Traumatic cerebral aneurysm associated with a contralateral traumatic carotid cavernous fistula. A case report.

SUMMARY: This report documents the management of a traumatic carotid aneurysm (TCA) with a traumatic carotid-cavernous fistula (T-CCF) of the contralateral internal carotid artery (ICA) following a closed head injury. A 38-year-old man presented with severe traumatic subarachnoid hemorrhage and pneumocephalus due to a severe head injury. Four months after the accident, the patient presented with clinical symptoms of exophthalmos and retroorbital bruit. Cerebral angiography showed a TCA of the IC-PC region, which coexisted with a contralateral T-CCF. Both lesions were successfully managed with an endovascular treatment using coils to isolate a fistula from the ICA, and direct surgical trapping of the intracranial ICA to eliminate a TCA. Post-operative angiography revealed a good cross-flow through the anterior communicating artery from the contralateral ICA, which was completely obliterated by the T-CCF. No additional surgical or endovascular procedure for traumatic vascular injuries was required. The patient remained asymptomatic during the clinical follow-up period of 24 months. The goal of traumatic carotid injuries is the selective elimination of the vascular pathologic injury with asymptomatic state, using direct surgery and/or an endovascular treatment.

Modulation of human c-mpl gene expression by thrombopoietin through protein kinase C.

The c-Mpl, thrombopoietin (TPO) receptor specificially controls megakaryocytic growth and differentiation. TPO increased the c-mpl promoter activity determined by a transient expression system using a vector containing the luciferase gene as a reporter in the human megakaryoblastic cell line CMK. The maximal promoter activity of c-mpl was obtained 24 hr after pretreatment with TPO for 3 hr and then declined with time. This increase was completely abolished by protein kinase C (PKC) inhibitors (GF109203, calphostin C and H7). Phorbol 12-myristate 13-acetate (PMA) treatment led to an increase in c-mpl promoter activity. These results demonstrate that the promoter activity of c-mpl is modulated by transcription through a PKC-dependent pathway.

Primary sclerosing cholangitis successfully treated by resection of the confluence of the hepatic duct.

Primary sclerosing cholangitis (PSC) is a cholestatic disease characterized by chronic inflammatory fibrosis of the extra- and intrahepatic bile ducts. Although the prognosis of patients with PSC was believed to be poor, some patients have not experienced the expected rapid clinical progression. A 51-year-old man with PSC was initially hospitalized for jaundice. Laboratory data showed low levels of the complement components C3, C4, and CH50. Percutaneous transhepatic biliary drainage was performed. Cholangiography revealed complete obstruction of the common bile duct below the confluence of the cystic duct. The confluence of the hepatic duct was resected and it was reconstructed by hepaticojejunostomy for palliation of the obstructive jaundice. Increased thickness of the walls of the common bile duct, right hepatic bile duct, and gallbladder was observed. Histopathological examination of the resected specimen revealed periductal fibrosis, with an onion-skin-like appearance. The patient is currently doing well, approximately 7 years after the surgery, without any signs of PSC recurrence. In this extraordinary patient, the laboratory data for C3, C4, and CH50 showed a complete return to normal levels. The positive results in this patient suggest that resection of the confluence of the hepatic duct may be an effective surgical treatment for noncirrhotic PSC patients who have dominant extrahepatic strictures.

Drainage for acute pancreatitis.

In severe acute pancreatitis, the drainage of activated pancreatic enzymes, infectious substances and necrotic tissue from the abdominal cavity is critical, especially after the operation. We use Faycon drainage tubes together with multi-use feeding tubes. Just after the operation, normal saline is added through the feeding tube and the Faycon drainage tube is suctioned continuously. Irrigation is necessary for more than two weeks.

Effect of gravity change on the production of thrombopoietic growth factors.

