Vanishing pancreatic grafts.

Comparison of pancreaticoduodenal transplants (PDT) and duct-ligated pancreas transplant (DLPT) were performed using syngeneic and allogeneic studies in rats. Both DLPT and PDT allogeneic grafts showed mild rejection. DLPT groups showed disorganized pathology and acini replaced by fat. Eventually, massive fibrosis was seen in the Islets of Langerhans, as well as rejection cellular infiltrates. In both PDT groups, normal histology was observed in the same period. Thus the effect of duct occlusion is highly detrimental for the grafts.

Consecutive en-bloc liver (30%)-pancreas-duodenum-spleen-stomach transplant in Lewis rats.

It is well-known that 30% of the remaining liver mass, following partial hepatectomy, regenerates to full original mass within 2 weeks in rats. In order to carry the transplanted rat liver to repeated transplantation, a technique of combining 30% of the liver with the pancreaticoduodenum and spleen transplantation is performed in this consecutive organ transplantation study. Our laboratory observed several 37-month-old transplanted rats by carrying through 2-3 generations, and histological disclosure were made. Because the partial liver transplants did not regenerate after the transplantation with other splanchnic organs, this technique is not so difficult though subsequent surgical maneuvers are needed and the liver histology proved entirely normal in every aspect when followed beyond the rat's life span of 24 months.

Needles to promote ventricular blood into the ischemic myocardium applied in a rat heart transplant model: an acute observation [corrected].

Two needles were designed in order to revascularize an ischemic myocardium in the event of left coronary artery occlusion. This study was conducted by performing the Lee modified Fox-Montorsi heart-lung transplant on 25 San Diego Microsurgical Institute-bred Sprague Dawley rats that were subjected to left coronary artery ligation in each case. Of these 25 rats, a straight-porous (SP) needling procedure was applied to 9 heterotopically transplanted rat hearts, and a distinct horseshoe (HS)-shaped needle application was performed on the remaining 16 heterotopically transplanted rat hearts. This report represents an acute study on the efficiency of these two needles to transmit oxygen-rich blood from the left ventricle into the ischemic myocardium. Doppler readings for male vs. female transplants showed that the control peak (PK) and mean (MN) kHz values are on the average of 0.20 kHz higher in males than in females. However, control heart rate values in both sexes are approximately equal. Ligation of the left coronary artery caused a dramatic decrease of PK and MN kHz values in both sexes, while heart rate showed no significant decrease from the original control values in response to ischemia. Application of the SP needle showed only a slight return of PK and MN values in both sexes, but heart rate values increased to levels higher than the original control values. The HS needling procedure was able to recover approximately 80% of the control PK and MN kHz values in both sexes. Thus, these data indicate that the HS needle can successfully transmit left ventricular blood into the myocardium.

Observations of rat ovarian-splenic consecutive transplants.

We examined the results after implantation of ovarian follicles by various modes in a total of 82 cases. One or five ovarian follicles were implanted into spleens in castrated female rats. In 20 cases among these, each five follicles were implanted into native and transplanted spleens after spleen transplantation (double implantation of the ovary). Through consecutive spleen transplantation, we observed the results beyond the rat's life span for a limited period. In many cases, we found a more aggressive form of malignant tumor, i.e., dysgerminoma. We present the results and discuss the modes of implantations and possible pathogenetic mechanisms of tumor formation.

Syngeneic consecutive rat spleen transplantation bearing infantile testis.

Seventy-seven Lewis adult rats received autologous testicular implants in the spleen. These spleens were retransplanted in a consecutive transplant fashion as we described earlier. Some were observed as long as 26 to 27 months. Although earlier splenic-testicular transplants showed benign granulosa cell tumors, some of the long-term follow-ups showed a seminoma-like transformation.

Mouse-to-rat testicle transplantation.

