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Biomedical subjects

D Franco

Publications and source records attributed to D Franco.

At least 73 records · Page 4Linked to original sources
PubMed1998

[Liver resection in patients with polycystic liver disease].

OBJECTIVES: Polycystic liver disease is sometimes responsible for chronic symptoms linked to hepatomegaly which can result in acute complications such hemorrhage or infection of cysts. The aim of this retrospective study was to evaluate the results of partial hepatic resection in patients with symptomatic or complicated polycystic liver disease. METHODS: Twelve patients (11 women and one man, mean age 49) with diffuse polycystic liver disease were treated by partial liver resection (left lateral lobectomy in 7, left hepatectomy in 4, and extended right hepatectomy in 1). Four patients had terminal renal failures and three had chronic haemodialysis. Median follow-up was 34 months. RESULTS: Ascites occurred postoperatively in 10 patients (83%) and was long-lasting (> 2 weeks) in 5; all patients with end-stage renal failure had long-lasting ascites. One of them died on the 40th postoperative day of ascites infection. Another patient with end-stage renal failure died two years postoperatively from chronic disabling ascites and malnutrition while awaiting kidney transplantation. The 10 other patients were markedly improved after partial liver resection, including a marked decrease in hepatomegaly, and the disappearance of chronic symptoms and cystic complications. This beneficial effect was incomplete in the two surviving patients with end-stage renal failure until kidney transplantation was performed. CONCLUSION: These results suggest that partial liver resection is a highly effective treatment in patients with symptomatic polycystic liver disease, preferably before the onset of end-stage renal failure.

Adult↗
PubMed1997

Regionalized transcriptional domains of myosin light chain 3f transgenes in the embryonic mouse heart: morphogenetic implications.

Within the embryonic heart, five segments can be distinguished: two fast-conducting atrial and ventricular compartments flanked by slow-conducting segments, the inflow tract, the atrioventricular canal, and the outflow tract. These compartments assume morphological identity as a result of looping of the linear heart tube. Subsequently, the formation of interatrial, interventricular, and outflow tract septa generates a four-chambered heart. The lack of markers that distinguish right and left compartments within the heart has prevented a precise understanding of these processes. Transgenic mice carrying an nlacZ reporter gene under transcriptional control of regulatory sequences from the MLC1F/3F gene provide specific markers to investigate such regionalization. Our results show that transgene expression is restricted to distinct regions of the myocardium: beta-galactosidase activity in 3F-nlacZ-2E mice is confined predominantly to the embryonic right atrium, atrioventricular canal, and left ventricle, whereas, in 3F-nlacZ-9 mice, the transgene is expressed in both atrial and ventricular segments (right/left) and in the atrioventricular canal, but not in the inflow and outflow tracts. These lines of mice illustrate that distinct embryonic cardiac regions have different transcriptional specificities and provide early markers of myocardial subdivisions. Regional differences in transgene expression are not detected in the linear heart tube but become apparent as the heart begins to loop. Subsequent regionalization of transgene expression provides new insights into later morphogenetic events, including the development of the atrioventricular canal and the fate of the outflow tract.

Animals↗
PubMed1997

Expression of the cholinergic signal-transduction pathway components during embryonic rat heart development.

BACKGROUND: Previous studies showed that acetylcholinesterase (AChE) activity is present in the downstream (arterial) part of the embryonic chick and rat heart, but its functional significance was unclear. To establish whether other components of a cholinergic signal-transduction pathway are present in the embryonic heart, we localised the mRNAs encoding choline acetyltransferase (ChAT), acetylcholinesterase (AChE), and the muscarinic receptor isoforms (mAChRs; m1-m5). METHODS: Messenger RNA detection and localisation by in situ hybridisation and reverse transcriptase-polymerase chain reaction were employed. RESULTS: Expression of ChAT and AChE mRNAs was observed from 15 embryonic days onward in the neural tissue covering the dorsocranial wall of the atria. Muscarinic receptors (m1, m2, m4) were observed at the same localisation as AChE and ChAT mRNAs, both during embryogenesis and after birth. In addition, m1 and m4 mAChRs showed a low level of expression in the atrial myocardium during the fetal period. No expression of the m3 or the m5 mAChRs was observed in or near the embryonic hearts. ChAT, AChE, and mAChRs (m1, m2, m4) mRNAs always colocalised in the cardiac ganglia. However, none of these mRNAs was found at a detectable level in the outflow tract and/or the ventricular trabeculations. CONCLUSIONS: The AChE activity in the arterial part of the embryonic heart is probably synthesised elsewhere and subserves a function different from the hydrolysis of locally produced acetylcholine.

