Management of diabetic macular edema in Japan: a review and expert opinion

Diabetic retinopathy is a frequent cause of visual impairment in working-age adults (≥ 30 years) and in Japan is most commonly observed in those aged 50–69 years. Diabetic macular edema (DME) is one of the main causes of vision disturbance in diabetic retinopathy, which is a clinically significant microvascular complication of diabetes. Anti-vascular endothelial growth factor (VEGF) therapy is becoming the mainstay of treatment for DME. However, to achieve sustained long-term improvement in visual acuity, conventional laser photocoagulation, vitrectomy and steroid therapy are also expected to play a role in the treatment of DME. This review summarizes the epidemiology and pathology of diabetic retinopathy and DME, evaluates the findings regarding the diagnosis and treatment of DME, and underscores the importance of systemic management of the disease in the context of the current health care situation in Japan. Finally, the unmet needs of patients with DME and prospects for research are discussed. The weight of evidence suggests that it is important to establish a multipronged treatment strategy centered on anti-VEGF therapy.     

Histopathological findings of the lower esophagus after total gastrectomy in rat

It is now accepted that the incidence of esophageal carcinoma is highest in the middle thoracic region. Esophageal carcinoma after gastrectomy, however, has a tendency to develop in the lower region. This study was designed to investigate the role of reflux of gastroduodenal juice in the genesis of carcinoma in the esophagus. We found a possible correlation between the development of esophageal carcinoma and gastrectomy, related to alkaline reflux into the esophagus. To elucidate this correlation, the role of alkaline reflux of duodenal contents in the development of esophageal squamous cell carcinoma was investigated in Wister rats. Gastrectomized rats with regurgitation of duodenal contents into the esophagus were not administered any carcinogen and were sacrificed some at the end of 8 weeks and others at 50 weeks for pathological examination. Hyperplasia was found in rats at 8 weeks, and the esophageal squamous cell carcinoma was found in rats at 50 weeks. The carcinomas were found exclusively in the area of the reflux esophagitis and were accompanied by severe dysplasia. These results suggested that alkaline reflux of duodenal contents was strongly correlated to the development of the esophageal squamous cell carcinoma.     

Employment status and termination among survivors of pediatric brain tumors: a cross-sectional survey

Background

Some childhood cancer survivors experience employment difficulties. This study aimed to describe pediatric brain-tumor survivors’ employment status.

Methods

A cross-sectional, observational study was conducted, with questionnaires distributed to 101 pediatric brain-tumor survivors (aged 15 years or older) and their attending physicians from nine institutions in Japan. We compared category and time-series histories for participants’ first-time employment using national census information. Factors related to delayed employment or early employment termination were examined using survival-time analyses.

Results

Excluding students and homemakers, 38 brain-tumor survivors (median age 27 years, with 15 years since diagnosis) were of working age. Of these, 12 (32%) were unemployed and 9 (24%) had never been employed. First-time employment occurred later for brain-tumor survivors than the general population, particularly in those with lower educational levels. The number of brain-tumor survivors whose first job was terminated within the first year was higher than that for the general population, particularly in male survivors and germ cell-tumor survivors. Brain-tumor survivors described their working patterns (irregular), job types (specialist or professional), reasons for early termination (unsuitable job), and thoughts about working (they wished to serve their communities but lacked confidence).

Conclusion

Brain-tumor survivors are associated with high unemployment rates and multiple unemployment-related factors. Education and welfare systems should identify individual methods of social participation for this group.

     

Effects of autonomic drugs on intraluminal pressure and excretion of rat seminal vesicles in vivo

The effects of intravenously administered autonomic drugs on the intraluminal pressure and the excretion volume of the seminal vesicles in rats were studied. Both alpha 1-adrenergic and cholinergic stimulants produced a rapid increase in pressure and fluid excretion. alpha 1-Adrenergic stimulants elicited a sharp and single increase in pressure, while cholinergic stimulants caused a sharp increase with multiple peaks.     