This report details mouse-to-rat testicular transplantation with immediate revascularization. Donor preparation involved grafting a long segment of aorta and inferior vena cava (IVC) containing the testicular artery and vein. The graft aorta and IVC were anastomosed to the rat aorta and IVC, respectively. Vasovasostomy was completed and the scrotal epithelia were anastomosed to draw the graft toward the host scrotal sac. Twenty-nine of 53 transplants were determined to be viable. Histologically, 6- to 18-hr-old grafts displayed moderate to minimal polymorphonuclear neutrophil (PMN) infiltrates. Ischemia set in somewhere between 18-24 hr postoperatively. Beyond 24 hr the grafts displayed progressive infiltration of PMN and perivascular and intertubular lymphocytes, disorganization of the germinal epithelium, and cessation of spermatogenesis.

Long-term fate of heterotopic liver transplants in rats with portal vein inflow only.

Previous studies have suggested that hepatic arterial flow in heterotopic partial liver transplants is necessary to ensure graft survival and regenerative capacity. This report presents findings in a syngeneic rat strain (Lewis) that partial liver transplants can be successfully heterotopically transplanted in the long term with the only inflow coming from the portal vein. When the host liver undergoes a nearly complete resection at 3-4 weeks, the transplanted liver regenerates to maintain the health of the host. Moderate to massive hepatocellular necrosis occurs in the first 3 months postoperatively, with recovery by 4-5 months. Liver transplants 8-10 months postoperatively appear architecturally normal. No host liver tissues were found to be regenerating after subtotal host liver resection. We conclude that portal vein reconstruction without hepatic arterial inflow can sustain a partial liver transplant in the long term, replacing the function of the host liver.

Update on sequential isologous rat organ transplantation: pancreaticoduodenal and kidney transplantations.

This periodic report includes intermittent results of consecutive pancreaticoduodenal (Pd) and kidney (Kt) transplants in inbred rats and results on double kidney transplants that did not follow sequential transplant protocol. Eight 24-month-old Lewis pancreas, kidney, and aorta served histological controls showing normal histological architecture with no atherosclerosis developed in the aorta. Thirty-four month old pancreas and thirty-two month old kidneys, which resided in young hosts for at least three occasions, appeared as youthful Pd and Kt grafts. They show normal histological appearance for more than the expected life span of a Lewis rat. The fact that not only pancreases but also kidneys outlived their host leads to the study of other different organs' viability as aged valuable grafts. Nevertheless, the threats by the development of atherosclerosis in graft-associated aortas resulted in slow progression of the follow-ups.

The O'Conor technique: the gold standard for supratrigonal vesicovaginal fistula repair.

PURPOSE: Several techniques have been used for repair of vesicovaginal fistula. Although surgical success is achieved in the majority of cases, a 4 to 35% failure rate occurs when a transvesical or transvaginal approach is used. We investigated the clinical efficacy of the O'Conor transperitoneal supravesical technique for supratrigonal vesicovaginal fistula. MATERIALS AND METHODS: A total of 29 patients with iatrogenic supratrigonal vesicovaginal fistula following hysterectomy or cesarean section were studied. An initial operation and prior attempts at fistula repair had been performed in 9 patients (34%) for benign (26) or malignant (3) uterine conditions. All patients were treated with the O'Conor technique 6 weeks to 48 months (median 8 weeks) after fistula diagnosis. RESULTS: The vesicovaginal fistula was successfully corrected in all patients at the first attempt and only 1 had stress urinary incontinence associated with urethral incompetence. No significant bladder dysfunction or decrease in bladder capacity was seen after repair. CONCLUSIONS: Considering the inferior clinical results of the transvaginal and transvesical approaches compared to the O'Conor technique for repair of supratrigonal vesicovaginal fistula, it would be unethical to conduct a randomized study to prove the superiority of the latter method. We suggest that the O'Conor technique be considered the gold standard surgical method of repair of supratrigonal vesicovaginal fistulas.

Sequential isologous organ transplantation in inbred rats: pancreaticoduodenal transplants.

