Wireless phone use in childhood and adolescence and neuroepithelial brain tumours: Results from the international MOBI-Kids study.

In recent decades, the possibility that use of mobile communicating devices, particularly wireless (mobile and cordless) phones, may increase brain tumour risk, has been a concern, particularly given the considerable increase in their use by young people. MOBI-Kids, a 14-country (Australia, Austria, Canada, France, Germany, Greece, India, Israel, Italy, Japan, Korea, the Netherlands, New Zealand, Spain) case-control study, was conducted to evaluate whether wireless phone use (and particularly resulting exposure to radiofrequency (RF) and extremely low frequency (ELF) electromagnetic fields (EMF)) increases risk of brain tumours in young people. Between 2010 and 2015, the study recruited 899 people with brain tumours aged 10 to 24 years old and 1,910 controls (operated for appendicitis) matched to the cases on date of diagnosis, study region and age. Participation rates were 72% for cases and 54% for controls. The mean ages of cases and controls were 16.5 and 16.6 years, respectively; 57% were males. The vast majority of study participants were wireless phones users, even in the youngest age group, and the study included substantial numbers of long-term (over 10 years) users: 22% overall, 51% in the 20-24-year-olds. Most tumours were of the neuroepithelial type (NBT; n = 671), mainly glioma. The odds ratios (OR) of NBT appeared to decrease with increasing time since start of use of wireless phones, cumulative number of calls and cumulative call time, particularly in the 15-19 years old age group. A decreasing trend in ORs was also observed with increasing estimated cumulative RF specific energy and ELF induced current density at the location of the tumour. Further analyses suggest that the large number of ORs below 1 in this study is unlikely to represent an unknown causal preventive effect of mobile phone exposure: they can be at least partially explained by differential recall by proxies and prodromal symptoms affecting phone use before diagnosis of the cases. We cannot rule out, however, residual confounding from sources we did not measure. Overall, our study provides no evidence of a causal association between wireless phone use and brain tumours in young people. However, the sources of bias summarised above prevent us from ruling out a small increased risk.

Airborne polycyclic aromatic compounds contribute to the induction of the tumour-suppressing P53 pathway in wild double-crested cormorants.

Polycyclic aromatic compounds (PACs), including polycyclic aromatic hydrocarbons (PAHs) and PAH-like compounds are known or probable environmental carcinogens released into the environment as a by-product of incomplete combustion of fossil fuels and other organic materials. Studies have shown that exposure to PACs in the environment can induce both genotoxicity and epigenetic toxicity, but few studies have related PAC exposure to molecular changes in free ranging wildlife. Previous work has suggested that double-crested cormorants (Phalacrocorax auritus; DCCO) exhibited a higher incidence of genetic mutations when their breeding sites were located in heavily industrialized areas (e.g., Hamilton Harbour, Hamilton, ON, Canada) as compared to sites located in more pristine environments, such as in Lake Erie. The aim of this study was to determine if airborne PACs from Hamilton Harbour alter the tumour-suppressing P53 pathway and/or global DNA methylation in DCCOs. Airborne PACs were measured using passive air samplers in the Hamilton Harbour area and low-resolution mass spectrometry analysis detected PACs in livers of DCCOs living in Hamilton Harbour. Further hepatic and lung transcriptional analysis demonstrated that the expression of the genes involved in the DNA repair and cellular apoptosis pathway were up-regulated in both tissues of DCCOs exposed to PACs, while genes involved in p53 regulation were down-regulated. However, global methylation levels did not differ between reference- and PAC-exposed DCCOs. Altogether, data suggest that PACs activate the P53 pathway in free-ranging DCCOs living nearby PAC-contaminated areas.

Outcome after laparoscopic versus open wedge resection for suspected gastric gastrointestinal stromal tumors: A matched-pair case-control study.

