Cyst fluid antibiotic concentrations in polycystic kidney disease: Differences between proximal and distal cysts

Cyst fluid antibiotic concentrations in polycystic kidney disease: Differences between proximal and distal cysts. The concentrations of several antibiotics were measured in the cyst fluid of six adult patients with polycystic kidney disease Seventy-nine cysts were aspirated at surgery or autopsy Sixty-one cysts could be categorized as arising from the proximal nephron and 16 from the distal nephron by cyst fluid to serum sodium ratios. Serum, urine, and cyst fluid were simultaneously analyzed for sodium, creatinine, and various antibiotics. Gentamicin, tobramycin, cephapirin, and ticarcillin were either undetectable or present in low concentrations in renal cysts. Cyst fluid antibiotic concentrations did not correlate with cyst volume or creatinine clearance. Cysts of proximal nephron origin had higher antibiotic concentrations than distal cysts. In one patient with normal renal function, inulin was undetectable in renal cysts after a continuous 36-hour i.v. infusion. Para-aminohippurate, however, was detected in the renal cysts of this patient. These data help explain the poor clinical response of infected renal cysts to antibiotic therapy. They also suggest that antibiotics and other solutes may enter cyst fluid across tubular cells in addition to entry by glomerular filtration.Concentration intra kystique d'antibiotiques dans la maladie poly kystique rénale: Différences entre les kystes proximaux et distaux. Les concentrations de plusieurs antibiotiques dans le liquide des kystes ont été mesurées chez six sujets adultes atteints de maladie polykystique. Soixante dix neuf kystes ont été ponctionnés pendant des interventions chirurgicales ou des autopsies. Soixante et un kystes ont pu être classés comme proximaux et seize comme distaux en fonction du rapport de concentration de sodium kyste/plasma. Des déterminations de concentration de sodium, de creatinine et de divers antibiotiques ont été réalisées simultanément pour le plasma, l'urine et le liquide des kystes. La gentamicine, la tobramycine, la cephapirine et la ticarcilline étaient soit non détectables soit à des concentrations très faibles dans les kystes. Les concentrations d'antibiotiques dans les kystes n'étaient pas corrélées avec le volume du kyste ou la clearance de la creatinine. Les kystes proximaux avaient des concentrations d'antibiotiques plus élevées que les kystes distaux. Chez un malade dont la fonction rénale était normale l'inuline n'était pas détectable dans les kystes après une perfusion continue de 36 heures. Le para-aminohippurate, cependant, a été détecté dans les mêmes kystes. Ces résultats permettent de comprendre la réponse clinique faible des kystes infectés au traitement antibiotique. Ils suggèrent aussi que les antibiotiques ainsi que d'autres substances dissoutes peuvent pénétrer dans les kystes à travers les cellules tubulaires en sus de la pénétration par filtration glomérulaire

Medication-related problem type and appearance rate in ambulatory hemodialysis patients

Abstract Background Hemodialysis (HD) patients are at risk for medication-related problems (MRP). The MRP number, type, and appearance rate over time in ambulatory HD patients has not been investigated. Methods Randomly selected HD patients were enrolled to receive monthly pharmaceutical care visits. At each visit, MRP were identified through review of the patient chart, electronic medical record, patient interview, and communications with other healthcare disciplines. All MRP were categorized by type and medication class. MRP appearance rate was determined as the number of MRP identified per month/number of months in study. The number of MRP per patient-drug exposures were determined using: {[(number of patients) × (mean number of medications)]/(number of months of study)} /number of MRP identified. Results were expressed as mean ± standard deviation or percentages. Results Patients were 62.6 ± 15.9 years old, had 6.4 ± 2.0 comorbid conditions, were taking 12.5 ± 4.2 medications, and 15.7 ± 7.2 doses per day at baseline. Medication-dosing problems (33.5%), adverse drug reactions (20.7%), and an indication that was not currently being treated (13.5%) were the most common MRP. 5,373 medication orders were reviewed and a MRP was identified every 15.2 medication exposures. Overall MRP appearance rate was 0.68 ± 0.46 per patient per month. Conclusion MRP continue to occur at a high rate in ambulatory HD patients. Healthcare providers taking care of HD patients should be aware of this problem and efforts to avoid or resolve MRP should be undertaken at all HD clinics.Peer Reviewe

Extent, causes, and consequences of small RNA expression variation in human adipose tissue.

Small RNAs are functional molecules that modulate mRNA transcripts and have been implicated in the aetiology of several common diseases. However, little is known about the extent of their variability within the human population. Here, we characterise the extent, causes, and effects of naturally occurring variation in expression and sequence of small RNAs from adipose tissue in relation to genotype, gene expression, and metabolic traits in the MuTHER reference cohort. We profiled the expression of 15 to 30 base pair RNA molecules in subcutaneous adipose tissue from 131 individuals using high-throughput sequencing, and quantified levels of 591 microRNAs and small nucleolar RNAs. We identified three genetic variants and three RNA editing events. Highly expressed small RNAs are more conserved within mammals than average, as are those with highly variable expression. We identified 14 genetic loci significantly associated with nearby small RNA expression levels, seven of which also regulate an mRNA transcript level in the same region. In addition, these loci are enriched for variants significant in genome-wide association studies for body mass index. Contrary to expectation, we found no evidence for negative correlation between expression level of a microRNA and its target mRNAs. Trunk fat mass, body mass index, and fasting insulin were associated with more than twenty small RNA expression levels each, while fasting glucose had no significant associations. This study highlights the similar genetic complexity and shared genetic control of small RNA and mRNA transcripts, and gives a quantitative picture of small RNA expression variation in the human population

Ultrastructural localization of carbonic anhydrase in gastric parietal cells with the immunoglobulin-enzyme bridge method

Ultrastructural immunostaining of carbonic anhydrase in gastric parietal cells was accomplished with the immunoglobulin-peroxidase bridge procedure applied to cryostat sections of fixed guinea-pig stomach prior to dehydration and embedment. Of a variety of fixatives tested, only freshly prepared paraformaldehyde buffered with calcium acetate provided both immunostaining and adequate preservation of ultrastructural morphology. Delipidization or exposure of specimens to detergent prior to staining enhanced the intensity of the immunostaining and increased the sensitivity of the method. Increased diaminobenzidine concentration in the peroxidase substrate appeared also to intensify the densification at the reactive site. Carbonic anhydrase was localized ultrastructurally with this pre-embedment immunobridge procedure in the hyaloplasm of gastric parietal cells and less consistently in the superficial surface epithelium. The basal portion of the parietal cells stained more intensely than the apical region and immunoreactivity appeared concentrated at the plasmalemma and around mitochondria.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42849/1/10735_2005_Article_BF01012020.pd