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Merkel cell carcinoma (MCC) is a rare malignant cutaneous neuroendocrine tumour affecting mainly elderly patients and is more common in the West than in Asia. It is associated with Merkel cell polyomavirus (MCPyV), immunosuppression, and ultraviolet light. In this study, we retrospectively investigated the first series of MCC from Taiwan and identified 19 cases from three tertiary centres. All patients were males with a median age of 67.5. Twelve (63%) cases occurred in the extremities, with one unique case presenting initially as nodal metastasis of unknown primary. Immunohistochemically, the great majority of tumours expressed CK20 (89%), synaptophysin (89%), and INSM1 (84%), with none positive for TTF1. Eleven (58%) cases were positive for MCPyV by immunohistochemistry (clone CM2B4). All patients were treated with excision, including four with additional radiotherapy and one with radiotherapy and chemotherapy. Nodal status and treatment modalities significantly affected survival. The median survival time of MCPyV-positive cases was much longer than the negative cases (median 40 vs. 10 months). In summary, we presented the first report on the clinicopathological features of MCC in Taiwan, with 58% cases associated with MCPyV. The prognosis of patients with MCPyV-positive tumours was better than those negative for MCPyV.

Follicular lymphoma (FL) is usually a nodal lymphoma expressing CD10, rarely with leukaemic presentation (FL-LP).We searched for FL-LP in our institution from 2000 to 2018 and characterised the neoplastic cells by flow cytometry, immunohistochemistry and fluorescence in situ hybridization. Thirteen (6.1%) of 212 FL cases were FL-LP, all de novo neoplasms. The leukaemic cells were small in 12 cases and large in one. All had concurrent FL, mostly (92%; 12/13) low-grade. The single case with large leukaemic cells had a concurrent primary splenic low-grade FL and a double-hit large B-cell lymphoma in the marrow.CD10 was expressed in the leukaemic cells in 38% (5/13) cases by flow cytometry and in 77% (10/13) cases in tumours (p= 0.0471). IGH/BCL2 reciprocal translocation was identified in 85% (11/13) cases. Most patients were treated with chemotherapy. In a median follow-up time of 36 months, nine patients were in complete remission. The 2- and 5-year survival rates were at 100% and 83%, respectively. In this study, we characterised a series of de novo FL-LP in Taiwan. All patients had concurrent nodal and/or tissue tumours, which might suggest that these patients seek medical help too late.The lower CD10 expression rate by flow cytometry than by immunohistochemistry might be due to different epitopes for these assays. Alternatively, loss of CD10 expression might play a role in the pathogenesis of leukaemic change. The clinical course of FL-LP could be aggressive, but a significant proportion of the patients obtained complete remission with chemotherapy.

Background: In stage I/II natural killer (NK)/T-cell lymphoma, concurrent chemoradiotherapy (CCRT) had previously been shown to result in superior outcome compared with anthracycline-containing regimens, which have since been considered ineffective. The role of CCRT in comparison with approaches employing nonanthracycline-containing chemotherapy (CT) and sequential radiotherapy (RT) in such patients remains to be defined. Patients and methods: Three hundred and three untreated patients (207 men, 96 women; median age: 51, 18-86 years) with stage I/II NK/T-cell lymphoma who had received nonanthracycline-containing regimens were collected from an international consortium and retrospectively analyzed. Treatment included single modality (CT and RT), sequential modalities (CT+RT; RT+CT) and concurrent modalities (CCRT; CCRT+CT). The impact of clinicopathologic parameters and types of treatment on complete response (CR) rate, progression-free-survival (PFS) and overall-survival (OS) was evaluated. Results: For CR, stage (P=0.027), prognostic index for NK/T-cell lymphoma (PINK) (P=0.026) and types of initial treatment (P=0.011) were significant prognostic factors on multivariate analysis. On Cox regression analysis, ECOG performance score (P=0.021) and PINK-EBV DNA (PINK-E) (P=0.002) significantly impacted on PFS; whereas ECOG performance score (P=0.008) and stage (P

High concentrations of sub-micron nanoparticles have been shown to be released during laser hair removal (LHR) procedures. These emissions pose a potential biohazard to healthcare workers that have prolonged exposure to LHR plume.We sought to demonstrate that cold sapphire skin cooling done in contact mode might suppress plume dispersion during LHR.A total of 11 patients were recruited for laser hair removal. They were treated on the legs and axilla with a 755 or 1064 nm millisecond-domain laser equipped with either (i) cryogen spray (CSC); (ii) refrigerated air (RA); or (iii) contact cooling with sapphire (CC). Concentration of ultrafine nanoparticles1 μm were measured just before and during LHR with the three respective cooling methods.For contact cooling (CC), counts remained at baseline levels, below 3,500 parts per cubic centimeter (ppc) for all treatments. In contrast, the CSC system produced large levels of plume, peaking at times to over 400,000 ppc. The CA cooled system produced intermediate levels of plume, about 35,000 ppc (or about 10× baseline).Cold Sapphire Skin cooling with gel suppresses plume during laser hair removal, potentially eliminating the need for smoke evacuators, custom ventilation systems, and respirators during LHR. Lasers Surg. Med. 50:280-283, 2018. © 2017 Wiley Periodicals, Inc.

The MAPK phosphatase MKP1 (DUSP1) is overexpressed in many human cancers, including chemoresistant and radioresistant breast cancer cells, but its functional contributions in these settings are unclear. Here, we report that after cell irradiation, MKP1 translocates into mitochondria, where it prevents apoptotic induction by limiting accumulation of phosphorylated active forms of the stress kinase JNK. Increased levels of mitochondrial MKP1 after irradiation occurred in the mitochondrial inner membrane space. Notably, cell survival regulated by mitochondrial MKP1 was responsible for conferring radioresistance in HER2-overexpressing breast cancer cells, due to the fact that MKP1 serves as a major downstream effector in the HER2-activated RAF–MEK–ERK pathway. Clinically, we documented MKP1 expression exclusively in HER2-positive breast tumors, relative to normal adjacent tissue from the same patients. MKP1 overexpression was also detected in irradiated HER2-positive breast cancer stem-like cells (HER2+/CD44+/CD24−/low) isolated from a radioresistant breast cancer cell population after long-term radiation treatment. MKP1 silencing reduced clonogenic survival and enhanced radiosensitivity in these stem-like cells. Combined inhibition of MKP1 and HER2 enhanced cell killing in breast cancer. Together, our findings identify a new mechanism of resistance in breast tumors and reveal MKP1 as a novel therapeutic target for radiosensitization. Cancer Res; 74(24); 7498–509. ©2014 AACR.

