Effect of laparoscopic splenectomy on portal haemodynamics in patients with liver cirrhosis and portal hypertension.

BACKGROUND: The effect of splenomegaly in patients with liver cirrhosis and portal hypertension is not fully understood. This study was designed to determine the effect of laparoscopic splenectomy on portal haemodynamics in these patients. METHODS: Patients with liver cirrhosis and portal hypertension who underwent laparoscopic splenectomy in Kyushu University Hospital from January 2006 to March 2009 were evaluated retrospectively. Correlations between splenic size and portal haemodynamics, and changes in portal haemodynamics and in levels of the vasoactive agents endothelin (ET) 1 and nitric oxide metabolites (NOx) before and 7-10 days after laparoscopic splenectomy were analysed. RESULTS: Portal venous (PV) blood flow, PV cross-sectional area and PV congestion index correlated significantly with splenic size (P < 0·050). All three were significantly reduced following splenectomy in 59 patients. The hepatic venous pressure gradient, measured in 18 patients, decreased by 25 per cent after splenectomy (P < 0·001). Portal vascular resistance was also reduced, by 21 per cent (P = 0·009). The peripheral blood concentration of ET-1 decreased from 2·95 to 2·11 pg/ml (P < 0·001), and that of NOx tended to decrease (from 29·2 to 25·0 pg/ml; P = 0·068). In hepatic venous blood, the level of ET-1 decreased from 2·37 to 1·83 pg/ml (P = 0·006), whereas NOx concentration tended to increase (from 24·5 to 30·9 pg/ml; P = 0·067). CONCLUSION: In patients with liver cirrhosis and portal hypertension, splenectomy reduced portal venous pressure. A decrease in splanchnic blood flow, by eliminating splenic blood flow, and reduction in intrahepatic vascular resistance, by normalizing hepatic concentrations of ET-1 and NOx, may both have contributed.

Socioeconomic inequalities in toothbrushing behaviours in young children: a children's lifestyle survey in a representative population of A city, Okinawa prefecture, Japan.

PURPOSE: We have less understanding of which socioeconomic status (SES) indicators may be reflective of latent socioeconomic inequalities in toothbrushing behaviours, especially finishing-toothbrushing by parents in young children. The aim of this study was to reveal the socioeconomic inequalities in children's toothbrushing and finishing-toothbrushing by parents and if it varies by SES indicators. METHODS: We used data from 'Survey on Children's Life' conducted by A city of Okinawa Prefecture, Japan. The multiple imputed data of 902 (boys, 453) included self-reported children's toothbrushing behaviour and finishing-toothbrushing by parents in three-to six-year-old children. SES was assessed using self-reported household income and parental educational attainment. Absolute and relative inequalities in toothbrushing behaviours were quantified using the slope index of inequality (SII) and relative index of inequality (RII), respectively. RESULTS: There were significant absolute and relative inequalities of children's toothbrushing for household income (SII and RII were 0.241 and 2.73, respectively), of finishing-toothbrushing by parents for household income (SII and RII were 0.133 and 3.28, respectively), and educational attainment (SII and RII were 0.166 and 5.55, respectively). The same inequality trends were observed after adjusting for covariates (child's age and sex, family structure, breakfast and dinner frequency, and sleep duration). CONCLUSION: Socioeconomic inequalities in children's toothbrushing and finishing-toothbrushing by parents varied according to SES indicators.

Modulation of CD4⁺ T cell responses following splenectomy in hepatitis C virus-related liver cirrhosis.

