Is Single-stage Microvascular Reconstruction for Facial Mucormycosis Safe?

Introduction This is a retrospective therapeutic series of eight cases of facial mucormycosis treated over a 15-year period to determine the safety of simultaneous debridement and free-flap reconstruction in facial mucormycosis. Methods Surgical debridement was done for three cases that presented acutely with systemic manifestations (group 1) and five cases that presented in the subacute phase without systemic manifestations (group 2). The debridement involved total maxillectomy with orbital exenteration in three cases, total maxillectomy with orbital preservation in two, and subtotal maxillectomy in three cases. A total of seven out of eight patients underwent reconstruction with free flap for defect closure; in one patient, only primary closure of mucosa was done. Results The mean follow-up was 20.5 months. Two patients with acute disease, where reconstruction was done, died in the postop period (on the 27th and 6th day post reconstruction, respectively) due to continuing infection and septic shock. One of the three (group 1), who presented acutely and underwent debridement alone, survived. Four of five patients in group 2 underwent successful free-flap reconstruction. The patient with free-flap loss was salvaged with an extracorporeal radial forearm flap. All except one patient had a soft-tissue free-flap reconstruction. Three of the six living patients reported for secondary surgery. The inability to achieve clear nonnecrotic surgical margins due to extensive disease was the reason for mortality in two patients in group 1. There was no mortality in any of the group 2 patients, even when debridement and free-flap coverage was done simultaneously. Conclusion Simultaneous debridement and free flap can be successfully implemented in select cases of facial mucormycosis.

A Matched-Paired Comparative Analysis of the Hemodynamics of the Trifecta and Perimount Aortic Bioprostheses.

BACKGROUND AND AIM OF THE STUDY: Current cohort studies comparing the Trifecta valve to alternative pericardial bioprostheses are limited by selection bias. The study aim was to determine if hemodynamics are improved after the aortic valve implantation of a Trifecta valve as compared to a standard pericardial valve, when evaluated using strict paired matching for specific key relevant confounders. METHODS: Valve hemodynamics were compared in patients undergoing implantation with a Trifecta or Perimount valve matched for left ventricular outflow tract (LVOT) diameter, gender, age, body size, and days since surgery, using a 1:1 matched-paired cohort analysis (n = 20 per group). RESULTS: Patients receiving a Trifecta valve had a larger increase in indexed stroke volume (SVi) relative to baseline compared to the Perimount patients (p = 0.013), in whom SVi was decreased. The mean transvalvular pressure gradient was lower in Trifecta patients despite the larger SVi (p = 0.02). The effective orifice area (EOA) and indexed EOA (EOAi) were significantly larger in Trifecta patients compared to Perimount patients (2.04 +/- 0.46 versus 1.77 +/- 0.45 cm2, p = 0.049; 1.10 +/- 0.22 versus 0.95 +/- 0.06 cm2/m2, p = 0.027, respectively), and there was a greater increase in EOA and EOAi from baseline (p = 0.010 for both). Severe prosthesis-patient mismatch (PPM) (EOAi < or = 0.65 cm2/m2) was seen in two (10%) of the Perimount cases, but in none of the patients with the Trifecta valve (p = 0.072). CONCLUSION: Trifecta valve implantation is associated with a significant improvement in EOA and a decreased incidence of PPM as compared to the Perimount valve. The superior hemodynamic outcomes observed support consideration of this valve for aortic valve replacement, particularly in patients with a small LVOT at risk for PPM.

Investigation of soft and living matter using a micro-extensional rheometer.

Rheological properties of a material often require to be probed under extensional deformation. Examples include fibrous materials such as spider-silk, high-molecular weight polymer melts, and the contractile response of living cells. Such materials have strong molecular-level anisotropies which are either inherent or are induced by an imposed extension. However, unlike shear rheology, which is well-established, techniques to perform extensional rheology are currently under development and setups are often custom-designed for the problem under study. In this article, we present a versatile device that can be used to conduct extensional deformation studies of samples at microscopic scales with simultaneous imaging. We discuss the operational features of this device and present a number of applications.

Improved survival after liver transplantation in patients with hepatopulmonary syndrome.