Background: Rituximab has been associated with hepatitis B virus reactivation (HBV-R). However, the characteristics and scope of this association remain largely undefined. Methods: We completed a comprehensive literature search of all published rituximab-associated HBV-R cases and from the Food and Drug Administration (FDA) Adverse Event Reporting System (AERS) MedWatch database. Literature and FDA cases were compared for completeness, and a meta-analysis was completed. Results: One hundred and eighty-three unique cases of rituximab-associated HBV-R were identified from the literature (n = 27 case reports, n = 156 case series). The time from last rituximab to reactivation was 3 months (range 0–12), although 29% occurred >6 months after last rituximab. Within FDA data (n = 118 cases), there was a strong signal for rituximab-associated HBV-R [proportional reporting ratio = 28.5, 95% confidence interval (CI) 23.9–34.1; Empiric Bayes Geometric Mean = 26.4, 95% CI 21.4–31.1]. However, the completeness of data in FDA reports was significantly inferior compared with literature cases (P < 0.0001). Among HBV core antibody (HBcAb(+)) series, the pooled effect of rituximab-based therapy showed a significantly increased risk of HBV-R compared with nonrituximab-treated patients (odds ratio 5.73, 95% CI 2.01–16.33; Z = 3.33, P = 0.0009) without heterogeneity (χ2 = 2.12, P = 0.5473). Conclusions: The FDA AERS provided strong HBV-R safety signals; however, literature-based cases provided a significantly more complete description. Furthermore, meta-analysis of HBcAb(+) series identified a more than fivefold increased rate of rituximab-associated HBV-R.

BACKGROUND Dermatologists have championed Mohs micrographic surgery (MMS) for its unsurpassed treatment success for skin cancers, safety profile, cost-effectiveness, and tissue-sparing quality. It is unclear whether patients undergoing MMS also value these characteristics. OBJECTIVE To evaluate patients' preoperative expectations of MMS and identify the factors that may influence such expectations METHODS The study prospectively recruited participants who were newly diagnosed with skin cancer and referred for MMS. A questionnaire listing the characteristics of MMS was given to the participants asking them to score the importance of each characteristic on a 10-point scale. The participants were also asked to provide information regarding their gender, age, subjective health status, education level, family annual income, and their referral source RESULTS On average, participants placed the highest value, in descending order, on a treatment that yielded the highest cure rate, reconstruction initiation only after complete tumor removal, and the surgeon being a skin cancer specialist. Overall, participants placed high values on characteristics of MMS that dermatologists have long esteemed. CONCLUSION Our data corroborate that MMS is a valuable procedure that meets the expectations not just of physicians, but also of patients. The authors have indicated no significant interest with commercial supporters.

The shell of the duck egg did not crack after pressure treatments (300 to 500 MPa; 25 degrees C; 10 min) in this study; therefore, the changes of physicochemical properties of egg white and yolk proteins from the intact shell egg by pressure treatment were first investigated and compared with those of pressurized hen liquid eggs. Although the proximate compositions of duck eggs and hen eggs were similar, the moisture and protein contents of hen whole eggs were higher than those of duck whole eggs. The protein contents of duck egg white and yolk were slightly lower than those of hen eggs, and the moisture content of duck egg white was equal to that of hen egg white, whereas that of duck egg yolk was lower than that of hen egg yolk. After pressure treatment at 500 MPa, the results of solubility, sulfhydryl content, surface hydrophobicity, and residual denaturation enthalpy showed that egg white proteins underwent slight but significant unfolding and aggregation, whereas pressure treatments below 500 MPa induced insignificant changes in the physicochemical properties. On the other hand, pressure treatments at 400 and 500 MPa significantly reduced the solubility and residual denaturation enthalpy of egg yolk proteins. However, the native PAGE result showed that pressure treatment up to 500 MPa did not affect the protein components of egg white and yolk. The results showed that the application of pressure treatment on duck shell egg may induce reversible denaturation of both egg white and yolk proteins. The egg white and yolk proteins may be prevented from denaturation after pressure treatment in the presence of the eggshell compared with the absence of the eggshell. As reported in the literature, pressure treatments at 300 to 500 MPa and 25 degrees C would be efficient for decontamination of duck shell eggs. Therefore, based on the consideration for food safety and functional properties, pressure processing can be a good preservation technique for duck shell eggs.

Background and aim: The pharmacokinetics of clenbuterol in equine urine and blood was investigated.Material and methods: Urine and blood samples were collected following 3-day multiple oral administrations. The samples were examined using enzyme-linked immunosorbent assay and further confirmed by solid phase extraction and capillary electrophoresis.Results: Urinary clenbuterol was detectable until day 14 after the last dose. The urinary excretion of clenbuterol was characterized by a biphasic pattern. The half-lives of the bi-exponential elimination (t1/2α and t1/2β) for urinary clenbuterol were about 12.1 and 48 hours. After a single oral administration (4 μg/kg) of clenbuterol, the half-life of serum clenbuterol was approximately 11.4 hours.

