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N Habib

Publications and source records attributed to N Habib.

At least 37 records · Page 2Linked to original sources
PubMed1999

Mutational analysis of the hydrolytic activity of yeast RNA polymerase III.

For 25 mutant alleles of ret1, encoding the second largest subunit of yeast RNA polymerase III, we have studied the polymerase III nuclease activity, measuring both the total yield and dinucleotide product composition. Mutations affecting amino acids 309-325 gave slightly elevated nuclease activity. In region 367-376, two mutations gave 12-15-fold increased nuclease activity. Our results do not support the catalytic role in nuclease activity proposed for the conserved DDRD motif in this region (Shirai, T., and Go, M. (1991) Proc. Natl. Acad. Sci. U. S. A. 88, 9056-9060). Mutations centered on a basic region from amino acids 480 to 490, which aligns with Escherichia coli beta-subunit sequences between Rif(r) clusters I and II, produce changes in the relative yields of A- and G-containing dinucleotides. Four such mutant polymerases pause during elongation at GPy sequences and, in addition, have a reduced frequency of termination at T(5) terminator sequences. We propose that the side chains of these mutationally altered amino acids are in direct contact with bases in the RNA-DNA hybrid very near the growing 3'-end. Two mutations in domain I near the C terminus produced very large increases in exonuclease activity and strongly increased termination, suggesting that this region also contacts the nascent RNA in the hybrid region.

Amino Acid Sequence↗
PubMed1999

Total vascular exclusion for liver resections: pros and cons.

Dramatic improvements in morbidity and mortality rates following liver resections have been reported in the past decade. Consequently, the indications for hepatectomy are becoming more liberal. Many techniques of liver resection with or without vascular clamping have been reported with excellent clinical results. Total vascular exclusion (TVE) of the liver during parenchymal transection has been advocated susceptible to increase the resectability of tumors that might not be safely approached by other techniques. Cirrhotic livers are probably more vulnerable to ischemic injury related to TVE than normal livers. The indications and technical and metabolic aspects of the technique are reviewed.

Constriction↗
PubMed1999

The effect of mechanically enhancing portal venous inflow on hepatic oxygenation, microcirculation, and function in a rabbit model with extensive hepatic fibrosis.

Enhancing the portal venous blood flow (PVBF) has been shown to reduce portal pressure and intrahepatic vascular resistance and to improve liver function in isolated cirrhotic rodent livers in vitro. The aim of this study was to assess the short-term effect of mechanically pumping the portal inflow on hepatic microcirculation (HM), oxygenation, and function in an animal model of extensive hepatic fibrosis. New Zealand white rabbits underwent laparotomy and exposure of the liver: group 1 (n = 7) were normal controls; group 2 (n = 7) had hepatic fibrosis. Total hepatic blood flow (THBF) and HM was measured along with continuous monitoring of intrahepatic tissue oxygenation using near infrared spectroscopy (NIRS). Baseline hepatic hemodynamics and liver function were measured in both groups. PVBF was then increased by 50% over a 3-hour period in the hepatic fibrosis group using a miniature portal pump designed for human implantation, and the hemodynamics were monitored continuously. Liver function tests were repeated after portal pumping. In comparison with normal controls, animals with hepatic fibrosis had a higher portal pressure (13.0 +/- 3.6 vs. 3.7 +/- 1.4 mm Hg, P <.001, mean +/- SD vs. controls), reduced PVBF (52.4 +/- 24.6 vs. 96.9 +/- 21.1 mL/min, P =.003), and increased portal vascular resistance (P =. 001). THBF and flow in the HM was lower than in controls, and liver function tests were abnormal. After a 3-hour period of enhanced portal flow in animals with hepatic fibrosis, the portal pressure greatly reduced (13.0 +/- 3.6 to 2.5 +/- 1.1 mm Hg, P <.001) as did the intrahepatic portal resistance (0.32 +/- 0.18 to 0.04 +/- 0.03 mm Hg/mL/min, P =.006). Flow in the HM improved (143 +/- 16 to 173 +/- 14 flux units, P =.006) and was associated with improved hepatic tissue oxygenation, tissue oxy-hemoglobin (HbO2) and cytochrome oxidase being increased by 24.4 +/- 7.5 and 5.65 +/- 2.30 micromol/L above the baseline value (P <.001), respectively. A 3-hour period of mechanical portal pumping produced a dramatic improvement in liver function, bilirubin (41.1 +/- 25.9 to 10.0 +/- 5.9 micromol/L, P =. 040), aspartate transaminase (AST) (135.5 +/- 52.3 to 56.3 +/- 19.8 U/L, P =.006) and lactate dehydrogenase (LDH) (2,030.1 +/- 796.3 to 1,309.8 +/- 431.6 IU/L, P =.006; prepumping vs. postpumping, all P <. 050). In conclusion, portal pumping in this rabbit model with extensive hepatic fibrosis improved liver parenchymal perfusion, oxygenation, and function.

