Propofol reduces liver dysfunction caused by tumor necrosis factor-α production in Kupffer cells

Purpose

The present study, conducted in rats, investigated whether propofol attenuates lipopolysaccharide (LPS)-triggered liver dysfunction via regulation of tumor necrosis factor (TNF)-α production in activated Kupffer cells.

Methods

Rats received LPS (500 μg/kg) under Urethane? sedation (1 g/kg) in combination with propofol (5 mg/kg/h) or Intralipid? from 1 h before to 6 h after LPS administration. Some rats were treated with 10 mg/kg gadolinium chloride (GdCl₃) to induce Kupffer cell depletion. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), TNF-α mRNA and protein expression, caspase-3 activation and apoptosis were evaluated in hepatocytes. Immunofluorescence staining revealed expression of the pan-macrophage marker CD68 as well as TNF-α in Kupffer cells.

Results

ALT and AST serum levels increased approximately four-fold in LPS-exposed rats compared with Intralipid?-treated rats at 6 h after LPS administration, whereas propofol and GdCl₃ reduced the LPS-induced increases. LPS simultaneously augmented TNF-α expression in Kupffer cells, followed by increased caspase-3 activity and apoptosis in hepatocytes. Immunofluorescence staining and immunoblotting assay showed that TNF-α expression in Kupffer cells was inhibited by propofol and GdCl₃, resulting in a reduction of caspase-3 activity and apoptosis in LPS-treated rat hepatocytes.

Conclusions

Propofol (5 mg/kg/h) attenuated LPS-triggered liver dysfunction via inhibition of TNF-α production in activated Kupffer cells. These results suggest that propofol is capable of inhibiting inflammation-induced liver dysfunction in vivo.

     

Effect of depression and neuropathic pain using questionnaires on quality of life in patients with low back pain; cross-sectional retrospective study

Purpose

The present study investigated the percentage of low back pain (LBP) patients who have depressive symptoms and neuropathic pain and analyzed the effects of these on the quality of life (QOL) in these patients.

Methods

Of the 650 new patients with LBP that visited the hospital between June 2012 and December 2013, 309 patients who completed questionnaires to assess LBP and QOL were included in the study. The questionnaire included demographic items, the self-rated depression scale (SDS)-Zung, the Japanese version of the PainDETECT questionnaire (PDQ-J), numerical pain rating scale (NRS), and QOL assessments. The patients were divided into two groups according to their SDS-Zung scores: a nondepressed group with SDS scores <40 and a depressed group with SDS-Zung scores ≥50.

Results

One hundred twenty-five patients (40.5 %) were classified as nondepressed and 63 (20.4 %) as depressed. The mean PDQ-J score was higher in depressed patients than in nondepressed patients. The frequency of neuropathic pain was greater in depressed patients, with neuropathic pain observed in 17 of the 63 (27 %) depressed LBP patients and 11 of the 125 (9 %) nondepressed LBP patients. The SDS-Zung and PDQ-J scores of LBP patients were correlated significantly (r = 0.261, p < 0.001). Depressed patients had higher pain NRS scores and lower QOL scores compared with nondepressed patients.

Conclusions

Both the depressed patients and those with neuropathic LBP had a higher level of pain, greater pain-related disability, and poorer QOL compared with nondepressed patients. This is the first study to use the SDS-Zung and PDQ-J screening questionnaires to estimate the presence of neuropathic pain associated with depressive symptoms in LBP patients and to evaluate the impact of these on QOL.

     

Solitary fibrous tumor of the pleura: morphogenesis and progression. A report of 36 cases

Purpose

We attempted to identify the exact point of tumor eruption of a solitary fibrous tumor of the pleura (SFTP).

Methods

We morphologically classified 36 SFTPs into 5 categories. Type A showed a connection that included a bloodstream with the pleura on both sides. Type B only showed a connection that included a bloodstream with the visceral pleura, and had a non-bloodstream connection with the parietal pleura. Type C only showed a connection that included a bloodstream with the visceral pleura, and had no connection with the parietal pleura. Type D showed a non-bloodstream connection with the visceral pleura, and only showed a connection that included a bloodstream with the parietal pleura. Finally, type E had no connection with the visceral pleura, and only showed a connection that included a bloodstream with the parietal pleura. The clinicopathological profiles of the tumors were investigated according to their type.

