The clue of Interstitial Cell of Cajalopathy (ICCpathy) in human diabetic gastropathy: The ultrastructural and electrical clues of ICCpathy in human diabetic gastropathy

Recent studies of diabetic animal models suggest an important role of ICC in the pathogenesis of gastropathy. The aim of this study was to characterize the ultrastructural features of ICC and record the electrical properties in the stomach of patients with type 2 DM. Gastric specimens were obtained from 13 diabetic patients and 6 control subjects with gastric cancer that underwent gastrectomy. All specimens were taken from disease-free areas. The samples were processed for both electron microscopic and electrophysiologic examination. The characteristic ultrastructural changes of the ICC were observed in both the nucleus and cytoplasm in patients with type 2 DM. Wrinkling of the nuclear envelope and changes in the cytoplasm such as dilatation of the endoplasmic reticulum, an increase of autophagic vacuoles, were more frequently observed in the diabetic patients. Apoptosis characterized by nuclear karyorrhexis or pyknosis was observed only in the diabetic patients. Slow waves were recorded in the circular muscle of stomach. In diabetic patients, the mean resting membrane potential was higher and amplitude was lower than controls. These changes of electrical activities of slow waves were accompanied with ultrastructural changes of ICC, particularly the characteristic nuclear changes. In human diabetic patients, the characteristic ultrastructural changes of ICC such as preapoptosis, accompanied with electrical dysrhythmia of slow waves, were observed. These results show several evidence converging to support that degeneration of the ICC may be associated with the pathogenesis of diabetic gastropathy.     

Haploidentical vs autologous hematopoietic stem cell transplantation in patients with acute leukemia beyond first remission

This is a retrospective comparison of partially mismatched related donor transplantation (PMRDT) and autotransplantation (ABMT) in advanced acute leukemia. Patients underwent T-cell-depleted PMRDT (n=164) or ABMT (n=131) for acute myeloid leukemia (n=130) or acute lymphoblastic leukemia (n=165). Fewer PMRDT patients were in remission (29 vs 85%; P<0.0001). The 5-year cumulative incidence of transplant-related mortality (TRM) was 52% after PMRDT and 16% after ABMT (P<0.0001). The 5-year cumulative incidence of relapse was 32% after PMRDT and 54% after ABMT (P=0.006). The actuarial unadjusted 5-year disease-free survival (DFS) was 16% after PMRDT and 30% after ABMT. In Cox's regression analysis, PMRDT (P<0.0001) and age >15 years (P=0.002) were associated with higher TRM, active disease (P=0.0021), ABMT (P=0.0074) and male sex (P=0.011) with higher relapse, and age >15 years (P=0.0007) and PMRDT (P=0.047) with lower DFS. Amongst second remission patients, TRM was higher after PMRDT (P=0.0003), relapse was higher after ABMT (P=0.034), and 5-year DFS was comparable (32% ABMT and 25% PMRDT). ABMT, if feasible, may be preferable to PMRDT in advanced acute leukemia patients since lower relapse after PMRDT is offset by higher TRM. If an autograft is not feasible because of nonavailability of autologous cells or very advanced disease, PMRDT is a potential alternative.     

Hyperglycemia per se can reduce plasma free fatty acid and glycerol levels in the acutely insulin-deficient dog

To evaluate the in vivo effect of hyperglycemia per se on plasma free fatty acid (FFA) and glycerol concentrations, euglycemic and hyperglycemic clamp studies were performed in six overnight fasted dogs in the state of insulin deficiency produced by somatostatin (SRIF) infusion. The mean blood glucose concentrations during the steady-state (the second hour of each study) averaged 4.65 +/- 0.10 mmol/L in euglycemic clamp and 14.11 +/- 0.10 mmol/L in hyperglycemic clamp. During the SRIF infusion, plasma FFA concentrations increased from 0.32 +/- 0.05 mumol/mL at the basal state to 0.76 +/- 0.04 mumol/mL at the steady-state in euglycemic clamp and from 0.26 +/- 0.04 mumol/mL to 0.43 +/- 0.02 mumol/mL in hyperglycemic clamp. Plasma glycerol concentrations increased from the basal value of 0.07 +/- 0.01 mumol/mL to 0.15 +/- 0.01 mumol/mL during the steady-state in euglycemic clamp and from 0.06 +/- 0.01 mumol/mL to 0.08 +/- 0.01 mumol/mL in hyperglycemic clamp. The steady-state concentrations of plasma FFA and glycerol in hyperglycemic clamp were significantly lower than those in euglycemic clamp (P less than .001; respectively). These results suggest that hyperglycemia per se might decrease plasma FFA and glycerol concentrations at least in part by decreasing lipolysis in the acutely insulin-deficient dog.     

