Internal carotid artery nasopharyngeal fistula treated with coil embolization.
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Adult↗
Biomedical subjects
M West
Publications and source records attributed to M West.
Myelin proteolipid protein: function in myelin structure is distinct from its role in oligodendrocyte development.
The myelin proteolipid proteins PLP and DM20 are essential for the compaction of central nervous system myelin and they play an important role in the maturation of the oligodendrocyte. The specific function of the less abundant DM20 isoform is still unknown, but rescue experiments previously indicated that both isoforms are necessary for oligodendrocyte maturation. In vitro experiments have suggested DM20 may assist in the translocation of PLP into the membrane. We tested this hypothesis in vivo, by investigating whether wild-type PLP derived from a transgene could be incorporated into the myelin membrane of Plp mutant rumpshaker mice. We previously demonstrated that expression of the PLP transgene alone in a more severe Plp mutant, jimpy mouse, did not result in PLP incorporation into the myelin. Here we report that there was significantly more PLP in white matter from rumpshaker expressing the PLP transgene than their nontransgenic rumpshaker littermates and that myelin structure was improved. The delay in oligodendrocyte development was not alleviated by expression of the PLP transgene however, supporting an essential role for DM20 in oligodendrocyte maturation.
Animals↗
Anxious attachment and self-reported depressive symptomatology in women.
OBJECTIVE: Lack of intimacy has been identified as an important provoking agent that increases the risk of depressive symptoms in women. This study precisely characterized lack of intimacy by assessing a woman's attachment style and investigated the specificity of association between depressive symptoms and an anxious attachment pattern. METHOD: Four hundred and twenty women participated in this cross-sectional study of depressive symptomatology and anxious attachment. All participants completed the following measures: a sociodemographic questionnaire, the Centre for Epidemiological Studies Depression Scale (CES-D), the Reciprocal Attachment Questionnaire, the Social Support Questionnaire, the Rosenberg Self-Esteem Scale, and the Global Assessment of Recent Stress Scale. RESULTS: A score of 16 or above on the CES-D, which indicates the presence of depressive symptoms, was used to divide the sample into 2 groups: a depressed group (N = 129) and a nondepressed group (N = 291). We found that women in the depressive symptomatology group were more likely than women in the nondepressive symptomatology group to exhibit anxious attachment and adverse social and cognitive characteristics. Lower levels of self-esteem and higher levels of recent stress were also predictive of depressive symptomatology. Feared loss of the attachment figure and a lack of use of the attachment figure were independent predictors of depressive symptomatology in the same model. CONCLUSION: The feared loss of security associated with an attachment figure seems to be related to an increased likelihood of depressive symptoms.
Adult↗
Quantitative comparison of autoradioluminographic and radiometric tissue distribution studies using carbon-14 labeled xenobiotics.
The tissue distribution of two 14C drugs were quantitatively compared using the techniques of whole body autoradioluminography (WBAL) and radiometry. Quantitative analysis of tissue radioactivity in whole body cryosections was accomplished from storage phosphor images using the MicroComputer Imaging Device. After obtaining whole body sections from four frozen rats and three frozen ferrets, each WBAL-sectioned specimen was partially thawed before obtaining tissue samples for radiometric analysis. For all tissues examined, concentrations of radioactivity determined by WBAL were comparable with those determined by dissection and liquid scintillation analysis (DLSA), except for renal tissue obtained from different kidneys of the same ferret and for rat ocular tissues. A 2-fold difference was observed between WBAL and DLSA evaluations of radioactivity in the contralateral kidneys of one ferret. DLSA evaluation only provided an assessment of total radioactivity in the eye, whereas WBAL evaluation determined the selective distribution of radioactivity to ocular tissues. Resolution in DLSA evaluation of ocular tissues was restricted by limitations of the dissection procedure. These results indicated that the quantitation of tissue radioactivity by WBAL was as precise as DLSA evaluation, and WBAL also provided results to the quantitative distribution of radioactivity to localized sites in organs not feasible by DLSA.
Administration, Oral↗
Conversion from bladder to enteric drainage after pancreaticoduodenal transplantations.
