Histocompatibility antigen transfer in utero: tolerance in progeny and sensitization in mother.

Subcellular antigens obtained from donor spleen and kidney were administered to pregnant rabbits treated with hyaluronidase. Partial immunological tolerance to the donor was thus induced in the fetuses during the adaptive phase. The duration of tolerance was proportional to the total dose of antigen administered to the mother. Maternal sensitization to the offspring was noted in all rabbits giving birth to partially tolerant progeny.

Medicine and ethics. How to allocate transplantable organs.

Organ transplantation has made tremendous strides in the last decade. The demand for transplantable organs has far outstripped the supply; waiting lists have grown long and patients are dying for want of vital organs. Therefore policies and criteria that guide the allocation of transplantable organs become ever more important. Over the years, allocation policies have evolved by including both medical and ethical considerations, and much work has gone into defining and analyzing components of such policies. However, they have often grown by accretion, and a parallel analysis of both sets of approaches did not occur. This article attempts to integrate medical and ethical considerations, and to develop a schema that will permit review, redefinition, and--it is hoped--development of a fairer, more equitable and responsive allocation system.

Lack of effect of oxygen-radical scavenging systems in the preserved reperfused rabbit kidney.

Previous studies showed the beneficial effects of superoxide dismutase +/- catalase in perfusion-preserved rabbit kidneys but failed to show benefit in flush-cooled organs. The current studies undertook to evaluate scavengers, xanthine oxidase inhibitors, and agents that prevent the release of myeloperoxidase in 3 systems: kidneys preserved by perfusion or by flush cooling for 24 hr, studied immediately, and warm ischemia-injured kidneys evaluated after a 24-hr recovery period. In none of these groups could we demonstrate any protective effects against preservational or warm ischemic injury by the above modalities. Even though biochemical and other evidence from previous studies suggested free radical-induced injury to occur in preserved rabbit kidneys, these studies using renal function as the indicator did not do so.

Pharmacological protection of rabbit kidneys from normothermic ischemia.

This study investigated the influence of the administration of pharmacological agents on the recovery of rabbit kidneys from the effects of 1 hr of situ normothermic ischemia, utilizing acute and chronic models. The agents tested included the diuretics mannitol and furosemide, the vasoactive agents phenoxybenzamine, propranolol, and dopamine, and the membrane stabilizers chlorpromazine and methylprednisolone. A beneficial effect was detected only with the diuretic agents and propranolol when given prior to the ischemic insult.

Humoral immunity in kidney transplant recipients.

Sera obtained from kidney transplant recipients at various times after the graft were investigated for the presence of cytotoxic antibodies to B and T human lymphoid cells and for their ability to inhibit mixed lymphocyte reaction between allogeneic lymphocytes. More than 50% of sera from 35 such patients contained cytotoxic antibodies to B lymphocytes and 27 of 33 sera blocked and miced lymphocyte reaction by 25 to 75%. A statistically significant association between the presence of cytotoxic antibodies to B cells and the ability to block the mixed lymphocyte reaction was found in the group of patients with functioning grafts. However, the presence of cytotoxic antibodies to B lymphocytes did not correlate with the outcome of the graft.

Improved function of perfused rabbit kidneys by prevention of oxidative injury.

This study explored the effect of adding small amounts of the reducing agents ascorbic acid and glutathione to a Ringer's-albumin perfusate used for 24-hr hypothermic perfusion of rabbit kidneys. Maintenance of function during preservation was evaluated with a shunt perfusion model and by measuring the ability of cortical slices to restore normal K/Na ratios after incubation in a electrolyte medium. When placed in contact with the unmodified perfusate, an electrode of pyrolytic carbon registered a potential of +190 mV relative to the silver-silver chloride couple. This reading fell rapidly by 100-125 mv when kidneys were placed on the circuit. The mean creatinine clearance after 24-hr perfusion was significantly improved from 162 +/- 56 ml/hr in controls to 284 +/- 92 ml/hr when the potential indicated by this electrode was preadjusted to 43-54 mv with reducing agents, and to 237 +/- 62 ml/hr when this adjustment was made after 2 hr. These creatinine clearances were similar to those of kidneys stored on ice for only 1 hr. These findings indicate minimal injury occurred in the chemically reduced groups and emphasize the importance of preventing oxidative damage to kidneys during hypothermic organ perfusion. The time course of the changes in potential registered by this electrode was consistent with our previous finding that much of the damage to perfused kidneys occurs very early in the course of perfusion. The tissue slice studies showed no detectable damage to the renal parenchyma of the kidneys in the control group despite diminished creatinine clearance. This suggests that the site of oxidation injury is the vascular compartment.

