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Biomedical subjects

D Franco

Publications and source records attributed to D Franco.

At least 91 records · Page 5Linked to original sources

Long-term hemodynamic effects of portocaval shunt and Sugiura procedure in patients with cirrhosis.

Systemic and splanchnic hemodynamics were studied before and six months after a portal systemic shunt (n = 6) or a Sugiura procedure (n = 9) in 15 patients with cirrhosis and a past history of variceal bleeding. Hepatic blood flow was estimated by hepatic extraction and clearance of continuous indocyanine green infusion. Azygos blood flow was measured with a continuous thermodilution catheter. After portocaval shunt, the cardiac index increased significantly from 4.0 +/- .4 to 5.4 +/- 0.8 l/min m2 (p < 0.05), the hepatic venous pressure gradient and hepatic blood flow were significantly decreased from 21 +/- 3 to 13 +/- 5 mm Hg (p < 0.05) and from 1.20 +/- 0.35 to 0.37 +/- 0.16 l/min (p < 0.05) respectively. The decrease in azygos blood flow was not significant (0.51 +/- 0.31 vs 0.25 +/- 0.33 l/min; p = 0.1). After Sugiura procedure, there was no significant change in cardiac index, hepatic venous pressure gradient, hepatic blood flow or azygos blood flow. This is the first study to show the long-term maintenance of splanchnic and systemic hemodynamics in patients with cirrhosis after Sugiura procedure. The absence of long-term hemodynamic alterations could explain the absence of encephalopathy after this procedure.

Azygos Vein↗

[Laparoscopic colectomy: technique and results].

Laparoscopic preparation before colectomy consists of freeing the colon laparoscopically followed by a small elective laparotomy for resection and anastomosis. From January 1993 to October 1994, we performed 86 consecutive planned colectomies including 16 (19%) which had laparoscopic preparation. In 3 of these cases (19%) the procedure was converted to laparotomy due to difficult dissection. The 13 patients with complete laparoscopically prepared colectomy were retained for this study. There were 9 men and 4 women, mean age 54 +/- 14 years (range 34-79). Indications for surgery were benign tumor (n = 4), metastatic cancer (n = 3), diverticulosis (n = 3), volvulus of the pelvic colon (n = 2), and endometriosis involving the sigmoid (n = 1). Operative procedures were: short segmentary colectomy (n = 6), sigmoidectomy (n = 5), right colectomy (n = 2). Surgery duration was 280 +/- 75 minutes (range 150-390). The post-operative period was uneventful in all patients. Bowel activity resumed on the second day after surgery in most patients. Mean hospitalization time was 7.4 +/- 1.4 days (range 5-10 days). Laparoscopically prepared colectomy is a reliable simple method providing good patient comfort post-operatively. This technique should find its place in surgery of the colon.

Adult↗

[Towards gene therapy in familial hypercholesterolemia].

Familial hypercholesterolemia (FH) is an inherited disease caused by a defect in the gene encoding the Low Density Lipoprotein receptor (LDL-R). The ex vivo hepatic gene therapy which restore the expression of the normal protein in hepatocytes should correct the disease. Improved transduction efficiency and long lasting expression of the transduced gene remain the main goals of gene therapy research. We developed an efficient and reliable method for in vivo transduction of human, mouse and primate primary hepatocytes. A retroviral vector bearing the LDL-R cDNA driven by the liver-type pyruvate kinase promoter allows high and tissue specific expression of the gene in primary hepatocytes. A second vector with a housekeeping promoter corrects the LDL-R deficiency in fibroblasts from a FH patient. Ex vivo preclinical studies in non-human primates will provide new insight in transduced cells biology after reimplantation.

Animals↗

An unusual cause for lumbar radiculopathy: a synovial facet joint cyst of the right L5 joint.

