Bilateral axillary metastases of occult breast carcinoma: report of a case with a review of the literature.

The case of a 47-year-old premenopausal woman is presented in whom axillary lymph node metastases occurred on both sides 3 years apart although no primary tumor was detectable in either breast is presented. An overview of the literature on this rare entity is given. Patients with occult breast carcinoma with axillary lymph node metastases should have a complete physical examination, radiologic analysis (mammography, ultrasonography, and MRI of both breasts) and screening for disseminated disease. If there is no evidence of a primary tumor and metastases other than in the axilla, an axillary dissection should be carried out. In addition, the patient should be offered the choice of irradiation of the breast or mastectomy. Postoperatively, patients should receive appropriate systemic therapy tailored to their age, menopausal status, and receptor status.

Prolongation of canine renal allograft survival. A study on the effect of donor pretreatment.

Treatment of kidney donors with procarbazine hydrochloride and methylprednisolone, respectively, 5 and 2 1/2 hr before harvesting the kidney, improved renal allograft survival in dogs significantly. Pretreatment of the donor did not have a deleterious effect on the early function of the kidney grafts. Donor blood transfused peroperatively into the recipient caused a significant reduction in survival of kidney grafts from pretreated donors, although it did not influence the survival of nontreated kidneys. Furthermore, it appeared that a peroperative injection of a suspension of nonirradiated donor lymphocytes as well as donor lymphocytes irradiated with 2,500 rad significantly decreased the survival time of pretreated kidneys. A peroperative transfusion of leukocyte-poor blood prepared with a leukocyte filtration column, which leaves erythrocytes, thrombocytes, and plasma and eliminates most of the leukocytes (99.9%), also abolished the effect of donor pretreatment. Thus, administration of donor blood constituents, whether lymphocytes or leukocyte-poor blood, can abrogate the beneficial effect of donor pretreatment on kidney graft survival. These data indicate that the effect of donor lymphocytes on the survival of pretreated kidneys is not because of a specific immunological activity of these lymphocytes but merely because of the presence of antigens on their cell surface.

Effect of blood transfusions on canine renal allograft survival.

In this study significantly prolonged canine renal allograft survival has been demonstrated after transfusion of 100 ml of third-party whole blood given peroperatively. Peroperative transfusions of third-party leukocyte-free blood or pure lymphocyte cell suspensions did not influence graft survival. Furthermore, no improvement in graft survival has been found after a peroperative transfusion of irradiated whole blood (2500 rad). These data suggest that delayed graft rejection after blood transfusions can only be expected after the administration of whole blood. The role of competent lymphocytes in whole blood is questionable, since a transfusion or irradiated whole blood in combination with nonirradiated lymphocytes did not lead to prolonged graft survival. Immunosuppression of the recipient directly after transfusion seems to be essential to induce the beneficial effect of blood transfusions. This has been demonstrated for a transfusion of whole blood 14 days before transplantation. A single transfusion of 100 ml of whole blood 14 days before transplantation could effectively prolong graft survival if immunosuppression with azathioprine and prednisone was started on the day of transfusion. No improvement in graft survival has been found with such a transfusion if preoperative immunosuppression has been omitted.

Lymphocyte stimulation by canine kidney cells.

Lymphocyte stimulation in mixed kidney cell-leukocyte cultures (MKLC) has been investigated in a canine model. Canine kidney cells were obtained by perfusion trypsinization. Cultured kidney cells, which appeared to be of epithelial origin by several criteria, have been used as stimulator cells. Maximal stimulation was obtained in the MKLC and mixed leukocyte culture (MLC) at stimulator to responder (S:R) cell ratios of 1:20 and 1 1/2:1, respectively. Lymphocyte proliferation has been observed in cultures with kidney cells in S:R cell ratios lower than 1:20. Stimulation has not been observed in MLCs at these low ratios. The addition of graded numbers of kidney cells of the responder to a one-way MLC inhibited the response gradually. The fact that kidney cells have both strong stimulator capacities and inhibitor capacities could explain the lower optimal S:R ratio. Lymphocyte stimulation has not been obtained in mixed kidney leukocyte cultures between major histocompatibility complex (MHC)-identical closely bred animals. The nature of the antigens present on canine kidney epithelial cells stimulatory to allogeneic lymphocytes is discussed.

A study on the mechanism of donor pretreatment: effect of procarbazine hydrochloride and methylprednisolone in immunocompetent cells.

