Ch Gips

DETERMINATION OF AMMONIA IN EAR-LOBE CAPILLARY BLOOD IS AN ALTERNATIVE TO ARTERIAL BLOOD AMMONIA

Blood ammonia determination is a laboratory test to diagnose hepatic encephalopathy. Arterial blood is superior to peripheral venous blood ammonia because of ammonia metabolism in muscle. We have compared capillary with arterial whole blood ammonia as capillary sampling is an attractive alternative. Ear-lobe capillary blood ammonia (ECA) was determined in all 173 persons studied, fingertip capillary blood ammonia (FCA) in 46 of these and arterial blood ammonia (AA) in 113. Of the 173, 60 were healthy (H), 64 were patients, not liver diseased (NLD) and 49 had liver disease (LD). Reference values, median and ranges, mumol NH3-N/l: AA, NLD, n = 64: 17 (7-42); ECA, H = NLD (P = 0.9), n = 124: 20 (7-45); FCA, H = NLD (P = 0.8), n = 33: 70 (29-151). Within the NLD group (n = 64) AA values (range 7-42) were little but significantly lower than the ECA values (range 7-45, P = 0.002). FCA NLD > AA NLD (n = 14, P < 0.0001); FCA H+NLD > ECA (n = 33, P < 0.0001). AA correlated very well with ECA, r = 0.87 (n = 113, P < 0.0001) and less well with FCA, r = 0.56 (n = 27, P < 0.01). ECA correlated with FCA, r = 0.51 (n = 46, P < 0.001). Ear-lobe capillary blood ammonia thus accurately reflects arterial ammonia and is an attractive alternative. The higher fingertip ammonia may be due to contamination with ammonia-rich sweat from finger grooves, regardless of the precautions taken.

ETRETINATE (TIGASON) HEPATITIS IN 2 PATIENTS

A histologically confirmed, clinically inapparent and reversible hepatitis occurred in 2 patients (1 psoriasis, 1 basal cell nevus syndrome) within the first months after introduction of etretinate therapy. Causes of hepatitis other than etretinate were not found. Reintroduction of etretinate resulted in reactivation and/or persistence of the hepatitis in both patients. These data strongly suggest that the hepatitis in both patients was caused by etretinate. Later the basal cell nevus syndrome patient was given 13-cis-retinoic acid, which caused no liver test disturbances during a follow-up period of 6 months.

Hepatic morphologic findings and viral antigens in acute hepatitis B

In the course of a prospective clinical study, 26 liver biopsies were taken in 24 previously healthy patients with an uncomplicated acute hepatitis B (AHB) and a subsequent complete recovery (UR group). Serum transaminase levels were used to distinguish four AHB stages, as the variability in duration made time dependent staging less appropriate. As a reference, a second group of 22 liver biopsies from 7 patients from the same prospective clinical study who eventually developed chronic hepatitis (CH group) was included. Due to fluctuations of transaminase levels in this group the stages two and three could not be separated, stage four was not reached within the follow-up period of median 5 years. Histopathological criteria and the distribution patterns of hepatitis B surface (HBsAg) and core (HBcAg) antigens were studied. Piecemeal necrosis and bridging hepatic necrosis were a frequently occurring feature in the liver biopsies of the UR group taken during the stage of peak transaminase levels. In this respect, no differences could be demonstrated between the UR group and the CH group. The occurrence of these features in AHB thus appears to have no prognostic value as risk factor for chronic liver disease. In contrast, diffuse cytoplasmic (‘ground glass’) HBsAg localization was only found in stage 2/3 of the CH group. It is concluded that apart from ground glass cells, care must be taken to interpret any histopathological feature in AHB as risk factor of progression to chronicity without reference to the duration of illness. The possible significance regarding the hosts immune mechanisms of some features that may persist during chronic liver disease is discussed.