Acetylcholinesterase↗
PubMed1997

Spontaneous and iatrogenic spreading of liver-derived cells into peripheral blood of patients with primary liver cancer.

The prognosis for patients with primary liver cancer (PLC) often depends on tumor recurrence and the development of extrahepatic metastases, particularly after liver transplantation. We have developed a sensitive test to detect both spontaneous circulation of tumor cells and the spread of liver cells due to chemoembolization and alcoholization. Reverse-transcription polymerase chain reaction was used to search for cells expressing alpha-fetoprotein (AFP) messenger RNA in the peripheral blood of 84 patients with PLC and 102 controls (55 patients with chronic hepatitis and/or cirrhosis, 10 patients with benign liver tumors or liver metastases from intestinal cancers, and 37 healthy individuals). By spiking the blood of healthy volunteers with HepG2 cells, we assessed the sensitivity limit: one HepG2 cell mixed with 10(7) leukocytes. All 102 controls tested negative. In contrast, 28 patients (33.3%) with PLC tested positive. Positivity for the test was significantly associated with portal thrombosis, tumor size, intravascular tumor emboli, serum AFP level, and extrahepatic metastases. Patients were followed up for a mean period of 39 +/- 51 weeks: the probability of developing extrahepatic metastases was significantly higher in positive than in negative patients. Eighteen negative patients with PLC were tested before, 1 hour after, and 24 hours after locoregional therapy: 9 tested positive either 1 or 24 hours after alcoholization or chemoembolization. In conclusion, we have developed a highly specific and sensitive test to detect circulating tumor cells in patients with PLC. This test is likely to be clinically useful in evaluating the risk of developing extrahepatic metastases and the possibility of iatrogenic spreading of liver-derived, possibly tumorous, cells.

Female↗
PubMed1997

Preoperative predictors of blood transfusion in liver resection for tumor.

BACKGROUND: Hepatic resection remains a hemorrhagic procedure. The purpose of this study was to investigate the preoperative predictive factors of intraoperative blood transfusion. METHODS: One hundred consecutive patients who underwent hepatic resection for tumor were included in this retrospective study. Resection was performed for primary malignancies (n = 52), metastases (n = 18), and benign tumors (n = 30). Liver resection was performed under intermittent clamping of the portal triad. Seventeen variables were analyzed. RESULTS: The operative blood loss was 1,872 mL (mean 1,104; range 650 to 4500) for the 22 transfused patients. The mean blood transfusion was 5.5 units (mean 3.2; range 2 to 12) of packed red cells. Multivariate analysis demonstrated that the size of liver resection (P <0.001) and the prothrombin rate (P <0.001) were independently correlated with blood transfusion. CONCLUSIONS: Patients undergoing extended resection or with abnormal coagulation could be considered for autologous blood transfusion.

Adolescent↗
PubMed1997

Chromosomal aberrations in hepatocellular carcinomas: relationship with pathological features.

Fluorescence in situ hybridization performed on tissue sections can reveal chromosomal abnormalities related to histopathological features. This technique was performed on serial frozen sections from seven normal livers and 29 hepatocellular carcinomas (HCCs) using pericentromeric repeat-specific probes for chromosomes 1, 4, 6, 7, 8, 16, and 17. For each HCC and each probe, the percentage of cells showing one, two, or more than two signals was counted and compared with the distribution in the normal liver. According to these results, HCCs were categorized as monosomic, disomic, or polysomic (more than two signals) for the chromosome tested. These data were compared with the main histopathological characteristics of HCC. Chromosome gains were very common, preferentially affecting chromosome 1 (23 of 27 cases, 85%), chromosome 16 (16 of 27 cases, 59%), chromosome 7 (16 of 29 cases, 55%), chromosome 6 (15 of 29 cases, 52%) and chromosome 8 (14 of 29 cases, 48%). Monosomy was seen more rarely, affecting preferentially chromosome 16 (19%), chromosome 17 (14%), and chromosome 4 (10%). A significant correlation was observed between aneusomy of chromosome 4 and tumor size (P < .05) or the presence of vascular embolism (P < .05). In conclusion, chromosomal gains are frequent genetic events in human HCC. A significant association between a gain in chromosome 4 and large tumor size or vascular embolism suggests that this genetic abnormality is a late event in liver carcinogenesis.

