A moderate dose of propofol and rapidly induced mild hypothermia with extracorporeal lung and heart assist (ECLHA) improve the neurological outcome after prolonged cardiac arrest in dogs

BACKGROUND AND PURPOSE: Propofol has been shown to protect against neuronal damage induced by brain ischaemia in small animal models. We reported previously that mild hypothermia (33 degrees C) in combination with extracorporeal lung and heart assist (ECLHA) improved the neurological outcome in dogs with cardiac arrest (CA) of 15 min induced during normothermia. In the present study, we investigated the neuroprotective effect of propofol infusion under mild hypothermia with ECLHA in this model. METHODS: Twenty-one female dogs (15 mongrel dogs and 6 beagles) were divided into three groups: Midazolam 0.1 mg/(kg h) infusion group (M, n=7), Propofol 2 mg/(kg h) infusion group (P2, n=7), Propofol 4 mg/(kg h) infusion group (P4, n=7). Normothermic ventricular fibrillation (VF) was induced in all dogs for 15 min, followed by brief ECLHA and 168 h of intensive care. The drug infusion was initiated at a constant rate after the restoration of spontaneous circulation (ROSC) to 24 h. Mild hypothermia (33 degrees C) was maintained for 20 h. Neurological deficit scores (NDS: 0%=normal, 100%=brain death) were evaluated for neurological function from 33 to 168 h. RESULTS: One dog in the M group died, and the remaining dogs survived for 168 h. The P4 group showed better neurological recovery compared with the M group (48 h, 21+/-16% versus 32+/-15%; 72 h, 7+/-6% versus 25+/-11%; 96 h, 6+/-6% versus 21+/-6%; 120 h, 5+/-5% versus 20+/-6%; 144 h, 4+/-4% versus 20+/-6%; 168 h, 4+/-4% versus 20+/-6%, p<0.05). One dog in the P2 and three dogs in the P4 group achieved full neurological recovery (NDS: 0%). The number of intact pyramidal cells in the hippocampal CA1 was greater in the propofol groups than midazolam group (p<0.05). CONCLUSION: The combination of propofol infusion at a rate of 4 mg/(kg h), 24h and rapidly induced mild hypothermia (33 degrees C) with ECLHA might provide a successful means of cerebral resuscitation from CA.     

ITIH4 and Gpx3 are potential biomarkers for amyotrophic lateral sclerosis

The diagnosis of amyotrophic lateral sclerosis (ALS) is difficult due to lack of definitive biomarkers. Our aim was to identify characteristic serum protein patterns that could provide candidate biomarkers for ALS. We divided mutant superoxide dismutase-1 (SOD1)^H46R rats into three groups based on disease progression: pre-symptom (90 days), onset, and end-stage. After separation of serum proteins using two-dimensional electrophoresis, we selected clear protein spots and identified two candidate proteins—inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4) and glutathione peroxidase 3 (Gpx3). The 120 kDa ITIH4 increased at the onset of the disease and the 85 kDa ITIH4, a cleaved form, at the end-stage in the sera of the SOD1^H46R rats. Expression of the 85 kDa ITIH4 was substantial in ALS compared with controls or patients with muscular dystrophy, Alzheimer diseases, or Parkinson diseases. The Gpx3 protein levels in the sera of SOD1^H46R rats were upregulated pre-symptom and gradually decreased as the disease progressed. The Gpx3 protein levels were lower in the sera of the patients with ALS than in other diseases. These results indicate that ITIH4 and Gpx3 are potential biomarkers for ALS.     

Effects of prostaglandin E1 infusion in the pre-operative management of critical congenital heart disease

Prostaglandin E1 (PGE1) was administered to 27 infants in whom pulmonary or systemic blood flow was entirely or significantly dependent upon the patency of the ductus arteriosus. In 12 patients with pulmonary atresia or severe pulmonary stenosis, PGE1 infusion was followed by an improvement in hypoxemia and acidemia (group I). In 2 patients with left ventricular outflow-tract obstruction, PGE1 infusion was followed by an improvement in arterial blood pressure, peripheral perfusion and urine output (group II). In 5 patients with d-transposition of the great arteries and intact ventricular septum who had persistent severe hypoxemia after creation of an interatrial communication, PGE1 infusion improved the arterial oxygenation with dilatation of the ductus arteriosus (group III). Seven patients (3 of group I, 2 of group II and 2 of group III) failed to respond to PGE1. There were no fatal side effects. It is concluded that PGE1 therapy is highly effective in stabilizing pre-operative conditions of infants with ductus-dependent congenital heart disease.     

Immunoaffinity purification of human erythrocyte prolidase

A procedure including immunoaffinity gel chromatography of an immobilized monoclonal antibody was used to isolate human erythrocyte prolidase (EC 3.4.13.9). The monoclonal antibody was developed against liver prolidase and the antibody recognized the erythrocyte enzyme. The purification procedure included three steps of DEAE cellulose (batcher), immunoaffinity gel chromatography and gel filtration column chromatography. The overall recovery was approximately 20% and the specific activity of the purified preparation was approximately 260 U/mg of protein, a value exceeding that obtained using conventional procedures.     