1Alpha,25-dihydroxyvitamin D3 (1,25D3) displays potent antiproliferative activity in a variety of tumor model systems and is currently under investigation in clinical trials in cancer. Studies were initiated to explore its potential in nonsmall cell lung cancer (NSCLC), as effective approaches to the treatment of that disease are needed. In evaluating factors that may affect activity in NSCLC, the authors found that CYP24 (25-hydroxyvitamin D3-24-hydroxylase), the enzyme that catabolizes 1,25D3, is frequently expressed in NSCLC cell lines but not in the nontumorigenic bronchial epithelial cell line, Beas2B. CYP24 expression by RT-PCR was also detected in 10/18 primary lung tumors but in only 1/11 normal lung tissue specimens. Tumor-specific CYP24 upregulation was confirmed at the protein level via immunoblot analysis of patient-matched normal lung tissue and lung tumor extracts. Enzymatically active CYP24 is expected to desensitize NSCLC cells to 1,25D3. The authors therefore implemented a high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) assay for 1,25D3 and its CYP24-generated metabolites to determine whether NSCLC cells express active enzyme. Analysis of NSCLC cell cultures revealed time-dependent loss of 1,25D3 coincident with the appearance of CYP24-generated metabolites. MK-24(S)-S(O)(NH)-Ph-1, a specific inhibitor of CYP24, slowed the loss of 1,25D3 and increased 1,25D3 half-life. Furthermore, combination of 1,25D3 with MK-24(S)-S(O)(NH)-Ph-1 resulted in a significant decrease in the concentration of 1,25D3 required to achieve maximum growth inhibition in NSCLC cells. These data suggest that increased CYP24 expression in lung tumors restricts 1,25D3 activity and support the preclinical evaluation of CYP24 inhibitors for lung cancer treatment.

4 páginas, 1 figura., Multiple cutaneous and uterine leiomyomata (MCL) is an autosomal dominant disorder characterized by the development of benign smooth muscle tumours (leiomyomas) in the skin and uterus of affected women, and in the skin of affected men. In rare cases, MCL has been associated with a predisposition to the rare type II papillary renal cell cancer, also known as hereditary leiomyomatosis and renal cell cancer. The genetic locus for MCL has been mapped to chromosome 1q42.3–43 and subsequently, germline mutations in the fumarate hydratase (FH) gene have been identified. In addition, analysis of FH in some tumours of MCL patients revealed a second mutation inactivating the wild-type allele, suggesting that FH may function as a tumour suppressor gene. Here, we report two cases of MCL patients with FH mutations, designated as T287P and R190L. T287P represents a novel mutation of a highly conserved amino acid of the FH protein. In addition, a patient with an unusual clinical presentation of MCL was found to have the recurrent mutation, R190L, raising the possibility of incorporating FH sequencing as a diagnostic tool. Our findings extend the allelic series of mutations in FH and support its status as the underlying cause of MCL., This work was supported in part by the Skin Disease Research Center, Department of Dermatology, Columbia University (P30 AR44535) and the Authority for Research and Development, Hebrew University of Jerusalem (to A. Zlotogorski).

Objectives To establish the upper limit for warm ischemia time (WIT) beyond which irreversible renal failure will occur in a single-kidney porcine model. The maximal renal tolerance during WIT is currently under revision. Traditionally, 30 minutes was defined as the safe limit for renal WIT. However, accumulating data have suggested that a WIT of up to 90 minutes may not result in permanent damage. Methods Twenty female pigs weighing 60 to 80 lb at arrival underwent initial right laparoscopic nephrectomy to create a single-kidney model. Twelve days later, the animals were randomized into four groups of 5 animals each: 120 minutes of open WIT, 120 minutes of laparoscopic WIT, 5 open controls, and 5 laparoscopic controls. Renal function was assessed with serial glomerular filtration rate and serum creatinine measurements, which were assessed preoperatively and on postoperative days (PODs) 1, 3, 8, and 15. Results No significant difference existed between the laparoscopic and open groups. The glomerular filtration rate reached the lowest value and the serum creatinine levels peaked on POD 3 and were significantly different from baseline at PODs 1, 3, 8, and 15. Renal function did not return to baseline by POD 15, and 66% of the animals showed significant renal insufficiency (more than 25% decline in glomerular filtration rate) in the study group. Conclusions After 120 minutes of WIT, no difference in renal function recovery was observed between the laparoscopic and open techniques. A WIT of 120 minutes produced significant renal failure and mortality. Thus, 120 minutes of WIT in the single kidney porcine model exceeds the kidney’s tolerance to ischemia.

The technical difficulty of laparoscopic partial nephrectomy (LPN) lies mainly in the steps required during warm ischemia time (WIT), which includes tumor excision and renal reconstruction. We present a renal-suspension traction system to place the tumor in stable optimal view during the critical steps of LPN.Thirty-three patients underwent LPN from October 2002 through December 2003. Eight had a renal sling placed intraoperatively because of difficult access to the tumor. Perioperative parameters were assessed. The renal hilum was dissected and the tumor exposed. To keep the tumor oriented perfectly toward the camera and the working ports, a 2-0 braided polyglactin (Vicryl) traction suture was passed through Gerota's fascia, catching the renal capsule; brought out through the abdominal wall; and secured to the skin with a clamp.All surgical margins were negative. For the traction and nontraction groups, the mean sizes of the tumor were 2.5 cm and 2.2 cm, respectively (P = 0.426). The estimated blood loss was 125 mL and 246 mL respectively (P = 0.041). The WIT average 27.4 minutes and 30.12 minutes (P = 0.470). The surgical time was 192 minutes and 235 minutes respectively, (P = 0.062). Based on our findings, we have devised a renal suspension traction algorithm for specific tumor locations during LPN.The renal suspension traction system allows precision in tumor excision and renal reconstruction during the critical steps of LPN. With the renal suspension system we devised, we are able to simplify LPN for tumors located away from optimal port access.

Researchers have shown that the five major dimensions of personality (extraversion, agreeableness, conscientiousness, neuroticism, and openness to experience) and two additional factors (irritability and positive activity) are evident from adolescence. This study attempted to replicate and extend these results in a longitudinal study of 102 Swedish children, followed from 2.3 to 15.2 years of age. Item analyses revealed consistently reliable irritability, conscientiousness, and positive activity factors, whereas the internal reliability of the extraversion, agreeableness, neuroticism, and openness to experience factors increased over time. Irritability and positive activity were not independent of the other factors. Scores on most of the personality factors were fairly stable over time. Over time, children became less extraverted, more agreeable, and more conscientious. Neuroticism and openness to experience increased in Phase III, although openness then decreased in Phase V. Validity of the original factors was demonstrated by correlations with independent assessments of the children's cognitive performance and adjustment to school.