Results

The distribution of the 36 SFTPs was as follows: A (19 %), B (6 %), C (67 %), D (0 %) and E (8 %). The tumors categorized as type A tended to be large in size.

Conclusions

SFTPs commonly arise from the visceral pleura and in accordance with tumor progression they will form a non-bloodstream connection with the parietal pleura. Finally, a vascular pedicle will arise with the parietal pleura.

     

Congenital diaphragmatic hernia in neonates: factors related to failure of thoracoscopic repair

Purpose

To evaluate factors related to conversion to open repair (OR) during thoracoscopic repair (TR) in congenital diaphragmatic hernia (CDH).

Methods

CDH subjects who were diagnosed prenatally or within 6 h of birth and underwent TR at our institution from 2007 to 2015 were reviewed. Two groups were defined: Group A, subjects who tolerated TR; and Group B, subjects who required conversion to OR.

Results

Twenty-nine subjects (Group A, 20; Group B, 9) underwent TR. Patients’ demographics were not significantly different between the two groups. In Group A, pre-operative arterial blood gas analysis showed mean PaCO₂ 37.4 mmHg, mean pH 7.45, and mean PaO₂ 201.6 mmHg, which were not significantly different from those of Group B (PaCO₂ 40.6 mmHg, pH 7.43, and PaO₂ 251.1 mmHg). Two Group B cases required conversion due to cardiopulmonary instability. The remaining seven cases were converted for technical reasons (large defect in two, anterior location of the defect in two, bleeding from short gastric vessels or spleen in two, and insufficient operative view in one).

Conclusions

TR can be performed safely in selected cases of CDH. CDH with a large defect and/or an unusual location of the defect remains a challenge for pediatric surgeons.

     

Nationwide survey of neonatal transportation practices in Japan

Rapid resuscitation and appropriate transportation of sick infants can greatly improve infant survival and neurological prognosis. To gain an understanding of the status of neonatal transport in Japan, we conducted a survey of neonatal transportation capabilities at perinatal medical centers across the country. Survey content included the number of neonatal transportation cases and the method of transportation. Twenty percent of infants admitted to neonatal intensive care units were transported to the medical centers from other institutions. Half of the level III perinatal medical centers owned an ambulance specialized for neonatal transport. A total of 36% of sick newborns, however, were transported by fire department ambulances that are ill‐equipped to care for infants. Thirteen percent of centers reported problems with the emergency transportation of newborns in fire department ambulances. Centers lacked specialized ambulances primarily because of financial constraints. Adequate medical insurance coverage is needed to increase the number of specialized ambulances at perinatal medical centers.     

Fatal warm autoimmune hemolytic anemia in a child due to IgM‐type autoantibodies

Herein is described a case of immunoglobulin M (IgM) warm autoimmune hemolytic anemia (AIHA) in a child who consequently died within 3 days of clinical onset. A previously healthy 11‐year‐old boy presented with fever, anemia, jaundice, and deteriorating consciousness. On direct agglutination test against group O red blood cells, agglutination was seen even at 37°C in saline, which was abolished on dithiothreitol treatment of the serum, indicating that the responsible autoantibody was IgM and had a warm‐reactive capacity. A diagnosis of IgM warm AIHA was therefore made. Hemagglutination in the visceral capillaries was considered as the direct cause of organ dysfunction. The patient died due to respiratory failure. IgM warm AIHA is a very severe condition that is difficult to reverse in an advanced state. Both prompt, definite diagnosis and intervention are therefore vital to prevent severe multi‐organ dysfunction in cases of IgM warm AIHA.     

