Value of pathological grading in prediction of renal survival in IgA nephropathy

Summary: In order to clarify the most reliable risk factor to predict renal outcome, 206 patients with IgA nephropathy were studied for mean period of 9.2 years. the histopathological changes of this disease using light microscopy were divided into four grades (grade 1–4). These grades included glomerular, interstitial and vascular lesions. the cumulative rate of kidney survival progressing to end stage renal failure (ESRF) in all patients was 94% at 5 years, 87% at 10 years and 80% at 15 years after renal biopsy. None of the patients in grade 1 reached ESRF. the cumulative rate of kidney survival in grade 2 was 99% at 5 years, 98% at 10 years and 89% at 15 years after renal biopsy. In grade 3, it was 94% at 5 years, 79% at 10 years and 75% at 15 years. In grade 4 it was 53% at 5 years, 33% at 10 years and 22% at 15 years after renal biopsy. Forward stepwise multivariate regression analysis revealed that, in addition to the histopathological findings, three more risk factors were found to influence actuarial renal survival rate. These factors were: (i) the levels of serum creatinine; (ii) the level of serum albumin; and (iii) the amount of proteinuria at the time of renal biopsy. In parallel studies, forward stepwise multivariate regression analysis isolated three risk factors that influenced the progression of the reciprocal of serum creatinine. These factors were: (i) the levels of total protein; (ii) the degree of our pathological grading; and (iii) the amount of proteinuria. It was concluded that our pathological grading was useful as a prognostic parameter because of its simplicity and availability in routine clinical activities.     

Direct effects of protein S in ameliorating acute lung injury

Summary. Objective: Protein S may exert an anticoagulant activity by enhancing the anticoagulant activity of activated protein C and/or by directly inhibiting the prothrombinase complex. Protein S itself may also directly regulate inflammatory responses and apoptosis. The role of protein S in acute lung injury (ALI) was unknown. This study evaluated the effect of protein S on ALI in the mouse. Methods: Animal ALI was induced in C57/BL6 mice by intratracheal instillation of lipopolysaccharide (LPS). Mice were treated with protein S or saline by intraperitoneal injection 1 h before LPS instillation. Results: Activated protein or protein S alone and combined activated protein C + protein S therapy decreased inflammatory markers and cytokines in mice with acute lung injury. In LPS‐treated mice compared with controls ALI was induced as shown by significantly increased levels of total protein, tumor necrosis factor‐α, interleukin‐6 and monocyte chemoattractant protein‐1 in the bronchoalveolar lavage fluid. Mice with ALI treated with protein S had significantly decreased concentrations of tumor necrosis factor‐α and interleukin‐6 in the lung compared with untreated animals. Thrombin‐antithrombin III, a marker of the activity of the coagulation cascade, was unchanged. Protein S inhibited the expression of cytokines in vitro and increased activation of the Axl tyrosine kinase pathway in A549 epithelial cells. Conclusion: Protein S protects against LPS‐induced ALI, possibly by directly inhibiting the local expression of inflammatory cytokines without affecting coagulation.     

Intestinal Ulcerations Complicating Takayasu's Arteritis

A 62-year-old female, with a forty year's history of Takayasu's arteritis, was admitted to Fukuoka University Hospital, with melena. Endoscopy showed multiple shallow ulcers and edematous mucosa in the terminal ileum, and also showed mucosal redness in the ascending colon. The cultures of feces and biopsy specimens taken from an ulcer in the terminal ileum were negative for bacteria and acid-fast bacilli. Medication such as nonsteroidal anti-inflammatory drugs, corticosteroids, and potassium chloride were not used before the onset of melena. She was treated with an elemental diet to rest her bowel. Two months later, the ulcers in the terminal ileum had disappeared. However, two years later, similar ulcers recurred in the terminal ileum. These clinical findings and course strongly suggested that her intestinal ulcers might be associated with Takayasu's disease. In Takayasu's arteritis, intestinal lesions have rarely been reported.     

