Interstitial Capillary in Normal and in Transplanted Kidneys: An Ultrastructural Study

Knowledge about the normal structure and pathology of interstitial capillary is limited. Splitting and multilayering of the basal membrane (BM), as a marker of chronic rejection, has been published in association with transplant glomerulopathy. The authors investigated the ultrastructural features of the interstitial capillary basal membrane in normal (15 biopsies) and in transplanted kidneys (27 biopsies from 21 patients), expressing transplant glomerulopathy (8 biopsies from 6 patients), acute tubulo-interstitial rejection (9 biopsies from 6 patients), and recurrent or de novo glomerulonephritis (10 biopsies from 8 patients). All biopsies were fixed in 1%OsO 4, embedded in Epon, and examined by electron microscope. Measurements of the interstitial capillary BM were made. The BM of interstitial capillary of intact kidney was a homogenous continuous structure, 88 nm in width on average. Thickening with diffuse multilayering of BM was most intensive in patients with transplant glomerulopathy, and much less intensive in patients with acute tubulointerstitial rejection and in patients with recurrent or de novo glomerulonephritis. These findings may provide the first information about the morphology of the normal basal lamina of interstitial capillary and support the diagnostic value of interstitial capillary changes in chronic rejection.     

Opposing relationships of childhood threat and deprivation with stria terminalis white matter

While stress may be a potential mechanism by which childhood threat and deprivation influence mental health, few studies have considered specific stress‐related white matter pathways, such as the stria terminalis (ST) and medial forebrain bundle (MFB). Our goal was to examine the relationships between childhood adversity and ST and MFB structural integrity and whether these pathways may provide a link between childhood adversity and affective symptoms and disorders. Participants were young adults (n = 100) with a full distribution of maltreatment history and affective symptom severity. Threat was determined by measures of childhood abuse and repeated traumatic events. Socioeconomic deprivation (SED) was determined by a measure of childhood socioeconomic status (parental education). Participants underwent diffusion spectrum imaging. Human Connectome Project data was used to perform ST and MFB tractography; these tracts were used as ROIs to extract generalized fractional anisotropy (gFA) from each participant. Childhood threat was associated with ST gFA, such that greater threat was associated with less ST gFA. SED was also associated with ST gFA, however, conversely to threat, greater SED was associated with greater ST gFA. Additionally, threat was negatively associated with MFB gFA, and MFB gFA was negatively associated with post‐traumatic stress symptoms. Our results suggest that childhood threat and deprivation have opposing influences on ST structural integrity, providing new evidence that the context of childhood adversity may have an important influence on its neurobiological effects, even on the same structure. Further, the MFB may provide a novel link between childhood threat and affective symptoms.     

Investigation of retinoic acid function during embryonic brain development using retinaldehyde‐rescued Rdh10 knockout mice

Background: Retinoic acid (RA) signaling controls patterning and neuronal differentiation within the hindbrain, but forebrain RA function remains controversial. RA is produced from metabolism of retinol to retinaldehyde by retinol dehydrogenase (RDH), followed by metabolism of retinaldehyde to RA by retinaldehyde dehydrogenase (RALDH). Previous studies on Raldh2?/? and Raldh3?/? mice demonstrated an RA requirement for γ‐aminobutyric acid (GABA)ergic and dopaminergic differentiation in forebrain basal ganglia, but no RA requirement was observed during early forebrain patterning or subsequent forebrain cortical expansion. However, other studies suggested that RA controls forebrain patterning, and analysis of ethylnitrosourea‐induced Rdh10 mutants suggested that RA synthesized in the meninges stimulates forebrain cortical expansion. Results: We generated Rdh10?/? mouse embryos that lack RA activity early in the head and later in the meninges. We observed defects in hindbrain patterning and eye RA signaling, but early forebrain patterning was unaffected. Retinaldehyde treatment of Rdh10?/? embryos from E7–E9 rescues a cranial skeletal defect, resulting in E14.5 embryos lacking meningeal RA activity but maintaining normal forebrain shape and cortical expansion. Conclusions: Rdh10?/? embryos demonstrate that RA controls hindbrain but not early forebrain patterning, while studies on retinaldehyde‐rescued Rdh10?/? embryos show that meningeal RA synthesis is unnecessary to stimulate forebrain cortical expansion. Developmental Dynamics 242:1056–1065, 2013. © 2013 Wiley Periodicals, Inc.     

Efficacy and safety of switching from basal insulin to once‐daily insulin degludec/insulin aspart in Japanese patients with inadequately controlled type 2 diabetes: A 4‐week,randomized, open‐label,treat‐to‐target study

Aims/Introduction

A prospective, 4‐week, single‐center, randomized, open‐label, parallel‐group, treat‐to‐target study was carried out to develop an algorithm for safe and effective switching from basal insulin to once‐daily insulin degludec/insulin aspart (IDegAsp) in patients with inadequately controlled type 2 diabetes.

Materials and Methods

Patients were randomly assigned to continue their current basal insulin therapy (n = 10) or to switch to IDegAsp on a 1:1 unit basis (n = 10). The insulin dose could be titrated once weekly, targeting a self‐measured blood glucose of 80–100 mg/dL before breakfast. A mixed meal test was carried out at baseline and after 4 weeks.

