Disorganized attachment in infancy: a review of the phenomenon and its implications for clinicians and policy-makers

Disorganized/Disoriented (D) attachment has seen widespread interest from policy makers, practitioners, and clinicians in recent years. However, some of this interest seems to have been based on some false assumptions that (1) attachment measures can be used as definitive assessments of the individual in forensic/child protection settings and that disorganized attachment (2) reliably indicates child maltreatment, (3) is a strong predictor of pathology, and (4) represents a fixed or static “trait” of the child, impervious to development or help. This paper summarizes the evidence showing that these four assumptions are false and misleading. The paper reviews what is known about disorganized infant attachment and clarifies the implications of the classification for clinical and welfare practice with children. In particular, the difference between disorganized attachment and attachment disorder is examined, and a strong case is made for the value of attachment theory for supportive work with families and for the development and evaluation of evidence-based caregiving interventions.     

Validation of proposed diagnostic criteria (the “Budapest Criteria”) for Complex Regional Pain Syndrome

Current IASP diagnostic criteria for CRPS have low specificity, potentially leading to overdiagnosis. This validation study compared current IASP diagnostic criteria for CRPS to proposed new diagnostic criteria (the “Budapest Criteria”) regarding diagnostic accuracy. Structured evaluations of CRPS-related signs and symptoms were conducted in 113 CRPS-I and 47 non-CRPS neuropathic pain patients. Discriminating between diagnostic groups based on presence of signs or symptoms meeting IASP criteria showed high diagnostic sensitivity (1.00), but poor specificity (0.41), replicating prior work. In comparison, the Budapest clinical criteria retained the exceptional sensitivity of the IASP criteria (0.99), but greatly improved upon the specificity (0.68). As designed, the Budapest research criteria resulted in the highest specificity (0.79), again replicating prior work. Analyses indicated that inclusion of four distinct CRPS components in the Budapest Criteria contributed to enhanced specificity. Overall, results corroborate the validity of the Budapest Criteria and suggest they improve upon existing IASP diagnostic criteria for CRPS.     

Valproate Induces in Vitro Accumulation of Long-Chain Fatty Acylcarnitines

To elucidate the interference mechanisms of valproate (VPA) with mitochondrial fatty acid β-oxidation (FAO), the profile of acylcarnitine formation was studied in vitro. Human fibroblasts were incubated with 0.2 mmol/L [U-¹³C]palmitate, 0.4 mmol/L -carnitine, ± VPA (2 mmol/L) (96 h at 37°C). Acylcarnitines (AC) were analyzed by GC-CI-MS. VPA induced an impaired production of acetylcarnitine (C2) and an increase on long-chain AC (C10 to C16) both in control and in FAO-deficient cell lines (VLCAD, LCHAD, MTP).     

Decreased plasma levels of metastin in early pregnancy are associated with small for gestational age neonates

OBJECTIVE: To investigate whether pregnancies with small for gestational age (SGA) neonates, defined as customized birth weight below the 10th centile, are associated with altered levels of metastin in maternal plasma in the first trimester. STUDY DESIGN: Maternal blood was obtained between 8 and 14 weeks of pregnancy. Levels of metastin were measured in pregnancies with (n = 31) or without SGA-neonates (n = 31), matched for gestational age at venipuncture. Measurement of beta-hCG was included to study the influence of gestational age and placental volume on plasma levels of the measured markers. RESULTS: Metastin was significantly lower in SGA-pregnancies compared to an equal number of matched uneventful pregnancies (metastin: 1376 +/- 1317 pmol/L vs 2035 +/- 1260 pmol/L, p = 0.035; mean +/- standard deviation). beta-hCG levels were not different. CONCLUSION: Metastin is significantly lower in maternal plasma in the first trimester, in pregnancies with SGA-neonates. It might therefore be used in combination with other markers for risk estimation of growth impairment in the first trimester.     

Rituximab improves the treatment results of DHAP-VIM-DHAP and ASCT in relapsed/progressive aggressive CD20+ NHL: a prospective randomized HOVON trial

We evaluated the role of rituximab during remission induction chemotherapy in relapsed aggressive CD20+ non-Hodgkin lymphoma. Of 239 patients, 225 were evaluable for analysis. Randomized to DHAP (cisplatin-cytarabine-dexamethasone)-VIM (etoposide-ifosfamide-methotrexate)-DHAP (cisplatin-cytarabine-dexamethasone) chemotherapy with rituximab (R; R-DHAP arm) were 119 patients (113 evaluable) and to chemotherapy without rituximab (DHAP arm) 120 patients (112 evaluable). Patients in complete remission (CR) and partial remission (PR) after 2 chemotherapy courses were eligible for autologous stem-cell transplantation. After the second chemotherapy cycle, 75% of the patients in the R-DHAP arm had responsive disease (CR or PR) versus 54% in the DHAP arm (P=.01). With a median follow-up of 24 months, there was a significant difference in failure-free survival (FFS24; 50% vs 24% vs, P<.001), and progression free survival (PFS24; 52% vs 31% P<.002) in favor of the R-DHAP arm. Cox-regression analysis demonstrated a significant effect of rituximab treatment on FFS24 (HR 0.41, 95% confidence interval [CI] 0.29-0.57 versus 0.51, 95% CI 0.37-0.70) and overall-survival (OS24: HR 0.60 [0.41-0.89] vs 0.76 [0.52-1.10]) when adjusted for time since upfront treatment, age, World Health Organization performance status, and secondary age-adjusted international prognostic index. These results demonstrate improved FFS and PFS for relapsed aggressive B-cell NHL if rituximab is added to the re-induction chemotherapy regimen.     