Dysfunction of T cells is a common feature in chronic persistent viral infections, including hepatitis C virus (HCV), and although hepatic and peripheral T cells have been studied extensively in chronic HCV hepatitis, the role of splenic T cell responses in such patients is poorly defined. This is an important issue, as thrombocytopenia is a complication of HCV-related liver cirrhosis (LC), due to splenic platelet sequestration and bone marrow suppression; splenectomy has been proposed to treat such patients. Herein, we studied peripheral blood mononuclear cells (PBMC) and splenic lymphoid subpopulations from a total of 22 patients, including 15 with HCV-related LC with marked thrombocytopenia treated with splenectomy, and seven controls. CD4(+) T cells from peripheral blood and spleen were isolated and phenotype and function evaluated. Splenic CD4(+) T cells in patients with LC expressed molecules associated with inhibitory signalling, including increased frequency of negative markers such as cytotoxic T lymphocyte associated antigen-4 (CTLA-4) and programmed death 1 (PD-1) and decreased production of cytokines. Patients with LC manifest higher levels of splenic CD4(+) regulatory T cells and PD-L1- and PD-L2-expressing cells than controls. Blocking of PD-1/PD-1 ligand interaction reconstituted proliferative and cytokine responses of splenic mononuclear cells (SMC) from patients with LC. Splenectomy was followed by an increase in the ratio of interferon (IFN)-γ to interleukin (IL)-10 and a reduction of PD-1-expressing CD4(+) T cells in peripheral blood. Our data suggest that peripheral tolerance is promoted by the spleen in LC via the up-regulated expression of PD-1 ligands.

Risk factors for portal venous thrombosis after splenectomy in patients with cirrhosis and portal hypertension.

BACKGROUND: Portal venous thrombosis (PVT) is a potentially fatal complication following splenectomy. Its mechanisms and risk factors are poorly understood, especially in patients with cirrhosis and portal hypertension. This study investigated risk factors for PVT following splenectomy in such patients. METHODS: All consecutive patients with cirrhosis who underwent splenectomy in Kyushu University Hospital between 1998 and 2004 were included in this retrospective study. They were divided into two groups based on the presence or absence of postoperative PVT. Preoperative and operative factors were compared, and the relationships between formation of PVT and its independent variables were analysed. In some cases, portal venous flow was measured before and after splenectomy using duplex Doppler ultrasonography. RESULTS: PVT developed after surgery in 17 (24 per cent) of 70 patients studied. Multivariable analysis showed that increased splenic vein diameter and low white cell count were significant independent risk factors for PVT. Portal venous flow after splenectomy was greatly reduced in the PVT group, but not in patients without PVT. CONCLUSION: Large splenic vein diameter and low white cell count are independent risk factors for PVT after splenectomy in patients with cirrhosis and portal hypertension.

Laparoscopic cholecystectomy using a newly developed laparoscope manipulator for 10 patients with cholelithiasis.

BACKGROUND: Laparoscopic surgery has continued to gain popularity in almost all fields of abdominal surgery, and robotic systems have been introduced in general surgery. Naviot is a new remote-controlled laparoscope manipulator system controlled by the operator's hand. This study assessed its introduction into clinical practice. METHODS: A group of 10 consecutive patients with cholelithiasis underwent laparoscopic cholecystectomy assisted by the Naviot system (Naviot group). Another group of 41 patients who underwent laparoscopic cholecystectomy with a conventional human camera holder (human camera group) were selected for a comparison of their operative results with those of the Naviot group. RESULTS: The operative time of 89.3 +/- 27.1 min for the Naviot group was significantly longer than that of 74.8 +/- 28.1 min for the human camera group (p < 0.05). However, when the setup time for the Naviot system was excluded, the operative time was not significantly different from that for the human camera group. Other operative results showed no significant difference between the two groups. CONCLUSIONS: The authors believe that the new Naviot system is feasible for clinical use, and that it enables surgeons to perform solo gastrointestinal surgery.

Locomotor projections from the pedunculopontine nucleus to the spinal cord.

Following injections of retrograde tracers into the spinal cord enlargements, the mesencephalic locomotor region (MLR) was electrically stimulated to induce locomotion in decerebrate rats. MLR sites coincided with cholinergic pedunculopontine nucleus (PPN) neurons, which were selectively labelled using NADPH diaphorase histochemistry. Retrogradely labelled (spinal-projecting) PPN neurons were scattered among cholinergic PPN neurons. The absence of retrogradely labelled, NADPH diaphorase positive PPN neurons indicates that spinal enlargement projections are non-cholinergic.