An estimated 18,000 individuals are trafficked into the United States each year from all over the world, and are forced into hard labor or commercial sex work. Despite their invisibility, some victims are known to have received medical care while under traffickers' control. Our project aimed to characterize trafficking victims' encounters in US health care settings.The study consisted of semi-structured interviews with six Key Informants who work closely with trafficking victims (Phase I) and 12 female trafficking survivors (Phase II). All survivors were recruited through the Coalition to Abolish Slavery and Trafficking, an NGO in Los Angeles, and all were trafficked into Los Angeles. Interviews were conducted in English and six other languages, with the assistance of professional interpreters. Using a framework analysis approach that focused on victims' encounters in health care settings, we assessed interview transcript content and coded for themes. We used an exploratory pile-sorting technique to aggregate similar ideas and identify overarching domains.The survivors came from 10 countries. Eight had experienced domestic servitude, three had survived sex trafficking, and one had experienced both. Half the survivors reported that they had visited a physician while in their traffickers' control, and another worked in a health care facility. All Key Informants described other victims who had received medical care. For domestic servants, medical visits were triggered by injury and respiratory or systemic illness, while sex trafficking victims were seen by health professionals for sexually transmitted infections and abortion. Trafficking victims were prevented from disclosing their status to health care providers by fear, shame, language barriers, and limited interaction with medical personnel, among other obstacles.This exploration of survivors' experiences in health care settings supports anecdotal reports that US health care providers may unwittingly encounter human trafficking victims. Increasing awareness of human trafficking, and modifying practice to facilitate disclosure, could improve victim identification.

Background Squamous cell carcinoma (SCC) in situ (SCCIS) is often treated without any pathologic confirmation of tumor clearance. It is unclear how often an invasive SCC is harbored within a lesion in which the initial biopsy demonstrated SCCIS because of inadequate sampling. This study examines the final histologic diagnosis of cases in which the initial biopsies were diagnosed as SCCIS and evaluates factors that may correlate with a histologic upstaging of the diagnosis. Methods We prospectively recruited 29 consecutive patients with biopsy-proven SCCIS sent for Mohs micrographic surgery (MMS). Each tumor underwent MMS, and the central blocks of the Mohs debulking specimens were horizontally sectioned at 30-μm intervals until exhausted. A fellowship-trained Mohs surgeon and a board-certified dermatopathologist processed and examined these sections to determine the final histologic diagnosis of the tumor. Results Of the 29 subjects with biopsy-proven SCCIS, nine were found to harbor invasive SCC on final histology. Of the remaining lesions, seven had residual SCCIS, whereas the rest exhibited only actinic keratoses or scars. Approximately 31% of lesions showed evidence of invasive SCC. Correlating the clinical characteristics of the lesions with their corresponding final histologic diagnoses, the lesions harboring invasive SCC were more likely to demonstrate clinical signs of residual tumor (scales and papular changes) and be larger than 1.4 cm in diameter. Limitations Our experience at a single institution in the northeastern United States may not be reflective of a wider population. There is also a possible referral bias, because only lesions with high clinical suspicion for invasive SCC were referred for MMS. Conclusion Although biopsy-proven SCCIS is often treated with modalities that are best suited for superficial disease and do not involve a final pathologic confirmation of clearance (e.g., cryotherapy, electrodesiccation and curettage), this study demonstrated that up to 31% of biopsy-proven SCCIS lesions may harbor invasive SCC. Clinical signs of residual tumor and a diameter larger than 1.4 cm are statistically significant predictors of underlying invasive SCC. These data suggest that treatment modalities that include histologic control of tumor removal should also be strongly considered for the treatment of select biopsy-proven SCCIS meeting the above criteria.

T cell and natural killer (NK)/T-cell neoplasms are rare and may occasionally present as leukaemia. We retrospectively searched T cell and NK/T-cell tumours in a single institution in Taiwan from January 2000 to December 2009 and identified 137 (19.1%) patients with T cell and NK/T-cell tumours among 718 patients with lymphoid neoplasms. Among these 137 patients, 18 (13.1%) presented with leukaemia including T-lymphoblastic lymphoma/leukaemia (T-LBL), T-cell prolymphocytic leukaemia, aggressive NK-cell leukaemia, adult T-cell lymphoma/leukaemia (ATLL), T-cell large granular lymphocytic (T-LGL) leukaemia and unspecified peripheral T-cell lymphoma. Cases with concurrent lymphoma, higher absolute leukaemic cell counts and elevated lactate dehydrogenase level carried a poorer prognosis. The survival was dichotomous, with a very poor prognosis for patients with T-LBL, T-cell prolymphocytic leukaemia, aggressive NK-cell leukaemia, ATLL in acute phase and unspecified peripheral T-cell lymphoma, while those with T-LGL leukaemia and ATLL in chronic phase had a favourable outcome.

This study explores maternal and paternal parenting practices (authoritative or authoritarian) and parental values and goals for toddlers among Chinese mothers and fathers in Canada and China. The participants included 126 families of 1-year-old toddlers (67 Chinese Canadians and 59 mainland Chinese). The findings revealed that Chinese Canadian parents were more supportive of authoritative practices, and Chinese parents were more likely to support authoritarian practices. Between mothers and fathers, gender differences were found within countries. Interparental agreement for parenting beliefs varied by infant gender and country. For parental values, parents generally endorsed self-confidence as the most important trait for their toddlers. Endorsement of other traits (collectivistic and individualistic) varied in importance. Links among parenting beliefs and desired personality traits for their children were also explored.

