Clinicopathological and Immunohistochemical Study of 14 Cases of Morbihan Disease: An Insight Into Its Pathogenesis.

INTRODUCTION: Morbihan disease (MORD) is rare with only 45 clear-cut cases previously reported. Histopathologic findings are supposed to be nonspecific. We report 14 patients and review the previous cases. OBJECTIVES: To characterize the clinicopathologic findings, outcomes, and immunophenotype of MORD. MATERIAL AND METHODS: Inclusion criteria were a clinical picture of persistent, nonpitting edema affecting the mid and or upper third of the face and histopathological findings fitting previous reports and exclusion of other entities. RESULTS: The majority of our patients were males (71.5%) with a male/female ratio of 10/4. The mean age when diagnosed was 58.8 years. Eyelids and forehead were the most frequently involved areas. Two of the patients presented previous rosacea. Most constant histopathological findings were lymphatic vessel dilatations in the upper dermis and the presence of mast cells (7.5 in 10 high-power field as a mean). Mild edema was also present in most of the cases. Granulomas were found in 7 of the cases, and immunostaining with CD68 and CD14 only revealed an additional case. CONCLUSIONS: MORD occurs more in middle-aged males, not associated with rosacea and mostly affects eyelids and forehead. Granulomas are not mandatory for the diagnosis. Histopathology of MORD fits within the spectrum of localized lymphedema.

Intraductal Carcinoma of Salivary Gland Originating from an Intraparotid Lymph Node: A Case Report.

INTRODUCTION: Salivary gland intraductal carcinoma (IDC) is rare. We present the second case of IDC originating from an intraparotid lymph node (LN) with a more detailed description of the histogenesis, immunohistochemistry (IHC) and updated molecular information. CASE REPORT: An 87-year-old male had a tumour nodule over the left parotid tail for about 20 years. Physical examinations revealed a 4.5 cm soft, non-tender and fixed mass. After the left parotidectomy, pathology confirmed the diagnosis of IDC arising within an intraparotid lymph node. The cystic component of the tumour was lined by single to multilayered ductal cells with micropapillary growth pattern. The solid part showed intraductal proliferation of neoplastic cells in solid, cribriform, micropapillary and Roman bridge-like structure. By immunohistochemistry (IHC), the tumour cells were positive for S-100, CK (AE1/AE3), mammaglobin, SOX10, and estrogen receptor (ER), with myoepithelial cell rimming highlighted by positive p63 and calponin IHC stains. The prognosis of this patient is excellent after complete excision. DISCUSSION: The mechanism of salivary gland tumour arising in the intra-parotid gland LN was assumed to be related to salivary duct inclusion within the intraparotid gland LN which is a normal occurrence during embryology development. Although the terminology may raise some confusion about the relationship between IDC and conventional salivary duct carcinoma (SDA), they are different in immunophenotype and clinicopathologic features. IDC is characterised by S100 (+) ER (+) with predominant intraductal growth and excellent prognosis; while SDC features S100 (-) androgen receptor (+) with predominant invasive growth and aggressive behavior. Recent discovery of recurrent RET gene rearrangement in IDC but not SDC also supports that IDC is not precursor lesion of the SDC.

[Prognostication of the puncture-draining sanation interventions efficacy performed under ultrasound investigation guidance for severe acute pancreatitis].

The results of treatment of 47 patients, in whom the focal accumulations of liquid (FAL) have appeared in severe acute pancreatitis (SAP), were analyzed. The puncture-draining sanation (PDS) was performed in all the patients. In 61.7% patients the PDS under ultrasonographic guidance have appeared the one-staged definite procedure. The staged PDS were conducted in 10.6% patients. In 27.6% patients after conduction of PDS under ultrasonographic guidance there was open necrsequesterectomy performed. There was a scale elaborated for the PDS efficacy estimation under ultrasonographic guidance. Dynamic estimation of the PDS efficacy in presence of FAL in patients, suffering SAP, have had promoted the treatment results improvement. The PDS efficacy depends on the disease duration, the infiltrate spreading, the sequesters presence and the FAL infectioning.

[Apoptosis of neutrophils in the patients with the high risk of peritonitis occurrence after operation for acute diseases of the abdominal organs].

The processes of apoptosis of neutrophils of peripheral blood were studied in 43 patients, who were operated on for an acute abdominal diseases on the first and fourth postoperative day. Dynamic changes of apoptotic processes in neutrophils were established postoperatively. Unfavorable course of early postoperative period in the patients owing primarily high and middle risk of postoperative peritonitis occurrence have coincided with inhibition of the apoptosis processes in neutrophils.

