duct strictures. METHODS: We prospectively examined 33 patients with jaundice due to bile duct strictures by ERCP plus IDUS and MRCP. The objectives were to assess diagnostic quality of imaging, complete presentation of the bile duct, and differentiation of malignant from benign lesions. Surgical and histopathological correlations, which were used as the gold standard, were available in all cases since all included patients underwent laparotomy. RESULTS: Diagnostic image quality for ERCP was 88% and 76% for MRCP (p > 0.05). Comparing ERCP and MRCP, complete presentation of the biliary tract was achieved in 94% and 82%, respectively (p > 0.05). ERCP and MRCP allowed correct differentiation of malignant from benign lesions in 76% and 58% (p= 0.057), respectively. By supplementing ERCP with IDUS, the accuracy of correct differentiation of malignant from benign lesions increased significantly to 88% (p= 0.0047). CONCLUSIONS: Comparing ERCP with MRCP, we found adequate presentation of bile duct strictures in high imaging quality for both techniques. ERCP supplemented by IDUS gives more reliable and precise information about differentiation of malignant and benign lesions than MRCP alone without additional imaging sequences.

Analysis of Variance↗

PubMed2004

Microbiological shifts in intra- and extraoral habitats following mechanical periodontal therapy.

OBJECTIVES: The aim of the present study was to analyze the intra- and extraoral colonization dynamics of periodontal pathogens following supra- and subgingival debridement. MATERIAL AND METHODS: Thirty five patients with chronic periodontitis were enrolled in the study. Supra- and subgingival plaque samples, saliva, and swab samples from mucosa and extraoral sites were taken at baseline and 6 weeks, 3 months and 6 months after mechanical periodontal therapy. Actinobacillus actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg), Eikenella corrodens (Ec), Tannerella forsythensis (Tf), Prevotella intermedia (Pi), Prevotella nigrescens (Pn), and Treponema denticola (Td) were identified by PCR. RESULTS: Supra- and subgingival debridement decreased the number of subgingival sites infected with the analyzed pathogens only transiently, if at all. However, the detection frequencies of Tf, Td, Ec, Pi, and Pn in the supragingival region, of Pg, Td, and Pn at the oral mucosa sites (mostly the tongue), and of all pathogens except Aa in saliva increased over the 6-month observation period. Td was the only pathogen recorded in notable quantities in the extraoral habitat (external ear canal). CONCLUSION: The results indicate that supra- and subgingival debridement results in a dissemination of periodontal pathogens within the oral cavity.

Bacteria, Anaerobic↗

PubMed2004

Increased fasting total homocysteine plasma levels as a risk factor for thromboembolism in children.

Elevated total homocysteine (tHcy) concentrations are an independent risk factor for thromboembolic events in adults. In children with moderate hyperhomocysteinemia data are sparse. Therefore, between 1995 and 2002 we consecutively recruited 163 white pediatric patients with a first symptomatic thromboembolic event and 255 healthy controls (mean age: 6.4 years in patients vs. 6.6 years in controls, range: 3 months to 18 years) and measured fasting tHcy levels. Median tHcy levels in patients were significantly higher (6.6 micromol/l, range 2.9-20.4 micromol/l) than in controls (5.7 micromol/l, 2.0-14.0 micromol/l, p<0.0001). 48 of the 163 patients with thromboembolism (29.5%) versus 26 of the 255 controls (10.2%) had tHcy levels above the age-specific normal 90th percentile (OR 2.9, 95%CI: 1.7-4.8). The odds ratio for children in the highest quintile compared to children with levels in the lowest quintile was 4.3 (1.6-8.1; highest quintile: median tHcy level 9.6 micromol, range 8.0-20.4), showing a significantly increased risk for thromboembolic disease with even mild hyperhomocysteinemia. We conclude that hyperhomocysteinemia above the age-specific cut-off values is a risk factor for thromboembolic events in children. Therefore, screening for elevated fasting tHcy levels of patients with thromboembolism is recommended to stratify the risk of thromboembolism.

Adolescent↗

PubMed2004

A new prognostic score for patients with acute myeloid leukemia based on cytogenetics and early blast clearance in trials of the German AML Cooperative Group.