Decreased expression of phospholipase C-beta 2 isozyme in human platelets with impaired function

Platelets from a patient with a mild inherited bleeding disorder and abnormal platelet aggregation and secretion show reduced generation of inositol 1,4,5-trisphosphate, mobilization of intracellular Ca2+, and phosphorylation of pleckstrin in response to several G protein mediated agonists, suggesting a possible defect at the level of phospholipase C (PLC) activation (see accompanying report). A procedure was developed that allows quantitation of platelet PLC isozymes. After fractionation of platelet extracts by high-performance liquid chromatography, 7 out of 10 known PLC isoforms were detected by immunoblot analysis. The amount of these isoforms in normal platelets decreased in the order PLC- gamma 2 > PLC-beta 2 > PLC-beta 3 > PLC-beta 1 > PLC-gamma 1 > PLC- delta 1 > PLC-beta 4. Compared with normal platelets, platelets from the patient contained approximately one-third the amount of PLC-beta 2, whereas PLC-beta 4 was increased threefold. These results suggest that the impaired platelet function in the patient in response to multiple G protein mediated agonists is attributable to a deficiency of PLC-beta 2. They document for the first time a specific PLC isozyme deficiency in human platelets and provide an unique opportunity to understand the role of different PLC isozymes in normal platelet function.     

Five-Year Subjective Outcomes of Obstructive Sleep Apnea Surgery: A Multiinstitutional Study

Objectives

To evaluate the effect of obstructive sleep apnea (OSA) surgery on long-term (5-year) subjective outcomes, including sleep disordered breathing (SDB) symptoms and other complications, in patients with OSA.

Methods

We enrolled patients who underwent diagnostic polysomnography for OSA between January 2006 and December 2006 in ten hospitals. Patients either were treated for OSA or were not treated for OSA. All patients completed a brief telephone survey regarding their SDB signs and symptoms (e.g., snoring, apnea, nocturnal arousals, and daytime sleepiness), positive airway pressure (PAP) compliance, and any adverse effects of either the surgery or PAP. A positive subjective outcome for either surgery or no treatment was taken to be the alleviation of apnea, defined as a ≥50% increase in score. A positive subjective outcome (compliance) for PAP was defined as a PAP usage of ≥4 hours per night and ≥5 days per week.

Results

A total of 229 patients were included in this study. Patients were divided into three groups: a surgery group (n=87), a PAP group (n=68), and a control (untreated) group (n=74). The surgery group exhibited significant improvement in all SDB symptoms compared with the control group. The long-term subjective outcomes of the surgery (52.9%) and PAP (54.4%) groups were significantly better than those of the control group (25.0%). The subjective outcome of the surgery group was not significantly different from that of the PAP group. The overall surgical complication rate was 23.0% (20 of 87) in the surgery group, and 55.0% (22 of 40) of all patients with PAP experienced adverse effects.

Conclusion

The extent of SDB symptoms was consistently improved in patients with OSA at 5 years postsurgery. Information about the potential long-term subjective outcomes should be provided to patients when considering surgery.     

Dual Antiplatelet Therapy Duration Determines Outcome After 2- But Not 1-Stent Strategy in Left Main Bifurcation Percutaneous Coronary Intervention

Objectives

The aim of this study was to investigate clinical outcomes after left main coronary artery (LM) bifurcation percutaneous coronary intervention (PCI) and the impact of the duration of dual antiplatelet therapy (DAPT) according to treatment strategy.

Glycated haemoglobin as a predictor for metabolic syndrome in non-diabetic Korean adults.

AIMS: With increasing prevalence of diabetes mellitus and metabolic syndrome (MS), the importance of early detection of insulin resistance is emphasized. However, a simple and practical method of measurement is not readily available. Therefore, we examined the sensitivity and specificity of HbA(1c) for predicting impaired fasting glucose (IFG) and MS and its association with cardiovascular risk factors, particularly in the normal range of HbA(1c) levels in non-diabetic Korean subjects. METHODS: In 40,155 participants (median age 40 years) participating in a medical check-up programme, analysis of the distribution of HbA(1c) and its association with various cardiovascular risk factors was performed. In 22,465 selected participants, an analysis was conducted of the ability of HbA(1c) to predict MS and IFG. Anthropometric measurements were made in all subjects and fasting glucose, lipid profiles and HbA(1c) were measured. The presence of MS was defined according to the definitions of the Adult Treatment Panel III (ATP III) guideline and the new International Diabetes Federation (IDF) guideline. Patients with diabetes were excluded from the study. RESULTS: The incidence of MS was 12.2% according to ATP III criteria and 7.6% according to IDF criteria. When subjects were grouped by quartile of HbA(1c), cardiovascular risk factors significantly increased as the HbA(1c) increased. An HbA(1c) of 5.45% predicted the presence of MS (ATP III: sensitivity/specificity 57.4/64.3%, area under the curve 64.8%; IDF: sensitivity 60.2/63.4%, area under the curve 66.1%) and fasting blood glucose > or = 5.6 mmol/l (sensitivity/specificity 53.7/70%, area under the curve 66.1%). When the analyses were done separately by gender, female subjects showed higher cut-off of HbA(1c) for the prediction of MS (5.55% for both ATP III and IDF criteria). CONCLUSIONS: HbA(1c) increased as cardiovascular risk factors increased and HbA(1c) of 5.45% predicted the presence of MS. HbA(1c) might be a predictive measure of IFG and MS, and also cardiovascular risk factors in the Korean population.