Peter Madras | Massachusetts Institute of Technology (MIT) (original) (raw)

Papers by Peter Madras

Transplantation Proceedings, 1997

Transactions - American Society for Artificial Internal Organs, 1980

Surgery, 1982

With better survival and extended indications for renal transplantation, it is anticipated that t... more With better survival and extended indications for renal transplantation, it is anticipated that the problem of aortoiliac disease in the posttransplant patient will be seen with increasing frequency. Two patients requiring aortoiliac reconstruction were successfully managed with improvement in graft function after surgery. One patient manifested atheroembolism resulting from aortoiliac occlusive disease; the other had a 2 cm rupture in an aortic aneurysm, which resulted in a large retroperitoneal hematoma, but without frank shock. Perfusion of the transplanted kidney was maintained by the use of a temporary axillofemoral graft, which was removed following aortoiliac repair. The use of this technique involves minimal physiologic disturbance to the patient and the renal graft and allows conventional aortoiliac reconstruction.

Transplantation Proceedings, 1998

Transplantation, 1997

Changes in creatine phosphate, inorganic phosphate, and the purine pattern in dog hearts with tim... more Changes in creatine phosphate, inorganic phosphate, and the purine pattern in dog hearts with time of coronary artery occlusion and effect thereon of mioflazine, a nucleoside transport inhibitor. Cardiovasc Res 1986: 20: 658. 35. Nees S. The adenosine hypothesis of metabolic regulation of coronary flow in the light of newly recognized properties of the coronary endothelium.

Transplantation, 1997

Refractory rejection and cyclosporine (CsA)-induced nephropathy remain important causes of renal ... more Refractory rejection and cyclosporine (CsA)-induced nephropathy remain important causes of renal allograft loss. Previous studies demonstrated that 70-85% of the episodes of refractory acute rejection (AR) occurring in renal allograft recipients on a CsA-based immunosuppressive regimen could be salvaged by conversion to tacrolimus. No data are available regarding the correlation between allograft histology at the time of conversion and the response to tacrolimus. We examined the response to tacrolimus conversion in relation to preconversion biopsies stratified by the Banff criteria. Since May 1992, we have converted 22 patients from CsA to tacrolimus as part of a rescue protocol. We report on 18 patients in whom 6-month follow-up was available after conversion for biopsy-proven AR (n=13) or CsA toxicity (n=5). Sixteen patients were recipients of renal allografts, including three second transplants, and two were recipients of kidney-pancreas transplants. All patients with AR were treated with one or more courses of methylprednisolone and OKT3 before conversion. Renal allograft biopsies were interpreted by a transplant pathologist blinded to the clinical history, and graded according to the Banff criteria. Responses to tacrolimus were scored as improved (creatinine returned to within 150% of baseline), stabilized (creatinine rise arrested), or failed (returned to dialysis). RESULTS; Mean follow-up was 17.3+/-8 months. Fourteen of 18 patients (78%) showed improvement or stabilization in renal function as assessed by creatinine at 6 months or 1 year (when available). Of the 13 patients with histological AR, nine (69%) improved, including five of six with borderline AR, two of three with grade I AR, and two of four with grade II AR. Of the four other patients with AR, two stabilized and two failed. Three of five patients with severe clinical rejection requiring dialysis (range 2-16 weeks) recovered renal function after conversion. Of five patients with CsA toxicity, two (40%) improved. Seven of eight patients who were converted to tacrolimus less than 90 days after transplantation improved, compared with only 4 of 10 who were converted more than 90 days after transplantation. No grafts were lost in patients with a creatinine <3.0 mg/dl at the time of conversion versus two of seven grafts lost when the creatinine was 3.1-5.0 mg/dl and two of eight grafts lost when the creatinine was >5.0 mg/dl. The majority of steroid and antilymphocyte antibody (OKT3 or ATGAM) unresponsive rejections in patients on CsA-based immunosuppression will improve or stabilize after conversion to tacrolimus. There was no correlation with allograft histology stratified by the Banff criteria and the response to tacrolimus. Although there was a trend toward a poorer response with more severe histological rejection, higher serum creatinine at the time of conversion, and longer time from transplantation to conversion, favorable responses were noted in all groups. This indicates that a trial of conversion is warranted, irrespective of the histological severity of injury.

Kidney International, 2000

Journal of Biomedical Materials Research, 1984

The activation of the rabbit complement system by each of three different synthetic materials is ... more The activation of the rabbit complement system by each of three different synthetic materials is reported. Samples of each primed, there was no correlation of the amount of complement activation with the critical surface tension of the material.