Intrarenal synthesis of IL-6 in IgA nephropathy

Summary: Recent in vitro studies have shown the synthesis of interleukin-6 (IL-6) in glomerular mesangial and epithelial cells, and suggested the involvement of IL-6 in mesangial proliferative glomerulonephritis. However, the expression site of IL-6 mRNA in renal tissue of IgA nephropathy (IgAN), the most common chronic mesangial proliferative glomerulonephritis, remains obscure. to localize IL-6 mRNA in renal biopsy specimens of IgAN, we used nonradioactive in situ hybridization (ISH) developed in our laboratory, sensitive in detecting individual cells positive for a specific mRNA. In some sections, periodic acid-Schiff staining was performed after ISH in order to identify the topographical relation between IL-6 mRNA positive cells and glomerular basement membrane and mesangial area. In situ hybridization for IL-6 mRNA and immunohistochemistry for CD3 and CD68, markers for lymphocytes and monocytes, respectively, were also performed on serial sections to examine the contribution of infiltrated mononuclear cells to cells positive for IL-6 mRNA in glomeruli. Glomerular resident cells, including glomerular mesangial and epithelial cells and cells of Bowman's capsule, as well as tubular epithelial cells and infiltrated mononuclear cells expressed IL-6 mRNA. We also compared the localization of IL-6 mRNA and protein and showed different distribution between the gene product and protein. the expression of IL-6 mRNA correlated with the degree of mesangial cell proliferation and tubulointerstitial changes. Our results indicate that IL-6 is synthesized in renal tissues of IgAN and suggest that the increased IL-6 expression may be important in the pathogenesis of IgAN.     

Effect of Bilateral Stellectomy on Electrical Instability of the Atrium in the Dog with Hypokalemia

To investigate the effect of sympathetic nerve activity on electrical instability of the atrium in the presence of hypokalemia, open chest electrophysiological study was performed before and after bilateral stellectomy (BS) in 15 dogs with hypokalemia (hypokalemia group) and in 15 dogs with normokalemia (control group). Hypokalemia was created by infusion of 5.0 g/kg of polystyrene sulfonic acid calcium into the colon. Serum level of potassium was significantly lower in the hypokalemia group (2.94 +/- 0.52 mEq/L) than in the control group (4.86 +/- 0.51 mEq/L, P less than 0.01) before BS. There was no significant change in serum level of potassium in the two groups after BS. Incidence of electrically induced atrial fibrillation (AF) was significantly higher in the hypokalemia group (80%) than in the control group (13%, P less than 0.001) before BS. It was significantly reduced in the hypokalemia group (40%, P less than 0.05), but not in the control group (6%) after BS. Dispersion of effective refractory period of the atrium (delta ERP) was significantly greater in the hypokalemia group (26.1 +/- 2.8 msec) than in the control group (22.0 +/- 3.3 msec, P less than 0.005) before BS. It was significantly decreased to 23.1 +/- 3.2 msec in the hypokalemia group (P less than 0.001) and to 20.6 +/- 2.5 msec in the control group (P less than 0.01) after BS. Maximum conduction delay in the atrium (MaxCD) was 36.1 +/- 3.5 msec before and 36.2 +/- 4.1 msec after BS in the hypokalemia group and 31.1 +/- 4.2 msec before and 32.3 +/- 4.9 msec after BS in the control group. There was a significant difference in MaxCD between the two groups before BS. Atrial fibrillation threshold (AFT) was significantly lower in the hypokalemia group (3.9 +/- 0.7 mA) than in the control group (13.8 +/- 3.1 mA, P less than 0.001) before BS. It was significantly increased both in the hypokalemia group (6.5 +/- 1.3 mA, P less than 0.001) and in the control group (15.0 +/- 2.7 mA, P less than 0.005) after BS. It is concluded that sympathetic nerve activity may play some role in the increase in electrical instability of the atrium in the presence of hypokalemia.     

Cellular immunity in IgA nephropathy

Summary: A comprehensive study on the role of various cytokines in the regulation of IgA synthesis and progression of glomerular damage in IgA nephropathy was attempted. Semi-quantitative PCR for IL-I, IL-2, IL-4, IL-6, IL-10, IL-12, interferon (IFN)-γ, transforming growth factor (TGF)-β, tumour necrosis factor (TNF)-α, platelet derived growth factor (PDGF) and monocyte chemoattractant protein-1 (MCP-1) was performed. In parallel studies, protein production of some cytokines was also determined. It was demonstrated that IL-4, IFN-γ and presumably IL-12 expressed predominantly in peripheral blood mononuclear cells in patients with IgA nephropathy. Some positive correlations between the mRNA expression of these cytokines and the degree of tissue damage were observed. It was concluded that these cytokines may play some role in the alteration of cellular immunity in this disease.     

Epidemiology of genotypes of hepatitis C virus in Japanese patients with type C chronic liver diseases: A multi-institution analysis

Sixteen medical institutions in Japan collaborated in this study of the epidemiology of hepatitis C virus (HCV) genotypes. A total of 4176 patients with type C chronic liver disease, from the four main islands of Japan, were evaluated. Of those evaluated, 2794 had chronic hepatitis, 727 had liver cirrhosis and 655 had hepatocellular carcinoma. The HCV genotype of the patients was determined by an enzyme-linked immunosorbent assay based on serological genotype 1- and 2-specific recombinant peptides (SG-1 and SG-2, respectively) of the NS4 region. The prevalence of SG-1 and SG-2 HCV was similar in the four main islands of Japan. SG-1 HCV predominated in each disease category (69–76%). The percentage of patients with SG-1 HCV increased by 7%, while that of patients with SG-2 HCV decreased by 7%, as liver disease progressed in severity from chronic hepatitis to carcinoma (P < 0.001). Patients with either SG-1 or SG-2 had a similar mean age and history of blood transfusion. In conclusion, SG-1 HCV was found to predominate in Japan, and the HCV genotype was found to be related to the stage of hepatitis C disease.     

