Magnetic resonance imaging of sequelae of central pontine myelinolysis in chronic alcohol abusers

Central pontine myelinolysis (CPM) is one of the serious neurological complications of alcoholism. This study evaluated magnetic resonance images of sequelae of CPM. Approximately 600 alcoholic patients were examined by a 1.0-T magnetic resonance imaging device, and 11 patients were retrospectively found to have a central pontine lesion, a presumed sequela of CPM. The lesions had various shapes and most were cavitary. In 3 of the 11 patients bilateral symmetrical oval lesions were faintly visible in the middle cerebellar peduncles. These middle cerebellar peduncular lesions were diagnosed as having Wallerian degeneration of the pontocerebellar tract secondary to CPM.     

Contributions of bronchoscopic microsampling in the supplemental diagnosis of small peripheral lung carcinoma

BACKGROUND: Making a preoperative pathologic diagnosis in patients with small lung nodules remains challenging. We have developed a new, noninvasive bronchoscopic microsampling probe to examine biochemical substances in epithelial lining fluid. We used this probe to measure tumor markers in fluid from tissues surrounding lung nodules less than 30 mm in diameter to test its adjunctive diagnostic utility in lung cancer. METHODS: In 12 patients, epithelial lining fluid was collected in triplicate or duplicate from tissue within 2 cm of small peripheral lung nodules and from the contralateral lung. The diagnosis of adenocarcinoma was surgically confirmed in all patients. Fifteen patients without lung cancer served as controls. Concentrations of carcinoembryonic antigen, cytokeratin fragment 19, and sialyl SSEA-1 were measured in the fluid. RESULTS: Carcinoembryonic antigen and cytokeratin fragment 19 concentrations were significantly higher in fluid near the nodules (median, 8.7 and 87.2 ng/mg, respectively) than on the contralateral sides (median, 1.5 and 3.7 ng/mg, respectively) or in fluid collected from the controls (median, 2.0 and 2.8 ng/mg, respectively). CONCLUSIONS: Measurements of carcinoembryonic antigen and cytokeratin fragment 19 collected by our microsampling probe may be a useful diagnostic adjunct in patients with small peripheral lung nodules.     

Five- and 10-year survival rates after surgery for biliary atresia: a report from the Japanese Biliary Atresia Registry

Purpose

The aim of this study was to elucidate the epidemiology and short- and long-term results of biliary atresia in Japan analyzing the data of the Japanese Biliary Atresia Registry (JBAR).

Methods

In 1989, the Japanese Biliary Atresia Society started a nationwide registry, JBAR, to investigate all aspects of biliary atresia. A total of 1,381 patients, 863 girls, 507 boys, and 11 unknown, were registered between 1989 and 1999. JBAR includes an initial and follow-up questionnaires. Using these patients’ data, the incidence, sex distribution, associated anomalies, the type of obstruction, the type of operation, and the surgical results were evaluated. The 5- and the 10-year results of 735 patients who were registered initially in or before 1994 also were analyzed.

Results

The incidence of biliary atresia was 1 in 9,640 live births. One hundred sixty-four patients (11.9%) had type I atresia of the common bile duct, 34 (2.5%) had type II atresia of the hepatic ducts, and 1,162 (84.1%) had type III atresia at the porta hepatis. Congenital associated anomalies were found in 19.6% of the patients including 33 cases associated with polysplenia. Impact of the age at operation on bile flow was not clear until 90 days of age, and after 90 days the bile flow rate worsened. The original Roux-en-Y procedure had been used in more than 50% of the patients since 1995. In 1999, 96% of the patients underwent the original Roux-en-Y procedure or the Roux-en-Y with an intestinal valve, and only 3 patients (3.5%) underwent other modifications. There were no significant differences in either the rate of disappearance of jaundice or the incidence of cholangitis among these 3 procedures. Of the 735 patients registered in or before 1994, 19 patients (2.6%) were lost to follow-up. The 5-year survival rates of patients registered in 1989, 1990, 1991, 1992, 1993, and 1994 were 62%, 64.5%, 61.3%, 59.0%, 58.7%, and 52.7% without liver transplantation (LTx), and 69.4%, 74.2%, 75.2%, 79.5%, 78%, and 78.3% with LTx, respectively. Although the overall 5-year survival rate changed from 69.4% to 78.3%, the difference was not statistically significant. According to the 10-year follow-up results of the 108 patients initially registered in 1989, 72 (66.7%) and 57 (52.8%) survived with and without the aid of LTx, respectively.