BACKGROUND: Bladder drainage is the most common technique for managing the exocrine secretions of pancreaticoduodenal grafts. However, bladder drainage can cause urinary, pancreatic, and metabolic complications that may require conversion to enteric drainage. With enteric drainage, urinary amylase levels cannot be monitored as a marker for rejection. After enteric conversion, rejection is the major cause of graft loss. Timing the conversion to reduce immunologic graft loss would greatly improve patient and graft survival rates. Our study was designed to assess the incidence of, indications for, and complications of converting from bladder to enteric drainage after pancreaticoduodenal transplantations. METHODS: We retrospectively reviewed our experience with 80 recipients who underwent enteric conversion. We studied the recipient category, the interval from transplantation to conversion, the interval from the last rejection episode to conversion, the indications for conversion, the type of enteric drainage at conversion (loop versus Roux-en-Y), the results of the conversion, and postconversion complications. RESULTS: The major indications for conversion were metabolic acidosis (n = 26, 33%), recurrent urinary tract infections (UTIs) (n = 16, 20%), reflux pancreatitis (n = 15, 19%), and hematuria (n = 12, 15%). For most recipients, their symptoms resolved after conversion (n = 76, 95%). The cumulative probability of undergoing conversion was 13% at 12 months, 21% at 36 months, and 25% at 60 months. Of the recipients with surgical complications after conversion (n = 12, 15%), one lost his graft as a result of pancreatitis. Overall, of the 80 recipients who underwent conversion, 12 (15%) lost their graft, most due to rejection (n = 8, 75%). Immunologic graft loss was highest for recipients of pancreas transplants alone who underwent conversion < or = 6 months after transplantation or < or = 1 year after their last rejection episode. CONCLUSIONS: Enteric conversion is safe and therapeutic in recipients with complications related to the exocrine secretions of bladder-drained pancreas grafts. After conversion, rejection accounted for 75% of the grafts lost. However, waiting at least 1 year after the last rejection episode significantly reduced immunologic graft loss.
Acidosis↗
Serious adverse event after unrecognized substitution of one amphotericin B lipid preparation for another.
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Aged↗
A multicenter, double-blind, one-year study comparing safety and efficacy of atorvastatin versus simvastatin in patients with hypercholesterolemia.
We directly compared the safety and efficacy of atorvastatin and simvastatin in hypercholesterolemic patients. This 1-year, randomized, double-blind study was performed at 9 community- and university-based research hospitals in Australia. One-hundred seventy-seven patients between the ages of 18 and 80 years with baseline low-density-lipoprotein (LDL) cholesterol > or = 4.14 and < or = 7.76 mmol/L (160 and 300 mg/dl, respectively) and triglycerides < or = 4.52 mmol/L (400 mg/dl) received once-daily dosing with atorvastatin (Lipitor) 10 mg or simvastatin (Zocor) 10 mg. At week 16, the dose of medication was titrated to atorvastatin 20 mg or simvastatin 20 mg if patients did not meet LDL cholesterol target of < or = 3.36 mmol/L (130 mg/dl). Efficacy was reported as percent change from baseline in LDL cholesterol, total cholesterol, very low density lipoprotein cholesterol, total triglycerides, high-density lipoprotein cholesterol, apolipoproteins AI and B, and lipoprotein(a). Atorvastatin caused significantly greater reductions from baseline than did simvastatin for LDL cholesterol, total cholesterol, very low density lipoprotein cholesterol, triglycerides, and apolipoprotein B (p <0.05). No patient in either treatment group had clinically important elevations in creatine phosphokinase, alanine aminotransaminase, or aspartate aminotransaminase. No serious adverse events were considered associated with treatment. With atorvastatin 10 mg, 46% of the patients achieved LDL cholesterol target goal by week 16, whereas only 27% of the simvastatin patients achieved the target goal at the 10-mg dose. This cholesterol-lowering profile affords utility in many patient types.
Adult↗
Excitatory synaptic site heterogeneity during paired pulse plasticity in CA1 pyramidal cells in rat hippocampus in vitro.
1. The properties of individual excitatory synaptic sites onto adult CA1 hippocampal neurons were investigated using paired pulse minimal stimulation and low noise whole-cell recordings. Non-NMDA receptor-mediated synaptic responses were isolated using a pharmacological blockade of NMDA and GABAA receptors. Amongst the twenty-five stationary ensembles there were twelve showing paired pulse potentiation, two showing paired pulse depression and eleven with no significant net change. The signal-to-noise ratio averaged 4.5:1. There was no correlation between the amplitude of the first and second responses after separation of failures: the percentage of failures averaged 33.6% for the conditioning pulse and 31.7% for the test pulse. 2. Site-directed Bayesian statistical analysis was developed to predict the likely number of activated synapses, synaptic response amplitudes, probability of release and intrinsic variation at each individual synaptic site. Extensive simulations showed the usefulness of this model and defined appropriate parameters. These simulations demonstrated only small errors in estimating parameters of data sets with a small number of sites (< 10) and similar characteristics to the physiological data sets. 3. Physiological ensembles showed between one and three synaptic sites, which exhibited a wide range of values for release probability (0.03-0.99), synaptic amplitudes (1.46-16.8 pA; approximately 62% coefficient of variation between sites) and intrinsic variation over time (approximately 36%). Paired pulse plasticity occurred primarily from alterations in the release probabilities but a few ensembles also showed small changes in site amplitude. Initial release probability correlated negatively with the degree of paired pulse potentiation. Whilst it was possible to use simple assumptions regarding site homogeneity (such as required for a binomial process) for 48% (12 out of 25) of the data sets, the Bayesian analysis was necessary to reveal the complex changes and heterogeneity that occurred in the other 52% of the data sets. The Bayesian site analysis robustly indicated the presence of considerable site heterogeneity, significant intrinsic site variation over time and changes in parameters at individual synaptic sites with plasticity.