BACKGROUND AND OBJECTIVES: To refine cytogenetically based risk-stratification in acute myeloid leukemia (AML). DESIGN AND METHODS: Stratification was improved by combining cytogenetics and day 16 bone marrow blasts and by subdividing unfavorable cytogenetics. The new score identifying five prognostically different groups was developed in 321 patients (AMLCG 1992 trial) and subsequently validated in 680 patients (AMLCG 1999 trial). RESULTS: Subgroups defined were: 1) favorable cytogenetics (t(8;21), inv(16)); 2) intermediate cytogenetics (normal karyotype, other abnormalities not rated favorable or unfavorable) and day 16 blasts <10%; 3) intermediate cytogenetics and day 16 blasts >or=10%; 4) unfavorable cytogenetics (-5/5q-, -7/7q-, 3q21q26 aberrations, 11q23 aberrations, 12p-, 17p-) excluding complex aberrations; 5) complex aberrant karyotypes (>or=3 aberrations). In AMLCG 1992 patients significant differences were observed with regard to complete remission (CR) rate (82%, 83%, 58%, 76%, 53%), persistent leukemia (PL) rate (7%, 8%, 33%, 14%, 31%), median event-free survival (EFS; 25, 14, 5, 6, 2 months), median overall survival (OS; not reached, 26, 12, 14, 6 months), and median relapse-free survival (RFS; 26, 19, 13, 8, 4 months). The prospective validation of the score proved its significant power (AMLCG 1999 cohort) with regard to CR (63%, 65%, 51%, 45%, 35%), PL (17%, 18%, 40%, 35%, 48%), median EFS (14, 7, 3, 2, 2 months), median OS (25, 15, 12, 6, 4 months), and median RFS (not reached, 15, 10, 8, 5 months). INTERPRETATION AND CONCLUSIONS: This new prognostic score provides a highly valuable tool for future clinical trials in AML focusing on distinct and subgroup-specific treatment effects.

Acute Disease↗

PubMed2003

6-Thioguanine, cytarabine, and daunorubicin (TAD) and high-dose cytarabine and mitoxantrone (HAM) for induction, TAD for consolidation, and either prolonged maintenance by reduced monthly TAD or TAD-HAM-TAD and one course of intensive consolidation by sequential HAM in adult patients at all ages with de novo acute myeloid leukemia (AML): a randomized trial of the German AML Cooperative Group.

PURPOSE: To examine the efficacy of prolonged maintenance chemotherapy versus intensified consolidation therapy for patients with acute myeloid leukemia (AML). MATERIALS AND METHODS: Eight hundred thirty-two patients (median age, 54 years; range, 16 to 82 years) with de novo AML were randomly assigned to receive 6-thioguanine, cytarabine, and daunorubicin (TAD) plus cytarabine and mitoxantrone (HAM; cytarabine 3 g/m2 [age < 60 years] or 1 g/m2 [age > or = 60 years] x 6) induction, TAD consolidation, and monthly modified TAD maintenance for 3 years, or TAD-HAM-TAD and one course of intensive consolidation with sequential HAM (S-HAM) with cytarabine 1 g/m2 (age < 60 years) or 0.5 g/m2 (age > or = 60 years) x 8 instead of maintenance. RESULTS: A total of 69.2% patients went into complete remission (CR). Median relapse-free survival (RFS) was 19 months for patients on the maintenance arm, with 31.4% of patients relapse-free at 5 years, versus 12 months for patients on the S-HAM arm, with 24.7% of patients relapse-free at 5 years (P =.0118). RFS from maintenance was superior in patients with poor risk by unfavorable karyotype, age > or = 60 years, lactate dehydrogenase level greater than 700 U/L, or day 16 bone marrow blasts greater than 40% (P =.0061) but not in patients with good risk by complete absence of any poor risk factors. Although a survival benefit in the CR patients is not significant (P =.085), more surviving patients in the maintenance than in the S-HAM arm remain in first CR (P =.026). CONCLUSION: We conclude that TAD-HAM-TAD-maintenance first-line treatment has a higher curative potential than TAD-HAM-TAD-S-HAM and improves prognosis even among patients with poor prognosis.

Adolescent↗

PubMed2003

Cerebral venous thrombosis in children: a multifactorial origin.

