[Open surgical treatment of thoracoabdominal aortic aneurysm. Experience in 45 patients]. / Cirugía convencional del aneurisma tóraco-abdominal.

BACKGROUND: Thoracoabdominal aortic aneurysm (TAAA) is an infrequent disease and demands a highly specialized and experienced management. Open repair (OR) is the gold standard but it is associated with significant morbidity and mortality. Paraplegia and renal failure are the most important complications. AIM: To report our results with OR treatment of TAAA. MATERIAL AND METHODS: Descriptive study including all patients with TAAA operated electively and consecutively by OR between 1983 and 2019. Main outcomes are operative mortality, renal and neurological morbidity, and long-term survival. RESULTS: We report 45 operated patients aged 33 to 84 years, 74% males. Aneurysm extension according to Crawford classification was I in 18%, II in 18 %, III in 36% and IV in 29%. Operative mortality was 4%. The frequency of paraplegia or paraparesis at discharge was 9%. No patient was discharged on hemodialysis. Survival at 5 and 10 years were 60% and 40% respectively. CONCLUSIONS: OR of TAAA is a complex procedure. Our results show perioperative mortality rates comparable to highly experienced centers. Although being a major procedure, OR remains an alternative to treat this serious condition.

Transient spectral events in resting state MEG predict individual task responses.

Even in response to simple tasks such as hand movement, human brain activity shows remarkable inter-subject variability. Recently, it has been shown that individual spatial variability in fMRI task responses can be predicted from measurements collected at rest; suggesting that the spatial variability is a stable feature, inherent to the individual's brain. However, it is not clear if this is also true for individual variability in the spatio-spectral content of oscillatory brain activity. Here, we show using MEG (N â€‹= â€‹89) that we can predict the spatial and spectral content of an individual's task response using features estimated from the individual's resting MEG data. This works by learning when transient spectral 'bursts' or events in the resting state tend to reoccur in the task responses. We applied our method to motor, working memory and language comprehension tasks. All task conditions were predicted significantly above chance. Finally, we found a systematic relationship between genetic similarity (e.g. unrelated subjects vs. twins) and predictability. Our approach can predict individual differences in brain activity and suggests a link between transient spectral events in task and rest that can be captured at the level of individuals.

Risk of overconstraining femorotibial rotation after anatomical ACL reconstruction using bone patella tendon bone autograft.

INTRODUCTION: Numerous studies have focused on the anteroposterior stability after anterior cruciate ligament (ACL) reconstruction, with less emphasis on rotational stability. It has been hypothesized that bone patella tendon bone (BTB) autograft for ACL reconstruction restores knee rotation closely to normal due to its comparable fiber orientation to the native ACL. MATERIALS AND METHODS: Twenty patients with unilateral ACL rupture and an uninjured contralateral knee were included in this study. The ACL was reconstructed using the medial third of the patellar tendon. Tunnel placement was controlled by fluoroscopy. Implant-free press-fit graft fixation was used on both femoral and tibial side. Bone blocks were carefully placed to restore fiber orientation of both the anteromedial and posterolateral bundle, similar to the native ACL. Rotatory laxity of both knees was measured at 0° and 25° of flexion pre- and post-surgery, using an active opto-electronical motion-analysis system (LUKOTRONIC AS 100®). All measurements were performed under general anesthesia during surgery. RESULTS: Knee rotation was reduced significantly in both 0°and 25° of flexion following ACL reconstruction (p < 0.001). The side to side difference (SSD) of the rotatory laxity in extension was greater in the ACL-deficient knee (14.9° ± 8.9°), but decreased significantly after ACL reconstruction (- 5.9° ± 7.7°, minus value means less than in the uninjured knee). There was a similar finding at 25° of knee flexion where greater rotation of the ACL-deficient knee (5.7° ± 10.3°) prior to surgery changed to lower degree of rotation after surgery (- 11.3° ± 8.4°) in comparison to the uninjured knee. CONCLUSIONS: ACL reconstruction with a BTB graft in anatomical position using press-fit implant-free fixation is able to restore rotatory knee stability close to the intact contralateral knee. Despite the fact that the BTB graft offers fiber orientation close to the natural ACL, the surgeon should be aware of the potential risk of over-constraining the knee in terms of rotation. LEVEL OF EVIDENCE: II.