Conclusions

The overall 5- and 10-year survival rates were 75.3% (553 of 734) and 66.7% (72 of 108), respectively. In spite of the increasing number of survivors after LTx, there was no significant improvement in the 5-year survival rate. It was shown that the JBAR system was functioning well with only 19 patients lost to follow-up among the 743 patients registered from 1989 to 1994.     

The application of molecular biology to anti-endotoxin therapies

Toll-like receptors (TLRs), recently identified on macrophages and dendritic cells in mammals, recognize a specific pattern of pathogen components, including endotoxins(lipopolysaccharide). Pathogen recognition by TLRs activates the innate immune system through the signaling pathway and provokes inflammatory responses, such as inducing the production of cytokines. Therefore the specific inhibition of the signaling pathway and the administration of excess inflammatory responses have useful potential in the management of sepsis syndrome. Currently, several monoclonal antibodies are applicable to the treatment of autoimmune diseases and cancer. On the other hand, immunotherapies against proinflammatory cytokines in septic shock have failed to demonstrate clinical benefit. In this review, we summarize recent views of novel therapeutic targets, provided from molecular biologic studies of gram-negative infection.     

Pathophysiology and treatment of postoperative acute respiratory disturbance

One major concern after surgery is postoperative pulmonary complications such as atelectasis, aspiration, pneumonia, and respiratory failure. Progress in preoperative and postoperative rehabilitation, in systemic management including respiratory management, and progress in understanding the pathophysiology of acute respiratory failure have improved prevention and the outcome of treatment. However, some conditions remain very difficult to treat, like respiratory failure accompanied by infection or multiple organ failure. In the 1960s, the concept of acute respiratory distress syndrome or adult respiratory distress syndrome was postulated. Tremendous amounts of basic and clinical research have been done to clarify the pathophysiology of and to establish treatment modalities for acute respiratory failure. Our understanding of acute respiratory failure has progressed from the role of microembolism syndrome to cellular components such as neutrophils and platelets and then to humoral factors such as endotoxins, complement factors, and numerous cytokines. In this article, the pathophysiology of acute lung injury and its diagnostic criteria, treatment modalities such as respirator management to protect lung tissue from barotrama and volutrauma by yielding hypercapnea (permissive hypercapnea), drug therapy with neutrophil elastase inhibitor, mechanical support using extracorporeal membrane oxygenation, liquid ventilation, continuous hemodiafiltration, and endotoxin elimination columns are discussed. Early diagnosis and early treatment are mandatory to improve survival in patients with acute respiratory failure, although we have not yet fully understood the pathophysiology of this disease entity sufficiently.     

Hepatic Resection Combined with Portal Vein or Hepatic Artery Reconstruction for Advanced Carcinoma of the Hilar Bile Duct and Gallbladder

Hepatectomy with vascular reconstruction for biliary malignancy remains controversial. This study aimed to clarify the indications for surgery. Patients with advanced hilar bile duct cancer (HBDC) (n = 26) and gallbladder cancer (GBC) involving the hepatoduodenal ligament (n = 13) who underwent hepatectomy were enrolled. They were divided into two groups on the basis of whether vascular reconstruction was performed (HBDC, 10 yes vs. 16 no; GBC, 5 yes vs. 8 no). Portal vein (PV) reconstruction was performed on the right branch in seven patients and on the left branch in two; hepatic artery (HA) reconstruction was done on the right branch in 11 patients and on the left branch in 1. Five patients with HBDC and one with GBC underwent both PV and HA reconstruction. Patency rates were 88.0% and 83.3% for PV and HA reconstructions, respectively. Vascular reconstruction-related morbidity occurred in one patient with fatal liver failure owing to a portal thrombus and in two patients with multiple liver abscesses caused by arterial obstruction. Microsurgery eliminated reconstruction-related morbidity. Mortality in vascular reconstruction cases was 13.3% (2/15), and in those without reconstruction it was 8.3% (2/24). Curability rates (R0 and R1+R2) were 50.0% and 56.0% for HBDC and 40.0% and 62.5% for GBC, respectively. The 3-year survivals of HBDC patients were, respectively, 33% and 42%, and the 5-year survivals were 18% and 25%, whereas for GBC the 1-year survivals were 20% and 60% and the 2-year survivals 0% and 25%. Two patients with vascular involvement who underwent PV with HA reconstruction survived more than 3 years. Hepatectomy with vascular reconstruction for selected HBDC patients offers low surgical risk and increased survival by curable resection, but it is not recommended for advanced GBC.     

