Gas chromatography/tandem mass spectrometry method for the simultaneous analysis of 19 brominated compounds in environmental and biological samples.

A methodology for the simultaneous analysis of eight polybrominated diphenyl ethers (PBDEs); eight methoxylated PBDEs (MeO-PBDEs); and three emerging flame retardants, hexabromobenzene (HBB), pentabromoethyl benzene (PBEB), and decabromodiphenyl ethane (DBDPE) by gas chromatography coupled to tandem mass spectrometry (GC-MS-MS) was developed for two environmental matrices (sediment and sludge) and three biological matrices (fish, dolphin blubber, and bird eggs). The use of selective reaction monitoring (SRM) allows a high selectivity, which is critical in the analysis of complex samples like blubber. Analytical parameters such as linearity, reproducibility, or accuracy were evaluated. Method limits of detection and quantification were evaluated and compared with GC-EI-MS and GC-NCI-MS. Method detection limits were valid for the environmental analysis in all cases, with values between 0.01 and 1.65 ng/g dw for sediment, 0.05 and 2.78 ng/g dw for sludge, 0.04 and 10.6 ng/g lw for fish, 0.01 and 1.11 ng/g lw for dolphin blubber, and 0.03 and 3.20 ng/g lw for bird eggs. The developed method was applied to five samples of each matrix. PBDEs were detected in all samples, while MeO-PBDEs were only detected in dolphin blubber. DBDPE was detected in sediment and sludge.

Advanced UV/H2O2 oxidation of deca-bromo diphenyl ether in sediments.

Removal of BDE-209 from contaminated sediments by UV/H2O2 treatment was investigated under different reaction conditions (different UV irradiance and H2O2 concentrations). After 10h of UV/H2O2 treatment, 90% of BDE-209 was removed with a half-life time (t1/2) of 3.5h and a kinetic constant (k) of 0.22 h(-1). Possible formation of OH-PBDEs and debrominated polybromodiphenyl ethers was investigated by GC-MS and LC-MS/MS. None of the abovementioned BDE-209 by-products was found after 2.5, 5.5 and 10h of UV/H2O2 treatment. Toxicity experiments carried out with zebrafish embryos exposed to the sediment before and after the UV/H2O2 treatment did not show any morphological or behavioural alterations, suggesting that no putative debrominated or oxidation products were originated by the treatment in concentrations high enough to elicit significant toxic effects in zebrafish embryos.

Screening and pathways to maternal mental health care in a South African antenatal setting.

In low-resource settings, a stepped care approach is necessary to screen and provide care for pregnant women with mental health problems. This study sought to identify screening items that were most robust at differentiating women experiencing psychological distress and requiring counselling [assessed by screening with the Edinburgh Postnatal Depression Scale (EPDS) and a Risk Factor Assessment (RFA)] from those with a psychiatric disorder as diagnosed by a psychiatrist. Case records of women in an antenatal mental health service in Cape Town were reviewed. Composite scores and individual items on screening scales (EPDS, RFA) of participants who qualified for counselling (n = 308) were compared to those of participants who were diagnosed with a psychiatric disorder (n = 58). All participants with a psychiatric disorder were diagnosed with either depression or anxiety disorders. These participants had higher mean scores on the EPDS and RFA than those who qualified for counselling (p < 0.01). Logistic regression and ROC analyses suggested that the best items to distinguish women with depression or anxiety from those qualifying for counselling were 'I have felt sad and miserable', 'I am not pleased about being pregnant' and 'I have had serious depression, panic attacks or problems with anxiety before' (sensitivity 0.655, specificity 0.750 for this combination of three items). A small number of items may be useful in screening for mental illness in pregnancy which requires higher levels of care. Such screening may contribute to a more efficient stepped care approach.

Increased plasma concentration of vascular endothelial growth factor in patients with atopic dermatitis and its relation to disease severity and platelet activation.

BACKGROUND: Overproduction of vascular endothelial growth factor (VEGF) in atopic dermatitis (AD) lesions has previously been observed. It is also known that platelet is an important source of VEGF and platelet factor 4 (PF-4), a potential marker of AD severity. AIM: To evaluate concentrations of VEGF and its soluble receptors (sVEGF-R1 and sVEGF-R2) in the plasma of AD patients and to examine its possible correlation with disease severity and plasma concentrations of PF-4, a platelet activation marker. METHODS: Plasma concentrations of VEGF and its receptors and levels of PF-4 were measured by an immunoenzymatic assay in 51 AD patients and in 35 healthy non-atopic controls. The severity of the disease was evaluated using the eczema area and severity index. RESULTS: AD patients showed significantly increased VEGF and PF-4 plasma concentrations as compared with the controls. Plasma concentrations of sVEGF-R1 and sVEGF-R2 did not differ between the groups. There were no remarkable correlations between plasma VEGF concentration and disease severity or between VEGF and PF-4 concentration. CONCLUSIONS: This study shows that plasma concentration of VEGF may be increased in patients suffering from AD. It seems that plasma VEGF concentration is not a useful marker of disease severity and, apart from platelets, other cells might also release the cytokine.

