Deficient natural killer (NK) cells in paroxysmal nocturnal haemoglobinuria (PNH): studies of lymphoid cells fractionated by discontinuous density gradient centrifugation

Non-adherent, non-B lymphoid cells from six patients with PNH and six healthy subjects were fractionated by Percoll discontinuous density gradient centrifugation (DDGC). The cell distribution pattern, NK cell activity (NKA), large granular lymphocytes (LGL) count and surface marker phenotypes were studied. The distribution patterns of patients' cells did not significantly differ from the controls. The peak of the NKA was found in low density fractions where the maximum counts of LGL, Leu-7+2- cells and Leu-11+ cells were present. The NKA and the proportion of Leu-7+2- cells and Leu-11+ cells were significantly lower in patients with PNH (P less than 0.001 for NKA and surface phenotypes; P less than 0.02 for LGL counts). NKA in the Percoll fractions was correlated with the counts of LGL (r=0.69, P less than 0.001), Leu-7+2- cells (r = 0.75, P less than 0.001) and Leu-11+ cells (r = 0.89, P less than 0.001). Therefore, we concluded that NKA is deficient in PNH because of decreased NK cell counts.     

Characteristics and prognostic factors in patients with differentiated thyroid cancer who underwent a total or subtotal thyroidectomy: Surgical approach for high-risk patients

Differentiated thyroid cancer grows slowly in general. But some patients repeat recurrence and progress finally to death. To clarify the difference of their prognosis and establish the appropriate thyroid surgery, we studied 105 patients with differentiated thyroid cancer who were treated with total or subtotal thyroidectomy, excluding those with small tumors, under uniform conditions regarding thyroidectomy. There were 77 women and 28 men aged 19 to 76 years (mean 54.7 years). More than 60% (alive) were followed up for longer than 10 years. Thirty-eight (36%) patients had recurrences. There were 19 deaths. Twelve of 31 patients with locoregional recurrence died and 7 of these 12 died of locoregional control failure (neck and mediastinum). Age at first operation, tumor size, and local tumor extension increased the rate of recurrence significantly. Multivariate analysis confirmed that age, locoregional recurrence, and distant metastasis significantly affected survival. Although lymph node metastases were not a prognostic factor, for patients at high risk for recurrence who are older, and have large tumors with invasion, complete resection of cervical lymph nodes is advised to prevent local recurrence and prolong the disease-free interval. Prolongation of the disease-free interval may lead to prolonged survival time.     

Evaluation of blood flow patterns of true and false lumens in dissecting aneurysms using MR phase-contrast techniques

The magnetic resonance phase-contrast technique for the measurement of flow velocity and volume in true and false lumens was studied in six patients with chronic dissecting aneurysms. Phase-contrast images were obtained at a level perpendicular to the dissecting aneurysms of the descending aorta. As the maximum diameter of aneurysms increased, the ratio of the cross-sectional area of the false to the true lumen increased and the peak average velocity in the true lumen during systole was decreased. This technique proved invaluable for determining prognosis and operability for this condition.     

Resection of the Colon Simultaneously with Pancreaticoduodenectomy for Tumors of the Pancreas and Periampullary Region: Short-term and Long-term Results

Simultaneous resection of the colon with pancreaticoduodenectomy (PD) is occasionally inevitable to accomplish curative resection in instances when a periampullary tumor involves the mesentery of the colon. However, there is little information regarding short- and long-term outcomes of this aggressive surgery. Among 95 consecutive patients who underwent PD for periampullary malignant tumors, 12 had simultaneous resection of the right colon (group 1) and 83 underwent PD alone (group 2). Intraoperative variables, postoperative morbidity and mortality, and the length of the hospital stay were comparatively analyzed. Survival was also compared between the groups in a subset of 36 pancreatic adenocarcinoma patients. Group 1 included more patients with pancreatic cancer, and portal vein resection was more frequently performed, which seemed to be associated with a significantly longer operating time (640 vs. 510 minutes) and increased total blood loss (1965 vs. 1220 ml). However, morbidity and mortality rates did not differ between the groups (50,0% and 0%, respectively, in group 1; 44.6% and 1.2%, respectively, in group 2). The median hospital stays were 67 and 48 days in groups 1 and 2, respectively. In a subset of 36 pancreatic adenocarcinoma patients, the median progression-free survivals were 6 months in both groups 1 and 2; the median overall survivals were 14 months in group 1 and 12 months in group 2. There was no statistically significant difference in survival between the groups. Simultaneous right hemicolectomy with curative intent at the time of PD could thus be performed safely and may offer a survival benefit even for individuals who have advanced pancreatic cancers with involvement of the transverse mesocolon.     