JAMA: The Journal of the American Medical Association, 1981

A 33-year-old man with a nonatherosclerotic vasculopathy of undetermined origin had progressive o... more A 33-year-old man with a nonatherosclerotic vasculopathy of undetermined origin had progressive occlusive disease of the lower limb vessels. The resultant severe rest pain and ischemic ulceration of his foot were inoperable and unresponsive to conventional drug therapy. Treatment was begun with intra-arterially administered alprostadil (prostaglandin E1), a vasodilator and inhibitor of platelet aggregation. Although immediate benefit was equivocal, his rest pain had disappeared six weeks after infusion, and the ischemic ulcer almost healed completely. Blood flow studies showed increased flow to the feet, consistent with the subjective improvement. The beneficial effect of alprostadil suggests that further studies with this agent are warranted for patients with nonatherosclerotic vasculopathy.

BJU International, 2012

What&... more What's known on the subject? and What does the study add? Lumagel™ is a reverse thermosensitive polymer (RTP) that has previously been described in the literature as providing temporary vascular occlusion to allow for bloodless partial nephrectomy (PN) while maintaining blood flow to the untargeted portion of the kidney. At body temperature, Lumagel™ has the consistency of a viscous gel but upon cooling rapidly converts to a liquid state and does not reconstitute thereafter. This property has allowed for it to be used in situations requiring temporary vascular occlusion. Previous experience with similar RTPs in coronary arteries proved successful, with no detectable adverse events. We have previously described our technique for temporary vascular occlusion of the main renal artery, as well as segmental and sub-segmental renal branches, to allow for bloodless PN in either an open or minimally invasive approach. These experiments were performed in the acute setting. This study is a two-armed survival trial to assess whether this RTP is as safe as hilar clamping for bloodless PN. Surviving animals showed normal growth after using the RTP, absence of toxicity, no organ dysfunction, and no pathological changes attributable to the RTP. We conclude that Lumagel™ is as safe as conventional PN with hilar clamping, while adding the advantage of uninterrupted perfusion during renal resection. To examine whether randomly selected regions of the kidney could undergo temporary flow interruption with a reverse thermosensitive polymer (RTP), Lumagel™ (Pluromed, Inc., Woburn, MA, USA), followed by partial nephrectomy (PN), without adding risks beyond those encountered in the same procedure with the use of hilar clamping. A two-armed (RTP vs hilar clamp), 6-week swine survival study was performed. Four swine underwent PN using hilar clamps, while six underwent PN with flow interruption using the RTP. The RTP, administered angiographically, was used for intraluminal occlusion of segmental or subsegmental arteries and was compared with main renal artery clamping with hilar clamps. The resection site was randomized for each swine. Laboratory studies were performed preoperatively, and at weeks 1, 3 and 6. Before killing the swine, repeat angiography was performed with emphasis on the site of previous flow interruption. Gross and microscopic examination of kidney, liver, lung, heart, skeletal muscle was later performed, and the vessel that had supported the previous plug was examined. All animals survived. No abnormal chemistry or haematology results were encountered over the 6 weeks. There were no surgical complications in either group. Using angiography we found 100% patency of vessels that had been occluded with the polymer 6 weeks previously for PN. The only gross or microscopic abnormalities were related to the renal resection and scar formation, and were similar in the two groups. Targeted flow interruption with the RTP added no additional risk to PN while allowing bloodless resection and uninterrupted flow to untargeted renal tissue.

Artificial Organs, 1981

The Stagnation Point Flow Experiment is a popular means for studying blood-surface interactions i... more The Stagnation Point Flow Experiment is a popular means for studying blood-surface interactions in a surface strain rate gradient. The strain rate distribution on the test surface of the flow chamber used in this experiment was originally assumed to be simply proportional to the radial distance from the stagnation point. A numerical simulation of the flows through the five most frequently used chambers shows that this is true only for one of the chambers, approximately so for another, and not true for the other three. An additional numerical simulation indicates the blood should purge the saline priming liquid within a few seconds at the beginning of the experiment.

Archives of Surgery, 1998

To assess donor morbidity, recipient outcome, and changing trends during the past decade in donor... more To assess donor morbidity, recipient outcome, and changing trends during the past decade in donor nephrectomy for living-donor kidney transplantation. Design and Setting: Retrospective review at an academic tertiary care referral center.