Hepatopulmonary syndrome (HPS) is present in 10-32% of chronic liver disease patients, carries a poor prognosis and is treatable by liver transplantation (LT). Previous reports have shown high LT mortality in HPS and severe HPS (arterial oxygen (PaO(2)) < or =50 mmHg). We reviewed outcomes in HPS patients who received LT between 2002 and 2008 at two transplant centers supported by a dedicated HPS clinic. We assessed mortality, complications and gas exchange in 21 HPS patients (mean age 51 years, MELD score 14), including 11/21 (52%) with severe HPS and 5/21 (24%) with living donor LT (median follow-up 20.2 months after LT). Overall mortality was 1/21 (5%); mortality in severe HPS was 1/11 (9%). Peritransplant hypoxemic respiratory failure occurred in 5/21 (24%), biliary complications in 8/21 (38%) and bleeding or vascular complications in 6/21 (29%). Oxygenation improved in all 19 patients in whom PaO(2) or SaO(2) were recorded. PaO(2) increased from 52.2 +/- 13.2 to 90.3 +/- 11.5 mmHg (room air) (p < 0.0001) (12 patients); a higher baseline macroaggregated albumin shunt fraction predicted a lower rate of postoperative improvement (p = 0.045) (7 patients). Liver transplant survival in HPS and severe HPS was higher than previously demonstrated. Severity of HPS should not be the basis for transplant refusal.

Effect of biofouling on anodized and sol-gel treated titanium surfaces: a comparative study.

Anodization and sol-gel treatments of titanium (Ti) were evaluated as biofilm control measures on surfaces exposed to seawater exposed to ultraviolet light. Anodized and sol-gel treated specimens were characterized using Raman spectroscopy to confirm the presence of TiO(2). The single anatase phase was observed at the anodized surfaces whereas the anatase/rutile mixed phase was detected on the sol-gel coated surfaces. After exposure of the specimens to seawater, biofilms were characterized by total viable counts, and epifluorescence and Raman microscopy. These techniques confirmed the reduction in biofilm formation on both the anodized and sol-gel coated Ti specimens compared to the untreated specimens. Biofilm control by anodization was found to be more effective than by sol-gel treatment of the specimens. The higher particle size and the inhomogeneity at the sol-gel coated surfaces produced less effective biofilm control.

Triangulating the ledge: radiographic study of the floor of orbit and derivation of a novel template.

In orbital floor reconstruction, the need for the orbital implant to reach the exact position of the posteromedial ledge is essential, but owing to the complex anatomy of the region, visualisation of the ledge may be difficult. Several morphometric studies, both radiographic and cadaveric, have calculated a mean length from the orbital rim to the ledge. However, those linear measurements are unreliable and possess a higher margin of error for intraoperative guidance. This study attempts to triangulate the position of the posterior ledge from three easily accessible and reproducible points on the orbit and tries to provide a better guideline. A total of 50 patients (25 male and 25 female) with no history of orbital trauma or orbital surgery were selected randomly for this study. Computed tomography (CT) of both orbits, was done from three anatomically consistent and reproducible points: the infraorbital rim just above the infraorbital foramen (point A), hamulus lacrimalis (point B), and the most anterior point of the inferior orbital fissure (point C). The distance from these landmarks to the posterior ledge was measured using DICOM imaging software. A polygonal template was fabricated using the data obtained, which was used for intraoperative guidance. The mean (SD) distance to the posterior ledge from point A was 32.99 (1.35) mm, from point B was 31.36 (1.31) mm, and from point C was 20.19 (1.40) mm. There were no significant differences between left and right orbit or between male and female subjects. The template guides the shape, size, and direction of the orbital implant, reducing the risk of undersized or misplaced implants.

Endoplasmic reticulum stress-induced cell death mediated by the proteasome.

Cells exposed to sustained endoplasmic reticulum (ER) stress undergo programmed cell death and display features typical of apoptosis, such as cysteine aspartyl protease (caspase) activation, cytochrome c release, and DNA fragmentation. Here, we show that the execution of cell death induced by ER stress is mediated via the proteasome. Inhibition of the proteasome by lactacystin prevented ER stress-induced degradation of Bcl-2, release of cytochrome c, processing of effector caspase-3, and exposure of phosphatidylserine. Owing to the ability of lactacystin to inhibit cytochrome c release, we propose that the pro-apoptotic activity of the proteasome lies upstream of mitochondrial activation. Thus, the proteasome serves as a principal mediator of ER stress-induced cell death in this system.

Supramolecular helical fluid columns from self-assembly of homomeric dipeptides.

