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At least 523 records · Page 29Linked to original sources

Focused parathyroid surgery with intraoperative parathyroid hormone measurement as a day-case procedure.

BACKGROUND: This study assessed the feasibility, efficacy and safety of focused parathyroidectomy combined with intraoperative parathyroid hormone (IOPTH) measurement in a day-case setting. METHODS: Over 28 months 50 consecutive patients (mean age 63 (range 33-92) years) with clear evidence of unifocal disease on sestamibi scanning or ultrasonography underwent unilateral neck exploration via a small lateral incision. Blood samples for measurement of IOPTH were taken at induction of anaesthesia, before adenoma excision and after adenoma excision (at 5, 10 and 20 min). Ten patients were discharged within 23 h and 40 patients on the day of surgery. RESULTS: A solitary adenoma was identified in all but one patient, with a mean operating time of 30 (range 16-57) min. After parathyroidectomy, IOPTH levels fell appropriately except in one patient with multiglandular hyperplasia. No patient developed symptomatic hypocalcaemia during the 2 weeks after operation, enabling cessation of oral supplements. All patients remained normocalcaemic on follow-up (mean 26 (range 8-84) weeks) and histological examination confirmed parathyroid adenoma (48 patients), hyperplasia (one) or carcinoma (one). CONCLUSION: After accurate preoperative localization of uniglandular disease, patients with primary hyperparathyroidism may be managed successfully and safely by focused parathyroidectomy with IOPTH measurement as a day-case procedure.

Adenoma↗

Photoinduced electron transfer in alpha-cyclodextrin-based supramolecular dyads: a free-energy-dependence study.

Photoinduced electron transfer (PET) between alpha-cyclodextrin-appended pyrene (PYCD) and a few acceptor molecules was studied in aqueous solutions. The pyrene moiety in PYCD is located above the narrower rim of the alpha-CD and is fully exposed to water. The acceptors are monocyclic organic molecules and, upon dissolution in water in the presence of PYCD, a fraction of the donor-acceptor systems is present as supramolecular dyads and the remaining fraction as free molecules. Free-energy-dependence studies showed that electron transfer in the supramolecular dyads follows the Marcus equation. The donor-acceptor coupling and the reorganization energy were determined from fits of the data to the Marcus equation. The electronic coupling was found to be similar to those reported for hydrogen-bonded systems. It appears that the actual lambdaout values are somewhat lower than values calculated with the continuum model. The experimental design has also allowed, for the first time, a visual demonstration of the inverted region on the basis of the raw fluorescence lifetime data.

Journal Article↗

The prediction of risk of recurrence and time to recurrence of hepatocellular carcinoma after orthotopic liver transplantation: a pilot study.

Orthotopic liver transplantation (OLTx) in the presence of hepatocellular carcinoma (HCC) has been complicated by high recurrence rates. The ability to determine the risk and timing of HCC recurrence on an individual basis would greatly aid in the candidate selection process resulting in a more efficient use of donated organs and allow the individualization and better evaluation of adjuvant chemotherapy. The 214 patients who underwent OLTx in the presence of HCC were analyzed. From the 178 patients who survived more than 150 days, 71 (40%) have suffered HCC recurrence. Based on five risk factors, that is, gender, tumor number, lobar tumor distribution, tumor size, grade of vascular invasion, artificial neural network models predicting the likelihood of HCC recurrence within 1, 2, and 3 consecutive years after transplantation were developed. Based on model predictions, those combinations of risk factors that should/should not lead to recurrence were generated, allowing stratification of patients into the following three groups: 1) patients who should not suffer HCC recurrence and who should not need adjuvant therapy, 2) patients who will suffer recurrence and for whom postoperative chemotherapy significantly prolonged survival (but did not prevent recurrence), and 3) patients who may or may not suffer HCC recurrence and whose recurrence may be prevented by adjuvant chemotherapy. The outcome of OLTx for patients with HCC can be prognosticated based on a number of clinical variables. If verified through multicenter trials, these models could be made available to transplantation programs performing OLTx in the presence of HCC.

Adolescent↗

Human papillomaviruses in 91 oral cancers from Indian betel quid chewers--high prevalence and multiplicity of infections.

India has one of the world's highest incidences of oral cancer. The habit of chewing betel quid is widespread and is suspected to play a role in the etiology of this disease. Studies in many other countries have also pointed to a role for human papilloma-viruses (HPVs) in the etiology of some oral cancers. In this study we analyzed biopsies from 91 Indian oral cancer patients, most of whom were betel quid chewers, by PCR amplification and direct DNA sequencing. HPV DNA was detected in 74% of these lesions, of which 41% had multiple HPV infections. Among the lesions from different oral sites, lesions of the tongue had the highest rate (9 of 11) of HPV infection. These HPV prevalences are among the highest ever reported in oral cancers. As to individual HPV types, prevalences of HPV-6, HPV-11, HPV-16 and HPV-18 were 13%, 20%, 42% and 47%, respectively. No additional known or novel HPV types were detected. To understand the unexpectedly high prevalences of the "low-risk" types HPV-6 and HPV-11, we compared the subtypes and variants that were found in oral cancers against those from benign genital warts from the same patient population but found no differences. The high prevalence of HPV in the oral cancers of these Indian patients suggests that viral infection is an important etiological component, with betel quid probably causing additional mutagenic steps in the carcinogenic process.

