The incidence of diabetes mellitus is increasing among companion animals. This disease has similar characteristics in both humans and animals. Diabetes is frequently identified as an independent risk factor for infections associated with increased mortality. In the present study, homozygous diabetic (db/db) mice were infected with Listeria (L.) monocytogenes and then treated with the anti-diabetic drug exendin-4, a glucagon-like peptide 1 analogue. In aged db/db mice, decreased CD11b+ macrophage populations with higher lipid content and lower phagocytic activity were observed. Exendin-4 lowered high lipid levels and enhanced phagocytosis in macrophages from db/db mice infected with L. monocytogenes. Exendin-4 also ameliorated obesity and hyperglycemia, and improved ex vivo bacteria clearance by macrophages in the animals. Liver histology examined during L. monocytogenes infection indicated that abscess formation was much milder in exendin-4-treated db/db mice than in the control animals. Moreover, mechanistic studies demonstrated that expression of ATP binding cassette transporter 1, a sterol transporter, was higher in macrophages isolated from the exendin-4-treated db/db mice. Overall, our results suggest that exendin-4 decreases the risk of infection in diabetic animals by modifying the interaction between intracellular lipids and phagocytic macrophages.
ATP-Binding Cassette Transporters/metabolism ; Age Factors ; Animals ; Blood Chemical Analysis ; Cholesterol/metabolism ; Diabetes Mellitus, Type 2/*drug therapy/genetics ; Dyslipidemias/drug therapy/genetics ; Female ; Hyperglycemia/drug therapy/genetics ; Hypoglycemic Agents/*therapeutic use ; Injections, Intraperitoneal ; *Lipid Metabolism/drug effects ; Listeria monocytogenes/*drug effects/immunology ; Listeriosis/*drug therapy/immunology/microbiology ; Macrophages/drug effects/*metabolism ; Mice ; Obesity/drug therapy/genetics ; Peptides/*therapeutic use ; Phagocytosis/drug effects ; Venoms/*therapeutic use

INTRODUCTIONCardiopulmonary resuscitation (CPR) guidelines were revised in 2005 based on new evidence and expert consensus. However, the benefits of the new guidelines remain undetermined and their influence has not been published in Asia. This study aimed to evaluate the impact of implementing the new resuscitation guidelines and identify factors that influence the discharge survival of out-of-hospital cardiac arrest (OHCA) patients in an Asian metropolitan city.

MATERIALS AND METHODSThis was an observational cohort study of all OHCA patients seen by the emergency medical service during the period before (Nov 2003 to Oct 2005) and after (May 2006 to Oct 2008) implementing the new resuscitation guidelines. Detailed clinical information was recorded using the Ustein style template. Statistical analysis was done using X2 test or t-test for univariate analysis and the logistic regression model for multivariate analysis.

RESULTSThere were 463 patients before and 430 patients after the new guidelines who received resuscitation. The rate of recovery of spontaneous circulation (ROSC), survival-to-intensive care unit (ICU) admission, and survival-to-hospital discharge all showed no benefits regarding the new resuscitation guidelines (ROSC: 42% vs 39%, P = 0.32; Survival-to-ICU admission: 33% vs 30%, P = 0.27; survival-to-hospital discharge: 10% vs 7%, P = 0.09). The rate of ventricular fibrillation/pulseless ventricular tachycardia (VF/pulseless VT), rate of witnessed arrest, and rate of bystander CPR were much lower than in Western studies. After multivariate logistic regression, factors related to discharge survival were witnessed arrest and initial rhythm with VF/pulseless VT. The new resuscitation guidelines did not significantly influence the discharge survival.

CONCLUSIONSWe did not observe any improvement in survival after implementing the new guidelines. Independent factors of survival-to-hospital discharge are witnessed arrest and initial rhythm with VF/pulseless VT. Because the rates of VF/pulseless VT and bystander CPR in Asia are low, popularising CPR training programmes and increasing the rate of bystander CPR may be more important for improving OHCA survival rates than frequent guideline changes.