Archives of Surgery, 1991

American Journal of Transplantation, 2002

Renal allograft recipients with thrombophilia (a hypercoagulable state) are at higher risk for ea... more Renal allograft recipients with thrombophilia (a hypercoagulable state) are at higher risk for early allograft loss. Following an episode of allograft renal vein thrombosis in a patient subsequently diagnosed with protein C deficiency, we adopted universal screening for hypercoagulable risk factors. Patients with a history of a thromboembolic event underwent laboratory screening for thrombophilia. Eight patients with a defined hypercoagulable disorder or a strong clinical history of thrombosis even in the absence of hematologic abnormalities were treated with anticoagulation following renal transplantation. We reviewed the outcomes of these eight patients and all renal transplant recipients at our center who developed thrombotic complications after renal transplantation. Since the introduction of universal screening for hypercoagulable risk factors, 235 consecutive transplants were performed without allograft thrombosis. Eight patients with evidence of thrombophilia, recognized before renal transplantation, received perioperative heparin and postoperative oral anticoagulation. Two of these eight patients developed perinephric hematomas requiring evacuation, blood transfusion, and temporary withholding of anticoagulation. Of interest, two of the remaining 227 patients, not identified with thrombophilia before surgery, developed thrombotic complications after renal transplantation. A hypercoagulable disorder was subsequently documented in each. Identifying patients with thrombophilia before transplantation and defining their management presents many challenges. The risk of allograft thrombosis must be weighed against the risk of perioperative bleeding and the need for long-term anticoagulation. Recommendations for managing thrombophilia in renal transplant recipients are suggested based on our experience and review of the literature.

Surgery, gynecology & obstetrics, 1981

Two patients with heterozygous familial type 2 hypercholesterolemia are reported upon following t... more Two patients with heterozygous familial type 2 hypercholesterolemia are reported upon following treatment with end-to-side portacaval shunting. In both, the portacaval shunt decreased the cholesterol level by about 40 per cent. No adverse effects of the operation could be seen in either patient at 30 months, and no return of cardiovascular disease is evident in either patient. In one patient with large xanthelasmas, the lesions became a much duller yellow color and regressed from an elevated to flat appearance. However, the margins of the lesions did not change significantly. In young patients with heterozygous type 2 hypercholesterolemia in whom cardiovascular complications pose a major threat to life, a portacaval shunt is an effective means of reducing the cholesterol level. The benefits to the patient outweight the risks of operation. In one patient, an anxiety reaction developed which her psychiatrist related to a stressful situation. There were no clinical signs of encephalopa...

Journal of the American College of Surgeons

Transplantation Proceedings, 1997

Transactions - American Society for Artificial Internal Organs, 1980

Surgery, 1982

With better survival and extended indications for renal transplantation, it is anticipated that t... more With better survival and extended indications for renal transplantation, it is anticipated that the problem of aortoiliac disease in the posttransplant patient will be seen with increasing frequency. Two patients requiring aortoiliac reconstruction were successfully managed with improvement in graft function after surgery. One patient manifested atheroembolism resulting from aortoiliac occlusive disease; the other had a 2 cm rupture in an aortic aneurysm, which resulted in a large retroperitoneal hematoma, but without frank shock. Perfusion of the transplanted kidney was maintained by the use of a temporary axillofemoral graft, which was removed following aortoiliac repair. The use of this technique involves minimal physiologic disturbance to the patient and the renal graft and allows conventional aortoiliac reconstruction.

Transplantation Proceedings, 1998

Transplantation, 1997

Changes in creatine phosphate, inorganic phosphate, and the purine pattern in dog hearts with tim... more Changes in creatine phosphate, inorganic phosphate, and the purine pattern in dog hearts with time of coronary artery occlusion and effect thereon of mioflazine, a nucleoside transport inhibitor. Cardiovasc Res 1986: 20: 658. 35. Nees S. The adenosine hypothesis of metabolic regulation of coronary flow in the light of newly recognized properties of the coronary endothelium.