Oxygen nano-bubble water reduces calcium oxalate deposits and tubular cell injury in ethylene glycol-treated rat kidney

Renal tubular cell injury induced by oxalate plays an important role in kidney stone formation. Water containing oxygen nano-bubbles (nanometer-sized bubbles generated from oxygen micro-bubbles; ONB) has anti-inflammatory effects. Therefore, we investigated the inhibitory effects of ONB water on kidney stone formation in ethylene glycol (EG)-treated rats. We divided 60 rats, aged 4 weeks, into 5 groups: control, the water-fed group; 100 % ONB, the 100 % ONB water-fed group; EG, the EG treated water-fed group; EG + 50 % ONB and EG + 100 % ONB, water containing EG and 50 % or 100 % ONB, respectively. Renal calcium oxalate (CaOx) deposition, urinary excretion of N-acetyl-β-d-glucosaminidase (NAG), and renal expression of inflammation-related proteins, oxidative stress biomarkers, and the crystal-binding molecule hyaluronic acid were compared among the 5 groups. In the control and 100 % ONB groups, no renal CaOx deposits were detected. In the EG + 50 % ONB and EG + 100 % ONB groups, ONB water significantly decreased renal CaOx deposits, urinary NAG excretion, and renal monocyte chemoattractant protein-1, osteopontin, and hyaluronic acid expression and increased renal superoxide dismutase-1 expression compared with the EG group. ONB water substantially affected kidney stone formation in the rat kidney by reducing renal tubular cell injury. ONB water is a potential prophylactic agent for kidney stones.     

Oral ADSORBENT AST-120 decreases carotid intima-media thickness and arterial stiffness in patients with chronic renal failure

BACKGROUND/AIM: Intima media thickness (IMT) and stiffness of the carotid arteries is related to coronary artery disease, and chronic renal failure patients are at high risk for such diseases. An oral adsorbent, AST-120 (Kremezin; Kureha Chemical Industry, Tokyo, Japan), can delay the progression of chronic renal failure in undialyzed uremic patients. The aim of the present study was to determine whether AST-120 affects carotid artery IMT and pulse wave velocity (PWV) in patients with chronic renal failure not undergoing dialysis. METHODS: Fifty patients with non-diabetic chronic renal failure were randomly divided into two groups: 30 patients (18 men and 12 women; mean age 53.5 years; mean serum creatinine 3.2 mg/dl) who were given AST-120 (6.0 g/day) and 20 patients (12 men and 8 women; mean age 52.0 years; mean serum creatinine 3.5 mg/dl) who were not given AST-120. Thirty healthy age-matched subjects (18 men and 12 women; mean age 51.5 years; mean serum creatinine 0.9 mg/dl) were also included. The treatment period was 24 months. IMT and arterial stiffness were measured before and after treatment. RESULTS: The slope of the reciprocal serum creatinine concentration over time became significantly less steep in the AST-120 group than in the non-AST-120 group (p < 0.001). Before treatment, carotid artery IMT differed little between the AST-120 group (0.90 +/- 0.22 mm) and the non-AST-120 group (0.88 +/- 0.20 mm). IMT in these two groups was significantly greater than IMT in the control group (0.64 +/- 0.14 mm) (p < 0.01). Carotid IMT in the AST-120 group decreased slightly but not significantly to 0.84 +/- 0.20 mm after 12 months and then significantly after 24 months to 0.78 +/- 0.18 mm (p < 0.05). Carotid IMT in the non-AST group showed little change throughout the experimental period. PWV differed little between the AST-120 group (1,980 +/- 330 cm/s) and the non-AST group (1,940 +/- 360 cm/s) before treatment. PWV values in these two groups were significantly greater than PWV in the control group (1,280 +/- 240 cm/s) (p < 0.01). After 12 and 24 months, PWV in the AST-120 group decreased significantly to 1,840 +/- 280 cm/s (p < 0.05) and to 1,780 +/- 260 cm/s (p < 0.05), respectively; however, PWV in the non-AST group showed a slight increase during the experimental period. CONCLUSION: The data suggest that AST-120 may reduce arterial stiffness and IMT in non-diabetic chronic renal failure patients before dialysis.     