A pilot study of intraoperative localization of peripheral small pulmonary tumors by cone-beam computed tomography: sandwich marking technique

BackgroundIntraoperative identification of small pulmonary nodules has been an important technical issue. We aimed to develop a new localization method which is much safer and simple procedure compared with conventional methods.MethodsThis was a retrospective study including patients with resected peripheral pulmonary nodules between November 2017 and April 2021 at Teikyo University School of Medicine, and Saitama Cardiovascular and Respiratory Center. All surgical procedure was wedge resection, and the tumor size was equal to or less than 20 mm which were detected by cone-beam computed tomography (CBCT; Philips Allura Xper FD 20, Philips). Some metal clips were put on several places of visceral pleura, where the target lesion was sandwiched by marking clips (sandwich marking technique). CBCT detected both the target lesion and metal clips, and video-assisted thoracoscopic surgery (VATS) was performed. Radiological and pathological findings were analyzed, and the correlation coefficient of tumor size was examined among pre-, intra-, and post-operative tumor sizes.ResultsThe average age of 90 patients was 65.2 years, and 47 were male (52.2%). All procedure was wedge resection including twelve bi-wedge resections, and one hundred nine peripheral pulmonary lesions were obtained by sandwich marking technique. The detection rate was 100%, and there was no marking-related complication.ConclusionsAll small peripheral pulmonary lesions were successfully detected and resected by using CBCT with no marking-related complication. Sandwich marking technique was demonstrated to provide safe, reliable, and simple localization procedure for small peripheral pulmonary lesions.     

Tumor size before image-guided brachytherapy is an important factor of local control after radiotherapy for cervical squamous cell carcinoma: analysis in cases using central shielding

We analyzed the local control (LC) of cervical squamous cell carcinoma treated by computed tomography (CT)-based image-guided brachytherapy (IGBT) using central shielding (CS). We also examined the value of tumor diameter before brachytherapy (BT) as a factor of LC. In total, 97 patients were analyzed between April 2016 and March 2020. Whole-pelvic (WP) radiotherapy (RT) with CS was performed, and the total pelvic sidewall dose was 50 or 50.4 Gy; IGBT was delivered in 3–4 fractions. The total dose was calculated as the biologically equivalent dose in 2 Gy fractions, and distribution was modified manually by graphical optimization. The median follow-up period was 31.8 months (6.3–63.2 months). The 1- and 2-year LC rates were 89% and 87%, respectively. The hazard ratio was 10.11 (95% confidence interval: 1.48–68.99) for local recurrence in those with a horizontal tumor diameter ≥ 4 cm compared to those with < 4 cm before BT. In CT-based IGBT for squamous cell carcinoma, favorable LC can be obtained in patients with a tumor diameter < 4 cm before BT. However, if the tumor diameter is ≥ 4 cm, different treatment strategies such as employing interstitial-BT for dose escalation may be necessary.     

Muscular Metastasis of Hepatocellular Carcinoma: Case Report and Literature Review

There are few case reports of hepatocellular carcinoma (HCC) metastasis to the skeletal muscle. A 78-year-old man developed a mass in the right shoulder. Washout of contrast medium during contrast-enhanced ultrasonography (CEUS) in both the primary HCC and the metastatic site was detected. Several nodules were scattered throughout the liver on an autopsy. In addition, the moderately differentiated HCC had metastasized to the right teres major muscle. Rare muscular metastasis should be considered if a hepatic tumor is moderately or poorly differentiated HCC. Early washout during CEUS is consistent with a pathological diagnosis of moderately or poorly differentiated HCC.     

The Body Fat Percentage Rather Than the BMI Is Associated with the CD4 Count among HIV Positive Japanese Individuals

Maintenance of the cluster of differentiation 4 (CD4) positive lymphocyte count (CD4 count) is important for human immunodeficiency virus (HIV) positive individuals. Although a higher body mass index (BMI) is shown to be associated with a higher CD4 count, BMI itself does not reflect body composition. Therefore, we examined the association of body weight, body composition and the CD4 count, and determined the optimal ranges of CD4 count associated factors in Japanese HIV positive individuals. This cross-sectional study included 338 male patients treated with antiretroviral therapy for ≥12 months. Multiple logistic regression analysis was used to identify factors significantly associated with a CD4 count of ≥500 cells (mm³)⁻¹. The cutoff values of factors for a CD4 ≥ 500 cells (mm³)⁻¹ and cardiovascular disease risk were obtained by receiver operating characteristic curves. Age, body fat percentage (BF%), nadir CD4 count, duration of antiretroviral therapy (ART), years since the HIV-positive diagnosis and cholesterol intake showed significant associations with the CD4 count. The cutoff value of BF% for a CD4 ≥ 500 cells (mm³)⁻¹ and lower cardiovascular disease risk were ≥25.1% and ≤25.5%, respectively. The BF%, but not the BMI, was associated with CD4 count. For the management of HIV positive individuals, 25% appears to be the optimal BF% when considering the balance between CD4 count management and cardiovascular disease risk.