Herein, we demonstrate that with the widespread theme of residue patterning and stereochemical restraints of self-complimenting proteinogenic amino acids, a new and rich class of homomeric dipeptides exhibiting two-dimensional fluid aggregates with hierarchical ordering can be obtained. In particular, a simple way of achieving a class of functional dipeptides, wherein the first and the second residues chosen are L-/D-alanines and L-/D-leucines, has been accomplished. The supramolecules synthesized can be regarded as intermediates between polycatenars and taper-shaped amphiphiles because they possess two lipophilic segments interlinked by a peptide unit (spacer). Two pairs of enantiomers and their respective diastereomers derived from these amino acids are evidenced to self-organize into a helical columnar phase through hydrogen bonding by means of FTIR, UV/Vis, and chiroptical circular dichroism (CD) spectral analyses as well as by optical, calorimetric, electrical switching, and X-ray studies. The CD and X-ray studies have revealed that the form chirality (handedness) and the magnitude of out-of-plane fluctuations of the lattice planes of the fluid supramolecular columnar structures are solely directed by the stereochemistry encoded in the spacer. Of special significance, the less frequently found oblique helical columnar phase formed by a pair of enantiomers derived from L-/D-alanines, unlike those derived from other amino acids, exhibit ferroelectric behavior; the measured spontaneous polarization is as high as 440 nC cm(-2). Besides, all these supramolecules form stable organogels in ethanol and the CD and SEM studies on a representative gel suggest the presence of helical structures.

Assessment of serum macro and trace element homeostasis and the complexity of inter-element relations in bipolar mood disorders.

BACKGROUND: Bipolar disorders are complex neuropsychiatric in nature and are clinically classified as Type I, Type II, and Type V. The etiological factors include environmental-genetic inter-relations. Trace metals play a significant role in neurological disorders. There is very limited information on the role of macro and trace elements in bipolar disorders. METHODS: Trace elements namely Na, K, S, Ca, Mg, P, Cu, Fe, Zn, Mn and Al were analyzed in serum samples of 3 bipolar types: bipolar I, bipolar II and bipolar V with a control group using inductively coupled plasma-atomic emission spectrometry (ICP-AES). The patients were assessed as per the standard diagnostic criteria and classified into the bipolar type I, II hypomanic, II depressives and V. RESULTS: In bipolar I (mania), Na, K, P, Cu, Al and Mn were increased significantly (p<0.001). In bipolar II hypomania, Na, S, Al and Mn were increased significantly (p<0.02), while in bipolar II depression, Na, K, Cu and Al were increased (p<0.001). In bipolar V, Na, Mg, P, Cu, and Al were increased significantly (p<0.002), though S (p<0.00001), Fe (p<0.002) and Zn (p<0.004) were decreased in all 3 bipolar groups. CONCLUSIONS: There is a disturbance in the charge distribution and element-element interdependency in bipolar serum when compared to controls. These results suggest that there is a definite imbalance in macro and trace element homeostasis as evidenced by element inter-relationships in serum samples of bipolar groups when compared to controls.

Coupling endoplasmic reticulum stress to the cell-death program: a novel HSP90-independent role for the small chaperone protein p23.

The endoplasmic reticulum (ER) is the principal organelle for the biosynthesis of proteins, steroids and many lipids, and is highly sensitive to alterations in its environment. Perturbation of Ca(2+) homeostasis, elevated secretory protein synthesis, deprivation of glucose or other sugars, altered glycosylation and/or the accumulation of misfolded proteins may all result in ER stress, and prolonged ER stress triggers cell death. Studies from multiple laboratories have identified the roles of several ER stress-induced cell-death modulators and effectors through the use of biochemical, pharmacological and genetic tools. In the present work, we describe the role of p23, a small chaperone protein, in preventing ER stress-induced cell death. p23 is a highly conserved chaperone protein that modulates HSP90 activity and is also a component of the steroid receptors. p23 is cleaved during ER stress-induced cell death; this cleavage, which occurs close to the carboxy-terminus, requires caspase-3 and/or caspase-7, but not caspase-8. Blockage of the caspase cleavage site of p23 was associated with decreased cell death induced by ER stress. Immunodepletion of p23 or inhibition of p23 expression by siRNA resulted in enhancement of ER stress-induced cell death. While p23 co-immunoprecipitated with the BH3-only protein PUMA (p53-upregulated modulator of apoptosis) in untreated cells, prolonged ER stress disrupted this interaction. The results define a protective role for p23, and provide further support for a model in which ER stress is coupled to the mitochondrial intrinsic apoptotic pathway through the activities of BH3 family proteins.