Incidental appendectomy during robotic laparoscopic prostatectomy-safe and worth to perform?

PURPOSE: The purpose of this study is to investigate the safety and patients' benefit of incidental appendectomy during robot-assisted laparoscopic radical prostatectomy (RALRP). METHODS: Fifty-three patients, who had incidental appendectomy during RALRP between January 2012 and March 2014, were enrolled to this study. To evaluate the safety of the procedure, following parameters were evaluated: patient age, duration of surgery, perioperative complications (classified by Clavien-Dindo), time to bowel movement, and length of hospital stay. Furthermore, intraoperative visual appearance, location, and histopathological evaluation of the appendix were evaluated. Data was analyzed by descriptive statistics. RESULTS: Mean age of patients was 61 years, the average hospital stay 5 days. No perioperative complications occurred. The appendix was unsuspicious in 39 patients (73.6%); 14 patients (26.4%) had macroscopically signs of inflammation. Of the 53 resected appendixes, the histopathological evaluation showed 33 (62.2%) inconspicuous appendices, 11 (20.8%) post-inflammatory changes, 4 (7.5%) with chronical signs of inflammation and 3 (5.7%) with signs of acute inflammation. In 2 patients (3.8%), low-grade mucinous neoplasms were found in the specimens. CONCLUSIONS: Incidental appendectomy during RALRP is a feasible procedure. With regard to inflammation and neoplastic changes, incidental appendectomy can be considered for patients scheduled for robot-assisted prostate surgery.

In-vivo three-dimensional MR imaging of the intact anterior cruciate ligament shows a variable insertion pattern of the femoral and tibial footprints.

PURPOSE: Failure to reconstruct the natural footprints of the ruptured anterior cruciate ligament (ACL) may lead to premature graft-failure. Therefore, precise analyses of insertion site anatomy and inter-individual variations of the morphology of the ACL are highly important to facilitate optimal individualized graft placement. Therefore, the purpose of this study was to analyze the inter-individual variation of the morphology of the femoral and tibial ACL footprints. METHODS: Thirty subjects with an intact ACL were included in this study for MR imaging of their knee joint. A three-dimensional (3D) dual-echo steady-state sequence with near 0.8 mm isotropic resolution was acquired on a 3 T system with a 15-channel knee-coil. The ACL was subsequently manually segmented using dedicated medical imaging software (VitreaAdvanced®, Vital Images). The lengths and widths of the footprints were measured after reconstructing an axial oblique (tibial footprint) or coronal oblique (femoral footprint) section at the bone-ligament junction and descriptive analysis was conducted to describe morphology orientation of the footprint. RESULTS: The femoral footprint measured on average 14 mm ± 2 mm (range 8-19 mm) in length and 5 mm ± 1 mm (range 3-8 mm) in width. The mean value of the tibial footprint measured 10 mm ± 2 mm (range 5-14 mm) in length and 7 mm ± 2 mm (range 5-13 mm) in width. Descriptive analysis showed a stretched, ribbon-like appearance of the femoral footprint, while the tibial footprint revealed larger variability, stretching from anterolateral to posteromedial around the anterior horn of the lateral meniscus. CONCLUSION: 3D imaging of the ACL footprints reveals a distinct difference in insertion site morphology and fiber bundle orientation between the femoral and tibial footprint. This questions the concept of strict anatomical separation of the ACL into an anteromedial and posterolateral bundle.

[Cardiac Magnetic Resonance in long term follow-up of Tetralogy of Fallot]. / Resonancia magnética cardíaca en el seguimiento alejado de pacientes con tetralogía de Fallot.