THE PHARMACOKINETICS OF THEOPHYLLINE AND ENPROFYLLINE IN PATIENTS WITH LIVER-CIRRHOSIS AND IN PATIENTS WITH CHRONIC RENAL-DISEASE

SummaryWe have studied the pharmacokinetics of theophylline and enprofylline in patients with liver cirrhosis, patients with chronic renal failure, and healthy subjects, and have assessed the predictive value of routine tests of liver function and renal function (creatinine clearance) for theophylline and enprofylline total body clearances.Theophylline clearance was significantly decreased in the patients with liver cirrhosis compared with both the patients with renal failure and the healthy subjects (the mean values in the three groups were 24, 47, and 46 ml·h−1·kg−1 respectively.Enprofylline clearance was significantly decreased in the patients with chronic renal failure, compared with both the patients with liver cirrhosis and the healthy subjects (the values in the three groups were 64, 250, and 289 ml·h−1·kg−1 respectively.There was a strong correlation between creatinine clearance and enprofylline clearance, while there was only a poor correlation between the liver function tests and theophylline clearance.It appears that in various clinical situations enprofylline elimination can be predicted more precisely than theophylline elimination, which may make the drug safer in clinical practice.

Comparison of the precision of seven analytical methods for the H2O concentration in human serum and urine

In order to calculate a true renal H2O clearance (U X V/P), serum and urine H2O concentrations have to be known. In this investigation we compared the precision (repeatability) and the ease of performance of 7 H2O assays in human serum and urine. The 3 gravimetric assays (oven-drying, freeze-drying or freeze-drying as well as oven-drying) had a very high precision (coefficients of variation (CV) 0.2-0.4%) and were easy to perform. The precision of mass spectrometry, gas chromatography and titrimetry (Karl Fischer) was better in urine than in serum (ranges of CV 1.2-1.5% in urine vs. 2.4-4.3% in serum), but the precision of osmometry was better in serum than in urine (CV 1.0 vs. 1.6%). Accuracy was not determined as storage effects at 4 degrees C and at -20 degrees C caused insuperable logistic problems. Only small sample volumes are used in titrimetry and gas chromatography, making them more suitable for determinations in babies and animal studies. With titrimetry determinations can be done in a short time. The gravimetric assays appear to reflect the true H2O content of serum and urine, thus enabling calculation of the true renal H2O clearance, which can be of clinical importance in liver, renal and cardiac disease.

GRAVIMETRIC-DETERMINATION OF THE WATER CONCENTRATION IN WHOLE-BLOOD, PLASMA AND ERYTHROCYTES AND CORRELATIONS WITH HEMATOLOGICAL AND CLINICOCHEMICAL PARAMETERS

We have assessed gravimetric methods for determination of intravascular water, established whole blood-, plasma- and erythrocyte water reference values in a healthy volunteer group (n = 97, 48 females) and correlated these variables with 30 simultaneous hematological, clinicochemical and body parameters. The water standard was 55.56 mol/kg = 100 mass %. For erythrocyte water determination three methods were evaluated: 2 indirect methods were easy to perform, the third, using a hematocrit centrifuge, was the most reliable. Imprecision (within-batch coefficient of variation (CV), %) was excellent: whole blood 0.2, plasma 0.1, erythrocytes 0.7-2.2 and recoveries (means, %) 99.7-100.1. Serum water was found to be slightly higher than plasma water. Volunteer group, mean reference values, mass %: whole blood water 79.7, plasma water 91.2, erythrocyte water, three methods 66.2, 64.6 and 64.2, respectively. Females had mean 1.6 mass % higher whole blood water and 0.9-1.0 mass % higher erythrocyte water than males with no difference in plasma water. In the volunteer group whole blood water correlated strongly with hematocrit (r = -0.96), hemoglobin (r = -0.94) and erythrocytes (r = -0.85) and centrifuge hematocrit (r = -0.91). Plasma water correlated strongly with plasma total protein (r = -0.74, all correlations P < 0.001). Hemoglobin and hematocrit can serve as surrogate parameters for whole blood water when water determination is not available; total protein reflects plasma water.