OBJECTIVE: To report a rare cause of lumbar radiculopathy. CLINICAL FEATURES: A 72-yr-old man suffered from pain that radiated down the posterior thigh and calf for 3 wk. The right foot and first toe extensors were weak and sensation was decreased over the dorsum of the foot. Straight leg raising was positive at 50 degrees on the right. Computed tomography with contrast revealed a large cyst with focal vacuum change with displacement of the dural sac at the L4-5 level. INTERVENTION AND OUTCOME: An L4-5 laminectomy and facetectomy was performed with relief of the patient's complaint. The patient resumed full activity at 3 months. CONCLUSION: An unusual cause of an L5 radiculopathy is discussed. Of the reported cases, surgical intervention has been the treatment of choice. Conservative treatment, including injections with corticosteroids and chiropractic management, have been reported to be successful. Further investigations using controls are needed to determine if conservative care is more cost-effective than surgical intervention.

Aged↗

[Treatment of digestive hemorrhages caused by rupture of esophagogastric varices in liver cirrhosis].

Bleeding from oesophageal and gastric varices is one of the most dramatic and important complications of cirrhosis. Non surgical options are favoured as first line treatment because the operative mortality in cirrhotic patients is high. These options include vasoactive drugs (terlipressin or somatostatin) and endoscopic treatment or a combination of these two treatments. Vasoactive drugs could be given before endoscopic treatment and perhaps even earlier during transfer to hospital to permit a therapeutic measure to be given at initial diagnostic endoscopy when bleeding is controlled and the patient stable. Balloon tamponade should be used only in patients with uncontrolled bleeding. Surgical portacaval shunt or transjugular intrahepatic portosystemic stent shunts is used as a second line treatment when all else has failed to control bleeding and because of an increased mortality risk surgery should never be too much delayed.

Esophageal and Gastric Varices↗

Cholangitis associated with paroxysmal nocturnal hemoglobinuria: another instance of ischemic cholangiopathy?

Ischemia is increasingly recognized as a cause of cholangiopathy. The aim of this study was to report a case of association of paroxysmal nocturnal hemoglobinuria with abrupt-onset cholangiopathy. Anomalies resembling sclerosing cholangitis were documented in a patient suffering from recurrent biliary pain. None of the conditions that have been associated with primary sclerosing cholangitis or other forms of cholangiopathy was present, but shortly thereafter, paroxysmal nocturnal hemoglobinuria occurred. Hepatic vein thrombosis later complicated the course of the disease. Because the fortuitous coincidence of these uncommon conditions is unlikely, this case indicates that paroxysmal nocturnal hemoglobinuria is a cause of ischemic cholangiopathy. Other thrombogenic conditions may also be implicated in some instances of apparently idiopathic cholangiopathy.

Adult↗

Structure and expression of the cyclin A gene in human primary liver cancer. Correlation with flow cytometric parameters.

BACKGROUND/AIMS: The cyclin A gene plays an important role in both the S and G2-M phases of the cell cycle, and has been identified at a site of hepatitis B virus DNA integration in a human liver cancer. We analyzed tumorous and non-tumorous samples from patients with primary liver cancer to determine whether a) the cyclin A gene is rearranged in liver tumors and b) the cyclin A transcript level correlates with the percentage of proliferating cells. METHODS: Samples from 43 patients were analyzed by Southern blot. Cyclin A RNA accumulation was evaluated in 18 cases by slot blot and correlated with the percentage of cells in S plus G2-M phases defined by flow cytometry. RESULTS: No rearrangement of the cyclin A gene was found in tumorous compared to non-tumorous tissue. A very strong positive correlation was found between the cyclin A RNA level and the cumulative percentage of cells in S plus G2-M phases (r = 0.99; p < 0.0001). CONCLUSIONS: This in vivo study shows that the expression of cyclin A RNA correlates with the percentage of proliferating cells in primary liver cancer. Thus, cyclin A is a new potential liver tumor cell proliferation index.

Blotting, Southern↗

Effects of ursodeoxycholic acid and chenodeoxycholic acid on human hepatocytes in primary culture.

