Acute and chronic renal failure in liver transplantation

We have performed a retrospective review of the incidence and etiologies of acute renal failure (ARF) in 105 adult patients receiving liver transplants. The prevalence of chronic renal failure was also determined. ARF occurred in 94.2% of these patients. Acute tubular necrosis was the leading cause of ARF and was associated with the highest mortality. Factors associated with increased mortality included: (1) peak serum creatinine greater than 3 mg/dl, (2) multiple liver transplants and (3) the need for dialysis. Pretransplant renal failure did not increase mortality. Chronic renal failure developed in 83% of patients at latest follow-up (mean: 30.5 +/- 7.9 months).     

Effect of distension on adrenergic innervation of the rat urinary bladder

Summary The effect of distension on adrenergic innervation was investigated in the rat urinary bladder. Bladders were distended for 3 h by forced diuresis and ballon obstruction, and specimens were taken from the bladder dome, body and neck for the demonstration of glyoxylic acid-induced fluorescence of catecholamines. Depletion of catecholamines started after 10 h and was almost complete after 2 days. The fluorescence had recovered part way after 5–7 days and was practically normal after 21 days. Small, intensely fluorescent (SIF) cells in the ganglia continued to leak catecholamines throughout the 21-day study period. The primary clinical success of distension therapy for the treatment of unstable bladder may be at least partly due to a reversible disturbance in the function of the adrenergic nerves, which have an excitatory alpha-adrenergic dominance in such cases, but the persistent leakage from SIF cells raises the question of whether distension causes prolonged disturbances in bladder function.     

Abnormal magnetic-resonance scans of the lumbar spine in asymptomatic subjects. A prospective investigation

We performed magnetic resonance imaging on sixty-seven individuals who had never had low-back pain, sciatica, or neurogenic claudication. The scans were interpreted independently by three neuro-radiologists who had no knowledge about the presence or absence of clinical symptoms in the subjects. About one-third of the subjects were found to have a substantial abnormality. Of those who were less than sixty years old, 20 per cent had a herniated nucleus pulposus and one had spinal stenosis. In the group that was sixty years old or older, the findings were abnormal on about 57 per cent of the scans: 36 per cent of the subjects had a herniated nucleus pulposus and 21 per cent had spinal stenosis. There was degeneration or bulging of a disc at at least one lumbar level in 35 per cent of the subjects between twenty and thirty-nine years old and in all but one of the sixty to eighty-year-old subjects. In view of these findings in asymptomatic subjects, we concluded that abnormalities on magnetic resonance images must be strictly correlated with age and any clinical signs and symptoms before operative treatment is contemplated.     

Computed tomography and nonoperative treatment for blunt abdominal trauma

Studies were undertaken to determine if computed tomography (CT) could reliably assist physical examination in the initial assessment of blunt abdominal trauma, and also to examine how various abdominal injuries were managed with the guidance of CT. A total of 255 patients underwent emergency abdominal CT following blunt abdominal trauma over a period of seven years. One hundred and fifty two patients had abnormal CT scans, including 58 hepatic, 36 renal, 25 splenic and 9 pancreatic injuries as well as 67 patients with intra-abdominal hemorrhage and 21 patients with free abdominal air. A comparative study on the detection of pneumoperitoneum revealed CT to be far superior to plain radiography. One hundred and three patients had normal CT scans, all of whom were managed nonoperatively, except for three false-negative cases and two nontherapeutic cases. The patients with injury to the parenchymal organs were given nonoperative treatment if they had stable vital signs and no evidence of associated injuries demanding immediate surgery and the majority of these patients were managed well nonoperatively. CT was thus found to be a useful adjunct in the management of victims of blunt abdominal trauma, since in a rapid and noninvasive fashion, CT accurately defined the extent of parenchymal organ injury and also disclosed any other abdominal injuries.     