Areca↗

Structural analysis of the murine IgG3 constant region gene.

We have determined the complete sequence of the gamma 3 heavy chain constant (C gamma 3) region gene of the BALB/c mouse including the 5'-flanking region up to the switch site and the 3'-flanking region past the end of the membrane exons. The C gamma 3 coding region, typical of other IgGs, is divided into six exons corresponding to the protein domains (C gamma (3)1, hinge, C gamma (3)2, and C gamma (3)3) and to the membrane carboxyl terminus (M1 and M2). The predicted amino acid sequence of the gamma 3 chain has three potential N-linked carbohydrate addition sites (including one in the membrane spacer segment), as compared with a single occurrence in the other mouse IgGs. Between the switch recombination region and the body of the C gamma 3 gene, there is a remarkable homology with a sequence between C mu and C delta which provides a rationale for an alternative, T cell-independent class-switch mechanism. We have used a computer to analyze the secondary structure of the gamma 3 mRNA precursor for the membrane form. We predict that this RNA precursor (approximately 12 000 bp) folds into four leaf-like domains which correspond to the variable region, the large IVS, the body of the constant region, and the membrane exons. This organization may have a role to play in the function of the mRNA precursor.

Amino Acid Sequence↗

Development of a recombinant human collagen-type III based hemostat.

Animal-tissue-derived collagen, containing mostly type I collagen with a minor amount of type III collagen, has been widely used in the production of hemostats for many decades, although it has been known for a long time that type III collagen is more likely to induce platelet aggregation in vitro. Because it is hard to purify type III from animal tissue, it has not been possible to correlate this finding with in vivo data. In this report, it is demonstrated that recombinant human collagen III fibrils are more capable of inducing platelet aggregation in vitro than those comprised of bovine collagen I, in agreement with previously published data on tissue-derived type III collagen. When formed into three-dimensional matrices, the use of type III collagen results in formulations with better mechanical integrity, larger surface area, and higher hemostatic activity in a rabbit spleen injury model as compared with commercially available hemostats formed from bovine type I collagen.

Animals↗

In vitro-in vivo correlation (IVIVC) models for metformin after administration of modified-release (MR) oral dosage forms to healthy human volunteers.

The objective of the current study was to develop and evaluate the internal predictability for level C and A in vitro-in vivo correlation (IVIVC) models for prototype modified-release (MR) dosage forms of metformin. In vitro dissolution data for metformin were collected for 22 h using a USP II (paddle) method. In vivo plasma concentration data were obtained from 8 healthy volunteers after administration of immediate-release (IR) and MR dosage forms of metformin. Linear level C IVIVC models were developed using dissolution data at 2.0 and 4.0 h and in vitro mean dissolution time (MDT). A deconvolution-based level A model was attempted through a correlation of percent in vivo input obtained through deconvolution and percent in vitro dissolution obtained experimentally. Further, basic and extended convolution level A IVIVC models were attempted for metformin. Internal predictability for the IVIVC models was assessed by comparing observed and predicted values for C(max) and AUC(INF). The results suggest that highly predictive level C models with prediction errors (%PE) of <5% could be developed. Mean percent in vivo input for metformin was incomplete from all formulations and did not exceed 35% of dose. The deconvolution-based level A models for all MR formulations were curvilinear. However, a unique IVIVC model applicable to all MR formulations could not be developed using the deconvolution approach. The basic convolution level A model, which used in vitro dissolution as the in vivo input, had %PE values as high as 103%. Using an extended convolution approach, which modeled the absorption of metformin using a Hill function, a level A IVIVC model with %PE as low as 11% was developed. In conclusion, the current work indicates that level C and A IVIVC models with good internal predictability may be developed for a permeability- and absorption window-limited drug such as metformin.

Administration, Oral↗

Liver transplantation for hepatocellular carcinoma: the MELD impact.

