X-linked Alport Syndrome with Type IV Collagen α5 Chain Staining Revealing Normal Expression in the Glomerular Basement Membrane and Negative on Bowman's Capsule and Distal Tubular Basement Membrane: A Case Report.

X-linked Alport syndrome is a hereditary progressive renal disease resulting from the disruption of collagen α3α4α5 (IV) heterotrimerization caused by pathogenic variants in the COL4A5 gene. This study aimed to report a male case of X-linked Alport syndrome with a mild phenotype accompanied by an atypical expression pattern of type IV collagen α5 [α5 (IV)] chain in glomerulus. A 38-year-old male presented with proteinuria (2.3 g/day) and hematuria. He has been detected urinary protein and occult blood since childhood. A renal biopsy was performed at the age of 29 years; however, a diagnosis of Alport syndrome was not considered. A renal biopsy 9 years later revealed diffuse thinning and lamellation of the glomerular basement membrane. Α staining for α5 (IV) revealed a normal expression pattern in the glomerular basement membrane and a complete negative expression in Bowman's capsule and distal tubular basement membrane. Using next-generation sequencing, we detected a COL4A5 missense variant within exon 35 (NM_000495.5: c.3088G>A, p. G1030S). The possibility of X-linked Alport syndrome should be considered when negative expression of α5 (IV) staining on Bowman's capsule was observed.

Aural stimulation with capsaicin prevented pneumonia in dementia patients.

OBJECTIVE: In the present study, we examined the effects of daily application of capsaicin ointment to the external auditory canal for 6 months on the development of pneumonia in elderly dementia patients at high risk of aspiration. METHODS: Twenty-nine oldest-old bedridden dementia inpatients at high risk of aspiration were enrolled in the present study. Ointment containing 0.025% capsaicin was applied to each external auditory canal with a cotton swab alternatively once a day for 6 months. RESULTS: The incidence of pneumonia during the 6 months before the intervention was 1.80±0.37 in these patients. However, this incidence significantly decreased to 0.40±0.29 (p<0.01) during the 6 months of the alternative application of capsaicin ointment to each auditory canal. No adverse effect such as otalgia was observed. CONCLUSION: These findings suggest that daily long-term aural stimulation with capsaicin ointment enhanced the cough reflex via Arnold's ear-cough reflex as a glottis protective measure, resulting in the reduction of incidence of pneumonia in elderly dementia patients at high risk of aspiration. The daily aural stimulation with capsaicin ointment may be a safe and promising intervention to prevent aspiration pneumonia in elderly people, especially those who cannot undergo swallowing exercise.

Comparison of the efficacy and safety of 10-mg empagliflozin every day versus every other day in Japanese patients with Type 2 Diabetes Mellitus: a pilot trial.

The terminal elimination half-life (t1/2) of empagliflozin is 13.1 hours. Accordingly, we hypothesized that the administration of empagliflozin every other day might improve glycemic control in patients with type 2 diabetes mellitus, not being inferior to the therapy every day. We investigated the clinical effects and safety of the addition of empagliflozin every day or every other day to type 2 diabetic patients with a poor control in glycemia. Thirteen Japanese patients diagnosed as type 2 diabetes mellitus recruited to this study. Subjects were divided into two groups; one was treatment with 10 mg of empagliflozin every day (Group A), the other was 10 mg of empagliflozin every other day (Group B). The comparable study of multiple clinical indexes between the 2 groups was made before and 8, 16, and 24 weeks after the treatment. After the treatment for 24 weeks, the HbA1c level was decreased both in group A (from 7.5%±1.1% to 6.5%±0.8%) and in group B (from 7.6%±0.8% to 7.2%±0.5%). This pilot trial suggested the possibility of 10-mg every other day administration with empagliflozin for Japanese patients with type 2 diabetes mellitus. J. Med. Invest. 64: 50-57, February, 2017.

Drip-and-Ship Thrombolytic Therapy Supported by the Telestroke System for Acute Ischemic Stroke Patients Living in Medically Under-served Areas.