Although heat shock protein 70 (HSP70) has been suggested to be a stress marker or to play a protective role in brain injury, the relevance of its pathological expression in epilepsy is unclear. We investigated the expression of HSP70 in brain tissue from human temporal lobe epilepsy (TLE) patients and from kainic acid (KA)-induced seizure-related neuronal damage in vivo and in vitro. The human TLE tissue showed severe neuronal loss and gliosis in hippocampal CA3 area. The KA-induced neuronal damage was similar to pathological changes of the TLE hippocampus. An increased number of TUNEL-positive cells were observed at day 5 when compared with day 2 after seizure induction. Intense HSP70 immunofluorescence was observed in hippocampal CA3 pyramidal neurons of rat, 2 days following KA administration, which then declined in labeling by day 5. No HSP70 expression was found in Fluoro-Jade B positive dying neurons by double staining. Western blot analysis showed an increased level of p53 and Bax expression following KA treatment. In vitro, there was no apparent difference in the degree of apoptosis between HSP70 siRNA- and control empty vector-transfected primary neurons following KA treatment. Our results revealed that HSP70 was a useful indicator of stressed neurons in acute phase of epilepsy, but not associated with neuronal death, thereby suggesting that HSP70 played no role in neuroprotection during an epileptogenic state.

Our previous report has confirmed that visually presented words can elicit neuromagnetic activities from the visual cortex, angular gyrus and Broca's area. It is not clear how the words are visuospatially transformed and recognized by the human brain. Mirror reading is characterized by reading which runs in the opposite direction to normal reading, with reversals of letters. It would be very interesting to find out if there are any neuromagnetic differences between the mirror reading and normal reading. Four right-handed healthy adults have been studied with a whole cortex Magnetoencephalography (MEG) system. The stimuli consisted of eight normal oriented words and eight inverted exclamation mark section "reversed words" (mirror-image of the words). All stimuli were randomly presented on the screen in front of the subjects using DirectX. MEG data were analyzed using both single dipole modeling and synthetic aperture magnetometry (SAM). Four responses to the reversed words were identified in all four subjects. In comparison to the normally oriented words, the reversed words elicited a stronger response at a latency of 248+/-6 ms. SAM results indicated that the reversed words invoked strong activations in the left and right parietal cortices but the normally oriented words did not. The mirror reading elicited one magnetic response which is different from that of the normal reading. The difference between the mirror reading and the normal reading in terms of neuromagnetic activation may reflect the development of novel representations for reversed words.

Our previous studies have demonstrated that there is a motion-related magnetic response evoked by moving sound but not stationary sound. The motion-related response reflects the dynamic activities of brain processing of auditory motion. This study focuses on the effect of attention on the response. Six normal hearing subjects were studied using a 151-channel whole-cortex magnetoencephalography (MEG) system. Four sound stimuli were designed: two sounds moved from left to right (rightward) and the other two sounds moved from right to left (leftward). Two sounds moving in the same direction were separated with an attention task. The attention task was a mathematical calculation. The results showed that when subjects listened to the moving sound, there was a clearly auditory motion related response at a latency of 649 +/- 14.2 ms. However, when subjects were doing the calculation while listening to the moving sounds, the motion related response completely disappeared. Strikingly, there was a dent at a latency of 600 ms. To our knowledge, this is probably the first study showing a neuromagnetic response which can be clearly elicited or inhibited by an attention task. We consider that the motion related response has the potential to be an objective index for the study of attention.

Conventional visual identification of epileptic spike is a challenging problem in the clinical application of magnetoencephalography (MEG). More importantly, the conventional method has problems of detecting other abnormalities such as high frequency oscillation in the human epileptic brain. The objective of this study was to develop a new approach using magnetic spectral analysis and spatial filtering. Twelve patients with seizure have been studied with a whole cortex MEG system. Fifteen epochs were recorded for each patient; each epoch was 120 seconds. Neuromagnetic spectrum was analyzed using a new method called accumulated spectrogram. Focal increases of spectral power were localized using synthetic aperture magnetometry (SAM). The MEG results were then compared with clinical findings. Focal increases of spectral power have been identified in all patients (12/12, 100%). The locations of the focal increases of spectral power were in agreement with dipole locations of spikes in 9 patients (9/12, 75%). A comparison between MEG results and clinical findings indicated that SAM revealed focal epileptic activities in two patients when dipole fitting failed. The results suggest that epileptic regions could be quantitatively identified and accurately localized using accumulated spectrogram and SAM. In comparison to visual identification of spike, the new approach is objective and sensitive, and provides the possibility of analyzing much wider frequency bands.

It is difficult to localize the somatosensory cortex in children under 6 years using magnetoencephalography (MEG) with conventional median nerve stimulation. One main reason is that MEG data recorded from small children have poor signal-to-noise ratio due to their small heads and short hands. To find a better approach, this study investigated neuromagnetic activities following finger stimulation using spatially filtered MEG. Four healthy children have been studied with a whole cortex MEG system. Electric stimulation was applied to the thumb and the middle fingers with two Digital Rings. Two trials were recorded for each hand. Focal increases of spectral power were localized using spectrogram and synthetic aperture magnetometry (SAM). A clear response at a latency of 21 ms was identified in 3 children (3/4). Dipole modeling localized the somatosensory cortex in 2 children (2/4). SAM successfully localized the somatosensory cortex in 4 children (4/4). Interestingly, the functional region estimated for the thumb was significantly larger than that of the middle finger (p0.01). However, it is possible that this effect is due to a larger source amplitude rather than larger source volume. Our results demonstrated that the developed approach could map the somatosensory cortex in children ranging in age from 3 to 6. To our knowledge, this is the first report using non-invasive methods to provide quantitative data indicating that the functional area of the thumb is larger than that of the middle finger in small children.

23 páginas, 3 figuras, 1 tabla., Multiple cutaneous and uterine leiomyomata syndrome (MCL) is an autosomal dominant disease characterized by the presence of concurrent benign tumors of smooth muscle origin (leiomyoma) in the skin and uterus of affected females, and in the skin of affected males. MCL can also be associated with type II papillary renal cell cancer (HLRCC). The genetic locus for MCL and HLRCC was recently mapped to chromosome 1q42.3-43 and subsequently, dominantly inherited mutations in the fumarate hydratase gene (FH) were identified. Importantly, analysis of the FH gene in tumors of MCL patients revealed a second mutation inactivating the wild-type allele in some tumors. Based on these findings, it has been suggested that FH may function as a tumor suppressor gene in MCL. Here, we report the analysis of the FH gene in a group of 11 MCL families, with the identification of 8 different mutations accounting for the disease in all families. One of the mutations, 905-1G>A, has been identified in 4 families of Iranian origin. The analysis of highly polymorphic markers in the vicinity of the FH gene showed a shared haplotype in these 4 families, suggesting that 905-1G>A represents a founder mutation. Collectively, identification of 5 novel and 3 recurrent mutations further supports the role of FH in the pathogenesis of MCL., Supported in part by the Skin Disease Research Center, Department of Dermatology, Columbia University (P30 AR44535), a National Institutes of Health research grant (K01-HG0005501), and a research grant from the Women's Health Program, supported by HWZOA. G. S. C. is a fellow of Howard Hughes Medical Institute-Medical Student Training Fellowship.

