Clinical manifestations of autosomal recessive polycystic kidney disease (ARPKD): kidney-related and non-kidney-related phenotypes

Autosomal recessive polycystic kidney disease (ARPKD), although less frequent than the dominant form, is a common, inherited ciliopathy of childhood that is caused by mutations in the PKHD1-gene on chromosome 6. The characteristic dilatation of the renal collecting ducts starts in utero and can present at any stage from infancy to adulthood. Renal insufficiency may already begin in utero and may lead to early abortion or oligohydramnios and lung hypoplasia in the newborn. However, there are also affected children who have no evidence of renal dysfunction in utero and who are born with normal renal function. Up to 30 % of patients die in the perinatal period, and those surviving the neonatal period reach end stage renal disease (ESRD) in infancy, early childhood or adolescence. In contrast, some affected patients have been diagnosed as adults with renal function ranging from normal to moderate renal insufficiency to ESRD. The clinical spectrum of ARPKD is broader than previously recognized. While bilateral renal enlargement with microcystic dilatation is the predominant clinical feature, arterial hypertension, intrahepatic biliary dysgenesis remain important manifestations that affect approximately 45 % of infants. All patients with ARPKD develop clinical findings of congenital hepatic fibrosis (CHF); however, non-obstructive dilation of the intrahepatic bile ducts in the liver (Caroli’s disease) is seen at the histological level in only a subset of patients. Cholangitis and variceal bleeding, sequelae of portal hypertension, are life-threatening complications that may occur more often in advanced cases of liver disease. In this review we focus on common and uncommon kidney-related and non-kidney-related phenotypes. Clinical management of ARPKD patients should include consideration of potential problems related to these manifestations.     

Esophageal carcinoma cell line with high EGFR polysomy is responsive to gefitinib

Purpose

It has previously been shown that gefitinib-treated patients with epidermal growth factor receptor (EGFR) gene amplification or high polysomy had a statistically significant improvement in response, time to progression, and survival in non-small cell lung cancer (NSCLC). Only few studies utilizing anti-EGFR treatment in advanced esophageal adenocarcinomas have been performed and the results have been heterogeneous. The aim of this study was to evaluate EGFR-targeted therapy with gefitinib in esophageal adenocarcinoma with a high EGFR polysomy.

Methods

Novel esophageal cell lines PT6216 and LN6216c were established from primary tumor and lymph node metastasis of a patient with highly aggressive and metastatic adenocarcinoma. Pathological examination including tumor differentiation and prognostic marker analysis, immunohistochemical EGFR expression analysis, EGFR fluorescence in situ hybridization, and mutation analysis were performed. Response of novel cell lines to gefitinib treatment was evaluated by cell proliferation and vitality assays. Fifty-four esophageal adenocarcinoma specimens were evaluated for EGFR gene copy gain.

Results

The primary tumor cell line PT6216 and the lymph node cell line LN6216c show a homogenously high polysomy for EGFR determined by FISH analysis. Cell proliferation and vitality are highly sensitive to the tyrosine kinase inhibitor gefitinib compared to esophageal control cells without a high polysomy for EGFR. High polysomy for EGFR was found in 35 % of patients.

Conclusion

We show for the first time a significant treatment response to the EGFR tyrosine kinase inhibitor gefitinib in esophageal tumor cells with a high polysomy for EGFR, suggesting a future role of anti-EGFR therapy for esophageal adenocarcinoma patients with a high EGFR polysomy.     

Neutrophil gelatinase-associated lipocalin protects renal tubular epithelial cells in hypoxia–reperfusion by reducing apoptosis

Purpose

The aim of this study was to elucidate the role of neutrophil gelatinase-associated lipocalin (NGAL) in regulating apoptosis of tubular epithelial cells in a hypoxia–reperfusion model.

Methods

A hypoxia–reperfusion model was established with NRK-52E cells to assess apoptosis and cell cycle progression after the addition of NGAL. We investigated the expression of four apoptosis factors, Bcl-2, Bax, Fas and FasL, as well as the expression level of two NGAL receptors, 24p3R and megalin, by both Western blot and real-time PCR.

