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Biomedical subjects

P E Cole

Publications and source records attributed to P E Cole.

At least 19 recordsLinked to original sources
PubMed1999

Intravascular brachytherapy physics: report of the AAPM Radiation Therapy Committee Task Group no. 60. American Association of Physicists in Medicine.

Recent preclinical and clinical studies indicate that irradiation using ionizing radiation in the dose range of 15 to 30 Gy may reduce the occurrence of restenosis in patients who have undergone an angioplasty. Several delivery systems of intravascular brachytherapy have been developed to deliver radiation doses in this range with minimal normal tissue toxicity. In late 1995 the American Association of Physicists in Medicine (AAPM) formed a task group to investigate these issues and to report the current state of the art of intravascular brachytherapy physics. The report of this task group is presented here.

Angioplasty, Balloon, Coronary↗
PubMed1997

Transjugular intrahepatic portosystemic shunts compared with endoscopic sclerotherapy for the prevention of recurrent variceal hemorrhage. A randomized, controlled trial.

BACKGROUND: Transjugular intrahepatic portosystemic shunts (TIPS) have widened the use of portal decompression as therapy for variceal hemorrhage. However, no controlled studies have examined the efficacy of TIPS compared with that of other treatments. OBJECTIVE: To compare the efficacy and safety of TIPS with those of endoscopic sclerotherapy for the prevention of recurrent variceal hemorrhage. DESIGN: Randomized, controlled trial. SETTING: Tertiary-care academic medical center. PATIENTS: 100 patients with cirrhosis were evaluated a mean of approximately 10 days after an episode of acute variceal bleeding; 20 patients were excluded because of portal venous thrombosis (n = 6), hepatoma (n = 3), florid alcoholic hepatitis (n = 6), and refusal to give consent (n = 5). INTERVENTIONS: TIPS (n = 41) or sclerotherapy (n = 39). The latter was performed by freehand injections of 5% Na morrhuate at 2- to 3-week intervals. Recurrent variceal hemorrhage was managed by sclerotherapy followed by angiographic assessment of TIPS and dilatation of the stents (TIPS group) or crossover to TIPS (sclerotherapy group). MEASUREMENTS: Rebleeding and survival were the primary end points. Complications and rates of rehospitalization were secondary end points. RESULTS: During a mean follow-up of approximately 1000 days, recurrent gastrointestinal bleeding resulted from variceal hemorrhage (9 patients in the TIPS group and 8 in the sclerotherapy group), portal gastropathy (1 patient in each group), and gastric lipoma (0 and 1 patients, respectively). A higher mortality rate was seen with TIPS (P = 0.03). Death resulted from variceal bleeding (5 patients in the TIPS group and 3 in the sclerotherapy group), sepsis (3 and 2 patients, respectively), liver failure (2 patients in each group), hepatoma (1 and 0 patients, respectively), and hemoperitoneum (1 and 0 patients, respectively). Encephalopathy was the most common complication in the TIPS group (n = 12), and pain developing after sclerotherapy was the most common in the sclerotherapy group (n = 10). The two groups had similar rates of rehospitalization. CONCLUSIONS: Endoscopic sclerotherapy and TIPS are equivalent with respect to rebleeding developing over the long term. However, sclerotherapy may be superior to TIPS with respect to survival.

Adult↗
PubMed1997

Hepatocyte transplantation as a bridge to orthotopic liver transplantation in terminal liver failure.

The limited donor organ supply has led to several bridging techniques to sustain patients with acute and subacute liver failure. We report here the prospective, controlled trial of transplanted isolated fresh and cryopreserved human hepatocytes as a bridge to orthotopic liver transplantation. Five hepatocyte transplant recipients with grade IV encephalopathy and multisystem organ failure and four patients of equal illness severity due to liver failure were studied. Medical therapy resulted in a significant (P<0.05), but not normal, fall in blood ammonia, and a significant (P<0.02) resolving biochemical marker of liver injury that did not improve cardiovascular or cerebral stability; this lead to death within 3 days in all control patients. The five hepatocyte-treated patients maintained normal cerebral perfusion and cardiac stability, with withdrawal of medical support for 2 to 10 days before orthotopic liver transplantation. Biochemical evidence of liver injury improved significantly (P=0.004) and blood ammonia levels decreased significantly (P=0.0005) to normal levels in the hepatocyte-treated patients. Three of five patients who successfully bridged to whole liver allograft transplant are alive, home, and normal with more than 20 months of follow-up. No infections or embolic or pulmonary complications resulted from intra-arterial splenic hepatocyte infusion. Specific antiprotease production in a patients with genetically deficient alpha-1-antitrypsin disease, and immunohistochemical and electron microscopic evidence of splenic "hepatization" are presented as evidence of the viability of hepatocyte splenic seeding. In conclusion, splenic transplantation of differentiated adult hepatocytes can control hyper-ammonemia, correct genetic defects in liver function, and bridge life to orthotopic liver transplantation in human liver failure.