Dose-finding study of imatinib in combination with intravenous cytarabine: feasibility in newly diagnosed patients with chronic myeloid leukemia

The HOVON cooperative study group performed a feasibility study of escalated imatinib and intravenous cytarabine in 165 patients with early chronic-phase chronic myeloid leukemia (CML). Patients received 2 cycles of intravenous cytarabine (200 mg/m(2) or 1000 mg/m(2) days 1-7) in conjunction with imatinib (200 mg, 400 mg, 600 mg, or 800 mg), according to predefined, successive dose levels. All dose levels proved feasible. Seven dose-limiting toxicities (DLTs) were observed in 302 cycles of chemotherapy, which were caused by streptococcal bacteremia in 5 cases. Intermediate-dose cytarabine (1000 mg/m(2)) prolonged time to neutrophil recovery and platelet recovery compared with a standard dose (200 mg/m(2)). High-dose imatinib (600 mg or 800 mg) extended the time to platelet recovery compared with a standard dose (400 mg). More infectious complications common toxicity criteria (CTC) grade 3 or 4 were observed after intermediate-dose cytarabine compared with a standard-dose of cytarabine. Early response data after combination therapy included a complete cytogenetic response in 48% and a major molecular response in 30% of patients, which increased to 46% major molecular responses at 1 year, including 13% complete molecular responses. We conclude that combination therapy of escalating dosages of imatinib and cytarabine is feasible. This study was registered at www.kankerbestrijding.nl as no. CKTO-2001-03.     

Genetic HLA Associations in Complex Regional Pain Syndrome With and Without Dystonia

We previously showed evidence for a genetic association of the human leukocyte antigen (HLA) system and complex regional pain syndrome (CRPS) with dystonia. Involvement of the HLA system suggests that CRPS has a genetic component with perturbed regulation of inflammation and neuroplasticity as possible disease mechanisms. However, it is at present unclear whether the observed association with HLA-B62 and HLA-DQ8 in CRPS patients with dystonia also holds true for patients without dystonia. Therefore, we tested the possible association with HLA-B62 and HLA-DQ8 in a clinically homogeneous group of 131 CRPS patients without dystonia. In addition, we investigated the possible association with other alleles of the HLA-A, HLA-B, HLA-C, HLA-DR, and HLA-DQ loci. We showed an increased prevalence of HLA-DQ8 (molecularly typed as HLA-DQB1*03:02; OR = 1.65 [95% CI 1.12–2.42], P = .014) in CRPS without dystonia, whereas no association was observed for HLA-B62 (molecularly typed as HLA-B*15:01; OR = 1.22 [95% CI .78–1.92], P = .458). Our data suggest that CRPS with and CRPS without dystonia may be genetically different, but overlapping, disease entities because only HLA-DQ8 is associated with both. The findings also indicate that distinct biological pathways may play a role in both CRPS subtypes.PerspectiveThis study is the first to replicate a specific HLA region conferring genetic risk for the development of CRPS. Moreover, associations of HLA-DQ8 with both CRPS with and CRPS without dystonia, and HLA-B62 only with CRPS with dystonia, suggest that these disease entities may be genetically different, but overlapping.     

Staging of esophageal carcinoma in a low-volume EUS center compared with reported results from high-volume centers

BACKGROUND: It is well known that a learning curve exists for performing EUS. OBJECTIVE: To determine whether the number of EUS investigations performed in a center affects the results of esophageal cancer staging. DESIGN: We compared EUS in the evaluation of T stage and the presence of regional and celiac lymph nodes in a low-volume center where <50 EUS/endoscopist/y were performed with reported results from 7 high-volume EUS centers. SETTING: A reference center for esophageal cancer (>90 cases/y) but a low-volume center for EUS when it comes to individual endoscopists. PATIENTS: From 1994 to 2003, 244 patients underwent EUS, without specific measures to pass a stenotic tumor or FNA and with postoperative TNM stage as the criterion standard in the low-volume EUS center. In the high-volume centers, 670 EUS investigations for esophageal cancer were performed, if needed, with dilation, and with postoperative TNM stage and/or FNA as the criterion standard. INTERVENTIONS: Retrospective analysis. MAIN OUTCOME MEASUREMENTS: Sensitivity and specificity of EUS for esophageal cancer staging. RESULTS: In the low-volume center, results of EUS for T3 staging in patients in whom passage of the EUS probe was possible were almost comparable for sensitivity (85% vs 88%-94%) but were lower for specificity (57% vs 75%-90%), whereas both sensitivity (58% vs 75%-90%) and specificity (87% vs 94%-97%) for T1 or T2 stages were lower than those reported in the high-volume centers. In the low-volume center, sensitivities of EUS for regional (45% vs 63%-89%) and celiac (19% vs 72%-83%) lymph nodes were lower, whereas specificities (75% vs 63%-82% and 99% vs 85%-100%, respectively) were comparable with those from high-volume centers. Results in the low-volume EUS center were worse if the EUS probe could not pass the stricture, which occurred in almost 30% of patients. LIMITATIONS: Both FNA and dilation before EUS for stenotic tumors were not performed in the low-volume EUS center. CONCLUSIONS: The results of EUS performed in a low-volume EUS center compared unfavorably with those reported from high-volume EUS centers. The results of this study suggest that preoperative staging by EUS should be performed by experienced and dedicated EUS endoscopists to optimize staging of esophageal cancer.