Significantly prolonged canine renal allograft survival can be obtained by donor pretreatment with procarbazine hydrochloride and methylprednisolone. This is thought to be caused either by a reduced antigenicity of the graft or by a local immunosuppressive effect by drugs transplanted with the graft. In this study a decrease in the number of peripheral donor T and B lymphocytes was observed at the time of procuring. Leukocytes harvested from dogs pretreated with a combination of procarbazine hydrochloride and methylprednisolone showed a decrease in their ability either to stimulate or respond to mixed leukocyte cultures (MLCs). Complete restoration of MLC responses was obtained however by purification and washing of these leukocytes. Sera of pretreated animals were not able to reduce MLC responses. It was concluded that drug metabolites in or on the cells were apparently responsible. A local inhibition of the immunocompetence of host lymphocytes by small amounts of transplanted drug metabolites in or on the graft cells might be responsible for the beneficial effect of donor pretreatment with procarbazine hydrochloride and methylprednisolone. Furthermore, this postulation explains the abrogation of prolonged survival of pretreated grafts after systemic administration of nontreated donor blood or donor leukocyte-free blood, as we reported earlier.

In vitro stimulation of lymphocytes by vascular endothelial cells. A study with canine arterial and venous endothelial cells.

Data are presented on the ability of arterial and venous endothelial cells to stimulate allogeneic leukocytes. Mixed cultures of allogeneic endothelium and lymphocytes result in proliferation of lymphocytes and generation of cell-mediated cytotoxicity, which do not occur in cultures of syngeneic combinations of endothelium and lymphocytes. Studies of kinetics showed a peak in proliferation at days 6-7. The optimal responder-stimulator ratio appeared to be 15:1. Lymphocytes stimulated with venous endothelial cells were cytotoxic both for arterial and for venous endothelial cells and PHA blasts of the stimulator dog, whereas lymphocytes stimulated with arterial endothelial cells lysed only arterial endothelial cells and PHA blasts of the stimulator. Lysis of syngeneic or third-party allogeneic control targets was virtually absent. Optimal conditions for long-term culture of effector cells from mixed leukocyte endothelial cell cultures were analyzed. Addition of Il 2 every 3 days and the original stimulating antigen every 6 days permitted continuous proliferation of these cytotoxic lymphocytes with preservation of the cytotoxicity pattern.

Limiting dilution analysis of canine alloantigen-reactive T lymphocytes.

A sensitive limiting dilution assay for the determination of canine cytotoxic T lymphocyte precursors (CTL-P) has been developed. Murine second MLC supernatant as a source of Interleukin 2 (IL 2) was used to expand stimulated CTL-P to numbers that were easily detectable with the classic 51Cr lysis assay. The frequencies of CTL-P that reacted to allogeneic stimulator cells in canine peripheral blood ranged from 1:1000 to 1:2000 lymphocytes. During in vitro stimulation in a mixed leukocyte culture a rapid increase in frequency was noted, and at day 7 a frequency as high as 1:5.4 was found. The presence of irradiated stimulator cells during limiting dilution culture restricted proliferation of the CTL-P; only those which recognized the stimulator cells proliferated. The determination of cytotoxicity in large numbers of individual microcultures with CTL-P seeded at clonal conditions toward 2 allogeneic target cells permitted quantitation of the frequency of CTL-P with specificity for different alloantigens. These techniques greatly facilitate monitoring of cellular immune reactions after renal allografting because both determination of the influence of cytostatic drug treatment on CTL-P frequency, and analysis of the specificity and function of allograft infiltrating cells are now possible.

Cell-mediated cytotoxicity toward canine kidney epithelial cells.

Cellular cytotoxicity toward kidney cell targets has been studied in a model using in vitro cultured canine kidney cells obtained after perfusion trypsinization of kidneys from one-haplotype-mismatched beagles. To study whether cytotoxic effector cells recognize identical antigens on kidney cells as on phytohemagglutinin (PHA)-stimulated lymphoblasts, adsorption studies with different monolayers have been performed. Both leukocyte and kidney cell monolayers reduced cytotoxicity against 51Cr-labeled PHA-stimulated lymphoblasts very effectively. The average reduction of cytotoxicity was 86% in six consecutive experiments after one adsorption on either one of these two types of target-specific monolayers. Nonspecific monolayers reduced cytotoxicity only for 13%. Specific kidney cell monolayers reduced cytotoxicity against kidney cells almost completely, however leukocyte monolayers reduced cytotoxicity toward kidney cells for only 40%. There results and cold target inhibition data strongly suggest that kidney cells present antigens to which a selective population of cytotoxic T lymphocytes (CTLs) is directed. These CTLs are not cytotoxic for PHA-stimulated lymphoblasts. It is discussed whether the relevant antigens on the kidney cells are organ-specific antigens comparable to the endothelial monocyte antigen system as described by Moreas and Stastny or that class II antigens are involved in cytotoxicity toward kidney cells.