To our knowledge the effects of renal warm ischemia (WI) during laparoscopic vs open surgery have not been investigated. Decreased renal blood flow during pneumoperitoneum may precondition the kidney to tolerate longer WI time. Traditionally 30 minutes has defined the limit of renal WI time in open surgery. However, recent reports show renal function recovery at WI times of 45 to 120 minutes. We assessed renal function recovery after prolonged WI during laparoscopic vs open surgery in a solitary kidney porcine model.A total of 32 female farm pigs underwent right laparoscopic nephrectomy to create a single kidney model. At 12 days later the animals were randomized into open and laparoscopic groups, each with 4 subgroups, namely 30, 60 and 90 minutes of WI, and a 90-minute control. Serum creatinine and the glomerular filtration rate were assessed preoperatively and on postoperative days 1, 3, 8 and 15.There was no statistical difference in renal function between the laparoscopic and open groups. Although the early decrease in renal function (72 hours) was highest in the 60 and 90-minute WI groups, by postoperative day 15 this difference was not statistically significant. Postoperative day 15 glomerular filtration rate and serum creatinine values were not significantly different from baseline in any of the WI groups.We found no difference in renal function recovery when comparing laparoscopic and open WI. Although WI up to 90 minutes resulted in initial renal dysfunction, by 2 weeks postoperatively function normalized. Our results indicate that in a single kidney porcine model the renal unit can fully recover from WI times of up to 90 minutes.

13 páginas, 2 figuras., Epidermolysis bullosa (EB) pruriginosa is a subtype of dominant dystrophic EB (DDEB), characterized by severe pruritus and blistering localized to the extensor surface of the extremities. EB pruriginosa exhibits extensive clinical heterogeneity with variable expression and delayed age of onset. Mutations in the COL7A1 gene, especially in glycine residues within Gly-X-Y repeats, have been shown to cause this form of DDEB. Here, we report a novel COL7A1 mutation in a Taiwanese pedigree with EB pruriginosa. Using PCR and direct sequence analysis we have identified a G→T transversion at nucleotide 7097 in exon 92 of COL7A1, converting a glycine residue to valine (G2366V). The mutation resides within a consecutive, uninterrupted stretch of 17 Gly-X-Y residues in the triple-helical domain of type VII collagen. Interestingly, an affected member of this family also displayed elevated IgE levels, previously reported in some patients with this disorder. Our finding further implicates COL7A1 mutation in the pathogenesis of EB pruriginosa and underscores the heterogeneous clinical symptoms of glycine mutations in DDEB., This work was supported in part by NIH R01 AR43602 (A.M.C) and R03 AR47184 (P.B.C). G.S.C. is a fellow of Howard Hughes Medical Institute-Medical Student Training Fellowship.

9 páginas, 2 figuras, 2 tablas., Germline mutations in the fumarate hydratase gene (FH) predispose to multiple cutaneous and uterine leiomyoma syndrome (MCL) and MCL associated with renal cell cancer. MCL is inherited in an autosomal dominant pattern, manifesting as skin leiomyoma and uterine fibroids in affected individuals. Fumarate hydratase, a component of the tricarboxylic acid cycle, acts as a tumor suppressor gene in the development of cutaneous and uterine leiomyoma and renal cell cancer in this syndrome. Here we report the clinical and mutational analysis of five families with MCL, with the identification of five new mutations affecting highly conserved residues of the FH protein. These results provide further evidence for the role of the FH gene in the pathogenesis of MCL., This work was supported in part by the Skin Disease Research Center, Department of Dermatology, Columbia University (P30 AR44535); a research grant K01-HG0005501 (to D.G.); and a research grant from the Women's Health Program, supported by HWZOA (to A.Z. and B.G.). G.S.C. is a Medical Student Research Training Fellow of Howard Hughes Medical Institute.

Atrichia with papular lesions (APL) is a rare autosomal recessive disorder resulting in complete and irreversible hair loss shortly after birth. Affected individuals also develop papular lesions of keratin-filled follicular cysts over extensive areas of the body. Mutations in the hairless gene, a putative single zinc-finger transcription factor protein, have been implicated in the pathogenesis of APL. In this report, we describe a novel missense mutation, E583V, in the hairless gene in an Italian family affected with APL. The mutation resides between the LXXLL motif found in TRIPs (thyroid hormone receptor interacting proteins) in exon 5 and the six-cysteine zinc-finger motif in exon 6. The amino acid sequence neighbouring the LXXLL motif and zinc-finger domain is highly conserved in human, monkey, rat, and mouse hairless proteins. Our finding extends the body of evidence that supports the importance of the zinc-finger and LXXLL domains in the function of the hairless protein. Moreover, we continue to find small APL families without consanguinity from around the world.

Exceptionally excess leukocytosis or leukemoid reaction may develop in association with carcinomas of the lung and stomach. The authors describe a 72-year-old lady with FIGO stage III ovarian undifferentiated carcinoma who presented with fever and abdominal pain. Her serial WBC counts were up to 143,000/microl with elevated leukocyte alkaline phosphatase score. She received extended total hysterectomy, left salpingo-oophorectomy, and de-bulking of the retroperitoneal mass. Her left ovarian cancer was composed of diffuse sheets of large undifferentiated cells that were immunoreactive for cytokeratin, confirming the epithelial nature. She passed away one week after operation and five weeks after presentation without autopsy. This is the first report of ovarian cancer associated with leukemoid reaction in the English literature.