Adult↗
PubMed1997

The natural history of portal hypertension after transjugular intrahepatic portosystemic shunts.

BACKGROUND & AIMS: The effects of transjugular intrahepatic portosystemic shunt (TIPS) on portal hemodynamics, esophageal and gastric varices, and hepatic function have not been fully defined. The aim of this study was to define prospectively the effects of TIPS on portal pressures and flow, variceal resolution, and hepatic function. METHODS: Pressure and flow measurements were made by angiography and Doppler sonography, respectively. Varices were assessed by endoscopy and angiography. Liver functions were evaluated by a battery of tests. RESULTS: In 100 consecutive subjects, mean portosystemic gradient decreased from 24 to 11 mm Hg (means) (P < 0.001) after TIPS. Recurrent portal hypertension caused by stent thrombosis (n = 5), stent retraction (n = 2), and stent stenosis (n = 51) occurred at 6 months but, by year 5, was not present in survivors (n = 0 of 8). Fundic gastric varices failed to resolve in 6 of 12 cases. Systemic venous pressures of >15 mm Hg, stent dysfunction, and continued alcoholism were risk factors for recurrent hemorrhage. Angiography was superior to endoscopy, which was superior to Doppler sonography for detection of recurrent portal hypertension. Progressive liver failure occurred in 8 patients. CONCLUSIONS: Recurrent portal hypertension caused by stent stenosis occurs commonly in the first 2 years after TIPS. Fundic gastric varices often fail to disappear after TIPS. The effects of TIPS on liver function are unpredictable.

Adult↗
PubMed1996

Transjugular intrahepatic portosystemic shunts for patients with active variceal hemorrhage unresponsive to sclerotherapy.

BACKGROUND & AIMS: Despite urgent sclerotherapy, active variceal hemorrhage has a 70%-90% mortality rate in patients with advanced age, sepsis, renal or pulmonary compromise, tense ascites, or deep coma. The aim of this study was to test the safety and efficacy of transjugular intrahepatic portosystemic shunt (TIPS) performed semiemergently and preceded by stabilization by balloon tamponade in such patients. METHODS: Patients with actively bleeding esophageal or contiguous gastric varices despite sclerotherapy were assessed for risk of dying after emergent portacaval shunt. Those considered to be at high risk were stabilized by balloon tamponade and vasopressin/nitroglycerin and TIPS placed semiurgently within 12 hours. Balloon tamponade and pharmacological therapy were discontinued within 24 hours after TIPS in all cases. RESULTS: Thirty-two patients met entry criteria, and 2 were excluded due to portal vein thrombosis. TIPS was successfully placed in 29 of 30 patients and achieved hemostasis in all. Thirty-day and 6-week survival rates were 63% and 60%, respectively; in those without aspiration, the 6-week survival rate was 90%. After a median follow-up period of 920 days, 46% of the original cohort was alive. Only 2 episodes of early rebleeding and 4 late rebleeds occurred. Eight patients developed encephalopathy. Stent stenosis requiring dilation occurred in 6 of 11 patients within 6 months. CONCLUSIONS: TIPS is highly effective as salvage therapy in high-risk patients with active variceal hemorrhage despite endoscopic sclerotherapy.

Adult↗
PubMed1993

Complications of transjugular intrahepatic portosystemic shunt: a comprehensive review.

It is generally accepted that the transjugular intrahepatic portosystemic shunt (TIPS) procedure has lower morbidity and mortality rates than those of surgical shunting. Nevertheless, complications occur. The authors have reviewed their experience and that of other institutions in compiling an extensive list of complications. Complications are categorized according to those related to transhepatic needle puncture, transvenous access to the portal vein, portal venous cannulation, the stent, the puncture site, portosystemic shunting, and contrast material. Excluding hepatic encephalopathy and delayed stenosis or occlusion of the shunt, an overall complication rate of less than 10% can be expected for TIPS. The prevalence of aggravated or new cases of encephalopathy is 5%-35%, and over the long term, up to 75% of shunts may undergo stenosis or occlusion. The direct procedural mortality rate is less than 2%, and the 30-day mortality rate ranges from 4% to 45%, depending on several factors. The role to which TIPS is relegated will be influenced by the long-term success rate in the prevention of recurrent variceal hemorrhage.

