Persistent left superior vena cava with thrombus formed in the catheter lumen 4 h after dialysis catheter placed.

Persistent left superior vena cava (PLSVC) is one of the most common thoracic venous anomaly and rarely noticed, because it is asymptomatic. However, for nephrologists, it is frequent enough to be encountered while placing hemodialysis catheters through the jugular vein. We report the case of 66-year-old patient with PLSVC presenting intrinsic thrombosis formation 4 h after dialysis catheter placed. Dialysis catheter was placed in the left internal jugular vein without resistance and any complication. PLSVC was detected after dialysis catheter insertion. We decided to remove the catheter, because the patient has other veins in which the catheter can be placed. When it was removed 4 h after catheter placing, thrombus was recognized in the catheter lumen. Transesophageal echocardiography was performed and no thrombus formation was observed in the heart chamber. For patients with PLSVC, if there were other veins in which the catheter can be placed, catheter replacement should be considered.

Pulsed magnetic stimulation with a high-frequency continuous magnetic stimulator (SMN-X) does not exert an adverse effect on genital organs and the estrous cycle in female Iar:Wistar-Imamichi rats.

AIMS: To histopathologically verify whether high-frequency continuous stimulation exerts adverse effects on genital organs (uterus and ovaries) and the estrous cycle in rats through comparison of 3 groups. METHODS: The device studied was a high-frequency continuous magnetic stimulator (SMN-X, Nihon Kohden, Tokyo). Thirteen female Iar:Wistar-Imamichi rats (SPF) were randomly divided into 3 groups: active treatment (MS) group (n = 7), sham treatment group, where rats were placed on a table 1 m away from the stimulator so that they could hear the sounds of the stimulator (n = 3) and control (no treatment) group (n = 3). The MS group underwent thirty-six 25-minute sessions of pulsed magnetic stimulation at the maximum output level (560 mT peak) (once/day, 5 days/week). At the end of the study period, the uterus and ovaries were removed for histological examinations. Estradiol and progesterone levels were assayed and the estrous cycle, bodyweight gain and daily behaviors were recorded. RESULTS: From results of histopathology and endocrinology, assays of the estrous cycle, and recordings of bodyweight gain and organ weight, no adverse effects of long-term pulsed magnetic stimulation were noted. There were no significant intergroup differences with regard to any item evaluated. CONCLUSION: In the study setting, SMN-X did not exert any adverse effect on the uterus, ovaries, estrous cycle and hormone levels as well as blood cell counts, bodyweight gain and daily behavior in female SPF rats. The present results may be a step forward in the discussion of the safety of SMN-X for clinical use in humans.

The potential dermal irritating effect of residual (meth)acrylic monomers in pressure sensitive adhesive tapes.

It is generally thought that residual unpolymerized (meth)acrylic monomers commonly found in pressure sensitive adhesive tapes for medical use may cause dermal irritation, but a systematic study has never been carried out. Therefore, we assessed the potential dermal irritating effect of residual (meth)acrylic monomers. We studied seven acrylic monomers, acrylic acid (AA), methyl acrylate (MA), ethyl acrylate (EA), n-butyl acrylate (n-BA), n-hexyl acrylate (n-HA), 2-ethylhexyl acrylate (2-EHA) and 2-hydroxyethyl acrylate (HEA), as well as three methacrylic monomers, methacrylic acid (MAA), methyl methacrylate (MMA) and 2-hydroxyethyl methacrylate (2-HEMA). We first examined their cytotoxic effect on a cultured dermis model using the MTT method to determine their EC(50) and then performed a primary irritation test in rabbits using the monomers at three different concentrations (i.e., EC(50) , one-tenth EC(50) and 10 times EC(50)). Marked variations were found in cytotoxic and dermal irritating activities among the (meth)acrylic monomers tested. HEA exhibited the most potent dermal irritation having the lowest erythema dose (the concentration which gives a primary dermal irritation index of 1.00) of 460 ppm. But the other monomers exhibited less potent dermal irritation (lowest erythema doses > or =1000 ppm). For the monomers, significant correlation was found between cytotoxic activity and in vivo dermal irritating activity. Our results show that residual unpolymerized (meth)acrylic monomers in adhesive tapes are unlikely to induce skin irritation except for HEA. This study also suggests that cultured skin models are extremely useful as a screening method for chemical substances that could potentially cause dermal irritating activity.

