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Biomedical subjects

M C Carr

Publications and source records attributed to M C Carr.

At least 37 records · Page 2Linked to original sources
PubMed1996

Developmental regulation of collagen differential expression in the rabbit bladder.

PURPOSE: It has been suggested that the amount and relative ratios of different types of collagen influence bladder compliance. To understand the mechanisms regulating collagen synthesis and degradation in the bladder we investigated the gene expression of collagen types I and III in the rabbit bladder during normal development. MATERIALS AND METHODS: New Zealand white rabbits ages fetus to adult were used for this study. The mid portion of the bladder wall was harvested. Northern blot hybridization was performed to analyze quantitatively collagen types I and III messenger (m) ribonucleic acid (RNA), and in situ hybridization was done to localize the messages. Corresponding protein distributions were obtained by immunohistochemical staining. RESULTS: Types I and III collagen are developmentally regulated at the level of gene expression. The temporal and spatial distribution of the mRNA transcripts of alpha 1(I) and alpha 1(III) correlates with extracellular protein deposition. Differential distribution of the mRNA transcripts is also developmentally regulated. CONCLUSIONS: This study characterizes the relationship between collagen gene expression and normal rabbit bladder development. The expression of alpha 1(I) and alpha 1(III) alters as the bladder grows. High levels and nonconcordant up and down regulation of different types of collagen mRNA during early development demonstrate the complexity of the extracellular matrix in a young bladder. This observation may be important in our understanding of the injury response in a developing versus mature bladder.

Animals↗
PubMed1996

Collagen types I and III localization by in situ hybridization and immunohistochemistry in the partially obstructed young rabbit bladder.

PURPOSE: The objective of the study was to investigate the alteration of collagen expression patterns at the transcription and translation levels during partial outlet obstruction and to compare changes in collagen types I and III gene expression, and protein deposition during early and subacute phases of obstruction. MATERIALS AND METHODS: Following 1, 2, 7, 14 and 21 days of partial bladder obstruction in 2-week-old rabbits bladder tissues were evaluated for collagen types I and III messenger ribonucleic acid localization by in situ hybridization and for protein localization by immunohistochemical study. RESULTS: There is up regulation of collagen types I and III gene expression after obstruction. Up regulation of collagen gene expression immediately after obstruction is within the lamina propria and the message moves into the muscular layer as obstruction progresses. Protein deposition for both collagen types is analogous to that of gene expression. CONCLUSIONS: Up regulation of collagen types I and III gene expression, and increased protein deposition after partial obstruction demonstrate that the alteration in collagen synthesis is at least partially transcription regulated. This alteration starts from superficial layers of the bladder wall and becomes deeper as the pathological process progresses.

Age Factors↗
PubMed1996

Interstitial cystitis in children.

PURPOSE: Interstitial cystitis has been rarely reported in children. We present our experience with 16 children in whom clinical symptomatology and cystoscopic findings were consistent with the diagnosis of interstitial cystitis. MATERIALS AND METHODS: We retrospectively reviewed the charts of 20 children referred for chronic sensory urgency, frequency and bladder pain who underwent cystoscopy and hydrodistension. Four patients were excluded from study because of infection identified at cystoscopy or lack of cystoscopic changes with hydro-distension. RESULTS: Patient age at onset of first symptoms ranged from 2 to 11 years (median 4.5) and age at diagnosis ranged from 3 to 16 years (mean 8.2). Of the 16 children 14 (88%) presented with symptoms of urinary frequency and sensory urgency, and in 13 (81%) lower abdominal pain was relieved by voiding. None of the children had motor urgency. Urodynamic evaluation in 8 cases revealed early bladder sensation with no evidence of involuntary bladder contractions. Diffuse glomerulations and terminal hematuria were demonstrated in all patients after hydro-distension. Followup was available for 14 patients. Relief of symptoms occurred after hydro-distension in all children except 1. Seven children (50%) required repeat hydro-distension. CONCLUSIONS: Children with symptoms of bladder pain, urinary frequency and sensory urgency have bladder changes on cystoscopy consistent with interstitial cystitis. Although rare, this condition is recognizable and it should not be confused with dysfunctional voiding in which complaints are secondary to involuntary bladder contractions.

