Time course of hypertension and myocardial dysfunction following anthracycline chemotherapy in pediatric patients.

Background: Anthracyclines are associated with cardiac dysfunction. Little is known about the interplay of pre-existing hypertension and treatment response. We aimed to investigate the relationship between hypertension and the development of cancer therapy-related cardiac dysfunction (CTRCD) in pediatric patients treated with anthracycline chemotherapy. Methods: Pediatric patients with cancer who received anthracycline chemotherapy from 2013 to 2021 were retrospectively included. Serial cardiac assessments were conducted during and after chemotherapy. The primary outcome was the development of CTRCD, classified as mild, moderate, or severe according to contemporary definitions. Results: Among 190 patients undergoing anthracycline chemotherapy, 34 patients (17.9 %) had hypertension (24 patients Stage 1, and 10 patients Stage 2) at baseline evaluation. Patients underwent chemotherapy for a median of 234.4 days (interquartile range 127.8-690.3 days) and were subsequently followed up. Hypertension was frequent during follow-up 31.3 % (0-3 months), 15.8 % (3-6 months), 21.9 % (0.5-1 years), 24.7 % (1-2 years), 31.1 % (2-4 years) and 35.8 % (beyond 4 years) (P for trend < 0.001). Freedom from mild CTRCD at 5 years was 45.0 %, freedom from moderate CTRCD was 87.8 % at 5 years. Baseline hypertension did not increase the risk of mild (HR 0.77, 95 % CI: 0.41-1.42, P = 0.385) or moderate CTRCD (HR 0.62, 95 % CI: 0.14-2.72, P = 0.504). Patients with baseline hypertension showed different global longitudinal strain (P < 0.001) and LVEF (P < 0.001) patterns during follow-up. Conclusions: Pediatric patients often develop CTRCD post-anthracycline chemotherapy. Those with pre-existing hypertension show a unique treatment response, despite no increased CTRCD risk, warranting further investigation.

Systemic inhibition or global deletion of CaMKK2 protects against post-traumatic osteoarthritis.

OBJECTIVE: To investigate the role of Ca2+/calmodulin-dependent protein kinase 2 (CaMKK2) in post-traumatic osteoarthritis (PTOA). METHODS: Destabilization of the medial meniscus (DMM) or sham surgeries were performed on 10-week-old male wild-type (WT) and Camkk2-/- mice. Half of the DMM-WT mice and all other cohorts (n = 6/group) received tri-weekly intraperitoneal (i.p.) injections of saline whereas the remaining DMM-WT mice (n = 6/group) received i.p. injections of the CaMKK2 inhibitor STO-609 (0.033 mg/kg body weight) thrice a week. Study was terminated at 8- or 12-weeks post-surgery, and knee joints processed for microcomputed tomography imaging followed by histology and immunohistochemistry. Primary articular chondrocytes were isolated from knee joints of 4-6-day-old WT and Camkk2-/- mice, and treated with 10 ng/ml interleukin-1ß (IL)-1ß for 24 or 48 h to investigate gene and protein expression. RESULTS: CaMKK2 levels and activity became elevated in articular chondrocytes following IL-1ß treatment or DMM surgery. Inhibition or absence of CaMKK2 protected against DMM-associated destruction of the cartilage, subchondral bone alterations and synovial inflammation. When challenged with IL-1ß, chondrocytes lacking CaMKK2 displayed attenuated inflammation, cartilage catabolism, and resistance to suppression of matrix synthesis. IL-1ß-treated CaMKK2-null chondrocytes displayed decreased IL-6 production, activation of signal transducer and activator of transcription 3 (Stat3) and matrix metalloproteinase 13 (MMP13), indicating a potential mechanism for the regulation of inflammatory responses in chondrocytes by CaMKK2. CONCLUSIONS: Our findings reveal a novel function for CaMKK2 in chondrocytes and highlight the potential for its inhibition as an innovative therapeutic strategy in the prevention of PTOA.

Suppression of cancer-associated bone loss through dynamic mechanical loading.

