Primary splenic hodgkin lymphoma masquerading as splenic abscess.

Hodgkin lymphoma is a form of malignant lymphoid neoplasm. It can have various clinical presentations such as prolonged fever, night sweats, weight loss and asymptomatic lymphadenopathy. It has a distinct fever pattern known as Pel Ebstein fever. However, in some instances, its clinical presentation can mimic some tropical infections. Here, we present a case of primary splenic lymphoma masquerading as splenic abscess in a 53-yearold man with underlying dyslipidemia.

Sodium-ion diffusion mechanisms in the low cost high voltage cathode material Na(2+δ)Fe(2-δ/2)(SO4)3.

Bond-valence site energy modelling, classical molecular dynamics and DFT simulations were employed to clarify Na(+) ion migration in monoclinic Na2+δFe2-δ/2(SO4)3, the recently reported first representative of a new promising class of alluaudite-type high voltage cathode materials for sodium-ion batteries. Empirical potential parameters derived from our softBV bond valence parameter set reproduce experimental unit-cell parameters. Migration energy barrier calculations based on both these empirical and on ab initio approaches consistently show a strongly anisotropic and fairly fast Na(+) ion mobility along partially occupied Na(3) channels in the c-direction. Nominally fully occupied Na(1) sites are attached to these paths with a moderate activation energy as sources of mobile ions. At elevated temperatures separate parallel Na(2) channels contribute to the ionic conductivity. As such one-dimensional pathways are highly vulnerable to blocking by structural defects, the experimentally observed favourable rate performance can only be understood as a consequence of cross-linking of the channels to a more robust higher-dimensional migration pathway network. Our static and dynamic bond valence pathway models for representative local structure models reveal that this cross-linking is achieved by the iron deficiency of the compound: iron vacancies act as low-lying interstitial sites that can be reached from both types of channels with moderate activation energies. Structural relaxations around the vacancies however reduce the sodium mobility along the channels. An analogous dual effect of blocking migration along the channels and promoting perpendicular migration would result from Na(+)/Fe(2+) antisite defects. Hence, further new alluaudite type transition metal sulphates can only be expected to yield a high rate performance, if their synthesis ensures the presence of a comparable transition metal sub-stoichiometry and/or a suitably tailored concentration of sodium/transition metal antisite defects.

A validation study of the Hong Kong version of Montreal Cognitive Assessment (HK-MoCA) in Chinese older adults in Hong Kong.

OBJECTIVE: To validate the Hong Kong version of Montreal Cognitive Assessment (HK-MoCA) in identification of mild cognitive impairment and dementia in Chinese older adults. DESIGN: Cross-sectional study. SETTING: Cognition clinic and memory clinic of a public hospital in Hong Kong. PARTICIPANTS: A total of 272 participants (dementia, n=130; mild cognitive impairment, n=93; normal controls, n=49) aged 60 years or above were assessed using HK-MoCA. The HK-MoCA scores were validated against expert diagnosis according to the Diagnostic and Statistical Manual of Mental Disorders (4th ed) criteria for dementia and Petersen's criteria for mild cognitive impairment. Statistical analysis was performed using receiver operating characteristic curve and regression analyses. Additionally, comparison was made with the Cantonese version of Mini-Mental State Examination and Global Deterioration Scale. RESULTS: The optimal cutoff score for the HK-MoCA to differentiate cognitive impaired persons (mild cognitive impairment and dementia) from normal controls was 21/22 after adjustment of education level, giving a sensitivity of 0.928, specificity of 0.735, and area under the curve of 0.920. Moreover, the cutoff to detect mild cognitive impairment was 21/22 with a sensitivity of 0.828, specificity of 0.735, and area under the curve of 0.847. Score of the Cantonese version of the Mini-Mental State Examination to detect mild cognitive impairment was 26/27 with a sensitivity of 0.785, specificity of 0.816, and area under the curve of 0.857. At the optimal cutoff of 18/19, HK-MoCA identified dementia from controls with a sensitivity of 0.923, specificity of 0.918, and area under the curve of 0.971. CONCLUSION: The HK-MoCA is a useful cognitive screening instrument for use in Chinese older adults in Hong Kong. A score of less than 22 should prompt further diagnostic assessment. It has comparable sensitivity with the Cantonese version of Mini-Mental State Examination for detection of mild cognitive impairment. It is brief and feasible to conduct in the clinical setting, and can be completed in less than 15 minutes. Thus, HK-MoCA provides an attractive alternative screening instrument to Mini-Mental State Examination which has ceiling effect (ie may fail to detect mild/moderate cognitive impairment in people with high education level or premorbid intelligence) and needs to be purchased due to copyright issues.

