Docetaxel plus S-1 as a second-line chemotherapy for metastasis or recurrence of esophageal cancer

Although chemotherapy consisting of cisplatin and 5-fluorouracil(CF)has been a standard regimen for esophageal cancer, it might be difficult to use continuously. This study evaluated the response and safety of docetaxel plus S-1 used as a second line therapy. We reviewed 21 patients(postoperatively, 11; after definitive chemoradiotherapy, 8; after chemotherapy, 2) who received chemotherapy between 2006 and 2010. Metastatic or recurrent disease was detected in the organs(n=8), lymph nodes(n=8), main tumors(n=3), mediastinum(n=1), and pleura(n=1). Docetaxel 30mg/m2 was infused every 2 weeks, and S-1 80mg/m2 was taken for 2 weeks, then with 2 weeks rest until progression. Almost all of the patients received docetaxel in the outpatient chemotherapy room. The median number of treatment cycles was 3, ranging from 1-12. Among the 14 patients with a therapeutic response, three(21%)achieved PR, 8 showed SD, and 3 had PD. Toxicity which included grade 3/4 was neutropenia in 6 patients, and anemia in one patient. After a follow-up of over one year, the median overall survival was 10 months, and the one-year survival rate was 38%. Docetaxel plus S-1 might be a feasible regimen as a second-line chemotherapy for metastasis or recurrence of esophageal cancer.     

Electron microscopic localization of substance P and enkephalin in axon terminals related to dendrites of catecholaminergic neurons

Morphological and pharmacological data suggest that catecholaminergic neurons receive afferent axons positively labeled for the peptides, substance P and [Met⁵]enkephalin. In the present study, electron microscopic immunocytochemistry was used to determine whether a positive reaction for these peptides could be localized to axon terminals forming synapses with catecholaminergic neurons in the locus coeruleus and A2 regions of rat brain. Adjacent sections through these areas were incubated with antiserum to either substance P, [Met⁵]-enkephalin, or tyrosine hydroxylase, a specific marker for catecholaminergic neurons. The sections were subsequently processes by the peroxidase-antiperoxidase immunocytochemical technique. In both the locus coeruleus and A2 region, tyrosine hydroxylase was localized primarily to perikarya and dendrites of intrinsic neurons; whereas substance P and enkephalin-like immunoreactivity was localized to axons and axon terminals. The axon terminals showing positive reactions for substance P and [Met⁵]-enkephalin were morphologically similar to each other and to one type of axon terminal which formed synapses with dendrites labeled for tyrosine hydroxylase. This type of axon terminal always formed asymmetric synaptic junctions and contained 3–4 large (75–100 nm) dense vesicles (LDVs) and many small (40–60 nm) clear vesicles (SCVs). The reaction product for substance P and [Met⁵]-enkephalin was distributed throughout the lumen of the LDVs and formed a rim of labeling around the outer boundaries of the SCVs. These findings demonstrate that substance P and [Met⁵]-enkephalin-positive reactions are selectively localized to subcellular organelles in axon terminals in the locus coeruleus and A2 region of rat brain. They further suggest that the labeled axon terminals form synapses with dendrites of the catecholaminergic neurons.     

Influence of the COVID-19 Pandemic on Overall Physician Visits and Telemedicine Use Among Patients With Type 1 or Type 2 Diabetes in Japan

BackgroundRegular visits with healthcare professionals are important for preventing serious complications in patients with diabetes. The purpose of this retrospective cohort study was to clarify whether there was any suppression of physician visits among patients with diabetes during the spread of the novel coronavirus 2019 (COVID-19) in Japan and to assess whether telemedicine contributed to continued visits.MethodsWe used the JMDC Claims database, which contains the monthly claims reported from July 2018 to May 2020 and included 4,595 (type 1) and 123,686 (type 2) patients with diabetes. Using a difference-in-differences analysis, we estimated the changes in the monthly numbers of physician visits or telemedicine per 100 patients in April and May 2020 compared with the same months in 2019.ResultsFor patients with type 1 diabetes, the estimates for total overall physician visits were −2.53 (95% confidence interval [CI], −4.63 to 0.44) in April and −8.80 (95% CI, −10.85 to −6.74) in May; those for telemedicine visits were 0.71 (95% CI, 0.47–0.96) in April and 0.54 (95% CI, 0.32–0.76) in May. For patients with type 2 diabetes, the estimates for overall physician visits were −2.50 (95% CI, −2.95 to −2.04) in April and −3.74 (95% CI, −4.16 to −3.32) in May; those for telemedicine visits were 1.13 (95% CI, 1.07–1.20) in April and 0.73 (95% CI, 0.68–0.78) in May.ConclusionThe COVID-19 pandemic was associated with suppression of physician visits and a slight increase in the utilization of telemedicine among patients with diabetes during April and May 2020.Key words: COVID-19, telemedicine, outpatient, diabetes     

Crosstalk between high-molecular-weight adiponectin and T-cadherin during liver fibrosis development in rats

