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Biomedical subjects

N Habib

Publications and source records attributed to N Habib.

At least 19 recordsLinked to original sources
PubMed2006

Hepatic resection using heat coagulative necrosis. First report of successful trisegmentectomy after hypertrophy induction.

INTRODUCTION: Intraoperative blood loss has been identified as one of the major mortality predictors for liver surgery. Different strategies have been used in the past to minimize blood loss during resection. A new method using heat coagulative necrosis in healthy tissue at the resection plane to achieve a bloodless resection has been described 3 years ago and has already gained acceptance for peripheral resections. A further developmental stage of this method is now available with the so-called Habib 4x sealer. So far, only resections ranging from segmentectomies to hemihepatectomies are reported. MATERIALS AND METHODS: In the case reported here, the new method was challenged to perform an extended hepatic resection in a patient suffering from colorectal liver metastases. The resection was performed in a hybrid technique of regular hilar preparation and parenchymal dissection using the sealer. CONCLUSION: The method showed to be safe and efficient even for an extended resection.

Aged↗
PubMed2006

Anti-inflammatory, anti-nociceptive and antipyretic effects of extracts of Phrygilanthus acutifolius flowers.

This study was intended to evaluate the anti-inflammatory, antipyretic and analgesic activities of aqueous and ethanol extracts of Phrygilanthus acutifolius flowers in several experimental standard models in rats, following oral administration. The results showed that the aqueous extract significantly reduced the oedema induced by carrageenan within 1-5 h post-dosing at all dose levels used. On the analgesia property, acetic acid-induced writhing was significantly reduced. In the formalin test, the extract also significantly decreased the painful stimulus in both phases of the test. The tail immersion confirms central acting analgesic property of the extracts. Overall, the analgesic tests conducted revealed that the extract had central and peripheral properties. Its effects on pyresis were also appreciable. It significantly reduced fever at doses greater than 200 mg/kg within 2 h on yeast-induced hyperthermia in rats.

Acetic Acid↗
PubMed2005

Interferon-alpha2a is sufficient for promoting dendritic cell immunogenicity.

Type I interferons (IFNs) are widely used therapeutically. IFN-alpha2a in particular is used as an antiviral agent, but its immunomodulatory properties are poorly understood. Dendritic cells (DCs) are the only antigen-presenting cells able to prime naive T cells and therefore play a crucial role in initiating the adaptive phase of the immune response. We studied the effects of IFN-alpha2a on DC maturation and its role in determining Th1/Th2 equilibrium. We found that IFN-alpha2a induced phenotypic maturation of DCs and increased their allostimulatory capacity. When dendritic cells were stimulated simultaneously by CD40 ligation and IFN-alpha2a, the production of interleukin (IL)-10 and IL-12 was increased. In contrast, lipopolysaccharide (LPS) stimulation in the presence of IFN-alpha2a mainly induced IL-10 release. The production of IFN-gamma and IL-5 by the responder naive T cells was also amplified in response to IFN-alpha2a-treated DCs. Furthermore, IL-12 production by IFN-alpha2a-treated DCs was enhanced further in the presence of anti-IL-10 antibody. Different results were obtained when DCs were treated simultaneously with IFN-alpha2a and other maturation factors, in particular LPS, and then stimulated by CD40 ligation 36 h later. Under these circumstances, IFN-alpha2a did not modify the DC phenotype, and the production of IL-10/IL-12 and IFN-gamma/IL-5 by DCs and by DC-stimulated naive T cells, respectively, was inhibited compared to the effects on DCs treated with maturation factors alone. Altogether, this work suggests that IFN-alpha2a in isolation is sufficient to promote DC activation, however, other concomitant events, such as exposure to LPS during a bacterial infection, can inhibit its effects. These results clarify some of the in vivo findings obtained with IFN-alpha2a and have direct implications for the design of IFN-alpha-based vaccines for immunotherapy.

Animals↗
PubMed2004

[Modification of the liver resection technique with radiofrequency coagulation].