Adolescent↗
PubMed1996

Demucosalized augmentation gastrocystoplasty with bladder autoaugmentation in pediatric patients.

PURPOSE: Potential metabolic complications in urinary reconstruction with bowel or stomach are due to the presence of the gastrointestinal mucosal layer. The advantage or disadvantage of each tissue has been debated. We report a procedure in which the mucosa of a gastric pedicle flap is removed and the remaining muscularis flap is transferred to an autoaugmented bladder. MATERIALS AND METHODS: Seven female and 4 male patients underwent the procedure at our institutions from October 1992 to November 1994. A retrospective chart review was performed to compare preoperative to postoperative urodynamic findings, continence status and complications. RESULTS: Mean followup was 23 months (range 8 to 33). Preoperative urodynamics showed an average bladder capacity of 109 cc (range 45 to 200) and compliance of 3 ml./cm. water (range 1 to 6). Urinary continence was achieved in 10 patients on clean intermittent catherization every 3 to 4 hours and 1 was wet due to low urethral resistance. All patients underwent postoperative urodynamics. Bladder capacity increased to 236 cc (range 150 to 300) with an average compliance of 9 ml./cm. water (range 5 to 14). No metabolic complications were noted. CONCLUSIONS: The gastric muscularis appears to be preserved along with the native urothelium to provide a compliant tissue that can be an alternative to bowel and stomach for bladder augmentation. Because the procedure involves demucosalizing the gastric patch as well as performing bladder autoaugmentation, operative time is increased compared to normal gastrocystoplasty or enterocystoplasty. However, the lack of metabolic complications and mucus-free urine are important considerations and substantial advantages.

Adolescent↗
PubMed1996

Bladder stimulation therapy improves bladder compliance: results from a multi-institutional trial.

PURPOSE: We examined data from multiple institutions to determine whether intravesical bladder stimulation therapy is effective in improving bladder compliance by increasing bladder capacity and lowering bladder storage pressures. MATERIALS AND METHODS: The charts of 568 patients from 11 institutions were evaluated. Of the 568 patients 335 had adequate and accurate pretreatment and posttreatment urodynamic studies, and were included in this study. A total of 155 patients was from Children's Memorial Hospital, while the remaining 180 were from 10 other institutions. Bladder capacity and bladder capacity pressure were determined for each patient before and after therapy. RESULTS: Overall, 53% of patients had increased bladder capacity of 20% or greater after treatment (average increase 105 cc), which represents a 63% increase from pretreatment values. This increase occurred in an average of 1.9 years. Further analysis of this subset of patients revealed that in 90% intravesical storage pressures were decreased or maintained within a safe range (less than 40 cm. water). Evaluation of patients who did not respond to bladder stimulation with a 20% or greater increase in bladder capacity revealed that they had nearly normal bladder capacity before therapy. When the data on bladder capacity and bladder capacity pressure from Children's Memorial Hospital were compared to results from the 10 other institutions, there were no appreciable differences. CONCLUSIONS: Bladder stimulation is effective in increasing bladder capacity without significantly elevating storage pressure in a majority of patients. We conclude that this technique is safe and effective in improving bladder compliance, and that it is reproducible elsewhere.

Adolescent↗
PubMed1995

Prenatally diagnosed bilateral hyperechoic kidneys with normal amniotic fluid: postnatal outcome.

We evaluated a subset of infants with bilateral markedly hyperechoic "bright" kidneys noted prenatally in association with normal amniotic fluid volume during gestation. Prenatal ultrasound showed increased renal parenchymal echogenicity bilaterally with preservation of the medullary pyramid architecture. These children were followed for up to 3 years to determine potential changes in the sonographic appearance of the echogenic renal parenchyma and to assess renal function. In 3 years 8 cases of bilateral hyperechoic fetal kidneys were identified. During postnatal followup renal echogenicity resolved in 4 cases, diminished in 1 and remained the same in 3. The serum creatinine and electrolytes were normal in all cases followed for more than 3 months. Other renal findings included vesicoureteral reflux in 2 of 7 cases, mild pelvic ectasia in 1 and tiny medullary calcifications in 1. The specific etiology of increased echogenicity is unknown, although 1 infant appeared to have a form of autosomal recessive disease with liver hyperechogenicity as well. We conclude that fetuses with bilateral hyperechoic kidneys associated with normal amniotic fluid volume have a favorable outcome. Ultrasonographic finding of marked parenchymal hyperechogenicity appears to improve with time; in our experience renal function is normal and the infants thrive. Continued followup is necessary to determine the long-term natural history of this phenomenon, as is subsequent prenatal and postnatal evaluation of future siblings to assess genetic risk.