Analysis of buoyant density of canine peripheral blood leukocytes with PVP-Silica (Percoll) density gradients.

Isolation of canine peripheral blood mononuclear cells with a one step centrifugal separation procedure has not been very successful sofar. Significant contamination with polymorphonuclear cells has been reported. An analysis of the buoyant density of canine peripheral blood leukocytes on a self-generating Percoll gradient showed that the buoyant densities of polymorphonuclear cells and lymphocytes are so near that separation with high purity and yield is not possible with the use of a density gradient. Transient changes in buoyant density of polymorphonuclear cells have been observed. In such situations differences in buoyant density between cell types have been observed which permit separation of mononuclear cells from polymorphonuclear cells at a reasonable yield.

Hip fracture surgery and performance indicators: an analysis of 941 patients operated in a large teaching hospital.

BACKGROUND: In the Netherlands, two performance indicators for the treatment of hip fracture patients have been recently implemented. Both indicators state that surgery within 24 h after admission improves the outcome with regard to 1-year mortality and the amount of re-operations within 1 year. To determine the value of these performance indicators, we conducted a retrospective analysis of 941 hip fracture patients. METHODS: In the period from January 2003 to December 2006, a total of 941 consecutive hip fracture patients were included in this study. We determined the amount of re-operations and the mortality at 1 year after surgery. From June 2005 to December 2006, we could determine whether patients were operated on within 24 h after admission. In this group of 379 patients, we determined if there were differences in the 1-year mortality and the number of re-operations at 1 year with regard to the time window in which these patients were operated on (<24 h or >24 h). RESULTS: Our overall mortality rate at 1 year is 21% (202 patients) and the amount of re-operations within 1 year is 8% (77 procedures). In our subgroup analysis, we found no significant difference in mortality or re-operations if patients were operated on within 24 h or not (number needed to treat of 59 and -31, respectively). CONCLUSION: We conclude that hip fracture surgery within 24 h does not provide significantly better results in terms of 1-year mortality and the amount of re-operations within 1 year.

Modification of kidney graft survival in dog and man by pre-operative transfusion to the donor.

The present experiments indicate that the transplantation reaction is not solely caused by immunocompetent cells of the recipient, but also by immunocompetent cells in the donor organ. Immunisation of the donor did modify the immune response as demonstrated with kidney grafts in rat, dog and man. In the dog prolonged kidney graft survival by one peroperative blood transfusion was reduced to control level by transfusion of the donor on day -1 with 100ml third party blood. In the rat third party blood transfusion to the donor reduced kidney graft survival significantly, but donor pretreatment with recipient lymphocytes induced significantly prolonged survival. This suggests that the modification of graft survival by donor transfusion is an immunological phenomenon. Immunisation of the donor with recipient cells may induce specific immunoreactive cells in the graft that causes a local graft versus host reaction, which inhibits the rejection reaction. In man 44 recipients were studied who only received blood peroperatively. Significantly impaired graft survival was noted if the donor was not transfused, resulting in 19% 3-month kidney function, versus 61% with transfused donors.

Randomized clinical trial of non-mesh versus mesh repair of primary inguinal hernia.

BACKGROUND: The optimum method for inguinal hernia repair has not yet been determined. The recurrence rate for non-mesh methods varies between 0.2 and 33 per cent. The value of tension-free repair with prosthetic mesh remains to be confirmed. The aim of this study was to compare mesh and non-mesh suture repair of primary inguinal hernias with respect to clinical outcome, quality of life and cost in a multicentre randomized trial in general hospitals. METHODS: Between September 1993 and January 1996, all patients scheduled for repair of a unilateral primary inguinal hernia were randomized to non-mesh or mesh repair. The patients were followed up at 1 week and at 1, 6, 12, 18, 24 and 36 months. Clinical outcome, quality of life and costs were registered. RESULTS: Three hundred patients were randomized of whom 11 were excluded. Three-year recurrence rates differed significantly: 7 per cent for non-mesh repair (n = 143) and 1 per cent for mesh repair (n = 146) (P = 0.009). There were no differences in clinical variables, quality of life and costs. CONCLUSION: Mesh repair of primary inguinal hernia repair is superior to non-mesh repair with regard to hernia recurrence and is cost-effective. Postoperative complications, pain and quality of life did not differ between groups.