Results

NGAL induced cell proliferation and reduced apoptosis by regulating four apoptosis factors Bcl-2, Bax, Fas and FasL. Western blot demonstrated that the two NGAL receptors, 24p3R and megalin, were increased after hypoxia–reperfusion, which was reduced by exogenous NGAL. Moreover, overexpression of the two receptors induced the expression of the anti-apoptotic factor Bcl-2 and reduced the expression of pro-apoptotic Bax, Fas and FasL.

Conclusions

These findings indicate that NGAL reduces apoptosis by regulating the four apoptosis factors Bcl-2, Bax, Fas and FasL through its two receptors 24p3R and megalin. These results also suggest that ectopic expression of NGAL in renal cells might provide a therapeutic strategy in ischemia–reperfusion by reducing apoptosis and promoting renal cell proliferation.     

Predictors that Influence Contralateral Prophylactic Mastectomy Election Among Women with Ductal Carcinoma In Situ Who Were Evaluated for BRCA Genetic Testing

Background

Patients with ductal carcinoma in situ (DCIS) are at increased risk for developing contralateral breast cancer (CBC). Consequently, more women with DCIS are electing to undergo contralateral prophylactic mastectomy (CPM). We evaluated factors associated with CPM in patients with DCIS who underwent genetic counseling for BRCA testing.

Methods

This retrospective study involved 165 women with DCIS referred for genetic counseling between 2003 and 2011. Patient characteristics were age, marital and educational status, tumor markers, nuclear grade, family history of breast cancer (BC) and ovarian cancer (OC), race, Ashkenazi Jewish ancestry, and BRCA results. Univariate and multivariate logistic regression analyses were used to determine predictive factors associated with CPM election.

Results

Of 165 patients, 44 (27 %) underwent CPM. Patients <45 years of age were more likely to elect CPM (p = 0.0098). A BRCA+ mutation was found in 17 patients (10.3 %), and BRCA+ women were more likely to elect CPM than BRCA or untested women (p = 0.0001). Patients who had a family history of OC (57.7 %) were more likely to choose CPM than those with no family history (p = 0.0004). Younger age, BRCA+, and an OC family history remained significant in the multivariate model (p < 0.008).

Conclusion

The CPM rate among patients with DCIS who undergo genetic counseling is high. Factors associated with increased likelihood of CPM among this group were age, BRCA+, and a family history of OC. Further studies are needed to evaluate patients’ perceptions of CBC risk and their role in the likelihood of CPM choice.     

The effects of fatigue on robotic surgical skill training in Urology residents

This study reports on the effect of fatigue on Urology residents using the daVinci surgical skills simulator (dVSS). Seven Urology residents performed a series of selected exercises on the dVSS while pre-call and post-call. Prior to dVSS performance a survey of subjective fatigue was taken and residents were tested with the Epworth Sleepiness Scale (ESS). Using the metrics available in the dVSS software, the performance of each resident was evaluated. The Urology residents slept an average of 4.07 h (range 2.5–6 h) while on call compared to an average of 5.43 h while not on call (range 3–7 h, p = 0.08). Post-call residents were significantly more likely to be identified as fatigued by the Epworth Sleepiness Score than pre-call residents (p = 0.01). Significant differences were observed in fatigued residents performing the exercises, Tubes and Match Board 2 (p = 0.05, 0.02). Additionally, there were significant differences in the total number of critical errors during the training session (9.29 vs. 3.14, p = 0.04). Fatigue in post-call Urology residents leads to poorer performance on the dVSS simulator. The dVSS may become a useful instrument in the education of fatigued residents and a tool to identify fatigue in trainees.     

Association between non-alcoholic fatty liver disease and chronic kidney disease in population with prediabetes or diabetes

Purpose

The relationship between chronic kidney disease (CKD) and non-alcoholic fatty liver disease (NAFLD) in population with diabetes remains controversial. Our current study aimed to explore the association between NAFLD and CKD in population with prediabetes or diabetes.

