A single nucleotide polymorphism in the 5' untranslated region of RAD51 and ovarian cancer risk in Polish women.

BACKGROUND: DNA repair gene polymorphisms are known to influence cancer risk. The RAD51 gene encodes proteins essential for maintaining genomic stability by playing a central role in holmology-dependent recombinational repair of the DNA double-strand breaks. Aims. We investigated the association of polymorphisms in the DNA repair genes RAD51-135G > C and 172G >T with ovarian cancer risk. METHODS: 120 Polish ovarian cancer patients and 120 healthy controls were genotyped for RAD51 (135G > C and 172G > T) by PCR-RFLP. RESULTS: In the present work no association was detected between ovarian cancer risk and 172G > T polymorphism of the RAD51 gene. The 135G > C polymorphism was associated with ovarian cancer risk. We found evidence of an increased ovarian cancer risk in CC homozygotes (OR 12.97 [95% confidence interval {CI} (5.73-29.36)]) but not in heterozygotes (OR 0.55 [95% CI 0.23-1.29]). We demonstrated a significant positive association between the RAD51 variant 135C allele and ovarian carcinoma, with an adjusted odds ratio (OR) of 6.24 (p < .0001). CONCLUSION: The results indicated that the polymorphism 135G > C of RAD51 may be positively associated with ovarian carcinoma in the Polish population. Further studies on the role of the RAD51 gene on ovarian cancer are warranted.

The T/C polymorphism of the CYP17 gene and G/A polymorphism of the CYP19 gene in endometrial cancer.

Endogenous estrogen exposure is an important determinant of endometrial cancer risk. The CYP17 and CYP19 genes encode 17 hydroxylase/17,20-lyase and aromatase, respectively, both involved in sex hormone synthesis. The gene CYP17 and CYP19 are polymorphic and gene variability could contribute to the level of protein biosynthesis. In the present work the distribution of genotypes and frequency of alleles of the C/T polymorphism in promoter region of CYP17 and G/A polymorphism at position Val80 in CYP19 in subjects with endometrial cancer were investigated. Paraffin embedded tumour tissues were obtained from 100 women with endometrial cancer. DNA from normal endometrial tissue (n = 106) served as control. The polymorphisms were determined by PCR-RFLP. The distribution of the genotypes of the C/T polymorphism of CYP17 and G/A polymorphism of CYP19 in both control and patients did not differ significantly (p > 0.05) from those predicted by the Hardy-Weinberg distribution. There were no significant differences (p > 0.05) in genotype distributions and allele frequencies between subgroups assigned to histological stage. The results suggest that C/T polymorphism of the CYP17 gene as well as G/A polymorphism of CYP19 may not be linked with onset and development of endometrial cancer.

[Evaluation of peripheral blood neutrophils activity in women with endometriosis]. / Ocena aktywnosci neutrofilów krwi obwodowej u kobiet z endometrioza.

Authors evaluated the neutrophils ability of creating reactive oxygen intermediates (ROI) in peripheral blood of 14 patients with endometriosis. These tests were performed using the chemiluminescence method. Enhanced ROI production and in vivo priming phenomenon of neutrophils in endometriosis were reported. The observed increase in oxygen activity of neutrophils was statistically significant only in reaction with the use of fMLP. However performed neutrophils preactivation with TNF-alpha followed by the chemiluminescence test revealed the occurrence of in vivo neutrophil activation in women with endometriosis. Reported data confirm the existence of local inflammatory reaction in the course of endometriosis.

[Evaluation of the generation of interleukin-10 by peripheral blood lymphocytes in women with endometriosis]. / Ocena generacji interleukiny-10 przez limfocyty krwi obwodowej u kobiet z endometrioza.

The aim of study was the evaluation of generating the IL-10 by peripheral blood lymphocytes in women with endometriosis according to the stage of of the disease. Cytokine was estimated by immunoenzymatic method Elisa. The generation of IL-10 by peripheral blood lymphocytes was lower in patients with all stages of endometriosis than in control group. Decreased IL-10 generating observed in our study was not statistically significant, but it may correlate with disorders of immunological cell response. It may also play a role in a development and progression of endometriosis.