BACKGROUND: Laparoscopic resection of gastric gastrointestinal stromal tumors (GISTs) has been shown by several retrospective studies to be technically feasible and associated with favorable outcomes when compared to the open approach. This study aims to mitigate potential selection bias by performing a case control study of laparoscopic (LWR) versus open wedge resection (OWR) matched by resection type, location and tumor size. METHODS: We retrospectively identified 50 consecutive patients who underwent LWR for a suspected gastric GIST from a prospective database and matched this cohort with 50 patients who underwent OWR. RESULTS: There was no statistical difference between the key baseline clinicopathological features of patients' who underwent LWR versus OWR. Patients who underwent LWR had longer operating times [150 (range, 65-270) minutes vs 92.5 (25-200) minutes, P < .001] but decreased median blood loss [0 (0-300) ml vs 0 (0-1200) ml, P = .015], decreased frequency of intraoperative or postoperative blood transfusion [1 (2%) vs 8 (16%), P = .031], decreased median time to liquid diet [2 (0-5) vs 3 (1-7) days, P < .001], decreased median time to solid diet [3 (1-6) vs 5 (2-11) days, P < .001] and decreased postoperative stay [4 (2-10) vs 4.5 (3-17), P < .001] compared to OWR. There was no difference in oncological outcomes such as frequency of close margins (≤ 1 mm) and recurrence-free survival. CONCLUSION: This matched case-control study provides supporting evidence that LWR results in superior perioperative outcomes compared to OWR without compromising on oncological outcomes.

Preoperative planning simulator for spinal deformity surgeries.

STUDY DESIGN: Proof of concept of a spine surgery simulator (S3) for the assessment of scoliosis instrumentation configuration strategies. OBJECTIVE: To develop and assess a surgeon-friendly spine surgery simulator that predicts the correction of a scoliotic spine as a function of the patient characteristics and instrumentation variables. SUMMARY OF BACKGROUND DATA: There is currently no clinical tool sufficiently user-friendly, reliable and refined for the preoperative planning and prediction of correction using different instrumentation configurations. METHODS: A kinetic model using flexible mechanisms has been developed to represent patient-specific spine geometry and flexibility, and to simulate individual substeps of correction with an instrumentation system. The surgeon-friendly simulator interface allows interactive specification of the instrumentation components, surgical correction maneuvers and display of simulation results. RESULTS: The simulations of spinal instrumentation procedures of 10 scoliotic cases agreed well with postoperative results and the expected behavior of the instrumented spine (average Cobb angle differences of 3.5 degrees to 4.6 degrees in the frontal plane and of 3.6 degrees to 4.7 degrees in the sagittal plane). Forces generated at the implant-vertebra link were mostly below reported pull-out values, with more important values at the extremities of the instrumentation. CONCLUSION: The spine surgery simulator S3 has proven its technical feasibility and clinical relevance to assist in the preoperative planning of instrumentation strategies for the correction of scoliotic deformities.

Molecular characterization of Sp serotype strains of infectious pancreatic necrosis virus exhibiting differences in virulence.

Infectious pancreatic necrosis virus (IPNV), a prototype virus of the family Birnaviridae, exhibits a high degree of antigenic variability, pathogenicity and virulence in salmonid species. The Genomic Segment A encodes all the structural (VP2 and VP3) and nonstructural (NS) proteins, whereas Segment B encodes the viral RNA-dependent RNA polymerase (VP1). We tested 3 different IPNV isolates (Sp103, Sp116 and Sp122) isolated during field outbreaks in Norway for their ability to cause mortality in fry and post-smolt of Atlantic salmon Salmo salar L. The cumulative mortality following experimental challenge in fry was 29% for Sp122 followed by 19% for Sp116 and 15% for Sp103. In post-smolt, the corresponding mortality rates were 79, 46 and 16%, respectively. Comparisons of the deduced amino acid sequences of Segments A and B of all 3 Sp strains revealed substitutions of residues in 13 positions, of which 6 are in VP2, 2 in VP3, and 5 in VP1. Our results suggest that these residues, especially those in the outer capsid VP2, may be involved in the virulence of IPNV. Genome Segment A of the Sp serotype is 3097 nucleotides long and contains a major open reading frame (ORF) encoding a polyprotein of 972 amino acids, which initiates at the second in-frame start codon at Position 119. This was ascertained by making mutants of Segment A clone using site-directed mutagenesis, followed by in vitro transcription-coupled translation reaction and immunoprecipitation analyses. In addition, Segment A also encodes a 15 kDa arginine-rich non-structural protein from a small ORF, preceding and partially overlapping the polyprotein ORF, which is truncated to 12 kDa in the virulent Sp122 strain. Moreover, Segment A could encode a novel, putative 25 kDa protein from another ORF between VP2 and VP4 coding regions, which is only detected in the Sp serotype. Segment B is 2777 nucleotides long and encodes in a single large ORF (a polypeptide of 844 amino acid residues), VP1.