Methods

A cross-sectional study was conducted in Zhuhai city from June to October 2012. A total of 190 out of 334 participants with prediabetes or diabetes were enrolled in this study. CKD was defined as estimated GFR <60 ml/min per 1.73 m² and/or albumin-to-creatinine ratio ≥30 mg/g. NAFLD was diagnosed on the basis of ultrasonographic and excluded fatty liver disease caused by other reasons such as drinking. The association between NAFLD and CKD was then analyzed using SPSS (version 19.0).

Results

Subjects with NAFLD were more likely with a higher urinary albumin-to-creatinine ratio (P < 0.001). CKD were common among patients with NAFLD than those without NAFLD (P < 0.05). NAFLD was significantly associated with CKD (P < 0.05) in the unadjusted analyses as well as after adjustment for potential confounders. The unadjusted odd ratio and adjusted odd ratio for CKD were 2.25 (95 % CI 1.07–4.77, P = 0.034) and 2.68 (95 % CI 1.12–6.01, P = 0.016). When further adjusted for hypertension, serum high-density lipoprotein and serum fasting glucose, the association of NAFLD with CKD was still significant (OR 2.78, 95 % CI 1.03–7.52, P = 0.044).

Conclusions

Our current study suggests that ultrasound-diagnosed NAFLD is associated with CKD among population with prediabetes or diabetes.     

Renin inhibition ameliorates renal damage through prominent suppression of both angiotensin I and II in human renin angiotensinogen transgenic mice with high salt loading

Background

The renin–angiotensin–aldosterone system (RAAS) plays pivotal roles in the pathogenesis of chronic kidney disease (CKD) progression. Aliskiren, a direct renin inhibitor, inhibits the rate-limiting step of the RAAS without any alternative pathway. It is proven to reduce albuminuria in CKD patients treated with angiotensin blockade. However, there are few reports which evaluate the advantage of aliskiren as the first-line drug against CKD progression in RAAS-activated hypertensive patients.

Methods

Tsukuba hypertensive mice (THM), double transgenic mice carrying both the human renin and human angiotensinogen genes, were fed a high-salt diet and treated with hydraladine, ramipril and aliskiren for 10 weeks. Blood pressure and urinary albumin excretion were measured every 2 weeks during the experimental period. We evaluated renal histological changes and gene expression. Plasma angiotensin concentration was measured to evaluate the RAAS inhibitory effect.

Results

High-salt-loaded THM showed severe hypertension and renal injury. All antihypertensive drugs suppressed blood pressure and prevented renal disease progression. RAAS blockade showed a higher renoprotective effect than hydraladine despite an equivalent blood pressure lowering effect. Aliskiren exhibited even stronger renoprotection than ramipril. Plasma angiotensin concentration was increased in THM fed both normal salt and high salt. Hydraladine did not alter the plasma angiotensin concentration. Ramipril significantly decreased angiotensin II concentration. Aliskiren treatment almost completely suppressed angiotensin I and resulted in lower angiotensin II concentration than ramipril treatment.

Conclusion

Aliskiren prevents renal disease progression by suppressing both angiotensin I and II in RAAS-activated pathology. Our data suggest the application of a renin inhibitor for preventing kidney disease progression in CKD patients.     

Postoperative Nonsteroidal Anti-inflammatory Drugs and Risk of Anastomotic Leak: Meta-analysis of Clinical and Experimental Studies

Background

Enhanced recovery programs following colorectal resection recommend the use of nonsteroidal anti-inflammatory drugs (NSAIDs) as part of multimodal analgesia. The present study aimed to assess whether postoperative NSAID use increased the risk of anastomotic leak.

Methods

A systematic review of published literature was performed for studies comparing anastomotic leak following NSAID administration versus control. Meta-analysis was conducted for studies in human patients and experimental animal models. The primary endpoint was anastomotic leak.