The subdivision of the T4 (CD4) subset on the basis of the differential expression of L-C/T200 antigens.

The T4 (CD4) subset of T lymphocytes has been subdivided into two major subsets, a suppressor/inducer subset (T4+,2H4+) and a helper subset (T4+,2H4-) on the basis of the differential expression of the L-C/T200 (CD45) antigens. The 2H4 antigen itself comprises at least three distinct polypeptides at 125,200, and 220 X 10(3) Mr, of which the 200 and 220 X 10(3) Mr polypeptides constitute the highest Mr isoforms of a pool of five distinct L-C/T200 antigens. The T4+,2H4+ subset expresses at least four of these isoforms at 180, 190, 200, and 220 X 10(3) on the cell surface, while the T4+,2H4- subset expresses only the 180 and 190 X 10(3) Mr forms. Pulse-chase analysis and endoglycosidase treatment revealed that the 125 X 10(3) Mr chain of the 2H4 antigen is nonglycosylated, while the 200 and 220 X 10(3) polypeptides are structurally related and derived by N- and O-linked glycosylation from two nascent subunits at 150 and 160 X 10(3) Mr. The function of the T4+,2H4+ subset could be blocked only by an antibody reactive with the L-C/T200 isoforms enriched with O-linked oligosaccharides at 200 and 220 X 10(3) Mr.

Fracture-induced subbandgap absorption as a precursor to optical damage on fused silica surfaces.

The optical damage threshold of indentation-induced flaws on fused silica surfaces was explored. Mechanical flaws were characterized by laser damage testing, as well as by optical, secondary electron, and photoluminescence microscopy. Localized polishing, chemical leaching, and the control of indentation morphology were used to isolate the structural features that limit optical damage. A thin defect layer on fracture surfaces, including those smaller than the wavelength of visible light, was found to be the dominant source of laser damage initiation during illumination with 355 nm, 3 ns laser pulses. Little evidence was found that either displaced or densified material or fluence intensification plays a significant role in optical damage at fluences >35 J/cm(2). Elimination of the defect layer was shown to increase the overall damage performance of fused silica optics.

Montreal Cognitive Assessment - Single Cutoff Achieves Screening Purpose.

BACKGROUND AND PURPOSE: The study evaluated the performance between norm-derived age and education adjusted vs single cutoff scores of the Montreal Cognitive Assessment, Hong Kong version (HK-MoCA) in classifying cognitive impairment in Chinese older adults. METHODS: Total scores of HK-MoCA were collected from 315 subjects (128 with dementia, 122 with mild cognitive impairment (MCI) and 65 normal) attending a public district hospital-based cognition clinic from 2012 to 2017. The HK-MoCA total scores were evaluated using different cutoffs. Norm-derived age and education adjusted cutoff scores were at 16th, 7th, and 2nd percentiles. Comparison was made with the single cutoff scores validated in a local study with 21/22 for MCI and 18/19 for dementia. RESULTS: Single cutoff score of HK-MoCA differentiated MCI from normal with sensitivity of 0.861 and specificity of 0.723. To detect dementia, its sensitivity was 0.922, and specificity was 0.923. In identifying cognitive impairment, the sensitivity and specificity were 0.932 and 0.723, respectively. However, age and education adjusted cutoff scores achieved high specificities at all levels of cognitive impairment with trade-off of sensitivities. The accuracy of correctly classifying tested subjects into appropriate groups was 85.3% if single cutoff was used though the consistency between norm-derived cutoffs and expert diagnoses were only 59.0%, 54.2%, and 53.9% at 16th, 7th, and 2nd percentiles, respectively. The consistency decreased with older age and lower education level, and majority of misclassifications were false negatives. CONCLUSION: HK-MoCA is a convenient screening tool to detect cognitive impairment. Administration time is relatively short, and it has incorporated essential cognitive domains. Single cutoff scores with inherent simple education adjustment achieved screening purpose of mild cognitive impairment and dementia in Chinese older adults.