Patients afflicted with or being treated for cancer constitute a distinct and alarming subpopulation who exhibit elevated fracture risk and heightened susceptibility to developing secondary osteoporosis. Cancer cells uncouple the regulatory processes central for the adequate regulation of musculoskeletal tissue. Systemically taxing treatments to target tumors or disrupt the molecular elements driving tumor growth place considerable strain on recovery efforts. Skeletal tissue is inherently sensitive to mechanical forces, therefore attention to exercise and mechanical loading as non-pharmacological means to preserve bone during treatment and in post-treatment rehabilitative efforts have been topics of recent focus. This review discusses the dysregulation that cancers and the ensuing metabolic dysfunction that confer adverse effects on musculoskeletal tissues. Additionally, we describe foundational mechanotransduction pathways and the mechanisms by which they influence both musculoskeletal and cancerous cells. Functional and biological implications of mechanical loading at the tissue and cellular levels will be discussed, highlighting the current understanding in the field. Herein, in vitro, translational, and clinical data are summarized to consider the positive impact of exercise and low magnitude mechanical loading on tumor-bearing skeletal tissue.

The importance of evaluating specific myeloid malignancies in epidemiological studies of environmental carcinogens.

INTRODUCTION: Although myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), myeloproliferative neoplasms (MPN) - including chronic myeloid leukemia (CML) - and myelodysplastic/myeloproliferative neoplasms (MDS/MPN) are largely clinically distinct myeloid malignancies, epidemiological studies rarely examine them separately and often combine them with lymphoid malignancies, limiting possible etiological interpretations for specific myeloid malignancies. METHODS: We systematically evaluated the epidemiological literature on the four chemical agents (1,3-butadiene, formaldehyde, benzene, and tobacco smoking, excluding pharmaceutical, microbial and radioactive agents, and pesticides) classified by the International Agency for Research on Cancer as having sufficient epidemiological evidence to conclude that each causes "myeloid malignancies." Literature searches of IARC Monographs and PubMed identified 85 studies that we critically assessed, and for appropriate subsets, summarized results using meta-analysis. RESULTS: Only two epidemiological studies on 1,3-butadiene were identified, but reported findings were inadequate to evaluate specific myeloid malignancies. Studies on formaldehyde reported results for AML and CML - and not for MDS or MPN - but reported no increased risks. For benzene, several specific myeloid malignancies were evaluated, with consistent associations reported with AML and MDS and mixed results for CML. Studies of tobacco smoking examined all major myeloid malignancies, demonstrating consistent relationships with AML, MDS and MPN, but not with CML. CONCLUSIONS: Surprisingly few epidemiological studies present results for specific myeloid malignancies, and those identified were inconsistent across studies of the same exposure, as well as across chemical agents. This exercise illustrates that even for agents classified as having sufficient evidence of causing "myeloid malignancies," the epidemiological evidence for specific myeloid malignancies is generally limited and inconsistent. Future epidemiological studies should report findings for the specific myeloid malignancies, as combining them post hoc - where appropriate - always remains possible, whereas disaggregation may not. Furthermore, combining results across possibly discrete diseases reduces the chances of identifying important malignancy-specific causal associations.

Exercise-Induced Abnormalities of Regional Myocardial Deformation in Anomalous Aortic Origin of the Right Coronary Artery.

AIMS: Congenital coronary artery anomalies are uncommon and may result in sudden death. Management of asymptomatic patients with anomalous aortic origin of the right coronary artery (AAORCA) remains controversial with a lack of evidence to guide decision-making. We hypothesized that patients with AAORCA may have exercise-inducible ischemia detectable as abnormalities in regional myocardial deformation on exercise stress echocardiography (ESE). METHODS: We reviewed clinical data, computed tomography angiography, and treadmill ESE from 33 AAORCA patients (21 unoperated, 12 operated) and 11 controls. Regional wall motion on ESE was visually assessed. Doppler tissue imaging was done pre and post exercise to evaluate regional myocardial wall deformation. The post- to pre-exercise time to peak systolic strain corrected for heart rate ratio (TPScR) for the left ventricular inferior and anterior walls of AAORCA patients was compared to controls. RESULTS: No regional wall motion abnormalities were noted. The TPScR of the inferior wall was higher in unoperated (0.96 ± 0.41) but not operated (0.84 ± 0.28) AAORCA patients compared to controls (0.76 ± 0.18, P = .03 vs .23, respectively). There was no significant difference in TPScR of the anterior wall between unoperated patients and controls (P = .08). CONCLUSION: In some AAORCA patients undergoing ESE, TPScR of the left ventricular inferior wall is elevated, suggestive of ischemia induced by exercise in myocardium supplied by the right coronary artery. Further work is needed to understand the potential role of this finding in risk assessment.

Sagittal balance of the spine.