BACKGROUND: The present study was performed to assess the association of prothrombotic risk factors and underlying conditions (infections, vascular trauma, immobilization, malignancies, autoimmune diseases, renal diseases, metabolic disorders, obesity, birth asphyxia, cardiac malformations, and use of prothrombotic drugs) with cerebral venous thrombosis (CVT) in children. METHODS AND RESULTS: From 1995 to 2002, 149 pediatric patients aged newborn to <18 years (median 6 years) with CVT were consecutively enrolled. In patients and in 149 age- and gender-matched children with similar underlying clinical conditions but without CVT, the factor V G1691A mutation, the factor II G20210A variant, lipoprotein(a) [Lp(a)], protein C, protein S, antithrombin, and antiphospholipid antibodies, as well as associated clinical conditions, were investigated. Eighty-four (56.4%) of the patients had at least 1 prothrombotic risk factor compared with 31 control children (20.8%; P<0.0001). In addition, 105 (70.5%) of 149 patients with CVT presented with an underlying predisposing condition. On univariate analysis, factor V, protein C, protein S, and elevated Lp(a) were found to be significantly associated with CVT. However, in multivariate analysis, only the combination of a prothrombotic risk factor with an underlying condition (OR 3.9, 95% CI 1.8 to 8.6), increased Lp(a) (OR 4.1, 95% CI 2.0 to 8.7), and protein C deficiency (OR 11.1, 95% CI 1.2 to 104.4) had independent associations with CVT in the children investigated. CONCLUSIONS: CVT in children is a multifactorial disease that, in the majority of cases, results from a combination of prothrombotic risk factors and/or underlying clinical condition.

Adolescent↗

PubMed2003

Analysis of cyclooxygenase-2 expression in human breast cancer: high throughput tissue microarray analysis.

PURPOSE: The objective of this study was to evaluate breast carcinomas for the expression of cyclooxygenase-2 (Cox-2) using a tissue microarray (TMA) and to determine its clinical and prognostic relevance. METHODS: We analyzed Cox-2 expression in 600 samples from 200 breast carcinomas immunohistochemically performing TMA technology and semiquantitative analysis. Results were correlated with various clinicopathological variables and follow-up data. Expression of estrogen receptor, progesterone receptor, Ki-67, and Her-2/neu-oncogene was analyzed and correlated with Cox-2 status. RESULTS: We observed a moderate or strong cytoplasmic staining for Cox-2 in 78 (40.6%) of breast carcinomas. Increased Cox-2 expression corresponded to higher pT stage ( P=0.038), amplification of Her-2/neu ( P=0.032), lymphovascular invasion ( P=0.006), a high MIB-1 labeling index (LI) ( P<0.001), and histological grading ( P=0.013). We also observed an inverse relationship between strong Cox-2 expression and estrogen and progesterone receptor content of tumors ( P=0.037 and P=0.010). However, we could not demonstrate a significant association between Cox-2 staining and overall survival or disease free survival time. CONCLUSIONS: These results suggest that Cox-2 expression is significantly associated with less differentiated and more aggressive breast carcinomas and might therefore be a useful prognostic indicator as well as a target for therapy.

Breast Neoplasms↗

PubMed2003

Morphologic dysplasia in de novo acute myeloid leukemia (AML) is related to unfavorable cytogenetics but has no independent prognostic relevance under the conditions of intensive induction therapy: results of a multiparameter analysis from the German AML Cooperative Group studies.

PURPOSE: On the basis of cytomorphology according to the French-American-British (FAB) classification, we evaluated the prognostic impact of dysplastic features and other parameters in de novo acute myeloid leukemia (AML). We also assessed the clinical significance of the recently introduced World Health Organization (WHO) classification for AML, which proposed dysplasia as a new parameter for classification. PATIENTS AND METHODS: We analyzed prospectively 614 patients with de novo AML, all of whom were diagnosed by central morphologic analysis and treated within the German AML Cooperative Group (AMLCG)-92 or the AMLCG-acute promyalocytic leukemia study. RESULTS: Patients with AML M3, M3v, or M4eo demonstrated a better outcome compared with all other FAB subtypes (P <.001); no prognostic difference was observed among other FAB subtypes. The presence or absence of dysplasia failed to demonstrate prognostic relevance. Other prognostic markers, such as age, cytogenetics, presence of Auer rods, and lactate dehydrogenase (LDH) level at diagnosis, all showed significant impact on overall and event-free survival in univariate analyses (P <.001 for all parameters tested). However, in a multivariate analysis, only cytogenetics (unfavorable or favorable), age, and high LDH maintained their prognostic impact. Dysplasia was not found to be an independent prognostic parameter, but the detection of trilineage dysplasia correlated with unfavorable cytogenetics. CONCLUSION: Our results indicate that cytomorphology and classification according to FAB criteria are still necessary for the diagnosis of AML but have no relevance for prognosis in addition to cytogenetics. Our results suggest that the WHO classification should be further developed by using cytogenetics as the main determinant of biology. Dysplastic features, in particular, have no additional impact on predicting prognosis when cytogenetics are taken into account.