Results

The final analysis included 8 studies in humans and 12 experimental animal studies. Use of NSAIDs was significantly associated with anastomotic leak in humans (8 studies, 4,464 patients, odds ratio [OR] 2.14; p < 0.001). This effect was seen with nonselective NSAIDs (6 studies, 3,074 patients, OR 2.37; p < 0.001), but not with selective NSAIDs (4 studies, 1,223 patients, OR 2.32; p = 0.170). There was strong evidence of selection bias from all clinical studies, with additional inconsistent definitions and outcomes assessment. From experimental animal models, anastomotic leak was more likely with NSAID use (ten studies, 575 animals, OR 9.51; p < 0.001). Bursting pressures at day 7 were significantly lower in NSAID versus controls (7 studies, 168 animals, weighted mean difference ?35.7 mmHg; p < 0.001).

Conclusions

Emerging data strongly suggest that postoperative NSAIDs are linked to anastomotic leak, although most studies are flawed and may be describing pre-existing selection bias. However, when combined with experimental data, these increasing concerns suggest caution is needed when prescribing NSAIDs to patients with pre-existing risk factors for leak, until more definitive evidence emerges.     

Treatment with hydrogen molecules prevents RANKL-induced osteoclast differentiation associated with inhibition of ROS formation and inactivation of MAPK,AKT and NF-kappa B pathways in murine RAW264.7 cells

The bone protective effects of the hydrogen molecule (H₂) have been demonstrated in several osteoporosis models while the underlying molecular mechanism has remained unclear. Osteoclast differentiation is an important factor related to the pathogenesis of bone-loss related diseases. In this work, we evaluated the effects of incubation with H₂ on receptor activator of NFκB ligand (RANKL)-induced osteoclast differentiation. We found that treatment with H₂ prevented RANKL-induced osteoclast differentiation in RAW264.7 cells and BMMs. Treatment with H₂ inhibits the ability to form resorption pits of BMMs stimulated by RANKL. Treatment with H₂ reduced mRNA levels of osteoclast-specific markers including tartrate resistant acid phosphatase, calcitonin receptor, cathepsin K, metalloproteinase-9, carbonic anhydrase typeII, and vacuolar-type H⁺-ATPase. Treatment with H₂ decreased intracellular reactive oxygen species (ROS) formation, suppressed NADPH oxidase activity, down-regulated Rac1 activity and Nox1 expression, reduced mitochondrial ROS formation, and enhanced nuclear factor E2-related factor 2 nuclear translocation and heme oxygenase-1 activity. In addition, treatment with H₂ suppressed RANKL-induced expression of nuclear factor of activated T cells c1 and c-Fos. Furthermore, treatment with H₂ suppressed NF-κB activation and reduced phosphorylation of p38, extracellular signal-regulated kinase, c-Jun-N-terminal kinase, and protein kinases B (AKT) stimulated with RANKL. In conclusion, hydrogen molecules prevented RANKL-induced osteoclast differentiation associated with inhibition of reactive oxygen species formation and inactivation of NF-κB, mitogen-activated protein kinase and AKT pathways.     

Association of miR-146a rs2910164 with childhood IgA nephropathy

Background

Micro-RNAs (miRNAs) play important roles in the regulation of immune response and inflammation. The purpose of this study was to investigate the association between three single nucleotide polymorphisms (SNPs) (mir-146a rs2910164, let-7a-2 rs1143770, miR-196a2 rs11614913) and susceptibility to and severity of childhood immunoglobulin A (IgA) nephropathy (IgAN).

Methods

We genotyped three miRNA SNPs in two independent Han Chinese populations composed of 158 patients and 265 controls (discovery set), and 246 patients and 446 controls (validation set), respectively.

Results

We found that rs2910164 was significantly associated with IgAN in the discovery but not the validation set. Combined analysis revealed that rs2910164 CC and CG genotypes were associated with increased risk of IgAN compared with the GG genotype [adjusted odds ratios (OR)?=?1.684, 95 % confidence interval (CI)1.190–2.384, P?=?0.003; adjusted OR?=?1.472, 95 % CI 1.079–2.007, P?=?0.015, respectively). We also found that the frequency of the rs2910164 CC genotype was significantly higher in patients with Haas grade III–V than in those with Haas grade I–II for all study populations (P?P?=?0.038).