PDT in squamous cell carcinoma of the skin.

Topical photodynamic therapy (PDT) has been demonstrated to be an effective and safe treatment option for pre-malignancies such as actinic keratoses (AK) and Bowen's disease (BD), with an increasing amount of evidence indicating good long term outcomes. Studies comparing PDT to other options such as cryotherapy and 5-fluorouracil generally demonstrate that PDT is equal to or better than these therapies with respect to patient satisfaction, cosmesis, and efficacy for AK and BD. While there are studies using squamous cell carcinoma (SCC) cells to elucidate the cellular and molecular mechanisms of PDT, this therapy is currently not indicated for treating SCC and surgery is still the first line of therapy. There has been special interest in using PDT to prevent warts, basal cell carcinoma, AK, and BD in solid organ transplant recipients, as these skin lesions are more common in immunosuppressed patients, and trials have been somewhat successful and very promising. Pain remains an obstacle for some patients and techniques such as nerve blocks, cooling packs, and hydration have been attempted to mitigate pain with an overall reduction in pain scores. Optimizing PDT is still a priority and the delivery of pro-drug as well as induction of cellular differentiation are being explored as ways to improve the efficacy of PDT. Perhaps the most interesting use of PDT in treating SCC is the potential for a tumor-specific vaccine, which is currently being developed.

Ten sessions of adjunctive left prefrontal rTMS significantly reduces fibromyalgia pain: a randomized, controlled pilot study.

Transcranial magnetic stimulation (TMS) of the prefrontal cortex can cause changes in acute pain perception. Several weeks of daily left prefrontal TMS has been shown to treat depression. We recruited 20 patients with fibromyalgia, defined by American College of Rheumatology criteria, and randomized them to receive 4000 pulses at 10 Hz TMS (n=10), or sham TMS (n=10) treatment for 10 sessions over 2 weeks along with their standard medications, which were fixed and stable for at least 4 weeks before starting sessions. Subjects recorded daily pain, mood, and activity. Blinded raters assessed pain, mood, functional status, and tender points weekly with the Brief Pain Inventory, Hamilton Depression Rating Scale, and Fibromyalgia Impact Questionnaire. No statistically significant differences between groups were observed. Patients who received active TMS had a mean 29% (statistically significant) reduction in pain symptoms in comparison to their baseline pain. Sham TMS participants had a 4% nonsignificant change in daily pain from their baseline pain. At 2 weeks after treatment, there was a significant improvement in depression symptoms in the active group compared to baseline. Pain reduction preceded antidepressant effects. TMS was well tolerated, with few side effects. Further studies that address study limitations are needed to determine whether daily prefrontal TMS may be an effective, durable, and clinically useful treatment for fibromyalgia symptoms.

Successful cutaneous delivery of the photosensitizer silicon phthalocyanine 4 for photodynamic therapy.

BACKGROUND: Photodynamic therapy (PDT) has been shown to be effective in the treatment of malignancies of a variety of organ systems, including the lungs, bladder, gastrointestinal tract and skin. Cutaneous lesions serve as ideal targets of PDT because of the accessibility of the skin to light. To achieve optimum results, the photosensitizer must be delivered effectively into the target layers of the skin within a practical timeframe, via noninvasive methods. AIM: To determine whether topical application of a second-generation photosensitizer, silicon phthalocyanine (Pc) 4 [SiPc(OSi(CH3)2 (CH2)3 N(CH3)2)(OH)], results in effective penetration of the skin barrier. METHODS: Penetration of Pc 4 was evaluated using standard Franz-type vertical diffusion cell experiments on surrogate materials (silicone membranes) and laser-scanning confocal microscopy of normal skin biopsy samples from human volunteers. RESULTS: The Franz diffusion data indicate that Pc 4 formulated in an ethanol/propylene glycol solution (70/30%, v/v) can penetrate the membrane at a flux that is appreciable and relatively invariant. Using the same formulation, Pc 4 uptake could be detected in human skin via laser-scanning confocal microscopy. CONCLUSION: After topical application, Pc 4 is absorbed into the epidermis in as little as 1 h, and the absorption increased with increasing time and dose. Pc 4 can be effectively delivered into human skin via topical application. The data also suggest that the degree of penetration is time- and dose-dependent.