Surgical influence on TH1/TH2 balance and monocyte surface antigen expression and its relation to infectious complications

Abstract Malignancy and operation for it cause several alterations in immune function that are considered to be concerned with the development of infectious complications. Forty-three patients who underwent curative surgery for gastrointestinal malignancies were entered into this study and were divided into two groups, those with and those without postoperative infection. Changes in the proportion of Th1/Th2 subsets in CD4⁺ T cells and the expression of human leukocyte antigen (HLA)-DR and CD16a molecules on monocytes were measured by flow cytometry before and after surgery. We performed intracellular cytokine stainings to exactly detect Th1/Th2 subsets. The proportions of interferon-γ-producing CD4⁺ T (Th1) cells in the preoperative state were almost equal in the two groups, and the proportion decreased on postoperative day (POD) 1 in both groups. On POD 7, the proportion of Th1 cells recovered to the preoperative level in the noninfection group, while the suppression was further reinforced in the infection group (26.8% versus 18.3%, p < 0.005). In contrast, the proportion of interleukin-4-producing CD4⁺ T (Th2) cells in the infection group (11.3%) was already suppressed in the preoperative state when compared with the noninfection group (17.3%, p < 0.005). Changes in HLA-DR and CD16a expression on monocytes were similar to the changes in the proportion of Th1 cells. These results indicate that the suppression of Th1 cell and monocyte functions during the early phase of the postoperative course was directly related to the occurrence of infectious complications and that several immunological impairments have already occurred in the preoperative state in cancer patients. Electronic Publication     

A case of pseudo-Bartter's syndrome induced by long-term ingestion of furosemide delivered orally through health tea

A 32-year-old woman with a three-year history of muscle weakness and hypokalemia, was admitted to our hospital because of hypokalemic periodic paralysis. Clinical and laboratory findings were consistent with Bartter's syndrome. Although she denied any ingestion of diuretics substantial quantities of furosemide were detected in her urine. She had been drinking health tea which contained about 90 mg of furosemide per teabag daily for five years. Four years after discontinuation of drinking the tea, the hypokalemia was completely ameliorated, but poor renal concentration ability is still present. We conclude that is a case of pseudo-Bartter's syndrome that was caused by long-term ingestion of the health tea supplemented illegally with furosemide, and suspect that such cases may be observed more frequently than currently thought.     

Ki16425, a subtype-selective antagonist for EDG-family lysophosphatidic acid receptors

Lysophosphatidic acid (LPA) exerts a variety of biological responses through specific receptors: three subtypes of the EDG-family receptors, LPA1, LPA2, and LPA3 (formerly known as EDG-2, EDG-4, and EDG-7, respectively), and LPA4/GPR23, structurally distinct from the EDG-family receptors, have so far been identified. In the present study, we characterized the action mechanisms of 3-(4-[4-([1-(2-chlorophenyl)ethoxy]carbonyl amino)-3-methyl-5-isoxazolyl] benzylsulfanyl) propanoic acid (Ki16425) on the EDG-family LPA receptors. Ki16425 inhibited several responses specific to LPA, depending on the cell types, without any appreciable effect on the responses to other related lipid receptor agonists, including sphingosine 1-phosphate. With the cells overexpressing LPA1, LPA2, or LPA3, we examined the selectivity and mode of inhibition by Ki16425 against the LPA-induced actions and compared them with those of dioctyl glycerol pyrophosphate (DGPP 8:0), a recently identified antagonist for LPA receptors. Ki16425 inhibited the LPA-induced response in the decreasing order of LPA1 >/= LPA3 > LPA2, whereas DGPP 8:0 preferentially inhibited the LPA3-induced actions. Ki16425 inhibited LPA-induced guanosine 5'-O-(3-thio)triphosphate binding as well as LPA receptor binding to membrane fractions with a same pharmacological specificity as in intact cells. The difference in the inhibition profile of Ki16425 and DGPP 8:0 was exploited for the evaluation of receptor subtypes involved in responses to LPA in A431 cells. Finally, Ki16425 also inhibited LPA-induced long-term responses, including DNA synthesis and cell migration. In conclusion, Ki16425 selectively inhibits LPA receptor-mediated actions, especially through LPA1 and LPA3; therefore, it may be useful in evaluating the role of LPA and its receptor subtypes involved in biological actions.