The effects of disseminating performance data to health plans: results of qualitative research with the Medicare Managed Care plans.

OBJECTIVE: To assess the information needs and responses of managed care plans to the Medicare Managed Care Consumer Assessment of Health Plans Study (MMC-CAHPS). DATA SOURCES/STUDY SETTING: One hundred sixty-five representatives of Medicare managed care plans participated in focus groups or interviews in the spring of 1998, 1999, and 2000. STUDY DESIGN: In 1998 focus groups were conducted with representatives of managed care plans to develop and test a print report of MMC-CAHPS results. After the reports were disseminated focus groups and interviews were conducted in 1999 and 2000 to identify perceptions, uses, and potential enhancements of the report. DATA COLLECTION/EXTRACTION METHODS: The study team conducted a total of 23 focus groups and 12 telephone interviews and analyzed the transcripts to identify major themes. PRINCIPAL FINDINGS: In 1998 participants identified the report content and format that best enabled them to assess their performance relative to other Medicare managed care plans. In 1999 and 2000 participants described their responses to and uses of the report. They reported comparing the MMC-CAHPS results to internal surveys and presenting the results to senior managers, market analysts, and quality-improvement teams. They also indicated that the report's usefulness would be enhanced if it were received within six months of survey completion and if additional data analysis was presented. CONCLUSIONS: Focus group results suggest that the MMC-CAHPS report enhances awareness and knowledge of the comparative performance of Medicare managed care plans. However, participants reported needing additional analysis of survey results to target quality-improvement activities on the populations with the most reported problems.

Treatment of children in the U.S. with end-stage renal disease (ESRD).

USA 10,434 children with End State Renal Disease or chronic renal insufficiency have been followed by NAPRTCS. 5958 renal transplants have been performed. Haemoidalysis preceeded Tx in 28%, PD in 47% and 24% were preemptive transplants. The most common diagnoses were obstructive uropathy, renal dysplasia, FSGN, reflux nephropathy and CGN. 20.4 were < 5 and 24.9% < 12 years or age a transplant. 57.7% had living related donors. The most common therapy is with prednisone, cyclosporine and mycophenalate mofetile. Time to 1st rejection episode is 755 days in LRD and 98 days in CD. 5 year patient survival is 93.5% and 5 year graft survival in LRD is 80% and in CD is 65%. 75 cases of PTLD have been reported. 3748 patients have had maintenance dialysis. Peritoneal dialysis was the main modality in 67% and hemodialysis in 39%. 0.86 episodes/year of peritonitis has occurred in PD patients. 94% of patients received EPO therapy and 15% received growth hormone therapy. 3 year patient survival on dialysis is 86.5% (69.5% in those < 1 to 92.4% in those > 12 yrs of age). 3863 patients with chronic renal insufficiency have been followed. Mean height by standard deviation score is -1.41 with one third -1.88. Growth hormone for one year increased SDS by -0.30.

Hemodiafiltration for vancomycin overdose in a neonate with end-stage renal failure.

We describe continuous venovenous hemodiafiltration (CVVHD) with a high-flux membrane as a novel treatment modality for vancomycin overdose associated with renal insufficiency. CVVHD was used in a 6-day-old male with a solitary hypodysplastic kidney, suspected sepsis, and anuric renal failure who subsequently received an accidental tenfold overdose of vancomycin. We furthermore present evidence for the importance of countercurrent dialysis in addition to continuous hemofiltration for optimal vancomycin removal.

Oxybutynin lowers elevated renal pelvic pressures in a rat congenital unilateral hydronephrosis.