Amniotic Fluid↗
PubMed1995

Expression of cell growth regulated genes in the fetal kidney: relevance to in utero obstruction.

Previous studies of fetal urinary tract obstruction (bladder outlet obstruction and ureteral obstruction) in lambs have shown that obstructions created relatively early in gestation (4/10 to 6/10 term) can significantly affect growth of the developing kidney. This suggests that urinary tract obstruction in utero can alter normal mechanisms of kidney growth. However, a mechanism for these effects has not yet been proposed. In this study we have used mRNA expression analysis to characterize the temporal sequence of expression of several growth-regulated genes during normal ovine kidney development. The purpose of this study was to test the hypothesis that early obstructions, such as those believed to arise in congenital obstructive uropathy in humans, might have a disproportionate effect on hyperplastic growth if the cellular growth fraction (percent of cells in the organ undergoing DNA synthesis) was greater in the second trimester than in the last. Northern blot analysis of the cell cycle-dependent genes histone H3, c-myc and ornithine decarboxylase (ODC) indicated a progressive, gradual decline in cellular proliferation in the kidney from approximately 60 to 135 days (4/10 term to term) gestation, as evidenced by decreases in the respective mRNA levels. The greatest levels of cell proliferation occurred near the midpoint of gestation. This indirect measurement of decline in cellular growth fraction was reflected in direct measurements of change in relative kidney weight. To test whether this decline in mRNA levels occurs widely among genes expressed in the fetal kidney during this period, relative expression levels of more than 300 anonymous mRNA transcripts were evaluated by differential display analysis. This method showed that genes whose expression patterns resembled the growth-regulated genes constituted less than 5% of the expressed mRNAs identified. These data indicate that intrauterine urinary tract obstructions that arise at or near the midpoint of gestation coincide with the highest rates of cell proliferation occurring in the second and third trimesters and, therefore, might adversely affect mechanisms of cell proliferation.

Animals↗
PubMed1995

Overcoming the limitations of proprietary computerized billing systems to enhance patient care.

Most physician offices have proprietary computerized billing systems, but these are not designed for monitoring utilization or addressing patient care issues, and they are difficult or impossible to modify. These systems do, however, contain valuable diagnosis and demographic information. An open-ended, relational x-base system is described that downloads this billing information and combines it with additional input to provide the practitioner with: current problem lists; medication and allergy lists; health screening reminders that are age, sex and disease specific; and commonly used demographic information. Several popular query/reporting tools are used to generate standard reports and ad hoc inquiries that relate directly to patient care. Two studies, one involving alerting physicians to possible adverse medication effects on specific patients, and one investigating appropriate use and billing of stool occult blood testing are summarized. In the constantly evolving arenas of utilization, outcomes research and cost efficiency, such an open ended, time efficient system has unlimited potential to improve patient care.

Drug-Related Side Effects and Adverse Reactions↗
PubMed1994

Urinary levels of the renal tubular enzyme N-acetyl-beta-D-glucosaminidase in unilateral obstructive uropathy.