Results

After 4 weeks, the mean daily dose of insulin was similarly increased by 60% in both groups, and there was a significant decrease of mean plasma glucose and glucose area under the glucose concentration vs time curve for 2 h in the meal test. The mean estimated treatment difference (IDegAsp group ? basal insulin group) of the mean plasma glucose level was ?28 mg/dL (95% confidence interval ?47 to ?8, P = 0.008) after 4 weeks and that of the area under the glucose concentration vs time curve for 2 h was ?2,800 mg/min/dL (95% confidence interval ?5,300 to ?350, P = 0.028), confirming the superiority of IDegAsp to basal insulin. In the IDegAsp group, the 2‐h postprandial plasma glucose level was significantly decreased to the fasting plasma glucose range. There were no confirmed hypoglycemic episodes in either group during the 4‐week study period.

Conclusions

After switching from basal insulin, the IDegAsp dose can be uptitrated by 60% based on fasting plasma glucose data. However, monitoring of postprandial glucose should be considered before further uptitration of IDegAsp.

     

Ten years of experience in chronic ulcers and malignant transformation

Malignant degeneration of wounds is rare and often misdiagnosed. Delay in diagnosis may result in a worse prognosis. The aim of this study is to determine the number of skin cancers associated with chronic skin ulcers in our facility over a period of 10 years. Between January 2002 and December 2012, a total of about 1000 patients had consulted with us for chronic wounds, especially of vascular, diabetic and traumatic origin and pressure ulcers. Thirteen skin cancers had been detected: seven squamous cell and five basal cell carcinomas and one melanoma. We highlight how important it is to be aware of the signs suggesting a malignant change and the importance of biopsy at regular intervals during the life cycle of any chronic wound.     

Basal cell adenoma of the parotid gland: clinical and pathological findings in 29 cases

Objective: To determine the clinical and pathological features of basal cell adenoma (BCA) of the parotid gland. Methods: This is a retrospective study of 29 parotid BCAs in 28 patients who underwent surgery at the Department of Otolaryngology Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, between October 2000 and June 2013. The tumors were categorized according to their location in the parotid gland as superior superficial lobe, inferior superficial lobe and deep lobe. Results: The mean age was 57.0 years (range, 32-83 years). The clinical manifestations of parotid BCAs were consistent with those of other benign parotid tumors. There were no significant differences in age, average disease duration and tumor size among the three tumor groups. There were 11 deep tumors (11/29, 37.9%), and five of them exhibited cystic degeneration (5/11, 45.5%). A total of 15 patients underwent FNAB examination, and the results were positive in seven patients (7/15, 46.7%). Mild facial nerve function impairment occurred in five patients (House-Brackmann grade II), of whom, three had recovered by the 6-month follow-up. No cases of local recurrence or malignant transformation were observed during follow-up. Conclusion: The clinical features of BCA are consistent with those of other benign tumors. The deep lobe of the parotid gland is more likely to develop BCAs, and thus, this diagnosis should be considered in patients with deep-lobe tumors, especially when accompanied with cystic degeneration. FNAB can increase the rate of preoperative diagnoses.     

改良大骨瓣减压术在高血压基底节区脑出血伴脑疝中的应用

目的探讨评价改良大骨瓣减压术治疗高血压基底节区脑出血伴脑疝患者的效果,并与常规颞顶骨瓣减压术比较疗效差异。方法将我科2008年1月至2012年12月收治的60例高血压基底节区脑出血伴脑疝患者随机分为两组,每组30例。改良组采用改良大骨瓣减压术,常规组采用常规颞顶骨瓣减压术。术后治疗方案基本相同,术后随访6个月,按日常生活能力分级(ADL)评定疗效。结果改良组ADLⅠ级3例,Ⅱ级14例,Ⅲ级9例,Ⅳ级2例,V级1例,死亡1例。常规组ADLⅠ级1例,Ⅱ级9例,Ⅲ级10例,Ⅳ级6例,V级2例,死亡2例。需二次开颅手术常规组5例,改良组1例。经统计学处理,两组疗效的差异有统计学意义(P<0.05)。结论改良大骨瓣减压术在治疗高血压基底节区脑出血伴脑疝患者中有良好的效果,与常规颞顶瓣减压术比较,能减少二次开颅的概率,改善患者预后。     

Basal insulin requirement of youth with type 1 diabetes differs according to age

We investigated the percentage of total basal insulin dose to total daily insulin dose (%TBD) among Japanese youth of different ages with type 1 diabetes. The study enrolled 69 patients with type 1 diabetes who were treated with multiple daily injections of insulin. The participants were divided into the following age groups: group A, 0 to <10 years (n = 18); group B, 10 to <20 years (n = 31) and group C, 20 to <25 years (n = 20). We found no difference in the sex ratio, body mass index, and glycated hemoglobin and 2‐h postprandial C‐peptide levels among the three groups. Participants assigned to group B had a significantly higher percentage of total daily insulin dose than those in group A and group C (49.7 ± 10.4% vs 38.5 ± 13.7% and 38.3 ± 8.2%, P = 0.0005). In conclusion, the basal insulin requirements of Japanese youth with type 1 diabetes might have an age effect that is associated with puberty.