INTRODUCTION: Since the introduction of liver resection, intraoperative blood loss is considered to be a major risk factor for perioperative morbidity and mortality. Radiofrequency energy-an established technique for in situ ablation-was used to facilitate liver resection by creating a nearly bloodless tissue plane. METHODS: After thorough manual and sonographic exploration of the liver, the planned and marked resection plane was coagulated by radiofrequency and then transected. Seven patients with liver metastases of colorectal carcinoma were operated on employing this technique. RESULTS: A nearly bloodless transection of the parenchyma could be achieved in all cases. Only two patients received blood transfusions: one due to a low preoperative hemoglobin and one due to extended additional abdominal surgery. Procedure-related complications included one case of a second-degree burn to the thigh and one case of postoperative bile leakage requiring hemihepatectomy. CONCLUSIONS: Radiofrequency-assisted resection offers a valuable additional option in liver surgery, especially in patients with an increased risk of intraoperative bleeding (cirrhosis, coagulopathy).

Adult↗
PubMed2003

DNA adducts, detected by 32P postlabelling, in human cholangiocarcinoma.

BACKGROUND: Reported mortality from intrahepatic cholangiocarcinoma (CCa) has risen steeply in the UK and other industrialised countries over the past 30 years, the cause of which has not been explained. DNA adduct formation is promutagenic and demonstrates exposure to a DNA damaging agent. It is a key step in chemically induced carcinogenesis. We hypothesise that the increase in CCa mortality is caused by a rise in a genotoxic environmental agent(s), causing cholangiocyte DNA damage. AIMS: To investigate and compare tumour and tumour adjacent CCa tissue, and non-cancer control bile duct tissue, for DNA adducts as a biomarker of genotoxin exposure. METHODS: DNA from 32 intrahepatic CCa patients (and in 28 cases DNA from adjacent non-tumour tissue) and from biliary ducts of seven non-cancer patients were investigated for the presence of DNA adducts using the nuclease P1 method of (32)P postlabelling. DNA adduct levels (number of adducts/10(8) nucleotides) were quantified. RESULTS: There was no significant difference in relative adduct labellings (RALs) between tumour adjacent DNA (median 8.6, range 1.2-51.6) and CCa DNA (7.2, 1.8-48.4). However, RALs were significantly higher in DNA from cancer patients (tumour adjacent and CCa DNA) compared with non-cancer patient DNA (2.9, 0.6-11.5; p=0.032, two tailed Mann-Whitney U test). Different adduct patterns were also seen in CCa compared with non-cancer patients. CONCLUSION: Quantitative and qualitative differences in adducts between cancer and non-cancer patients support the hypothesis that genotoxins may play a role in the development of intrahepatic CCa.

Adult↗
PubMed2003

Vitamin A status of patients presenting with pulmonary tuberculosis and asymptomatic HIV-infected individuals, Dar es Salaam, Tanzania.

Serum vitamin A was determined in a cross-sectional study of 100 HIV-positive and -negative tuberculosis patients and 144 blood donors. Tuberculosis patients were seen again after 2 months of treatment. Mean vitamin A was lowest among tuberculosis patients co-infected with HIV, and was lower among HIV-positive than -negative donors. Mean vitamin A rose significantly at 2 months in HIV-negative patients, and not in -positive patients. HIV infection was the strongest predictor of low vitamin A. Vitamin A deficiency is common in tuberculosis and HIV infection, particularly in those patients who are dually infected, and nutritional supplementation may be beneficial.

Adult↗
PubMed2003

[Gene therapy of liver tumors: results of the first clinical studies].

Only a small percentage of primary and secondary liver tumours is suitable for surgical resection. Gene therapy represents a novel strategy that seems to be effective both, in vitro and in vivo. The use of tumour suppressor gene p53 therapy, suicide gene therapy, immune gene therapy and therapy with replication-competent oncolytic adenoviruses in liver tumours already entered the first clinical trials. In patients with hepatocellular carcinoma, the first clinical trials in phase I and II showed good tolerance and low toxicity to gene therapy. However, the clinical benefit for the patients treated either with wild type p53 or E1B deleted adenoviruses were marginal.

Clinical Trials as Topic↗
PubMed2001

Intravascular micropump for augmented liver perfusion: first in vivo experience.

The aim of this study was to assess the in vivo performance of a new microaxial rotary blood pump developed for long-term intraportal implantation. The pump, measuring 7 mm in diameter, has a single stage impeller and is powered by a microelectric motor. The pump was implanted into the portal vein in 13 large white pigs under general anesthesia. All animals recovered after the portal pump implantation, and they were observed until the pump failed. The 2 longest running pumps performed for 40 and 36 h, respectively. Either thrombus formation or technical problems, especially in the bearings, were the main causes of pump failure during the experiment. No local or systemic adverse effects were observed during the portal pumping period. Full recovery of the animals following intraportal pump implantation was achieved. However, further technical improvements to the pump are required to maintain a longer performance in vivo.