A total of 847 inbred Lewis rats of mixed sex were used in this pancreaticoduodenal (Pd) donor aging study. Pd grafts were taken from 9- to 12-month-old donors and transplanted into 3-month-old recipients (thus, the first generation Pd graft, or 1 Pd). After 9 to 12 months, the same Pd grafts were again harvested and transplanted into 3-month-old rats (thus the 2 Pd generation). This cycle was repeated to obtain the 3, 4, and 5 Pd series. Sequential transplantation was able to extend the Pd grafts' mean survival time to 32 months for fourteen 4 Pd grafts, and to 39.2 months for four 5 Pd grafts (the longest lived graft survived for 42 months). The pancreas and duodenal sections of the grafts remained normal throughout the entire study. However, the aortic sections of the grafts (which were harvested to include the superior mesenteric and celiac arteries) all exhibited moderate to massive atherosclerotic changes by the 5 Pd mean survival age of 39.2 months. Such histological changes commenced even before 21 months of Pd graft age in some animals, gradually progressing to dilation of the aorta (and subsequent narrowing of aortic tributaries), as well as formation of an eggshell-like inner membrane shielding the aortic intima, by 42 months. Such atherosclerotic changes precluded transplantations beyond the 5 Pd series.

Female urethral syndrome. A female prostatitis?

The cause of the female urethral syndrome has previously been obscure, as it has been associated by definition with a lack of objective findings but a plethora of subjective complaints of retropubic pressure, dyspareunia, urinary frequency, and dysuria. There is now strong evidence that the microscopic paraurethral glands connected to the distal third of the urethra in the prevaginal space are homologous to the prostate. They stain histologically for prostate-specific antigen and, like the prostate, are subject to both infection and cancer. The most important aspect of recognizing this microscopic "female prostate" as an anatomic feature is that its infections may completely explain many cases of the urethral syndrome. Further, the diagnosis is not elusive if trained clinicians palpate for localized and objective paraurethral tenderness through the anterior vagina wall to one or both sides of the urethra. Treatment parallel to that for male prostatitis is usually rewarded by the elimination of symptoms and the objective finding of the loss of tenderness of the paraurethral glands. As with prostatitis, the localized problem often recurs. It is time to alert primary care physicians to this disorder and to eliminate the widespread practice of treating affected women with either invasive urethral dilation or tranquilizers.

Prostate specific antigen-alpha 2-macroglobulin complexes in prostate cancer patient sera.

Quantitative immunoblotting of prostate cancer patient sera revealed that most prostate specific antigen was in complexes with alpha 1-antichymotrypsin or alpha 2-macroglobulin with little of it being free antigen. Complexes of prostate specific antigen with these protease inhibitors in patient sera comigrated during electrophoresis with the respective purified complexes. Each complex was selectively removed from patient sera by absorption with specific antibodies. When prostate specific antigen was added to normal plasma, complexes with alpha 2-macroglobulin appeared first and after 1 hr, the distribution was approximately 40% free antigen, approximately 40% complexes with alpha 2-macroglobulin, and approximately 20% complexes with alpha 1-antichymotrypsin. These data show that prostate specific antigen reacts more readily with alpha 2-macroglobulin than with any other protease inhibitor in plasma and that the antigen complexes with alpha 2-macroglobulin in vivo in cancer patients.

Transplantation of reproductive organs.

A historical review of the literature concerning replantation and transplantation of reproductive organs has included studies from this laboratory, using rats, over the past 25 years. From the basic observation of ischemic and traumatic injury due to the transplantation, syngeneic testicle transplants, resulting in a partner's impregnation and histological restoration of the testicles, led to human testicular transplantation. As to the ovarian transplants, granulosa-theca cell tumors may transform into malignancies if followed for a prolonged period as intrasplenic ovaries, and high doses (15 to 20 mg/kg b.w.) of azathioprine can produce such malignant tumors in a shorter period. By caval-portal shunt, ovarian hormones enter directly into the portal blood stream and no typical granulosa-theca cell tumors were produced, owing to the fact that the liver cannot degrade all the hormones secreted by both ovaries. While en-bloc vagino-utero-ovarian transplantation in the rat is possible, no impregnation has been yet achieved. Finally, it is hypothesized that those who have acquired microsurgical techniques and have a full understanding of the anatomy of the reproductive system will not only be able to perform replantation of the penis, but also will be capable of allogeneic transplantation of genital organs, whether ethically approved or not, and sooner than one may think. In such cases a penile part may be obtained at a sex-change surgery or from a cadaveric donor, similar to other vital organ transplantation practices.

Autoantibodies in interstitial cystitis.

