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Biomedical subjects

A Atala

Publications and source records attributed to A Atala.

At least 109 records · Page 6Linked to original sources

Injectable alginate seeded with chondrocytes as a potential treatment for vesicoureteral reflux.

Injection of polytetrafluoroethylene (Teflon) or collagen has been used in the endoscopic treatment of vesicoureteral reflux. Although the principle of an endoscopic treatment is valid, there are concerns regarding the long-term safety and effectiveness of these substances. The goal of several investigators has been to find alternate implant materials that would be safe for human use. Toward this goal we conducted a study to determine the effect of chondrocytes using a biodegradable polymer solution as a template. Hyaline cartilage was obtained from the articular surfaces of calf shoulders and chondrocytes were harvested. Chondrocyte suspensions were concentrated to 20, 30 and 40 x 10(6) cells per cc and mixed with dry alginate powder (a biodegradable polymer) to form a gel. Twelve athymic mice were injected subcutaneously with a chondrocyte-alginate solution. Each mouse had 4 injection sites, consisting of control, 10, 15 and 20 x 10(6) chondrocyte cells (48 injection sites). Mice were sacrificed at 2, 4, 6 and 12 weeks after injection. Histological examination of the injection sites demonstrated evidence of cartilage formation in 34 of the 36 experimental injection sites. Gross examination of the injection sites with increasing time showed that the polymer gels were progressively replaced by cartilage. The ultimate size of the cartilage formed was related to the initial chondrocyte concentration injected, and appeared to be uniform and stable within each category. There was no evidence of cartilage formation in the 12 controls. Histological analyses of distant organs showed no evidence of cartilage or alginate gel migration, or granuloma formation. In conclusion, chondrocyte-alginate gel suspensions are injectable, appear to be nonmigratory and are able to conserve their volume. In addition, the use of autologous cartilage cells would preclude an immunological reaction. These preliminary studies indicate that autologous cartilage-polymer gel solutions may be potentially useful in the endoscopic treatment of reflux.

Alginates↗

Laparoscopic correction of vesicoureteral reflux.

Major advances have been made in the area of laparoscopic surgery. The advantages of this approach include smaller incisions, shorter hospitalizations, a more rapid convalescence and decreased postoperative discomfort. To explore the technical feasibility of performing antireflux surgery laparoscopically, we conducted a pilot study in 4 mini-pigs in which bilateral vesicoureteral reflux had been created surgically. We applied a modification of the Lich extravesical ureteral approach to perform laparoscopic antireflux surgery. All mini-pigs underwent successful unilateral mobilization, creation of a bladder wall trough and creation of a new ureteral tunnel laparoscopically. Examinations were performed postoperatively, and then serially at 1, 2, 3 and 5 months after repair. Fluoroscopic cystograms demonstrated the resolution of reflux in the corrected ureters and persistence of reflux in the uncorrected control ureters in all animals. Excretory urography showed no evidence of obstruction. Laparoscopic correction of vesicoureteral reflux appears to be technically feasible in the animal model. Long-term followup is necessary to determine the possible applicability of this technique in humans.

Animals↗

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↗

The effect of gastric augmentation on bladder function.

Gastrocystoplasty was performed in 29 female and 14 male patients 1 to 23 years old (average age 11 years). Urodynamic studies were completed in 20 patients preoperatively and within 6 months postoperatively. When postoperative studies were compared with the preoperative evaluation, it was noted that overall capacity increased an average of 220% (range 20 to 750%). Compliance also improved dramatically postoperatively. Bladder pressures increased from a mean volume of 34% of capacity preoperatively to 73% of the post-augment capacity. The average maximum filling pressure decreased by 32%, from 57 to 39 cm. water. Uninhibited contractions resolved completely in 6 of 10 patients who had them preoperatively. No one had uninhibited contractions postoperatively. Cyclical contractions of the stomach segment not exceeding 50 cm. water developed in 6 patients. The gastric patch seems to be an adequate source for improving the dynamics of a poorly functioning detrusor muscle in most patients. When a diamond-shaped patch of stomach is harvested and added to the bladder a spherical configuration is created, enhancing the storage properties. This result is in sharp contrast to other bowel segments, which must be detubularized to produce a suitable reservoir. The long-term effects of gastric augmentation remain to be determined.