Abnormalities of Electrocardiographic P Wave Morphology and Their Relation to Electrophysiological Parameters of the Atrium in Patients with Sick Sinus Syndrome

We examined the incidence, of long P wave duration in lead II and increased P terminal force in lead V1(PTFV1), and their relationship to electrophysiological findings of atrial muscle in 34 patients with sick sinus syndrome (SSS). Patients were divided into three groups: Group I, consisting of 20 patients with various cardiac arrhythmias other than SSS and paroxysmal atrial fibrillation (PAF) who served as controls; Group II, consisting of 18 patients with SSS but without PAF; and Group III consisted of 16 patients with SSS and PAF. P wave duration was significantly longer in Group III (122 ± 11ms, mean ± SD, P < 0.0001) and Group II (111 ± 15 ms, P < 0.002) than in Group I (98 ± 10 ms). PTFV1 was greater in Group III (0.052 ± 0.025 ms) than in Group I (0.028 ± 0.011 ms, P < 0.05). P wave duration and PTFV1 had significantly and/or borderline correlations with longest duration of right atrial electrograms (r = 0.84, P < 0.0001 and 0.47, P < 0.02, respectively), maximal number of fragmented deflections of atrial electrograms (r = 0.69, P < 0.0001 and r = 0.51, P < 0.02, respectively), repetitive atrial firing zone (RAFZ) (r = 0.81, P < 0.0001 and 0.48, P < 0.05, respectively) and fragmented atrial activity zone (FAAZ)(r - 0.53, P < 0.01 and r = 0.45, P = 0.06, respectively). We concluded that long P wave duration and increased PTFV1 are electrocardiographic indicators for coexistence of electrophysiological abnormalities in the atria in SSS without recognizable heart disease.     

Ultra-high Magnification Endoscopy of the Normal Esophageal Mucosa

Abstract: The normal esophageal mucosa was observed in detail using ultra-high magnification endoscopy (UHM endoscopy). The UHM endoscope has a magnification capacity ranging from eight to 150x. High-quality UHM endoscopic pictures can be continuously obtained by attaching a 2-mm depth soft distal attachment to the tip of the UHM endoscope. The vascular architecture, which extends from the submucosal vessels through the proper mucosal layer, can be continuously visualized, thereby demonstrating the characteristic fine-vascular network pattern, and the intrapapillary capillaries in the epithelium. With UHM endoscopy, intrapapillary capillaries can be clearly demonstrated as single loop vessels which we have termed “intrapapillary loops.” These structures cannot be observed with an ordinary magnifying endoscope which is capable of only 35x magnification. We conclude that a technique for obtaining high-resolution endoscopic pictures has been established. The images obtained are useful for elucidating the microstructure of the esophageal mucosa, especially the fine-vascular network and the newly recognized intrapapillary loop.     

Portless endoscopic radical nephrectomy via a single minimum incision in 80 patients

AIM: To assess the feasibility of our portless endoscopic radical nephrectomy via a single minimum incision, which narrowly permitted extraction of the specimen in the initial 80 patients. METHODS: Radical nephrectomy was carried out extraperitoneally in patients with T1-3aN0M0 renal tumors using an endoscope through a single minimum incision without trocar ports and gas. All the instruments used were reusable. RESULTS: The average length of incision, operative time and estimated blood loss were 6.6 cm (range, 4-9 cm), 3. 1 h (range, 1.7-5.6 h) and 324 mL (range, 10-2288 mL), respectively. The complication rate was 2.5% (2/80); complications included injury of the pleura and hemorrhage from the vena cava, both of which were repaired by suture during operation. Transfusion was performed in three patients (3.8%). Average times to oral feeding and walking were both 1.4 days. Wound pain was minimal and analgesics were generally not required by the second postoperative day. In patients with larger incisions (7 cm or more), estimated blood loss increased (approximately 100 mL on average) and oral feeding resumed later (0.3 days on average), relative to patients with smaller incisions (6 cm or less). However, overall results were similar between the two patient groups. In patients with a large tumor (7 cm or greater), operative time did not increase and complications and transfusions were both avoided. CONCLUSION: Portless endoscopic radical nephrectomy via a single minimum incision is a safe, reproducible, cost-effective and minimally invasive treatment option for patients with T1-3aN0M0 renal tumors.