Pathogenesis and biological significance of seminal vesicle invasion in prostatic adenocarcinoma

Seminal vesicle invasion and the percentage involvement by cancer of each seminal vesicle were related to cancer volume, quantitative histological grade and presence or absence of lymph node metastases in 243 radical prostatectomy specimens. There were 47 prostates with seminal vesicle invasion. Frequency and extent of seminal vesicle invasion were strongly correlated with cancer volume, with minimal invasion noted in only 6% of the cases less than 4 cc. The relationship of seminal vesicle invasion to lymph node metastasis was statistically significant but cancer volume and histological grade were much stronger predictors of lymph node metastasis. The route of invasion from the prostate in 46 cases involved direct tumor spread into the midbase region near the ejaculatory ducts. Seminal vesicle invasion often may not be identified if the tissue nearest the ejaculatory ducts at the prostate base is not sampled.     

Long-term followup of subclinical human papillomavirus infection treated with the carbon dioxide laser and intraurethral 5-fluorouracil: a treatment protocol

We evaluated 162 high risk male patients for the presence of subclinical anogenital human papillomavirus infection with magnified penile surface scanning. Infected patients were treated as outpatients with the carbon dioxide laser under local anesthesia. Of the patients 43 were followed for a mean of 8.7 months or 2.1 treatments after the initial treatment (range 3 to 30 months). A subset of 10 patients was followed for more than 20 months or 6.2 treatments. To date a 51% recurrence rate has been observed in the over-all population and a 50% recurrence rate was noted in the 20-month followup population. In a separate arm of this study a small number of patients (15) with deoxyribonucleic acid typed subclinical intraurethral disease plus subclinical skin lesions were treated with topical carbon dioxide laser therapy for the penile lesions and adjuvant intraurethral 5% 5-fluorouracil. Mean followup in the group was approximately 4 months. The addition of intraurethral therapy in this positive human papillomavirus reservoir group had no significant effect on the high rate of human papillomavirus recurrence.     

Correction of immunologic disorders in patients with burns

Addition of immunomodulating therapy with Thymalin, a thymus agent, to the multimodality therapy of burnt patients contributes to a rapid normalization of immunological parameters. The most marked immune response was observed 7-10 days after a therapy course initiated in the early periods of burn disease in patients with severely depressed T-system immunity and a high sensitivity to the drug. Inclusion of a donor blood leukomass transfusion course activates the cellular link of the immune system just after the treatment course, but fails to favour a stable normalization of thymus-dependent lymphocyte ratios.     

Early postoperative rejection crises after transplantation of the kidney from the living related donors

The frequency of the development of rejection crises in the early postoperative period in 32 recipients of allogeneic kidneys from alive related donors was analysed depending on the histocompatibility according to the antigens of the HLA-AB system and the nature of the immunosuppressant therapy. The results of the analysis showed that the frequency of rejection crises was 100% when the donor and recipient were compatible in 1-2 antigens, and 40% in compatibility according to 3-4 antigens. The incidence of rejection crises was 71.4% among patients who received the standard immunosuppressant therapy (corticosteroids + azathioprine) and 36% among those given also sandimmune. Analysis of the frequency of rejection crises according to the ABO blood group system to which the donor-recipient pair occurred, showed that rejection crises occurred most frequently among patients with A (II) blood group.     

State of natural killer cells after surgical treatment of oncologic patients

In 53 patients with gastric and intestinal cancer, the content and functional activity of the natural killer cells was studied. The suppression of these indices at the first days after the operation, and restoration of their preoperative levels within 2-2.5 weeks was noted.     