Animals↗
PubMed2000

Profile of p53 expression in bladder and oral tumours. Effects of in vitro manipulations of p53 on the behaviour of established human tumour cell lines.

In this investigation the profile of p53 and epidermal growth factor receptor (EGFR) expression in tumour tissue biopsies of transitional cell carcinoma of bladder (TCC) and of oral-pharyngeal carcinoma (OP) were compared using an immunocytochemical staining method. In addition, various techniques including sodium dodecyl sulphate-polyacrylamide gel elecrophoresis (SDS-PAGE), colorimetric assay and gene transfection were used to investigate the influence of p53 on the behaviour of human tumour cell lines in vitro. The results showed that: (a) p53 was detectable in more than 45% of cases in both tumour types, although the profile and intensity of expression differed. (b) Concomitant strong expression of EGFR and p53 for TCC and OP was 21% and 38% (P>0.05%), respectively. (c) Treatment of tumour cells by either gamma radiation or by cisplatin resulted in the induction of p53 independent of the origin of the tumour. (d) Susceptibility of two cell lines, one with and one without constitutive expression of p53 showed that the expressing cells were more sensitive to gamma radiation (the percentage inhibition at 250 cGy was 57% versus -15%, P<0.01), and also cisplatin (the percentage inhibition at 1 microgram/ml was 71.0+/-6.0 versus 2.6+/-7.0, P<0.001). (e) Transfection of wild-type TP53 gene into a bladder tumour cell line resulted in a rapid cell apoptosis (by as much as 90%) whereas cells receiving mutated TP53 survived. A similar frequency of TP53 mutation in TCCs and OPs was observed. In addition, the pattern of p53 expression within the squamous type of TCC was similar to that in OPs. If the data from the in vitro studies could be translated into an in vivo setting, one could envisage a situation where the introduction of wild-type TP53 gene by gene transfection into tumour cells (independent of their TP53 gene mutational status), would prove to be beneficial. If the cellular TP53 gene is mutated, then an introduction of the normal TP53 gene would induce cells to undergo apoptosis. Alternatively, if TP53 is wild-type, then the increased levels of p53 expression would enable the cells to become more susceptible to DNA damaging treatments such as cisplatin or gamma radiation.

Carcinoma, Transitional Cell↗
PubMed2000

Enhancement of immunogenicity of tumor cells by cotransfection with genes encoding antisense insulin-like growth factor-1 and B7.1 molecules.

Insulin-like growth factor-1 (IGF-1) is expressed in many tumor cell lines and has a role in both normal cell proliferation and in the growth of cancers. Tumor cells transfected with a vector encoding an IGF-1 antisense cDNA transcriptional cassette driven by the mouse metallothionein-1 promoter become immunogenic and lose their tumorigenicity in syngeneic animals. The enhanced immunogenicity is associated with an up-regulation in the expression of major histocompatibility complex class I molecule on cell surfaces. Blockade of the expression of IGF-1 in tumor cells by the IGF-1 antisense RNA approach is not uniformly effective in the induction of antitumoral protective immunity in low and nonimmunogenic tumor model systems. Here, we report that the immunogenicity of hepa 1-6 hepatoma and SMCC-1 colon carcinoma cells, which are poorly immunogenic and unresponsive to antisense IGF-1 gene transfer, can be induced by cotransfection with genes encoding antisense IGF-1 and mouse B7.1 molecules. The tumor cells modified in this manner become strongly immunogenic and can be used as a cellular vaccine to induce a protective immune response in vivo. Immunization with the transfected tumor cells also results in regression of the established hepa 1-6 hepatoma and SMCC-1 colon cancer. The immunity is tumor-specific and is mediated by CD3+ CD8+ T cells. Cytotoxic T lymphocytes generated in vitro by priming naive spleen cells and in vivo by immunizing mice with the double-transfected tumor cells specifically lysed autologous tumors cells and were effective in adoptive immunotherapy. The data suggest that modification of tumor cells in vitro by cotransfection with genes encoding antisense IGF-1 and B7.1 molecules may open a new avenue for cancer immunogene therapy.

Adjuvants, Immunologic↗
PubMed2000

Effect of liver blood flow and function on hepatic indocyanine green clearance measured directly in a cirrhotic animal model.