Photoprotection with clothing and sunscreens.

Skin cancer is an ever-expanding global health issue. UV radiation is the main etiological agent of most types of skin cancer. Photoprotection is critical to in skin cancer prevention. Sunscreens and physical barriers are the two primary photoprotective measures. This review summarizes current options in photoprotection, including physical barrier such as shade and clothing as well as sunscreens. In addition we look at how these photoprotective measures have influenced skin cancer rates and what can be done to improve the efficacy of existing photoprotective agents and devices.

Mixed infection involving Actinomyces, Aggregatibacter, and Fusobacterium species presenting as perispinal tumor.

A representative case in which a polymicrobial infection involving Fusobacterium nucleatum, Actinomyces israelii and Aggregatibacter (formerly Actinobacillus) actinomycetemcomitans was initially diagnosed as malignancy in an edentulous patient. Additional history obtained after the nature of the syndrome was elucidated revealed that he had had his two remaining teeth extracted four months prior to this episode.

Análisis retrospectivo del carcinoma cutáneo tipo basoceluar y escamocelular en Bogotá-Colombia: epidemiología, prevención y tratamiento / A retrospective analysis of basal cell and squamous cell skin cancer in Bogota, Colombia: its epidemiology, prevention and treatment

Antecedentes. El carcinoma cutáneo no melanoma del tipo basocelular (CBC) y escamocelular (CEC), tiene tasas de incidencia cercanas al 13 por ciento y es el más prevalente en la población blanca. Trae elevada morbilidad para el paciente y altos costos para el sistema de salud, y aunque es la neoplasia maligna mas frecuentemente diagnosticada, en Colombia sólo se tienen estadísticas en instituciones oncológicas, haciendo énfasis principalmente en melanomas. Entre los principales factores de riesgo se encuentra la exposición a los RUVB, tipo de piel, la radiación, el virus del papiloma humano (HPV) y su tratamiento incluye medicación tópica, crioterapia, electrofulguración y cirugía.Objetivo. Analizar algunas características epidemiológicas del cáncer cutáneo (CBC - CEC) en nuestro medio, estableciendo similitudes y diferencias respecto a la literatura actual.Material y métodos. En la clínica San Pedro Claver se revisaron 202 historias clínicas de pacientes con diagnóstico confirmado de CBC O CEC de 2004 a 2006 en un estudio retrospectivo de serie de casos y se analizaron las variables más comunes como el tipo de lesión, su ubicación, tamaño, patrón histológico y tratamiento.Resultados. Ingresaron en el estudio 112 pacientes, de los cuales cerca del 60 por ciento eran hombres, con una edad media de 69.5 años. El 90 por ciento de las lesiones se localizaban en cara (mejillas, párpados, nariz). Del 70 por ciento de las lesiones que correspondían a CBC el tipo histológico más frecuente fue sólido nodular y del 22 por ciento de lesiones que correspondían a CEC, el moderadamente diferenciado de célula grande fue el más común. Conclusiones. En Colombia las estadísticas del carcinoma cutáneo (CBC y CEC) tienen un patrón de comportamiento similar a los reportados en la literatura y el pronóstico depende de un adecuado diagnóstico y tratamiento, así como de una intervención oportuna en los factores de riesgo.

ICER expression inhibits leukemia phenotype and controls tumor progression.

The inducible cyclic AMP (cAMP) early repressor (ICER) and cAMP response element-binding protein (CREB) are transcriptional regulators of the cAMP-mediated signaling pathway. CREB has been demonstrated to be upregulated in the majority of childhood leukemias contributing to disease progression, whereas ICER, its endogenous repressor, was found to be downregulated. Our research focus has been the function of restored ICER expression. ICER exogenously expressed in cell lines decreases CREB protein level and induces a lowered clonogenic potential in vitro. It decreases the ability of HL60 to invade the extramedullary sites and to promote bone marrow angiogenesis in nonobese diabetic-severe combined immunodeficient mice, demonstrating its potential effects on tumor progression. ICER represses the majority of 96 target genes upregulated by CREB. It binds CRE promoters and controls gene expression restoring the normal regulation of major cellular pathways. ICER is subjected to degradation through a constitutively active form of the extracellular signal-regulated protein kinase, which drives it to the proteasome. We propose that ICER is downregulated in HL60 to preserve CREB overexpression, which disrupts normal myelopoiesis and promotes blast proliferation. These findings define the function of ICER as a tumor suppressor in leukemia. Unbalanced CREB/ICER expression needs to be considered a pathogenetic feature in leukemogenesis. The molecular characterization of this pathway could be useful for novel therapeutic strategies.

