Comparison of recombinant human thrombomodulin and gabexate mesylate for treatment of disseminated intravascular coagulation (DIC) with sepsis following emergent gastrointestinal surgery: a retrospective study.

PURPOSE: Recombinant thrombomodulin (rTM) has been available in Japan since 2008, but there is concern about its association with postoperative hemorrhage. The efficacy and safety of rTM were examined in patients with disseminated intravascular coagulation (DIC) caused by a septic condition after gastrointestinal surgery. METHODS: Forty-two patients were emergently admitted to the intensive care unit after emergent gastrointestinal surgery in Kyushu University Hospital from May 2008 to April 2013. Of these patients, 22 had DIC (defined as an acute DIC score ≥ 4). All but three patients received treatment with gabexate mesylate (GM) (n = 9) or rTM (n = 10). The causes of sepsis were peritonitis with colorectal perforation, anastomotic leakage, and intestinal necrosis. Acute DIC score, sepsis-related organ failure assessment score, platelet count, and a variety of biochemical parameters were compared between rTM and GM recipients after treatment administration. RESULTS: There were no significant differences between the groups for any parameter except C-reactive protein levels. The CRP level tended to be lower in the rTM group than in the GM group. Acute DIC score in the rTM group resolved significantly earlier than that in the GM group. No patient stopped the administration of rTM because of postoperative bleeding. CONCLUSION: rTM may be an effective therapeutic drug for the treatment of septic patients with DIC following emergent gastrointestinal surgery.

A comparative study of single-incision versus conventional multiport laparoscopic ileocecal resection for Crohn's disease with strictures.

INTRODUCTION: Single-incision laparoscopic surgery (SILS) offers excellent cosmetic results compared with conventional multiport laparoscopic surgery. Recently, this technique has been applied to colorectal disease. However, there have been few reports about its application to Crohn's disease (CD) in the literature. The aim of this study is to describe our early experience with SILS for 11 patients with CD and make comparisons with the conventional multiport laparoscopic surgery. METHODS: We reviewed all patients with CD who underwent laparoscopic surgery for the presence of ileocolic strictures at our institution between January 2006 and March 2011. Data from consecutive patients undergoing SILS were analyzed and compared with those from conventional multiport laparoscopic surgeries. RESULTS: During the study period, 11 patients underwent SILS. All surgeries were completed with SILS. Operative time, blood loss and conversions were not significantly different between the two groups. Postoperative complications and length of hospital stay also had no significant difference. CONCLUSION: In conclusion, SILS for CD may be safe and feasible in selected patients, and have better cosmetic results than conventional multiport laparoscopic surgery. Further studies are needed to evaluate the outcome of SILS compared to that of conventional laparoscopic surgery.

Transient encephalopathy with reversible white matter lesions in children.

We report on two children with acute encephalopathy showing mild clinical manifestations and reversible white matter lesions. In both patients, MRI revealed high intensities on T (2)-weighted imaging and marked reductions of water diffusion in the white matter of the bilateral centrum semiovale and the corpus callosum. These abnormalities disappeared along with the neurological symptoms within a week in both patients. These children represent a characteristic group of patients among childhood acute encephalopathy.

Importance of cerebral perfusion pressure management using cerebrospinal drainage in severe traumatic brain injury.

OBJECTIVE: To evaluate hemodynamics in patients with severe traumatic brain injury (TBI) after cerebral perfusion pressure (CPP) management using cerebrospinal fluid (CSF) drainage. METHODS: Twenty-six patients with TBI (Glasgow Coma Score = 8 or less) were investigated. Mean arterial blood pressure, CPP, cardiac index (CI), systemic vascular resistance index (SVRI), and central venous pressure were measured. The patients were divided into 2 groups after craniotomy: the intraparenchymal ICP (IP-ICP) monitoring group (n = 14) and ventricular ICP (V-ICP) monitoring group (n = 12). Patient hemodynamics were investigated on the second hospital day to identify differences. Measurements indicated a target CPP above 70 mmHg and a central venous pressure of 8 10 mmHg in both groups. Mannitol administration (IP-ICP group) or CSF drainage (V-ICP group) was performed whenever the CPP remained below 70 mmHg. RESULTS: High SVRI and low CI (p < 0.05) were observed in the IP-ICP group. The V-ICP group exhibited a reduction in the total fluid infusion volume of crystalloid (p < 0.01) and a reduction in the frequency of hypotensive episodes after the mannitol infusion. CONCLUSIONS: CPP management using CSF drainage decreases the total infusion volume of crystalloid and may reduce the risk of aggravated brain edema after excess fluid resuscitation.