Animals↗
PubMed1999

Clinical short-term results of radiofrequency ablation in primary and secondary liver tumors.

BACKGROUND: Radiofrequency ablation (RFA) is emerging as a new therapeutic method for management of solid tumors. We report here our experience in the use of this technique for management of primary and secondary unresectable liver cancers. METHODS: Thirty-five patients with liver cancers were considered not suitable for curative resection at presentation: 8 with primary hepatocellular carcinoma ([HCC] 6 HCC and 2 fibrolamellar); 27 with metastatic liver cancer (17 colorectal carcinoma and 10 others). They were treated either with radiofrequency heat ablation (Radionics Europe N.V., Wettdren, Belgium) alone percutaneously and/or intraoperatively or in conjunction with surgical resections. The quality of RFA was based on the subjective feeling of whether the tumor was completely destroyed or not. The effectiveness of RFA was assessed according to clinical findings, radiographic images, and tumor markers at follow-up. RESULTS: In 8 primary liver cases, 4 patients with a high level of alpha fetoprotein (AFP) benefited from the RFA with a 83.3% to 99.7% reduction of AFP. One with fibrolamellar hepatocellular carcinoma died 2 months after an incomplete percutaneous RFA from recurrence. The rest all had stable disease at the time of follow-up (mean 10.4 months). In patients with colorectal liver metastases, there were 4 deaths: 1 patient died postoperatively on the 30th day from a severe chest infection having shown a considerable reduction of carcinoembryonic antigen level (CEA, 8 versus 36 microg/L); 3 died from local and systemic disease, 1 at 12 months and 2 at 1 month, having had an incomplete RFA. The others had stable disease at follow-up (mean 7.6 months). Five patients underwent liver resections successfully with the application of RFA for residual lesions in the remaining contralateral lobe. In 10 patients with other liver tumors, 7 patients had stable disease at follow-up (mean 13.4 months); 1 patient had evidence of local and systemic recurrence 10 months after surgical resections with the intraoperative RFA and 2 patients died of systemic recurrence of disease 3 and 6 months after RFA alone. Two patients had liver resections in conjunction with the intraoperative RFA. The mean follow-up in our series was 8.5 months. CONCLUSION: Radiofrequency heat ablation is useful as a primary treatment for unresectable liver cancers. The procedure can be used to treat the small residual tumor load in the contralateral lobe following liver resection in those considered unresectable at the first presentation. This new therapeutic strategy seems to increase surgical resectability in patients judged unresectable.

Carcinoembryonic Antigen↗
PubMed1999

Arterialisation of the portal vein with an aortoportal jump graft for portal vein thrombosis following liver resection for malignancy.

Fibrolamellar hepatocellular carcinoma (FHCC) is a variant of hepatocellular carcinoma, which mainly affects a young age group and carries a relatively good prognosis. It is widely accepted that aggressive curative resection is still the best option for FHCC. We report here a case of successful arterialisation of the portal vein with an aortoportal jump graft for portal vein thrombosis, which developed postoperatively in an already comprised portal vein with tumour invasion following an extensive liver resection for FHCC.

Adolescent↗
PubMed1999

Central nervous system infection caused by Borrelia burgdorferi. Clinico-pathological correlation of three post-mortem cases.

The spirochete Borrelia burgdorferi (B. burgdorferi) may cause severe meningoencephalomyelitis as the sole manifestation of Lyme borreliosis. We would like to present three such cases, where definite neuroborreliosis was clinically diagnosed in two cases and possible neuroborreliosis was recognized in one case. Alive spirochetes were isolated and cultured from blood and cerebrospinal fluid (CSF) in both definite cases. B. burgdorferi as the causative agent of the infection was confirmed in CSF by polymerase chain reaction (PCR) in one definite case. In the possible case spirochetes were cultured from blood and CSF. Alive spirochetes were not isolated, however anti-B. burgdorferi antibody value in serum was significantly elevated. On necropsy gross examination brain edema without focal changes was detected in two cases. Cerebral atrophy was seen in Case 3. Microscopically, lymphocytic infiltrates, microglial diffuse and nodular activation, spongiform changes, diffuse demyelination of the cerebral and cerebellar white matter, and diffuse astrocytosis, were characteristic pathological features in all presented cases. Multifocal, perivascular degenerative changes in the cerebral and cerebellar white matter were observed in the first case. Inflammatory changes in the nuclei and roots of cranial nerves were present in the third case.