The new allocation policy of the United Network of Organ Sharing (UNOS) based on the model for end-stage liver disease (MELD) gives candidates with stage T1 or stage T2 hepatocellular carcinoma (HCC) a priority MELD score beyond their degree of hepatic decompensation. The aim of this study was to determine the impact of the new allocation policy on HCC candidates before and after the institution of MELD. The UNOS database was reviewed for all HCC candidates listed between July 1999 and July 2002. The candidates were grouped by two time periods, based on the date of implementation of new allocation policy of February 27, 2002. Pre-MELD candidates were listed for deceased donor liver transplantation (DDLT) before February 27,2002, and post-MELD candidates were listed after February 27, 2002. Candidates were compared by incidence of DDLT, time to DDLT, and dropout rate from the waiting list because of clinical deterioration or death, and survival while waiting and after DDLT. Incidence rates calculated for pre-MELD and post-MELD periods were expressed in person years. During the study, 2,074 HCC candidates were listed for DDLT in the UNOS database. The DDLT incidence rate was 0.439 transplant/person years pre-MELD and 1.454 transplant/person years post-MELD (P < 0.001). The time to DDLT was 2.28 years pre-MELD and 0.69 years post-MELD (P < 0.001). The 5-month dropout rate was 16.5% pre-MELD and 8.5% post-MELD (P < 0.001). The 5-month waiting-list survival was 90.3% pre-MELD and 95.7% post-MELD (P < 0.001). The 5-month survival after DDLT was similar for both time periods. The new allocation policy has led to an increased incidence rate of DDLT in HCC candidates. Furthermore, the 5-month dropout rate has decreased significantly. In addition, 5-month survival while waiting has increased in the post-MELD period. Thus, the new MELD-based allocation policy has benefited HCC candidates.

Carcinoma, Hepatocellular↗

Hepatopulmonary syndrome after living donor liver transplantation and deceased donor liver transplantation: a single-center experience.

Hepatopulmonary syndrome (HPS) is a progressive, debilitating complication of end-stage liver disease. In contrast to the well-established reversal of HPS after deceased donor liver transplantation (DDLT), little has been written about the natural course of HPS after the newer procedure of living donor liver transplantation (LDLT). We describe HPS in a small series of 4 liver transplant recipients (2 DDLT; 2 LDLT) at a single center. Before transplantation, these 4 patients had a mean shunt fraction of 23.6 +/- 14.3% and a mean PaO2 of 58.5 +/- 11.3 mm Hg. All 4 patients used supplemental oxygen before transplantation. Sixteen weeks after transplantation, all 4 patients had normalized or improved shunt fraction and PaO2. These patients regained normal pulmonary function within a few months, despite the period of hepatic regeneration after LDLT. In conclusion, both DDLT and LDLT are associated with rapid and dramatic reversal of HPS.

Adult↗

Liver transplant in a patient with a ventriculoperitoneal shunt.

There are no published accounts of patients with ventriculoperitoneal shunts undergoing liver transplantation in the literature. Because patients with ventriculoperitoneal shunts are prone to infections, this may be a theoretical contraindication to transplantation. We present a case of a patient with cirrhosis who had a ventriculoperitoneal shunt placed many years prior to transplantation. The patient had no neurological complications and the shunt was intact and functioning. Prior to transplantation, the patient underwent a ventriculoperitoneal to ventriculopleural shunt conversion that was reversed posttransplantation. Apart from some minor complications, the patient has done remarkably well from a graft and neurological perspective. In conclusion, patients who have ventriculoperitoneal shunts may be considered for liver transplantation as the risk of infectious and neurological complications is low and there are no deleterious effects on graft survival.

Adult↗

Hepatic B-cell non-Hodgkin's lymphoma of MALT type in the liver explant of a patient with chronic hepatitis C infection.

B-cell non-Hodgkin's lymphoma (B-NHL) is a well-documented complication of hepatitis C virus (HCV) infection. Marginal zone (mucosa-associated lymphoid tissue; MALT) lymphomas constitute a less common type of B-NHL. In this article, we report a case of liver MALT in a cirrhotic patient, incidentally discovered after liver transplantation (LT). We discuss pertinent diagnostic and management strategies in this clinical setting.

Hepatitis C, Chronic↗

Living donor liver transplantation for hepatitis C-related cirrhosis: no difference in histological recurrence when compared to deceased donor liver transplantation recipients.

The question of possible earlier and more aggressive recurrence of hepatitis C virus (HCV) infection after living donor liver transplantation (LDLT) compared to deceased donor liver transplantation (DDLT) remains unanswered. To address this issue we retrospectively reviewed virological, histological, and clinical data in 67 patients (52 DDLT and 15 LDLT) who underwent liver transplant for their HCV-related cirrhosis since April 2001. Our data indicate that there is no statistical difference between LDLT and DDLT groups in mean age, Child-Turcotte-Pugh score, model for end-stage liver disease score, and gender distribution. The mean follow-up was 749 +/- 371 days in LDLT and 692 +/- 347 days in DDLT. The predominant genotype in the LDLT and DDLT are genotype 1 (LDLT, 91%; DDLT, 70%). All patients with histologically confirmed recurrent HCV had detectable HCV-RNA in serum. The histological recurrence rate of hepatitis C was 58% at 4 months, 90% at 1 year, and 100% at 2 years in LDLT patients vs. 71% at 4 months, 94% at 1 year, and 95% at 2 years in DDLT patients (not significant) Comparison of the activity of inflammation and fibrosis score at all time points failed to show a statistical difference. Kaplan-Meier survival analysis showed similar patient and graft survival rates between the 2 groups. Our data indicate that histological recurrence of HCV is an early event and virtually universal 2 years' posttransplantation, regardless of modality of donor procurement.