INTRODUCTION: Tetralogy of Fallot (TOF) is the most frequent cyanotic congenital heart disease. Pulmonary regurgitation (PR) and right ventricle (RV) enlargement and dysfunction are the most common long-term complications. Cardiac magnetic resonance (CMR) is the gold standard for RV evaluation. OBJECTIVE: To analyze CMR results in the follow-up of TOF patients. PATIENTS AND METHOD: All CMR performed between 2007 and 2012 in TOF patients with transannular patch (TAP) repair or infundibular widening, and without pulmonary valve replacement (PVR) were included. Pulmonary regurgitant fraction (PRF), ventricular end-diastolic (EDV) and end-systolic volume (ESV), and ejection fraction (EF) were examined. RESULTS: 122 CMR were performed in 114 patients. Average age at CMR was 15.4±7.4 years. 53.3% of them presented severe PR (> 40%). RVEDV was 157.3 ± 38.6 ml/m2, RVESV was 85.3 ± 27 ml/m2 and RVEF was 46.4 ± 7.1%. RVEDV was > 150 ml/ m2 in 48.4% and > 170 ml/m2 in 32.8% of patients. Patients with TAP showed larger RV volumes compared with those with infundibular widening. RVEDV > 170 ml/m2 showed worse RVEF that those with lower RVEDV (47.9 ± 7% vs 43.2 ± 6.4%, p < 0.01). CONCLUSION: Almost half of the pa tients showed significant RV enlargement, demonstrating that the indication of CMR is late in their follow-up. TAP was associated with higher RVEDV and RVESV, but no worse RVEF.

Surgical management of degenerative meniscus lesions: the 2016 ESSKA meniscus consensus.

PURPOSE: A degenerative meniscus lesion is a slowly developing process typically involving a horizontal cleavage in a middle-aged or older person. When the knee is symptomatic, arthroscopic partial meniscectomy has been practised for a long time with many case series reporting improved patient outcomes. Since 2002, several randomised clinical trials demonstrated no additional benefit of arthroscopic partial meniscectomy compared to non-operative treatment, sham surgery or sham arthroscopic partial meniscectomy. These results introduced controversy in the medical community and made clinical decision-making challenging in the daily clinical practice. To facilitate the clinical decision-making process, a consensus was developed. This initiative was endorsed by ESSKA. METHODS: A degenerative meniscus lesion was defined as a lesion occurring without any history of significant acute trauma in a patient older than 35 years. Congenital lesions, traumatic meniscus tears and degenerative lesions occurring in young patients, especially in athletes, were excluded. The project followed the so-called formal consensus process, involving a steering group, a rating group and a peer-review group. A total of 84 surgeons and scientists from 22 European countries were included in the process. Twenty questions, their associated answers and an algorithm based on extensive literature review and clinical expertise, were proposed. Each question and answer set was graded according to the scientific level of the corresponding literature. RESULTS: The main finding was that arthroscopic partial meniscectomy should not be proposed as a first line of treatment for degenerative meniscus lesions. Arthroscopic partial meniscectomy should only be considered after a proper standardised clinical and radiological evaluation and when the response to non-operative management has not been satisfactory. Magnetic resonance imaging of the knee is typically not indicated in the first-line work-up, but knee radiography should be used as an imaging tool to support a diagnosis of osteoarthritis or to detect certain rare pathologies, such as tumours or fractures of the knee. DISCUSSION: The present work offers a clear framework for the management of degenerative meniscus lesions, with the aim to balance information extracted from the scientific evidence and clinical expertise. Because of biases and weaknesses of the current literature and lack of definition of important criteria such as mechanical symptoms, it cannot be considered as an exact treatment algorithm. It summarises the results of the "ESSKA Meniscus Consensus Project" ( http://www.esska.org/education/projects ) and is the first official European consensus on this topic. The consensus may be updated and refined as more high-quality evidence emerges. LEVEL OF EVIDENCE: I.