Adolescent↗

Cryptorchidism and testicular torsion.

The cause of cryptorchidism remains obscure. Hormonal therapy is ineffective for most patients and initial response may be temporary. Surgery remains the most effective treatment for cryptorchidism. Testicular torsion is a surgical emergency in the postnatal infant and the pubertal male. Controversy surrounds the management of prenatal torsion.

Adolescent↗

Juvenile cystic kidneys (jck): a new mouse mutation which causes polycystic kidneys.

We have characterized a new recessive mutation in the mouse which predisposes to the development of polycystic kidney disease. This mutation, called juvenile cystic kidneys (jck), arose in a transgenic line of mice, but appears unrelated to the transgene since it segregates freely from it. While focal cysts are evident in affected animals as early as three days of life and the disease is progressive, the mice are fertile and generally survive to four or more months of age. Complementation analysis indicates that the jck mutation is not allelic with three other known recessive polycystic kidney mutations (cpk and two as yet unnamed mutations), and linkage studies demonstrate it is unlikely to be allelic with a fourth (pcy). The study of these five mutations and their interactions should prove useful for understanding the mechanisms required to maintain the normal integrity of renal tubules.

Alleles↗

Scrotal ultrasonography in Henoch-Schönlein purpura.

The vasculitis of Henoch-Schönlein purpura may involve the scrotum and clinically mimic diseases requiring surgical intervention, such as testicular torsion or an incarcerated inguinal hernia. The ultrasonographic features include marked edema of the scrotal skin and contents with intact vascular flow in the testicles. These findings may suggest the correct diagnosis and prevent unnecessary surgical exploration.

Child, Preschool↗

Diethylstilbestrol in treatment of postorchiectomy vasomotor symptoms and its relationship with serum follicle-stimulating hormone, luteinizing hormone, and testosterone.

Vasomotor symptoms such as hot flushes and profuse sweating have been described after bilateral orchiectomy. We evaluated 26 patients who had undergone bilateral orchiectomy for prostatic carcinoma to determine the incidence of vasomotor symptoms and the efficacy of low-dose diethylstilbestrol (DES) in the treatment of those symptoms. Measurements of serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone were performed to look for endocrine patterns which may be related to the presence of vasomotor symptoms. Fourteen patients (54%) reported the presence of vasomotor symptoms beginning one to four weeks after surgery. These patients were treated with DES or placebo in a double-blind crossover trial. The frequency and severity of hot flushes were significantly reduced during the time DES was given. This was accomplished with a low dose of 1 mg daily of DES which avoids the cardiovascular complications of higher doses. We found no correlation between the presence, severity, or frequency of hot flushes and serum gonadotropin or testosterone concentrations.

Climacteric↗

Priapism associated with asplenic state.

Priapism may be primary (idiopathic) or secondary to sickle cell anemia, trauma, leukemia, drugs, venous thromboembolic diseases, and other less common disorders. This study concerns 21 patients with priapism treated during a period of ten years. Nine patients (43%) had sickle cell anemia. Of the 12 individuals (57%) classified as idiopathic, 3 (25%) had previously undergone surgical splenectomy for benign conditions. Considering the propensity for this unusual condition to develop in patients with hemoglobinopathy-induced hyposplenism, the possibility of a relationship between the asplenic state and priapism is considered.

Adult↗

Bladder functional changes resulting from lipomyelomeningocele repair.

From 1986 to 1991, 12 boys and 23 girls underwent surgery for lipomyelomeningocele removal. Of these patients 29 were 15 months old or younger (average age 3 months), while 6 were 4.5 to 19 years old (average age 10 years). Preoperative and postoperative urodynamic studies, including external urethral sphincter electromyography, were done on everyone. All 29 infants had a cutaneous lesion overlying the lower back and 14 had an abnormal neurological examination. Preoperative urodynamic studies were abnormal in 11 patients, consisting of an upper motor neuron lesion in 6, and a mixed upper and lower motor neuron lesion in 5. Postoperatively, 10 of 14 children with an abnormal neurological examination improved, while 9 of 11 with abnormal lower urinary tract function normalized. In 1 of 18 children (6%) with normal preoperative urodynamic studies detrusor-sphincter dyssynergia developed postoperatively. In all 6 older children urinary incontinence developed, and this led to the diagnosis. Everyone had an abnormal neurological examination and abnormal preoperative urodynamic studies. One child had a lower motor neuron lesion, and 5 had a mixed upper and lower motor neuron lesion. Postoperatively, the neurological examination improved in only 1 patient (16%), and the urological symptoms and urodynamic findings improved in another child. Lipomyelomeningocele has a progressive effect on lower spinal cord function because infants tend to present with fewer urinary manifestations and physical findings than older children. Individuals who escape early detection tend to have a more subtle cutaneous abnormality. As a result, older children are more likely to present with urological and neurological complaints. Surgical correction in infancy provides a degree of reversibility not seen in older children. It is imperative that early identification, evaluation and treatment be undertaken to prevent this progression and permanency of neurological changes and urinary dysfunction.