Aged ; Aged, 80 and over ; Cardiopulmonary Resuscitation ; methods ; standards ; Emergency Service, Hospital ; statistics & numerical data ; Female ; Hospitals, University ; statistics & numerical data ; Humans ; Male ; Middle Aged ; Out-of-Hospital Cardiac Arrest ; mortality ; therapy ; Patient Discharge ; statistics & numerical data ; Practice Guidelines as Topic ; Survival Analysis ; Taiwan ; epidemiology

Mutations in the synaptic nuclear envelope protein 1 (SYNE1) gene are associated with substantial clinical heterogeneity. Here, we report the first case of SYNE1 ataxia in Taiwan due to two novel truncating mutations. Our patient, a 53-year-old female, exhibited pure cerebellar ataxia with c.1922del in exon 18 and c. C3883T mutations in exon 31. Previous studies have indicated that the prevalence of SYNE1 ataxia among East Asian populations is low. In this study, we identified 27 cases of SYNE1 ataxia from 22 families in East Asia. Of the 28 patients recruited in this study (including our patient), 10 exhibited pure cerebellar ataxia, and 18 exhibited ataxia plus syndromes. We could not find an exact correlation between genotypes and phenotypes. Additionally, we established a precise molecular diagnosis in our patient’s family and extended the findings on the ethnic, phenotypic, and genotypic diversity of the SYNE1 mutational spectrum.

Currently, the optimal resuscitation fluid remains debatable. Therefore, in the present study, we designed a trometamol-balanced solution (TBS) for use as a resuscitation fluid for hemorrhagic shock. Hemorrhagic shock was induced in 18 male Wistar-Kyoto rats, which were assigned to normal saline (NS), Ringer's solution (RS), and TBS groups. During the hemorrhagic state, their hemodynamic parameters were recorded using an Abbott i-STAT analyzer with the CG4+ cartridge (for pH, pressure of carbon dioxide, pressure of oxygen, total carbon dioxide, bicarbonate, base excess, oxygen saturation, and lactate), the CG6+ cartridge (for sodium, potassium, chloride, blood glucose, blood urea nitrogen, hematocrit, and hemoglobin), and enzyme-linked immunosorbent assay kits (calcium, magnesium, creatinine, aspartate aminotransferase, alanine aminotransferase, bilirubin, and albumin). Similar trends were found for the parameters of biochemistries, electrolytes, and blood gas, and they revealed no significant changes after blood withdrawal-induced hemorrhagic shock. However, the TBS group showed more effective ability to correct metabolic acidosis than the NS and RS groups. TBS was a feasible and safe resuscitation solution in this study and may be an alternative to NS and RS for resuscitation in hemorrhagic shock patients without liver damage.

We studied a family with Gorlin-Goltz syndrome. The novel mutations of our cases were located on the 21st exon of the PTCH1 gene (c.3450C>G). The father, who received a strategic 56-day vismodegib treatment for disease control, was the first patient with Gorlin syndrome treated with the hedgehog inhibitor in Taiwan. The lesions regressed gradually, with scar formation, and were subsequently removed via a wide excision. Further details are provided below.
Basal Cell Nevus Syndrome* ; Cicatrix ; Exons ; Fathers ; Hedgehogs ; Humans ; Taiwan

Acidosis ; Alanine Transaminase ; Animals ; Aspartate Aminotransferases ; Bilirubin ; Blood Glucose ; Blood Urea Nitrogen ; Carbon Dioxide ; Creatinine ; Electrolytes ; Enzyme-Linked Immunosorbent Assay ; Hematocrit ; Hemodynamics ; Humans ; Hydrogen-Ion Concentration ; Liver ; Magnesium ; Male ; Oxygen ; Potassium ; Rats ; Resuscitation ; Shock, Hemorrhagic ; Sodium

Currently, the optimal resuscitation fluid remains debatable. Therefore, in the present study, we designed a trometamol-balanced solution (TBS) for use as a resuscitation fluid for hemorrhagic shock. Hemorrhagic shock was induced in 18 male Wistar-Kyoto rats, which were assigned to normal saline (NS), Ringer's solution (RS), and TBS groups. During the hemorrhagic state, their hemodynamic parameters were recorded using an Abbott i-STAT analyzer with the CG4+ cartridge (for pH, pressure of carbon dioxide, pressure of oxygen, total carbon dioxide, bicarbonate, base excess, oxygen saturation, and lactate), the CG6+ cartridge (for sodium, potassium, chloride, blood glucose, blood urea nitrogen, hematocrit, and hemoglobin), and enzyme-linked immunosorbent assay kits (calcium, magnesium, creatinine, aspartate aminotransferase, alanine aminotransferase, bilirubin, and albumin). Similar trends were found for the parameters of biochemistries, electrolytes, and blood gas, and they revealed no significant changes after blood withdrawal-induced hemorrhagic shock. However, the TBS group showed more effective ability to correct metabolic acidosis than the NS and RS groups. TBS was a feasible and safe resuscitation solution in this study and may be an alternative to NS and RS for resuscitation in hemorrhagic shock patients without liver damage.