[Meniscal root lesions: clinical relevance and treatment]. / Meniskuswurzelläsionen: Klinische Relevanz und Therapie.

Meniscal roots play an important role in load distribution of the tibiofemoral knee joint. Thus, meniscal root tears are severe injuries of the knee, which significantly expose cartilage to increased stress. Two entities are distinguished: (i) acute root tears that mainly affect the posterolateral root and often occur with ruptures of the anterior cruciate ligament; and (ii) chronic, degenerative root tears that mainly affect the posteromedial root. For diagnosis of both entities, the patient's medical history, a knee examination and especially MRI play key roles. The treatment of choice is in general transtibial fixation of the torn root, which leads to an increased clinical improvement and a decrease of the progression of arthritis.

[Indication and limitations of meniscus replacement]. / Indikation und Grenzen des Meniskusersatzes.

BACKGROUND: Meniscal lesions are among the most important musculoskeletal disorders and are the most common indication for knee joint arthroplasty. However, the structural integrity and function is rarely retained, and a loss of tissue results. Thus, there is a huge demand for meniscal replacement options. CURRENT PROCEDURES: Autografts were used in the past but did not fulfill expectations. Meniscus allografts have been developed to be a viable treatment option. However, availability is limited and evidence of a long-term chondroprotective effect scarce. Artificial scaffolds made from either collagen or PCU foam are available, which aid the regeneration of meniscal tissue and are rather intended as a partial replacement with an intact peripheral rim. Those implants thus have a limited spectrum of indication. While they seem to be symptomatically effective, it remains unclear whether they can reduce secondary cartilage damage. Newer developments aim at a permanent replacement of lost meniscal tissue. LIMITATIONS: In summary, there is currently no meniscal replacement available for a broad range of indications and with a solid scientific foundation. Prophylactic use should be limited to cases with a high chance of progression to osteoarthritis, like a lateral total meniscectomy. Otherwise meniscal replacement should be considered in younger, symptomatic patients with mild to moderate secondary changes. Potential causes of the initial meniscal injury like instability or deformities should be carefully assessed and addressed. In many cases, osteotomy might be a viable alternative to meniscus replacement.

[Treatment of degenerative meniscal lesions : From eminence to evidence-based medicine]. / Therapie degenerativer Meniskusläsionen : Von der eminenz- zur evidenzbasierten Medizin.

BACKGROUND: The treatment of degenerative meniscal lesions has received increased attention since the publication of several Level 1 studies over the last few years. The following review of literature including the consensus statement given by ESSKA reports on the management of patients with degenerative meniscal lesions. MATERIAL AND METHODS: The analysis includes the literature of Level 1 to 4 studies and the statement of the consensus group of ESSKA concerning the surgical or conservative management of these patients. RESULTS: Meniscal lesions cause progression in osteoarthritis. Patients presenting a combination of degenerative meniscal lesion and osteoarthritis show inferior clinical outcome. The average clinical outcome after surgical treatment was 70 points based on the Lysholm score. Level 1 studies show no difference in clinical outcome. However, over 30% of these patients require arthroscopy at the second stage after an interval of 3 to 6 months. Patients presenting a flap tear or complaining about mechanical symptoms show poor outcome after conservative treatment. DISCUSSION: Level 1 studies have focused on very selected patients. These patients do not represent the daily practice of orthopaedic surgeons. The findings of the level 1 studies should, therefore, not be generalized. According to the consensus statement of ESSKA, the treatment of degenerative meniscal lesions should start with conservative management. In the case of persistent symptoms, surgery should be considered after 3 months. In the case of mechanical symptoms, arthroscopy might be indicated earlier. Arthroscopy in advanced osteoarthritic knees is not indicated due to inferior clinical outcome.