The static sagittal balance of the normal spine is a physiological alignment of the spine in the most efficient manner by the muscular forces. During gait, this balance is constantly thwarted by single-foot support. This analysis involves the study of parameters which are now well defined. The pelvic incidence is constant, and the sacral slope and the pelvic tilt are positional. The cervical parameters are the upper (O-C2) and lower cervical curvatures (C2-C7), the C7 slope, the spino-cranial angle and the vertical cervical offset. At the thoracic and lumbar level, they are, respectively, kyphosis and lordosis. The OD-HA (odontoid hip axis) angle is the most efficient parameter to analyse the global balance. The average values of these parameters are reported with the new 3D measurements by Le Huec et al. The relationship between these different parameters was analysed, and Roussouly proposed his classification of the different spine shape. Ageing makes it possible to show compensation mechanisms at three levels: spinal, pelvic and lower limbs. Understanding these different data allows for better planning of the surgical management of the patients. Global evaluation of the entire spine and the measurement of the aforementioned parameters allow to determine the extent of the correction to be performed during surgery. Taking these parameters into account also enables us to understand the complications involved in this type of surgery: transitional syndromes or junctional syndromes. Integration of these parameters into the study of gait is an area still under investigation. These slides can be retrieved under Electronic Supplementary Material .

Feeding methods for infants with single ventricle physiology are associated with length of stay during stage 2 surgery hospitalization.

BACKGROUND: Tube feedings are often needed to achieve the growth and nutrition goals associated with decreased morbidity and mortality in patients with single ventricle anatomy. Variability in feeding method through the interstage period has been previously described, however, comparable information following stage 2 palliation is lacking. OBJECTIVES: To identify types of feeding methods following stage 2 palliation and their influence on length of stay. DESIGN: Secondary analysis of the National Pediatric Cardiology Quality Improvement Collaborative registry was performed on 932 patients. Demographic data, medical characteristics, postoperative complications, type of feeding method, and length of stay for stage 2 palliation were analyzed. RESULTS: Type of feeding method remained relatively unchanged during hospitalization for stage 2 palliation. Gastrostomy tube fed only patients were the oldest at time of surgery (182.7 ± 57.7 days, P < .001) and had the lowest weight-for-age z scores at admission (-1.6 ± 1.4, P < .001). Oral + gastrostomy tube groups had the longest median bypass times (172.5 minutes, P = .001) and longest length of stay (median 12 days, P < .001). Multivariable modeling revealed that feeding by tube only (P < .001), oral + tube feeding (P ≤ .001), reintubation (P < .001), and prolonged intubation (P < .001) were associated with increased length of stay. Neither age (P = .156) nor weight-for-age z score at admission (P = .066) was predictive of length of stay. CONCLUSIONS: Feeding methods established at admission for stage 2 palliation are not likely to change by discharge. Length of stay is more likely to be impacted by tube feeding and intubation history than age or weight-for-age z score at admission. Better understanding for selection of feeding methods and their impact on patient outcomes is needed to develop evidence-based guidelines to decrease variability in clinical practice patterns and provide appropriate counseling to caregivers.

Analysis of cervical sagittal alignment variations after lumbar pedicle subtraction osteotomy for severe imbalance: study of 59 cases.

OBJECTIVE: To evaluate postoperative changes within the cervical alignment following surgical lumbar correction by pedicle subtraction osteotomy (PSO) in patients affected with sagittal global malalignment disease. METHODS: This was a monocentric, radiographic, and prospective study. 79 patients, who underwent sagittal correction by PSO, performed an EOS imaging pre- and postoperatively between January 2008 and December 2013 at the University Hospital of Bordeaux. Inclusion criteria were a performed pre- and postoperative EOS imaging and a preoperative C7SVA > 5 cm. Were excluded patients who did not allow EOS with a viewable cervical spine due to hyperkyphosis. The study involved the analysis of pelvic, lumbar, thoracic, cervical, and cranial parameters before and after the surgery. RESULTS: 59 patients met the criteria. Mean follow-up was 38 months. The lumbar PSO significantly improved sagittal alignment including L1S1 lordosis, T1T12 kyphosis, and C7SVA (p < 0.001). We did not reported a significant change within cervical parameters after PSO (C2C7 lordosis 22.7°-21.5° p = 0.64, C1C7 lordosis 50.6°-48.8° p = 0.56, C1C2 angle 28.2°-27.9° p = 0.82, C7 slope stayed constant 32.3°-30.5° p = 0.47, OC2 angle 15.54°-15.56° p = 0.99). However, cranial slope decreased significantly (p < 0.05). We did not find correlation between lumbar lordosis and cervical lordosis variations (R = 0.265). Cervical lordosis was highly correlated with the C7 slope (R = 0.597) and with the Spino Cranial Angle (R = - 0.867). CONCLUSION: Reciprocal changes in cervical spine after PSO are difficult to approach. Maintaining a horizontal gaze involves locoregional mechanisms of compensation adapting to the slope of C7. The cranial system by decreasing the cranial slope allows the gaze alignment and is the first compensation mechanism to get involved after a loss of lumbar lordosis. Restoring optimal C7SVA is necessary to prevent the development of secondary cervical painful symptomatology when the cranial compensation is outdated.