Adolescent↗

Formation of urothelial structures in vivo from dissociated cells attached to biodegradable polymer scaffolds in vitro.

The use of autologous urothelium would be advantageous for urothelial replacement in many genitourinary reconstructive procedures. Urothelial tissue grafts might be created using isolated populations of transitional epithelium or tissue in concert with an appropriate synthetic substrate. We describe the results of experiments designed to determine the feasibility of using biodegradable polymers as delivery vehicles for the creation of new urothelial structures in vivo from dissociated cells. Primary cultures enriched in uroepithelial cells were obtained from New Zealand white rabbits using a new technique of cell harvest. Cells were seeded onto nonwoven meshes of polyglycolic acid polymers in culture and, after 1 to 4 days in vitro, the cell-polymer scaffolds were implanted into the mesentery, omentum or retroperitoneum of athymic mice. Polymers implanted without cells served as controls. Animals were sacrificed at 5, 10, 20 and 30 days after implantation and 75 implants were examined histologically. Ten days after implantation isolated single cell layers were seen lining the polymer fibers. At 20 and 30 days polymer degradation was evident and urothelial cells lined the polymer in continuous layers of 1 to 3-cell thickness. Anticytokeratin western blots demonstrated the presence of a urothelium-associated cytokeratin in cell-polymer implants recovered after 30 days. These results demonstrate that urothelial cells can be successfully harvested, survive in culture and attach to artificial biodegradable polymers. The urothelial-polymer scaffolds can be implanted into host animals and the implanted cells can achieve spatial orientation as the polymer undergoes biodegradation. These findings suggest that it may be possible to use autologous urothelium, reconfigured on a synthetic substrate, in reconstructive procedures involving the ureter, bladder and urethra.

Animals↗

Endoscopic treatment of vesicoureteral reflux with a self-detachable balloon system.

There is controversy about the use of polytetrafluoroethylene (Teflon) paste in children for the endoscopic treatment of vesicoureteral reflux due to evidence of particle migration. However, there are definite advantages in treating patients endoscopically. It is evident that the ideal substance should be able to be delivered endoscopically, conserve its volume, and be nonmigratory and nonantigenic. Towards this goal we developed a catheter with an inflatable, detachable and self-sealing silicone balloon that would fit through a 19 gauge cystoscopic needle. Hydroxy-ethyl-methyl acrylate, a hydrophilic polymer that solidifies within 60 minutes after the addition of ferrous sulfate, was chosen as the filling material for the balloon. Conceptually, the sealed balloon would prevent the migration of hydroxy-ethyl-methyl acrylate and the solidified polymer would prevent volume loss. To test this system reflux was created in 6 Hanford mini-pigs by unroofing the ureters bilaterally. In 2 pigs a previously described method of open surgery was used and in the other 4 reflux was created endoscopically using the resectoscope and laparoscopic scissors. The presence of bilateral reflux was confirmed 4 weeks later with a cystogram and the balloon was implanted unilaterally through a cystoscope. The opposite ureter served as an internal control in all animals. A repeat cystogram was performed 2 to 4 weeks after implantation, demonstrating resolution of reflux in the treated side and persistence of reflux in the opposite untreated ureter. Serial cystograms, ultrasound and excretory urography showed no reflux on the implanted side nor any evidence of obstruction. Tissue sections from various organs showed no evidence of particle migration, granuloma formation or inflammatory reaction. Short-term results show that the balloon implants are able to correct reflux without evidence of obstruction.

Animals↗

Current concepts in the treatment of genitourinary tract disorders in the older individual.