6-Cyano-7-nitroquinoxaline-2,3-dione↗
Long-term results of four-wall orbital decompression for Graves' ophthalmopathy.
A long-term (average 5 years, 4 months) follow-up of four-wall orbital decompression for Graves' ophthalmopathy in 22 patients is presented. Surgical decompression was reserved for patients who failed to respond to medical therapy. Six patients had undergone previous limited surgical decompression (3-wall decompression in one patient, 2-wall decompression in 4 patients, and orbital floor resection in 1 patient). All patients had moderate to severe proptosis. Fifteen of the 44 eyes (34%) had visual acuity of 20/200 or less. There were only 6 eyes with normal visual acuity (20/20) preoperatively (13.6%). Postoperatively visual acuity was normal in 34 eyes (77%). Globe recession varied from 2 to 14 mm (mean 6.1 mm). Apart from diplopia, symptomatic improvement was noted in nearly all patients.
Adult↗
Functional outcome of discordant xenoislet grafts from a large animal donor after recipient defibrinogenation with Ancrod.
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Ancrod↗
Fluoroquinolone (ciprofloxacin) secretion by human intestinal epithelial (Caco-2) cells.
1. Human intestinal epithelial Caco-2 cells were used to investigate the mechanistic basis of transepithelial secretion of the fluoroquinolone antibiotic ciprofloxacin. 2. Net secretion and cellular uptake of ciprofloxacin (at 0.1 mM) were not subject to competitive inhibition by sulphate, thiosulphate, oxalate, succinate and para-amino hippurate, probenecid (10 mM), taurocholate (100 microM) or bromosulphophthalein (100 microM). Similarly tetraethylammonium and N-'methylnicotinamide (10 mM) were without effect. 3. Net secretion of ciprofloxacin was inhibited by the organic exchange inhibitor 4,4'-diisothiocyanostilbene-2-2'-disulphonic acid (DIDS, 400 microM). 4. Net secretion of ciprofloxacin was partially inhibited by 100 microM verapamil, whilst net secretion of the P-glycoprotein substrate vinblastine was totally abolished under these conditions. Ciprofloxacin secretion was unaltered after preincubation of cells with two anti-P-glycoprotein antibodies (UIC2 and MRK16), which both significantly reduced secretory vinblastine flux (measured in the same cell batch). Ciprofloxacin (3 mM) failed to inhibit vinblastine net secretin in Caco-2 epithelia, and was not itself secreted by the P-glycoprotein expressing and vinblastine secreting dog kidney cell line, MDCK. 5. Net secretion and cellular uptake of ciprofloxacin (at 0.1 mM) were not subject to alterations of either cytosolic or medium pH, or dependent on the presence of medium Na+, Cl- or K+ in the bathing media. 6. The substrate specificity of the ciprofloxacin secretory transport in Caco-2 epithelia is distinct from both the renal organic anion and cation transport. A role for P-glycoprotein in ciprofloxacin secretion may also be excluded. A novel transport mechanism, sensitive to both DIDS and verapamil mediates secretion of ciprofloxacin by human intestinal Caco-2 epithelia.
4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
Transepithelial transport of the fluoroquinolone ciprofloxacin by human airway epithelial Calu-3 cells.