Age-related change in tissue-to-plasma partition coefficient of cefazolin for noneliminating organs in the rat

Age-related changes in tissue distribution characteristics of cefazolin, a cephalosporin antibiotic, were examined for noneliminating organs of rats. The in vivo tissue-to-plasma partition coefficients (Kp,vivo) varied markedly among different ages and organs. In particular, muscle and skin acted as reservoirs for cefazolin distribution. There were also marked differences in interstitial fluid space (IS), determined using [14C]inulin, among different ages and organs. For muscle and bone, the magnitude of the age-related changes in Kp,vivo of cefazolin and IS was in the order of 1-week-old greater than 7-week-old = 100-week-old greater than 50-week-old rats. This is well correlated with the age-related changes in the volume of distribution at the steady state of cefazolin per body weight (Vdss/BW) and the extracellular fluid volume per body weight (Vecw/BW) determined previously using [14C]inulin. The predicted Kp value (Kp,pred) was estimated by incorporating the serum protein binding parameters of cefazolin, the IS values, and an interstitial-to-plasma albumin concentration ratio (AR) into equations derived from an extracellular fluid model. The Kp,pred values exhibited a fairly good correspondence with the Kp,vivo values determined for various organs, except gut, in rats of all four ages. These results suggest that the determinant of the age-related change in Vdss/BW is the difference in the IS value of muscle and bone, while the age-related change in serum protein binding plays only a modest role.     

Selection of radioresistant cells by vitamin A deficiency in a small cell lung cancer cell line

Radiation sensitivity of a human small cell lung cancer cell line, Lu-134-B cells, cultured in serum-supplemented medium and of cells transferred to and cultured in delipidized serum-supplemented (vitamin A-deficient) medium was studied. The cells cultured in serum-supplemented medium showed the phenotype of classic small cell lung cancer sensitive to radiation, while cells transferred to delipidized serum-supplemented medium showed partial squamous cell differentiation and became resistant to radiation. These results suggest that some small cell lung cancer cells in vitro change their morphology and radiosensitivity depending on the culture conditions. The change in radiosensitivity was reproducible, and was not reversible by culture of the radioresistant cells in delipidized serum-supplemented medium with addition of retinoic acid (vitamin A-sufficient medium) for two months, although squamous cells disappeared. Acquisition of radioresistancy was considered to occur as the result of clonal selective growth in delipidized medium of a minor cell population in the original cell culture, based on a study of chromosome number. It was also found that there was no association of myc-family oncogenes with the changes of radiosensitivity in this cell line.     

Cardioembolic stroke manifested by isolated tonic seizure of the left upper limb]

We reported a 61-year old man with cardioembolic stroke manifested by isolated tonic seizure of the left upper limb. He had a history of chronic atrial fibrillation and transient ischemic attack. He was brought to our hospital by ambulance, when he suddenly had isolated tonic seizure of left upper limb. On admission, he had no neurological symptoms and signs. Brain diffusion weighted MR image disclosed high intensity area in the right parietal lobe, although T2-weighted image did not show any abnormalities. On 8th day, a high intensity area was observed both on the diffusion-weighted and T2-weighted MR images. In case of isolated tonic seizure of left upper limb, careful examination of stroke is required especially if the patient had a high risk of stroke.     

Immunocytochemical identification of monoclonal antibodies with binding activity to acinar cells but not islets.

The development of techniques for separating islets from acinar cells on a mass scale is a prerequisite to successful clinical attempts at islet transplantation. We have identified and partially characterized two blood group-reactive monoclonal antibodies (McAb), CAC1 and CAC2, with specific binding activity to acinar cells but not islets. These McAb are of the IgM subclass, and were found on immunocytochemical analysis to possess broad interspecies cross-reactivity, binding to antigens expressed in the acinar tissue of rats, dogs, and man. The antigens that these McAb recognize are glycolipid in nature and thus were not denatured by collagenase digestion of the pancreas. These properties, together with their ability to effect complement-mediated lysis, may make the McAb generally useful reagents in islet isolation and purification.