The role of CD4+ helper T cells in the destruction of microencapsulated islet xenografts in nod mice

Islet transplants for large numbers of patients with diabetes will require xenografts. Microencapsulation is an appealing method for islet xenografting. However, graft function has been limited by a cellular reaction, particularly intense in spontaneously diabetic, NOD mice. The purpose of this study was to elucidate the mechanism of this reaction. Poly-1-lysine-alginate microcapsules containing 4000-12,000 dog or 1800-2000 rat islets were xenografted intraperitoneally into streptozotocin (SZN)-diabetic C57BL/6J and NOD mice, with or without recipient treatment with GK 1.5 (anti-CD4 monoclonal antibody) (20-30 microliters i.p. every 5 days, begun on day -7. Grafts were considered technically successful if random blood glucose (BG) was normalized (less than 150 mg/dl) within 36 hr. Graft failure was defined as BG greater than 250 mg/dl. Dog and rat islets in microcapsules normalized BG in both SZN and NOD mice within 24 hr routinely. Empty microcapsules and GK 1.5 treatments alone did not affect BG. NODs destroyed both microencapsulated dog and rat islets more rapidly than did SZN-diabetic mice (P less than .01). Graft biopsies showed an intense cellular reaction, composed of lymphocytes, macrophages and giant cells, and no viable islets. GK 1.5 treatment significantly prolonged both dog-to-NOD and rat-to-NOD grafts (P less than 0.01). Biopsies of long-term functioning grafts (on days 65-85) demonstrated viable islets and no cellular reaction around microcapsules; 1/4 rat and 1/8 dog islet xenografts continued to function indefinitely in NOD recipients, even after cessation of GK 1.5 therapy. Prediabetic NODs receiving encapsulated dog or rat islets mounted a moderate cellular reaction to grafts. Empty microcapsules excited no cellular reaction in diabetic or prediabetic NODs. We conclude that the NOD reaction to microencapsulated xenogeneic islets is helper T cell-dependent, and that the target of this reaction is not the microcapsule itself, but the donor cells within.     

Increase in survival time of liver transplants by protease inhibitors and a calcium channel blocker, nisoldipine

Kupffer cells are activated by calcium and release a variety of toxic mediators, including proteases. The purpose of these studies, therefore, was to determine if protease inhibitors and a calcium channel blocker could increase survival time in the rat model of orthotopic liver transplantation. Survival for 30 days was greater than 90% in this model when livers were stored for 1 hr in Ringer's solution (survival conditions)--however, grafts stored for 4 hr in Euro-Collins solution or 8 hr in University of Wisconsin (UW) solution survived postoperatively only 1.2 and 0.7 days, respectively (nonsurvival conditions). When livers were stored for 4 hr in Euro-Collins containing a cocktail of protease inhibitors (leupeptin, pepstatin A, phenylmethylsulfonyl fluoride, 20 ng/ml each; diisopropyl fluorophosphate, 100 microM) and subsequently transplanted, however, survival time was increased significantly to 11.5 days. Inclusion of a calcium channel blocker, nisoldipine (1.4 microM), in the protease inhibitor cocktail increased survival time to 23 days. Actually, nisoldipine alone increased survival time to 25 days. Nisoldipine alone also increased survival time in livers stored for 8 or 16 hr in UW solution to between 15 and 20 days. Serum transaminase levels reached peak values greater than 2400 U/L one day postoperatively in the nonsurvival groups, and liver injury assessed histologically was apparent. Under these conditions, pulmonary infiltration of inflammatory cells was observed in about 60% of the lungs examined and was associated with massive bleeding. Inclusion of the protease cocktail, nisoldipine, or both in the storage solutions decreased maximal SGOT levels and injury to both liver and lung significantly by about 50% postoperatively. Nisoldipine also decreased phagocytosis of carbon particles by the perfused liver 2- to 3-fold following storage under nonsurvival conditions (half-maximal effect = 0.3-0.4 microM nisoldipine). Moreover, nisoldipine improved hepatic microcirculation. It accelerated blood flow into the liver, as indexed by hemoglobin reflectance from the liver surface. These data support the hypothesis that Kupffer cells are activated early in the sequence of events that causes graft failure leading to endothelial cell-mediated alterations in the microcirculation. This work demonstrates clearly that dihydropyridine-type calcium channel blockers such as nisoldipine may be clinically useful in storage solutions for liver prior to transplantation.