Occurrence of foam cells in the choroid plexus of rats injected intraperitoneally with methylcellulose.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to D R Roth.
Explore the source record for details and available documents.
BACKGROUND: Transfilter culture systems with enzymatically isolated human vascular cells were established to imitate the morphologic situation of the inner parts of a vessel wall. METHODS: In transfilter cultures, only smooth muscle cells were seeded on one side of the filter, whereas in transfilter cocultures, smooth muscle cells were cultivated in the presence of confluent or nonconfluent (injured) endothelial cells on the other side of the filter. The filter mimics the porous internal elastic lamina. Fourteen days after seeding, cultures were fixed, embedded in Araldite (Serva, Heidelberg, Germany), and prepared for histologic examination (light microscopy, indirect immunofluorescence staining of von Willebrand factor- and alpha-smooth muscle actin-antigen). RESULTS: In transfilter cultures, smooth muscle cells migrated through the pores to the opposite side of the filter, replicated there, and formed fibromuscular proliferates (two to four layers of smooth muscle cells). The proliferation rates of the smooth muscle cells were similar on both sides of the filter and showed an optimum rate on day 4 in culture as determined by 5-bromo-2'-deoxyuridine labeling. By cocultivating a confluent endothelial cell layer on one side of the filter, migratory activity of smooth muscle cells was inhibited. However, when smooth muscle cells were cultivated together with proliferating endothelial cells (injured state), proliferation of smooth muscle cells was massively stimulated (up to 12 layers of smooth muscle cells). CONCLUSIONS: The results indicate that the confluency of the endothelial cells and their proliferation rate influence the migratory and proliferative behavior of smooth muscle cells. The transfilter system may be a suitable model for prescreening of potential antiproliferative and antiarteriosclerotic drugs.
The increased susceptibility of newborns to infection may in part be related to impaired in vitro functions of neonatal polymorphonuclear neutrophils (PMNs). To evaluate early steps in the activation cycle of bovine PMNs we determined the expression of Fc receptors (FcRs) with an erythrocyte rosetting assay utilizing bovine anti-sheep immunoglobulin G2 IgG2 and the accumulation of ligand receptor complexes or "caps" with fluorochrome-coupled concanavalin A (Con A caps) on neutrophils from adult (A-PMN) and newborn (N-PMN) bovines. In addition, the levels of myeloperoxidase (MPO) and alkaline phosphatase (AP) were determined. FcR expression is reduced in N-PMNs (P less than .001), in contrast to results observed with human N-PMNs. Basal capping of Con A binding sites is reduced (P less than .05) in N-PMNs but is enhanced (P less than .001) upon pretreatment with colchicine (0.5, 5.0, and 50.0 microns). These findings are again contrary to results observed with human N-PMNs. Consistent with findings in human neonates, however, are reduced levels of cellular MPO (P less than .05) and elevated cellular AP (P less than .001) in the neonate. The functional significance of elevated AP levels and altered Con A capping in N-PMNs is unclear. However, diminished expression of FcR could potentially contribute to impaired adherence and phagocytosis of bacteria, and reduced activity of neutrophil MPO could indicate weaker microbicidal capacity of neonatal cells. The demonstrated impairment of N-PMN functions could potentially contribute to reducing the effectiveness of the cellular host defense system in neonatal calves.
Explore the source record for details and available documents.
Neonates demonstrate an increased susceptibility to infection. Defects in locomotory functions of newborn neutrophils may play a crucial role in this context. We therefore compared the migratory response of newborn (N-PMN) and adult (A-PMN) bovine neutrophils in a microwell filter assay. Stimulation with four different endotoxins (E. coli O128B:4 and O55B:5; S. abortus equi; S. typhimurium), with zymosan-activated plasma (ZAP) and with C5a induced dose-dependent migration of A-PMNs and N-PMNs. Migration of unstimulated cells and of cells stimulated with diluted ZAP or C5a was higher (P less than 0.05) in N-PMNs. Migration of A- and N-PMNs towards C5a was inhibited (P less than 0.001) by preincubation with either a steroidal (122 microM flumethasone) or nonsteroidal (3.3 microM phenylbutazone) antiinflammatory drug. Migratory responses of N-PMNs were inhibited less by SAIDs than were responses of A-PMNs (P less than 0.05); indeed dexamethasone slightly enhanced N-PMN responses towards C5a, and 510 microM flunixin meglumine enhanced C5a-induced migration in both age groups. Endotoxins from E. coli O55:B4, S. abortus equi, and S. typhimurium induced a higher rate of migration (P less than 0.05) in N-PMNs. In contrast to the above findings, measurement of the maximal distance of migration by the leading-front method did not reveal age-related differences. Migration speed of PMNs was lower after stimulation with C5a than with ZAP, but could be restored partly by adding human vitamin D-binding protein (Gc-globulin). The demonstrated hyperirritability of bovine N-PMNs represents a major functional difference to neonatal neutrophils from other species, including man. It may additionally be related to altered PMN functions and neonatal disease susceptibility.