Association between expression of vascular endothelial growth factor C, chemokine receptor CXCR4 and lymph node metastasis in colorectal cancer.

OBJECTIVES: Lymph node metastasis is one of the determining factors of a poor prognosis for colorectal cancer. Recent studies have reported that cancer cells can promote lymphangiogenesis and that chemokine receptors expressed by cancer cells might play a role in metastasis. In this study, we examined the correlation between the expression of vascular endothelial growth factor (VEGF) C, the chemokine receptor CXCR4 and lymph node metastasis in colorectal cancer. METHODS: One hundred and sixty-one consecutive patients who underwent resection at our department were studied. Lymph node metastasis was observed in 69 cases (43%) and lymphatic involvement was present in 105 cases (65%). Immunohistochemical staining was performed using antibodies for VEGF-C and CXCR4. Moreover, lymphatic vessel density (LVD) was evaluated within the tumor by immunostaining with a D2-40 antibody. RESULTS: VEGF-C expression was found in 81 cases (50%) and CXCR4 expression in 87 cases (54%). Regarding the correlation between nodal metastasis and the expression of CXCR4 and VEGF-C, the incidence of nodal metastasis was significantly (p < 0.01) higher in patients with CXCR4-positive tumors than in those with CXCR4-negative tumors. In addition, a significant correlation was observed between CXCR4 and VEGF-C expression and lymphatic invasion (p < 0.01). LVD was significantly higher in VEGF-C-positive tumors compared with VEGF-C-negative tumors. However, there was no significant correlation between LVD and CXCR4 expression. Using multivariate analysis, VEGF-C, CXCR4, lymphatic invasion and wall invasion were found to be independent risk factors for lymph node metastasis. CONCLUSIONS: This study suggests that although the mechanism that promoted lymph node metastasis was different between VEGF-C and CXCR4, both VEGF-C and CXCR4 contributed to lymphatic involvement and nodal metastasis in colorectal cancer.

Diabetes mellitus: new therapeutic approaches to treat an old disease

Diabetes mellitus is a widespread disease whose frequency increases constantly and is expected to reach alarming levels by the year 2025. Introduction of insulin therapy represented a major breakthrough; however, a very strict regimen is required to maintain blood glucose levels within the normal range and to prevent or postpone chronic complications associated with this disease. Frequent hyper- and hypoglycemia seriously affect the quality of life of these patients. Reversion of this situation can only be achieved through whole organ (pancreas) transplant or pancreatic islet transplant, the former being a high-risk surgical procedure, while the latter is a much simpler and may be accomplished in only 20-40 min. The advantages and perspectives of islet cell transplantation will be discussed, in the light of tissue engineering and gene therapy. Ongoing research carried out in our laboratory, aimed at developing clinical cell and molecular therapy protocols for diabetes will also be focused

New concept regarding chest pain due to hypoxia of the internal mammary arteries in more than 1,600 operated patients with cerebral thoracic neurovascular syndrome (CTNVS).