Elevated urinary levels of the renal tubular enzyme, N-acetyl-beta-D-glucosaminidase (NAG), have been shown to be associated with reversible tubular damage and, therefore, may serve as an indicator of tubular damage in the setting of presumed obstruction uropathy. This study compares urinary NAG levels in children with apparent upper tract obstruction with normal children to assess the sensitivity of this assay for the detection of possible renal tubular damage. The study included 40 children 3 weeks to 16 years old with unilateral ureteropelvic junction obstruction (30) or primary obstructive megaureter (10). Urine was obtained from the bladder in all children and from the renal pelvis or ureter in 30 patients at surgery. Pelvic and ureteral urinary NAG levels were consistently higher than bladder levels. In patients with ureteropelvic junction obstruction NAG levels were 7 times higher than normal (76 units per mg., p < 0.0001) and 3 times higher than normal in patients with obstructive megaureter (29 units per mg., p < 0.001). The mean bladder urinary NAG levels in patients with ureteropelvic junction obstruction (17.6 units per mg. creatinine, standard error of mean 2.01, p < 0.001) and megaureters (19.2 units per mg. creatinine, standard error of mean 3.6, p < 0.049) were elevated above control patients (10.6 units per mg. creatinine, standard error of mean 1.02). Elevated urinary NAG levels in the renal pelvis, ureter and bladder may be helpful in identifying upper tract obstruction, which if left untreated, might cause progressive renal deterioration.

Acetylglucosaminidase↗
PubMed1994

Detection of human androgen receptor mRNA expression abnormalities by competitive PCR.

A competitive polymerase chain reaction (PCR) method for analysis of androgen receptor (AR) mRNA expression is described. The technique involves the use of an in vitro-transcribed RNA (cRNA) corresponding to a region of the AR mRNA transcript as a competitor in reverse transcription and PCR (RT-PCR) using total cellular RNA. The competitor RNA contains a site-directed mutation that produces a restriction fragment length polymorphism after RT-PCR and endonuclease digestion. We demonstrate that incorporation of the competitor RNA into RT-PCR reactions allows rapid semiquantitative determination of relative AR mRNA levels without the necessity of following PCR product formation kinetically; reaction products are assessed at the conclusion of the reaction sequence and without the use of radioactive probes or other specialized detection systems. We have used competitive PCR to demonstrate low levels of AR mRNA in an androgen-unresponsive human prostate cell line (PC3). In addition, we have also used this method to confirm that genital fibroblasts obtained from a subject with penoscrotal hypospadias (a non-intersex masculinization defect) that exhibit low levels of high-affinity androgen binding also exhibit abnormally low AR mRNA levels. These last results suggest that some non-intersex malformations of the urogenital tract are associated with abnormalities in the expression of the androgen receptor.

Base Sequence↗
PubMed1993

Fetal compensatory renal growth due to unilateral ureteral obstruction.

To determine whether fetal compensatory renal growth occurs in response to early gestational unilateral renal obstruction and to help elucidate the characteristics of this response, a fetal lamb model was developed in which unilateral ureteral obstruction was created at 60 days of gestation (term 135 to 140 days) and the effects of the obstruction were studied at varying periods thereafter. Kidneys were retrieved at 2 weeks (75 days in 3 cases), 5 weeks (95 days in 4) and 10 weeks (135 days in 9) after obstruction, weighed and preserved for histology and biochemical studies. Deoxyribonucleic acid (DNA), ribonucleic acid and protein were quantitated using standard assays. Morphometric studies to estimate glomerular number were performed using standard stereological methods. Contralateral kidney weight was increased compared to normals in 55 cases at all ages. The relative difference increased from 75 to 95 days. The fractional increase at 135 days (49.5%, p < 0.001 versus normal) was not different from 95 days (46.4%, p = 0.87), indicating that growth rate acceleration occurred predominantly before 95 days. Total renal DNA was increased above normal at each time point, with an ultimate increment proportionate to weight. Protein concentration was unchanged, suggesting that weight increase was not due to changes in renal water. Protein/DNA ratios were unchanged, indicating a predominantly hyperplastic process. Ribonucleic acid/DNA ratios decreased, possibly indicating a high rate of proliferation. Total glomerular number at term did not increase with in utero compensatory renal growth. Unilateral ureteral obstruction created early in gestation produced compensatory renal growth of the intact kidney in the fetal lamb. This process demonstrates an early but transient growth rate acceleration, hyperplasia and no increase in total glomerular or nephron number. The occurrence of compensatory renal growth in the fetal kidney with minimal functional renal demand would suggest that its mechanisms may be independent of functional demand. This model is unique and well suited to study compensatory renal growth.

Adaptation, Physiological↗
PubMed1993

Sonography with sonicated albumin in the detection of vesicoureteral reflux.