Catheterization, Peripheral↗
PubMed1983

The activity of discrete fragments of ribosomal protein S1 in Q beta replicase function.

As a subunit of bacteriophage Q beta replicase, ribosomal protein S1 is required for tight binding of the enzyme to Q beta RNA and for the initiation of Q beta RNA transcription. To compare these properties of S1 with its functions in protein synthesis, we have reconstituted altered replicase enzymes by adding discrete fragments of S1 to Q beta replicase lacking S1 (R(-S1]. We show that the NH2-terminal region of S1 is required for S1 subunit interactions in replicase since a trypsin-resistant fragment (denoted S1-F1) lacking the NH2-terminal 31% of S1 is functionally inactive and does not seem to bind to R(-S1). Previous studies with S1-F1 indicated that this NH2-terminal region is required for S1 to bind to the ribosome. Our results also show that the COOH-terminal region of S1 is dispensable for S1's function in replicase because a mutant of S1 (m1-S1) lacking 21% of the COOH-terminal portion of the chain is as active as wild type S1 in replicase and binds to R(-S1) with comparable affinity. In protein synthesis, the mutant m1-S1 is known to substitute for S1 but is only about 75% as efficient as wild type S1.

Escherichia coli↗
PubMed1983

pH dependence of the reduction-oxidation reaction of azurin with cytochrome c-551: role of histidine-35 of azurin in electron transfer.

A fluorescence quenching experiment confirms that in the redox reaction between cytochrome c-551 and azurin, protein complexing is negligible. Azurin-pH indicator T-jump experiments show that Pseudomonas aeruginosa (Ps.) azurin exhibits a slow time constant, tau, in its return to pH equilibrium but Alcaligenes faecalis (Alc.) azurin does not. The decrease of l/tau with increasing pH shows that the rate-determining process is a slow transformation of the imidazolium form of histidine-35 from a conformation where it cannot ionize to one in which it can. The fast relaxation time constant of the redox reaction varies little with pH, but the slow time constant increased by a factor of approximately 2.5 increasing pH between pH 5 and pH 8. The corresponding amplitudes, especially the slow one, vary with pH. On the basis of all the present evidence it is concluded that, while some differences of redox reactivity do occur on protonation, these differences are not major. In general, the two proteins cyt c-551 and azurin react with each other with rates only weakly dependent upon pH. A classical pH titration was carried out on the reduced and oxidized form of Ps. and Alc. azurin with the result that two protons were released between pH 6 and pH 8, in the former from His-35 and -83 and in the latter from His-83 and Ala-1.

Azurin↗
PubMed1983

Melting order of successively longer yeast phenylalanine-accepting transfer ribonucleic acid fragments with a common 5' end.

Temperature-jump methods were used to study the kinetics of the helix to coil transition in three fragments of yeast tRNAPhe that share a common 5' terminus (the 5' end of the mature tRNA). Correlation of the extrapolated helix dissociation time constants with NMR exchange broadening results allows assignment of the structural basis of the optical melting transition in the fragments. The results confirm nuclear magnetic resonance findings on these fragments: the 5' 1/4 fragment has no helical structure; the 5' 1/2 fragment contains the D stem; and the 5' 3/5 fragment contains the D stem and the anticodon stem. These are the structures expected if sequential folding of the tRNA during biosynthesis were to occur. The D stem is the last helix to melt in the 5' 3/5 fragment. We suggest that structural elements in addition to the four Watson-Crick base pairs of the D-stem helix are responsible for the anomalously high Tm of that hairpin.

Kinetics↗
PubMed1982

Q beta replicase containing altered forms of ribosomal protein S1.