Adult↗
PubMed1999

[Can mechanical augmentation of portal vein flow be an alternative treatment for portal hypertension and liver failure?].

In the past few years in vivo and ex vivo experiments using mechanical augmentation of portal inflow have shown a reduction in mesenteric portal venous pressure, intrahepatic portal vascular resistance and an improvement in liver function in cirrhotic animals. The latest technical development has allowed a construction of a miniature portal pump for human implantation. The aim of this study was to assess the short-term effect of mechanically increasing portal blood flow on hepatic haemodynamics and liver function in a cirrhotic porcine model. Liver cirrhosis was established by ligation of common bile duct in pigs. After four weeks, when the animals had become cirrhotic, the miniature pump was placed in the portal vein and blood flow was increased by 50% for one hour. Enhanced portal flow in the cirrhotic animals decreased mesenteric portal pressure, improved liver function and hepatic haemodynamics. However, long-term experiments will be needed to confirm the concept of enhancement of portal inflow as a feasible treatment for portal hypertension and liver failure in humans.

Animals↗
PubMed1998

Is radical hepatic surgery safe?

BACKGROUND: A prospective review of 200 consecutive liver resections performed for benign and malignant disease, between 1989 and 1995 at the Hammersmith Hospital, was undertaken to evaluate the safety of radical hepatic resection. METHODS: The indications for operation were: hepatocellular carcinoma (n = 39), cholangiocarcinoma (n = 21), gall bladder carcinoma (n = 8), colorectal secondaries (n = 75), noncolorectal secondaries (n = 35), and benign disease (n = 26). Twenty patients were cirrhotic and 36 were jaundiced. Major resections were performed in 74% of cases and included 63 extended hepatectomies, 17 repeated resections for recurrent colorectal metastases, and 17 resections combined with vascular reconstruction. Total vascular exclusion of the liver was used in the majority of cases. RESULTS: The overall mortality rate was 5%. Thirty-day mortality was 2.5%. Sepsis and not hemorrhage was the most common cause of death. There were 101 complications that occurred in 37% of the patients. The main complications were subphrenic abscess and biliary leak. The extent of liver resection (major versus minor) significantly increased the risk of morbidity (46% versus 16%). Blood loss greater than 100 mL increased the risk of morbidity from 12% to 25%. CONCLUSIONS: Major hepatic resection can be achieved with acceptable mortality but high morbidity rates.

Adolescent↗
PubMed1998

Implantable micropump system for augmented liver perfusion.

Liver cirrhosis, a worldwide health problem, decreases the blood flow through the liver. This in turn leads to dangerous portal hypertension and decreased metabolic function within the liver. To improve this situation, a new concept is proposed which involves introducing a microaxial blood pump into the portal vein. This device is intended to increase blood flow through the liver and to enhance hepatic function. Furthermore, high pressures will be reduced to physiological levels. The microaxial pump with its single stage impeller is powered by a proximally integrated microelectric motor. The pump unit is completely immersed within the blood vessel. Heat caused by electrical and mechanical losses will be transported into the blood. In vitro optimization of the pump design was accomplished using both hydraulic and hemolysis tests.

Biocompatible Materials↗
PubMed1995

In situ splitting of the liver in the heart-beating cadaveric organ donor for transplantation in two recipients.

SLT presents an interesting concept to alleviate the organ shortage for children with end-stage liver disease. The procedure has, however, not gained wide acceptance. This is not only related to the complexity of the procedure, but also to the poorer results and the complications reported on the right side graft. We report on a first case in which we applied a new concept for splitting. The liver was split in situ in the heart-beating cadaveric donor with the aim of reducing the problems with the right side graft. This procedure makes splitting of the liver possible without submitting the recipient of the right side to increased risk. Therefore, in situ splitting of the liver has the potential of making splitting of liver grafts the rule rather than the exception, thus increasing the organ pool for small children presently carrying a high risk of dying on the waiting list.

Adult↗
PubMed1995

Living-related liver transplantation in adult recipients: a hypothesis.

Living-related liver transplantation (LRLT) in pediatric recipients has been successful with 90% 1-year survival (1, 2). LRLT in adults is yet to succeed. We hypothesize a management strategy based on the donor graft weight-to-recipient body weight ratio (GRBWR) and the Redox Tolerance Index (RTI) (3). Favorable recipients (GRBWR above 0.7%) are candidates for left liver orthotopic transplantation. Unfavorable recipients (GRBWR 0.5-0.7% and RTI above 0.5%) are suitable for left liver auxiliary-orthotopic transplantation. Compromized recipients (GRBWR below 0.5% or RTI below 0.5%) might be suitable for a left liver auxiliary-heterotopic transplantation. The above hypothesis remains to be validated.

Adult↗