Effect of daily oral vitamin D and calcium therapy, hypophosphatemia, and endogenous 1-25 dihydroxycholecalciferol on parathyroid hormone and phosphate wasting in renal transplant recipients.

Ten stable, normocalcemic renal transplant patients with good allograft function, hyperparathyroidism, and variable hypophosphatemia were treated for 2 to 9 months with oral calcium carbonate and replacement doses of vitamin D analogues. Parathyroid hormone levels (PTH) and renal phosphate wasting were not autonomous or fixed but decreased with therapy. Although serum 1-25(OH)2D3 levels could be shown to rise appropriately during oral vitamin D therapy and fall afterwards, a separate study in a larger group of patients showed no effect of elevated parathyroid hormone or hypophosphatemia to increase endogenous 1-25(OH)2D3 levels. Some 42% of patients with elevated carboxy-terminal PTH, had elevated N-terminal PTH, which was closely associated with more severe phosphate wasting. Aggressive oral calcium and vitamin D supplementation in certain normocalcemic renal transplant patients may decrease endogenous PTH levels, improve hypophosphatemia, and provide a physiologic increase in levels of 1-25(OH)2D3.

Studies of the ideal [H+] for perfusional preservation.

The neutral point of water, being a function of its dissociation constant, is temperature dependent. This is also true of protein-buffered solutions such as perfusates. In organ preservation these facts have been long ignored and, as a result, perfusions have been carried out in a relatively acidotic environment. These studies evaluated the effects of correcting the pH partially or completely for the level of hypothermia involved in perfusional preservation. The findings both in rabbits and dogs were that a pH of 7.4 (measured at 7 C) is dangerously close to the pH below which there is rapid deterioration of function. On the other hand, perfusate pHs up to 7.75 in dogs and 8.25 in rabbits were tolerated at no detriment. As a result, the recommendation is made to carry out hypothermic organ perfusion at a pH well above 7.4; 7.60 or 7.65 seems reasonable.

Gas exchange after pulmonary fat embolism in dogs.

Gas exchange following moderately severe experimental pulmonary fat embolism was studied in nine dogs. A new method designed to describe the distribution of ventilation-perfusion ratios in the lung was applied before and after intravenous injection of homologous neutral fat. The dose of fat (0.75 ml/kg) was low enough to produce a small but significant decrease in arterial PO2 (mean change of 10 mm Hg) in the first 15 minutes after the embolism but high enough to result in the death of two of the four dogs that were allowed to survive the initial postembolism period. Pulmonary artery pressure and pulmonary vascular resistance both rose significantly within 5 minutes of the fat injection and remained elevated for the 2 hour experimental period. Immediately after the embolism there was an increase in the percentage of the total ventilation going to areas of the lung with ventilation-perfusion ratios between 10 and 100, which usually appeared as a discrete mode in the ventilation distribution. This mismatching of ventilation and perfusion partially resolved within 2 hours after the embolism, as indicated by the gradual disappearance of this population of gas exchanging units with relatively decreased blood flow. At no time within 2 hours after the embolism was there a significant increase in shunt or in ventilation to totally unperfused lung. The gas exchange pattern in the two dogs that subsequently died was indistinguishable from that of the other seven in the immediate postembolism period.

Warm ischemic injury of the lung.

Canine left lower lobes which were subjected to 3 hours of warm ischemia in an atelectatic condition were compared to lobes which had not been stored. During short-term reimplantation studies, the injured lobes were characterized by marked weight gain, diminution in blood flow, increased vascular resistance, and peak airway pressure. The ventilation/perfusion ratios were high and considerable dead-space ventilation was present. Hypoxic vasoconstriction occurred in both control and stored lobes, and shunt determinations did not vary because of the low blood flows observed. Some or all of these physiological changes may serve to develop a simple screening method to evaluate techniques of pulmonary preservation.

Forty-eight hour ice storage of kidneys: importance of cation content.

The importance of the cation content of flush solutions used for simple hypothermic storage has been investigated in a 48 hour canine kidney preservation model. Uniformly successful 48 hour storage was achieved with solution C2. However, inclusion of procaine (0.1 Gm. per 100 ml.) in the flushing solution as in C3 produced significant kidney damage. Without procaine, Sacks solution was no better than was C2 and the latter proved significantly superior to a sodium-based solution having identical anion content and osmolarity. The magnesium content of the sodium appeared to favorably influence the outcome of the kidney storage experiments.

Cholecystectomy and hepatic artery injuries.

This study included 71 cadavers used for anatomical dissection that had undergone cholecystectomies. Of these five, 7% had some type of hepatic artery injury. The subjects all had survived at least 1 year after cholecystectomy and had normal livers. The mechanisms of this injury, its pathophysiology, and its prevention are discussed.