Acute Disease↗

PubMed2003

Acute toxicity of adjuvant radiotherapy in locally advanced differentiated thyroid carcinoma. First results of the multicenter study differentiated thyroid carcinoma (MSDS).

BACKGROUND AND PURPOSE: The indication for adjuvant postoperative radiotherapy in patients with differentiated thyroid carcinoma (DTC) extending beyond the thyroid capsule has been an issue of controversy during the past 2 decades. No randomized studies evaluating the benefit of radiotherapy have been published so far. In the Multicenter Study Differentiated Thyroid Carcinoma (MSDS), a randomization has been performed concerning external-beam radiotherapy in patients with DTC extending beyond the thyroid capsule (pT4 pN0/1/x cM0, TNM classification, 5th edition, 1997) following surgery and radioiodine therapy. Radiation-associated toxicity has been prospectively evaluated. PATIENTS AND METHODS: Radiotherapy was performed with 50.4 Gy (pN0) or 54.0 Gy (pN1/x) to the cervical, supraclavicular and upper mediastinal lymph nodes. A total dose of 59.4 Gy (R0 resection) or 66.6 Gy (R1) was used to treat the tumor bed. Conventional fractionation was used with 1.8 Gy/d. At the time of the analysis, 36 patients were randomized or allocated to treatment arm A (with external-beam radiotherapy). Of these, 22 were treated with radiotherapy, and documentation of acute toxicity was available. Toxicity was evaluated prospectively according to the RTOG/EORTC criteria. RESULTS: The maximal acute toxicity observed during radiotherapy was grade I in four patients, grade II in 16 patients, and grade III in two patients (9.1%; 95% confidence interval [95% CI] 1.1-29.2%). Toxicity was mainly observed at the pharynx, larynx, and skin. In 19 patients, residual toxicity within 100 days following radiotherapy was evaluated. No residual toxicity was observed in two patients. Maximal residual toxicity was grade I in 13 patients and grade II in four. No further grade III toxicity could be observed. CONCLUSION: The majority of patients experience mild to moderate side effects from adjuvant external-beam radiotherapy. At the first follow-up examination, most side effects have subsided. Acute toxicity is tolerable in these patients.

Adenocarcinoma, Follicular↗

PubMed2003

Semi-quantitative immunochromatographic test for prostate specific antigen in whole blood: tossing the coin to predict prostate cancer?

OBJECTIVES: A strip test for the semi-quantitative determination of prostate specific antigen (PSA) based on whole blood was evaluated by the Working Group on Laboratory Diagnostics of the German Urological Association. METHODS: In 301 men (156 volunteers and 145 referred patients, mean ages 57 years and 64 years) handling and capability of the strip test to predict PSA serum concentrations (Access Hybritech, Beckman Coulter, Inc., Fullerton, CA, USA) relative to a cutoff of 4 micro g/l were investigated. For patients, the strip test was performed by investigators, volunteers accomplished it according to leaflet instructions. Each test result was interpreted by both, the patient/volunteer and an investigator. RESULTS: 24% of the volunteers required assistance with test performance. The overall agreement between Access PSA (range 0.1-29.7) and strip test was 76% (read by participants) and 79% (read by investigators). Within the PSA ranges 0.1-3, 3.1-5 and 5.1-10, participants yielded agreement rates of 89%, 40% and 56%, respectively. Studying the 2.1-10 PSA range most relevant for prostate cancer screening, agreement rate (53%), sensitivity (50%) and specificity (67%) were barely superior to random chance. Volunteers alone (PSA range 0.1-11.3 micro g/l) yielded a specificity of 92%, however, all PSA values above the cutoff (n=8) went unrecognized and all positive strip tests (n=12) were incorrect (sensitivity 0%, positive predictive value 0%). CONCLUSIONS: Test handling and interpretation was difficult. The rate of false strip test results is disappointing even for PSA ranges remote from the cutoff. In its present form the strip test fails to meet the clinical requirements and its launch to the market was therefore discontinued.