Primary cerebral anaplastic large cell lymphoma (ALCL) is very rare. We report on our experience with such a case and review the literature. A 46-year-old Taiwanese woman presented with headache, weakness of her right extremity, and limited eye movement. A solid mass (5 cm x 4 cm) at the left occipital lobe was almost completely removed. The neoplastic cells, some of which had reniform or embryo-like nuclei, were large and were admixed with abundant eosinophils, histiocytes, and some small lymphocytes. These neoplastic cells expressed CD30, CD43, granzyme B and T-cell intracellular antigen-1, but not ALK1, CD3, CD20, CD45, CD79a, cytokeratin, and EMA. They were positive for Epstein-Barr virus-encoded mRNA by in situ hybridization. Polymerase chain reaction study of formalin-fixed tissue showed a clonal gene arrangement of the T-cell receptor-gamma chain. ALCL of T-cell lineage with cytotoxic phenotype was diagnosed. The patient received cranial irradiation and has remained with no evidence of disease for 25 months of follow-up.

Uterine leiomyoma with massive lymphoid infiltration is very rare and may simulate malignant lymphoma. To the best of our knowledge, this is the first description of such a lesion occurring in an Oriental, and the ninth case in the English literature. A 50-year-old Taiwanese woman had urinary frequency and nocturia because of a uterine myoma. The myomectomy specimen was identified as a well-defined tumor, 6.5-cm in diameter, the cut surface of which was pale, white and whorled. A massive lymphocytic infiltration accompanied by plasma cells and histiocytes was noted in the leiomyoma but not in the surrounding non-neoplastic myometrial fibers. Most infiltrating lymphocytes were positive for CD3 and T cell intracellular antigen-1, a cytotoxic marker. The postoperative course was uneventful, and the urinary symptoms improved within a 6-month follow-up period.

From March 1995 to May 1997, 66 free radial forearm flaps were used for orofacial reconstructions. All flaps were elevated following the suprafascial technique. Donor-site closure was performed with split-thickness skin grafts in 54 cases, and with full-thickness skin grafts in 12 patients. Investigations after six months included grip strength, pulp-to-pulp pinch strength, range of motion as compared to preoperative values, aesthetical self-assessment, cold intolerance, and dysesthesias. The latter evaluation could be performed in 42 patients, whereas the complete follow-up protocol included 36 patients. Primary wound healing with immediate complete take of skin grafts was achieved in 93.9%. Grip strength and pulp-to-pulp pinch strength showed no decrease postoperatively. An impairment of range of motion of the wrist was observed in 2.8%. There was no cold intolerance. Aesthetical outcome was rated as good or fair in 97.3%. Slight numbness distally to the donor-site was found in 59.5%. The results of this prospective study show a superiority of suprafascial elevation of the radial foream flap as compared to the classic elevation technique, particularly in a higher rate of primary wound healing, thus avoiding impairment of range of motion and strength of the donor hand.

Bizarre parosteal osteochondromatous proliferation is a rare bone lesion. We report a case from a 47-year-old female patient who had pain and swelling of the right index finger for two months. On the basis of the frozen section diagnosis of benign lesion, probably myositis ossificans, she received tumor excision and has been free of recurrence in two years and ten months duration since. This case emphasized the importance of clinical, radiological and pathological correlation on approaching the diagnosis and treatment of the lesion.

PURPOSE: To describe the clinical and radiologic manifestations of juvenile Huntington disease and to determine whether adult imaging criteria for Huntington disease are helpful for pediatric patients. METHODS: Six patients (3 to 18 years of age; mean age, 9.8 +/- 5.6 years; 3 female, 3 male) with juvenile Huntington disease were studied with CT (n = 6) and/or MR (n = 3). CT and MR studies were evaluated for frontal horn distance/intercaudate distance and bicaudate ratios, which were compared with those of 24 age-matched healthy children and 12 age-matched patients with Leigh (n = 9) or Wilson (n = 3) disease. RESULTS: Atrophy of the caudate nuclei was identified in all Huntington patients. The frontal horn distance/intercaudate distance (1.64 +/- 0.39) and bicaudate (0.205 +/- 0.060) ratios of the patients with juvenile Huntington disease were found to be significantly different from those of healthy children and that of those patients with Leigh/Wilson disease. The 3 patients with Huntington disease who underwent MR evaluation were noted to have increased proton density- and T2-weighted signal in the caudate nuclei and putamina. CONCLUSION: As in adult patients, the use of frontal horn distance/intercaudate distance and bicaudate ratios are helpful for the diagnosis of Huntington disease in pediatric patients. On MR, increased proton density- and T2-weighted signal in the atrophic caudate nuclei and putamina are additional features of juvenile Huntington disease.

Granulosa cell tumor combined with dermoid cyst in the same ovary is extremely rare. This report describes such a case in a 55-year-old postmenopausal woman presenting with left lower abdominal pain. The resected fist-sized left ovary disclosed a dermoid cyst containing a mural nodule which was found to be a sarcomatoid granulosa cell tumor histologically. She has been disease free for two years after the operation.

Renal angiomyolipoma is a benign tumor of hamartomatous nature. A case of asymptomatic renal angiomyolipoma in a 57-year-old female is reported. Her right renal mass was incidentally discovered during the evaluation of acute hepatitis by abdominal sonography. She received right simple nephrectomy. The renal pelvic tumor was found to be an angiomyolipoma with a prominent angiomatous component containing hematopoietic elements. Unfortunately, the patient died of peritoneal carcinomatosis because of adenocarcinoma of the transverse colon five years later.

Localization of the sympathetic postganglionic neurons innervating the cardiac coronary arteries in monkeys was investigated by using retrograde axonal transport of horseradish peroxidase (HRP). HRP was applied to the main trunk of the left and right coronary arteries, and to the terminal branches of the ventral and dorsal descending vessels of the left and right coronary arteries, respectively. The animals were sacrificed 84-96 hours later and perfused via the left ventricle. The paravertebral sympathetic ganglia from the superior cervical, middle cervical and stellate ganglia to the T9 ganglia, and nodose ganglia were removed and processed for HRP identification. After HRP was applied into the main trunk of the right coronary artery, and into the main trunk and the terminal branches of the descending vessels of the left coronary artery, the HRP-labeled sympathetic neurons were localized predominantly in the right superior cervical ganglion, and next in the left superior cervical ganglia. However, labeled cells were found in the stellate ganglia bilaterally. After HRP applications to the terminal branches of the dorsal descending vessels of the right coronary artery, HRP-labeled cells were mainly present in the left superior cervical ganglion and next in the right superior cervical ganglion. Some labeled cells were found in the middle cervical and stellate ganglia. No labeled cell was found in ganglia below the second thoracic ganglia on either side in these four groups.

