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Biomedical subjects

R F Gittes

Publications and source records attributed to R F Gittes.

At least 19 recordsLinked to original sources

Indium-labeled presensitized T cells for diagnosis of graft rejection.

The aim of this experiment was to test a safe, noninvasive method for necessary, accurate diagnosis of early allograft rejection. Heart-lung allograft was performed heterotopically using Brown Norway (BN) rats as the donor and Lewis (LEW) rats as the recipient. T cell suspensions were prepared from lymphnodes of specifically sensitized LEW rats that had acutely rejected full-thickness BN skin graft. Cell count was adjusted 50 x 10(6) cells/ml. The suspension was incubated in vitro with 111I oxide (1 m Ci-ml). An aliquot of labeled cell suspension containing 40 x 10(6) cells and a total radioactivity of 200 mCi was administered intravenously to each animal 3 and 6 days after heart-lung transplant. The traffic of T cells was followed in vivo and in isolated organs under large field view gamma camera. The gamma camera revealed radioactivity on the graft starting Postoperative Day 5 when the heart was actively beating; no radioactivity was revealed at the site of the isografted organs. The histology showed mild to moderate cellular infiltration parallel to the grade of radioimaging intensity. The injection of indium-labeled presensitized T cells was able to detect the rejection process in an early phase when there are no clinical symptoms of rejection and/or the rejection cascade can be reversed. These results suggest that a similar method can be used in human organ transplantation for early diagnosis of rejection.

Animals

Rat kidney transplantation update with special reference to vesical calculi.

A technical update on rat kidney transplantation is given. In this study, the bladder-bladder union was made using silk, polyglycolic acid (Dexon), polyglactin (Vicryl), and chromic catgut. The propensity of these sutures to form vesical calculi was investigated in both first and second generation transplants. The results of our study indicate that there is no significant difference (P greater than 0.01) in their calculogenic ability. Special problems attendant with first and second generation kidney transplants are described. The concept and technique of second generation kidney transplants are also described.

Animals

Arterialization of the liver. III. Influence of systemic and portal pressure gradients following heterotopic partial liver transplantation.

An acute study was designed to compare blood pressures across a heterotopically transplanted partial liver graft using arterialized and nonarterialized models. Eight partial liver transplants (PLT) were done in each group, using Wistar rats. The data gathered from them are the basis for the results obtained herein. Whereas there was no significant difference (P greater than 0.01) in inflow, outflow, or the pressure difference across the PLT between nonarterialized and arterialized groups, host portal venous pressures were significantly higher (P less than 0.01) in the arterialized group. A 1 mm arteriovenous fistula (AVF) was used to arterialize the PLTs in this study. It was proved that arterializing a PLT using a 1 mm AVF did not alter the pressure difference across the transplanted liver compared with the situation in the nonarterialized setting.

Animals

Review of an 8-year experience with modifications of endoscopic suspension of the bladder neck for female stress urinary incontinence.

Several modifications of endoscopic suspension of the bladder neck for treatment of female stress urinary incontinence have been used during an 8-year period. Of 154 patients treated 25 failures occurred, for an over-all success rate of 84%. Fifteen patients had postoperative complications for an over-all complication rate of 9.8%. Hospital stay decreased steadily throughout the review period to a current average of 2.2 days, with many patients presently undergoing an operation on an outpatient basis.

Adult

The physiologic basis of the TUR syndrome.

To better assess the role of hyperammonemia versus hypoosmolarity versus hyponatremia in the TUR syndrome, we developed a rat model. Sprague-Dawley female rats received an intraperitoneal injection (250 cc/kg body weight) of either 1.5% glycine, 2.0% glycine, 2.0% glycine plus 1.5% mannitol, 3.0% mannitol, 5.0% mannitol, or 2.0% glycine plus 0.25% saline. Arterial blood samples were obtained prior to injection, at 2, 8, 16, and 24 hr and analyzed for osmolarity, sodium, and ammonia. Those animals receiving 2.0% glycine, 2.0% glycine plus 1.5% mannitol, and 5.0% mannitol all died within 24 hr with lethargy, convulsions, and coma. Hyponatremia developed in all animals; death, however, occurred only when the sodium concentration declined to 90-95 meq/dl. Mannitol maintained serum osmolarity but did not prevent coma and death. Including 0.25% saline in the initial injection, or an iv injection of 5.0% saline delayed 8 hr achieved 100% survival. Ammonia concentrations increased 15-fold by 8 hr in groups receiving 2.0% glycine; it rapidly decreased to near normal by 24 hr. Decreasing the rise in ammonia by 50% with iv arginine had no effect on survival. Our results suggest that hyponatremia rather than hyperammonemia or hypoosmolarity accounts for the major morbidity and mortality secondary to the TUR syndrome.