There are a few stroke specialists in medically under-served areas in Japan. Consequently, in remote area patients may not receive thrombolysis with intravenous recombinant tissue plasminogen activator (iv rt-PA), the standard treatment for acute ischemic stroke. Using a mobile telestroke support system (TSS) that accesses the internet via a smart phone, we implemented iv rt-PA infusion therapy under a drip-and-ship protocol to treat the stroke patients in medically under-served areas. The physicians at the Tokushima Prefectural Kaifu Hospital (TPKH), located in rural Japan, can relay CT or MRI scans and other patient data via their smart phone to off-site stroke specialists. In the course of 34 months, we used the TSS in 321 emergencies. A total of 9 of 188 (4.8%) with acute ischemic stroke, received iv rt-PA infusion therapy using a mobile TSS; in 5 among these (55.6%), we obtained partial or complete recanalization of occluded arteries. None suffered post-treatment hemorrhage and their average NIH stroke score fell from 14.6 at the time of admission to 6.8 at 24 h post-infusion. The drip-and-ship protocol contributed to the safe and effective treatment of the stroke patients living in medically under-served rural areas.

Community-based clinical education increases motivation of medical students to medicine of remote area: comparison between lecture and practice.

In this study, we administered a questionnaire to medical students to evaluate the effect of community-based clinical education on their attitudes to community medicine and medicine in remote area. Questionnaires were given 4 times to all the students from first-year to sixth-year. Of 95 students, 65 students (68.4%) who completed all questionnaires, were used in this study. The intensity of students' attitudes was estimated by using visual analogue scale. The intensity of interest, a sense of fulfillment and passion in medicine of remote area was significantly increased after the community-based practice. On the other hand, the level of understanding in medicine in remote area was increased by the lecture not by the practice. The intensity of desire both to become a generalist and a specialist was significantly increased when the grade went up. Most of sixth-year students desired to have abilities of a generalist and a specialist simultaneously. This study shows that the community-based practice is more meaningful in increasing motivation in medicine in remote area than the lecture, and suggests that it is important to prepare more courses to experience community medicine to increase the number of physicians who desire to work in remote area.

Epidemiological and clinical features of lung cancer patients from 1999 to 2009 in Tokushima Prefecture of Japan.

Lung cancer is the leading cause of malignancy-related death worldwide. In the present study, we reviewed the epidemiologic and clinical features of lung cancer in Tokushima Prefecture, Japan. Between January 1999 and December 2009, 2,183 patients with lung cancer were enrolled in this study. One thousand five hundred ninety-one (73%) patients were male and 592 (27%) patients were female. Median age was 70 years, with a range of 15-93 years. Seventy-six percent of patients had smoking history. One thousand nine hundred five (87%) patients were non-small cell lung cancer and the predominant histological type was adenocarcinoma (51%). Among all 2,183 patients, 702 (32%) belonged to elderly population. Four hundred seventy-one (22%), 213 (10%), 24 (1%), 116 (5%), 238 (11%), 370 (17%) and 678 (31%) patients had stage IA, IB, IIA, IIB, IIIA, IIIB and IV lung cancer, respectively. In Tokushima University Hospital, 516 (29%), 191 (11%), 58 (3%), 755 (43%) and 216 (12%) patients were initially treated with chemotherapy, chemo-radiotherapy, thoracic radiotherapy, operation and best supportive care, respectively. The median time to progression (TTP) and the median survival time (MST) of patients treated with chemotherapy and chemo-radiotherapy were 3.5 months, 13.0 months and 7.0 months, 18.0 months, respectively. The median TTP and the MST of 33 elderly patients treated with chemotherapy were 3.3 months and 18.0 months, respectively, which were comparable with those of total population. These results indicated the benefit of chemotherapy in elderly patients with advanced lung cancer by proper selection.

Elevation of macrophage-derived chemokine in eosinophilic pneumonia: a role of alveolar macrophages.