It is reported that the stay in the space develops anemia, thrombocytopenia, and altered function and structure of red blood cell. The mechanism of these abnormalities was not clarified yet. The cloning of the thrombopoietin (TPO), followed by the analysis of TPO and c-mpl (its cellular receptor) knockout mice confirmed its role as the primary regulator of thrombopoiesis. TPO has been shown to stimulate both megakaryocyte colony growth from marrow progenitor cells and the maturation of immature megakaryocyte to form functional platelet. This process includes the massive cytoskeletal rearrangement, such as proplatelet formation and fragmentation of proplatelet. In this study we have focused on the production of thrombopoietic growth factors in mice those were exposed to gravity change by parabolic flight (PF).

Effect of gravity change on thrombopoiesis in mice.

It is reported that the stay in the space develops anemia, thrombocytopenia, and altered function and structure of red blood cell. The mechanism of these abnormalities was not clarified yet. Therefore, it is necessary to elucidate the mechanism of the effect of the gravity change on the thrombocytopoiesis, which plays the important role for the hemostasis, using animal models. The cloning of thrombopoietin (TPO), followed by the analysis of TPO and c-mpl (its cellular receptor) knockout mice confirmed its role as the primary regulator of thrombopoiesis. TPO has been shown to stimulate both megakaryocyte colony growth from marrow progenitor cells and the maturation of immature megakaryocyte to form functional platelet. This process includes the massive cytoskeletal rearrangement, such as proplatelet formation and fragmentation of proplatelet. In this study we have focused on the thrombopoiesis in mice those were exposed to gravity change by parabolic flight (PF).

Current status of bacterial contamination of autologous blood for transfusion.

Autologous transfusion, although not without risk, does decrease the risk of transmitted diseases via homologous transfusion. However, strict quality control is required for autologous transfusion. In Japan, a recent enactment requires that written informed consent be obtained prior to blood transfusion, which therefore requires that clinicians provide sufficient explanation of the risks involved with this procedure. To the best of our knowledge, this is the first study to comprehensively evaluate the manner in which the safety of autologous blood transfusion can be compromised by bacterial contamination. For a 24-month period, between April 1996 and March 1998, bacterial contamination of all kinds of autologous blood samples was tested by sampling the culture immediately prior to transfusion. Subculturing, identification and susceptibility testing of the isolates were performed. From the 287 units of all kinds of autologous blood transfused, 18 were culture positive (6.3%). Positive blood cultures were obtained in two of the 59 units (3.4%) of autologous transfusion donated preoperatively (ATDP) that was infused intraoperatively, in three of the 117 units (2.6%) of hemodilution/autologous transfusion (HAT) and in three of the 81 (3.7%) of ATDP infused postoperatively. There was a high percentage (33.3%) of positive blood cultures in the cases of intraoperative blood salvage (IOBS). The total rate of positive blood cultures was 6.3% including IOBS and 3.1% excluding IOBS. The most common microorganism isolated from autologous blood was coagulase-negative Staphylococci in 12 of 18 culture-positive units (66.7%). Alpha Streptococcus uiridans was isolated in 2 units (11%) and Staphylococcus aureus was isolated in 1 unit (5.5%). However, none of the patients who received the culture-positive autotransfusion blood showed clinical signs or laboratory findings of bacteremia. Safe ATDP is threatened by bacterial contamination that can be introduced by numerous sources, such as the donors' blood, the skin at the site of venipuncture, the environment and the phlebotomist's finger. In the cases of IOBS, protection against bacterial contamination at the surgical site is crucial. Here we discuss the relevance of our findings to the efforts to minimize the risks of contamination associated with autologous blood transfusion; risks that must be communicated to the patient in the process of informed consent. Continued research is required to identify the safest method of autologous blood transfusion.

Successful resection of a liver metastasis from gastric leiomyoblastoma: report of a case.