Derivation of a No-significant-risk-level (NSRL) for dermal exposures to diethanolamine.

Diethanolamine (DEA) has been found to produce liver and kidney tumors in mice following lifetime dermal exposures. Data regarding the mode of action by which DEA produces these tumors were used to support a dose-response assessment that resulted in a no-significant-risk-level (NSRL) for dermal exposures to DEA. DEA and its metabolites are structural analogs to endogenous agents important to choline homeostasis. Sufficient information is available to support an epigenetic MOA involving the perturbation of choline homeostasis and hepatic methylation reactions in the formation of mouse liver tumors. This MOA may also apply to mouse kidney tumors, but direct measurements for key events in kidney are lacking. For both tumor types, dose-response data were pooled across four cancer bioassays conducted for DEA and DEA-containing condensates in order to provide a more robust characterization of the dose-response relationships. Doses were expressed in terms of dermally absorbed dose so that the dose-dependency and species differences in the dermal absorption of DEA were addressed. The resulting NSRL value of 3400 ug/day for dermal exposures to DEA is considered to be protective of human health for both tumor endpoints.

Phytotoxicity as an indicator of stability of broiler production residues.

Beddings used for successive broiler lots act as substrate to absorb water and feed from the excreta and may be subsequently used as agricultural fertilizers. This study evaluated the physicochemical characteristics and the phytotoxicity of beddings used to raise five consecutive broiler lots in five aviaries. Samples were collected for beddings not used yet and for beddings used at each of the five broiler lots. Lettuce and cucumber seeds were considered as phytotoxicity bioindicators. As beddings were used for greater number of lots, N, Ca, K, Mg and P contents generally increased, but the C content decreased, the pH alkalinized and humidity was reduced (P < 0.05). The germination index for lettuce and cucumber seeds was reduced with increased bedding (P < 0.05). Beddings used for at least five broiler lots presented decreased C:N ratio and would not recommended for agricultural use due to its toxicity for both tested seeds.

Low within- and between-day variability in exposure to new insulin glargine 300 U/ml.

AIMS: To characterize the variability in exposure and metabolic effect of insulin glargine 300 U/ml (Gla-300) at steady state in people with type 1 diabetes (T1DM). METHODS: A total of 50 participants with T1DM underwent two 24-h euglycaemic clamps in steady-state conditions after six once-daily administrations of 0.4 U/kg Gla-300 in a double-blind, randomized, two-treatment, two-period, crossover clamp study. Participants were randomized to receive Gla-300 as a standard cartridge formulation in the first treatment period, and as a formulation with enhanced stability through polysorbate-20 addition in the second treatment period, or vice versa. This design allowed the assessment of bioequivalence between formulations and, subsequently, within- and between-day variability. RESULTS: The cumulative exposure and effect of Gla-300 developed linearly over 24 h, and were evenly distributed across 6- and 12-h intervals. Diurnal fluctuation in exposure (within-day variability) was low; the peak-to-trough ratio of insulin concentration profiles was <2, and both the swing and peak-to-trough fluctuation were <1. Day-to-day reproducibility of exposure was high: the between-day within-subject coefficients of variation for total systemic exposure (area under the serum insulin glargine concentration time curve from time 0 to 24 h after dosing) and maximum insulin concentration were 17.4% [95% confidence interval (CI) 15-21] and 33.4% (95% CI 28-41), respectively. Reproducibility of the metabolic effect was lower than that of exposure. CONCLUSIONS: Gla-300 provides predictable, evenly distributed 24-h coverage as a result of low fluctuation and high reproducibility in insulin exposure, and appears suitable for effective basal insulin use.

Single-dose new insulin glargine 300 U/ml provides prolonged, stable glycaemic control in Japanese and European people with type 1 diabetes.