A Japanese-specific recurrent mutation and a novel splice site mutation in the LAMC2 gene identified in two Japanese families with Herlitz junctional epidermolysis bullosa.

BACKGROUND: Herlitz junctional epidermolysis bullosa (H-JEB) is an extremely rare genodermatosis characterized by lethality owing to severe blister formation. We report two unrelated Japanese patients with H-JEB. Genetic analyses detected a single nonsense mutation on the LAMC2 gene in these two patients. AIM: To identify the mutation involved and describe the first reported Japanese recurrent mutation in the LAMC2 gene. METHODS: Direct sequencing was performed of DNA from either peripheral blood or fetal cells in amniotic fluid. Reverse transcriptase PCR was used to confirm that an aberrant transcript resulted from the splice site mutation. A haplotype analysis was performed to define the origin of the recurrent mutation. RESULTS: Both patients had blisters and erosions on the trunk and limbs at birth, with nail dystrophy. Patient 1 died as a result of sepsis at 30 weeks of age, and patient 2 died as a result of disseminated intravascular coagulation at 20 weeks of age. Mutation analysis of the LAMC2 gene revealed that patient 1 was compound heterozygous for a nonsense mutation (p.Cys553X) and a novel splice site mutation (c.2868+1delG), and patient 2 was a homozygous for p.Cys553X. Prenatal diagnosis performed during a subsequent pregnancy in family 2 revealed that this second child was heterozygous for p.Cys553X, and was thus not affected. Haplotype analysis suggested that a p.Cys553X allele derived from the same origin had been independently inherited by these two unrelated families. CONCLUSIONS: p.Cys553X in the LAMC2 gene may be a Japanese-specific recurrent mutation as a result of a founder effect, and it may therefore be useful for initial screening in the mutation analysis of H-JEB.

Effect of the proton irradiation on the thermally activated flux flow in superconducting SmBCO coated conductors.

We investigate changes in the vortex pinning mechanism caused by proton irradiation through the measurement of the in-plane electrical resistivity for H//c in a pristine and two proton-irradiated (total doses of 1 × 1015 and 1 × 1016 cm-2) SmBa2Cu3O7-δ (SmBCO) superconducting tapes. Even though proton irradiation has no effect on the critical temperature (Tc), the resulting artificial point defect causes an increase in normal state electrical resistivity. The electrical resistivity data around Tc shows no evidence of a phase transition to the vortex glass state but only broadens with increasing magnetic field due to the vortex depinning in the vortex liquid state. The vortex depinning is well interpreted by a thermally activated flux flow model in which the activation energy shows a nonlinear temperature change [Formula: see text] (q = 2). The field dependence of activation energy shows a [Formula: see text] with larger exponents above 4 T. This field dependence is mainly due to correlated disorders in pristine sample and artificially created point defects in irradiated samples. Compared with the vortex pinning due to correlated disorders, the vortex pinning due to the appropriate amount of point defects reduces the magnitude of Uo(H) in the low magnetic field region and slowly reduces Uo(H) in high magnetic fields.

The current status of percutaneous nephrolithotomy in the management of kidney stones.

Large kidney stones (>2 cm) is a common problem affecting all population groups across the globe and may result in significant complications if left untreated. The treatment for this condition has evolved dramatically over the past seven decades with the advent of minimally invasive treatment options. At the forefront of this paradigm shift is the development of percutaneous nephrolithotomy (PCNL). This has resulted in shorter hospital stays, reduced postoperative pain, and quicker convalescence compared with the previous criterion standard of open stone surgery. PCNL is only one of the many minimally invasive treatment options available for this condition, but remains the most efficient in all patient groups. However, it continues to be one of the more challenging urological procedures, which if not performed well, can be associated with significant complications. Refinements in techniques, improvement in equipment and increasing clinical experience have led to improved stone free rates being achieved with acceptably low patient morbidity. In this article, authors review the technical aspects, outcomes, and current role of PCNL in the treatment of large kidney stones.

68Ga-PSMA PET/CT vs. mpMRI for locoregional prostate cancer staging: correlation with final histopathology.