In this article we describe the role of compression of the vertebral, subclavian, internal mammary, internal carotid arteries, brachial plexus and coiling and kinking of the vertebral and basilar arteries, the faulty irrigation of blood supply and oxygen of the cerebellum and basal ganglia and other areas of the brain followed by metabolic processes. Among the effects are: a decrease in the secretion of dopamine at the level of the putamen, which produces the symptoms of symptomatic Parkinson's disease, chorea due to chronic transitory faulty blood supply and oxygen to the caudate nucleus, ballism by hypoxia at the level of sub-thalamic and thalamus nuclei and athetosis in the lenticular nucleus. This compression is caused by hypertrophy of the anterior scalenus muscles and the cervical ribs at the level of the vertebrae C6-C7; by the sternocleidomastoid at the level of the cervical atlas, by the pectoralis minor muscles and coiling and kinking of the vertebral, basilar and the internal carotid arteries. The decreased blood supply to the cerebellum and basal ganglia is the cause of the cerebral thoracic neuro vascular syndrome (CTNVS) and its neurological complications, among which are ipsilateral paralysis, symptomatic Parkinson's disease, functional Alzheimer's disease multiple sclerosis and others. We are presently engaged in genetic studies to widen our understanding of these illness.

Midazolam for continuous sedation in Japanese critical care patients: phase II study.

This prospective study was undertaken to evaluate the efficacy and safety of midazolam as a sedative agent in 14 critically ill patients without coma admitted to the intensive care unit at Nihon University Itabashi Hospital, Japan. Adequate sedation (sedation score [SS] 4-6) was induced with 0.058- 0.372 mg/ kg midazolam and maintained with a dose range of 0.03-0.4 mg/kg per h. Most burn or trauma patients required higher midazolam doses than patients with cardiovascular disease. The most frequent adverse events observed were hypotension, heart-rate fluctuation and electrocardiogram abnormalities. Pharmacokinetic analysis of the population suggested that lower drug clearance rates correlated with presence of complications. Plasma concentrations (EC50) of SS 5, estimated by logistic regression analysis, varied among patients (mean 194 ng/ml). Midazolam infusion achieved successful sedation in this critical care setting, but the optimum dose differed by patient and was influenced by the presence of complications.

Late occurrence of diffuse cerebral swelling after intracerebral hemorrhage in a patient with the HELLP syndrome--Case report.

Hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome can occur at any time in the course of pregnancy and is associated with many complications including fatal stroke. A 37-year-old female presented with HELLP syndrome causing an intracerebral hematoma, which was treated by evacuation and mild hypothermia. Unexpected diffuse cerebral swelling occurred on the 15th day of the initially favorable postoperative course. Considerable impairment of consciousness persisted despite conservative therapy. Serial computed tomographic findings indicated delayed cerebral vasospasm as the cause of the swelling. Particularly careful management is required even beyond the first 2 weeks for patients with stroke as a complication of HELLP syndrome.

Serum levels of neutrophil activation cytokines in Kawasaki disease.

BACKGROUND: The aim of the present study was to investigate whether neutrophils are early effector cells for vascular endothelial damage in the acute phase of Kawasaki disease (KD) by examining serial changes in neutrophil counts and serum levels of neutrophil activation cytokines, such as granulocyte colony stimulating factor (G-CSF) and interleukin (IL)-8. METHODS: From October 1994 to June 1998, a total of 52 patients with KD were included in the study. Thirty-three patients had some infectious diseases, while 20 healthy children served as control subjects. Serial changes in neutrophils were counted by the optimal Wright-Giemsa staining method and serum levels of IL-8 and G-CSF in patients with KD were measured by an enzyme-linked immunosorbent assay system. RESULTS: Serum G-CSF levels both before and after intravenous immunoglobulin therapy (IVIG; P<0.05) and neutrophil counts after IVIG (P<0.005) were higher in KD patients with coronary arterial lesions (CAL) than those without CAL. However, serum IL-8 levels before and after IVIG showed no significant differences in these two groups. CONCLUSIONS: These data suggest that neutrophils may be important as early effector cells for vascular endothelial damage and that G-CSF may play a more important role than IL-8 in KD.

Rectal and vaginal immunization with a macromolecular multicomponent peptide vaccine candidate for HIV-1 infection induces HIV-specific protective immune responses.

