Insulin–glucagon‐like peptide‐1 receptor agonist relay and glucagon‐like peptide‐1 receptor agonist first regimens in individuals with type 2 diabetes: A randomized,open‐label trial study

Aims/IntroductionGlucagon‐like peptide‐1 receptor agonists (GLP‐1 RA) might be less effective in patients with severe hyperglycemia, because hyperglycemia downregulated the GLP‐1 receptor in an animal study. To examine this hypothesis clinically, we compared the glucose‐lowering effects of GLP‐1 receptor agonist liraglutide with and without prior glycemic control.Materials and MethodsIn an open‐label, parallel trial, participants with poorly controlled type 2 diabetes were recruited and randomized to receive once‐daily insulin therapy, degludec (Insulin–GLP‐1 RA relay group, mean 16.8 ± 11.4 IU/day), for 12 weeks and then liraglutide for 12 weeks or subcutaneous injections of GLP‐1 RA, liraglutide (GLP‐1 RA first group, 0.9 mg), for 24 weeks. The primary efficacy end‐points consisted of changes in the levels of fasting plasma glucose and glycated hemoglobin (HbA1c).ResultsThe median fasting plasma glucose and HbA1c before the study were 210.0 mg/dL and 9.8%, respectively. The levels of fasting plasma glucose and HbA1c significantly decreased in the Insulin–GLP‐1 RA relay group (P < 0.001) and GLP‐1 RA first group (P < 0.001) by week 24, although no intergroup differences were observed. The reduction of HbA1c in the Insulin–GLP‐1 RA relay group tended to be larger than that in the GLP‐1 RA first group in the lowest CPR (C‐peptide immunoreactivity) quartile (P = 0.072). The adverse events consisted of gastrointestinal problems, followed by hypoglycemia.ConclusionsThe GLP‐1 receptor agonist is overall effective without prior glycemic control with insulin in participants with poorly controlled type 2 diabetes. However, in participants with insulinopenic type 2 diabetes, prior glycemic control with insulin might overcome glucose toxicity‐induced GLP‐1 resistance.     

Thirty-One Autopsy Cases of Trisomy 18: Clinical Features and Pathological Findings

The clinical features and morphological findings in 31 Japanese infants with trisomy 18 are presented. The majority were small-for-date infants. There was no sex predominance in our series, as opposed to male female ratios of 1:3 reported in the literature. The average age at death was greater in females than in males. Cardiovascular anomalies were consistently present; ventricular septar defect and patent ductus arteriosus being the most common malformations. Various other internal malformations including the Arnold-Chiari malformation were observed.     

Wavefront analysis of acrylic spherical and aspherical intraocular lenses

PURPOSE: To compare higher order wavefront aberrations in eyes implanted with acrylic aspherical intraocular lenses (IOLs) with a modified prolate anterior surface with conventional acrylic spherical IOLs by using the optical path difference method. METHODS: In a nonrandomized parallel cohort investigation, 36 eyes of 31 patients implanted with aspherical IOLs (Tecnis ZA9003) and 37 eyes of 23 age-matched patients implanted with spherical IOLs (SENSOR AR40e) were evaluated with a wavefront analyzer (OPD-Scan II) preoperatively and 1 month after surgery. The higher order aberrations for a 4.0-mm pupil diameter were expanded into Zernike's polynomial expression. Coma aberration, spherical aberration, and total higher order aberrations were evaluated as root mean square values. RESULTS: Postoperatively, coma and total higher order aberrations of spherical and aspherical IOLs significantly improved in both eyes. Spherical aberration improved in eyes with aspherical IOLs only (P < 0.01). CONCLUSION: After implantation of acrylic aspherical IOLs, postoperative higher order aberrations were not necessarily lower than after implantation of acrylic spherical IOLs, but compared with levels following implantation of acrylic spherical IOLs, a significant reduction in spherical aberration was achieved.     

A multicenter phase II study of carboplatin and paclitaxel with a biweekly schedule in patients with advanced non-small-cell lung cancer: Kyushu thoracic oncology group trial

Purpose: This multicenter phase II study was conducted to investigate the efficacy and safety of carboplatin in combination with paclitaxel administered according to a biweekly schedule as a first-line chemotherapy for advanced non-small-cell lung cancer (NSCLC). Patients and methods: Eligibility criteria included histologically or cytologically confirmed NSCLC (stage IIIb or IV), no prior treatment, and measurable or evaluable disease. Paclitaxel (140 mg/m²) was administered intravenously on day 1, in combination with carboplatin at an area under the concentration time curve (AUC) of 3, every 2 weeks. Results: Seventy-four patients (45 men) with a median age of 62 years (range 40–74) and a median ECOG performance status of 1 (range 0–2) were enrolled. The response rate was 35.1% [95% confidence interval (CI): 24.4–47.1%], with 26 partial responses. The median survival was 357 days, and the median time to progression was 218 days. Toxicity was generally mild; National Cancer Institute-Common Toxicity Criteria (NCI-CTC) grades 3 and 4 neutropenia was observeded in 50.0% of the patients, and grades 3 and 4 nausea/vomiting in 4.1%. Conclusions: Biweekly carboplatin combined with paclitaxel demonstrated anti-tumor activity in advanced NSCLC, with response and survival rates similar to those of carboplatin combined with paclitaxel administered every 3 weeks but with a more favorable toxicity profile, and the present data indicate that the regimen is suitable for use on an outpatient basis.     

Effects of habu (Trimeresurus flavoviridis) venom on isolated and perfused hearts of rats

Crude habu venom decreased coronary perfusion pressure and produced a small increase in myocardial tension of isolated and perfused rat hearts. Indomethacin infusion depressed the fall in perfusion pressure caused by the venom, without affecting the increase in tension. Heated venom decreased perfusion pressure, but did not increase myocardial tension. These results suggest that crude habu venom has coronary vasodilating and positive inotropic effects, possibly through actions of a phospholipase A2 and a heat-labile component, respectively.     

Seizure Deterioration with Increased Levetiracetam Blood Concentration during the Postpartum Period in Refractory Temporal Lobe Epilepsy

We evaluated a 39-year-old pregnant woman with right temporal lobe epilepsy. During the second trimester, seizure deterioration was responsive to an increased daily dose of levetiracetam (LEV). However, immediately after delivery, new non-habitual seizures emerged along with a sharply increased LEV concentration. The frequency of habitual seizures also slightly increased. The non-habitual seizures completely disappeared, and the frequency of the habitual seizures improved to the baseline level after the LEV dosage was reduced. Thus, a paradoxical effect of an increased LEV blood concentration was assumed to be a potential cause of these events. Peripartum pharmacokinetic fluctuations in LEV levels should be monitored carefully.     

Fatigue-induced changes in longitudinal relaxation time determined by magnetic resonance imaging

Longitudinal relaxation time (T₁) determined by 3.0-T magnetic resonance imaging of the tibialis anterior and extensor digitorum longus muscles increased gradually with muscle fatigue caused by three 120-s periods of repeated ankle dorsiflexion separated by 5-min rest periods. T₁ values decreased in the recovery period, although they remained higher than the preexercise values. T₁ values for the soleus muscle were unchanged throughout the experiment. Results suggest that muscle T₁ values increase with increasing muscle fatigue.