BACKGROUND: Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) can be used to locate lesions based on PSMA avidity, however guidelines on its use are limited by its infancy. We aimed to compare multiparametric magnetic resonance imaging (mpMRI) and PSMA PET/CT to prostatectomy histopathology. METHODS: We conducted a chart review from February 2015 to January 2017 of 50 male patients staged for prostate cancer using PSMA PET/CT and mpMRI who then underwent radical prostatectomy. Pre-operative PSMA PET/CT and mpMRI were paired with corresponding histopathology. Correlations, sensitivity, and specificity were used for comparisons. RESULTS: A total of 81 lesions were confirmed by histopathology. Fifty index lesions were detected by histopathology, all of which were detected by PSMA PET/CT (100% detection), and 47 by mpMRI (94% detection). Thirty-one histologically confirmed secondary lesions were detected, 29 of which were detected by PSMA PET/CT (93.5% detection), and 16 by mpMRI (51.6% detection). PSMA had better sensitivity for index lesion localization than mpMRI (81.1 vs. 64.8%). Specificity was similar for PSMA PET/CT and mpMRI (84.6 vs. 82.7%). SUVmax of index lesions ranged from 2.9 to 39.6 (M = 9.27 ± 6.41). Index lesion SUVmax was positively correlated with PSA (rho = 0.48, p < 0.001) and ISUP grade (rho = 0.51, p < 0.001). CONCLUSIONS: PSMA-PET/CT provided superior detection of prostate cancer lesions with better sensitivity than mpMRI. PSMA-PET/CT can be used to enhance locoregional mpMRI to provide improved detection and characterization of lesions.

Surgical treatment of simple syndactylism with secondary deep digital flexor tendon contracture in a Basset Hound.

A five-month-old, female Basset Hound was presented for lameness associated with a fused 3rd and 4th digital pad on the left hind limb (simple incomplete syndactyly), and secondary contracture of the deep digital flexure tendon of the 3rd and 4th digit. An onychectomy of the third phalanx of the third and fourth digits was performed. Following the operation, the dog gained good use of the affected limb for one month until intermittent non-weight bearing lameness developed. A second surgery was performed six months later, partially removing the second phalanx of digits three and four. Follow-up reports indicate that the dog is doing well and is without lameness. This is the first report of deep digital flexor tendon contracture and surgical treatment of this complication in canine simple syndactylism.

Validation of an Instrument to Assess the Mental Capacity to Sign an Enduring Power of Attorney.

OBJECTIVE: To describe the validation of an instrument to assess the mental capacity of an individual to sign an enduring power of attorney. METHODS: An instrument named Capacity Assessment to Sign an Enduring Power of Attorney (CASEPA) was developed following a literature review, focus group discussions, expert reviews, and pilot testing. Chinese persons aged ≥ 60 years who had a range of cognitive abilities were recruited from elderly care centres in Hong Kong to explore its psychometric properties. RESULTS: A total of 85 participants were included. For inter-rater reliability, the intraclass correlation coefficient was 0.93 for understanding, 0.87 for appreciation, and 0.84 for reasoning. For internal consistency, the Cronbach's alpha was 0.75 for understanding, 0.74 for appreciation, and 0.86 for reasoning. The content validity was examined by an international expert in mental capacity and psychiatry and by 5 local experts in the fields of mental health, law, psychiatry, psychology, and geriatrics. The clinician ratings correlated with the ability score for understanding (r = 0.74, p < 0.001), appreciation (r = 0.73, p < 0.001) and reasoning (r = 0.73, p < 0.001). CONCLUSION: The CASEPA is a potentially useful tool to assess the mental capacity of an individual to sign an enduring power of attorney.

Coronavirus infections in horses in Saudi Arabia and Oman.

Equine coronaviruses (ECoV) are the only coronavirus known to infect horses. So far, data on ECoV infection in horses remain limited to the USA, France and Japan and its geographic distribution is not well understood. We carried out RT-PCR on 306 nasal and 315 rectal swabs and tested 243 sera for antibodies to detect coronavirus infections in apparently healthy horses in Saudi Arabia and Oman. We document evidence of infection with ECoV and HKU23 coronavirus by RT-PCR. There was no conclusive evidence of Middle East respiratory syndrome coronavirus infection in horses. Serological data suggest that lineage A betacoronavirus infections are commonly infecting horses in Saudi Arabia and Oman but antibody cross-reactivities between these viruses do not permit us to use serological data alone to identify which coronaviruses are causing these infections.

A case of takotsubo cardiomyopathy: transient left ventricular apical ballooning.

A 78-year-old woman was admitted to hospital with central chest pain and the electrocardiographic and cardiac marker changes typical of acute anterior myocardial infarction. Coronary angiography revealed normal epicardial coronary arteries, and left ventriculography showed apical akinesis as well as basal hyperkinesis. This is a case of transient left ventricular apical ballooning or takotsubo cardiomyopathy, possibly attributable to catecholamine-mediated myocardial stunning.

