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When preparing for amputation in 153 patients with acute ischemic gangrene of a lower extremity, the tourniquet-cold isolation was used. In 137 patients, the damaged extremity was freezed by means of a special portable freezing chamber, which can be used in any surgical in-patient department. The duration of cooling ranged from 18 hrs to 14 days. The state improved in 136 patients, the amputation of the extremity was performed in them. The use of freezing of the damaged extremity permitted to reduce the postoperative lethality from 41 to 19.1%. A high effectiveness of the method in gangrene of the extremity against the background of diabetes mellitus was noted.
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PMID:[Pre-amputation freezing of the extremity in acute ischemic gangrene]. 223 29

The influence of cold storage preservation time on graft survival and metabolic function of pancreatic transplants was studied in 130 recipients of bladder-drained grafts (47 simultaneous with, 33 after, and 50 without a kidney transplant) between October 1, 1984 and May 1, 1989. The recipients were divided into four groups according to the preservation time: less than 6 hr (n = 11), 6-12 hr (n = 24), 12-24 hr (n = 75), and greater than 24 hr (n = 20). Twenty-six grafts were procured by other transplant teams and sent to us. Silica gel fractionated plasma was used for preservation in 104 cases and the University of Wisconsin solution in 25 (1 in the less than 6 hr, 2 in the 6-12 hr, 16 in the 12-24 hr, and 6 in the greater than 24 hr groups). The technical failure rate at 1 month was 13% (17 grafts), 1 (9%) in the less than 6 hr, 5 (21%) in the 6-12 hr, 9 (12%) in the 12-24 hr, and 2 (10%) in the greater than 24 hr groups. At 1 month, 107 (82%) of the grafts were functioning, 10 (91%) in the less than 6 hr, 18 (75%) in the 6-12 hr, 62 (83%) in the 12-24 hr and 17 (85%) in the greater than 24 hr groups, the longest preserved for 30 hr. The respective 1-year graft survival rates were 51%, 50%, 57%, and 70%. Ninety patients (10 in the less than 6 hr, 16 in the 6-12 hr, 51 in the 12-24 hr, and 13 in the greater than 24 hr groups) had metabolic studies between 2 and 6 weeks postransplant. The results of 24-hour profiles (14 blood glucose determinations) were similar in each preservation time group; the means of the mean (+/- SD) profile glucose (mg/dl) values were 130 +/- 19, 126 +/- 31, 130 +/- 24, and 129 +/- 30, respectively (P greater than 0.6). Mean plasma glucose levels at 2 hr during OGTT were 141 +/- 32, 145 +/- 43. 163 +/- 49, and 184 +/- 100 in the respective preservation groups (P greater than or equal to 0.064). According to the National Diabetes Data Group classification, 75% of recipients in the less than 6 hr, 50% in the 6-12 hr, 44% in the 12-24 hr, and 33% in the greater than 24 hr groups had normal OGTT results.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Influence of preservation time on outcome and metabolic function of bladder-drained pancreas transplants. 230 59

Prolonged cold ischemia has been associated with impaired early cadaver renal allograft function. The role of CsA in potentiating these effects is not well understood, but CsA has been implicated in promoting delayed graft function and potentiating renal ischemic injury. In order to establish whether CsA is safely tolerated by kidneys subjected to protracted cold ischemia, we examined patient and graft outcome in a series of 1081 patients receiving cadaver-kidney transplants over an 8-year period (1981-1988). All patients received a standard immunosuppressive regimen that included CsA. Overall actuarial 1-year patient and graft survival rates were 96% and 80%, respectively. Renal preservation was achieved either by pulsatile perfusion (n = 261, 24%) or simple cold storage (n = 820, 76%). Results were analyzed according to total cold ischemic time as follows: 0-23 hr (n = 512; range, 0-23.9 hr); 24-35 hr (n = 380; range, 24.0-35.9 hr); 36-47 hr (n = 161; range, 36.0-47.7 hr); greater than or equal to 48 hr (n = 28; range, 48.0-70.6 hr). These groups did not differ significantly in recipient age, sex, incidence of diabetes, number of pretransplant blood transfusions, level of presensitization, or HLA match. There were no differences in overall actuarial 1-year patient or graft survival rates, incidence of rejection, or renal function at 1 year. There was a higher incidence of impaired early graft function for kidneys preserved greater than or equal to 48 hr, but eventual graft outcome, including serum creatinine at 1 year, was unchanged. Delayed introduction of CsA resulted in improved 1-year graft survival (84.4% vs. 74.7%, P less than 0.05) compared to CsA treatment begun at the time of transplantation ("initial CsA"). This improvement was present regardless of total cold ischemia time. The incidence of permanent graft nonfunction, which has been previously reported to increase with CsA therapy, was influenced by the timing of CsA therapy (initial: 12%; delayed: 3%, P less than 0.05) but was not affected by duration of cold ischemia. Thus, safe preservation of cadaver kidneys for up to 70 h can be achieved by standard techniques even when CsA is incorporated into the immunosuppressive regimen. The most important determinants of graft survival in these patients are the timing of CsA therapy and the presence of early graft function, not the duration of renal preservation.
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PMID:The role of cold ischemia in a provincial organ-sharing program in the cyclosporine era. 230 66