Transcription of Q beta RNA replicase requires that the host-encoded Escherichia coli ribosomal protein S1 be present as a subunit of the replicase. To determine whether the activities of S1 in protein synthesis are operational in Q beta RNA transcription, we formed altered replicase enzymes by reconstituting replicase lacking S1 (R(-S1)) with modified S1 species whose properties in nucleic acid binding and protein synthesis had been previously established. S1 derivatized with N-ethylmaleimide reconstitutes a modified replicase that is 81% as active as replicase reconstituted with unmodified S1. S1 derivatized with N-ethylmaleimide and unmodified S1 bind with comparable affinity to R(-S1) (1 X 10(8) M-1). These results indicate that the helix-unwinding properties of S1, which are known to be inactivated by N-ethylmaleimide modification, are not required for Q beta RNA transcription and that the sulfhydryl-derivatized region of S1 is not utilized in replicase subunit contacts. In contrast with its established ability to replace E. coli S1 on the ribosome, Caulobacter crescentus S1 does not reconstitute Q beta RNA transcription activity when added to R(-S1). Our results suggest this inactivity may be due to poor binding to R(-S1).

Coliphages↗
PubMed1982

Problems of sampling and inference in the study of fluctuating dental asymmetry.

Randomly distributed or "fluctuating" dental asymmetry has been accorded evolutionary meaning and interpreted as a result of environmental stress. However, except for congenital malformation syndromes, the determinants of human crown size asymmetry are still equivocal. Both a computer simulated sampling experiment using a combined sample size of N = 3000, and the requirements of adequate statistical power show that sample sizes of several hundred are needed to detect population differences in dental asymmetry. Using the largest available sample of children with defined prenatal stresses, we are unable to find systematic increases in crown size asymmetry. Given sampling limitations and the current inability to link increased human dental asymmetry to defined prenatal stresses, we suggest that fluctuating dental asymmetry is not yet established as a useful and reliable measure of general stress in human populations.

Body Height↗
PubMed1981

Transfer RNA cross-linked to the elongation factor Tu subunit of Q beta replicase does not inhibit Q beta RNA replication.

One of the four subunits of bacteriophage Q beta RNA replicase is elongation factor Tu (EF-Tu), the host aminoacyl-tRNA (AA-tRNA) binding protein. To determine whether the RNA polymerase activity requires the tRNA binding site of EF-Tu, we reconstituted replicase with EF-Tu . GTP covalently bound to AA-tRNA. This cross-linked ternary complex (XLTC) was formed by the reaction of N epsilon-bromoacetyl-Lys-tRNA with EF-Tu-GTP. In an EF-Tu-dependent system for the reconstitution of replicase, XLTC restored polymerase activity at least as well as an equivalent amount of EF-Tu. Replicase reconstituted with XLTC was resolved from replicase containing EF-Tu by chromatography on phosphocellulose, a result which confirmed that the tRNA moiety was incorporated into the enzyme. Chromatographic analysis of reconstitution mixtures revealed that XLTC was incorporated into replicase as extensively as EF-Tu. From these results, it appears that the AA-tRNA binding site on EF-Tu is not required for the assembly or activity of Q beta RNA replicase. Furthermore, because the tRNA macromolecule is cross-linked to His-66 of the EF-Tu, the region surrounding His-66 must normally be exposed on the surface of the replicase.

Bacterial Proteins↗
PubMed1980

Modification of cytidines in a Q beta replicase template: analysis of conformation and localization of lethal nucleotide substitutions.

The solution conformation of MDV-1( + ) RNA, a small RNA template replicated autocatalytically in vitro by Q beta replicase, was investigated with sodium bisulfite, a reagent that selectively converts single-stranded cytidines to uridines. The reactivity of 45 of the 76 cytidines in MDV-1( + ) RNA was determined by nucleotide sequence analysis. Only 14 of these 45 cytidines were converted to uridine. Treatment of the RNA with methoxyamine, another single-strand-specific cytidine modification reagent, gave results in good agreement with the bisulfite data. The limited reactivity of MDV-1 ( + ) RNA with these reagents indicates that it is a highly structured molecule. A secondary structure consistent with the chemical modification data is proposed. Modification of MDV-1 ( + ) RNA by bisulfite renders it inactive as a template for RNA replication. This inactivation and the modification of the cytidines at the 3' end of the molecule occur at very similar rates. By using a short complementary RNA "mask" to protect just these cytidines, we demonstrated that the loss of activity resulted from their modification. This implies that one or more of the cytidines in the 3'-terminal sequence is required for template activity and that changes within this sequence can have lethal consequences. The effects of modification elsewhere in the sequence are discussed.

Base Sequence↗