Mapping synaptic glutamate transporter dysfunction in vivo to regions surrounding Aß plaques by iGluSnFR two-photon imaging.

Amyloid-ß (Aß) plaques, a hallmark of Alzheimer's disease (AD), are surrounded by regions of neuronal and glial hyperactivity. We use in vivo two-photon and wide-field imaging of the glutamate sensor iGluSnFR to determine whether pathological changes in glutamate dynamics in the immediate vicinity of Aß deposits in APPPS1 transgenic mice could alter neuronal activity in this microenvironment. In regions close to Aß plaques chronic states of high spontaneous glutamate fluctuations are observed and the timing of glutamate responses evoked by sensory stimulation exhibit slower decay rates in two cortical brain areas. GLT-1 expression is reduced around Aß plaques and upregulation of GLT-1 expression and activity by ceftriaxone partially restores glutamate dynamics to values in control regions. We conclude that the toxic microenvironment surrounding Aß plaques results, at least partially, from enhanced glutamate levels and that pharmacologically increasing GLT-1 expression and activity may be a new target for early therapeutic intervention.

A computer-based model to assess costs associated with the use of factor VIII and factor IX one-stage and chromogenic activity assays.

BACKGROUND: Measurement of coagulation factor factor VIII (FVIII) and factor IX (FIX) activity can be associated with a high level of variability using one-stage assays based on activated partial thromboplastin time (APTT). Chromogenic assays show less variability, but are less commonly used in clinical laboratories. In addition, one-stage assay accuracy using certain reagent and instrument combinations is compromised by some modified recombinant factor concentrates. Reluctance among some in the hematology laboratory community to adopt the use of chromogenic assays may be partly attributable to lack of familiarity and perceived higher associated costs. OBJECTIVES: To identify and characterize key cost parameters associated with one-stage APTT and chromogenic assays for FVIII and FIX activity using a computer-based cost analysis model. METHODS: A cost model for FVIII and FIX chromogenic assays relative to APTT assays was generated using assumptions derived from interviews with hematologists and laboratory scientists, common clinical laboratory practise, manufacturer list prices and assay kit configurations. RESULTS: Key factors that contribute to costs are factor-deficient plasma and kit reagents for one-stage and chromogenic assays, respectively. The stability of chromogenic assay kit reagents also limits the cost efficiency compared with APTT testing. Costs for chromogenic assays might be reduced by 50-75% using batch testing, aliquoting and freezing of kit reagents. CONCLUSIONS: Both batch testing and aliquoting of chromogenic kit reagents might improve cost efficiency for FVIII and FIX chromogenic assays, but would require validation. Laboratory validation and regulatory approval as well as education and training in the use of chromogenic assays might facilitate wider adoption by clinical laboratories.

Identification and characterization of two distinct GnRH receptor subtypes in a teleost, the medaka Oryzias latipes.

We report the identification and characterization of two distinct GnRH receptor (GnRH-R) subtypes, designated GnRH-R1 and GnRH-R2, in a model teleost, the medaka Oryzias latipes. These seven-transmembrane receptors of the medaka contain a cytoplasmic C-terminal tail, which has been found in all other nonmammalian GnRH-Rs cloned to date. The GnRH-R1 gene is composed of three exons separated by two introns, whereas the GnRH-R2 gene has an additional intron and therefore consists of four exons and three introns. The GnRH-R1 and GnRH-R2 genes, both of which exist as single-copy genes in the medaka genome, were mapped to linkage groups 3 and 16, respectively. Inositol phosphate assays using COS-7 cells transfected with GnRH-R1 and GnRH-R2 demonstrated that they had remarkably different ligand sensitivities, although both receptors showed highest preference for chicken-II-type GnRH. Phylogenetic analysis showed the presence of three paralogous lineages for vertebrate GnRH-Rs and indicated that neither GnRH-R1 nor GnRH-R2 is the medaka ortholog to mammalian GnRH-Rs that lack a cytoplasmic tail. This, together with an observation that medaka-type GnRH had low affinity for GnRH-R1 and GnRH-R2, suggests that a third GnRH-R may exist in the medaka.

Pathways of pyrimidine nucleotide biosynthesis in gravid Angiostrongylus cantonensis.