Limited magnetic resonance imaging (MRI) and the occult hip fracture.

INTRODUCTION: Diagnosis of hip fracture is normally readily made from clinical evaluation and plain radiographs. Occasionally, clinical suspicion of fracture is not confirmed on plain X-rays. MATERIALS AND METHOD: Between January 2001 and March 2002, 422 patients were admitted to our department for post-traumatic hip pain. The diagnosis of hip fracture was unequivocally made in 365 patients (86%). Fifty-seven (14%) patients had a negative or equivocal radiograph. RESULTS: Limited magnetic resonance imaging (MRI) of the hip in this group of 57 patients confirmed that 8 (14%) sustained a femoral neck fracture, while 5 (9%) had an intertrochanteric fracture. In 19 patients (33%), some other pathology was found, mainly stable fractures of the femoral trochanters and pubic rami. Overall, 32 scans (56%) were positive and 25 (44%) were negative. Limited MRI detected patients with undisplaced hip fractures and identified them as candidates for surgery. CONCLUSION: The use of MRI in this specific and 'limited' way provides orthopaedic surgeons with a rapid, accurate and cost-effective diagnostic tool in this clinical scenario. Definitive diagnosis allows the correct management plan to be implemented early. We recommend that patients, who have significant hip pain following injury but indeterminate plain radiographs, undergo a limited MRI scan as a matter of routine.

Effect of progesterone on the invasive properties and tumor growth of progesterone receptor-transfected breast cancer cells MDA-MB-231.

One of the potential therapeutic interventions to hormone-independent breast cancer would be to reactivate the expression of estrogen receptor or progesterone receptor (PR) in the tumor cells so as to render the tumor responsive to the hormones. We have reported previously that progesterone markedly inhibited cell growth and induced remarkable focal adhesions in PR-transfected MDA-MB-231 cells. The aim of this study was to determine the effects of progesterone on the invasive properties and in vivo tumor growth of PR-transfected MDA-MB-231 cells. It was found that progesterone has increased cell resistance to trypsin digestion and increased cell attachment to extracellular matrix proteins, especially laminin and fibronectin. In vitro invasion assays using modified Boyden chambers showed that progesterone increased cell migration through matrix protein-coated membranes. However, Northern blotting analysis demonstrated that progesterone strongly down-regulated (up to 60-fold) the gene expression of urokinase plasminogen activator and increased (up to 5-fold) the expression of tissue-type plasminogen activator in these cells. This pattern of gene regulation suggested an inhibition of cell invasiveness because numerous clinical studies have indicated that low levels of urokinase plasminogen activator and high levels of tissue-type plasminogen activator in breast cancer are associated with favorable prognosis. Furthermore, animal studies showed that progesterone strongly inhibited the tumor formation and growth in Scid mice. After 12 weeks of inoculation, the median weight of tumors in the progesterone-treated group was 25 mg compared with 203 mg in the placebo group (P < 0.001). These results suggest that progesterone may provide effective treatment for estrogen receptor- and PR-negative breast cancer if the PR expression were reactivated. Alternatively, activation of progesterone-mediated molecular pathways in hormone-independent breast cancer may achieve similar therapeutic effects.

Breast and cutaneous mycobacteriosis: diagnosis by fine-needle aspiration biopsy.

The breast and skin are considered to be rare sites of extrapulmonary mycobacterial infection, comprising 0.1% to 0.5% of all tuberculosis cases, respectively. Fine-needle aspiration biopsy (FNAB) is a rapid and minimally invasive approach to diagnose extrapulmonary tuberculosis, and has been used successfully in identifying tuberculous lesions in the lymph nodes, thyroid, kidney, pancreas, vertebrae, and testis. Two cases of extrapulmonary mycobacteriosis diagnosed by FNAB are described: a 59-year-old Hispanic male with cutaneous mycobacterial infection of the head and neck region, and a 58-year-old white male with a unilateral tuberculous mastitis. In both instances, the FNAB material demonstrated acute neutrophilic exudate, few isolated aggregates of epithelioid histiocytes and lymphocytes, and on Fite-Farraco stain mycobacteria. Reported cases of tuberculosis diagnosed by FNAB have been few; this is the first case of cutaneous tuberculosis diagnosed by FNAB.