Diagnostic Errors↗

PubMed2003

Hyperfractionated cyclophosphamide in combination with pulsed dexamethasone and thalidomide (HyperCDT) in primary refractory or relapsed multiple myeloma.

Sixty patients with advanced multiple myeloma received 2-6 monthly treatment courses combining hyperfractionated cyclophosphamide (300 mg/m2 i.v. over 3 h q 12 h x 6, d 1-3) with pulsed dexamethasone (20 mg/m2/d p.o., d 1-4, 9-12, 17-20) and once daily thalidomide at individually escalating doses (100-400 mg/d) depending on tolerability (HyperCDT). Responding patients were maintained on daily thalidomide and monthly dexamethasone pulses. Complete, partial and minor response rates were 4%, 68% and 12% respectively; overall response rate was 84% (efficacy analysis). Median event-free and overall survival was 11 and 19 months respectively. During at least one treatment cycle, 67% of patients experienced grade 4 neutropenia resulting in 17% grade 3 and 9% grade 4 infections. Side-effects, presumably related to thalidomide, included neuropathy (40% grade 2, 16% grade 3), constipation (17%), oedema (5%), bradycardia (5%), skin reactions (3%), cerebrovascular events (5%) and deep vein thromboses (8%). Thromboses were not related to known thrombophilic risk factors. Four patients with prior myeloma therapy > 50 months developed myelodysplastic syndrome or secondary acute myeloid leukaemia 2-4 months after study entry. HyperCDT is a highly active and reasonably well-tolerated salvage regimen in advanced or refractory multiple myeloma.

Acute Disease↗

PubMed2003

Speech performance in lingual orthodontic patients measured by sonagraphy and auditive analysis.

Esthetically appealing, externally invisible, lingually applied orthodontic brackets are in increasing demand. Because the brackets are placed lingually, however, they appear to cause some problems with respect to speech. This study is the first to present a prospective evaluation of the articulation of 23 patients with lingual brackets by means of an innovative combination of test methods. An acoustic, objective evaluation of articulation measured by digital sonagraphy was related to a semiobjective auditive evaluation by 10 speech professionals, to a semiobjective auditive evaluation by close contacts of the patients, and to a subjective auditive evaluation by the patients themselves, the latter 2 using standardized questionnaires. The tests were performed before (T1), within 24 hours after (T2), and 3 months (+/- 1 week) after (T3) the start of therapy. In comparison with the initial findings, a significant deterioration in articulation was recorded with all test methods at T2 and T3. Using a new combination of methods, our investigations show the need for detailed briefing of patients about the extent and duration of changes in speech resulting from lingual brackets.

Adult↗

PubMed2003

A new modification of the Chiron ACS assay for total prostate-specific antigen achieves equimolar response characteristics and improves the detection of prostate cancer.

Nonequimolar-response assays for prostate-specific antigen (PSA) are criticized for overestimating total PSA in some men without prostate cancer (PCA), and underestimating total PSA in some men with PCA. We recently studied three nonequimolar-response PSA assays that had undergone modifications. While two of the studied assays achieved equimolar-response characteristics with improved areas under receiver operating characteristic (ROC) curves (AUC), the modification of the Chiron ACS PSA assay (ACS PSA2, Chiron) failed to achieve this. Recently, the ACS assay underwent another modification (ACS PSA, Bayer), which we investigated. Sera from 305 men (155 without and 150 with PCA, PSA > or = 2 and < or = 30 microg/l, Tandem-E) were measured using both modifications of the ACS assay and equimolar-response reference methods (Tandem-R free and Tandem-E, Hybritech). Molar response relative to the reference method and clinical performance (comparison of AUCs) between the previous and new ACS assay modifications were studied. The new modification of the ACS assay (ACS PSA, Bayer) achieved equimolar-response characteristics but reported lower values (average 10%) than the Tandem-E assay. Compared to the previous modification (ACS PSA2, Chiron), a 3% improvement in AUC (p = 0.01) was found. Using results of the redesigned equimolar-response assay (ACS PSA, Bayer), we calculated that 6 of 155 men without PCA in this sample set could be spared unnecessary biopsy compared with the previous nonequimolar-response assay (ACS PSA2, Chiron) without missing additional PCA (90% sensitivity). These data provide additional evidence for clinical advantages of equimolar-response over nonequimolar-response PSA assay formats.