Tissue polarity genes of Drosophila regulate the subcellular location for prehair initiation in pupal wing cells.

The Drosophila wing is decorated with a regular array of distally pointing hairs. In the pupal wing, the hairs are formed from micro-villus like prehairs that contain large bundles of actin filaments. The distal orientation of the actin bundles reveals the proximal-distal polarity within the pupal wing epithelium. We have used F-actin staining to examine early stages of prehair development in both wild-type and mutant pupal wings. We have found a striking correlation between hair polarity and the subcellular location for assembly of the prehair. In a wild-type wing, all of the distally pointing hairs are derived from prehairs that are formed at the distal vertex of the hexagonally shaped pupal wing cells. Mutations in six tissue polarity genes result in abnormal hair polarity on the adult wing, and all also alter the subcellular location for prehair initiation. Based on their cellular phenotypes, we can place these six genes into three phenotypic groups. Double mutant analysis indicates that these phenotypic groups correspond to epistasis groups. This suggests that the tissue polarity genes function in or on a pathway that controls hair polarity by regulating the subcellular location for prehair formation.

Urgent Liver Transplantation for Dietary Supplements: An Under-Recognized Problem.

BACKGROUND: The recent outbreak of acute liver failure caused by herbal/dietary supplements (HDS) in Hawaii prompted evaluation of those patients who underwent emergency liver transplantation (LT) for HDS in the United States. METHODS: We queried the Scientific Registry of Transplant Recipients (2003-2015) to identify patients who underwent urgent LT for acute hepatic necrosis (AHN) and identified those with HDS use. This group of patients was then characterized. RESULTS: Of 2408 adult cases, 625 were characterized as a drug-induced liver injury. The majority of cases (n = 300) were due to acetaminophen toxicity, but the fourth highest category was due to HDS (n = 21). Of these 21 cases caused by HDS, 13 did not list the specific agent responsible, mean age was 36 years, and all cases occurred after 2007. There probably are more cases because 25% of all LT cases in the study did not list a specific reason for liver failure and 20% of all drug-induced liver failure did not list a specific drug. CONCLUSIONS: Herbal/supplement use is the fourth most common cause of drug-induced AHN requiring LT, albeit an underestimation of the problem. Detailed questioning of patients and their support systems regarding herbal/supplement use and better reporting are imperative to further define this problem and identify products that have the potential to lead to liver failure.

Cytochrome P450 monooxygenases.

The field of P450 research is progressing rapidly. The active sites of structurally characterized bacterial P450 enzymes have been rationally re-engineered to alter both substrate specificity and selectivity of substrate oxidation. Many human P450 enzymes have been functionally expressed and new methods of substrate turnover described. These developments, arising from our increased understanding of the chemistry and molecular biology of P450 enzymes, open up new and exciting research directions.

The cost of dying of end-stage liver disease.