We have identified and partially characterized autoantibodies from the sera of patients with interstitial cystitis. Our characterization included initial screening by antinuclear antibody testing on human HEp-2 cell substrate and mouse kidney/stomach tissue substrate, titering and subtyping of positive sera, and Western blotting to identify target autoantigens. Of 96 interstitial cystitis patients 35 (36%) were positive for antinuclear antibodies at titers of 1/40 or greater. Among the antinuclear antibody patterns observed 24 were dense fine nuclear speckles, 7 were nucleolar, 3 were mitochondrial and 1 was coarse nuclear speckles. All but 4 of the antinuclear antibody positive sera were exclusively of the IgG class. As determined by unique antinuclear antibody staining patterns and by specificities on Western blots, interstitial cystitis autoantibodies appear to recognize novel autoantigens not previously described in patients with systemic autoimmune diseases, such as lupus, scleroderma and Sjögren's syndrome.

The natural history of interstitial cystitis: a survey of 374 patients.

A survey directed at determining the natural history of interstitial cystitis was conducted at our clinic. Information on demographics, risk factors, symptoms, pain and psychosocial factors was elicited from 374 patients who satisfied the National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases criteria for interstitial cystitis and had all been diagnosed as having interstitial cystitis by a urologist. With regard to demographics, patients were predominantly female (89.8%) and white (94.1%), with a mean age of 53.8 +/- 0.7 years (standard error) and age at the first symptoms of 42.5 +/- 0.8 years. Information on 25 potential risk factors included 44.4% of the women reporting hysterectomy, 38.2% of the patients having strong sensitivities or allergic reactions to medication and only 2.7% being diabetic. With regard to interstitial cystitis symptoms, frequency and urgency were reported by 91.7% and 89.3% of the patients, respectively, while pelvic pain, pelvic pressure and bladder spasms were reported by more than 60% of respondents and burning by 56%. Location and degree of pain were also reported. Urination relieved or lessened interstitial cystitis pain for 73.6% of the patients and medication was effective for 46.8%. Other behaviors (for example hot baths, heating pads, lying down or sitting) were less effective. Conversely, stress, constrictive clothing and intercourse increased interstitial cystitis pain in more than 50% of the patients. In addition, acidic, alcoholic or carbonated beverages, and coffee or tea increased interstitial cystitis pain in more than 50% of the patients. More than 60% of the patients were unable to enjoy usual activities or were excessively fatigued and 53.7% reported depression. Travel, employment, leisure activities and sleeping were adversely affected in more than 80% of the patients. Pain location and degree differed significantly between patients with and without ulcers in the bladder. In addition, there was an apparent plateau in the frequency and urgency among patients after approximately 5 years with symptoms.

Effect of caval-portal shunt on ovarian tissue in rats: I. Histological observation.

Forty-three female Sprague Dawley rats were divided into five groups, with groups 1-4 subjected to end-to-side caval-portal shunt (CPS). In addition to CPS, group 1 (n = 13), group 2 (n = 10), and group 3 (n = 7) rats had undergone removal of the right ovary and one-half of the left ovary, the left ovary, and one-half of the left ovary, respectively. Group 4 (n = 6) rats were not subjected to ovariectomy. Group 5 (n = 7) animals were not subjected to CPS but underwent left ovarian hemiresection. The ovarian volume of the hemiresected ovaries increased to 393.00 +/- 4.83 mm3 and 126.00 +/- 44.3 mm3 from 18.40 +/- 0.54 mm3 and 18.40 +/- 0.59 mm in groups 1 and 3, respectively, at the end of three postoperative months. The nonresected ovaries enlarged to 339.98 +/- 5.09 mm3 and 226.3 +/- 46.2 mm3 from 36.79 +/- 1.09 mm3 in groups 2 and 3, respectively. When no ovaries were resected, the CPS animals in group 4 showed an increment of ovarian volume of 1.75-2.2 times as much as the preoperative ones. In the animals that had undergone simple hemiovariectomy (group 5), the contralateral ovaries showed a significant increase in volume (40.2 +/- 8.3 mm3 to 243.1 +/- 114.8 mm3) at 3 months. The hemiresected ovarian volume increased from 27.1 +/- 5.5 mm3 to 44.1 +/- 11.8 mm3.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

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.