Protection against UV-induced suppression of contact hypersensitivity responses by sunscreens in humans.

Both in vivo skin immune responses and the skin's reaction to sun exposure integrate a complex interplay of biologic responses. The complexity and multiplicity of events that occur in the skin during an immune response make it a sensitive indication of both UVB and UVA-induced changes in the skin by sun damage, as well as those changes that are prevented by various sunscreens. Sunscreens are the most effective and widely available intervention for sun damage, other than sun avoidance or clothing. However, sunscreens vary widely in their relative ability to screen various UV waveband components, and their testing has been variably applied to outcomes other than for erythema to determine the sunburn protection factor (SPF), a measure primarily of UVB filtration only. Determination of an immune protection factor (IPF) has been proposed as an alternative or adjunctive measure to SPF, and recent studies show IPF can indeed detect added in vivo functionality of sunscreens, such as high levels of UVA protection, that SPF cannot. Clarification of the definition of IPF, however, is required. Excellent data are available on quantification of the IPF for restoring the afferent or induction arm of contact sensitivity, but other immune parameters have also been measured. Proposed here is nomenclature for whether the IPF is measured using contact sensitivity induction (IPF-CS-I), contact sensitivity elicitation (IPF-CS-E), delayed-type hypersensitivity elicitation (IPF-DTH-E), antigen-presenting cell function (IPF-APC-FXN) or numbers (IPF-APC-#), and cytokine modification such as IL-10 (i.e. IPF-cyto-IL-10). Similar nomenclatures could be used for other measures of skin function protection (i.e. DNA damage, p53 induction, oxidation products, etc.). A review of in vivo human studies, in which sunscreens are used to intervene in a UV-induced modulation of immune response, cells or cytokines, highlights the technical variables and statistical approaches which must also be standardized in the context of an IPF for regulatory or product claim purposes. Development of such IPF standards would allow the integration of both UVB and nonUVB (UVA, blue and possible IR) solar waveband effect-reversals, could be applied to integrate effects of other ingredients with protective function (i.e. antioxidants, retinoids, or other novel products), and would spur development of more advanced and complete protection products.

Anxiety reaction in children during removal of their plaster cast with a saw.

We have had experience of an 18-month-old boy with a cardiomyopathy who died a few minutes after removal of his cast with a saw, apparently from a malignant cardiac arrhythmia triggered by anxiety. We therefore examined the anxiety reaction to this method of removal of a plaster cast in 20 healthy children; ten were provided with hearing protectors and ten were not. The level of anxiety was assessed by measuring the heart rate, a known physiological indicator of anxiety, before, during and five minutes after removal of the cast. The noise level was also measured. The results showed a mean increase in heart rate during the procedure of 27.9 beats per minute (bpm) (26.9%) in the children with no hearing protectors and 10.4 bpm (11.1%) in children who used hearing protectors (p < 0.001). Five minutes after the procedure the heart rate had returned to the baseline rate in all patients. We recommend that hearing protectors should be used in children undergoing removal of a plaster cast to decrease the anxiety reaction. If possible, clinicians should avoid the use of a saw for this purpose in children with a cardiomyopathy.

Multinodular goiter: the surgical procedure of choice.

Surgical management of multinodular goiter (MNG) poses an ongoing dilemma between radical resection with its associated complications and partial resection, which carries the risk of recurrence and increased morbidity and difficulty for rethyroidectomy. This study was designed to evaluate the recurrence rate and need for reoperation in a carefully selected population of MNG patients, after nontotal thyroidectomy. The study addressed a highly selected population of patients who were treated and thoroughly evaluated at one surgical department for several years. We analyzed the recurrence rate of MNG in 124 patients. The follow-up duration extended from 6 to 516 months (mean 93 months). The general recurrence rate for all nontotal bilateral thyroidectomies was 21% (21/100 patients), increasing from 13.4% to 60% according to the extent of resection. The average time for recurrence was 105 months (8.75 years). Among the patients with recurrent MNG, only 4 (4% of the patients with nontotal bilateral thyroidectomy) required secondary surgical interventions with no resultant morbidity. In our series of very highly selected patients, the recurrence rate for nontotal thyroidectomy was high (21%); however, the need for secondary surgical intervention was low (4%). Thus nontotal thyroidectomy for MNG is legitimate. However, we suggest that the surgical procedure of choice be tailored according to the severity of the disease and the patient's general condition.

Prediction of bone loss in patients with primary hyperparathyroidism using quantitative bone SPECT.