Wound infection and topical antibiotics: the surgeon's dilemma.

The topical use of antibiotics in surgical wounds is critically reviewed and analyzed. Thirteen experimental and 19 clinical reports are included in this review. Prospective and retrospective clinical studies have been separated. The analysis evaluated clean vs contaminated/dirty wounds, as well as the effects of various antibiotics and combinations. The conclusion reached on the basis of the experimental and clinical data is that the application of carefully selected topical antibiotics to surgical wounds, particularly those that represent a high risk for the development of wound infection, can be expected to diminish the incidence of this complication in a significant fashion.

Forty-eight-hour kidney preservation. A comparison of flushing and ice storage with perfusion.

Cold nonperfusional (flushing and ice storage) with Collins or Sacks solution and perfusional preservation with cryoprecipitated plasma or albumin were compared in dog kidneys. All these methods were effective in achieving excellent 48-hour preservation of fresh kidneys. After exposure to 20 minutes of ischemia at 37 C, neither of the flushing solutions yielded kidneys that permitted survival of recipients after 48 hours of preservation, and flushed kidneys functioned poorly after 24 hours of preservation. In contrast, both plasma- and albumin-perfused kidneys exposed to ischemia supported life satisfactorily and with normal function. Therefore, simple and inexpensive flushing and ice storage techniques are entirely satisfactorily for the preservation of ideally harvested cadaver kidneys, while the more complex and expensive perfusional techniques must be employed in preserving ischemia-damaged organs.

Transplant renal artery stenosis occurring in both recipients from a single donor.

Stenosis of the renal artery is increasingly being recognized as a cause of hypertension and renal failure after kidney transplantation. To our knowledge, this is the first report of an almost simultaneous occurrence of this complication in both recipients of kidneys from a single donor. In both cases, surgical correction led to improved renal function and amelioration of the hypertension.

Nonaneurysmal suppurative aortitis.

Two patients had nonaneurysmal suppurative aortitis. In one, the aortic ruptured and the patient died. The second patient had Salmonella sepsis and occlusion of the infrarenal aorta. He was treated with aortic resection and extra-anatomic bypass, but died 20 months later of an unrelated illness. Patients with Salmonella sepsis who are over 50 years of age or who are suspected of having aortic atherosclerosis should be evaluated carefully for aortitis since rupture or aneurysm formation is associated with a dismal prognosis.

Transplant renal artery thrombosis. Revascularization after 51/2 hours of ischemia.

Restoration of blood flow to a transplanted kidney following renal artery thrombosis should provide a good model for determining the tolerance of the human kidney to normothermic ischemia. Two cases were seen in which function returned after two and 51/2 hours of occlusion. These, together with two other similar cases reported previously, suggest that attempted revascularization is worthwhile even after several hours of ischemia.

Kidney transplantation in the cyclosporine era.

Seventy-seven patients underwent transplantation, using a cyclosporine-prednisone immunosuppression protocol. No recipients died, and graft survival at one year was 100% for living related donor (LRD) recipients and 84% for cadaver donor (CD) recipients. Nineteen percent of locally harvested, flush-cooled kidney recipients required dialysis, whereas imported kidneys had a 66% dialysis rate. Infectious complications occurred in 17% of patients. Mean hospitalization was 12.8 days for LRD recipients and 13.6 days for CD recipients. Twenty-eight patients required 37 readmissions, mostly for treatment of rejection and infections. Total two-year cost for LRD transplants was +21,400; for CD transplants, +23,900.

Counterfeit cholecystitis, a common diagnostic dilemma.

Of 238 patients hospitalized with a diagnosis of acute cholecystitis, 20 per cent were ultimately found to have other conditions, namely, renal/ureteral problems most often, followed by diseases of the liver, pancreas, appendix, and thorax. Discriminant factors are discussed. Operations based on misdiagnoses occurred only in the patients undergoing early operation. Painstaking preoperative study and interval cholecystectomy, whenever possible, are recommended.

Drainage of intraabdominal abscesses. Tactics and choices.

The experience in treating 44 intraabdominal abscesses in 30 patients using percutaneous or surgical drainage was analyzed. Ultrasonography or computerized tomography-guided percutaneous drainage was highly satisfactory for the definitive treatment of single, accessible collections. Complex, multilocular, and phlegmonous lesions can also be treated by percutaneous drainage as a temporizing measure. Abscesses that are inaccessible, contain large amounts of necrotic material or are ill-defined, as well as those that have not responded to percutaneous drainage, require surgical exploration. Using these principles, there was only one death from sepsis in this series and three significant complications.