[Case of immune complex crescentic glomerulonephritis with consistently high titers of MPO-ANCA for 6 years].

A male patient, now 65 years old, experienced fever, hemoptysis, and respiratory failure about six years ago. Soon thereafter, he developed rapid progressive renal dysfunction with pulmonary hemorrhage and positive findings for MPO-ANCA. We commenced methylprednisolone pulse (MP) therapy followed by oral prednisolone (PSL) and intravenous cyclophosphamide (CY) for the treatment of ANCA-associated microscopic polyangiitis (MPA). Therapeutic efficacy was obtained comparatively rapidly. Light microscopic findings of a percutaneous renal biopsy demonstrated focal necrotizing and crescentic glomerulonephritis. Immunofluorescent microscopy indicated diffuse deposition of IgG and C3 along the periphery of the tufts and in the mesangium. On the basis of these findings, the condition was diagnosed as immune complex crescentic glomerulonephritis associated with MPO-ANCA. MPO-ANCA titers were high (714 EU) at onset and remained high (250-450 EU) over the ensuing 6 years with oral administration of PSL 5 mg. Though his condition remitted completely, his MPO-ANCA titers recently increased to above 600 EU once more. We conducted a follow-up renal biopsy to ascertain if the fluctuation of MPO-ANCA titers reflected an early stage of relapse. Light microscopic findings of the biopsied tissue revealed no signs of necrosis or crescentic formation of the glomeruli. Immunofluorescent microscopic findings were negative. The elevated MPO-ANCA titers were not valuable for the early prediction of relapse in our case, and the immune complex may have played an important role. When judging relapse and remission in ANCA-associated glomerulonephritis, it is important to evaluate the overall clinical findings and histopathological findings in addition to the serial ANCA titers.

Randomized, double-blind, sham-controlled evaluation of the effect of functional continuous magnetic stimulation in patients with urgency incontinence.

AIMS: To evaluate the effect of functional continuous magnetic stimulation (FCMS) on urgency incontinence in randomized, sham-controlled manner. METHODS: Thirty-nine patients with urgency incontinence, 16 males and 23 females (aged 66.0 +/- 16.5 years), who were refractory to pelvic floor muscle training (PFMT), were randomly assigned either to the treatment schedule performing 10-week active treatment, followed by 4-week non-treatment interval and then by 10-week sham treatment (A-S, n = 20) or to that performing the sham treatment first followed by 10-week active treatment (S-A, n = 19). RESULTS: At 10 weeks, the number of leaks/week, the total score of the International Consultation on Incontinence-Questionnaire: Short Form (ICIQ-SF), and maximum cystometric capacity (MCC) were significantly improved as compared with the initial levels (P < 0.001, P < 0.001, and P = 0.003, respectively) in the former group, but not in the latter group. Four (20.0%) patients were cured in the A-S group, while no patient was cured in the S-A group. At the end of the A-S schedule (24 weeks of study), the effect of the active treatment was still maintained at a significantly improved level, as compared with the initial level. At the end of the S-A schedule, the number of leaks/week was significantly improved as compared with the initial level and with its 10-week level (P < 0.001 and P = 0.049, respectively), as well as ICIQ-SF total score (P = 0.001 and P = 0.006, respectively). MCC significantly increased from its initial level (P = 0.030). CONCLUSION: Magnetic stimulation was effective on urgency incontinence in comparison to sham stimulation in this small patient group.

Postnatal expression of KLF12 in the inner medullary collecting ducts of kidney and its trans-activation of UT-A1 urea transporter promoter.

Maturation of the inner medulla of the kidney occurs after birth and is vital for mammals to acquire maximal urinary concentrating ability. During this process, expression of several kidney transporters and channels involved in urine concentrating mechanisms is known to be regulated. We previously isolated KLF15 as a transcription factor that regulates the expression of the ClC-K1 chloride channel. We have now found that another KLF transcription factor, KLF12, is expressed in the kidney from around 15 days after birth. To gain insight into its involvement in the maturation process of the inner medulla, we first determined the expression site of KLF12 within the kidney by in situ hybridization. By comparing the AQP2 immunolocalization in sequential sections, KLF12 was found to be expressed in the collecting ducts. Because expression of the urea transporter UT-A1 and amiloride-sensitive epithelial sodium channels ENaC is known to be tightly regulated in the collecting ducts after birth, we tested whether KLF12 has a regulatory role in the promoter activities of these genes. KLF12 is able to increase UT-A1 but not ENaC promoter activity through the binding to CACCC motif. These results suggest that KLF12 is involved in the maturation processes of collecting ducts after birth, and that UT-A1 is a target gene of KLF12.