The incorporation of radioactive precursors into pyrimidine nucleotides via de novo and salvage pathways was measured in gravid Angiostrongylus cantonensis by HPLC and thin-layer chromatography. 14C-labelled orotate, uridine, uracil and deoxyuridine were traced to UMP, UDP, UTP, UDP-glucose, dTMP, CMP, CDP and CTP. 3H-labelled cytidine was also incorporated into both uracil and cytosine nucleotides in a ratio of 2:1. Cytosine was a major end-product for all the precursors. Cytosine nucleotides were probably formed from UTP by the action of CTP synthetase whose activity in crude cell-free extract was 31.5 +/- 4.9 pmol min-1 (mg protein)-1. It was dependent on glutamine, ATP and GTP and was inhibited by CTP. The total amount of pyrimidine nucleotides formed from uridine was 3 times of that from uracil. The presence of uracil in the metabolism of uridine indicates that UMP is formed by uracil phosphoribosyltransferase as well as by uridine kinase. UMP is a key intermediate for cytidylate and thymidylate biosynthesis in the gravid worms.

Opioid agonists and antagonists. 6,6-Hydrazi and 6-oximino derivatives of 14-hydroxydihydromorphinones.

Naloxone (1a), naltrexone (1b), and oxymorphone (1c) were converted to the corresponding 6,6-diaziridines (4a-c), oximes (5a-c), and oxime O-methyl ethers (6a-c). The antagonist derivatives (R = CH2CH = CH2 and R = CH2-c-C3H7) were less active than the parent ketones in the tail-flick assay vs. morphine, by 2-10-fold, except for 6a, which was much less active. The agonist analogues (R = Me) were more active than morphine but less active than dihydromorphine in standard agonist assays. None were significantly longer in duration of action. Thus structural changes at the C-6 position to produce diaziridines, oximes, and oxime O-methyl ethers provide compounds retaining expected opioid activity.

Precursors of pyrimidine nucleotide biosynthesis for gravid Angiostrongylus cantonensis (Nematoda: Metastrongyloidea).

Gravid Angiostrongylus cantonensis can utilize radiolabelled bicarbonate, orotate, uracil, uridine and cytidine but not cytosine, thymine and thymidine for the synthesis of RNA and DNA. In cell-free extracts of the worm, a phosphoribosyltransferase was shown to convert orotate to OMP and uracil to UMP. A similar reaction was not observed with cytosine and thymine. Uridine was readily phosphorylated by a kinase but a similar reaction for thymidine and deoxyuridine was not found. Cytidine could be phosphorylated by a kinase or be deaminated by a deaminase to uridine. No deaminase for cytosine was detected. There was also no phosphotransferase activity for pyrimidine nucleosides in the cytosolic or membrane fractions. Pyrimidine nucleosides were, in general, converted to the bases by a phosphorylase reaction but only uracil and thymine could form nucleosides in the reverse reaction. The activity of thymidylate synthetase was also measured. These results indicate that the nematode synthesizes pyrimidine nucleotides by de novo synthesis and by utilization of uridine and uracil and that cytosine and thymine nucleotides are formed mainly through UMP. The thymidylate synthetase reaction appears to be vital for the growth of the parasite.

Effects of transdermal nicotine on attention and memory in healthy elderly non-smokers.

RATIONALE: Nicotine has been found to improve cognitive functions in patients with Alzheimer's disease, but little is known about its effects in the healthy non-smoking elderly. OBJECTIVES: This study aimed to investigate the effects of nicotine on cognitive function in healthy non-smoking or nicotine-naïve elderly subjects. METHODS: A transdermal patch containing either 5 mg nicotine or placebo was applied on the back of 63 healthy nicotine-naïve or non-smoking elderly Koreans. Cognitive functions were evaluated with the Short Blessed Test, Rey-Kim Memory Test, and digit span test of the Korean-WAIS, both before and 5.5 h after nicotine administration. The plasma level of nicotine after testing was measured using gas chromatography. RESULTS: The subjects' memory functions in trial 5 of the Rey-Kim Memory Tests improved significantly. Furthermore, the effect on memory slope was significantly correlated with the higher plasma level of nicotine. However, the other tests did not reveal any correlation to a significant degree. CONCLUSIONS: These results suggest that nicotine of lower plasma level can improve short-term verbal memory functions in non-smoking or nicotine-naïve healthy elderly people and that some effects are dependent on nicotine plasma levels.

Phase I toxicity and pharmacology study of trimethylcolchicinic acid in patients with advanced malignancies.

A phase I study of trimethylcolchicinic acid (TMCA) given orally once daily for 5 days every 3rd week was performed in 19 patients with advanced malignancies. Myelosuppression and mucositis were the major toxicities observed. Serum TMCA levels were monitored and appear to be useful in predicting toxicities. A partial response was seen in one lymphoma patient and stabilization of disease was noted in one patient each with prostatic and ovarian cancer.