Transplantation, 1997

Refractory rejection and cyclosporine (CsA)-induced nephropathy remain important causes of renal ... more Refractory rejection and cyclosporine (CsA)-induced nephropathy remain important causes of renal allograft loss. Previous studies demonstrated that 70-85% of the episodes of refractory acute rejection (AR) occurring in renal allograft recipients on a CsA-based immunosuppressive regimen could be salvaged by conversion to tacrolimus. No data are available regarding the correlation between allograft histology at the time of conversion and the response to tacrolimus. We examined the response to tacrolimus conversion in relation to preconversion biopsies stratified by the Banff criteria. Since May 1992, we have converted 22 patients from CsA to tacrolimus as part of a rescue protocol. We report on 18 patients in whom 6-month follow-up was available after conversion for biopsy-proven AR (n=13) or CsA toxicity (n=5). Sixteen patients were recipients of renal allografts, including three second transplants, and two were recipients of kidney-pancreas transplants. All patients with AR were treated with one or more courses of methylprednisolone and OKT3 before conversion. Renal allograft biopsies were interpreted by a transplant pathologist blinded to the clinical history, and graded according to the Banff criteria. Responses to tacrolimus were scored as improved (creatinine returned to within 150% of baseline), stabilized (creatinine rise arrested), or failed (returned to dialysis). RESULTS; Mean follow-up was 17.3+/-8 months. Fourteen of 18 patients (78%) showed improvement or stabilization in renal function as assessed by creatinine at 6 months or 1 year (when available). Of the 13 patients with histological AR, nine (69%) improved, including five of six with borderline AR, two of three with grade I AR, and two of four with grade II AR. Of the four other patients with AR, two stabilized and two failed. Three of five patients with severe clinical rejection requiring dialysis (range 2-16 weeks) recovered renal function after conversion. Of five patients with CsA toxicity, two (40%) improved. Seven of eight patients who were converted to tacrolimus less than 90 days after transplantation improved, compared with only 4 of 10 who were converted more than 90 days after transplantation. No grafts were lost in patients with a creatinine <3.0 mg/dl at the time of conversion versus two of seven grafts lost when the creatinine was 3.1-5.0 mg/dl and two of eight grafts lost when the creatinine was >5.0 mg/dl. The majority of steroid and antilymphocyte antibody (OKT3 or ATGAM) unresponsive rejections in patients on CsA-based immunosuppression will improve or stabilize after conversion to tacrolimus. There was no correlation with allograft histology stratified by the Banff criteria and the response to tacrolimus. Although there was a trend toward a poorer response with more severe histological rejection, higher serum creatinine at the time of conversion, and longer time from transplantation to conversion, favorable responses were noted in all groups. This indicates that a trial of conversion is warranted, irrespective of the histological severity of injury.

Kidney International, 2000

Journal of Biomedical Materials Research, 1984

The activation of the rabbit complement system by each of three different synthetic materials is ... more The activation of the rabbit complement system by each of three different synthetic materials is reported. Samples of each primed, there was no correlation of the amount of complement activation with the critical surface tension of the material.

JAMA: The Journal of the American Medical Association, 1981

A 33-year-old man with a nonatherosclerotic vasculopathy of undetermined origin had progressive o... more A 33-year-old man with a nonatherosclerotic vasculopathy of undetermined origin had progressive occlusive disease of the lower limb vessels. The resultant severe rest pain and ischemic ulceration of his foot were inoperable and unresponsive to conventional drug therapy. Treatment was begun with intra-arterially administered alprostadil (prostaglandin E1), a vasodilator and inhibitor of platelet aggregation. Although immediate benefit was equivocal, his rest pain had disappeared six weeks after infusion, and the ischemic ulcer almost healed completely. Blood flow studies showed increased flow to the feet, consistent with the subjective improvement. The beneficial effect of alprostadil suggests that further studies with this agent are warranted for patients with nonatherosclerotic vasculopathy.

BJU International, 2012

What&... more What's known on the subject? and What does the study add? Lumagel™ is a reverse thermosensitive polymer (RTP) that has previously been described in the literature as providing temporary vascular occlusion to allow for bloodless partial nephrectomy (PN) while maintaining blood flow to the untargeted portion of the kidney. At body temperature, Lumagel™ has the consistency of a viscous gel but upon cooling rapidly converts to a liquid state and does not reconstitute thereafter. This property has allowed for it to be used in situations requiring temporary vascular occlusion. Previous experience with similar RTPs in coronary arteries proved successful, with no detectable adverse events. We have previously described our technique for temporary vascular occlusion of the main renal artery, as well as segmental and sub-segmental renal branches, to allow for bloodless PN in either an open or minimally invasive approach. These experiments were performed in the acute setting. This study is a two-armed survival trial to assess whether this RTP is as safe as hilar clamping for bloodless PN. Surviving animals showed normal growth after using the RTP, absence of toxicity, no organ dysfunction, and no pathological changes attributable to the RTP. We conclude that Lumagel™ is as safe as conventional PN with hilar clamping, while adding the advantage of uninterrupted perfusion during renal resection. To examine whether randomly selected regions of the kidney could undergo temporary flow interruption with a reverse thermosensitive polymer (RTP), Lumagel™ (Pluromed, Inc., Woburn, MA, USA), followed by partial nephrectomy (PN), without adding risks beyond those encountered in the same procedure with the use of hilar clamping. A two-armed (RTP vs hilar clamp), 6-week swine survival study was performed. Four swine underwent PN using hilar clamps, while six underwent PN with flow interruption using the RTP. The RTP, administered angiographically, was used for intraluminal occlusion of segmental or subsegmental arteries and was compared with main renal artery clamping with hilar clamps. The resection site was randomized for each swine. Laboratory studies were performed preoperatively, and at weeks 1, 3 and 6. Before killing the swine, repeat angiography was performed with emphasis on the site of previous flow interruption. Gross and microscopic examination of kidney, liver, lung, heart, skeletal muscle was later performed, and the vessel that had supported the previous plug was examined. All animals survived. No abnormal chemistry or haematology results were encountered over the 6 weeks. There were no surgical complications in either group. Using angiography we found 100% patency of vessels that had been occluded with the polymer 6 weeks previously for PN. The only gross or microscopic abnormalities were related to the renal resection and scar formation, and were similar in the two groups. Targeted flow interruption with the RTP added no additional risk to PN while allowing bloodless resection and uninterrupted flow to untargeted renal tissue.