Utility of radioisotopic filtration markers in chronic renal insufficiency: simultaneous comparison of 125I-iothalamate, 169Yb-DTPA, 99mTc-DTPA, and inulin. The Modification of Diet in Renal Disease Study

Assessment of glomerular filtration rate (GFR) with inulin is cumbersome and time-consuming. Radioisotopic filtration markers have been studied as filtration markers because they can be used without continuous intravenous (IV) infusion and because analysis is relatively simple. Although the clearances of 99mTc-diethylenetriamine-pentaacetic acid (DTPA), 169Yb-DTPA, and 125I-iothalamate have each been compared with inulin, rarely has the comparability of radioisotopic filtration markers been directly evaluated in the same subject. To this purpose, we determined the renal clearance of inulin administered by continuous infusion and the above radioisotopic filtration markers administered as bolus injections, simultaneously in four subjects with normal renal function and 16 subjects with renal insufficiency. Subjects were studied twice in order to assess within-study and between-study variability. Unlabeled iothalamate was infused during the second half of each study to assess its effect on clearances. We found that renal clearance of 125I-iothalamate and 169Yb-DTPA significantly exceeded clearance of inulin in patients with renal insufficiency, but only by several mL.min-1.1.73m-2. Overestimation of inulin clearance by radioisotopic filtration markers was found in all normal subjects. No differences between markers were found in the coefficient of variation of clearances either between periods on a given study day (within-day variability) or between the two study days (between-day variability). The true test variability between days did not correlate with within-test variability. We conclude that the renal clearance of 99mTc-DTPA, 169Yb-DTPA, or 125I-iothalamate administered as a single IV or subcutaneous injection can be used to accurately measure GFR in subjects with renal insufficiency; use of the single injection technique may overestimate GFR in normal subjects.     

Hydroxylapatite-coated total prosthesis of the hip

Since 1987, 80 hydroxyapatite-coated (HA) cementless total hip prostheses have been implanted. Thirty patients were examined 21 months postoperatively and the results compared with data for uncoated prosthesis. Earlier mobilization and freedom from pain, together with evidence of bone ingrowth without connective tissue membrane formation, confirmed the benefits of HA-coated prostheses.     

Uptake of Adriamycin in tumour and surrounding brain tissue in patients with malignant gliomas

Summary Eight patients with malignant gliomas verified on CT scan, received an intravenous injection of 50 mg of Adriamycin R, 24 hours prior to surgical removal of the tumour. Peroperatively, both tumour and surrounding tissue specimens were obtained for determination of the tissue concentrations of Adriamycin and its reduced metabolite Adriamycinol. It was found that Adriamycin could be detected in tumour tissue from all patients. The concentration varied between 0,9 and 4,6 nmol/g tissue. In contrast, Adriamycin could only be detected in surrounding brain tissue from one patient.In anin vitro study a human malignant glioma cell line (U-251 MG) was exposed to various concentrations of Adriamycin for 24 hours. It was found that an intracellular drug concentration above 30 nmol/g cells caused a concentration dependent inhibition of cell growth. Thus, it is likely that the poor effect of Adriamycin on patients with malignant gliomas is due to an ineffective drug accumulation in the tumour tissue.     

Hydroxylation of chlorzoxazone as a specific probe for human liver cytochrome P-450IIE1

Human cytochrome P-450IIE1 has been implicated in the oxidation of a number of substrates, including protoxins and -carcinogens. To date, no drugs have been identified that are exclusive substrates for the protein and are applicable for use as noninvasive probes of the in vivo function of the enzyme in humans. Chlorzoxazone was found to be oxidized only to 6-hydroxychlorzoxazone in human liver microsomes. Results of steady-state kinetics are consistent with the view that only a single enzyme catalyzes the reaction. The microsomal reaction was strongly inhibited by rabbit anti-P-450IIE1 and, in a competitive manner, by known P-450IIE1 substrates. Rates of chlorzoxazone 6-hydroxylation in different human liver microsomal preparations were well correlated with levels of immunochemically measured P-450IIE1 and rates of (CH3)2NNO oxidation. Chlorzoxazone 6-hydroxylation was also found to be catalyzed by purified human liver P-450IIE1. These results provide strong evidence that P-450IIE1 is the primary catalyst of chlorzoxazone 6-hydroxylation in human liver. Rates of chlorzoxazone 6-hydroxylation vary considerably among human liver samples, and chlorzoxazone 6-hydroxylation may have potential use as a noninvasive probe in estimating the in vivo expression of human P-450IIE1 and its significance as a risk factor in the toxicity and carcinogenicity of a number of solvents, nitrosamines, and drugs.