Molecular mechanisms of the inhibitory effects of propofol and thiamylal on sarcolemmal adenosine triphosphate-sensitive potassium channels

BACKGROUND: Both propofol and thiamylal inhibit adenosine triphosphate-sensitive potassium (KATP) channels. In the current study, the authors investigated the effects of these anesthetics on the activity of recombinant sarcolemmal KATP channels encoded by inwardly rectifying potassium channel (Kir6.1 or Kir6.2) genes and sulfonylurea receptor (SUR1, SUR2A, or SUR2B) genes. METHODS: The authors used inside-out patch clamp configurations to investigate the effects of propofol and thiamylal on the activity of recombinant KATP channels using COS-7 cells transfected with various types of KATP channel subunits. RESULTS: Propofol inhibited the activities of the SUR1/Kir6.2 (EC50 = 77 microm), SUR2A/Kir6.2 (EC50 = 72 microm), and SUR2B/Kir6.2 (EC50 = 71 microm) channels but had no significant effects on the SUR2B/Kir6.1 channels. Propofol inhibited the truncated isoform of Kir6.2 (Kir6.2DeltaC36) channels (EC50 = 78 microm) that can form functional KATP channels in the absence of SUR molecules. Furthermore, the authors identified two distinct mutations R31E (arginine residue at position 31 to glutamic acid) and K185Q (lysine residue at position 185 to glutamine) of the Kir6.2DeltaC36 channel that significantly reduce the inhibition of propofol. In contrast, thiamylal inhibited the SUR1/Kir6.2 (EC50 = 541 microm), SUR2A/Kir6.2 (EC50 = 248 microm), SUR2B/Kir6.2 (EC50 = 183 microm), SUR2B/Kir6.1 (EC50 = 170 microm), and Kir6.2DeltaC36 channels (EC50 = 719 microm). None of the mutants significantly affects the sensitivity of thiamylal. CONCLUSIONS: These results suggest that the major effects of both propofol and thiamylal on KATP channel activity are mediated via the Kir6.2 subunit. Site-directed mutagenesis study suggests that propofol and thiamylal may influence Kir6.2 activity by different molecular mechanisms; in thiamylal, the SUR subunit seems to modulate anesthetic sensitivity.     

Preoperative chemotherapy increases cytokine production after lung cancer surgery.

OBJECTIVE: Many phase II trials have shown that preoperative chemotherapy for lung cancer is feasible but associated with postoperative morbidity and mortality. However, little is known about the effect of preoperative chemotherapy on surgical stress and postoperative complications associated with surgical intervention. We evaluated the effect of preoperative chemotherapy on perioperative inflammatory cytokine production as a surgical stress marker. METHODS: The study group comprised 38 patients undergoing anatomical lung resection and mediastinal nodal dissection for clinical stage IB/II non-small cell lung cancer during the period October 2001-December 2003. Nineteen patients received a single cycle of cisplatin (80 mg/m(2)) and docetaxel (60 mg/m(2)) chemotherapy prior to surgery (neoadjuvant group), and 19 patients underwent surgery without any previous chemotherapy (control group). White blood cell and neutrophil counts and serum concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), and granulocyte colony-stimulating factor (GCSF) were determined before surgery and on postoperative days 1 and 3. Postoperative complications were reviewed. Differences were assessed by repeated analysis of variance. RESULTS: Serum concentrations of IL-6 and GCSF rose significantly on postoperative days 1 and 3 in the neoadjuvant group in comparison to concentrations in the control group, but white blood cell count, neutrophil count, and CRP did not differ between the groups. No major complication occurred in either group. CONCLUSIONS: A single cycle of cisplatin and docetaxel chemotherapy followed by surgery can exacerbate overproduction of inflammatory cytokines during the perioperative period in lung cancer patients.     