BACKGROUND: The high cost of liver transplantation is well known. The cost of dying of complications of end-stage liver disease (ESLD) without transplant, however, has not been well documented. METHODS: For a 5-year period (1991-1995), in 153 patients, mean inpatient hospital charges and length of stay were analyzed in 6 groups of patients: (1) patients admitted with the primary diagnosis of esophageal varices, (1a) the subset of group 1 patients who died on this admission, (2) patients admitted to the liver team who died of complications from ESLD, (3) patients who underwent transjugular intrahepatic portosystemic shunts, (4) patients who underwent surgical shunt for bleeding varices, and (5) patients who underwent liver transplantation. RESULTS: One hundred twenty-nine patients with esophageal varices were hospitalized 13.7 days with a mean charge of $30,980 for each of 202 admissions. Of these, 38 died after 24 days with a mean charge of $67,091. Seven patients admitted to the liver team died of complications of ESLD at $110,576 per admission. Transjugular intrahepatic portosystemic shunt was performed in 17 patients with a mean charge of $43,209. Six patients underwent surgical shunt for $53,994. Mean charge for 7 liver transplantations was $222,968. During the study period, 36.7% of all charges were for patients who died. CONCLUSIONS: It is difficult to estimate the total cost of ESLD; however, in evaluating inpatient costs, we see that it is expensive and significant amounts are spent on patients who die. Further study is necessary to determine which factors can optimize the cost of ESLD.

Vasopressin V2 receptor antagonists.

Hyponatremia due to the syndrome of inappropriate antidiuretic hormone secretion (SIADH) and disorders of water retention such as congestive heart failure and cirrhosis is a common problem encountered in the care of the medical patient. Thus far, available treatment modalities for disorders of excess arginine vasopressin (AVP) secretion or action have been suboptimal. The development of nonpeptide AVP V2 receptor antagonists represents a promising treatment option to directly antagonize the effects of elevated plasma AVP concentrations by increasing the water permeability of renal collecting tubules, thereby promoting excretion of retained water and normalizing hypoosmolar hyponatremia. In this review, SIADH and other water retaining disorders are briefly discussed, after which the published preclinical and clinical studies in the development of several nonpeptide AVP V2 receptor antagonists are summarized. The likely therapeutic indications and potential complications of these compounds, as well as their vascular effects, are also described.

N-(2-ferrocene-ethyl)maleimide: a new electroactive sulphydryl-specific reagent for cysteine-containing peptides and proteins.

We report the synthesis and application of a specific electroactive label, N-(2-ferrocene-ethyl)maleimide, which provides new redox properties to organic compounds and proteins possessing sulphydryl groups. Its reaction conditions with the cysteine-containing peptide, glutathione, and a terminal monooxygenase enzyme, cytochrome P450cam are presented. The labelled peptide and enzyme acquired reversible electrochemical properties due to the attached ferrocene moiety.

Surface-modified mutants of cytochrome P450cam: enzymatic properties and electrochemistry.

We report the electrochemistry of genetic variants of the haem monooxygenase cytochrome P450cam. A surface cysteine-free mutant (abbreviated as SCF) was prepared in which the five surface cysteine residues Cys-58, Cys-85, Cys-136, Cys-148 and Cys-334 were changed to alanines. Four single surface cysteine mutants with an additional mutation, R72C, R112C, K344C or R364C, were also prepared. The haem spin-state equilibria, NADH turnover rates and camphor-hydroxylation properties, as well as the electrochemistry of these mutants are reported. The coupling of a redox-active label, N-ferrocenylmaleimide, to the single surface cysteine mutant SCF-K344C, and the electrochemistry of this modified mutant are also described.

The thermodynamics and kinetics of electron transfer in the cytochrome P450cam enzyme system.

In anaerobic environments the first electron transfer in substrate-free P450cam is known to be thermodynamically unfavourable, but in the presence of dioxygen the reduction potential for the reaction shifts positively to make electron transfer thermodynamically favourable. Nevertheless a slower rate of electron transfer is observed in the substrate-free P450cam compared to substrate-bound P450cam. The ferric haem centre in substrate-free P450cam changes from six co-ordinate to five co-ordinate when reduced whereas in substrate-bound P450cam the iron centre remains five co-ordinate in both oxidation states. The slower rate of electron transfer in the substrate-free P450cam is therefore attributed to a larger reorganisation energy as predicted by Marcus theory.

The catalytic activity of cytochrome P450cam towards styrene oxidation is increased by site-specific mutagenesis.