Although fluoroquinolone antibiotics such as ciprofloxacin are able to gain access to lung tissue and both pleural and bronchial secretions, the characteristics of transport and cellular uptake of ciprofloxacin in human epithelial lung tissue remain obscure. We have chosen human airway epithelial (Calu-3) cells, reconstituted as functional epithelial layers grown on permeable filter supports, as a model with which to assess both transepithelial transport and cellular uptake of ciprofloxacin. Transepithelial ciprofloxacin fluxes in absorptive (apical-to-basal) and secretory (basal-to-apical) directions were similar throughout the concentration range studied (1.0 microM to 3.0 mM). Transepithelial mannitol fluxes measured concurrently were substantially smaller than ciprofloxacin fluxes in Calu-3 epithelia, suggesting the existence of a mediated transcellular route in addition to a paracellular route for transepithelial permeation. Apical-to-basal ciprofloxacin flux (at 10 microM) was inhibited by a 100-fold excess of unlabelled norfloxacin, enoxacin, and ofloxacin, while secretory flux was unaffected. Cellular uptake of ciprofloxacin, determined as a cell/medium ratio, was greater from the basal compartment (2.7-fold) than apical uptake (1.39-fold) measured at 100 microM ciprofloxacin and showed no saturation up to 3 mM ciprofloxacin. Comparison of the permeation of ciprofloxacin was made with that of lipophilic substrates such as vinblastine and digoxin. There was a linear correlation between transepithelial permeability (Pa-b) and their oil/water partition coefficients with mannitol < ciprofloxacin < digoxin < vinblastine. Comparison of transport of ciprofloxacin across human airway Calu-3 epithelia with that across intestinal Caco-2 epithelia emphasizes the absence of a specific secretory pathway; ciprofloxacin permeation in Calu-3 epithelia appears to be mediated primarily by a transcellular route, with mediated transfer at apical and basal membranes occurring via transporters with low affinity to ciprofloxacin.
Anti-Infective Agents↗
Epstein-Barr virus EBNA3C represses Cp, the major promoter for EBNA expression, but has no effect on the promoter of the cell gene CD21.
EBNA3C is a potent repressor of transcription when bound to DNA as a fusion with the DNA binding domain (DBD) of GALA. A survey of promoters has revealed that the wild-type, unfused EBNA3C can specifically repress expression from reporter plasmids containing the Epstein-Barr virus Cp latency-associated promoter. Repression of Cp activity required amino acids 207 to 368, which encompasses a region resembling a basic DBD adjacent to a leucine zipper DNA binding motif and a site which binds to the cellular factor CBF1/RBP-Jkappa. However, amino acids 207 to 368 are dispensable when the protein is bound to DNA as a fusion with the GAL4 DBD, thus implicating this region in DNA binding. Mutation of the CBF1/RBP-Jkappa binding site in EBNA3C abrogated repression, strongly suggesting that CBF1/RBP-Jkappa is necessary for targeting the viral protein to Cp. Consistent with this result, mutation of the EBNA2 response element (a CBF1/RBP-Jkappa binding site) in Cp also prevented significant repression. In addition, amino acids 346 to 543, which were previously defined as important for the repressor activity of the GAL4-EBNA3C fusion proteins, also appear to be necessary for the repression of Cp. Since repression by these fusions was not observed in all cell types, it seems likely that EBNA3C either depends on a corepressor which may interact with amino acids 346 to 543 or is modified in a cell-specific manner in order to repress. These data are consistent with EBNA3C contributing to the regulation of EBNA expression in latently infected B cells through CBF1/RBP-Jkappa and another factor, but this need not directly involve EBNA2. Finally, although it has been reported that EBNA3C can upregulate CD21 in some B cells, we were unable to demonstrate any effect of EBNA3C on reporter plasmids which contain the CD21 promoter.
B-Lymphocytes↗
Radiological and survival comparison of four methods of fixation of a proximal femoral stem.
We compared the radiological appearances and survival of four methods of fixation of a femoral stem in 538 hips after follow-up for five or ten years. The fixation groups were: 1) press-fit shot-blasted smooth Ti-A1-V stem; 2) press-fit shot-blasted proximally ridged stem; 3) proximal hydroxyapatite (HA) coating; and 4) cementing. Survival analysis at five to ten years showed better results in the HA-coated (100% at five to six years) and cemented stems (100% at 5 to 6 years) than in the two press-fit groups. There was a higher mean rate of migration in the smooth and ridged Ti-A1-V shot-blasted press-fit groups (0.8 mm/year and 0.6 mm/year, respectively) when compared with the HA-coated and cemented prostheses (both 0.3 mm/year). More radiolucent lines and osteolytic lesions were seen in the press-fit groups than in either the HA-coated or cemented implants, with a trend for a lower incidence of both in the HA compared with the cemented group. Proximal osteopenia increased in the press-fit and cemented prostheses with time, but did not do so in the HA group. There was a higher incidence of resorption of the femoral neck with time in the cemented group than in the other three. We conclude that the HA and the cemented interfaces both provide secure fixation with a trend in favour of HA. The cemented prosthesis meets the suggested National Institutes of Health definition of 'efficacious' at ten years.
Adult↗
Colon perforation after renal transplantation: a single-institution review.