Electrophysiological effects of anthracyclines in adult survivors of pediatric malignancy.

BACKGROUND: Anthracycline use is limited by cardiotoxicity, including arrhythmias and left ventricular (LV) dysfunction. We aim to characterize the association between electrophysiological changes and LV dysfunction. METHODS: A retrospective chart review was conducted, including all 147 pediatric cancer survivors at our institution over 18 years of age and treated with an anthracycline. One hundred thirty-four patients who had at least one electrocardiogram (ECG) and echocardiogram were analyzed. The association between dysfunction and baseline characteristics, treatment history, and electrocardigraphic parameters were analyzed using multivariable logistic regression. Additionally, a longitudinal generalized estimating equation (GEE) model was used to examine the temporal association between repeated measure corrected QT (QTc) intervals and subsequent LV function. RESULTS: In our population, 24% of patients had LV dysfunction. The initial posttreatment QTc interval was longer in patients with LV dysfunction (438 ± 35 vs. 420 ± 20 msec, P = 0.002). In logistic regression analysis, QTc interval (P < 0.001) and cumulative radiation dose (P = 0.027) were associated with LV dysfunction. On ECGs performed prior to evidence of LV dysfunction, the QTc was longer than on ECGs preceding a normal echocardiogram (451 ± 32 msec vs. 423 ± 25 msec, P < 0.001). Mean time from QTc ≥ 450 msec to evidence of LV dysfunction was 1.8 ± 2.9 years. In the longitudinal GEE model, QTc prolongation was associated with subsequent decreased fractional shortening. CONCLUSIONS: Among adult survivors of pediatric cancer treated with anthracyclines, prolongation of the QTc interval was associated with subsequent LV dysfunction.

Genetic evidence for role of integration of fast and slow neurotransmission in schizophrenia.

The most recent genome-wide association studies (GWAS) of schizophrenia (SCZ) identified hundreds of risk variants potentially implicated in the disease. Further, novel statistical methodology designed for polygenic architecture revealed more potential risk variants. This can provide a link between individual genetic factors and the mechanistic underpinnings of SCZ. Intriguingly, a large number of genes coding for ionotropic and metabotropic receptors for various neurotransmitters-glutamate, γ-aminobutyric acid (GABA), dopamine, serotonin, acetylcholine and opioids-and numerous ion channels were associated with SCZ. Here, we review these findings from the standpoint of classical neurobiological knowledge of neuronal synaptic transmission and regulation of electrical excitability. We show that a substantial proportion of the identified genes are involved in intracellular cascades known to integrate 'slow' (G-protein-coupled receptors) and 'fast' (ionotropic receptors) neurotransmission converging on the protein DARPP-32. Inspection of the Human Brain Transcriptome Project database confirms that that these genes are indeed expressed in the brain, with the expression profile following specific developmental trajectories, underscoring their relevance to brain organization and function. These findings extend the existing pathophysiology hypothesis by suggesting a unifying role of dysregulation in neuronal excitability and synaptic integration in SCZ. This emergent model supports the concept of SCZ as an 'associative' disorder-a breakdown in the communication across different slow and fast neurotransmitter systems through intracellular signaling pathways-and may unify a number of currently competing hypotheses of SCZ pathophysiology.

Microvascular coupling devices: neglected resource with a short learning curve.

Microvascular couplers have a record of efficiency and efficacy. They have been used in anastomoses in the head and neck in Sunderland since November 2013, where we have investigated the time taken for anastomosis, patency, and cost. We also completed a national survey of the use of couplers in the United Kingdom, in which we recorded the time of anastomosis. The mean (range) time was 4minutes (2minutes 40seconds - 4minutes 10seconds). One flap partially failed. This shows that couplers can save time, they have successful outcomes, and the technique is quick and easy to learn.

The use of magnetically-controlled growing rods to treat children with early-onset scoliosis: early radiological results in 19 children.