We investigated whether oxybutynin could lower elevated renal pelvic pressures measured in a rat with an inbred unilateral congenital hydronephrosis. Simultaneous renal pelvic and bladder pressures were measured in 8 hydronephrotic rats and compared to those of 10 hydronephrotic rats treated with intravenous injection of 1.6 mg./kg. oxybutynin. Pressures were recorded at different urinary flow rates and during bladder filling and emptying. Hydronephrotic rats not given oxybutynin showed significantly higher renal pelvic pressures (e.g. p-bladder at 50% capacity = 8.9 +/- 3.1 cm. H2O, corresponding p-pelvis = 20.8 +/- 2.1 at very high urinary flow rates) than rats treated with oxybutynin. The latter had renal pelvic pressures similar to rats with normal non-hydronephrotic kidneys (e.g. p-bladder at 50% capacity = 10.1 +/- 3.5 cm. H2O, corresponding p-pelvis = 6.3 +/- 1.1 at very high urinary flow rates). Renal pelvic pressures were, moreover, lower than corresponding bladder pressures in contrast to the untreated hydronephrotic pelvic pressure that exceeded bladder pressure. This effect of oxybutynin in lowering elevated renal pelvic pressures in the obstructed kidney has not been described before and suggests a possible role for oxybutynin in this condition.

Office evaluation of the child with hematuria.

Most children with an identifiable cause of hematuria will be properly diagnosed if an appropriate evaluation is completed. However, some children with persistent hematuria will not have an identifiable cause. This article provides clinical advice on properly diagnosing the child.

Growth rates in pediatric dialysis patients and renal transplant recipients.

We compared growth rates by modality over a 6- to 14-month period in 1,302 US pediatric end-stage renal disese (ESRD) patients treated during 1990. Modality comparisons were adjusted for age, sex, race, ethnicity, and ESRD duration using linear regression models by age group (0.5 to 4 years, 5 to 9 years, 10 to 14 years, and 15 to 18 years). Growth rates were higher in young children receiving a transplant compared with those receiving dialysis (ages 0.5 to 4 years, delta = 3.1 cm/yr v continuous cycling peritoneal dialysis [CCPD], P < 0.01; ages 5 to 9 years, delta = 2.0 to 2.6 cm/yr v CCPD, chronic ambulatory peritoneal dialysis (CAPD), and hemodialysis, P < 0.01). In contrast, growth rates in older children were not statistically different when comparing transplantation with each dialysis modality. For most age groups of transplant recipients, we observed faster growth with alternate-day versus daily steroids that was not fully explained by differences in allograft function. Younger patients (<15 years) grew at comparable rates with each dialysis modality, while older CAPD patients grew faster compared with hemodialysis or CCPD patients (P < 0.02). There was no substantial pubertal growth spurt in transplant or dialysis patients. This national US study of pediatric growth rates with dialysis and transplantation shows differences in growth by modality that vary by age group.

Congenital unilateral hydronephrosis in a rat model: continuous renal pelvic and bladder pressures.

We investigated a rat model with inbred unilateral congenital hydronephrosis. Simultaneous bladder and renal pelvic pressures were measured during different urinary flows, and during bladder filling and voiding in these congenitally hydronephrotic rats (approximately 45 days old) and normal nonhydronephrotic rats from the same colony. Differential pressures between pelvis and proximal ureter were determined. Upon termination of the experiment the urinary tract was removed and processed for histological examination. Hydronephrotic rats had significantly higher renal pelvic pressures throughout bladder filling at all urinary flow rates than normal rats. These elevated renal pelvic pressures exceeded bladder pressures at high flows (for example bladder pressure at 50% capacity was 8.9 +/- 3.1 cm. water and corresponding pelvic pressure was 20.8 +/- 2.1 [hydronephrosis] versus pelvic pressure 7.4 +/- 1.1 [control]). While pressures in the proximal ureter were higher than in the pelvis in normal rats the hydronephrotic rats showed significantly higher pressures in the pelvis, suggesting that the site of obstruction is the ureteropelvic junction. Histological evaluation of the excised kidneys revealed only minimal tubular changes. This study represents a unique animal model with unilateral hydronephrosis from a partially obstructing ureteropelvic junction. Moreover, the data indicate that partial urinary obstruction and the associated renal pelvic pressures should be defined with reference to bladder fullness and urinary flow rates.

Ultrafast contrast enhanced magnetic resonance imaging of congenital hydronephrosis in a rat model.