Acoustic measurements believed to reflect glottal characteristics were made on recordings collected from 21 male speakers. The waveforms and spectra of three nonhigh vowels (/ae, lambda, epsilon/) were analyzed to obtain acoustic parameters related to first-formant bandwidth, open quotient, spectral tilt, and aspiration noise. Comparisons were made with previous results obtained for 22 female speakers [H. M. Hanson, J. Acoust. Soc. Am. 101, 466-481 (1997)]. While there is considerable overlap across gender, the male data show lower average values and less interspeaker variation for all measures. In particular, the amplitude of the first harmonic relative to that of the third formant is 9.6 dB lower for the male speakers than for the female speakers, suggesting that spectral tilt is an especially significant parameter for differentiating male and female speech. These findings are consistent with fiberscopic studies which have shown that males tend to have a more complete glottal closure, leading to less energy loss at the glottis and less spectral tilt. Observations of the speech waveforms and spectra suggest the presence of a second glottal excitation within a glottal period for some of the male speakers. Possible causes and acoustic consequences of these second excitations are discussed.

A retrospective examination was performed to assess the accuracy of metrizamide myelography (MM) and computed tomographic metrizamide myelography (CTMM) in scoliosis. Of 81 consecutive scoliotic children studied by myelography, 30 had only MM while the remaining 51 had CTMM immediately afterward. CTMM added essential diagnostic information in 13 cases of dysraphism and 4 cases of idiopathic scoliosis; in the remaining cases, both methods gave the same information. The authors conclude that in patients with severe scoliosis, dysraphism, and scoliosis with localized neurological disturbances, CTMM should always be added to MM or be the only examination; while in idiopathic scoliosis with vague neurological disturbances a survey of the entire spine is essential, preferably with MM.

Two infants with severe congestive cardiac failure secondary to diffuse hepatic hemangiomas were treated by percutaneous transcatheter embolization of the hepatic arteries using detachable silicone balloons. One infant experienced dramatic improvement of the cardiac failure and showed no impairment of hepatic function. The other infant remained in a low cardiac output state following the procedure and developed acute hepatic and renal failure followed by generalized sepsis and death. Autopsy examination revealed massive hepatic hemangioendothelioma as well as areas of necrotic and viable liver parenchyma. A review of reported patients with hepatic hemangiomas treated by hepatic artery ligation or embolization showed no others who had hepatic failure. These techniques were curative in 14 of 18 patients (78%), an improvement compared with the results of other available methods of therapy.

Imaging studies from 13 patients with caudal regression were reviewed retrospectively to assess the spectrum and findings of this anomaly. Seven patients were evaluated with MR and six with myelography (supplemented with CT in three). The level of regression varied from T9 to the coccyx. Although osseous abnormalities were more readily identified and characterized by CT, MR effectively depicted the level of vertebral regression, presence of central spinal stenosis, and vertebral dysraphic anomalies. MR demonstrated a characteristic wedge-shaped (longer dorsally) cord terminus in seven of the patients. When this characteristic cord terminus is seen, imaging of the lower lumbar and sacral regions should be performed to verify the diagnosis of caudal regression. Tethered spinal cords have been described in patients with caudal regression and were seen in two of our patients. We present the first cases of individuals who have survived with absence of vertebrae above the T10 level and an unusual case of caudal regression with absent lumbar vertebrae and preserved lower sacral and coccygeal vertebrae. The syndrome of caudal regression encompasses a wide spectrum of pathology that is analyzed well by modern imaging techniques.

The phenomenology of the manic state and its response to lithium drug treatment were intensively studied as part of a larger NIMH Clinical Research Branch Collaborative Program on the Psychobiology of Depression. In view of the weaknesses in current methods for measuring the components of the manic state, a new instrument was developed, the Manic Diagnostic and Severity Scale (MADS). Its sensitivity in diagnosis and in measuring change was compared to other scales already in use. Finally baseline clinical data is presented that suggests that the presence of a "mixed" manic state is a predictor of lack of clinical response to lithium treatment.

Four children are reported in whom marked contrast enhancement of the spinal cord and roots was demonstrated by computed tomography months to years after relatively low dose therapeutic irradiation of paraspinal tumors, the radiation field including the cord. This phenomenon, previously unreported, probably represents subclinical radiation injury. None of the children had any neurologic abnormalities.

Preoperative diagnosis of intracranial cysts has been simplified and made more rapid and accurate with computed tomography (CT). By means of conventional CT and CT metrizamide ventriculography, the position and communication of intracranial cysts with the ventricular system and subarachnoid space or cisterns can be demonstrated. Suprasellar arachnoid cysts can produce significant neurologic and endocrinologic abnormalities due to their position. They are a surgically curable cause of hydrocephalus. Preoperative differentiation from aqueduct stenosis or other causes of a large third ventricle is important. The usefulness of coronal CT and CT metrizamide ventriculography in the investigation of these lesions is illustrated in six patients.

The effects of stellate ganglionectomy on cardiovascular function were assessed in pentobarbital-anesthetized cats. A right stellectomy produced much more profound bradycardiac effects than a left stellectomy. This finding demonstrated that the stellate ganglion exerted a lateralized influence on heart beat in the cat. The cardiovascular response of intact cats to phase 4 (overshoot) of the Valsalva-like maneuver (VM) was reflex bradycardia. In response to VM, however, reflex bradycardia was completely abolished by a right or bilateral stellectomy, or by pretreatment with propranolol, but not by a left stellectomy alone or with phentolamine. The data indicated that the right stellate ganglion in cats makes a major contribution to cardiovascular control, especially over reflex bradycardia mechanisms.