Conjunctival melanomas.

BACKGROUND: The nomenclature and the clinical and pathologic features of cutaneous and conjunctival melanomas are different. A comparison is made to familiarize dermatologists and ophthalmologists with these differences. METHODS: Five cases of conjunctival malignant melanoma from December 1983 to December 1990 were reviewed. RESULTS: The nomenclature of primary acquired melanosis is not used for cutaneous melanomas, and terms such as dysplasia and Clark's nevus are not used for conjunctival melanomas. Technical difficulties exist in orienting thin conjunctival tissues because of a tendency to curl during fixation, resulting in tangential sectioning and making a false diagnosis of a prognostically ominous pagetoid spread for an otherwise banal basilar hyperplastic pattern. Excision, cryotherapy, and rarely exenteration are the therapeutic measures in managing conjunctival melanomas; these have far more serious consequences for the patient compared with the excision of a skin melanoma. CONCLUSION: Differences exist in several aspects between melanomas located in the skin and the eye.

Structure of cis-polyisoprene from Lactarius mushrooms.

Sporophores from five species of Lactarius mushrooms had a liquid rubber content of 0.1% to 7% based on the dry weight. Rubber from L. volemus, L. chrysorrheus and L. hygrophoroides was found to be a homologue of polyprenol being composed of dimethylallyl group, two trans isoprene units, 160-300 cis isoprene units, and terminal hydroxyl or ester group aligned in that order by 13C-NMR analysis. The ratio of fatty acid ester group to hydroxyl group was about 9/1 to 5/5. The number of both terminal groups and trans units decreased during aging of sporophores. Rubber from L. piperatus, L. vellereus and L. subpiperatus was found to be cis polyisoprene having very small quantities of both terminal groups and trans units. The biosynthesis of cis polyisoprene in Lactarius mushrooms was found to start from trans, trans-farnesyl pyrophosphate. The termination was assumed to occur by esterification of polyisoprenyl pyrophosphate. Occurrence of some chemical modifications on both terminal groups was presumed during aging of sporophores.

Recurrent pyogenic granulomas: a form of lobular capillary hemangioma.

Two cases of pyogenic granuloma recurred despite what was originally thought to be a sufficient surgical excision. The granulomas presented clinically as polypoid structures, one on the finger and one on the chin. On histologic examination, all showed polypoid configuration with lobules of small vessels and endothelial cell proliferation. The recurrent lesions also showed similar lobules, but interspersed between the collagen bundles in the deeper dermis. Vascular tumors such as the lobular pyogenic granulomas, intravenous capillary hemangiomas, and acquired tufted angiomas were compared to our tumors.

Fine needle aspiration cytology of cutaneous metastases.

By fine needle aspiration biopsy, 58 cases of cutaneous metastases were clinically and cytologically diagnosed at the Hines Veterans Administration Hospital from January 1987 to December 1990. Immunologic and electron microscopic studies affirmed the diagnosis and in some instances defined the primary neoplasm. The age of the patients ranged from 54 to 83 years (mean, 65). All were men. Two groups of patients emerged: group 1, 37 patients with known cancer, constituted the majority (64%). Group 2 consisted of 21 patients with cutaneous metastasis as the presenting sign (36%). Our patient survival times, a few weeks to 16 months (average, 4 months) are consistent with previous reports.

Melanoma in childhood and adolescence: clinical and pathological features of 48 cases.

Forty-eight cases of melanoma occurring in patients under 20 years of age were reviewed from a 23-year period at a single center. Fourteen of the patients were preadolescent children and 44 were Caucasian. Histological review of 44 available primary tumors showed only superficial spreading and nodular types. Thickness ranged from 0.23 mm to 8.50 mm, with a median of 1.03 mm. Ulceration was present in 7%, necrosis in 35%, evidence of regression in 16%, and antecedent nevus in 49% of the cases. The overall 5-year survival is 77%, with a median follow-up of 48 months. There is no detectable survival difference between preadolescent children and adolescents. Several treatment failures occurred after improper biopsy and/or inaccurate original diagnosis of Spitz's nevus. Of 38 stage I and II patients given definitive surgical treatment by the authors, the 5-year survival is 90%. Although histological confusion with Spitz's nevi occasionally occurs, melanoma in this age group can be treated with good results.