We compare the results in recipients of cadaveric renal allografts immunosuppressed with cyclosporine and prednisone to those who received immunosuppression with cyclosporine, azathioprine and prednisone. The 2 groups were compared relative to HLA-ABDR matching, plasma reactive antibodies, cold ischemia time, diabetes as a cause of renal failure and recipient age greater than 50 years. The incidences of clinical allograft rejection and grafts lost to rejection were not significantly different in these 2 groups evaluated at 1 year. In the 2-drug immunosuppressed group the actual 3, 6 and 12-month graft function was 87, 86 and 85%, respectively, compared to 79, 78 and 74%, respectively, in the 3-drug immunosuppressed group. A difference in graft survival was due to graft loss secondary to vascular thrombosis and patient death, and not to immunological events. No advantage was demonstrated for the use of 3-drug immunosuppression for kidney allografts over a 2-drug protocol of cyclosporine and prednisone.
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PMID:Comparison of 2-drug and 3-drug immunosuppression for cadaveric renal transplantation. 232 2

Binding equilibria of long-chain fatty acids to human serum albumin, in serum or plasma, were studied by a dialysis exchange rate technique. Palmitate was added to citrated plasma in vitro and it was observed that between six and ten palmitate molecules were bound to albumin with nearly equal affinity. Observations in vivo gave similar results in the following series: (a) in two volunteers with increased fatty acid concentrations after fasting, exercise, and a cold shower: (b) in three male volunteers in whom high concentrations of non-esterified fatty acids, up to 4.6 mM, were induced by intravenous administration of a preparation of lecithin/glycocholate mixed micelles, and (c) in 81 patients with diabetes mellitus, type I. The binding pattern of palmitate in serum or plasma is essentially different from that observed with palmitate added to buffered solutions of pure albumin when two molecules are tightly bound and about four additional molecules with lower affinity. The differences may partly be explained by the presence of chloride ions in blood plasma, reducing the affinity for binding of the first two fatty acid molecules, and partly by facilitated binding of several molecules of mixed fatty acids, as found in plasma.
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PMID:Multiple fatty acid binding to albumin in human blood plasma. 233 79

The present study investigated changes of gastrointestinal transit in diabetes mellitus by a variant of the hydrogen exhalation method, which produces reliable estimates of oro-cecal transit times of a lactulose test meal. Relation to metabolic state and small fibre neuropathy was also evaluated. The latter was indexed by Airaksinen's variability score for resting pulse frequency, Ewing's index of respiratory sinus arrhythmia, and warm and cold thresholds at the foot. 15 inpatients with verified type I diabetes (nine female, six male) and eleven healthy controls (nine female, two male) were under investigation. Ages ranged from 19 to 47 and 27 to 49 years, respectively. No clearcut signs of angiopathy or neuropathy were present in patients. HbA1c values were moderately high (means +/- s = 8.2 +/- 1.6). Diabetes patients showed prolonged transit compared to controls (means +/- s = 102.7 +/- 28.2 min, and 79.6 +/- 15.4, resp.; p = 0.02, U-test). Two patients had extremely long transit times, none showed acceleration. However, neither indices of small fibre neuropathy nor metabolic parameters were significantly correlated with transit measures. Prolonged oro-cecal transit, therefore, seems to be due to a specific visceral-autonomic or primary enteric neuropathy, which is still limited to the gastrointestinal system in this stage, and/or metabolic effects.
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PMID:[Studies on orocecal transit in diabetes mellitus]. 235 97

The retrograde axonal transport of intravenously administered [125I]nerve growth factor ([125I]NGF) was examined in ileal mesenteric nerves maintained for short periods in vitro. [125I]NGF was injected systemically, and at various times thereafter mesenteric pedicles were ligated and incubated in vitro in Krebs-Henseleit medium under a number of different conditions. Retrogradely transported [125I]NGF began to accumulate distal to the ligature after an initial lag period and increased in a linear fashion for 3-4 h. The amount of retrogradely transported [125I]NGF was proportional to the length of the ileum innervated by each pedicle, which allowed for comparison of ileal segments of different lengths. Retrograde axonal transport of [125I]NGF was inhibited by vinblastine, colchicine and incubation in the cold, and was decreased by agents that interfere with oxidative or glycolytic metabolism. The accumulation of retrogradely transported [125I]NGF in ileal mesenteric nerves of 1-9 day streptozotocin diabetic animals placed in an in vitro bath containing normal (5.5 mM) glucose was decreased 40% compared to control animals. The induction of diabetes in vivo resulted in a greater decrease in the early phases of [125I]NGF export from ileal mesenteric nerve terminals compared to later phases. Ileal mesenteric nerve segments derived from untreated controls were incubated in vitro in media containing increased concentrations of glucose (27.5 and 50 mM) without reproducing the NGF transport defect found in diabetic animals.
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PMID:Retrograde axonal transport of [125I]nerve growth factor in ileal mesenteric nerves in vitro: effect of streptozotocin diabetes. 242 4