Deficient in vitro functions of neonatal neutrophils have been reported in various species. They may be functionally related to the well-known susceptibility of newborn individuals to microbial infections. To evaluate an early step in the sequence of neutrophil activation, neutrophils from adult cows (A-PMN) and newborn calves (N-PMN) were stimulated with zymosan-activated plasma (ZAP) or with the lipid mediator platelet-activating factor (PAF): Aggregation was recorded kinetically in a standard aggregometer and measured quantitatively as the area under the aggregation curve (AUAC). The mean +/- SEM of the AUAC of the first 2.5 min of the reaction induced with ZAP was similar in N-PMN and A-PMN. However, N-PMN deaggregated only partially, whereas A-PMN deaggregated almost completely (P less than 0.05). This may indicate a mechanism of microvascular sequestration in vivo with the potential to inhibit chemotaxis. PAF (10(-5)-10(-10) M) aggregated N- and A-PMNs similarly and dose-dependently with a maximal reaction at 10(-6) M. Inhibition of aggregation induced by 10(-6) M PAF was evaluated by preincubation with four antiinflammatory drugs: dexamethasone (Dex: 5.1, 51.0, 510.0 microM), flumethasone (Flu: 12.2 and 122.0 microM), phenylbutazone (PB: 0.33 and 3.3 mM), and flunixin meglumine (Flxin: 51 and 510 microM). Dex and Flu each inhibited (P less than 0.05) PAF-induced N-PMN aggregation at the highest dose, and A-PMN aggregation at the two higher doses. PB and Flxin each inhibited aggregation of N- and A-PMNs at all doses used. We compared the inhibition rate in both age groups and could demonstrate that Dex, Flu, and Flxin each at the highest dose, and PB at all doses used, inhibited PAF-induced aggregation less (P less than 0.05) in N-PMNs than in A-PMNs. These functional differences indicate hyperirritability of N-PMNs, and they need further elucidation to help understand mechanisms of increased neonatal susceptibility.
We reviewed 52 children with ureteroceles in an effort to evaluate the various facets of this disorder that influenced our surgical management. There were 12 single system ureteroceles and 40 duplex system ureteroceles. Total reconstruction was performed in 16 duplex system and 8 single system ureteroceles, of which 88 per cent required no further surgery. Upper pole heminephrectomy or ureteropyelostomy with partial ureterectomy was performed in 22 patients with duplex system ureteroceles with the goal of obviating lower tract surgery, of whom 12 (55 per cent) required subsequent surgery. In 6 patients, 4 with single system and 2 with duplex system ureteroceles transurethral incision of the ureterocele was the initial procedure with the expectation that improvement in function and hydronephrosis would facilitate subsequent lower tract surgery. Two of these patients required subsequent reconstruction. Recommendations regarding management are based on initial pathological condition, patient age and the presence of a single or duplex system ureterocele.
Nephrogenic adenoma is an uncommon entity, particularly in children. This benign lesion is believed to represent urothelial transformation in response to trauma or inflammation. Current treatment is local resection with fulguration of the base of the lesion, long-term antimicrobial therapy and periodic cystoscopy. Our 2 cases support not only the urothelial transformation theory but raise the possibility that immunosuppression may be a contributing factor in these lesions.
We report a case of a male newborn with complete epispadias and an umbilical lesion. Histological examination of the surgically removed lesion revealed a colonic remnant with no communication to the underlying bowel. This entity is one of the exstrophy/epispadias complex variants known as covered exstrophy with sequestered bowel, and is case 4 in the world literature. Simple excision of the lesion was accomplished with staged correction of the epispadias planned.
Two variations for resurfacing the penile shaft skin after repair of hypospadias defects are described. These techniques have been used in an effort to prevent some of the skin tags, tension at the penoscrotal angle, and oblique suture lines that may occur with the traditional Byars' flaps.
The natural history of vesicoureteral reflux in children is well documented. In most series girls comprise the majority of the children followed. We reviewed the presentation and course of 86 boys with primary vesicoureteral reflux to define the nature of reflux in that selected population. Of the boys 25 per cent presented when they were less than 3 months old and the youngest tended to have the most severe reflux. Presentation was usually with urinary tract infection but 14 per cent had dysfunctional voiding symptoms without urinary tract infection. Based upon their presentation and initial evaluation the patients were allocated to 1 of 3 treatment protocols: observation, chemoprophylaxis or surgery. No renal parenchymal loss was detected in the boys on observation. Surgical therapy was free of serious complications. Over-all, this modified approach to the management of reflux in boys is acceptable although further followup will be required to confirm these initial conclusions.
Urinary continence is one of the more difficult goals to achieve in patients with exstrophy or epispadias. The artificial genitourinary sphincter provides an alternative to reconstruction of the bladder neck for management of this problem. Although excellent continence can be obtained with bladder neck reconstruction, results of a second procedure of this type seldom are reported. We used the AS800 device in 16 patients with exstrophy and epispadias, 13 of whom had undergone a prior bladder neck operation. We defined our results as total success and continence success, and have achieved over-all rates of 69 per cent (excludes those awaiting revision) and 90 per cent (those with an active device), respectively. Although the frequency of revision and erosion was significant, the ultimate outcome in this difficult patient group was satisfactory.