BACKGROUND: Peripheral blood clearance of indocyanine green (ICG) has been used as a test of liver function but gives little information on biliary excretion. Hepatic ICG uptake and clearance can be measured directly by near-infrared spectroscopy (NIRS). Direct ICG measurement has not previously been correlated with liver blood flow and function in cirrhosis. METHODS: Two groups of New Zealand white rabbits (n = 12) underwent laparotomy for liver exposure. Cirrhosis was induced by feeding animals (n = 6) with a high-cholesterol (2 per cent) diet for 16 weeks. Hepatic blood flow and microcirculation were measured. Hepatic ICG concentration was measured directly using NIRS probes on the liver surface. From the ICG concentration-time curve, hepatic ICG uptake and excretion rates were calculated by a non-linear least square curve fitting method. RESULTS: There was a significant reduction in ICG uptake rate (mean(s.d.) 0.300(0.130) versus 2.040(0.420) min-1; P = 0.0001) and ICG excretion rate (0.007(0.009) versus 0.227(0.096) min-1; P = 0. 002) in cirrhotic animals. The hepatic ICG uptake rate correlated with hepatic blood flow and flow in the microcirculation (r = 0.81, P = 0.002; r = 0.92, P < 0.001, respectively). The hepatic ICG excretion rate was significantly associated with indicators of impaired liver function including bilirubin (r = - 0.86, P = 0.0004), aspartate aminotransferase (r = - 0.81, P = 0.001) and lactate dehydrogenase (r = - 0.83, P = 0.0008). CONCLUSION: ICG uptake measured directly by NIRS reflects the reduced liver blood flow and perfusion in cirrhosis and its excretion correlates with the degree of liver parenchymal dysfunction. This technique may allow a more accurate method of liver function assessment than peripheral blood ICG clearance.

Animals↗
PubMed2000

In vivo evaluation of an implantable portal pump system for augmenting liver perfusion.

BACKGROUND: Increasing portal inflow in cirrhosis using a mechanical pump reduces portal venous pressure and improves liver function. A pump has been developed for portal vein implantation in human cirrhosis. This study describes the initial in vivo evaluation in a porcine model. METHODS: Five Large White pigs underwent laparotomy and exposure of the liver. Flow in the hepatic artery, portal vein and hepatic microcirculation was monitored continuously. Hepatic tissue oxygenation was measured by near-infrared spectroscopy. After baseline measurements the pump was inserted into the portal vein. Pump flow rate was then increased stepwise to 50 per cent over the baseline value for a period of 2 h. The pump was then stopped for 20 min and left in situ while continuing to collect systemic and hepatic haemodynamic data. The animal was killed and biopsies for histological examination were taken from the liver, small intestine and spleen. RESULTS: The baseline total hepatic blood flow was 626(39) ml/min; the hepatic artery supplied 18.4(2.1) per cent and the portal vein 81.6(2.1) per cent. The pump was inserted successfully in all animals without surgical complications. During surgical insertion of the pump, the temporary portal vein occlusion resulted in a significant rise in hepatic artery blood flow (22(3) per cent; P < 0.01 versus baseline). Portal vein flow was augmented by pumping; there was a significant correlation between the pump motor speed and portal vein flow (P < 0.0001). This inflow correlated directly with flow in the hepatic microcirculation and hepatic tissue oxygenation (P < 0.001). The pump ran satisfactorily throughout the study. Histological examination revealed no evidence of structural damage to the liver or ischaemic changes in the small intestine or spleen. CONCLUSION: It is technically possible and safe to insert an implantable pump in the portal vein. Portal venous blood flow can be increased up to 50 per cent with a resultant increase in flow in the hepatic microcirculation and hepatic oxygenation and without adverse effects on either hepatic or systemic haemodynamics.

Animals↗
PubMed2000

Portal flow augmentation for liver cirrhosis.

BACKGROUND: Portal hypertension due to chronic liver disease is a major cause of death worldwide. Orthotopic liver transplantation offers the best therapeutic option but is available to only a minority of patients. In the past few years mechanically pumping portal venous inflow has been reported to reduce portal hypertension and improve liver function. METHODS: A review of the published data on augmented portal perfusion for the treatment of portal hypertension in cirrhosis was carried out by searching Medline and other online databases. From each published study portal pressure and blood flow data before and after augmented portal perfusion were used to calculate the change in mean intrahepatic portal vascular resistance (IHPR). The standardized data were then combined to allow meta-analysis. RESULTS: Seven papers were identified on normal and cirrhotic animal and human livers with augmented flow (50% to fourfold over baseline) for 30-180 min. Meta-analysis revealed that the increased portal venous inflow was associated with a significant rise in portal venous pressure on the hepatic side (P < 0.001), a significant reduction on the mesenteric side (P < 0.001) and a significant reduction in IHPR (P = 0.013). Limited data were available to support improved liver function. CONCLUSION: Detailed in vivo cirrhotic liver studies on augmented portal flow in experimental models assessing haemodynamic and functional changes are required before clinical evaluation.