Conclusions

These results indicated that rs2910164 may affect the susceptibility and severity of pediatric IgAN. Further studies are needed to validate these findings.     

Development of a novel marking system for laparoscopic gastrectomy using endoclips with radio frequency identification tags: feasibility study in a canine model

Background

Intraoperative identification of early gastric cancer is difficult to conduct during laparoscopic procedures. In this study, we investigated the feasibility and accuracy of a newly developed marking system using endoclips with radio frequency identification (RFID) tags in a canine model.

Methods

RFID is a wireless near field communication technology. Among the open frequency bands available for medical use, 13.56 MHz is suitable for a surgical marking system because of the similar and linear signal decay both in air and in biological tissues. The proposed system consists of four parts: (a) endoclips with RFID tags, (b) endoclip applier equipment, (c) laparoscopic locating probe, and (d) signal processing units with audio interface. In the experimental setting using canine models, RFID-tagged endoclips were applied to the mucosa of each dog’s stomach. During the subsequent operation, the clips with RFID tags placed in five dogs were located by the detection of the RFID signal from the tag (RFID group), and the conventional clips in the other six dogs were located by finger palpation (FP group). The detected sites were marked by ablation on the serosal surface. Distance between the clips and the metal pin needles indicating ablated sites were measured with X-ray radiographs of the resected specimen.

Results

All clips were successfully detected by the marking system in the RFID group (10/10) and by finger palpation in the FP group (17/17). The medians of detection times were 31.5 and 25.0 s, respectively; the distances were 5.63 and 7.62 mm, respectively. The differences were not statistically significant. No adverse event related to the procedures was observed.

Conclusions

Endoclips with RFID tags were located by our novel marking system in an experimental laparoscopic setting using canine stomachs with substantial accuracy comparable to conventional endoclips located by finger palpation through an open approach.     

Mechanisms of graft versus host disease produced by small bowel transplantation

Mechanisms of graft versus host disease have been studied in Lew x BN animals transplanted with a Lew small bowel. Grafted mesenteric lymph nodes but not host mesenteric lymph nodes or host spleen, in small bowel transplanted rats undergoing lethal GVHD, provide a source of CTL with specific anti-recipient cytotoxic activity. Host MLN and host spleen display anti-recipient CTL activity only when GVHD is provoked by intraperitoneal lymphocyte injection. These data demonstrate that lethal GVHD after SBTx may occur in the absence of detectable cytotoxic activity in host lymphoid tissues, suggesting that other mechanisms are involved in the pathogenesis of GVHD after SBTx. GVHD after SBTx or lymphocyte transfer is associated with the appearance of TNF in the serum. The intensity and reversibility of this phenomenon correlate with both the clinical severity and the lethality of GVHD. Taken together these data highly suggest that TNF is directly involved in the pathogenesis of GVHD after SBTx.     

Role of the VEGF 936 gene polymorphism and VEGF-A levels in the late-term arteriovenous fistula thrombosis in patients undergoing hemodialysis

Purpose

Vascular access is vital for hemodialysis patients. A major factor that facilitates arteriovenous (AV) fistula failure is stenosis and thrombosis due to intimal hyperplasia developing in the venous segment of AV fistula. It has been reported that VEGF accelerated re-endothelialization, reduction in intimal thickening, and/or mural thrombus formed in the injured vascular structures. In this study, we aimed to identify the effect of the VEGF 936 gene polymorphism and vascular endothelial growth factor-A (VEGF-A) levels in the late period of AV fistula loss in hemodialysis patients.

Methods

The study was carried out with a patient group of 42 individuals who experienced two or more fistula thrombosis in the late period after the AV fistula operation and also a control group of 38 patients who have not had any AV fistula thrombosis history for 3 years or more. All participants were assessed for VEGF-936C/T gene polymorphism and VEGF-A levels.