Intracellular localization of ClC chloride channels and their ability to form hetero-oligomers.

ClC chloride channels (ClCs) can be classified into two groups in terms of their cellular localizations: ClCs present in the plasma membranes and those residing in intracellular organelles. Members of the latter group, including ClC-3, ClC-4, ClC-5, ClC-6, and ClC-7, are often co-expressed in a variety of cell types in many organs. Although the localization of individual channels within cells has been investigated, the degree of overlap between the locations of different ClCs in the same cell has not been clarified. To address this question, different combinations of ClCs, engineered to encode specific epitope tags (FLAG or HA), were either transiently or stably transfected into HEK293 cells, and we then compared the intracellular localization of the expressed channel proteins by immunofluorescence microscopy. Immunofluorescence images of the alternatively labeled channels clearly showed significant co-localization between all pair-wise combinations of ClCs. In particular, ClC-3, ClC-4, and ClC-5 showed a high degree of co-localization. As a significant degree of co-localization between ClCs was observed, we used co-immunoprecipitation to evaluate oligomer formation, and found that each ClC tested could form homo-oligomers, and that any pair-wise combination of ClC-3, ClC-4, and ClC-5 could also form hetero-oligomers. Neither ClC-6 nor ClC-7 was co-precipitated with any other channel protein. These results suggest that within cells ClC-3, ClC-4, and ClC-5 may have combinatorial functions, whereas ClC-6 and ClC-7 are more likely to function as homo-oligomers.

Skin irritation due to repetitive application of adhesive tape: the influence of adhesive strength and seasonal variability.

BACKGROUND/PURPOSE: Influence of the repetitive application of pressure-sensitive adhesive tapes on skin was evaluated. METHODS: Two kinds of tapes with different adhesive strengths were repetitively applied to the inside of the forearm of six volunteers in winter and summer, in order to examine the dermal peeling force, the amount of stripped corneocytes, transepidermal water loss (TEWL), hydration and deepened skin furrows (changes in skin surface topography) in the epidermal stratum corneum. RESULTS AND CONCLUSION: As adhesive tapes were applied repetitively, dermal peeling force gradually increased while the amount of stripped corneocytes decreased. As the cumulative amount of stripped corneocytes increased with repetitive applications, the skin irritation worsened as measured by increased destruction of the skin surface topography and TEWL. These phenomena were more marked with the stronger adhesive tape, and there was seasonal variability.

Regulation of apical localization of the thiazide-sensitive NaCl cotransporter by WNK4 in polarized epithelial cells.

Missense mutations in the WNK4 gene have been postulated to cause pseudohypoaldosteronism type II (PHAII), an autosomal-dominant disorder characterized by hyperkalemia and hypertension. Previous reports using Xenopus oocytes showed that wild-type WNK4 expression inhibited surface expression of the thiazide-sensitive NaCl cotransporter (NCC), while a disease-causing mutant lost the inhibitory effect on NCC surface expression. To determine if these changes observed in oocytes really occur in polarized epithelial cells, we generated stable MDCK II cell lines expressing NCC alone or NCC plus wild-type WNK4 or a disease-causing (D564A) WNK4. In contrast to the apical localization of NCC without co-expression of WNK4, immunofluorescence microscopy and biotin surface labeling revealed that this apical localization was equally decreased by both the wild-type and the mutant WNK4 expression. Apical localizations of two PHAII-unrelated apical transporters, sodium-independent amino acid transporter, BAT1 and bile salt export pump, Bsep, were also found to be decreased by both wild-type and mutant WNK4 expression. These results indicate that the regulation of NCC was not related to the disease-causing mutation and not restricted to the PHAII-related specific transporters. The regulation of intracellular localization of NCC by WNK4 might not be involved in the pathogenesis of PHAII.

Disease-causing mutant WNK4 increases paracellular chloride permeability and phosphorylates claudins.