Adiponectin, a circulating adipocyte-derived secretory protein, reportedly plays an important role in liver fibrosis development, although the biological role of adiponectin in liver fibrogenesis is still controversial. Adiponectin is present in the serum as three oligometric complexes; namely, high-, middle-, and low-molecular weight (HMW, MMW, and LMW, respectively). Adiponectin exerts different biological activities in an oligomerization-dependent manner. The aim of our current study was to examine the alteration of each isoform of adiponectin and its receptors (AdipoR1, AdipoR2, and T-cadherin) during the choline-deficient L-amino acid-defined (CDAA) diet-induced rat liver fibrosis development. We also elucidated the methylation status of all receptors. The serum level of total adiponectin significantly increased during the liver fibrosis development. Among the three isoforms, only HMW adiponectin was significantly up-regulated whereas MMW and LMW were not. The expression of T-cadherin, which exclusively binds with HMW adiponectin, was significantly augmented as well. The AdipoR2 expression was markedly decreased and showed no marked difference from that of AdipoR1. No obvious methylation change was observed in all three receptors, suggesting that another mechanism is involved in the alteration of receptor gene expression. Collectively, since the specific ligand and receptor were augmented together, crosstalk between HMW adiponectin and T-cadherin may play an important role during liver fibrosis development in rats.     

Autosomal recessive cystinuria caused by genome‐wide paternal uniparental isodisomy in a patient with Beckwith–Wiedemann syndrome

Approximately 20% of Beckwith–Wiedemann syndrome (BWS) cases are caused by mosaic paternal uniparental disomy of chromosome 11 (pUPD11). Although pUPD11 is usually limited to the short arm of chromosome 11, a small minority of BWS cases show genome‐wide mosaic pUPD (GWpUPD). These patients show variable clinical features depending on mosaic ratio, imprinting status of other chromosomes, and paternally inherited recessive mutations. To date, there have been no reports of a mosaic GWpUPD patient with an autosomal recessive disease caused by a paternally inherited recessive mutation. Here, we describe a patient concurrently showing the clinical features of BWS and autosomal recessive cystinuria. Genetic analyses revealed that the patient has mosaic GWpUPD and an inherited paternal homozygous mutation in SLC7A9. This is the first report indicating that a paternally inherited recessive mutation can cause an autosomal recessive disease in cases of GWpUPD mosaicism. Investigation into recessive mutations and the dysregulation of imprinting domains is critical in understanding precise clinical conditions of patients with mosaic GWpUPD.     

Renal Complications and Their Prognosis in Korean Patients with Middle East Respiratory Syndrome-Coronavirus from the Central MERS-CoV Designated Hospital

Some cases of Middle East Respiratory Syndrome-Coronavirus (MERS-CoV) infection presented renal function impairment after the first MERS-CoV patient died of progressive respiratory and renal failure. Thus, MERS-CoV may include kidney tropism. However, reports about the natural courses of MERS-CoV infection in terms of renal complications are scarce. We examined 30 MERS-CoV patients admitted to National Medical Center, Korea. We conducted a retrospective analysis of the serum creatinine (SCr), estimated glomerular filtration rate (eGFR), urine dipstick tests, urinary protein quantitation (ACR or PCR), and other clinical parameters in all patients. Two consecutive results of more than trace (or 1+) of albumin and blood on dipstick test occurred in 18 (60%) (12 [40%]) and 22 (73.3%) (19 [63.3%]) patients, respectively. Fifteen (50.0%) patients showed a random urine ACR or PCR more than 100 mg/g Cr. Eight (26.7%) patients showed acute kidney injury (AKI), and the mean and median durations to the occurrence of AKI from symptom onset were 18 and 16 days, respectively. Old age was associated with a higher occurrence of AKI in the univariate analysis (HR [95% CI]: 1.069 [1.013-1.128], P = 0.016) and remained a significant predictor of the occurrence of AKI after adjustment for comorbidities and the application of a mechanical ventilator. Diabetes, AKI, and the application of a continuous renal replacement therapy (CRRT) were risk factors for mortality in the univariate analysis (HR [95% CI]: diabetes; 10.133 [1.692-60.697], AKI; 12.744 [1.418-114.565], CRRT; 10.254 [1.626-64.666], respectively). Here, we report renal complications and their prognosis in 30 Korean patients with MERS-CoV.     

Postischemic angiogenic factor expression in stroke-prone rats

Spontaneously hypertensive stroke-prone rats (SHRSP), a model for genetic stroke susceptibility, suffer spontaneous stroke and enhanced injury after experimental stroke, in part due to abnormal cerebrovascular development. We hypothesized that angiopoietin system genes in SHRSP may follow unique patterns of expression after experimentally induced stroke. SHRSP, hypertensive control rats (SHR), and normotensive controls (WKY) were subjected to experimental middle cerebral artery occlusion, and brain RNA was analyzed for expression of angiogenic genes. Expression of angiopoietin-2 increased after stroke in all rat strains and was significantly enhanced in SHRSP compared with control strains. In addition, expression of angiopoietin-1 and the angiopoietin receptor dropped markedly after stroke in SHRSP animals, but was not different after ischemia in SHR and WKY strains. Thus, the SHRSP brain elaborates a unique and specific pattern of angiopoietin system gene expression after stroke which may underlie stroke susceptibility of these rats.