Genitourinary problems, including neurogenic dysfunction, impotence, prostatism, urinary tract infections, and prostate cancer, are common in the elderly, and most of the symptoms can be alleviated through pharmacological management. Patients with neurogenic dysfunction who present with symptoms such as incontinence and urinary retention can be appropriately managed with bladder and sphincter relaxants or stimulants. Anticholinergic agents in the form of oxybutynin, flavoxate, and propantheline are effective bladder relaxants, and phenoxybenzamine, prazosin, and terazosin are commonly used as sphincter relaxants. Bethanechol chloride is the agent most commonly used to stimulate bladder contraction, but physicians should be careful when prescribing it for elderly patients with cardiovascular problems. Organic and psychogenic causes of impotence usually overlap, and oral agents have limited use in the treatment process. The use of yohimbine has increased recently, but its value and rate of success remains questionable. Testosterone is being used widely to treat impotence, but it is only helpful to patients with hypogonadism and should be used with discretion in the elderly, who have a high incidence of prostate cancer. Vasoactive intracavernous pharmacotherapy, on the other hand, is a recently discovered alternative to testosterone with promising results. Although the treatment of choice for benign prostatic hypertrophy is surgery, there have been important pharmacological advances in treating this disorder. alpha-Adrenergic antagonists and anti-androgenic agents have been found to relieve the symptoms of prostatic enlargement. The use of chemotherapeutic and antibiotic agents to treat and suppress acute and chronic urinary tract infections is reviewed; these are second only to pulmonary infections as the most frequent cause of febrile episodes in patients over the age of 65. Lower urinary tract infections can be treated with almost any antibacterial agent. Upper urinary tract infections require full genitourinary evaluation and appropriate antibiotics should be used according to the urine culture sensitivity studies. With the advent of new hormonal agents, more choices are now available for the management of prostate cancer, which is the second most common malignancy in men. Diethylstilbestrol (stilboestrol), an oral estrogen, remains a commonly used agent to achieve castrate levels of androgens in advanced prostatic carcinoma. Agonist analogues, such as goserelin and leuprorelin, of gonadotrophin-releasing hormone (GnRH) [luteinising hormone-releasing hormone (LHRH); or gonadorelin] achieve the same results as diethylstilbestrol but without the cardiovascular side effects. Antiandrogens are also being used in combination with GnRH agonists to produce complete androgen blockage, with mixed results.

Aged↗

Preliminary vascular control for renal trauma.

Preliminary control of the renal vascular pedicle prior to opening Gerota's fascia is advocated as the standard approach for decreasing the rate of nephrectomy from trauma. This method, however, has not been studied widely. Previous reports failed to grade the severity of the renal injury and involved small patient series and historic control for comparison of nephrectomy rates. We studied 297 patients with renal trauma during a ten year period. Sixty-three of 75 patients with penetrating injuries and 12 of 222 patients with blunt injuries underwent renal exploration. We obtained vascular control prior to opening Gerota's fascia in 32 patients; it was obtained in 43 patients after opening Gerota's fascia. The nephrectomy rate depended on the degree of injury rather than on the type of renal vascular control obtained. Obtaining vascular control after opening Gerota's fascia did not increase the nephrectomy rate and shortened operative time by an average of 58 minutes. We recommend vascular control after opening Gerota's fascia when there is a large hematoma crossing the midline, a rapidly expanding renal hematoma, if the patient is unstable, or if Gerota's fascia has already been opened by the injury.

Accidents, Traffic↗

Extracorporeal shock-wave lithotripsy of renal calculi.

Extracorporeal shock-wave lithotripsy (ESWL) is a noninvasive technique that utilizes focused shock waves to fragment stones into sand-sized particles, which then pass spontaneously with urination. The clinical use of this technique was introduced in 1980 in Germany by Chaussy and associates and has replaced most open surgery and percutaneous endoscopy for stone removal. The physics of shock waves, equipment, techniques, and patient selection in ESWL are discussed. Results of treatment of renal, upper ureteral, and lower ureteral calculi are reviewed and compared. Complications of treatment, including ureteral obstruction, hemorrhage, and tissue damage, are discussed. The advent of second-generation lithotripters has widened the parameters for patient selection in the treatment of ESWL and has increased the availability of this treatment modality.

Humans↗