Adult↗
PubMed1997

Aprotinin reduces blood loss in patients undergoing elective liver resection.

Ninety-seven patients undergoing elective liver resection through a subcostal incision were assigned to large-dose aprotinin treatment or placebo in a double-blind, prospective, randomized fashion. Randomization was stratified by diagnosis: (a) cancer in cirrhosis, (b) cancer in healthy liver, and (c) benign tumor in healthy liver. Intraoperative blood loss, percentage of transfused patients, and total transfusion requirement per group were significantly lower in the aprotinin group than in the placebo group (1217 +/- 966 mL vs 1653 +/- 1221 mL, P = 0.048; 17% vs 39%, P = 0.02; 30 vs 77 red blood cell packs, P = 0.015, respectively). Assessment of hematological markers (a) prior to surgery, (b) at the end of surgery, and (c) 24 h after surgery showed an identical intraoperative increase in thrombin-antithrombin III complexes in patients of both groups (P = 0.86), which indicates a similar activation of coagulation. Intraoperative hyperfibrinolysis was significantly less pronounced in the aprotinin group than in the placebo group (P = 0.0002 and P = 0.004 for D-dimers and fibrinogen, respectively). No adverse drug effects were detected (circulatory disturbances, deep venous thrombosis, increase in serum creatinine). These results suggest that aprotinin significantly reduces blood loss and transfusion requirement in patients undergoing elective liver resection through a subcostal incision.

Adult↗
PubMed1997

Turcot syndrome: case report and nosological aspects.

The Turcot syndrome has been defined as the simultaneous presence of multiple polyposis of the colon and a malignant brain tumor. This association is supposed to be genetically transmitted, even though we still do not exactly know whether this occurs in a dominant or recessive way. The case of a 47-year-old man submitted to a right hemicolectomy for cancer and polyposis, following a series of endoscopic polypectomies and, finally, removal of left temporal glioma is here presented.

Adenomatous Polyposis Coli↗
PubMed1996

Hepatocyte growth factor expressed by a retrovirus-producing cell line enhances retroviral transduction of primary hepatocytes: implications for in vivo gene transfer.

Hepatocyte Growth Factor (HGF) is the more potent mitogen of mature hepatocytes. We have examined the effect of human HGF expression by a recombinant retroviral cell line (MFG-LacZ) on retroviral transduction of primary mouse and human hepatocytes. The HGF in the supernatant of MFG-LacZ cell line was correctly processed and biologically active. Transduction of mouse and human hepatocytes with the supernatant of transfected cells was increased 5-fold, as determined by beta-galactosidase activity. The production of HGF was stable and did not interfere with the viral titers of the producer cells. This study provides evidence that expression of HGF within a retrovirus-producer cell line increases the transduction rate of primary hepatocytes. Since the number of corrected cells is a limiting step for phenotypic correction of liver deficiencies, our approach should improve hepatic gene therapy efficiency. Furthermore this cell line should be useful for in vivo liver gene therapy.

Animals↗
PubMed1996

Expression of a recombinant kringle V of human apolipoprotein(a): antibody characterization and species specificity.

Lipoprotein(a) is a macromolecular complex consisting of a low-density lipoprotein-like particle with an additional glycoprotein, apolipoprotein(a) [apo(a)], linked to apolipoprotein B-100 via a disulfide bond. Apo(a) is highly homologous to plasminogen. We have cloned the sequence corresponding to the kringle V domain of apo(a) from human liver cDNA using an experimental approach involving use of the polymerase chain reaction. The protein product of this clone was expressed in the cytoplasmic compartment of Escherichia coli as a MalE fusion protein. Fusion apo(a) Kr V was isolated from cytoplasmic extracts and purified by amylose-agarose affinity chromatography by eluting with 10 mM maltose. The fusion protein was injected into sheep in order to generate a polyclonal anti-apo(a) Kr V antibody. The antibody raised reacted against both reduced Lp(a) and the C-terminal domain of apo(a), corresponding to a sequence extending from Kr 33 to the C-terminal residue, but did not react with the N-terminal domain containing the repeated Kr IV sequences. The presence of the Kr V sequence was detected in every human apo(a) size isoform tested but only in apo(a) from human and chimpanzee among a panel of apo(a) proteins derived from different animal species.

ATP-Binding Cassette Transporters↗
PubMed1996

Comparison of a modified Sugiura procedure with portal systemic shunt for prevention of recurrent variceal bleeding in cirrhosis.