An effective vaccine for human immunodeficiency virus (HIV) is needed to stimulate the immune response of the genital mucus to prevent mucosal transmission of the virus. We have developed a macromolecular multicomponent peptide vaccine candidate, VC1. Both rectal and vaginal immunization of VC1 mixed with cholera toxin (CT) induced HIV-1-specific IgA antibody in mouse fecal extract solution and vaginal wash. These antibody productions were enhanced by the combination with IL-4 or GM-CSF expressing plasmids. Either fecal extract or vaginal wash solution from immunized mice inhibited production of HIV-1IIIB p24 protein. The mononuclear cells from spleen, intestinal lymph nodes, or Peyer's patches from VC1- and CT-immunized mice released IFN-gamma or IL-4, when these cells were co-cultured with VC1 antigen. In addition, the regional lymphoid cells from rectal and vaginal region of mice immunized with VC1 and CT also elicited a substantial level of HIV-1-specific cytotoxic T cell (CTL) response. This CTL response was enhanced by the addition of IL-12 expressing plasmid. Our results clearly demonstrated that both rectal and vaginal immunization could induce systemic and mucosal immunities specific for HIV-1.

Surgical treatment of the substernal goitre.

This report describes the surgical experience gained from 32 patients with substernal goitre, operated on during January 1995 to December 1997. The material corresponds to 15.7% of the total thyroidectomies performed. The diagnosis was clinical. In spite of 65.6% of the patients being asymptomatic, breathing problems, dysphagia and hyperthyroidism were observed. The patients underwent tests of thyroid function, simple chest radiograph and computerized tomography of mediastinum. All patients underwent surgical treatment through a transverse cervical incision. Two patients (6.25%) needed median sternotomy. Vocal cord palsy (3.12%), transient hypocalcemia (6.25%) and one death due to cardiac causes (3.12%) were the complications that occurred.

Hemidiaphragmatic paralysis following subclavian vein catheterization.

The right subclavian artery was inadvertently punctured during attempted preoperative insertion of a right subclavian venous catheter in a 59-yr-old woman undergoing radical hysterectomy. Large supraclavicular swelling became apparent soon after the arterial puncture. The postoperative chest X-ray obtained approximately 24 h after the catheterization revealed significant elevation of the right hemidiaphragm, which was further augmented on the 2nd to 4th postoperative days; oxygenation was concurrently impaired during these days. It was clinically judged that the hemidiaphragmatic paralysis was responsible for the elevated diaphragm. Both chest roentogenogram and arterial blood gas analyses started to improve on the 5th day, finally returning to normal on the 6th day. It is unlikely that the surgical procedure caused the paralysis, because it dealt only with the lower abdomen. Rather, the attempts at the subclavian venous catheterization probably caused the phrenic nerve paralysis, because the phrenic nerve travels very close to the subclavian vessels. Both the large haematoma formation following the arterial puncture and the time course of the paralysis suggest that compression of the right phrenic nerve by the haematoma, rather than needle trauma, was responsible for the paralysis.

Neck and brain transitory vascular compression causing neurological complications. Results of surgical treatment on 1,300 patients.

In this brief article we describe the role of compression of the vertebral subclavian arteries, internal mammary, internal carotid arteries, brachial plexus and coiling and kinking of the vertebral and basilar arteries, the faulty irrigation of blood supply and oxygen of the cerebellum and basal ganglia of the brain. Among the effects are: a decrease in the secretion of dopamine at the level of the putamen, which produces the symptoms of Parkinson's disease, and chorea due to chronic transitory faulty blood supply and oxygen to the caudate nucleus, ballism by hypoxia at the level of subthalamic nuclei and athetosis in the lenticular nucleus. This compression is caused by the anterior scalene muscles and the cervical ribs at the level of the vertebrae C6-C7; by the sternocleidomastoid at the level of the cervical atlas; and coiling and kinking of the vertebral, basilar and the internal carotid arteries. The decreased blood supply to the cerebellum and basal ganglia is the cause of the Cerebellar Thoracic Outlet Syndrome (CTOS) and its neurological complications, among which are ipsilateral paralysis, Parkinson disease and others. We are presently engaged in several studies to widen our understanding of this phenomenon.