The primary radiological procedures for diagnosing vesicoureteral reflux are fluoroscopic and radionuclide cystography. Ultrasonography, with no ionizing radiation, would be useful as a screening tool for the diagnosis of reflux due to its absence of radiation exposure. We evaluated the usefulness of ultrasonography with sonicated albumin in the diagnosis of vesicoureteral reflux. Sonicated albumin contains approximately 3 to 5 x 10(8) microspheres per ml., which are echogenic. Sonicated albumin was tested in vitro, alone, and in human and porcine urine to assess microsphere stability. Urine dilutions, specific gravity, temperature and pH were used as variables. The mode of delivery was also tested in vitro and in vivo. These studies showed that sonicated albumin microspheres were stable over a wide range of chemical variables and urine composition. Sonicated albumin produced an image of uniform echogenicity when it was pre-loaded into a Foley catheter and followed by saline infusion in vitro. Fluoroscopic cystograms, using standard radiopaque contrast media, in 5 Hanford mini-swine in which unilateral reflux had been created previously confirmed the presence of reflux unilaterally. Sonographic cystograms with various dilutions of sonicated albumin in 0.9% sodium chloride (1:100, 1:250, 1:500, 1:750 and 1:1,000) were performed. At a dilution of 1:100 sonicated albumin produced dramatic echogenicity in the bladder and refluxing ureters during sonographic imaging. The microspheres appeared to be stable for prolonged periods (more than 40 minutes), thus allowing for a careful sonographic assessment of the entire genitourinary tract. Sonicated albumin may be valuable for the sonographic detection of vesicoureteral reflux.

Albumins↗
PubMed1992

The response of the fetal kidney to obstruction.

In a fetal ovine model the renal effects of different anatomic levels of fetal urinary obstruction were studied. Parameters of prenatal renal growth and differentiation were characterized and correlated with the patterns of renal response to in utero obstruction. Complete ureteral or urethral obstruction was produced in the sheep fetus at 55 to 60 days of gestation. Animals were delivered and sacrificed at near term (140 days), and the kidneys were removed and prepared for analysis. Parameters examined included weight, histology, glomerular number and total surface area, as well as urinary sodium, creatinine, osmolarity and N-acetyl glucosaminidase. Three patterns of response were identified, producing hydronephrotic, cystic or dysgenetic kidneys. Hydronephrotic kidneys were usually the result of bladder outlet obstruction or ureteral obstruction with spontaneous urinary decompression. These kidneys were large (20.7 gm. versus normal 10.8 gm., p less than 0.0001), with thinning of cortical parenchyma that was structurally intact. Glomerular number and surface area were normal. Cystic kidneys were large (14.2 gm., p less than 0.05) with grossly visible cysts and an effaced medulla. Cortical structure was distorted by cysts but basic elements were intact. Glomerular number and surface area were not reduced. Dysgenetic kidneys were small (3.9 gm., p less than 0.0001) with markedly abnormal cortical structure and little recognizable medulla. Histological elements similar to fetal structures were present, including cuboidal/columnar tubular epithelium and peritubular mesenchymal collars. Glomerular number and surface area were significantly less than normal (p less than 0.001). The kidneys contralateral to unilaterally obstructed kidneys were significantly larger than normal (16.2 gm., p less than 0.0001), with normal histology, glomerular number and surface area, indicating in utero contralateral renal hypertrophy. Urinary sodium was variably affected in the hydronephrotic kidneys and was identical to plasma in the dysgenetic kidneys. These results indicate the technical feasibility of in utero models of urinary obstruction. Renal growth and patterns of differentiation were markedly affected by in utero obstruction. They should be a major focus in the investigation of congenital obstructive uropathy, since normal processes of renal growth and differentiation form the basis for postnatal function.

Animals↗
PubMed1991

Redox and flavin-binding properties of recombinant flavodoxin from Desulfovibrio vulgaris (Hildenborough).