Locomotor projections from the pedunculopontine nucleus to the medioventral medulla.

Retrograde tracers were injected into the rat medioventral medulla (MED) and the injection site was identified as a locomotion- inducing area by electrical stimulation in the decerebrate preparation. Histological reconstructions showed that about 10% of cholinergic pedunculopontine (PPN) and laterodorsal tegmental (LDT) neurons project to the MED. Also, large numbers of non-cholinergic cells in and around the PPN and LDT were found to project to the MED.

A study of NADPH-diaphorase positive septohippocampal neurons in rat.

Retrograde transport of fluorescent tracers and nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemical techniques were combined in a study of septohippocampal projections in the rat. The dorsal (DH) and ventral (VH) hippocampus were simultaneously injected with different tracers (Fast Blue or Fluoro-Gold). Histochemical procedures revealed many NADPH-d positive cells located in the medial septum and the horizontal limb of the diagonal band. In the medial septum, NADPH-d positive neurons were mostly located lateral to the midline region and some of these were double-labeled by the tracer injected into the VH. Also, NADPH-d positive cells were found in the horizontal diagonal band and some of these were double-labeled following injections into the DH. No fluorescence/NADPH-d double-labeled neurons were observed in other structures known to project to the hippocampus.

Topographic organization and collateralization of the projections of the anterior and laterodorsal thalamic nuclei to cingulate areas 24 and 29 in the rat.

Fast blue and Rhodamine microspheres were used to analyze the topography and collateralization of the limbic nuclei of the thalamus to 4 defined areas of the cingulate gyrus (anterior 24, posterior 24, anterior 29, and posterior 29). The anterodorsal nucleus and the anteroventral nucleus project to posterior area 24 and all of area 29. The anteromedial nucleus projects generally to both areas 24 and 29, but principally to anterior area 24. The laterodorsal nucleus projects only to area 29. The anterior and posterior portions of the thalamic nuclei topographically project to the anterior and posterior regions of the cingulate gyrus, respectively. Neurons in the medial region of the anterior nuclei project to the anterior area of the cingulate gyrus while neurons located in the lateral region project to posterior areas. Collaterals (9-13%) from the anteromedial nucleus project diffusely to areas 24 and 29, while collaterals from other nuclei project primarily to areas adjacent to each other. Modulation of limbic system functions probably occurs via these projection fibers. Furthermore, the idea appears to be reinforced that at least a dual and coupled function exists for these direct thalamocingulate connections.

Medioventral medulla-induced locomotion.

Previous anatomical studies demonstrated the presence of descending projections from the physiologically identified mesencephalic locomotor region (MLR) to the medioventral medulla (MED) in the cat. The present experiments were designed to determine if a similar low threshold locomotion-inducing area is present in the rat medulla. In addition, the nature of the neurochemical control of this area of the brain was explored using localized injections of neurochemical agents in the decerebrate rat during locomotion on a treadmill. A region virtually identical to that reported in the cat was found to lead to controlled locomotion on a treadmill following stimulation at low amplitude currents (less than or equal to 60 microA). Injections of cholinergic agonists into the MED of the rat induced locomotion which could be blocked by injections of cholinergic antagonists. In addition, injections of GABA antagonists were found to induce stepping which could be blocked by injections of GABA or GABA agonists. Substance P (SP) also was found to induce walking following injection into the MED of the rat. Injections of an excitatory amino acid agonist (NMDA) also were found to induce locomotion in the rat. These effects were blocked by injections of an excitatory amino acid antagonist (APV). Since these results had not been reported for the cat MED, a short series of experiments revealed that the MED in the cat also responded to NMDA.

Posterior midbrain-induced locomotion.