AIMS: Two single-dose studies were conducted in Japan and Europe to compare the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of new insulin glargine 300 U/ml (Gla-300) and insulin glargine 100 U/ml (Gla-100) in people with type 1 diabetes mellitus. METHODS: In two double-blind, randomized, crossover studies, 18 Japanese participants (aged 20-65 years) and 24 European participants (aged 18-65 years) with glycated haemoglobin levels ≤9.0% (≤75 mmol/mol) received single subcutaneous doses of Gla-300, 0.4, 0.6 and 0.9 U/kg (0.9 U/kg in the European study only), and Gla-100, 0.4 U/kg. A 36-h euglycaemic clamp procedure was performed after each dosing. RESULTS: The serum insulin glargine concentration (INS) and glucose infusion rate (GIR) developed more gradually into more constant and prolonged profiles with Gla-300 than with Gla-100. In support of this, the times to 50% of glargine exposure and insulin activity were longer for all Gla-300 doses than for Gla-100 during the 36-h clamp period, indicating a more evenly distributed exposure and metabolic effect beyond 24 h. Exposure to insulin glargine and glucose utilization were lower with the 0.4 and 0.6 U/ml Gla-300 doses in both studies compared with the 0.4 U/ml Gla-100 dose. Glucose-lowering activity was detected for up to 36 h with all doses of Gla-300. CONCLUSIONS: Single-dose injections of Gla-300 present more constant and prolonged PK and PD profiles compared with Gla-100, maintaining blood glucose control for up to 36 h in euglycaemic clamp settings in Japanese and European participants with type 1 diabetes.

Building scientific confidence in the development and evaluation of read-across.

Read-across is an alternative approach exploited to address information requirements for risk assessment and for regulatory programmes such as the European Union's REACH regulation. Whilst read-across approaches are accepted in principle, difficulties still remain in applying them consistently in practice. Recent work within Cefic LRI and ECETOC attempted to summarize the state-of-the-art and identify some of the barriers to broader acceptance of read-across approaches to overcome these. Acceptance is undoubtedly thwarted partly by the lack of a systematic framework to characterize the read-across justification and identify the uncertainties particularly for complex regulatory endpoints such as repeated-dose toxicity or prenatal developmental toxicity. Efforts are underway by the European Chemical's Agency (ECHA) to develop a Read-Across Assessment Framework (RAAF) and private sector experts have also considered the development of a similar framework. At the same time, mechanistic chemical categories are being proposed which are underpinned by Adverse Outcome Pathways (AOPs). Currently such frameworks are only focusing on discrete organic substances, though the AOP approach could conceivably be applied to evaluate more complex substances such as mixtures. Here we summarize the deliberations of the Cefic LRI read-across team in characterizing scientific confidence in the development and evaluation of read-across.

DNA barcoding and morphological identification of neotropical ichthyoplankton from the Upper Paraná and São Francisco.

The identification of fish larvae from two neotropical hydrographic basins using traditional morphological taxonomy and DNA barcoding revealed no conflicting results between the morphological and barcode identification of larvae. A lower rate (25%) of correct morphological identification of eggs as belonging to migratory or non-migratory species was achieved. Accurate identification of ichthyoplankton by DNA barcoding is an important tool for fish reproductive behaviour studies, correct estimation of biodiversity by detecting eggs from rare species, as well as defining environmental and management strategies for fish conservation in the neotropics.

Investigational new insulin glargine 300 U/ml has the same metabolism as insulin glargine 100 U/ml.

Insulin glargine is processed in vivo into soluble 21(A) -Gly-human insulin (M1), the principal moiety responsible for metabolic effects, and subsequently into M2. This sub-study compared metabolism and metabolite pharmacokinetic (PK) profiles of investigational new insulin glargine U300 (Gla-300) with insulin glargine 100 U/ml (Gla-100, Lantus®, Sanofi-Aventis Deutschland GmbH, Frankfurt am Main, Germany) in people with type 1 diabetes. Participants received 0.4 (n = 18) or 0.6 U/kg Gla-300 (n = 12), and 0.4 U/kg Gla-100 (n = 30) once daily in randomized order for 8 days prior to a 36-h euglycaemic clamp. Metabolites were quantified using immunoaffinity enrichment and liquid chromatography tandem mass spectrometry (LC-MS/MS). Glargine metabolism was the same regardless of Gla-100 or Gla-300 administration; M1 was confirmed as the principal active moiety circulating in blood. Steady state concentrations of M1 were achieved after 2 days for Gla-100, and 4 days for Gla-300. Steady state M1 values defined prolonged and even flatter PK profiles after Gla-300 administration compared with M1 profiles after Gla-100.