Mutations in the WNK4 gene cause pseudohypoaldosteronism type II (PHAII), an autosomal-dominant disorder of hyperkalemia and hypertension. The target molecules of this putative kinase and the molecular mechanisms by which the mutations cause the phenotypes are currently unknown. Although recent reports found that expression of WNK4 in Xenopus oocytes causes inhibition of the thiazide-sensitive NaCl cotransporter and the renal K channel ROMK, there may be additional targets of WNK4. For example, an increase in paracellular chloride permeability has been postulated to be a mediator of PHAII pathogenesis, a possibility supported by the localization of WNK4 at tight junctions in vivo. To determine the validity of this hypothesis, we measured transepithelial Na and Cl permeability in Madin-Darby canine kidney II cells stably expressing wild-type or a pathogenic mutant of WNK4. We found that transepithelial paracellular Cl permeability was increased in cells expressing a disease-causing mutant WNK4 (D564A) but that Na permeability was decreased slightly. Furthermore, WNK4 bound and phosphorylated claudins 1-4, major tight-junction membrane proteins known to be involved in the regulation of paracellular ion permeability. The increases in phosphorylation of claudins were greater in cells expressing the mutant WNK4 than in cells expressing wild-type protein. These results clearly indicate that the pathogenic WNK4 mutant possesses a gain-of-function activity and that the claudins may be important molecular targets of WNK4 kinase. The increased paracellular "chloride shunt" caused by the mutant WNK4 could be the pathogenic mechanism of PHAII.

Antiproteinuric effect of niceritrol, a nicotinic acid derivative, in chronic renal disease with hyperlipidemia: a randomized trial.

PURPOSE: Lipoprotein (a) [Lp(a)] levels increase in patients with renal disease. We administered niceritrol, a nicotinic acid derivative, to patients with chronic renal disease and a high serum Lp(a) level, and studied its effects on lipid metabolism, proteinuria, and renal function. METHODS: Thirty-three patients with chronic renal disease whose serum Lp(a) levels were > or = 15 mg/dL were randomly (but not blindly) assigned to treatment with niceritrol (n = 16) or to an untreated control group (n = 17). Parameters of lipid metabolism, excretion of urinary protein, and renal function were examined for 12 months. RESULTS: Changes in urinary protein excretion, as well as Lp(a) levels, differed significantly between the two groups. The mean (+/- SD) change from baseline in excretion of urinary protein was 0.77 +/- 1.23 g/d in the control group compared with -1.41 +/- 2.26 g/d in the niceritrol group at 12 months (P =0.003). Mean Lp(a) levels increased by 3 +/- 10 mg/dL in the control group compared with a decrease of 10 +/- 13 mg/dL in the niceritrol group at 12 months (P =0.004). The mean creatinine clearance declined by 10 +/- 12 mL/min in the control group, compared with 1 +/- 13 mL/min in the niceritrol group at 12 months (P =0.06). CONCLUSION: Lipid levels improved with niceritrol treatment, whereas the excretion of urinary protein decreased, perhaps slowing the rate of loss of renal function in chronic renal disease.

Effect of long-term administration of prostaglandin I(2) in incipient diabetic nephropathy.

BACKGROUND/AIMS: Diabetic nephropathy is one of the primary diseases of refractory renal failure and heads the list of patients undergoing dialysis. Therefore, it is very important to get treatment in incipient nephropathy. METHODS: Twenty-seven patients in incipient diabetic nephropathy of type 2 diabetes mellitus who showed signs of microalbuminuria were randomly, but not blindly, assigned to two groups, either the beraprost sodium (PGI(2)) group or the control group, and effects of the preparation on urinary albumin excretion or other parameters were examined for 24 months. RESULTS: Urinary albumin excretion was significantly decreased after 18 months in beraprost sodium group; however, there was no change in the control group. Difference was observed between the two groups after month 12; however, it was not significant (p = 0.0673 at month 24). Three factors that affect urinary albumin excretion, e.g. blood pressure, blood sugar and protein intake, were almost constant during the study period. The level of creatinine clearance was significantly decreased in beraprost sodium group after 24 months as compared with the control group. CONCLUSION: In this study, we found that the long-term 24-month administration of PGI(2) preparation, beraprost sodium, decreased albuminuria in patients of incipient diabetic nephropathy. The possible mechanisms are that the PGI(2) may have alleviated constriction effect of angiotensin II on efferent glomerular arteriole and attenuated glomerular hyperfiltration, and inhibited growth of mesangial cells by platelet-derived growth factor as well.