Animals↗
PubMed2000

Hypomethylation of LINE1 retrotransposon in human hepatocellular carcinomas, but not in surrounding liver cirrhosis.

BACKGROUND: Cytosine methylation of LINE1 (L1) elements, some of which are capable of retrotransposition in human cells, is known to play important roles in transcriptional repression of these retrotransposons. We have previously identified consistent hypomethylation of L1 elements in mouse liver tumors by a genome-wide search technique for aberrant methylations. In this study, we analyzed the methylation status of the L1 elements in human hepatocellular carcinomas (HCCs). METHODS: Nine pairs of an HCC and its surrounding tissue were obtained from clinical cases. Genomic DNA was digested with HpaII, a methylation-sensitive restriction enzyme, and hybridized with a probe derived from the promoter region of the L1 elements. RESULTS: Hypomethylation of the L1 elements was detected in eight of the nine HCCs, but never in the surrounding liver tissues, whether or not liver cirrhosis was present. CONCLUSION: Specific occurrence of the hypomethylation of the L1 elements in the HCCs indicated its diagnostic value for malignancy. The hypomethylation could also lead to increased incidence of retrotransposition and resultant genomic instability in HCCs.

Aged↗
PubMed2000

Measurement of hepatic tissue hypoxia using near infrared spectroscopy: comparison with hepatic vein oxygen partial pressure.

Hepatic hypoxia occurs during liver surgery and transplantation. The critical level associated with irreversible hepatocellular damage is unknown. Measurement of hepatic tissue oxygenation and hepatic vein oxygen partial pressure (HVPO(2)) reflects oxygen supply and consumption. Near infrared spectroscopy (NIRS) can be used to monitor hepatic oxyhaemoglobin (HbO(2)), deoxyhaemoglobin (Hb) and cytochrome oxidase (Cyt Ox) oxidation. This study compared regional hepatic tissue oxygenation (HbO(2), Hb and Cyt Ox) using NIRS with HVPO(2). The use of tissue oxygenation measured by NIRS and HVPO(2) as indicators of hepatic tissue hypoxia was also investigated. Large Landrace pigs (n = 5) underwent laparotomy and liver exposure. Systemic and hepatic haemodynamics were monitored continuously. NIRS probes were placed on the liver to record continuously HbO(2), Hb and Cyt Ox. Graded hypoxaemia was achieved by stepwise reduction of the fraction of inspired oxygen (FiO(2)) from 30% (baseline) to 4%. A significant decrease in hepatic arterial blood flow and total hepatic blood flow was seen with severe hypoxaemia while there was no significant change to portal vein blood flow. Oxygen partial pressures in the hepatic artery, portal vein and hepatic vein decreased progressively with all grades of hypoxaemia. There was an immediate reduction of hepatic HbO(2) and simultaneous increase in hepatic Hb with all grades of hypoxaemia. Hepatic Cyt Ox was reduced significantly only with FiO(2) < or =10%. A significant correlation (p<0.001) was found between the changes in hepatic oxygenation parameters measured by NIRS and HVPO(2). HVPO(2) measurement did not predict the reduction in intracellular tissue oxygenation demonstrated by NIRS with a decrease of Cyt Ox oxidation. In conclusion there was a good correlation between the tissue oxygenation parameters measured by NIRS and HVPO(2). However, the reduction of intracellular oxygenation found with severe hypoxaemia was demonstrated only by NIRS.

Animals↗
PubMed2000

Hepatic malignancy: challenges and opportunities for the surgeon.

The management of hepatic malignancy has changed from a previously nihilistic approach to a more positive one. Every patient should be considered for curative surgical resection, either at first presentation or after cytoreductive treatment. The surgeon is faced with the challenge of adapting modern surgical techniques to increase resectability rates. Although the majority of patients are unsuitable for resection, effective palliation can be achieved using a wide variety of techniques. The rational implementation of these palliative modalities requires a multidisciplinary approach which provides the surgeon with the opportunity to play a key role in the ongoing management of these patients.

Algorithms↗