BACKGROUND: There is no agreement on the management of patients with cirrhosis and recurrent variceal bleeding after failure of medical or endoscopic treatments or both. Portal systemic shunts are highly effective in preventing rebleeding but are associated with a high incidence of chronic encephalopathy. This study compared the results of a slightly modified Sugiura procedure (esophageal transection plus esophagogastric devascularization plus splenectomy) with those of nonselective portal systemic shunts in patients with previous variceal bleeding. METHODS: Fifty-four patients were included in this randomized controlled study between January 1984 and April 1989. The major end point was chronic encephalopathy. Secondary end points were recurrent variceal bleeding, survival, ascites, and hepatocellular carcinoma. RESULTS: Twenty-seven patients were assigned to each group. The rate of chronic encephalopathy was significantly (p = 0.002) lower after modified Sugiura procedure than after portal systemic shunt. Recurrent variceal bleeding was more frequent after modified Sugiura procedure than after portal systemic shunt, but the difference is not significant. One-, two-, and three-year survival rates were 93%, 81%, and 67%, respectively, in the modified Sugiura group and 78%, 66%, and 39%, respectively, in the portal systemic shunt group (p = 0.044). CONCLUSIONS: These results suggest that the modified Sugiura procedure is better overall than the nonselective portal systemic shunt in the management of patients with cirrhosis and recurrent variceal bleeding. Although the rebleeding rate is higher after the modified Sugiura procedure, this does not seem to affect mortality in these patients.

Carcinoma, Hepatocellular↗
PubMed1996

Primary cultured normal human hepatocytes for hepatitis B virus receptor studies.

BACKGROUND/AIMS: We analyzed the hepatitis B virus envelope specificities (HBs, preS2 and preS1) involved in virus attachment to normal human hepatocytes, and we performed in vitro hepatitis B virus infection experiments without addition of dimethyl sulfoxide and polyethylene glycol, which may affect cell membrane integrity, in order to study further the early steps of the life cycle of the hepatitis B virus. METHODS: Primary normal human hepatocytes were prepared from surgical biopsies by the two-step collagenase perfusion technique, and cultured in a fetal calf serum-free medium supplemented with 10(-6) M dexamethasone. Cell-binding assays, ligand blotting and immunohistochemistry experiments were carried out using our anti-idiotypic (Ab2) antibodies (Ab2s/preS1, Ab2s/preS2 and Ab2s/HBs). RESULTS: Probing primary normal human hepatocytes, the 35-kDa major preS1-binding protein (preS1-BP35) we have previously identified in human hepatoma HepG2 cells was recognized in blotting, whereas both HBs- and preS1-specificities of the hepatitis B virus envelope interacted strongly with normal human hepatocyte cell membrane in cell-binding assays and immunohistochemistry experiments. Hepatitis B virus infectivity studies confirmed a great inter-experimental variability depending on donors and liver perfusion, and demonstrated a great intra-experimental variability depending on the serum-derived hepatitis B virus isolate used for the inoculation. In our culture conditions, only increased detection of the RC and CCC DNA forms of hepatitis B virus in cells and of hepatitis B virus surface antigens in medium was observed 4 to 8 days after exposure of cells to hepatitis B virus. CONCLUSION: These findings support a potential role for preS1-BP35 as a receptor protein for hepatitis B virus. In our hands, limitation(s) in the hepatitis B virus life cycle may occur at some step after virion binding, and likely result from complex regulation of reverse transcription of the RNA and translation of core protein by extrahepatic host factors or/and by the virus itself. However, the normal human hepatocyte model developed here is available for studying the initial steps in hepatitis B virus entry into cells.

Cell Membrane↗
PubMed1996

A case-control study of Salmonella gastrointestinal infection in Italian children.

A case-control study of 85 cases with non-typhoid Salmonella gastroenteritis, 85 outpatient controls and 79 inpatient controls was conducted among children in Monfalcone, north-east Italy, between June 1989 and June 1994. Logistic regression was used to evaluate the effect of demographic and socio-economic characteristics, duration of breastfeeding, history of intestinal illnesses and household diarrhoea, and the recent use of antimicrobials. Breastfeeding was the single most important factor associated with a 5-fold decreased risk of Salmonella infection. In addition, children who were treated with antimicrobials before onset of gastroenteritis had a 3-fold increased risk. Low social class and history of other chronic non-infectious intestinal diseases were also directly associated with illness.

Adolescent↗