Artificial Organs, 1981

The Stagnation Point Flow Experiment is a popular means for studying blood-surface interactions i... more The Stagnation Point Flow Experiment is a popular means for studying blood-surface interactions in a surface strain rate gradient. The strain rate distribution on the test surface of the flow chamber used in this experiment was originally assumed to be simply proportional to the radial distance from the stagnation point. A numerical simulation of the flows through the five most frequently used chambers shows that this is true only for one of the chambers, approximately so for another, and not true for the other three. An additional numerical simulation indicates the blood should purge the saline priming liquid within a few seconds at the beginning of the experiment.

Archives of Surgery, 1998

To assess donor morbidity, recipient outcome, and changing trends during the past decade in donor... more To assess donor morbidity, recipient outcome, and changing trends during the past decade in donor nephrectomy for living-donor kidney transplantation. Design and Setting: Retrospective review at an academic tertiary care referral center.

Archives of Surgery, 1991

American Journal of Transplantation, 2002

Renal allograft recipients with thrombophilia (a hypercoagulable state) are at higher risk for ea... more Renal allograft recipients with thrombophilia (a hypercoagulable state) are at higher risk for early allograft loss. Following an episode of allograft renal vein thrombosis in a patient subsequently diagnosed with protein C deficiency, we adopted universal screening for hypercoagulable risk factors. Patients with a history of a thromboembolic event underwent laboratory screening for thrombophilia. Eight patients with a defined hypercoagulable disorder or a strong clinical history of thrombosis even in the absence of hematologic abnormalities were treated with anticoagulation following renal transplantation. We reviewed the outcomes of these eight patients and all renal transplant recipients at our center who developed thrombotic complications after renal transplantation. Since the introduction of universal screening for hypercoagulable risk factors, 235 consecutive transplants were performed without allograft thrombosis. Eight patients with evidence of thrombophilia, recognized before renal transplantation, received perioperative heparin and postoperative oral anticoagulation. Two of these eight patients developed perinephric hematomas requiring evacuation, blood transfusion, and temporary withholding of anticoagulation. Of interest, two of the remaining 227 patients, not identified with thrombophilia before surgery, developed thrombotic complications after renal transplantation. A hypercoagulable disorder was subsequently documented in each. Identifying patients with thrombophilia before transplantation and defining their management presents many challenges. The risk of allograft thrombosis must be weighed against the risk of perioperative bleeding and the need for long-term anticoagulation. Recommendations for managing thrombophilia in renal transplant recipients are suggested based on our experience and review of the literature.

Surgery, gynecology & obstetrics, 1981

Two patients with heterozygous familial type 2 hypercholesterolemia are reported upon following t... more Two patients with heterozygous familial type 2 hypercholesterolemia are reported upon following treatment with end-to-side portacaval shunting. In both, the portacaval shunt decreased the cholesterol level by about 40 per cent. No adverse effects of the operation could be seen in either patient at 30 months, and no return of cardiovascular disease is evident in either patient. In one patient with large xanthelasmas, the lesions became a much duller yellow color and regressed from an elevated to flat appearance. However, the margins of the lesions did not change significantly. In young patients with heterozygous type 2 hypercholesterolemia in whom cardiovascular complications pose a major threat to life, a portacaval shunt is an effective means of reducing the cholesterol level. The benefits to the patient outweight the risks of operation. In one patient, an anxiety reaction developed which her psychiatrist related to a stressful situation. There were no clinical signs of encephalopa...

Journal of the American College of Surgeons