Increase in survival time of liver transplants by protease inhibitors and a calcium channel blocker, nisoldipine

Kupffer cells are activated by calcium and release a variety of toxic mediators, including proteases. The purpose of these studies, therefore, was to determine if protease inhibitors and a calcium channel blocker could increase survival time in the rat model of orthotopic liver transplantation. Survival for 30 days was greater than 90% in this model when livers were stored for 1 hr in Ringer's solution (survival conditions)--however, grafts stored for 4 hr in Euro-Collins solution or 8 hr in University of Wisconsin (UW) solution survived postoperatively only 1.2 and 0.7 days, respectively (nonsurvival conditions). When livers were stored for 4 hr in Euro-Collins containing a cocktail of protease inhibitors (leupeptin, pepstatin A, phenylmethylsulfonyl fluoride, 20 ng/ml each; diisopropyl fluorophosphate, 100 microM) and subsequently transplanted, however, survival time was increased significantly to 11.5 days. Inclusion of a calcium channel blocker, nisoldipine (1.4 microM), in the protease inhibitor cocktail increased survival time to 23 days. Actually, nisoldipine alone increased survival time to 25 days. Nisoldipine alone also increased survival time in livers stored for 8 or 16 hr in UW solution to between 15 and 20 days. Serum transaminase levels reached peak values greater than 2400 U/L one day postoperatively in the nonsurvival groups, and liver injury assessed histologically was apparent. Under these conditions, pulmonary infiltration of inflammatory cells was observed in about 60% of the lungs examined and was associated with massive bleeding. Inclusion of the protease cocktail, nisoldipine, or both in the storage solutions decreased maximal SGOT levels and injury to both liver and lung significantly by about 50% postoperatively. Nisoldipine also decreased phagocytosis of carbon particles by the perfused liver 2- to 3-fold following storage under nonsurvival conditions (half-maximal effect = 0.3-0.4 microM nisoldipine). Moreover, nisoldipine improved hepatic microcirculation. It accelerated blood flow into the liver, as indexed by hemoglobin reflectance from the liver surface. These data support the hypothesis that Kupffer cells are activated early in the sequence of events that causes graft failure leading to endothelial cell-mediated alterations in the microcirculation. This work demonstrates clearly that dihydropyridine-type calcium channel blockers such as nisoldipine may be clinically useful in storage solutions for liver prior to transplantation.     

Internal fixation of children's fractures of the lower extremity

Lower grade fractures are by definition stable and almost always treated with casting or functional splinting. The best kind of fixation for the higher grade fractures, however, differs between adults and children. Appropriate treatments are discussed, and case-study illustrations are provided. Background on the anatomy of the tibia and femur is included.     

Cerebral sparganosis mansoni. Report of two cases

Among diseases due to cerebral parasitism, that caused by Sparganum mansoni, the larva of Spirometra mansoni, is very rare. We have encountered two such cases. A computed tomography scan in both revealed a nodular high density contrast enhanced area against an extensive low density background area. Neither calcification nor cyst formation was recognized. These computed tomography scan findings were thought to be characteristic for cerebral sparganosis mansoni and were difficult to differentiate from those of a cerebral tumor. In both cases, definitive diagnosis was achieved by identification of the worm after excision of the lesion. The best treatment for cerebral sparganosis mansoni is surgical excision of the lesion, and in the two cases presented the postoperative outcome was good.     

Leg length equalization during total hip replacement

A method of equalization of leg lengths during total hip replacement surgery was developed which utilizes the concept of equalizing the vertical dimensions of the resected femoral head and neck segment and the remaining hip joint cartilage space, which are removed during the procedure, with the vertical dimensions of the femoral and acetabular prostheses, which are implanted into that void. This was accomplished by determining the dimensions of the prostheses from careful preoperative templating technique and by using a simple arithmetic formula to determine the level of the femoral neck osteotomy. The level of the osteotomy was made by a measurement from the top of the dislocated head of the femur to the medial femoral neck calcar. The radiologic postoperative leg length differences of a consecutive series of 84 patients undergoing primary total hip replacement using this method were determined. The average discrepancy was 2.8 mm. Seventy-five patients (89%) were found to have a postoperative leg length discrepancy of 6 mm (1/4 inch) or less. Six patients (7%) had a discrepancy of 7 to 13 mm, and only three patients (4%) had more than 13 mm (1/2 inch) leg length difference. Using this technique only two patients (2.5%) with unilateral hip replacements had leg lengthening of more than 6 mm.     

Neurogenic bladder after operation of rectal cancer

Of the patients who had had a urodynamic examination during the five year period from 1982 to 1987 in our clinic, 48 patients underwent operations for rectal cancer prior to the study. In 35 of them, the operation mode was known. If the pelvic nerve is damaged by operative modes for rectal cancer, urinary disturbances of severe kinds may occur. In spite of such disturbances, 71.4% of those who had had excision of the low anterior part and 51.9% of those with Miles' operation could be weaned from the clean intermittent self-catheterization and take up spontaneous urination. Even in patients who developed severe dysuria, if catheterized at an early stage, many of them could urinate by abdominal pressure with in several months after operation, without the aid of a catheter. This transition took place mostly within one year after operation. When a patient develops dysuria after radical surgery for rectum cancer, treatment mainly with self-catheterization is an effective method at present.     

Combined operation for renovascular hypertension and ischemic heart disease

We have experienced two patients of ischemic heart disease associated with renovascular hypertension. Patient 1 (60-year-old man) underwent LV aneurysmectomy and triple aortocoronary bypass grafting (saphenous vein to diagonal branch, left internal mammary artery to obtuse marginal branch, and right gastroepiploic artery to right coronary artery). Seventy five days after the initial cardiac surgery endarterectomy for the left renal artery and bifurcated Dacron graft implantation for the iliac artery obstruction were performed. Patient 2 (62-year-old woman) underwent simultaneous operation of both right nephrectomy and triple aortocoronary bypass grafting (saphenous vein grafts to obtuse marginal branch and right coronary artery, and left internal mammary artery to left anterior descending artery). Their postoperative courses were uneventful except unstable and high blood pressure for four to seven days after the operation. It appears that it should be decided to achieve either simultaneous or two stage approach for ischemic heart disease associated with renovascular hypertension based on the preoperative cardiac function. And both postoperative cardiac function and hypertension should be carefully managed until the blood pressure becomes stable after the surgery.     

Anesthetic management of a patient with osteogenesis imperfecta congenita

We experienced anesthetic management of three cases of osteogenesis imperfecta. Case 1: A 2-year-old boy weighing 8.6 kg was premedicated with chloral hydrate 250 mg intrarectally, but he was very excited on arrival at the operating room. Induction of anesthesia was performed by intramuscular injection of ketamine 40 mg. Case 2: A 4-year-old girl underwent three surgeries (2 osteomies and 1 intramedullary nailing of the tibias) during the past two years. On the second and third procedures, marked hyperthermia (over 39.2 degrees C as rectal temperature) developed during halothane (1-2%) and enflurane (1.5-2.5%) anesthesia. However, on the first surgery, hyperthermia did not occur under combined light halothane (0.3-0.5%) anesthesia with caudal epidural block. Case 3: A 14-year-old female underwent osteotomy of the radius under brachial plexus block without any anesthetic complications. In conclusion, anesthetic considerations for children with this disease are as follows; 1) It is necessary to premedicate to provide good preoperative sedation. 2) Care should be taken to use inhaled anesthetic agents (halothane and enflurane) because of tendency to develop abnormal hyperthermia. 3) It is desirable to use regional anesthesia.