AIMS: We undertook a prospective non-randomised radiological study to evaluate the preliminary results of using magnetically-controlled growing rods (MAGEC System, Ellipse technology) to treat children with early-onset scoliosis. PATIENTS AND METHODS: Between January 2011 and January 2015, 19 children were treated with magnetically-controlled growing rods (MCGRs) and underwent distraction at three-monthly intervals. The mean age of our cohort was 9.1 years (4 to 14) and the mean follow-up 22.4 months (5.1 to 35.2). Of the 19 children, eight underwent conversion from traditional growing rods. Whole spine radiographs were carried out pre- and post-operatively: image intensification was used during each lengthening in the outpatient department. The measurements evaluated were Cobb angle, thoracic kyphosis, proximal junctional kyphosis and spinal growth from T1 to S1. RESULTS: The mean pre-, post-operative and latest follow-up Cobb angles were 62° (37.4 to 95.8), 45.1° (16.6 to 96.2) and 43.2° (11.9 to 90.5), respectively (p < 0.05). The mean pre-, post-operative and latest follow-up T1-S1 lengths were 288.1 mm (223.2 to 351.7), 298.8 mm (251 to 355.7) and 331.1 mm (275 to 391.9), respectively (p < 0.05). In all, three patients developed proximal pull-out of their fixation and required revision surgery: there were no subsequent complications. There were no complications of outpatient distraction. CONCLUSIONS: Our study shows that MCGRs provide stable correction of the deformity in early-onset scoliosis in both primary and revision procedures. They have the potential to reduce the need for multiple operations and thereby minimise the potential complications associated with traditional growing rod systems. Cite this article: Bone Joint J 2016;98-B:1240-47.

Chromium Is Elevated in Fin Whale (Balaenoptera physalus) Skin Tissue and Is Genotoxic to Fin Whale Skin Cells.

Hexavalent chromium (Cr(VI)) is present in the marine environment and is a known carcinogen and reproductive toxicant. Cr(VI) is the form of chromium that is well absorbed through the cell membrane. It is also the most prevalent form in seawater. We measured the total Cr levels in skin biopsies obtained from healthy free-ranging fin whales from the Gulf of Maine and found elevated levels relative to marine mammals in other parts of the world. The levels in fin whale biopsies ranged from 1.71 to 19.6 µg/g with an average level of 10.07 µg/g. We also measured the cytotoxicity and genotoxicity of Cr(VI) in fin whale skin cells. We found that particulate and soluble Cr(VI) are both cytotoxic and genotoxic to fin whale skin cells in a concentration-dependent manner. The concentration range used in our cell culture studies used environmentally relevant concentrations based on the biopsy measurements. These data suggest that Cr(VI) may be a concern for whales in the Gulf of Maine.

Chemical dispersants used in the Gulf of Mexico oil crisis are cytotoxic and genotoxic to sperm whale skin cells.

The 2010 Deepwater Horizon oil rig explosion in the Gulf of Mexico drew attention to the need for toxicological studies of chemical dispersants. We are still learning the effects these spills had on wildlife. Little is known about the toxicity of these substances in marine mammals. The objective of this study was to determine the toxicity of the two dispersants (Corexit 9500 and 9527). Corexit 9500 and 9527 were both cytotoxic to sperm whale skin fibroblasts. Corexit 9527 was less cytotoxic than 9500. S9 mediated metabolism did not alter cytotoxicity of either dispersant. Both dispersants were genotoxic to sperm whale skin fibroblasts; S9 mediated metabolism increased Corexit 9527 genotoxicity.

Multi-parametric flow cytometric and genetic investigation of the peripheral B cell compartment in human type 1 diabetes.

The appearance of circulating islet-specific autoantibodies before disease diagnosis is a hallmark of human type 1 diabetes (T1D), and suggests a role for B cells in the pathogenesis of the disease. Alterations in the peripheral B cell compartment have been reported in T1D patients; however, to date, such studies have produced conflicting results and have been limited by sample size. In this study, we have performed a detailed characterization of the B cell compartment in T1D patients (n = 45) and healthy controls (n = 46), and assessed the secretion of the anti-inflammatory cytokine interleukin (IL)-10 in purified B cells from the same donors. Overall, we found no evidence for a profound alteration of the B cell compartment or in the production of IL-10 in peripheral blood of T1D patients. We also investigated age-related changes in peripheral B cell subsets and confirmed the sharp decrease with age of transitional CD19(+) CD27(-) CD24(hi) CD38(hi) B cells, a subset that has recently been ascribed a putative regulatory function. Genetic analysis of the B cell compartment revealed evidence for association of the IL2-IL21 T1D locus with IL-10 production by both memory B cells (P = 6·4 × 10(-4) ) and islet-specific CD4(+) T cells (P = 2·9 × 10(-3) ). In contrast to previous reports, we found no evidence for an alteration of the B cell compartment in healthy individuals homozygous for the non-synonymous PTPN22 Trp(620) T1D risk allele (rs2476601; Arg(620) Trp). The IL2-IL21 association we have identified, if confirmed, suggests a novel role for B cells in T1D pathogenesis through the production of IL-10, and reinforces the importance of IL-10 production by autoreactive CD4(+) T cells.