Coupling endoplasmic reticulum stress to the cell death program.

The endoplasmic reticulum (ER) regulates protein synthesis, protein folding and trafficking, cellular responses to stress and intracellular calcium (Ca(2+)) levels. Alterations in Ca(2+) homeostasis and accumulation of misfolded proteins in the ER cause ER stress that ultimately leads to apoptosis. Prolonged ER stress is linked to the pathogenesis of several different neurodegenerative disorders. Apoptosis is a form of cell death that involves the concerted action of a number of intracellular signaling pathways including members of the caspase family of cysteine proteases. The two main apoptotic pathways, the death receptor ('extrinsic') and mitochondrial ('intrinsic') pathways, are activated by caspase-8 and -9, respectively, both of which are found in the cytoplasm. Recent studies point to the ER as a third subcellular compartment implicated in apoptotic execution. Here, we review evidence for the contribution of various cellular molecules that contribute to ER stress and subsequent cellular death. It is hoped that dissection of the molecular components and pathways that alter ER structure and function and ultimately promote cellular death will provide a framework for understanding degenerative disorders that feature misfolded proteins.

A ligand-receptor pair that triggers a non-apoptotic form of programmed cell death.

Several receptors that mediate apoptosis have been identified, such as Fas and tumor necrosis factor receptor I. Studies of the signal transduction pathways utilized by these receptors have played an important role in the understanding of apoptosis. Here we report the first ligand-receptor pair-the neuropeptide substance P and its receptor, neurokinin-1 receptor (NK(1)R)-that mediates an alternative, non-apoptotic form of programmed cell death. This pair is widely distributed in the central and peripheral nervous systems, and has been implicated in pain mediation and depression, among other effects. Here we demonstrate that substance P induces a non-apoptotic form of programmed cell death in hippocampal, striatal, and cortical neurons. This cell death requires gene expression, displays a non-apoptotic morphology, and is independent of caspase activation. The same form of cell death is induced by substance P in NK(1)R-transfected human embryonic kidney cells. These results argue that NK(1)R activates a death pathway different than apoptosis, and provide a signal transduction system by which to study an alternative, non-apoptotic cell death program.

Xanthogranulomatous cholecystitis: differentiation from associated gall bladder carcinoma.

Xanthogranulomatous cholecystitis (XGC) is a destructive form of chronic cholecystitis. In some patients it coexists with gall bladder carcinoma (GBC) and is often difficult to differentiate between the two. Present study was performed with an aim to identify differentiating features of XGC and those of XGC with associated Gall bladder carcinoma (XGC ass. GBC). A retrospective analysis of prospectively maintained data of 4800 cholecystectomies performed from January 1988 to December 2003 was carried out. On histopathology 453 cholecystectomy specimens revealed XGC. These patients were divided into two groups, those with associated GBC (n=26) and those without GBC (n=427). Clinical, radiological and operative findings were compared in these two groups. P value of < 0.05 was considered statistically significant. The incidence of associated GBC in present series was 6%. XGC patients with associated GBC, at presentation were older than those with XGC alone and there was male preponderance. XGC patients with associated GBC were more likely to present with anorexia, weight loss, palpable lump and jaundice. Gall stones were present in majority of patients in both the groups. GB wall thickening, GB mass, enlarged abdominal lymph nodes may be found on imaging in both the groups but more so in patients with associated GBC. Both preoperative FNAC and peroperative FNAC/imprint cytology failed to reveal the associated GBC with XGC in some patients.

Concurrent infection of the central nervous system by Borrelia burgdorferi and Bartonella henselae: evidence for a novel tick-borne disease complex.

OBJECTIVES: To investigate Bartonella henselae as a potential human tick-borne pathogen and to evaluate its role as a coinfecting agent of the central nervous system in the presence of neuroborreliosis. DESIGN: Case report study. SETTING: A primary health care center in Flemington, NJ, and the Department of Research and Development at Medical Diagnostic Laboratories LLC in Mt Laurel, NJ. SUBJECTS: Two male patients (aged 14 and 36 years) and 2 female patients (aged 15 and 30 years, respectively) with a history of tick bites and Lyme disease. MAIN OUTCOME MEASURES: Laboratory and diagnostic findings before and after antimicrobial therapy. RESULTS: Patients residing in a Lyme-endemic area of New Jersey with ongoing symptoms attributed to chronic Lyme disease were evaluated for possible coinfection with Bartonella species. Elevated levels of B henselae-specific antibodies were found in these patients using the immunofluorescent assay. Bartonella henselae-specific DNA was detected in their blood. None of these patients exhibited the clinical characteristics of cat-scratch disease. Findings of cerebrospinal fluid analysis revealed the presence of both B henselae- and Borrelia burgdorferi-specific DNA. Bartonella henselae-specific DNA was also detected in live deer ticks obtained from the households of 2 of these patients. CONCLUSIONS: Our data implicate B henselae as a potential human tick-borne pathogen. Patients with a history of neuroborreliosis who have incomplete resolution of symptoms should be evaluated for B henselae infection.