Colon perforation (CP) is an uncommon but dramatic complication after renal transplantation. Of 1530 consecutive kidney transplants performed at our center, 8 recipients had an CP (incidence of 0.5%), either early (n = 5, 2-14 days) or late (n = 3, 8-48 months) post transplant. Clinical symptoms were generally vague. Biological findings were inconstant. Risk factors for CP included a cadaver graft (versus a living donor), high body weight, history of diverticulitis, and Kayexalate use. Crucial to outcome were: 1) immediate diagnosis and 2) aggressive surgical care consisting of resectional therapy, broad-spectrum antibiotics, and reduced immunosuppression. Applying these principles, mortality in our patients (25%) was lower than in previously reported series (33-64%). All grafts were functioning at the time of diagnosis; graft function was preserved in recipients who recovered from CP. Patients with a documented history of diverticulitis should undergo prophylactic colonic resection. Constipation and colonic dilatation should be treated aggressively in the early post-operative period.
Adolescent↗
Laparoscopic biopsy after pancreaticoduodenal transplantation. A first report.
Over the past 5 years, graft biopsy has become the gold standard for diagnosing rejection or graft dysfunction after pancreas transplantation. Until now, only three types of pancreas graft biopsies have been described: percutaneous, transcystoscopic, and open laparotomy. Percutaneous biopsy (whether computerized tomography scan or ultrasound guided) is unsuccessful 20% of the time. In recipients of enterically drained pancreas grafts, a transcystoscopic biopsy cannot be done. The only other alternative has been an open laparotomy. We report one case of laparoscopic biopsy of an enterically drained pancreas graft, after a percutaneous biopsy was unsuccessful. We conclude that laparoscopic pancreas graft biopsy is a safe and effective method for diagnosing graft dysfunction. It also avoids the complications and prolonged hospitalization of an open laparotomy. Laparoscopic biopsy should become another valuable tool for diagnosing pancreas graft dysfunction.
Adult↗
Rapamycin inhibits protein kinase C activity and stimulates Na+ transport in A6 cells.
Rapamycin and FK506 have unique cellular effects despite the fact that they bind to the same set of immunophilins, the FK506 binding proteins (FKBP). We have previously reported that rapamycin (RAP) stimulates sodium transport in A6 cells. FK506 did not stimulate sodium transport but did inhibit the stimulation seen in RAP-treated cells. Since FKBP12 has been shown to have sequence homology with an endogenous inhibitor of protein kinase C (PKC) and PKC inhibition has been shown to increase Na+ channel activity in A6 cells, studies to determine the effect of RAP on PKC activity and its relationship to sodium transport were performed. Here we report that RAP stimulates sodium transport, and the effect is not additive to that seen with a cell-permeant inhibitor of PKCalpha and -beta subtypes. RAP significantly inhibits endogenous PKC activity in A6 cells both in membrane and cytosolic preparations. There is a strong correlation between the degree of inhibition of PKC activity and the stimulation of sodium transport by RAP. RAP has no effect on Na+/K+-ATPase activity over this time course. Purified recombinant FKBP12 with or without FK506 has no effect on PKC activity when incubated with a rat brain-derived PKC preparation of known activity. By contrast, RAP plus FKBP12 significantly inhibits PKC activity. RAP plus FKBP12 inhibits the PKCalpha and not the -beta subtype. The results demonstrate inhibition of PKC activity by RAP and not FK506 through its binding to FKBP12. The inhibition of PKC activity by RAP stimulates sodium transport in A6. The results therefore imply the existence of an endogenous RAP-like ligand which when bound to FKBP12 could regulate Na+ channel activity through this mechanism.
Animals↗
Kidney transplant recipients who die with functioning grafts: serum creatinine level and cause of death.
How to analyze death with function (DWF) in transplant survival statistics has become an important issue. DWF is a predominant cause of late graft loss. We recognize that some deaths may be related to the transplant. However, considering DWF as a graft loss may obscure some analyses. An additional consideration is whether patients who "die with function" actually had good kidney function or whether their death was related to or hastened by impaired function. To answer this question, we studied the serum creatinine level and cause of death for kidney recipients who died with function. Between January 1, 1985, and December 31, 1994, we did 1932 kidney transplants for 1806 recipients. Of these, 220 died with function. For the 220, we assessed the time posttransplant that death occurred, the serum creatinine level before the terminal event, and the cause of death. The most common causes of death were infection (22%), myocardial infarction (17%), and sudden death (15%). Mean serum creatinine levels were less than 2 mg/100 ml at 1 year before and at the time of death for the vast majority of these recipients. Our findings demonstrate that kidney recipients who die with function have good renal function--additional support for presenting graft survival data both with and without death censored.
Cause of Death↗