A 20-year-old woman was referred to our hospital for detailed investigation of a gastric submucosal tumor. A leiomyoma was preoperatively diagnosed and laparoscopic-assisted enucleation was performed. The resected tumor was 4 x 3 x 1.5 cm in size and postoperative histological examination identified it as a gastric leiomyoblastoma. Therefore, a secondary resection in the form of a distal gastrectomy was carried out. No tumor cells were found in the gastric specimen or in the lymph nodes; however, 5 months after the operation, an abdominal computed tomography scan revealed a recurrence in the liver, and she was readmitted for further examinations. The lesion was diagnosed as a single liver metastasis from the gastric leiomyoblastoma and successfully resected. The histopathological findings of the liver tumor resembled those of the primary gastric tumor. Her postoperative course was uneventful and she has been well, without any evidence of recurrence, to date. Only 12 other cases of leiomyoblastoma of the stomach with liver metastasis have been reported in Japan, all of which were associated with a very poor prognosis. Therefore, patients with this unusual disease entity should be carefully followed up after resection of the primary tumor.

Measurements of cortical cellular pH by intracranial tonometer in severe head injury.

OBJECTIVE: To evaluate the cortical cellular damage in acute severe head injury, we measured the cortical cellular pH by using an intracranial tonometer made in our institution. DESIGN: Prospective, 3.5-yr data collection. SETTING: University hospital trauma intensive care unit. PATIENTS: Severely head-injured patients (n = 29) with Glasgow Coma Scale score <8. INTERVENTION: Routine emergency neurologic procedure. MEASUREMENTS AND MAIN RESULTS: We made 98 measurements of cortical cellular pH by intracranial tonometer in 29 severely head-injured patients in the acute phase. Each patient's intracranial pressure was recorded, and in 16 patients, the saturation of jugular venous oxygen was monitored. The outcome at 6 months after injury was significantly better in patients having a cortical cellular pH of >7.2 than those with <7.2. The cerebral perfusion pressure and cortical cellular pH correlated significantly (p < .0001). CONCLUSIONS: Our study suggests the usefulness of measurement of cortical cellular pH by intracranial tonometer for evaluating the severity of focal anaerobic cerebral metabolism and predicting patient prognosis.

HIV infection of megakaryocytic cell lines.

Thrombocytopenia is a common hematologic disorder in HIV infection and occurs in both asymptomatic and AIDS patients. An autoimmune mechanism has been postulated for the platelet destruction associated with some forms of thrombocytopenia. However, recent studies revealed that megakaryocytes are susceptible to HIV infection and suggested the possibility that HIV can directly impair the platelet production from megakaryocytes. This study was designed to characterize the HIV receptor expression in megakaryocytic cells and the responsiveness to HIV infection. Four different megakaryocytic cell lines at different stages of differentiation were established from the peripheral blood of different individuals with hematologic malignancies. CMK and CMY cells (differentiated cell lines) expressed CD4, but CMS and CTS cells (poorly differentiated cell lines) did not. The HIV coreceptor CXCR4 was also expressed in CMY and CMK cells. HIV-1 (HTLV-IIIB) replicated in CMY cells persistently but not in other three cell lines. CMY cells as well as CMK cells were also susceptible to the lytic infection of HIV-2 (LAV2). Pretreatment of the CMY cells with anti-CD4 antibody inhibited the infection by both HIV-1 and HIV-2. Our results indicate that mature megakaryocytic cells express CD4 along with HIV coreceptors and are susceptible to HIV infection.

Endovascular Management of Intradural Berry Aneurysms. Review of 203 Consecutive Patients Managed between 1993 and 1998 Morphological and Clinical Results at Mid-Term Follow-up.