Quantification of trace elements in normal human brain by inductively coupled plasma atomic emission spectrometry.

Eight normal human brain autopsy samples were analyzed for Na, K, P, Ca, Mg, Si, Cr, Cu, Ni, Zn, Fe, Al, Cd, Pb and As in 12 regions of brain (frontal cerebrum, temporal cerebrum, parietal cerebrum, somatosensory cortex, occipital cerebrum, cerebellum, mid-brain, pons, hypothalamus, thalamus, hippocampus and medulla oblongata) using inductively coupled plasma atomic emission spectrometry (ICPAES). The distribution of these 15 elements varied significantly from region to region of the brain. Potassium was most abundant in nearly all regions of the brain, followed by sodium and phosphorus (mg/g). The concentration of Al was found to be comparatively high and varied in different areas of the brain (58-196 microg/g). Moderate levels of Pb, Cd and As were observed in different regions. Ratios of Al to Fe were found to be high in temporal cerebrum (8.07) and hippocampus (9.05) and these two regions are significantly involved in Alzheimer's disease. The concentration of Na in mole percentage showed an inverse correlation with that of K, Ca, Mg, Fe and Cr. Direct correlation was observed in the concentration of all analyzed elements, which indicated for the first time the direct dependency of concentration of trace elements in one brain region to other regions. The mole ratios between different elements in different brain regions and total amounts of the elements in an average weight of 1.4 kg human brain were also computed. The present study provides new and in-depth data which may be used as base line data for normal human brains.

Human cerebrospinal fluid acetylcholinesterase and butyrylcholinesterase. Evidence for identity between the serum and cerebrospinal fluid butyrylcholinesterase.

Human cerebrospinal fluid contained both acetylcholinesterase (EC 3.1.1.7) and butyrylcholinesterase (EC 3.1.1.8) and they were estimated in the presence of selective inhibitors. Butyrylcholinesterase of human cerebrospinal fluid was similar to human serum butyrylcholinesterase in its electrophoretic mobility, glycoprotein nature and tyramine activation of the aryl acylamidase (EC 3.5.1.13) activity exhibited by butyrylcholinesterase. Moreover antibody raised against human serum purified butyrylcholinesterase could completely immunoprecipitate butyrylcholinesterase from human cerebrospinal fluid without affecting acetylcholinesterase. It is suggested that a useful method for the precise determination of acetylcholinesterase in human cerebrospinal fluid would be removal of butyrylcholinesterase by immunoprecipitation using antibody raised against human serum butyrylcholinesterase.

Histochemical changes in the testes of lead induced experimental rats.

The experiments were performed on mature male rats divided in five groups, one control and four experimental in which the animals received 1 mg, 2 mg, 4 mg and 6 mg/kg body weight lead acetate intraperitoneally respectively, over a period of 30 days. ALA-D and lead was estimated in the blood by the use of atomic absorption spectrophotometer and ATP-ase, AMP-ase, Alk-ase were histochemically localized. Significant increase in blood and testis of lead levels along with decrease of ALA-D levels were observed. Changes in the testicular tissue were encountered. Other details concerned with the damage of the testicular tissue are discussed.

Evaluation of hypoglycemic and antihyperglycemic effects of Datura metel (Linn.) seeds in normal and alloxan-induced diabetic rats.

The seed powder of Datura metel was tested for its hypoglycemic activity in normal and alloxan-induced diabetic rats. Graded doses (25, 50 and 75 mg/kg, p.o.) of the seed powder when given to both normal and diabetic rats produced significant reduction in blood glucose at the 8 h. The effect was found to be dose dependent with all treatments at the doses administered.

Primary haemangiosarcoma of the tongue.

A 52-year-old male had a biopsy done from a tongue lesion and was reported to have primary haemangiosarcoma. The case has been reported because of the rarity of this tumour.