UNLABELLED: Bone loss is a major complication of primary hyperparathyroidism (PHPT), and it has significant implications in the treatment of this disease. Bone turnover was measured in patients with PHPT, using quantitative bone SPECT (QBS), to determine if the rate of bone loss could be predicted before a significant decrease in bone mass occurs. METHODS: Forty-six patients were included in the study. QBS and bone mineral density (BMD) of the lumbar spine (LS) and femoral neck (FN) were done at baseline. The percent deviation of QBS in patients with PHPT from the values in normal matched controls was calculated. BMD was measured again after a mean of 17.5 mo in 38 patients, and in 29 patients a repeat BMD study was done after a mean of 41.4 mo. The change in BMD in patients with high and normal QBS values was compared using the nonparametric Mann-Whitney test. Regression analysis tested the correlation between baseline QBS values and BMD changes over time. RESULTS: For the FN, there was a statistically significant difference in the BMD change between patients with high and normal QBS values for short-term follow-up (-2.82%+/-4.80% versus 1.45%+/-4.67%, p < 0.05) and for long-term follow-up (-3.53%+/-5.34% versus 0.92%+/-2.40, p < 0.02). There was a negative correlation in the FN, r=-0.48 between QBS values and the percentage of change in BMD. There was no significant difference between the percentage of change in BMD in the LS in patients with high and normal QBS values for either short- or long-term follow-up. CONCLUSION: The results of this study show that QBS can predict bone loss in the FN in patients with PHPT. QBS can thus indicate the need for surgery at an early stage of the disease to prevent bone loss.

Human fibroblasts expressing the human papillomavirus E6 gene are deficient in global genomic nucleotide excision repair and sensitive to ultraviolet irradiation.

We investigated the role of wild-type p53 activity in modulating nucleotide excision repair after UV irradiation in normal and p53-deficient primary human fibroblasts created by expression of the human papillomavirus 16 E6 gene. Compared with parental cells, the E6-expressing fibroblasts were deficient in global genomic repair of both UV-induced cyclobutane pyrimidine dimers and 6-4 photoproducts but exhibited normal transcription-coupled repair. The E6-expressing cells were also more sensitive than their parental counterparts to UV irradiation and displayed similar levels of UV-induced apoptosis. These results suggest that disruption of wild-type p53 function by E6 expression results in selective loss of p53-dependent global genomic nucleotide excision repair, but not UV-induced apoptosis, leading to enhanced UV sensitivity.

Cys 618 Arg mutation in the RET proto-oncogene associated with familial medullary thyroid carcinoma and maternally transmitted Hirschsprung's disease suggesting a role for imprinting.

The multiple endocrine neoplasia type 2 (MEN2) syndromes and Hirschsprung's disease (HSCR) are inherited neurocristopathies characterized by medullary thyroid carcinoma (MTC), pheochromocytoma, parathyroid disease, and gastrointestinal neuromatosis. Mutations in the RET proto-oncogene are the underlying cause of the MEN2 syndromes and some cases of HSCR. In this report, we show that Cys 618 Arg mutation cosegregates with familial MTC and HSCR in two Moroccan Jewish families in which no involvement of pheochromocytoma or parathyroidism was observed. A single haplotype shared by chromosomes bearing the Cys 618 Arg mutation in both families strongly suggests a founder effect for this mutation. We have observed in our and in several other previously reported families, an excess of maternal over paternal mutated RET alleles in offsprings affected by HSCR. We suggest that parental imprinting may play a role in the ethiology of HSCR caused by mutations in the RET protooncogene.

Treatment of chronic hepatitis B and C with alpha interferon in a renal transplant patient.

We report the case of a 51-year-old renal transplant patient, treated by interferon alpha (5MUI, three times a week) since he presented a coinfection by hepatitis B (HBV) and hepatitis C (HCV) virus for more than 7 years, associated with a chronic increase in serum alanine aminotransferase (ALT) levels and a chronic active hepatitis. The 4-month treatment was associated with a sustained normalization of ALT, a disappearance of HBV replication and a transient clearance of HCV viremia. Side effects were moderate and included thrombopenia (90,000/mm3), leucopenia (2200/mm3), an increase in serum creatinine (178 mumol/l). The withdrawal of alpha interferon was associated with the correction of these parameters. No rejection was observed on kidney biopsy. Meanwhile, liver histology was not affected by the treatment. To date, nineteen months after the end of alpha interferon therapy HBV DNA was still negative; ALT remained normal despite the early recurrence of HCV viremia; this emphasized the fact that HBV infection was certainly the most important factor involved in the patient's chronic hepatitis. It is concluded that alpha interferon therapy is able to decline HBV replication for a prolonged period in renal transplant patient although its use should be performed with caution due to the potential renal side effects.