SUMMARY: Endovascular management of intracranial arterial aneurysms (AA) is well described and performed by many teams. The aim of this work is to review a series of consecutive cases treated in our institution and to compare to the data available in the literature. 225 AA were seen in Bicêtre between 1993 and 1998 in 203 patients. 201 of them (in 180 patients) were treated by our group. The endovascular treatment, its indications, results and complications have been reviewed and studied. The clinical follow-up of the patients has been evaluated. A female dominance was noted (64.5%) with a mean age of patients of 44.3 years. 65.6% of patients were treated in the acute phase after intracranial haemorrhage, 72% of them being Hunt and Hess grade 1 or 2. Most of these AA (73.6%) were located in the anterior circulation. In 86.1% of cases the AA was smaller than 10 mm. 85.6% of the AA needed only one session of endovascular therapy. No mortality occurred in the group of unruptured AA. Overall management mortality was 11% in ruptured AA (3.5% in HH1-2, 30.3% in HH3-5).Technical or transient complications occured in 11.6% of cases, but permanent morbidity was seen in 3.1% of cases. Control angiograms were performed 3 months and one year after therapy. In doubtful cases a control at 6 months was also performed. 100% occlusion rate was noted in 60.8% of cases; 22.8% of AA were occluded between 90-99%, and 13.3% between 80-90%. Only 3.1% of AA had an occlusion rate of less than 80%. One patient with a ruptured basilar tip AA which was partially coiled regrew and rebled three months after. The patient declined the recommended complementary surgery. Clinical follow up of patients with ruptured AA treated by embolisation shows satisfactory results with 8.5% of GOS 1-2, 3.4% of GOS 3-4, and 11% of GOS 5 (mortality). Overpacking of the AA may not be necessary to protect patients from (re)bleeds over time. The related technical risks and increased costs of dense overpacking do not seem justified. Secondary thrombosis of the ruptured AA after coiling is more often seen than coil compaction. Analysis of the AA architecture and recognition of false aneurysms are mandatory in order to obtain good clinico-morphological logical results.

Change of liver function in hypertrophying lobe of rabbit liver after portal branch ligation.

Preoperative portal embolization (PE) is useful for the prevention of postoperative liver failure after extended hepatectomy. However, clinical evaluation of liver function in the hypertrophying lobe after PE has not been studied. Here we report functional changes in the hypertrophying lobe using a 80% portal-branch-ligation rabbit model. Liver function was evaluated by the expression of liver-specific genes detected by Northern blot analysis and plasma disappearance rate of indocyanine green (ICG). The weight of the unligated lobe after portal ligation increased about twofold on the 7th postoperative day (POD) and about threefold on the 14th POD. The mRNA levels of the liver-specific genes (albumin, aldolase B, and tyrosine aminotransferase) in the unligated lobe decreased to about 50% on the 1st POD and returned to the preoperative levels on the 7-14th POD. In contrast, the expression of histone H2B mRNA increased on the 3rd-7th POD. The plasma disappearance rate of ICG (K-ICG) in the rabbit that has only the unligated lobe did not significantly change during the first 7 days, but then improved and recovered to 80% of that in the rabbit that has whole liver on the 14th POD. These results indicate that liver function of the hypertrophying lobe after portal branch ligation does not increase during the first 7 days despite an increase in liver weight. This finding suggests that the compensatory hypertrophying liver is enlarging without functional augmentation in the early period after PE.

Experimental study on the bilirubin metabolism after major hepatectomy: alterations in the proportions of bile bilirubin subfractions.

Bilirubin metabolism after major hepatectomy was investigated experimentally using rats. After a 70% and an 80% hepatectomy, proportions of bilirubin diglucuronide (BDG) decreased, and reversely, those of bilirubin monoglucuronide (BMG) increased. These changes were even more remarkable after an 80% hepatectomy. Parallel to the decrease in the proportions of BDG, the concentrations of uridine diphosphoglucuronic acid (UDP-GA) in the remnant liver decreased, and there was a significant correlation between the changes in BDG and UDP-GA. Although UDP-glucuronyltransferase (UDP-GT) activity and energy charge of the remnant liver also decreased after surgery, these decreases were mild and returned to the control level earlier than BDG. And there was no significant correlation between the changes in BDG and those in UDP-GT activity and energy charge. In this study, the decrease of the proportions of BDG in the bile juice was long term after partial hepatectomy and the period of the decrease became longer according to the augmentation of the volume of the hepatectomized liver. We clarified that the process of the UDP-GA production was inhibited after hepatectomy and the decrease of the proportions of BDG was derived from a deficiency of substrate of the glucuronidation, UDP-GA.