Case-Control Studies↗

PubMed2003

Subgingival plaque removal at interdental sites using a low-abrasive air polishing powder.

BACKGROUND: The aim of the study was to test the efficacy of a novel low-abrasive air polishing powder in subgingival plaque removal at interdental sites during periodontal maintenance therapy (PMT). METHODS: Using a split mouth design, subgingival plaque was removed in 23 PMT patients using a low abrasive powder using a standard air polishing unit (test) or curets (positive control). Before and immediately after treatment, subgingival plaque samples were taken from interdental sites with 3 to 5 mm probing depth (PD) at 2 test teeth and 2 positive control teeth. To evaluate the influence of sampling on the microflora, plaque samples were also taken twice at 2 teeth without therapy with PD of 3 to 5 mm (negative control). PMT treatment and plaque sampling were repeated 3 times at quarterly intervals. Anaerobe cultivation was utilized to assess the mean reduction of total colony forming units (CFU) immediately after treatment. RESULTS: Test treatment resulted in a significantly greater reduction in subgingival bacterial counts (log 1.9 +/- 0.7) than positive control treatment (log 1.1 +/- 0.6) and subgingival plaque sampling alone (log 0.5 +/- 0.5; P < 0.05). Differences between positive and negative control were not significant (P < 0.05). CONCLUSION: The novel low-abrasive air polishing powder is superior to curets in removing subgingival plaque at interdental sites with up to 5 mm probing depth in PMT.

Adolescent↗

PubMed2003

A possible influence of gingival dimensions on attachment loss and gingival recession following placement of artificial crowns.

The aim of the present study was to determine the influence of gingival dimensions on the development of gingival recession following placement of artificial crowns. The study population consisted of 11 periodontally healthy patients in whom 44 maxillary anterior teeth and/or premolars had to be crowned. A total of 36 teeth (82%) had, after crown placement, a mean intracrevicular crown margin of 0.57 +/- 0.47 mm. Thirty-nine teeth without restorations served as controls. Immediately after incorporation, as well as after 3, 6, 9, and 12 months, periodontal examinations were carried out. Gingival thickness was determined sonometrically and averaged 1.25 +/- 0.40 mm. Mean periodontal probing depth was 1.80 +/- 0.54 mm. Twelve months later, crowned teeth had experienced a mean attachment loss of 0.17 +/- 0.99 mm as compared to an attachment gain of 0.18 +/- 0.46 mm at control teeth. At test teeth, the gingival margin had receded a mean of 0.43 +/- 0.74 mm. In multivariate analyses considering the correlated structure of the data employing generalized estimating equation methods, crown placement was identified as a major factor for attachment loss and development of gingival recession. In addition, a shallow probing depth and narrow band of gingiva negatively influenced the level of periodontal attachment. The present results point to the importance of a more detailed periodontal diagnosis of the dentogingival region before placement of artificial crowns.

Adult↗

PubMed2002

Prospective assessment of risk factors for recurrent stroke during childhood--a 5-year follow-up study.

BACKGROUND: Risk factors for arterial stroke in children include congenital heart malformations, vasculopathies, infectious diseases, collagen tissue diseases, and metabolic disorders. Results of previous case-control studies have shown an association between ischaemic stroke and hereditary prothrombotic risk factors: factor V G1691A and factor II G20210A mutations, raised lipoprotein (a), and deficiencies in antithrombin, protein C, and protein S. The relevance of these factors to a second ischaemic stroke event is not known. METHODS: We assessed the risk of a second arterial ischaemic stroke associated with these prothrombotic risk factors, with underlying diseases or stroke comorbidities, and with stroke subtypes (cardiac, vascular, infectious, idiopathic). 167 boys and 134 girls aged between 6 months and 18 years of age (median 7 years) with a first episode of ischaemic stroke were followed-up prospectively for a median of 44 months (range 20-56). FINDINGS: Recurrent ischaemic stroke was diagnosed in 20 of 301 children who survived (6.6%) at a median of 5 months (range 1.5-36) after first stroke onset. The relative risk of having a second stroke was significantly increased in patients with raised lipoprotein (a) (relative risk 4.4, 95% CI 1.9-10.5) and in children with familial protein C deficiency (3.5, 1.1-10.9). Additionally, survival analysis showed that a first ischaemic stroke of vascular origin was significantly associated with having a second stroke (odds ratio 3.9, 95% CI 1.4-10.6). INTERPRETATION: Raised lipoprotein (a), protein C deficiency, and stroke of vascular origin are risk factors for recurrent arterial ischaemic stroke in childhood.