Biotin deficiency in an infant fed with amino acid formula and hypoallergenic rice.

An amino acid formula produced in Japan is not supplemented with biotin since biotin is not permitted as a food additive. Biotin deficiency developed in an 11-month-old Japanese infant who had been diagnosed as a neonate with cow milk and soy bean allergy and fed with an amino acid formula and hypoallergenic rice processed by protease. Serum levels of zinc, essential fatty acids and biotinidase were within the normal range while that of biotin was below the normal range. Urinary 3-hydroxy-isovalerate and slightly elevated levels of plasma branched-chain amino acids disappeared 1 week after oral supplementation with 1 mg day-1 of biotin as did the symptoms of orificial skin lesions, lethargy, hypotonia and alopecia later. In summary, to prevent biotin deficiency, biotin should be added to the Japanese amino acid formula.

Effect of cytokines on mediator release from human dispersed lung mast cells.

To evaluate the contribution of human lung mast cells (HLMC) to allergic inflammation, we investigated whether or not cytokines, including stem-cell factor (SCF), monocyte chemotactic and activating factor (MCAF), and RANTES, activate HLMC. SCF induced histamine release from dispersed HLMC in a dose-dependent fashion (P < 0.01). The release was 7.8 +/- 1.0% at 500 ng/ml SCF (n = 9). This response was also observed in chopped lung tissue. HLMC from which surface IgE molecules had been removed by treatment with lactic acid responded to SCF, while these cells lost their response to anti-IgE. The process was relatively rapid and reached a maximum in 5 min. This response required extracellular calcium, and it was observed at 37 degrees C, but not at 4 degrees C or 20 degrees. A brief preincubation (10 min) with lower concentrations of SCF, which were ineffective in releasing histamine, enhanced anti-IgE-induced histamine release (P < 0.05), while its enhancing effect was lost by the longer preincubation (30 min). SCF did not prime basophils to enhance stimulated-histamine release. Interleukin (IL)-1 alpha, IL-1 beta, IL-3, IL-4, IL-5, granulocyte/macrophage-colony stimulating factor (GM-CSF), MCAF, and RANTES neither induced histamine release nor enhanced the release stimulated by anti-IgE after a 10- or 30-min preincubation. The combination of IL-3 and IL-4 showed no effect on histamine release from HLMC. Leukotriene (LT)C4/D4/E4 production by SCF was negligible, as compared with anti-IgE-induced LT production.(ABSTRACT TRUNCATED AT 250 WORDS)

[A case report of left ventricular-right atrial communication with tricuspid regurgitation due to infective endocarditis].

A case of 58-year-old man with a left ventricular-right atrial communication with tricuspid regurgitation due to infective endocarditis was reported. Surgical treatment was performed following intensive chemotherapy. The communication was found in the center of a vegetation on the septal leaflet. Closure of the communication and replacement of the tricuspid valve were done successfully. His postoperative course was uneventful.

[A case of operated invasive thymoma accompanied with the thrombocytopenia].

Thymoma with thrombocytopenia has rarely been reported. We recently encountered a case of operated invasive thymoma with thrombocytopenia. A 74-year-old woman was admitted to our hospital with the chief complaint of 'shortness of breath' and general fatigue. Chest X-ray, CT and MRI showed a mass 5 x 5 cm in size at the anterior mediastinum. In hematological test, a significant decrease in platelets count (1.6 x 10(4)/mm3) and a increase in PA-IgG (134.5 ng/10 cells) were found. This finding suggests that thrombocytopenia is due to immunological abnormality. Steroid therapy (prednisolone 60 mg) was begun but was not effective and then, extended thymectomy was performed. After operation, prednisolone (30 mg) therapy was continued. Although prednisolone therapy was gradually decreased and stopped, platelets count was gradually increased 10.8 x 10(4)/mm3. Extended thymectomy and steroid therapy were effective.