Results

VEGF-936C/T genotypes were determined in the large proportion in the control group (31.6 %), while VEGF-936C/C genotypes were determined in a large proportion in the patient group (90.5 %). Individuals carrying the VEGF-936C/C genotype had an increased risk of 5.54 for getting AV fistula thrombosis. The VEGF-A levels of patient group (27.3 ± 43.5 pg/ml) were significantly lower than those of the control group (70.7 ± 53.1 pg/ml).

Conclusion

There is an increased risk of AV fistula thrombosis in individuals carrying the VEGF-936C/C genotype. The other renal replacement modalities should be considered in patients with this genotype. As a result, it will be possible to prevent the morbidity and mortality due to fistula failure.     

Chemosensitivity Predicted by BluePrint 80-Gene Functional Subtype and MammaPrint in the Prospective Neoadjuvant Breast Registry Symphony Trial (NBRST)

Purpose

The purpose of the NBRST study is to compare a multigene classifier to conventional immunohistochemistry (IHC)/fluorescence in situ hybridization (FISH) subtyping to predict chemosensitivity as defined by pathological complete response (pCR) or endocrine sensitivity as defined by partial response.

Methods

The study includes women with histologically proven breast cancer, who will receive neoadjuvant chemotherapy (NCT) or neoadjuvant endocrine therapy. BluePrint in combination with MammaPrint classifies patients into four molecular subgroups: Luminal A, Luminal B, HER2, and Basal.

Results

A total of 426 patients had definitive surgery. Thirty-seven of 211 (18 %) IHC/FISH hormone receptor (HR)+/HER2? patients were reclassified by Blueprint as Basal (n = 35) or HER2 (n = 2). Fifty-three of 123 (43 %) IHC/FISH HER2+ patients were reclassified as Luminal (n = 36) or Basal (n = 17). Four of 92 (4 %) IHC/FISH triple-negative (TN) patients were reclassified as Luminal (n = 2) or HER2 (n = 2). NCT pCR rates were 2 % in Luminal A and 7 % Luminal B patients versus 10 % pCR in IHC/FISH HR+/HER2? patients. The NCT pCR rate was 53 % in BluePrint HER2 patients. This is significantly superior (p = 0.047) to the pCR rate in IHC/FISH HER2+ patients (38 %). The pCR rate of 36 of 75 IHC/FISH HER2+/HR+ patients reclassified as BPLuminal is 3 %. NCT pCR for BluePrint Basal patients was 49 of 140 (35 %), comparable to the 34 of 92 pCR rate (37 %) in IHC/FISH TN patients.

Conclusions

BluePrint molecular subtyping reclassifies 22 % (94/426) of tumors, reassigning more responsive patients to the HER2 and Basal categories while reassigning less responsive patients to the Luminal category. These findings suggest that compared with IHC/FISH, BluePrint more accurately identifies patients likely to respond (or not respond) to NCT.     

Postsurgical coagulopathy in a hemophilia A patient with inhibitors: efficacy of recombinant factor VIIa

Perioperative hemostatic management in patients with hemophilia A who develop the coagulation factor VIII (FVIII) inhibitor is challenging, because exogenous FVIII is neutralized, which boosts the inhibitor to provoke postoperative coagulopathy. Recombinant activated factor VII (rFVIIa) has become available for this type of patient, although FVIII is sometimes required. We treated a 56-year-old male patient with hemophilia A with FVIII inhibitor scheduled for total hip arthroplasty (THA) and total knee arthroplasty (TKA). We used rFVIIa for THA; however, the amount of bleeding was 2,500 ml and blood transfusion was required, which boosted FVIII inhibitor after surgery. The TKA was then scheduled for 19 months later, after the level of the inhibitor had reduced to the preoperative level. Unfortunately, rFVIIa failed to improve PT/APTT, and thus we used recombinant factor VIII (rFVIII). The amount of bleeding during TKA was 1,340 ml, while the level of the inhibitor increased to a greater level than that after THA, provoking uncontrollable bleeding. For anesthetic management in hemophilia A patients with FVIII inhibitor, anesthesiologists must pay attention to postoperative coagulopathy, and every effort should be used to minimize exposure to FVIII. Furthermore, when rFVIIa is ineffective, postponement of surgery until rFVIIa regains its efficacy may be beneficial as compared to an operation with FVIII.     