Adolescent↗

PubMed2002

Transjugular intrahepatic portosystemic shunt in the treatment of portal hypertension using memotherm stents: a prospective multicenter study.

PURPOSE: In a prospective multicenter study, efficacy and safety of transjugular intrahepatic portosystemic shunts (TIPS) were evaluated in the treatment of the complications of portal hypertension using a new self-expanding mesh-wire stent (Memotherm). METHODS: One hundred and eighty-one patients suffering from variceal bleeding (either acute or recurrent) or refractory ascites were enrolled. Postinterventional follow-up lasted for 8.4 months on average. Differences were analyzed by the log-rank test (chi-square) or Wilcoxon test. RESULTS: Shunt insertion was completed successfully in all patients (n = 181 patients, 100%). During follow-up, shunt occlusion was evident in 23 patients, and shunt stenosis was found in 33 patients (12.7% and 18.2%, respectively). Variceal rebleeding occurred in 20 of 139 patients (14.4%), with at least one episode of bleeding before TIPS treatment. The overall mortality rate of the patients treated by TIPS was 39.8%. In 51.4% of these cases (37 of 72 patients), however, the patients died within 30 days after TIPS placement. Analysis of subgroups showed that patients who underwent emergency TIPS for acute variceal bleeding had a significantly higher early mortality compared with other patient groups (p = 0.0014). CONCLUSION: In the present prospective multicenter study, we were able to show that insertion of Memotherm stents is an effective tool for TIPS. The occlusion rates seem to be comparable to those reported for the Palmaz stent. It could be shown that in particular, those patients who were treated for acute bleeding were at high risk of early mortality. Consequently, in such a critical condition, the indication for TIPS has to be set carefully.

Adult↗

PubMed2002

Early blast clearance by remission induction therapy is a major independent prognostic factor for both achievement of complete remission and long-term outcome in acute myeloid leukemia: data from the German AML Cooperative Group (AMLCG) 1992 Trial.

Risk assessment in acute myeloid leukemia (AML) using pretreatment characteristics may be improved by incorporating parameters of early response to therapy. In the 1992 trial of the German AML Cooperative Group (AMLCG), the amount of residual leukemic blasts in bone marrow was assessed one week after the first induction course (day 16 blasts). A total of 449 patients 16 to 76 years of age (median, 53 years) with de novo AML entered the trial and were evaluable. Treatment included TAD/HAM (thioguanine, cytosine arabinoside, and daunorubicin/high-dose cytosine arabinoside and mitoxantrone) double induction, TAD consolidation, and randomly either maintenance therapy or S-HAM consolidation. Cytogenetics were favorable, intermediate, unfavorable and not available in 10.0%, 48.3%, 13.1%, and 28.5%, respectively. Day 16 blasts ranged from 0% to 100% (median, 5%, mean +/- SD, 18.6 +/- 28.5%). Complete remission (CR) rate was 72.6%, 17.6% had persistent leukemia (PL), and 9.8% succumbed to hypoplastic death. Median overall survival (OS), event-free survival (EFS), and relapse-free survival (RFS) were 18, 9, and 15 months with 28.4%, 21.6%, and 30.1% at 5 years, respectively. As a continuous variable, day 16 blasts were related to CR rate (P < 0.0001), PL rate (P < 0.0001), OS (P < 0.0001), EFS (P < 0.0001), and RFS (P = 0.0049). Multivariate analyses identified the following parameters to be associated with the respective end points. CR rate: day 16 blasts (P <.0001), age (P =.0036), and LDH (P =.0072); OS: unfavorable cytogenetics (P <.0001), day 16 blasts (P <.0001), age (P <.0001), and LDH (P =.0040); EFS: unfavorable cytogenetics (P <.0001), LDH (P <.0001), day 16 blasts (P <.0001), and age (P =.0061); RFS: unfavorable cytogenetics (P <.0001), LDH (P <.0001), and day 16 blasts (P =.0359). The prognostic significance of day 16 blasts is independent of pretherapeutic parameters and predicts outcome even in patients achieving a CR.

Acute Disease↗