A retrospective analysis of 100 patients, each managed by an intubated urinary diversion after undergoing repair of hypospadias and/or chordee or for a complication of previous urethral surgery, was performed to determine whether there was any difference in the incidence of postoperative urinary infection relative to the technique of catheter drainage (closed or open). In group 1 (50 patients) a traditional closed urinary drainage system was used, while in group 2 (50 patients) an open drainage system into doubled diapers was used. No significant difference in occurrence of urinary tract infections could be identified. Urinary infections occurred equally (24 per cent) in each group regardless of whether antibiotics were used postoperatively. Our results suggest that open urinary drainage using the double diaper technique is a safe and effective method of short-term catheter management after pediatric urethral surgery. This technique is comfortable for the patient, and is easy for parents to understand and master.
Surgical correction of major hypospadias defects is a challenging problem. Bladder mucosa has been reported as an excellent tissue for construction of a neourethra. We used bladder mucosa in 13 boys to create 15 neourethras when there was inadequate preputial skin to perform a vascularized pedicle flap or a free preputial graft. In 3 cases a bladder mucosa graft was used for initial repair of the hypospadias. All other boys had undergone prior hypospadias surgery. In 4 boys the initial result was satisfactory. Seven minor complications occurred in 5 boys, while 4 had more major complications. In 2 boys severe problems with stricture necessitated graft replacement and a satisfactory outcome has not been achieved. Our problems with stricture and stenosis seem to be related to the use of a subcutaneous tunnel for the graft bed and coring of the glans to create the meatus. Over-all, in 11 of the 13 boys the bladder mucosal graft provided an excellent resolution of the complex problem with easily managed postoperative complications.
A total of 33 patients underwent hypospadias or epispadias repair by patch or tubular grafts of skin or bladder epithelium from July 1980 to January 1985. Indications included previous circumcision, proximal primary hypospadias, severe chordee alone, inadequate local skin during extended urethroplasty at 2-stage hypospadias repair, multiple previous reconstructions and failed epispadias repair. Genital skin grafts were used in 25 patients, extragenital skin grafts in 4 and bladder epithelial grafts in 4. Complications occurred in 13 patients (39.4 per cent): 8 required reoperation for a fistula, stricture or diverticulum, and 5 underwent internal urethrotomy or urethral dilation. Of the 8 patients 3 needed more than 1 revision. These revisions were short and generally uncomplicated. Final results uniformly were good functionally and cosmetically. Based on our experience and that of others we believe that despite a high incidence of minor complications a free graft serves as an excellent substitute urethra for treatment of a variety of urethral problems in children.
Bladder injury in children is an unusual event that usually is associated with trauma or a surgical mishap. We describe-2 premature male neonates who were treated by minimal stimulation therapy and systemic paralyzation. Despite normal urological anatomy, each patient had a bladder rupture that we attributed to atony of the bladder coupled with the Credé maneuver, which produced high intravesical pressures.
Single stage repair of moderately severe degrees of hypospadias with correction of chordee and reconstruction of the neourethra presents a difficult challenge for the surgeon. Traditionally, a 2-stage approach to correct these defects has been used. However, more recently a 1-stage repair with correction of chordee and creation of a neourethra has increased in popularity. From 1978 to 1985 we treated 86 patients with moderately severe hypospadias and chordee with a 1-stage technique using either a transverse island pedicle flap, a Hodgson III hypospadias repair or a free preputial skin graft. Despite an over-all complication rate of 50 per cent, our final results based on cosmesis and function were deemed excellent in 90 per cent of the cases. Of the 44 complications 23 were strictures, most frequently at the proximal anastomosis. Two-thirds of these strictures responded to a single dilation with the patient under anesthesia. Our fistula rate was 10 per cent and flap necrosis, meatal stenosis or prolapse and residual chordee accounted for the remaining 12 complications. Our experience indicates that a 1-stage repair for moderately severe hypospadias and chordee can be performed in patients with a satisfactory success rate of more than 90 per cent, minimal morbidity and an acceptable complication rate.
In most recent series of artificial sphincter implantations there has been a reduction in mechanical and surgical complications, with continence rates approaching 90 per cent. Despite initially excellent results in 47 children, with increasing durations of followup we noted a transient hydronephrosis related to incomplete bladder emptying in 5 and a persistent physiological alteration of detrusor dynamics consisting of a rigid, noncompliant bladder in 7. Preoperatively, all patients had had indepth radiological studies and most had a urodynamic evaluation, and were considered to be excellent candidates. The etiology of these alterations is not understood at this time. Bladder and even upper tract deterioration can occur without the appearance of urinary leakage. Therefore, children with an artificial sphincter must be monitored indefinitely with semiannual assessment of the upper tracts and periodic urodynamic evaluation.