Macrophage-derived chemokine (MDC/CCL22) and thymus-and activation-regulated chemokine (TARC/CCL17) are ligands for CC chemokine receptor 4. Recently, TARC has been reported to play a role in the pathogenesis of idiopathic eosinophilic pneumonia (IEP). The purpose of this study was to evaluate the role of MDC in IEP and other interstitial lung diseases (ILDs). MDC and TARC in the bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent assay in patients with ILDs and healthy volunteers (HV). We also examined the expression of MDC mRNA in alveolar macrophages (AM) by real-time quantitative reverse transcriptase-polymerase chain reaction. Both MDC and TARC were detected only in BALF obtained from IEP patients. The concentration of MDC was higher than that of TARC in all cases. The level of MDC in IEP correlated with that of TARC. AM from IEP patients expressed a significantly higher amount of MDC than that from HV at the levels of protein and mRNA. MDC in BALF from IEP dramatically decreased when patients achieved remission. These findings suggest that MDC, in addition to TARC, might be involved in the pathogenesis of IEP, and AM play a role in the elevation of MDC in IEP.

[A case of recurrent small cell lung cancer with symptoms improved by nogitecan hydrochloride].

A 68-year-old woman with recurrent advanced small cell lung cancer (SCLC), previously treated with 7 courses of carboplatin + etoposide, 4 courses of cisplatin + irinotecan and radiotherapy (primary site and whole brain irradiation), received 3 courses of a single nogitecan hydrochloride i.v. bolus with 4 consecutive days of administration, for a total dose of 7.5 mg. MR-imaging revealed a response in the brain metastasis, and tumor markers (NSE and ProGRP) were improved after the first course. Headache, her main complaint, was also alleviated. These observations suggest that nogitecan hydrochloride alone might be useful for treatment of recurrent SCLC in cases of poor performance status (PS), especially when the patient requires remission of symptoms.

Effect of vinorelbine monotherapy in taxane-treated patients with advanced non-small-cell lung cancer.

Taxane-based chemotherapy now plays an important role in the first-line treatment on patients with advanced non-small-cell lung cancer (NSCLC). Recent attention has been focused on the treatment of patients with NSCLC who failed to respond to taxane-based chemotherapy. In the present article, we report the effect of single-agent vinorelbine (VNR) in 10 patients with NSCLC previously treated with taxanes. An antitumor effect was observed in five patients, resulting in a response rate of 50.0% (5/10). The absence of vinca alkaloid pretreatment was an important factor in the clinical response in these patients. Further study is warranted to investigate the clinical efficacy of VNR monotherapy in taxane-resistant NSCLC patients.

IL-12-induced production of IL-10 and interferon-gamma by mononuclear cells in lung cancer-associated malignant pleural effusions.

Interleukin (IL)-12 enhances natural killer (NK) activity and induces interferon gamma (IFN-gamma) production. Recently, it was shown that IL-12 induces IL-10 production by human T cells and NK cells, as a negative feedback for IL-12-induced immune responses. In the present study, in order to investigate the functions of host immune cells existing in contact with cancer cells, we examined the effect of IL-12 on the induction of non-major histocompatibility complex (MHC)-restricted killer activity and of IFN-gamma and IL-10 production by pleural and peripheral blood mononuclear cells (MNC), isolated from 40 lung cancer patients and 20 control subjects. IL-12 induced significant killer activity in pleural MNC from lung cancer patients, as well as those in peripheral blood, against a small cell lung cancer cell line (SBC-3). In lung cancer patients, pleural MNC incubated with IL-12 produced more IFN-gamma than blood MNC. In addition, when stimulated with both IL-12 and IL-2, pleural MNC produced more IL-10 than blood MNC. This is the first study reporting that MNC from pleural effusions of patients with lung cancer can produce both type 1 (IFN-gamma) and type 2 (IL-10) cytokines following exposure to IL-2 and IL-12. These observations suggest that control of IL-10 production at the microenvironment level may be important for the efficacy of human lung cancer immunotherapy with IL-12.