Hepatic bile acid concentrations are elevated in chronic cholestasis because of reduced canalicular excretion and active ileal absorption of the fraction eliminated in the gut. Ursodeoxycholic acid (UDCA) reduces the intestinal absorption of endogenous bile acids, thereby diminishing the concentrations to which liver cells are exposed. In the isolated perfused liver (in which vectorial bile acid transport is maintained), UDCA reduces the cytotoxic and cholestatic effects of endogenous bile acids. As a result, it has been suggested that UDCA or one of its conjugates could have a direct protective effect on hepatocyte structure and function. We therefore studied the effects of chenodeoxycholic acid (CDCA) and tauroursodeoxycholic acid (TUDCA) alone and in combination on the viability and certain functions of human hepatocytes in primary culture. TUDCA did not affect intracellular concentrations of CDCA when added concomitantly. In other experiments, CDCA (100 to 500 mumol/L) induced concentration-dependent increases in lactate dehydrogenase (LDH) leakage and decreases in cellular protein synthesis and albumin secretion. Neither TUDCA nor UDCA had similar effects at the same concentrations, nor did they have a protective effect when added concomitantly with CDCA at equimolar or twice-equimolar concentrations. These results suggest that UDCA has no direct cytoprotective effect when the bile acid concentrations to which human hepatocytes are exposed are unchanged. They also suggest that the hepatoprotective effect of UDCA in cholestatic human liver diseases and in the isolated perfused liver loaded with hydrophobic bile acids occurs through its effect on intestinal and hepatocyte transport systems.

Bile Acids and Salts↗

Primary lymphoplasmacytic lymphoma of the liver associated with a serum monoclonal peak of IgG kappa.

We report a case of primary lymphoma of the liver successfully treated by major liver resection. The tumor exhibited the immunohistological features of a B-cell low-grade lymphoma of the lymphoplasmacytic type. Tumoral plasmacytic cells showed cytoplasmic-positive staining for IgG and kappa light chains. In addition, we detected a serum monoclonal peak of IgG kappa, a finding that has not been reported previously. Clinical, pathological, and immunohistochemical data from the literature are reviewed.

Adult↗

Selective accumulation of the X transcript of hepatitis B virus in patients negative for hepatitis B surface antigen with hepatocellular carcinoma.

In HBsAg-negative patients with hepatocellular carcinoma (HCC), hepatitis B virus (HBV) genomes are present at a low copy number per cell, and the role of HBV in liver transformation is still unclear. We have mapped by polymerase chain reaction (PCR) the HBV genome in 19 HBsAg-negative tumorous and 9 corresponding nontumorous tissues and evaluated, by RT-PCR, the presence of HBV S, X, and C transcripts in the tumorous and nontumorous tissue of nine HBsAg-negative and, for comparison, six HBsAg-positive patients. Disrupted, presumably integrated, HBV genomes were detected by PCR in 10 of 19 tumorous tissues and in only one of nine nontumorous tissues. Significant accumulation of viral RNAs containing X but not C or S sequences was shown in 7/9 tumors and 7/8 nontumorous tissues from HBsAg-negative patients. In contrast, viral RNAs revealed by X-as well as by S- and C-specific primers were detected in five of six tumors and in six of six nontumorous tissues from HBsAg-positive patients. In conclusion, our results suggest the frequent integration of the HBV genome and the accumulation of X-related RNAs in HCCs developing in HBsAg-negative patients. This finding is consistent with a role, in these cases, for the potentially transforming X protein.

Adolescent↗

Transforming growth factor-beta 1 (TGF-beta 1) and TGF-beta 1 receptors in normal, cirrhotic, and neoplastic human livers.