Concentrations of the genotoxic metals, chromium and nickel, in whales, tar balls, oil slicks, and released oil from the gulf of Mexico in the immediate aftermath of the deepwater horizon oil crisis: is genotoxic metal exposure part of the deepwater horizon legacy?

Concern regarding the Deepwater Horizon oil crisis has largely focused on oil and dispersants while the threat of genotoxic metals in the oil has gone largely overlooked. Genotoxic metals, such as chromium and nickel, damage DNA and bioaccumulate in organisms, resulting in persistent exposures. We found chromium and nickel concentrations ranged from 0.24 to 8.46 ppm in crude oil from the riser, oil from slicks on surface waters and tar balls from Gulf of Mexico beaches. We found nickel concentrations ranged from 1.7 to 94.6 ppm wet weight with a mean of 15.9 ± 3.5 ppm and chromium concentrations ranged from 2.0 to 73.6 ppm wet weight with a mean of 12.8 ± 2.6 ppm in tissue collected from Gulf of Mexico whales in the wake of the crisis. Mean tissue concentrations were significantly higher than those found in whales collected around the world prior to the spill. Given the capacity of these metals to damage DNA, their presence in the oil, and their elevated concentrations in whales, we suggest that metal exposure is an important understudied concern for the Deepwater Horizon oil disaster.

Excising squamous cell carcinomas: comparing the performance of GPs, hospital skin specialists and other hospital specialists.

BACKGROUND: GPs have no defined role in the excision of squamous cell carcinomas (SCCs). Current guidelines recommend that all skin lesions suspicious of SCC should be referred urgently to secondary care. Evidence regarding current management of SCC in primary care is limited. Existing audit data suggest that up to 10% of SCCs may be excised in primary care. GPs may be able to have a greater role in the management of SCC but more evidence is required before this can be advocated. OBJECTIVE: To compare the practice of GPs, skin specialists (dermatologists and plastic surgeons) and other hospital specialists in excising SCCs. Methods . A retrospective analysis of all SCCs excised in the Grampian region between 1 January and 31 December 2005. A total of 1184 reports were rated for source and adequacy of excision. RESULTS: GPs excised 23.7% of all SCC-positive biopsies. Whether the biopsy had been performed by a GP or a hospital skin specialist made no significant difference to excision adequacy. However, GPs were significantly more likely to excise adequately than hospital non-specialists (P < 0.001). Infrequent GP excisers appear to perform as well as frequent excisers in adequately excising SCCs. CONCLUSIONS: GPs excise a considerable number of SCCs in primary care. GPs compare favourably to skin specialists in excising SCCs. The performance of infrequent GP excisers does not appear to differ significantly from that of frequent GP excisers. Further work is required to define more clearly the role of GPs in the management of SCCs.

Comparative cytotoxicity and genotoxicity of particulate and soluble hexavalent chromium in human and sperm whale (Physeter macrocephalus) skin cells.

Chromium (Cr) is a global marine pollutant, present in marine mammal tissues. Hexavalent chromium [Cr(VI)] is a known human carcinogen. In this study, we compare the cytotoxic and clastogenic effects of Cr(VI) in human (Homo sapiens) and sperm whale (Physeter macrocephalus) skin fibroblasts. Our data show that increasing concentrations of both particulate and soluble Cr(VI) induce increasing amounts of cytotoxicity and clastogenicity in human and sperm whale skin cells. Furthermore, the data show that sperm whale cells are resistant to these effects exhibiting less cytotoxicity and genotoxicity than the human cells. Differences in Cr uptake accounted for some but not all of the differences in particulate and soluble Cr(VI) genotoxicity, although it did explain the differences in particulate Cr(VI) cytotoxicity. Altogether, the data indicate that Cr(VI) is a genotoxic threat to whales, but also suggest that whales have evolved cellular mechanisms to protect them against the genotoxicity of environmental agents such as Cr(VI).