Genetic background of hyperphenylalaninemia in Nagasaki,Japan

Phenylketonuria (PKU) and related hyperphenylalaninemia (HPA) are caused by a deficiency in hepatic phenylalanine hydroxylase (PAH). The incidence of PKU in Nagasaki prefecture is higher than that in all parts of Japan (1/15 894 vs 1/120 000). To investigate the genetic background of patients with HPA in Nagasaki prefecture, mutation analysis was done in 14 patients with PKU or mild HPA. Homozygous or compound heterozygous PAH mutations were identified in all the patients. The spectrum of PAH mutations in the cohort was broad and similar to those in all parts of Japan and East Asian countries. R53H is the most common mutation in patients with mild HPA. The present results provide further support for genotype–phenotype correlations in patients with HPA. The high incidence of PKU in Nagasaki, the westernmost part of Japan, might be due to migration of people with PAH mutations from China and Korea, and geographic factors.     

Anomalous origin of the right coronary artery: First familial cases in Asia

Congenital coronary artery abnormalities may cause sudden death, particularly in athletes. Two siblings, aged 10 and 9 years, respectively, were diagnosed with anomalous origin of the right coronary artery on multi‐detector computed tomography (MDCT). The right coronary artery arose from the left coronary cusp, and was wedged between the aorta and pulmonary artery. This was also noted on cardiac ultrasonography (UCG), but in general this might not be seen on electrocardiography at rest. Although the surgical indications are unclear in the case of unproven ischemia, early recognition of the condition may reduce risk of the cardiac events during exercise. The majority of proximal coronary artery anomalies can be screened for on UCG, and confirmed on MDCT, which yields more precise clinical details and is less invasive than angiography. This is the first report of familial cases of anomalous origin of the right coronary artery in Asia.     

Chronic Hyponatremia Causes Neurologic and Psychologic Impairments

Hyponatremia is the most common clinical electrolyte disorder. Once thought to be asymptomatic in response to adaptation by the brain, recent evidence suggests that chronic hyponatremia may be linked to attention deficits, gait disturbances, risk of falls, and cognitive impairments. Such neurologic defects are associated with a reduction in quality of life and may be a significant cause of mortality. However, because underlying diseases such as adrenal insufficiency, heart failure, liver cirrhosis, and cancer may also affect brain function, the contribution of hyponatremia alone to neurologic manifestations and the underlying mechanisms remain unclear. Using a syndrome of inappropriate secretion of antidiuretic hormone rat model, we show here that sustained reduction of serum sodium ion concentration induced gait disturbances; facilitated the extinction of a contextual fear memory; caused cognitive impairment in a novel object recognition test; and impaired long-term potentiation at hippocampal CA3–CA1 synapses. In vivo microdialysis revealed an elevated extracellular glutamate concentration in the hippocampus of chronically hyponatremic rats. A sustained low extracellular sodium ion concentration also decreased glutamate uptake by primary astrocyte cultures, suggesting an underlying mechanism of impaired long-term potentiation. Furthermore, gait and memory performances of corrected hyponatremic rats were equivalent to those of control rats. Thus, these results suggest chronic hyponatremia in humans may cause gait disturbance and cognitive impairment, but these abnormalities are reversible and careful correction of this condition may improve quality of life and reduce mortality.     

CD133 Expression at the Metastatic Site Predicts Patients’ Outcome in Colorectal Cancer with Synchronous Liver Metastasis

Background

CD133 is a transmembrane protein that is proposed to be a stem cell marker of colorectal cancer (CRC); however, the correlation between CD133 expression and survival of CRC patients with liver metastasis has not been fully examined.

Methods

CD133 expression was evaluated immunohistochemically, both in primary tumors and synchronous liver metastases of 88 consecutive CRC patients, as well as recurrent lesions in the remnant liver of 27 of these 88 patients. The relationship between CD133 expression and clinicopathological characteristics, recurrence-free survival, and overall survival (OS) was analyzed.

Results

CD133 expression in liver metastases (mCD133) was detected in 50 of 88 patients (56.8 %), and had significant correlation with CD133 expression in primary lesions (pCD133) (p < 0.001). CD133 expression in liver recurrent lesions (recCD133) also had a significant correlation with mCD133 (p < 0.001). mCD133+ patients had significantly longer disease-free survival (p = 0.043) and OS (p = 0.014) than mCD133? patients. In addition, mCD133+ patients had a significantly lower rate of extrahepatic recurrence (p < 0.001).

Conclusions

Patients without CD133 expression in liver metastasis had significantly shorter survival, perhaps because mCD133? patients had a significantly higher rate of extrahepatic recurrence.