The styrene oxidation activity of cytochrome P450cam, has been greatly improved by rational protein engineering. Compared to the wild-type enzyme, the active-site mutants Y96A and Y96F bound styrene more tightly, consumed NADH more rapidly, and were more efficient at utilising reducing equivalents for product formation. Styrene oxide formation rates were enhanced 9-fold in the Y96A mutant relative to wild-type, and 25-fold in the Y96F mutant, thus demonstrating the effectiveness of active-site redesign in improving the activity of a haem monooxygenase towards an unnatural substrate.

The oxidation of naphthalene and pyrene by cytochrome P450cam.

Mutants of the heme monooxygenase cytochrome P450cam in which Y96 had been replaced with hydrophobic residues, have been shown to oxidise naphthalene and pyrene with rates one to two orders of magnitude faster than the wild-type. Naphthalene was oxidised to 1- and 2-naphthol, probably via the 1,2-oxide intermediate. In the case of the Y96F mutant, naphthalene was oxidised at a rate comparable to camphor. Pyrene oxidation gave 1,6- and 1,8-pyrenequinone with no evidence for attack at the K-region, in contrast to mammalian enzymes. The results show that the Y96 residue plays a key role in controlling the substrate range of P450cam.

Calciphylaxis in patients on hemodialysis: a prevalence study.

BACKGROUND: Calciphylaxis is characterized by painful, violaceous, mottled skin lesions (livedo reticularis) that may progress to tissue necrosis, nonhealing ulcers, gangrene, and potentially amputation, sepsis, or death. The prevalence and characteristics of patients who have calciphylaxis need further identification to predict which patients on dialysis may benefit from close monitoring or early surgical intervention. METHODS: All 242 patients undergoing hemodialysis in an outpatient unit were reviewed retrospectively during a 15-month cross-sectional study of the prevalence and characteristics of calciphylaxis. RESULTS: Ten patients (prevalence, 4.1%) had calciphylaxis. Patients with calciphylaxis were significantly younger (49 versus 60 years; p = 0.01), had undergone hemodialysis longer (80 versus 20 months; p < 0.0001), and had higher median serum calcium (9.7 versus 9.2 mg/dl; p = 0.03), phosphate (8.2 versus 5.7 mg/dl; p = 0.001), calcium phosphate product (81.5 versus 52.9; p = 0.0004), parathyroid hormone (1496 versus 138 pg/ml; p < 0.0001), and alkaline phosphatase levels (188 versus 89 IU/L; p = 0.0001). Bone surveys were positive in all 10 patients with calciphylaxis compared with 49 (21%) of the 232 patients without calciphylaxis (p < 0.0001). All patients who underwent parathyroidectomy for calciphylaxis had dramatic healing of the ulcers. CONCLUSIONS: The presence of calciphylaxis is higher among younger patients who had undergone longer periods of hemodialysis. Therefore this group of patients should be monitored aggressively and treated expeditiously for complications of secondary hyperparathyroidism.

Safety and efficacy of radiofrequency thermal ablation in advanced liver tumors.

HYPOTHESIS: Radiofrequency thermal ablation (RFA) can be performed safely and effectively to control local disease in patients with advanced, unresectable liver tumors. DESIGN, SETTING, AND PATIENTS: Prospective study of 76 patients with unresectable liver tumors who underwent RFA at a private tertiary referral hospital. INTERVENTIONS: Ninety-nine RFA operations were performed to ablate 328 tumors. MAIN OUTCOME MEASURES: Complications and local recurrence. RESULTS: There was 1 death (1%), major complications occurred in 7 operations (7%), and minor complications occurred in 10 operations (10%). Local recurrence was identified in 30 tumors (9%) at a mean follow-up of 15 months. Size (P<.001), vascular invasion (P<.001), and total volume ablated (P<.001) were associated with recurrence but the number of tumors was not (P =.39). CONCLUSION: Radiofrequency thermal ablation provides local control of advanced liver tumors with low recurrence and acceptable morbidity.

Direct electrochemistry of pentachlorophenol hydroxylase.

The direct electrochemistry of the flavin-containing monooxygenase, pentachlorophenol hydroxylase (PCPH), at an edge plane graphite electrode was observed and a catalytic response, linear with concentration, was found with the substrate pentachlorophenol (PCP).