The role of skeletal muscle and liver on lactate metabolism during hypoxia in rats.

PURPOSE: This study was planned to investigate whether the skeletal muscle and liver produce or consume lactate under hypoxic conditions. METHODS: Wister rats were anesthetized and mechanically ventilated. Microdialysis probes were inserted into the rat skeletal muscle and liver, and arterial cannulation was performed. Hypoxia was induced for 30 min by the inhalation of 10% oxygen in nitrogen. Interstitial lactate concentrations in the skeletal muscle and liver were measured using an in vivo microdialysis method before, during, and after hypoxic hypoxia. The blood lactate concentration, mean arterial blood pressure, and blood gas were also measured. RESULTS: Before hypoxia, there was no significant difference among the blood lactate concentration and interstitial lactate concentrations of the skeletal muscle and liver. During hypoxia, arterial oxygen tension decreased to 34.2 +/- 1.3 mmHg, and the lactate concentrations in these tissues increased significantly in comparison to the control values. However, the lactate concentrations in the skeletal muscle and liver interstitium were significantly lower than that in the blood, with the peak lactate concentration in the skeletal muscle interstitium being only one-third of that in the blood. After correction of hypoxia, the blood lactate concentration decreased to levels comparable to the skeletal muscle and liver interstitial lactate concentrations. CONCLUSION: It is suggested that the skeletal muscle as well as the liver may consume lactate under hypoxic hypoxia.

Establishment of a new human megakaryoblastic cell line, CMY, with chromosome 17p abnormalities.

A new megakaryoblastic cell line CMY was established from a Down's syndrome patient suffering from acute megakaryoblastic leukemia. The karyotypes of CMY showed deletion of chromosome 17 or the translocation of 17p, whereas the blasts of the patient did not reveal these abnormalities of chromosome 17 by conventional karyotype analysis. Blasts of the patient failed to respond to chemotherapy and complete remission could not be attained. The abnormalities of 17p became progressively predominant in the patient. These results suggest that the blasts of a minor clone which had the abnormalities of chromosome 17p might have existed in the patient from the beginning and CMY was established from the minor clone. Investigation of p53 gene by PCR-SSCP analysis revealed that blasts of the patient showed normal patterns, while CMY showed an abnormally migrating band in exon 5 alone. This result suggests that another novel oncogenic factor(s) besides p53 might be present on chromosome 17p and other tumor suppresser genes need to be studied.

Altered biliary bilirubin profile in patients with persistent hyperbilirubinaemia after hepatic resection: analysis of bile bilirubin subfractions by high-performance liquid chromatography.

Subfractions of bilirubin in bile, obtained via biliary drainage tubes from 23 patients who had undergone radical surgery for bile duct cancer, were analysed by high-performance liquid chromatography for 14 days after surgery. Five principal conjugated bilirubins were resolved: bilirubin diglucuronide (BDG); bilirubin monoglucuronide monoglucoside (BGG); bilirubin monoglucuronide monoxyloside (BGX); and two isomers of bilirubin monoglucuronide. After surgery, depression in concentration of BDG and elevation of BGG and BGX were found. These alterations were of higher magnitude in patients who had undergone hepatectomy, and especially prolonged in patients with hyperbilirubinaemia. These results suggest that the alteration in proportions of bilirubin conjugates might be a cause of hyperbilirubinaemia after hepatectomy.

Binding and regulation of thrombopoietin to human megakaryocytes.