Transient bullous dermolysis of the newborn. Retention of anchoring fibril- and basal lamina-like structures in keratinocytes and evidence of collagenolysis.

In a freshly induced blister from transient bullous dermolysis of the newborn, we found in epidermal basal cells structures similar to anchoring fibrils and lamina densa, often in combination. In the upper dermis, collagenolysis and phagocytosis of degenerated collagen fragments were observed. It is concluded that the stellate inclusions previously reported in this disease are prematurely assembled anchoring fibrils and lamina densa. A disturbance of delivery mechanism of precursor materials for anchoring fibrils and lamina densa may cause the deficiency of these structures which are essential for the integrity of dermo-epidermal adhesion. The presence of many normal anchoring fibrils and lamina densa in perilesional skin and their prompt degeneration after rupture of the inclusions previously led us to conclude that lytic enzymes are involved in the formation of blisters in this disease. The new finding of collagen phagocytosis in the lesional dermis seemed to support this contention.

Cell cycle-dependent regulation of CDw75 (beta-galactoside alpha-2,6-sialyltransferase) on human B lymphocytes.

Within the hematopoietic system, CDw75 is primarily expressed on cells of the B cell lineage. Cloning and sequencing of the gene has shown CDw75 to be a beta-galactoside alpha-2,6-sialyltransferase. This enzyme plays an important role in the intracellular terminal glycosylation pathways in various cell types. In this article, we demonstrate that COS cells transfected with the CDw75 cDNA clone displayed sialyltransferase activity, in contrast to mock-transfected cells. We also found that activated B cells displayed an increased enzyme activity compared to resting cells, in accordance with the staining data. Moreover, CDw75 expression was found to be up-regulated approximately 7-9-fold from early G1 to the G2/M phases of the cell cycle in peripheral blood leukocyte B cells. This was shown by staining of in vitro activated B cells with the anti-CDw75 monoclonal antibody HH2, using cell fractions corresponding to different stages of the cell cycle. Using a combination of Hoechst 33258 and propidium iodide after bromodeoxyuridine incorporation, it is possible to distinguish between different phases of the first and second cell cycle. By combining this with HH2 immunofluorescence staining, using a multistation multiparameter flow cytometry program, we confirmed the cell cycle-dependent expression of CDw75. Immunocytochemical stainings of cytospin specimens of elutriated B cells showed that the antigen was up-regulated in late G1 before the appearance of the nuclear activation antigen Ki67. Finally, we showed that activated B cells secreted soluble CDw75 into the medium, as demonstrated by a specific blocking of HH2 staining of B cells using suboptimal concentrations of HH2. In accordance with this, we observed small, but detectable levels of soluble sialyltransferase activity in supernatants of activated B cells.

Eccrine acrospiroma of the eyelid with oncocytic, apocrine and sebaceous differentiation. Further evidence for pluripotentiality of the adnexal epithelia.

A wide variety of sweat gland tumors occur in the eyelids. We used light and electron microscopy to investigate an eccrine acrospiroma showing areas of oncocytic, apocrine and sebaceous differentiation. To our knowledge this is the first report of an oncocytic lesion arising from an eccrine sweat gland, and only the second report of such a lesion arising from the skin. Furthermore, apocrine and sebaceous differentiation are atypical in lesions originating from sweat glands. The wide spectrum of differentiation in this adenoma lends further support to the concept of pluripotentiality of the adnexal glandular epithelia.

Molecular cloning and characterization of the promoter region of the mouse regulatory subunit RII beta of type II cAMP-dependent protein kinase.

The promoter and exon 1 of the regulatory subunit (RII beta) of type II cAMP-dependent protein kinase were isolated from a mouse genomic library. The 5'-flanking DNA lacked TATA and CAAT sites but contained GC rich regions typically found in constitutively expressed house keeping genes. Fusion gene constructs, containing RII beta 5'-flanking sequences and the bacterial CAT structural gene, were transfected into NB2a neuroblastoma cells and CHO cells. The NB2a cells expressed high levels of CAT activity. CHO cells expressed CAT activity at 5% of the level seen in the NB2a cells. Transfection of deletion constructs into both cell lines was used to define the core promoter and enhancer elements. The core promoter was situated between bp -291/-121. An enhancer element was located between bp -1426/-1018.