Flavodoxin from Desulfovibrio vulgaris (Hildenborough) has been expressed at a high level (3-4% soluble protein) in Escherichia coli by subcloning a minimal insert carrying the gene behind the tac promoter of plasmid pDK6. The recombinant protein was readily isolated and its properties were shown to be identical to those of the wild-type protein obtained directly from D. vulgaris, with the exception that the recombinant protein lacks the N-terminal methionine residue. Detailed measurements of the redox potentials of this flavodoxin are reported for the first time. The redox potential, E2, for the couple oxidized flavodoxin/flavodoxin semiquinone at pH 7.0 is -143 mV (25 degrees C), while the value for the flavodoxin semiquinone/flavodoxin hydroquinone couple (E1) at the same pH is -440 mV. The effects of pH on the observed potentials were examined; E2 varies linearly with pH (slope = -59 mV), while E1 is independent of pH at high pH values, but below pH 7.5 the potential becomes less negative with decreasing pH, indicating a redox-linked protonation of the flavodoxin hydroquinone. D. vulgaris apoflavodoxin binds FMN very tightly, with a value of 0.24 nM for the dissociation constant (Kd) at pH 7.0 and 25 degrees C, similar to that observed with other flavodoxins. In addition, the apoflavodoxin readily binds riboflavin (Kd = 0.72 microM; 50 mM sodium phosphate, pH 7.0, 5 mM EDTA at 25 degrees C) and the complex is spectroscopically very similar to that formed with FMN. The redox potentials for the riboflavin complex were determined at pH 6.5 (E1 = -262 mV, E2 = -193 mV; 25 degrees C) and are discussed in the light of earlier proposals that charge/charge interactions between different parts of the flavin hydroquinone play a crucial role in determining E1 in flavodoxin.

Amino Acid Sequence↗
PubMed1991

Urinary levels of renal tubular enzyme N-acetyl-beta-D-glucosaminidase in relation to grade of vesicoureteral reflux.

Elevated urinary levels of the renal tubular enzyme N-acetyl-beta-D-glucosaminidase (NAG) have been shown to be associated with tubular damage. To determine whether urinary levels of NAG would be abnormal and/or vary with the severity of vesicoureteral reflux, bladder urine was obtained from 31 children without reflux and 32 children with various grades of reflux. Nonrefluxing controls were obtained from children undergoing evaluation for a history of infection, hematuria or voiding abnormality. Patients with evidence of obstruction, neuropathic bladder dysfunction, urinary tract infection or renal failure were excluded. Bladder (32 cases) and ureteral (5 cases) urine from children with reflux was obtained at cystography or at antireflux surgery. Control and reflux patients were not significantly different with regard to sex or age. The mean urinary NAG level in nonrefluxing control patients was 10.63 IU/mg. (range 0.94 to 26.61, standard error of mean 0.43). Mean urinary NAG for all patients with reflux was 16.47 IU/mg. (range 2.85 to 52.02, standard error of mean 0.9). Two children with intrarenal reflux had urinary NAG levels of 52 and 48 IU/mg. Urinary NAG levels are elevated with higher grades of reflux and this relatively simple assay may have clinical usefulness in the assessment of tubular dysfunction associated with reflux.

Acetylglucosaminidase↗
PubMed1990

Triamterene nephrolithiasis: renewed attention is warranted.

Although triamterene has been known to contribute to urinary calculus formation, it has been presumed to be a rare phenomenon. Our review of stone analyses performed during the last decade by a single laboratory reveals an increasing incidence of triamterene stones. Awareness of the calculogenic potential of triamterene-containing medications should be re-emphasized.

Humans↗
PubMed1990

Effects of substituting asparagine for glycine-61 in flavodoxin from Desulfovibrio vulgaris (Hildenborough).

Gly-61 in flavodoxin from Desulfovibrio vulgaris (Hildenborough) has been changed to Asn by site-directed mutagenesis of the cloned gene. Values determined for the dissociation constant for the dissociation of the mutant protein into apoprotein and FMN, and for the redox potentials of the two 1-electron steps in the reduction of the bound flavin showed that FMN in all three redox states is bound more weakly in the mutant protein than in the wild-type flavodoxin. However, the greatest effect was on the semiquinone, for which Kd is 920 times larger in the mutant. The side-chain of Asn-61 in the mutant may hinder a redox-linked conformational change that occurs in this region of the protein, and which is thought to lead to formation of a hydrogen bond between N(5)H of FMNH and the backbone carbonyl group of amino acid-61.

Asparagine↗