Ammonia

Treatment options for proximal ureteral urolithiasis: review and recommendations.

The treatment of proximal ureteral calculi has been altered markedly by recent developments in shock wave lithotripsy (bypass, pushback and in situ), ureterorenoscopy and percutaneous stone removal. In an effort to discern the proper role of these newer treatment options with respect to ureterolithotomy (flank approach or dorsal lumbotomy), we completed a multicentered study in which 142 upper ureteral stone patients in 7 different treatment categories were reviewed retrospectively and contacted for convalescence data. From these data we conclude that before extracorporeal shock wave lithotripsy an upper ureteral stone should be manipulated until it is either pushed back to the kidney or bypassed with a stent. This maneuver should result in successful extracorporeal shock wave lithotripsy in more than 90 per cent of the patients. For those few patients with an impacted upper ureteral calculus ureterorenoscopy is recommended. Given the presently available treatment modalities we conclude that less than 3 per cent of all upper ureteral calculi will require ureterolithotomy. In this last circumstance a dorsal lumbotomy incision appears to be less morbid and yet as effective as anterior ureterolithotomy.

Algorithms

Nitrate production and phagocyte activation: differences among Sprague-Dawley, Wistar-Furth and Lewis rats.

We have found that activated resident peritoneal macrophages from Wistar-Furth and Sprague-Dawley rats produce significantly more superoxide (2.2 +/- 0.4 and 3.6 +/- 0.8 nmol of cytochrome c reduced/10(6) cells/10 min respectively) than those from Lewis rats (1.0 +/- 0.3 nmol of cytochrome c reduced/10(6) cells/10 min). Similar results are found in macrophages elicited with intraperitoneal thioglycolate. Furthermore, nitrate excreted in the urine increased greatly when either Wistar-Furth or Sprague-Dawley rats are injected i.p. with iota carrageenan (0.25 g), a response that did not occur with Lewis rats. This strain difference in the manifestations of the inflammatory response correlates with previous observations that Wistar-Furth and Sprague-Dawley rats, but not Lewis rats, develop suture-line colonic tumors when the ureters and bladder base are implanted into the colon.

Animals

Transcutaneous incorporation of nonabsorbable monofilament sutures.

In rats and guinea pigs, transcutaneous through and through mattress sutures of different materials (silk, nylon and Prolene [polypropylene]) were tied under tension to plicate the abdominal wall or the scrotal wall. Knots were either buried subcutaneously or left outside. Monofilament sutures, with buried knots, cut through and became completely incorporated as the plicated normal tissue flattened out to a normal appearance in about three weeks. Silk sutures and bulky outside knots left suppurating sinuses. Histologic examination at seven weeks confirmed the incorporated nylon or Prolene mattress sutures were surrounded by a sheath of clean scar tissue trailing as a curtain back to the cut through skin. It is concluded that sutures of monofilament nylon or Prolene, with buried knots, can be tied under tension to include outside skin and will cut through cleanly to become incorporated without sinus or suppuration. Such incorporated sutures and their trailing curtains of clean scar tissue can provide an internal buttress against soft tissue displacement with potential clinical application.

Abdominal Muscles

The relationship of lactoferrin to the anemia of renal cell carcinoma.

This study was designed to examine whether lactoferrin, a glycoprotein contained in neutrophils which binds free iron, mediates the anemia associated with renal cell carcinoma. Preoperative hematocrit, urinalysis, serum iron, total iron binding capacity, and ferritin levels were obtained in 24 patients with hypernephroma. At the time of radical nephrectomy, a tumor specimen was obtained from all 24 patients and corresponding normal renal tissue was obtained from eight patients. Fifteen patients had low serum iron, whereas nine patients had normal serum iron. All tissue samples were snap frozen at the time of surgery and were subsequently sectioned into 3-microns slices using the cryostat. Then all the sectioned specimens were stained with FITC (fluorescein isothiocyanate) and peroxidase conjugated rabbit derived anti-human lactoferrin. Ten of the 15 patients with low serum iron had positive anti-lactoferrin staining in both the FITC and peroxidase systems. None of the tumors from patients with normal serum iron and none of the normal renal parenchyma exhibited positive anti-lactoferrin uptake. Stains for iron in the bone marrow of two patients with low serum iron showed increased iron stores. These studies suggest that lactoferrin mediates the anemia often seen in association with renal cell carcinoma.

Anemia

No-incision pubovaginal suspension for stress incontinence.