Thrombopoietin (TPO, c-Mpl ligand) is considered to play an important role in the regulation of megakaryocytopoiesis and platelet production by activating the cytokine receptor c-Mpl. We have examined the binding of 125I-TPO to the human megakaryocytic cell line, CMK, and to primary human megakaryocytes. Scatchard analysis of TPO binding to its cognate receptor in megakaryocytic cells suggested the existence of a single class of c-Mpl receptors. CMK cells exhibited 1223 receptors per cell with a dissociation constant (Kd) of Kd = 223 pM, whereas primary human megakaryocytes exhibited 12140 receptors per cell and a dissociation constant of Kd = 749 pM. The pretreatment of CMK cells and primary bone marrow megakaryocytes with TPO resulted in a decreased binding of TPO to the c-Mpl receptors. This down-regulation was observed within 3 h and was not inhibited by cycloheximide. Phorbol ester, an activator of protein kinase C, also inhibited TPO binding to the c-Mpl receptors by reducing the number of these receptors. The pretreatment of CMK cells with IL-3, IL-6 and DMSO, all of which induced the differentiation of CMK cells, did not affect the binding of TPO to the c-Mpl receptors. These results suggest an additional mechanism, where protein kinase C may help to regulate the binding of TPO to these cells.

Results of surgical treatments and prognostic factors for hepatic hilar bile duct cancer.

Results of surgical treatments for 57 patients who underwent resection for hepatic hilar bile duct cancer between 1984 and 1997 were studied. Bile duct resection was performed in eight patients, and combined resection of bile duct and liver was performed in 49 patients, of whom vascular reconstruction was added in 15 patients and pancreatoduodenectomy (PD) in six patients. All the operations of bile duct resection that were not combined with hepatectomy were non-curative. In the patients who underwent combined resection of the bile duct with liver, outcomes of the patients with well-differentiated adenocarcinoma were better than those with other lower-grade tumors. The factors related to the degree of tumor extension, such as serosal invasion, lymph node metastasis, lymphatic vessel invasion, perineural invasion, venous vessel invasion, and vascular involvement, were other factors which significantly influenced the survival. Curative resection yielded significantly better results than non-curative resection. Of all these variables, good tumor differentiation and vascular involvement were recognized as important prognostic factors by multivariate analysis. Most of the postoperative deaths were encountered in patients who underwent additional operations to hepatectomy, such as vascular reconstruction or PD. Improvement of surgical techniques and perioperative care has yielded better outcomes of vascular reconstruction. However, the application of hepatopancreatoduodenectomy should be limited due to poor outcomes of widespread bile duct cancer of which the histological grade is usually low. Whereas prognosis of bile duct cancer involving the hepatic hilus is mainly determined by the biologic characteristics of the tumor, surgeons should consider the fact that most patients die of local recurrence regardless of the biologic character of the tumor when curative resection is not performed.

Therapeutic efficacy of BO-3482, a novel dithiocarbamate carbapenem, in mice infected with methicillin-resistant Staphylococcus aureus.

The in vivo activity of BO-3482, which has a dithiocarbamate chain at the C-2 position of 1beta-methyl-carbapenem, was compared with those of vancomycin and imipenem in murine models of septicemia and thigh infection with methicillin-resistant Staphylococcus aureus (MRSA). Because BO-3482 was more susceptible than imipenem to renal dehydropeptidase I in a kinetic study of hydrolysis by this renal enzyme, the therapeutic efficacy of BO-3482 was determined during coadministration with cilastatin. In the septicemia models, which involved two homogeneous MRSA strains and one heterogeneous MRSA strain, the 50% effective doses were, respectively, 4.80, 6.06, and 0.46 mg/kg of body weight for BO-3482; 5.56, 2.15, and 1.79 mg/kg for vancomycin; and >200, >200, and 15.9 mg/kg for imipenem. BO-3482 was also as effective as vancomycin in an MRSA septicemia model with mice with cyclophosphamide-induced immunosuppression. In the thigh infection model with a homogeneous MRSA strain, the bacterial counts in tissues treated with BO-3482-cilastatin were significantly reduced in a dose-dependent manner compared with the counts in those treated with vancomycin and imipenem-cilastatin (P < 0.001). These results indicate that BO-3482-cilastatin is as effective as vancomycin in murine systemic infections and is more bactericidal than vancomycin in local-tissue infections. The potent in vivo activity of BO-3482-cilastatin against such MRSA infections can be ascribed to the good in vitro anti-MRSA activity and improved pharmacokinetics in mice when BO-3482 is combined with cilastatin and to the bactericidal nature of the carbapenem.