A case of hypertrophic obstructive cardiomyopathy and acquired von Willebrand syndrome: response to medical therapy

Heyde’s syndrome is the combined occurrence of acquired von Willebrand disease caused by aortic valve stenosis and gastrointestinal bleeding that occurs particularly in elderly patients. The bleeding may be linked to the intravascular shear-induced proteolysis of high-molecular-weight multimers (HMWMs) of von Willebrand factor (vWF). Hypertrophic obstructive cardiomyopathy (HOCM) in the left ventricular outflow tract generates a high shear stress condition that can induce such proteolysis. We report the case of a 70-year-old woman with HOCM who had severe anemia and loss of HMWMs. After reduction of the outflow gradient by medical treatment, vWF normalized, and her anemia alleviated.     

Protective effects of adiponectin on uncoupling of glomerular VEGF–NO axis in early streptozotocin-induced type 2 diabetic rats

Purpose

To determine whether adiponectin could reduce microalbuminuria and provide renal protective effects by improving endothelial dysfunction and uncoupling of the glomerular vascular endothelial growth factor (VEGF)–nitric oxide (NO) axis in streptozotocin-induced type 2 diabetic rats.

Methods

Wistar rats were randomly divided into normal control group, diabetic nephropathy (DN) group induced by high-fat feeding and streptozotocin, diabetic rats injected with adenovirus-expressed adiponectin (AD-AdipoQ), and diabetic rats injected with AD-IRES-EGFP as control. Blood and urine samples were collected. Endothelium-dependent vasodilatation (EDV) of the aorta was measured. Renal tissues were collected for CD34 immunohistochemistry. Glomerular NO and VEGF levels were measured by the Griess reaction and Western blot testing, respectively.

Results

Injections of AD-AdipoQ significantly increased serum adiponectin levels and reduced the urinary albumin-to-creatinine ratio in diabetic rats (P < 0.05). The levels of plasma glucose, serum insulin, high-sensitivity C-reactive protein, and malondialdehyde were significantly reduced in diabetic rats after injections of AD-AdipoQ (P < 0.05). Severe EDV impairment was observed in the DN group, which was improved by AD-AdipoQ. CD34 expression in the glomeruli was also higher in diabetic rats, indicating increased proliferation of glomerular endothelial cells. However, AD-AdipoQ improved the increased proliferation of endothelial cells in the glomeruli. Diabetic rats showed increased glomerular VEGF levels and reduced NO levels. This uncoupling of the VEGF–NO axis was partially improved by AD-AdipoQ.

Conclusion

Adiponectin reduces the degree of microalbuminuria and has renal protective effects by improving endothelial dysfunction and uncoupling of the glomerular VEGF–NO axis in early diabetic nephropathy.     

Detection of a metastatic lesion and tiny yolk sac tumors in two teenage patients by FDG-PET: report of two cases

We herein report the efficacy of FDG-PET for detecting yolk sac tumors in two teenage patients. One patient had a rare bone metastasis and the other had tiny recurrent lesions at the mediastinum. Both lesions were difficult to detect by conventional diagnostic modalities. In contrast, FDG-PET was very effective for detecting these lesions. Furthermore, the SUVmax of the lesion reflected the tumor activity, which was also suggested by the fluctuating values of serum alpha-fetoprotein (AFP), an established marker of yolk sac tumors. FDG-PET may be a useful procedure to detect tiny and metastatic, pediatric yolk sac tumors.     

Pulmonary oedema in two parturients with hypertrophic obstructive cardiomyopathy (HOCM)

Two patients with hypertrophic obstructive cardiomyopathy (HOCM) presented for delivery. The first had a repeat Caesarean section with general anaesthesia and the second gave birth vaginally with epidural analgesia. Both patients developed pulmonary oedema in the peripartum period. These cases highlight the delicate fluid requirements of the pregnant patient with HOCM. The fluid management of the parturient is discussed with particular emphasis on the pathophysiology of HOCM. The indications for invasive monitoring are presented.