Adult↗

Recurrence of autoimmune liver disease after liver transplantation: a systematic review.

Recurrence of autoimmune liver disease in allografts has long been a topic of debate. We conducted a systematic review of the literature to examine the reported incidence of recurrence after liver transplantation of primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), and autoimmune hepatitis (AIH). The MEDLINE, EMBASE, and Cochrane electronic databases were used to identify articles. The inclusion criteria used were articles on patients with at least 90 days of posttransplantation follow-up, histologic criteria for diagnosis of PBC and AIH recurrence, radiologic or histologic criteria or both for diagnosis of PSC recurrence, and exclusion of other causes of liver disease causing similar histologic findings. Incidence in individual studies was combined to calculate the overall recurrence. Risk factors were analyzed whenever crude data were available. Funnel plots were used to assess publication bias. Out of 90 articles identified, 43 met criteria for systematic review (PBC, 16; PSC, 14; AIH, 13). The calculated weighted recurrence rate was 18% for PBC, 11% for PSC, and 22% for AIH. No difference was found in PBC and AIH recurrence by type of primary immunosuppression. There were not enough data to assess this issue in PSC studies. There was evidence of publication bias among PSC and AIH studies but not among PBC studies. In conclusion, recurrence of autoimmune liver disease after liver transplantation appears to be a real concern. As these patients are followed long-term, recurrence of disease may become the primary cause of morbidity.

Autoimmune Diseases↗

A conditional suicide system for Saccharomyces cerevisiae relying on the intracellular production of the Serratia marcescens nuclease.

A conditional lethal system for biological containment of genetically modified strains of Saccharomyces cerevisiae is described. This suicide system is based on the intracellular production of the Serratia marcescens nuclease in the yeast cell, aiming at the destruction of the host genetic material. The S. marcescens nuclease, encoded by the nucA gene, is normally secreted by the bacterium into the medium. In the present work, the nucA gene, devoid of its signal peptide coding sequence, was cloned in a yeast expression vector, under control of the glucose-repressed S. cerevisiae alcohol dehydrogenase 2 gene (ADH2) promoter. When transformed into S. cerevisiae, the recombinant plasmid proved to be effective in killing the host cells upon glucose depletion from the medium, and the nuclease activity was found in lysates prepared from the transformants. In addition, the nuclease degrading effect was shown to reach chromosomal DNA in the yeast host. The killing effect of the nucA plasmid was also demonstrated in soil microcosm assays, indicating that whenever the GMM escapes into the environment where glucose is scarce, the nucA gene will be expressed and the resulting nuclease will destroy the genetic material and kill the cells. In contrast to other suicide systems that target the cell envelope, the advantage of the one described here is that it disfavours horizontal gene transfer from recombinant yeast cells to other microorganisms found in the environment.

Blotting, Western↗

Effect of sentence length on the production of linguistic stress by left- and right-hemisphere-damaged patients.

An acoustical/perceptual study of phonemic stress (e.g., HOTdog vs. hot DOG) was conducted to evaluate the effect of sentence length on stress production after brain damage. Productions of phonemic stress pairs were elicited in sentence contexts of increasing length from eight left-hemisphere-damaged nonfluent (LHD-NFL), fluent LHD-FL), right-hemisphere-damaged (RHD), and normal speakers (n = 32). Tape recordings of subjects' productions were presented to naïve listeners for perceptual identification of stress placement. Acoustic analysis focused on fundamental frequency, duration, and intensity of the initial and final syllables as well as pause duration between syllables. Perceptual tests indicated that regardless of sentence length, all brain-damaged groups exhibited an impairment in the production of linguistic stress when compared to normals. The LHD-NFL group experienced the greatest difficulty in signaling stress contrasts, followed in order by the LHD-FL and RHD groups. In medium-length sentences, the LHD-FL group's performance was degraded by comparison to short-length sentences. Acoustic analysis showed that pause duration was the strongest predictor of phonemic stress for all groups. Acoustic profiles of the RHD group were similar qualitatively to those of normals, but differed quantitatively in terms of magnitude of effect associated with shifts in stress patterns. Findings are brought to bear on the nature of the stress production deficit after unilateral brain damage, the role of the right hemisphere in linguistic prosody, and the concept of "subtle phonetic deficit" in fluent aphasia.

Acoustics↗