Since new ultrafast magnetic resonance imaging (MRI) might offer unique advantages for evaluating renal blood flow, anatomy and urinary excretion, we used this technique to characterize a rat model with congenital partial ureteropelvic junction obstruction. MRI of 9 rats from an inbred colony with unilateral congenital (nonsurgical) hydronephrosis was compared with the contralateral nonhydronephrotic kidney serving as control. Our new imaging technique consisted of a 1-minute ultrafast gradient recalled imaging sequence during the first minute (64 images per imaging time 960 milliseconds) after contrast bolus injection with gadolinium-diethylenetriaminepentaacetic acid for assessment of renal blood flow followed by a 30-minute period with image acquisition every 30 seconds to study contrast distribution and excretion. Signal intensities were analyzed continuously over selected, different regions of interest. Anatomic analysis of MRI noncontrast studies showed precise delineation of the hydronephrotic pelvis and corticomedullary junction. After contrast gadolinium-diethylenetriaminepentaacetic acid injection signal intensity from the region of interest from hydronephrotic kidneys differed from nonhydronephrotic kidneys by showing less cortical decrease, suggesting decreased blood flow, less medullary decrease and delayed contrast excretion. Clear contrast distribution among the cortex, medulla and collecting system allowed selective estimation of different regions of interest and excellent anatomic evaluation. Renal anatomy and renal pelvic pressures were confirmed after scans were completed. Ultrafast contrast enhanced MRI allows simultaneous assessment of renal morphology, blood flow and function. In hydronephrotic partially obstructed kidneys distinct flow and excretion patterns measured with contrast enhanced MRI allow differentiation between the obstructed and nonobstructed kidney on physiological rather than purely anatomic means. This imaging technique may provide a useful method of evaluating congenital hydronephrosis obviating the need for multiple different diagnostic procedures.

Alterations in glomerular dynamics in congenital, unilateral hydronephrosis.

We have previously shown that rats with congenital, unilateral hydronephrosis exhibit a reduction in GFR that returns to normal when either the renin angiotensin system or thromboxane A2 (TxA2) is blocked. The current study defines the single nephron defect in congenital, unilateral hydronephrosis and evaluates the roles of angiotensin II (Ang II) and TxA2 in this renal derangement. Renal micropuncture experiments were performed on the right kidney of rats from an inbred colony with unilateral right-sided hydronephrosis (HYDRO), or non-affected litter mates (CONTROL). In addition, four separate groups of hydronephrotic animals were treated with either the TxA2 receptor antagonist SQ-29548 (SQ), one of two Ang II receptor antagonists [saralasin (SAR) or DuP-753 (DUP)]; or combined treatment with DuP-753 and SQ-29,548 (S&D). SNGFR was significantly reduced (P < 0.05) in HYDRO compared to CONTROL (17.6 +/- 2.0 vs. 35.9 +/- 3.7 nl/min, respectively). Treatment with SQ-29,548 normalized SNGFR (29.0 +/- 3.0 nl/min), while saralasin and DuP-753 resulted in only a partial recovery of function (25.6 +/- 1.6 and 27.8 +/- 1.4 nl/min, respectively). Combined SQ-29,548 and DuP-753 treatment resulted in full recovery of SNGFR to 32.9 +/- 4.4 nl/min. The glomerular ultrafiltration coefficient (Kf) was reduced (P < 0.05) approximately 45% in HYDRO compared to CONTROL (1.64 +/- .08 vs. 2.84 +/- .22 nl/min/mm Hg, respectively). Kf returned to control levels in SAR, DUP and SQ, and increased above control in S&D (5.58 +/- 1.6 nl/min/mm Hg). There were no differences (P > 0.05) in hydrostatic or oncotic pressures across the glomerular capillary between any of the groups studied. The observation that Kf increases above CONTROL with combined blockade of TxA2 and Ang II suggests that these regulatory hormones decrease Kf via independent mechanisms. These data indicate that the reduction in SNGFR in congenital, unilateral hydronephrosis is a result of a marked fall in Kf that is mediated by both Ang II and TxA2.