The purpose of this study was to determine the nature of the neurochemical signals which impinge on the mesencephalic locomotor region (MLR) to produce locomotion in the rat. Injections of GABA antagonists into NADPH diaphorase-positive regions (PPN) were found to induce locomotion for short episodes (5-30 sec) which were repeated for several minutes (1-40 min). Such activity was blocked by injections of GABA and the GABA agonist, muscimol. Locomotion was induced by injection of substance P (SP), which also produced short, repeated episodes of locomotion. The more potent excitatory amino acid agonist, n-methyl-d-aspartic acid (NMDA), however, did produce dose-dependent, long-lasting (20 sec-5 min) locomotor episodes which were repeated over prolonged periods at the higher concentrations used (2-24 min). Additional injections of NMDA could drive stepping from a walk to a trot to a gallop. The effects of NMDA were blocked by injections of the excitatory amino acid antagonist, aminophosphonovalerionic acid (APV) (1-10 mM). Preliminary evidence suggests that carbachol (10-50 mM), a cholinergic agonist, inhibits NMDA-induced increases in muscle tone and episodes of stepping. The effect of carbachol was blocked by the cholinergic antagonist, atropine.

Cardiovascular effects of Acanthaster planci venom in the rat: possible involvement of PAF in its hypotensive effect.

Cardiovascular effects of the crowns-of-thorns starfish (Acanthaster planci) venom were examined in rats. The crude venom extracted from the spines of A. planci caused systemic hypotension associated with an increase in heart rate and a decrease in renal cortical blood flow when given i.v. The hypotensive effect of the venom was not inhibited by pretreatment with atropine, indomethacin or aprotinin, but was significantly inhibited by SRI 63-441, a platelet activating factor (PAF) antagonist. The venom caused dose-dependent vasorelaxation of the isolated rat aortic ring preparation precontracted by noradrenaline, an effect which was significantly attenuated by pretreatment with SRI 63-441, methylene blue or parabromophenacyl bromide. Denudation of the endothelium also diminished the vasorelaxing effect of the venom. Both the vasorelaxing and the hypotensive effects showed tachyphylaxis. These results suggest the release of PAF or a PAF-like substance from the endothelium by the venom.

Efficacy of ivermectin against Strongyloides stercoralis in humans.

Okinawa Prefecture is an endemic area of Strongyloides stercoralis infection. Since treatment of this infection remains unsatisfactory, we evaluated the efficacy of ivermectin. Twenty-three patients were treated with a single oral dose of ivermectin (mean +/- SD, 105.5 +/- 20.8 mcg/kg of body weight), followed by a second dose two weeks later. The rate of cure was 85.7% at 2 weeks after the first treatment, and 90.5% at 2 weeks after the second treatment. Side effects occurred in 2 patients (8.7%), but they were mild and transient. The results indicate that ivermectin might be useful and relatively safe for the therapy of Strongyloides stercoralis infection as an alternative to thiabendazole or mebendazole.

[Comparison of efficacy of powder and tablet of mebendazole in the treatment of strongyloidiasis].

We previously treated 47 patients with 100 mg of mebendazole (MBZ) twice a day by oral use for 5 days and this treatment was repeated 1, 3 and 4 weeks later. Although the cure rate was 100%, liver injury was observed in 48.9% of the patients. On this study, we reduced the periods of administration of MBZ (powder; 100 mg twice a day) to 4 days, and repeated it once after 3 days interval, and this initial treatment was performed one more time after 10 days interval (group 1). As Strongyloides stercoralis is mainly located in upper digestive systems, we used the drug reduced to powder for the purpose of better contact with the parasites. We considered that the powder should be absorbed well and liver injury occurred in high incidence. As group 2, we used the tablet itself in the same schedules of group 1. The results obtained were as follows; 1) The eradication rates at 10 days after the initial treatment were 97.8% (44 of 45 patients) in group 1 (powder) and 93.0% (40/43) in group 2 (tablet). 2) At 3 days after the whole treatment, the eradication rates were 100.0% in group 1, and 97.7% (42/43) in group 2. 3) Slight side effects such as constipation (6.7% in the group 1), dizziness or vertigo (6.7% in the group 1) and itching (6.7% in the group 2) were observed. 4) Liver injury was observed at 11.1% (5/45) 10 days after the initial treatment in the group 1 and 13.3% (6/45) in the group 2.(ABSTRACT TRUNCATED AT 250 WORDS)

[Clinical study on symptoms in patients with strongyloidiasis].