Lixisenatide resensitizes the insulin-secretory response to intravenous glucose challenge in people with type 2 diabetes--a study in both people with type 2 diabetes and healthy subjects.

AIMS: Glucagon-like peptide-1 (GLP-1) receptor agonists improve blood glucose control by enhancing glucose-sensitive insulin release, delaying gastric emptying and reducing postprandial glucagon secretion. The studies reported here investigated the insulin response to an intravenous (iv) glucose challenge after injection of lixisenatide (LIXI) 20 µg or placebo. METHODS: Two single-centre, double-blind, randomized, placebo-controlled, single-dose, crossover studies were performed in healthy subjects (HS) and people with type 2 diabetes mellitus (T2DM). Participants received subcutaneous LIXI or placebo 2 h before an iv glucose challenge. Study endpoints included first- and second-phase insulin response, insulin concentration (INS), glucagon response and glucose disposal rate (K(glucose)). LIXI exposure was measured over 12 h. RESULTS: LIXI 20 µg reached maximum concentration after 2 h and resensitized first-phase insulin secretion by 2.8-fold in T2DM to rates comparable with those in HS on placebo, and raised second-phase insulin secretion by 1.6-fold in T2DM. INS rose correspondingly and glucose disposal was accelerated by 1.8-fold in T2DM. First-phase insulin secretion and glucose disposal were also augmented by LIXI in HS, whereas second-phase insulin secretion reduced blood glucose concentrations to below fasting levels and then ceased, accompanied by a rapid, short-lasting rise in glucagon. Otherwise, suppression of glucagon release subsequent to augmentation of insulin release was unaffected in T2DM and in HS. CONCLUSIONS: LIXI resensitized the insulin response to an iv glucose challenge in people with T2DM, thereby accelerating glucose disposal to nearly physiological intensity, and did not impair counter-regulation to low glucose levels by glucagon.

Relationships of chemical concentrations in maternal and cord blood: a review of available data.

The developing fetus is likely to be exposed to the same environmental chemicals as the mother during critical periods of growth and development. The degree of maternal-fetal transfer of chemical compounds will be affected by chemical and physical properties such as lipophilicity, protein binding, and active transport mechanisms that influence absorption and distribution in maternal tissues. However, these transfer processes are not fully understood for most environmental chemicals. This review summarizes reported data from more than 100 studies on the ratios of cord:maternal blood concentrations for a range of chemicals including brominated flame-retardant compounds, polychlorinated biphenyls (PCB), polychlorinated dibenzodioxins and dibenzofurans, organochlorine pesticides, perfluorinated compounds, polyaromatic hydrocarbons, metals, and tobacco smoke components. The studies for the chemical classes represented suggest that chemicals frequently detected in maternal blood will also be detectable in cord blood. For most chemical classes, cord blood concentrations were found to be similar to or lower than those in maternal blood, with reported cord:maternal ratios generally between 0.1 and 1. Exceptions were observed for selected brominated flame-retardant compounds, polyaromatic hydrocarbons, and some metals, for which reported ratios were consistently greater than 1. Careful interpretation of the data in a risk assessment context is required because measured concentrations of environmental chemicals in cord blood (and thus the fetus) do not necessarily imply adverse effects or risk. Guidelines and recommendations for future cord:maternal blood biomonitoring studies are discussed.