We have recently reported successful 72-h preservation of the canine pancreas with a new cold-storage solution developed at the University of Wisconsin (UW solution). Over 10 mo, we performed 11 combined pancreas-kidney and 4 isolated-pancreas transplants with this solution. In situ cooling of the donor pancreas was performed with 1000 ml of UW solution followed by ex vivo perfusion with an additional 250-500 ml. Graft preservation times ranged from 3 to 19 h (mean 10.2 h). Pancreas transplants were vascularized whole-organ grafts with pancreaticoduodenocystostomy. Early graft function was excellent as assessed by immediate insulin independence, high urinary amylase and low serum amylase levels, and a technetium perfusion index indicating good pancreatic blood flow. There were no episodes of primary nonfunction, graft pancreatitis, or vascular thrombosis. Actuarial patient and graft survival at 1 mo was 92.9%. We conclude that UW solution provides excellent early graft function for up to 19 h of cold storage. Based on previously reported data on its efficacy in liver and kidney preservation, UW solution seems ideally suited as a universal intra-aortic flush and cold-storage solution.
Diabetes 1989 Jan
PMID:Use of UW solution in pancreas transplantation. 246

Utilizing the intrasplenic canine islet autograft model, it was possible to examine the effect of cold-storage of pancreatic tissue, both prior to and following dispersion, on functional outcome. A control group of dogs receiving freshly prepared autografts (n = 8) obtained durable euglycaemia in 75% of cases; the mean K value at two weeks being -1.70 (Standard Deviation (sd) = 0.06). In the first experimental group, animals (n = 8) were transplanted following 24 hours of whole pancreas cold-storage in silica gel fractionated plasma (SGF) using intraductal perfusion prior to preservation. None of these animals obtained euglycaemia; the transplanted material having a significantly reduced insulin content compared with controls (p = 0.0006). In the second experimental group, animals (n = 6) were transplanted following 24 hours of dispersed pancreatic tissue storage in SGF. This resulted in an 83% incidence of durable euglycaemia; the mean K value at two weeks being -1.60 (sd = 0.3). The glucose decay curve improved with time in this group and at three months the mean K value was -2.00 (sd = 0.38); this value being significantly superior to that of the control animals (K = -1.34, sd = 0.34, p less than 0.05). We conclude that while storage of the whole pancreas prior to islet isolation remains problematic, it is possible to reliably preserve dispersed pancreatic tissue for 24 hours by simple cold-storage, as assessed by the functional outcome of intrasplenic autografting in the dog model. These findings have important clinical implications.
Diabetes Res 1989 Jan
PMID:Successful transplantation of canine islets of Langerhans after 24 hours cold-storage. 247 3

This study aimed at evaluating vasomotor response of the hand in patients with diabetes mellitus. A skin temperature of the hand was measured before and after exposure to ice water, and the recovery rates of the skin temperature were determined at 3, 5, and 10 min after the cold exposure. Ninety-two diabetics ranging in age from 25 to 59 years and 43 normal subjects ranging from 23 to 69 years old participated in this study. Since the recovery rate was delayed in normal subjects over the age of 60, comparison was made between the diabetics and the normals under 60 years old. The skin temperature was significantly lower in 26 diabetics with severe peripheral neuropathy (PN) than 40 diabetics without PN. The recovery rate were markedly delayed in the patients with PN, and also delayed in diabetics with severe retinopathy. The recovery rate was not different between the patients with and without ischemic changes in electrocardiogram. The delayed recovery rate was most prominent in the diabetics who had both abnormal heart rate variation (HRV) and orthostatic hypotension, followed by those with abnormal HRV but without orthostatic hypotension. Recovery rates in the diabetics with abnormal HRV alone were within the normal range. Our data suggest that the dysfunction of the regulation of skin temperature in the patients with diabetes mellitus was due to peripheral sympathetic nerve abnormality. The cold exposure test would be useful in the estimation of the sympathetic nerve activity of the diabetics.
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PMID:Impaired regulation of skin temperature in patients with diabetes mellitus evaluated by the cold exposure test. 248 47


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