We describe a modified needle suspension for urinary incontinence that eliminates all incisions. The anterior vaginal wall is suspended from the rectus fascia with 2 heavy nonabsorbable monofilament mattress sutures. The sutures pass down through and back up through the full thickness of the vaginal wall, and are tied suprapubically to bury the knot into the fat in the suprapubic puncture site. The technique is based on our laboratory observation that in rats and guinea pigs monofilament mattress sutures that are tied under tension to include the outside abdominal skin will cut through the skin, and become internalized and accepted without any residual inflammation if the knot is buried initially. The simplified technique makes routine use of outpatient surgery and allows for the use of local anesthesia only in selected patients. At 2 1/2 years the continence rate in the first 38 patients exceeded 87 per cent. There were no failures among the last 14 patients after the technique was modified to include an extra full thickness pass of the mattress suture through the vaginal wall. There have been no significant complications.

Adult

Chemolysis of cystine calculi.

Historically, cystine stone chemolysis has been approached with 2 different categories of compounds--alkalizing agents (sodium bicarbonate and tromethamine) and, more recently, protonated thiols and disulfide compounds (alpha-mercaptopropionylglycine, N-acetylcysteine and penicillamine). To establish the relative efficacy of these agents an in vitro model was devised that simulates the clinical setting. The optimal molar concentrations for sodium bicarbonate, N-acetylcysteine and tromethamine were determined initially and then compared at these strengths. Lastly, a variety of solution combinations were made to determine if a synergistic effect could be demonstrated. Results of this study demonstrate that the combination of acetylcysteine, a protonated thiol, with the strong alkalizing agent sodium hydroxide yields the most effective solution for chemolysis of cystine stones. The mechanism of action is believed to occur by a synergistic combination of the pH dependent increase in cystine solubility, with a simultaneously occurring thiol disulfide interchange.

Acetylcysteine

Carcinogenesis in ureterosigmoidostomy.

Both clinical and experimental observations establish that an adenocarcinoma of the colon is likely to occur at the suture line of ureterosigmoidostomy. The carcinogenesis depends on the initial presence of urine, feces, urothelium, and colonic epithelium in close apposition at a healing suture line. It does not occur in isolated colon loops used for urinary diversion. In our rat model, tumors were completely prevented by interposing ileum between the urothelium and colon. Clinical prevention requires that accurate hospital registries of patients at risk be established and that repeated annual colonoscopy be carried out on all of them.

Adenocarcinoma

Experimental observations on dissolution of uric acid calculi.

An in vitro model was devised to evaluate the efficacy of the different irrigating solutions utilized for local dissolution of uric acid stones. Tris (hydroxymethyl) aminomethane proved to be several times faster than sodium bicarbonate in dissolving uric acid calculi. The maximal dissolution rate was obtained when the highest pH (10.5) of Tris buffer was used in concentrations at or above 0.2 M. This makes the commercially available THAM-E an optimal choice. Stones averaging 1 cm. in diameter were dissolved in less than 48 hours when this compound was used. Sodium bicarbonate should only be used in solutions with concentrations lower than 0.2 M and pH below 9, if some dissolution is to be attempted. Concentrations and pH's above these levels will coat the stones with hard shells of sodium urate, making it impossible to dissolve them. The in vitro findings were confirmed in vivo in a limited study in pigs with human uric acid calculi surgically placed in their kidneys. Our results indicate how to make the best use of the solutions clinically available in order to obtain total dissolution of uric acid stones in short periods of time. We recommend the use of a 0.3 molar concentration of this buffer (THAM-E) at flow rates of about 50 cc per hour.

Animals

The role of germinal epithelium and spermatogenesis in the privileged survival of intratesticular grafts.

The testis is an immunologically privileged site. Since earlier studies excluded testicular steroid production as an essential factor, the present study evaluates the role of germ cells and spermatogenesis in the privileged survival of allografts within the testis. We used a Sertoli cell-only testis model and adolescent unilateral cryptorchidism in inbred rats to eliminate germ cells and spermatogenesis selectively. Parathyroid allografts were implanted into these sites, normal testes and beneath the renal capsule (a nonprivileged site) in appropriately matched controls. With at least 15 rats in each group, privileged allograft survival was shown to be unaffected by eliminating germ cells and spermatogenesis (p less than .005). Experimental evidence suggests the presence of an active process which incidentally permits privileged allograft survival within the testis, but which exists teleologically to protect the developing sperm from autoimmune attack. This is in addition to the passive anatomical separation provided by the blood-testis barrier. Our cumulative data strongly implicates the Sertoli cell in this process.

Animals

Sexual impotence: the overlooked complication of a second renal transplant.

The incidence of sexual impotence in 20 men who have received at least 2 kidney transplants was 65% compared to 10% after the first transplant. The importance was transient (2 to 4 months) in both affected men after the first transplant but permanent (2 to 10 years) in 6 men after the second operation. We attribute this increased percentage of impotence to the second end-to-end arterial anastomosis that requires division of the internal iliac arteries. We suggest that the second transplant be placed end-to-side into the common iliac artery.

Adult