Transforming growth factor-Beta 1 (TGF-beta 1) is an important mediator of control of liver cell proliferation and replication. The aim of the current study was to compare TGF-beta 1 gene expression, protein synthesis, and cell membrane receptors in normal liver, cirrhotic nodules, and neoplastic human livers. Five surgical resections for metastasis in an otherwise normal liver and 25 resections for hepatocellular carcinoma with cirrhosis were included in this study. Messenger RNA (mRNA) and TGF-beta 1 protein were detected on serial tissue sections of normal, cirrhotic, and tumoral livers using in situ hybridization and immunohistochemistry. TGF-beta 1 type II receptors were detected on tissue sections using immunohistochemistry. In normal livers, TGF-beta 1 mRNA and protein were not significantly expressed. In cirrhotic nodules, a few sinusoidal cells and mesenchymal cells of fibrous septa displayed TGF-beta 1 mRNA. By immunohistochemistry, protein was detected in the extracellular matrix along the fibrous septa. Hepatocytes from normal and cirrhotic livers did not express TGF-beta 1. In contrast, the cytoplasm of hepatocytes in neoplastic nodules showed intense staining for TGF-beta 1 mRNA and protein. Although TGF-beta 1 receptor II was expressed on the plasma membrane of normal liver cells, tumoral hepatocytes no longer displayed membrane labeling but rather diffuse intracytoplasmic staining with perinuclear accumulation. This study suggests that the escape of tumoral hepatocytes from control of cell proliferation by TGF-beta 1, despite its overexpression by these cells, might be related to a defect in TGF-beta 1 receptor II processing on the liver cell membrane.

Carcinoma, Hepatocellular↗

[Giant hemangioma of the liver disclosed by fever and an inflammatory syndrome. Apropos of 3 cases].

Three cases of giant liver haemangioma were revealed by fever and biological inflammatory changes, which disappeared after resection of the haemangioma. These rare symptoms accompanying liver haemangioma may lead to misdiagnosis. Resection whenever possible results in the disappearance of symptoms. Anatomic necrotic changes inside the angioma seem to be the cause of these inflammatory patterns.

Aged↗

[Hormone-mediated calcium responses of rat and human hepatocytes. Study of multicellular systems by videomicroscopy].

OBJECTIVES AND METHODS: Activation of hepatocyte hormonal receptors leads to the mobilization of intracellular Ca2+ which is thought to be an elaborate system for encoding hormonal messages. We studied hormone-induced calcium signals in freshly isolated multicellular systems of normal rat and human hepatocytes. Calcium signals were recorded by videomicroscopy after stimulation with noradrenaline, angiotensin II, and vasopressin. RESULTS: Calcium signals were highly organized in multiplets: the different hepatocytes responded to Ca(2+)-mobilizing hormones in a sequentially ordered manner, with a first, a second (doublets) and a third (triplets) responding cells. This pattern was an intrinsic feature of the multicellular systems, and seemed to be a result of a gradual heterogeneity of the sensitivity of the different cells, to the hormones. The stimulation of the same multiplet with two different agonists and the removal of the hormone during cell responses provides some evidence for the major role of hormonal receptors in this heterogeneity. CONCLUSIONS: Hormone responses in multicellular systems of rat and human hepatocytes are highly elaborate. The density of hormonal receptors could be the major determinant of the sequential pattern of Ca2+ responses. Hormonal receptors may be gradually distributed among the different cells of the multiplets in vitro and along the porto-centrilobular axis in situ.

Angiotensin II↗

Results of major hepatectomy for large primary liver cancer in patients with cirrhosis.

Major hepatectomy is associated with a high operative risk in patients with cirrhosis. Between June 1983 and December 1991, 33 cirrhotic patients, 31 with good liver function, underwent major liver resection for a large hepatic primary cancer. The hospital mortality rate was 3 per cent; the only death resulted from liver failure after extended right hepatectomy. None of the patients had variceal bleeding during the postoperative period. Survival rates at 1, 2 and 3 years were 66, 43 and 37 per cent respectively. Recurrence was the most common reason for late death. These results suggest that the operative risk of major hepatectomy in cirrhotic patients with a large tumour and good liver function is comparable to that of minor liver resection. Late survival is also similar to that of patients with a small tumour. Cirrhotic patients with hepatic carcinoma and good liver function are suitable for major hepatectomy.

Adult↗