Early chemokine cascades in murine cardiac grafts regulate T cell recruitment and progression of acute allograft rejection.

The identification of early inflammatory events after transplant in solid tissue organ grafts that may direct T cell recruitment and promote acute allograft rejection remain largely unknown. To better understand temporal aspects of early inflammatory events in vascularized organ grafts, we tested the intragraft expression of four different chemokines in heterotopically transplanted A/J (H-2(a)) and syngeneic heart grafts in C57BL/6 (H-2(b)) recipient mice from 1.5 to 48 h after transplant. Similar temporal expression patterns and equivalent levels of chemokine expression were observed in both syngeneic and allogeneic cardiac allografts during this time period. Expression of the neutrophil chemoattractant growth-related oncogene alpha (KC) was observed first and reached peak levels by 6 h after transplant and was followed by the monocyte/macrophage chemoattractant protein-1 (JE) and then macrophage inflammatory proteins 1beta and 1alpha. Administration of rabbit KC antiserum to allograft recipients within 30 min of cardiac transplantation attenuated downstream events including intra-allograft expression of the T cell chemoattractants IFN-gamma-inducible protein-10 and monokine induced by IFN-gamma, cellular infiltration into the allograft, and graft rejection. Similarly, depletion of recipient neutrophils at the time of transplantation significantly extended allograft survival from day 8 to 10 in control-treated recipients up to day 21 after transplant. These results indicate the induction of highly organized cascades of neutrophil and macrophage chemoattractants in cardiac grafts and support the proposal that early inflammatory events are required for optimal recruitment of T cells into allografts during the progression of acute rejection of cardiac allografts.

Long-term continence and patient satisfaction after artificial sphincter implantation for urinary incontinence after prostatectomy.

PURPOSE: We assess long-term continence and patient satisfaction after implantation of the AMS Sphincter 800 (American Medical Systems, Minnetonka, Minnesota) in men who were incontinent after total and subtotal prostatectomy. MATERIALS AND METHODS: Patients who had an artificial urinary sphincter implanted for urinary incontinence after prostatectomy and a minimum of 20 months of followup were identified from a patient database. The medical records of these 209 patients were reviewed, and a questionnaire was mailed. Telephone contact was attempted with patients who did not respond to the questionnaire. Of the 209 patients 11 (5%) had undergone device removal, 34 (16%) were deceased and an additional 51 (24%) could not be contacted for followup. Our study group consisted of the 113 patients with artificial urinary sphincters who could be contacted for followup. Mean followup was 73 months (range 20 to 170). RESULTS: There were 4 (4%) patients who were dry and continent and 68 (60%) were incontinent using 0 to 1 pad daily. An additional 35 (31%) patients required 2 to 3 pads daily and 5 (4%) used more than 3 daily. There were 14 (12%) patients who had undergone surgical revision of the device. Of the 113 patients 31 (28%) were very satisfied, 50 (45%) satisfied, 20 (18%) neutral, 7 (6%) dissatisfied and 4 (4%) very dissatisfied. One patient was not using his device to control continence. CONCLUSIONS: Artificial urinary sphincter implantation offers men who are incontinent after prostatectomy a reasonable chance for obtaining long-term satisfactory urinary control, although complete continence is unusual.

Cryptococcal meningitis in renal transplant patients associated with environmental exposure.

Fungal infections in renal transplant recipients are less common than bacterial infections; however, the morbidity from fungal infections is high. There is limited information in the literature concerning post-transplantation cryptococcal infection due to environmental exposure of patients living in high-risk areas. We report three patients who were diagnosed with cryptococcal meningitis after kidney transplantation. Cryptococcal titers prior to transplant surgery were negative in all three patients. These patients all lived in rural areas and demonstrated evidence of environmental exposure leading to subsequent cryptococcal meningitis. All patients had exposure to pigeon and chicken excreta and, after treatment, two patients are alive and well with excellent allograft function. The third patient has marginal renal function but is currently not on dialysis. Early diagnosis is essential for salvage from these potentially lethal infections. Intense headache was a prominent feature in the clinical presentation of our patients, and should signal the need for early sampling and culture of spinal fluid. Meningismus was not present in any of our patients, even when other systemic symptoms were identified. We recommend a high index of suspicion post-transplantation for all patients who may have environmental or occupational exposure to cryptococcus. If infection is detected quickly and treatment instituted promptly, patient recovery and allograft survival are possible. Long-term therapy with fluconazole, a non-nephrotoxic agent, should permit eradication of the infection with preservation of kidney function.