Cardiac desensitization to adenosine analogues after prolonged R-PIA infusion in vivo.

To determine the effects of chronic in vivo stimulation of adenosine receptors, R-(-)-N6-(2-phenylisopropyl)adenosine (R-PIA), a selective A1 receptor agonist, was administered to rats as a continuous 7-day infusion (200 nmol/h). Inotropic and chronotropic responses of isolated atria to adenosine receptor agonists were markedly desensitized compared with the responses of atria from age-matched control animals. Carbachol's negative chronotropic effect was also attenuated, indicating a heterologous mode of desensitization. Antagonist radioligand binding assays indicated a 52% reduction in A1 adenosine receptor maximum binding, and competition binding assays revealed a significant loss of G protein-coupled high-affinity A1 receptors in atria from R-PIA-treated rats. Inhibitory G proteins (Gi) were significantly reduced, as quantified by immunoblot analysis, with no change in the amount of stimulatory G proteins. Ventricular membranes from R-PIA rats showed loss of Gi and uncoupling of A1 receptors, without a significant change in A1 receptor density. Thus chronic R-PIA infusion desensitized rat atrial muscle to the effects of adenosine receptor agonists via several regulatory adaptations, including downregulation of A1 adenosine receptors, uncoupling of A1 receptors from their associated G proteins, and loss of Gi proteins.

Angiotensin or thromboxane receptor antagonism in rats with congenital hydronephrosis.

A technique for the measurement of GFR without collection of urine in rats was experimentally validated and applied to experiments designed to: (1) evaluate the degree of reduction of GFR in rats with congenital, unilateral hydronephrosis; and (2) to determine if the reduction in renal function is mediated by angiotensin II and/or thromboxane A2 mechanisms. Simultaneous measurements of GFR by a constant-infusion technique and the traditional inulin clearance technique in rats with either one or two normal kidneys were highly correlated (r = 0.934; P < 0.001; N = 17). GFR was approximately 24% lower (P < 0.001) in rats with congenital unilateral hydronephrosis than in rats with a normal kidney. The GFR in rats with hydronephrosis infused with a receptor blocker for either angiotensin II or thromboxane A2 was greater than the GFR in hydronephrotic kidneys without blockade and was not significantly different (P > 0.05) from that in rats with normal kidneys. These results indicate that a constant inulin infusion technique without urine collections can be used to accurately measure GFR in congenitally hydronephrotic kidneys, rendering values free from possible residual pelvic volume artifact. In addition, these results also indicate that a significant 24% reduction in GFR occurs in congenital unilateral hydronephrosis and is mediated by angiotensin II and thromboxane A2 mechanisms.

Urinary tract obstruction and infection in the neonate.

Congenital urinary tract obstruction is a common cause of renal failure accounting for up to 20% of end-stage renal disease cases. Intrauterine obstruction often results in parenchymal loss and renal dysfunction. The pathophysiology of obstructive nephropathy and its further depression of renal function is related to severe renal vasoconstriction, which is in large part angiotensin mediated. Signs suggestive of urinary obstruction in the newborn may include an abdominal mass, hypertension, oligoanuria/polyuria, urosepsis, and hyperchloremic acidosis. The combination of renal ultrasound, diuretic renal scans, and voiding cystourethrogram are the main diagnostic modalities in infants with hydronephrosis. Nonsurgical management of ureteropelvic junction obstruction has become more popular, particularly in mild to moderate cases. Early fulguration or bypassing the obstruction of urethral valves is essential and a decrease in serum creatinine to below 1 mg/dL within 1 month of relief of obstruction is a favorable prognostic sign. Obstruction complicated by infection is dangerous and requires prompt intervention. Any newborn with a urinary tract infection, regardless of sex, should be presumed to have urinary obstruction or reflux until proven otherwise.

Estimation of parenteral fluid requirements.

This article reviews the normal physiologic losses of water and electrolytes from the body, the source of the loss, and the increased body loss of water associated with fever. The three different methods for estimating replacement of water and electrolyte losses are described in this review.