We treated strongyloidiasis patients and obtained the following results: Of the 299 patients (184 males and 115 females), 81 patients (27.1%) had no complaints before treatment, 218 patients complaints of some symptoms, including arthralgia and/or lumbago (28.4%), abdominal pain and/or borborygmus (19.3%), numbness of extremities (18.1%), constipation (16.3%) and itching (15.7). We treated 219 patients with mebendazole and symptoms improved after treatment described below: Thirty-seven of the 63 patients (58.7%) with arthralgia and/or lumbago improved. Twenty-seven of the 36 patients (75.0%) with numbness of extremities improved. Thirty-one of the 32 patients (96.9%) with heartburn improved. We treated 26 patients with mebendazole plus thiabendazole and twelve of 14 patients (85.7%) with abdominal pain and/or borborygmus were improved after treatment. We treated 54 patients with ivermectin and five of 18 patients (27.8%) with arthralgia and/or lumbago were improved after treatment.

[Chronic subdural hematoma secondary to coagulopathy].

Eleven cases of chronic subdural hematoma (CSH) secondary to coagulopathy were experienced in our department in the last 5 years. They were classified into 4 groups, I: secondary to diffuse metastatic carcinomatosis of the bone marrow (4 cases), II: malignant hematological disease (acute lymphocytic leukemia and myelodysplastic syndrome 1 case each), III: postreplacement of cardiac valves or vein graft having been treated with anticoagulants (warfarin) (3 cases) and IV: chronic renal failure after having been hemodialyzed (2 cases). The outcomes were all good in group III, and there was one good outcome in group IV. However, death was the outcome in all the other cases. Conservative treatment (mannitol and steroid for 2 weeks) was carried out in 4 cases, all of which improved clinically with diminished hematoma. In 9 cases, surgical treatment was attempted by means of burr hole irrigation of the hematoma. Two of them developed intracerebral hematoma, and one developed acute brain swelling. In conclusion, treatment of CSH secondary to coagulopathy should be selected as follows. 1. Conservative treatment is to be the first choice, if conditions allow it. 2. Surgery can be performed by burr hole irrigation when indicated. Precautions should be taken not to injure the inner membrane of the hematoma or the brain proper, and the need for slow decompression should be kept in mind.

[A case of successfully removed posttraumatic high flow dural arteriovenous fistula in the posterior fossa].

A 49-year-old male patient was admitted to Ryukyu University Hospital complaining chiefly of progressive loss of mental activity for one year. He had a history of head trauma at the right retromastoid region when he was 24. Generalized convulsions developed three years later, and left exophthalmos, facial varix and impairment of visual acuity developed seven years later. Dural arteriovenous fistula of the posterior fossa was diagnosed at the age of 32, and feeding EC and tentorial arteries were successively ligated on the right several times without any effect. Angiography during this admission revealed tremendous collateral flows; a marked dilated tortuous occipital artery fed from the right vertebral artery, meningeal branches of VA and PICA, the marginal tentorial artery, and the posterior temporal artery from MCA, PCA were drained into the right transverse sinus. But transverse sinuses were occluded bilaterally, and venous outflows were directed to the superior sagittal sinus retrograde via the ascending cortical vein, Trolard veins, and sphenoparietal and cavernous sinuses. The final drainer was the superior ophthalmic vein on the left. Normal deep veins were not visible. In park bench position, the nidus was totally resected with a part of the transverse and thrombosed sigmoid sinus. Postoperative course was uneventful, and an angiogram showed complete disappearance of the AVF. Dural AVG in the posterior fossa with characteristics such as high flow, and which is rich in collaterals following palliative treatment indicates that total surgical resection should be undertaken.