Relation between vertical orientation and stability of acetabular component in the dysplastic hip simulated by nonlinear three-dimensional finite element method

In acetabular dysplasia, more vertical orientation of the acetabular component is often used to minimize the superolateral bone grafting. This study was designed to determine the effects of vertical orientation of the cup on the stability and polyethylene wear of the acetabular component in uncemented total hip arthroplasty (THA). Three-dimensional finite element models of the hemipelvis with dysplastic acetabulum were developed. Metal-backed hemispherical cups were placed in the true acetabulum with abduction angles of 35, 45, 55, and 65 degrees. It was found that more vertical orientation of the cup was associated with larger relative motion of the metal shell between the acetabulum and metal shell. Furthermore, tilting and torsional shear stresses in the model of the cup abduction angle of 65 degrees were found to be 1.7 times larger than that in the model with 35 degrees at the bone-metal shell interface. More vertically oriented cups caused larger contact stresses at the articulating surfaces of the polyethylene liners. The results suggest that the abduction angle of the acetabular component significantly influences cup loosening and polyethylene wear in THA.     

The relationship between bispectral index and electroencephalographic parameters during isoflurane anesthesia

Bispectral index (BIS) integrates various electroencephalographic (EEG) parameters into a single variable. However, the exact algorithm used to synthesize the parameters to BIS values is not known. The relationship between BIS and EEG parameters was evaluated during nitrous oxide/isoflurane anesthesia. Twenty patients scheduled for elective ophthalmic surgery were enrolled in the study. After EEG recording with a BIS monitor (A-1050) was begun, general anesthesia was induced and maintained with 0.5%-2% isoflurane and 66% nitrous oxide. Using software we developed, we continuously recorded BIS, spectral edge frequency 95% (SEF95), and EEG parameters such as relative beta ratio (BetaRatio), relative synchrony of fast and slow wave (SynchFastSlow), and burst suppression ratio. BetaRatio was linearly correlated with BIS (r = 0.90; P < 0.01; n = 253) at BIS more than 60. At a BIS range of 30 to 80, SynchFastSlow (r = 0.60; P < 0.01; n = 3314) and SEF95 (r = 0.75; P < 0.01; n = 3339) were linearly correlated with BIS. The correlation between BIS and SEF95 was significantly better than the correlation between BIS and SynchFastSlow (P < 0.01). At BIS less than 30, the burst suppression ratio was inversely linearly correlated with BIS (r = 0.76; P < 0.01; n = 65). At BIS less than 80, burst-compensated SEF95 was linearly correlated with BIS (r = 0.78; P < 0.01; n = 3404). In the range of BIS from 60 to 100, BIS can be calculated from BetaRatio. At surgical levels of anesthesia, BIS and SynchFastSlow (a parameter derived from bispectral analysis) or burst-compensated SEF95 (derived from power spectral analysis) are well correlated. However, our results show that SynchFastSlow has no advantage over SEF95 in calculation of BIS. IMPLICATIONS: The relationship between bispectral index (BIS) and electroencephalographic parameters was evaluated during nitrous oxide/isoflurane anesthesia. At surgical levels of anesthesia, BIS and the relative synchrony of fast and slow wave (a parameter derived from bispectral analysis) or burst-compensated spectral edge frequency 95% (a parameter derived from power spectral analysis) are well correlated.