Whole blood and plasma water in health and disease: Longitudinal and transverse observations and correlations with several different hematological and clinicochemical parameters

In a healthy reference population, hemoglobin (Hgb) and hematocrit (Hct) have been proposed as surrogate markers for whole blood water (WBW). We have extended this study under different physiological and pathological conditions in two longitudinal series, viz. (1) acute hyper- and hypohydration experiments in a healthy individual and (2) three athletes running 5 km each, and in three transverse series, viz. (3) a young reference population (n = 97, 49 females), (4) an old reference population (n = 37, nine females) consisting of inhabitants of a nursing home and (5) cardiac, hematological and renal patients including severe anaemia, polycythaemia and abnormal protein levels (n = 50, 25 females) with suspected hydration disturbances. The only sex difference found was a lower WBW in males in the young reference group. The percentage change of PW was less than that of WBW. In all five groups together (n = 293) WBW correlated closely (P < 0.0001) with Hgb and Hct (both r = -0.95) and with erythrocyte count (r = -0.85), whereas PW correlated with total protein (Tprot) (r = -0.84). In the longitudinally studied groups (1) and (2) WBW also correlated (P < 0.0001) with cholesterol, Ca, Tprot, albumin, platelets, globulin and white blood cells (r +/- 0.98-0.37), while PW correlated (P < 0.0001) not only with the same clinicochemical parameters but also with Hct, Hgb and red blood cells (r +/- 0.98-0.44). The homeostasis of PW is more narrowly regulated than that of WBW. Hgb, Hct and erythrocyte count reflect WBW and Tprot reflects PW also under disease conditions. WBW (mass%) can be calculated from Hgb and Hct using the formulae: -0.09 x Hgb (g/l) + 91.7 and -28.6 x Hct (v/v) + 91.8 and PW (mass%) from Tprot using the formula: -0.09 x Tprot (g/l) + 97.6. Other correlations were observed only in a longitudinal setting and presumably are due to concentration and dilution.

EVALUATION OF GRAVIMETRIC ASSAYS OF THE H2O CONCENTRATION IN HUMAN-SERUM AND URINE

The oven-drying method and the combined freeze- and oven-drying method for gravimetrical measurement of human serum and urine H2O concentration, as well as two reported formulas for the calculation of the serum H2O concentration were evaluated. Day-to-day precision in serum and urine (coefficient of variation (CV) less than 0.95%), and recovery in serum (95-99%) were excellent. Storage at 4 degrees C and at -20 degrees C was safe at least for 3 wk and 2 mth, respectively. For the oven-drying method, which was the most practical, reference values after fasting overnight were determined (n = 47; 99% confidence interval; serum, 48.8-51.6 mol/l; urine, 51.2-53.8 mol/l). Patients in different disease categories were tested (n = 38), and had normal values mostly. Low serum values were found in a patient after hemodialysis with ultrafiltration (47.0 mol/l), and in two patients with an extreme hyperproteinemia (48.8 mol/l) and hypercholesterolemia (48.1 mol/l), respectively. Formulas for calculation of the serum H2O concentration proved unreliable. When direct measurement is impossible, a serum value of 50.5 mol/l can be substituted.

Vascular problems in paroxysmal nocturnal haemoglobinuria

SummaryTwo patients with paroxysmal nocturnal haemoglobinuria (PNH) are described who had severe vascular complications.The first patient developed extensive thrombosis of the abdominal veins leading to intractable ascites symptomatically treated with a peritoneo-venous shunt. The second patient had aneurysm of the abdominal aorta treated with a prosthetic graft. Although in both patients prosthetic grafts were implanted no signs of an increased activation of the P.N.H. cells were found and no thrombosis or severe haemolytic anaemia occurred.It is suggested that surgical intervention for vascular complications in PNH should not be delayed because of fear of activating the PNH.

Pancreatic and duodenal ammonia in dogs: lowering by glucose infusion.

SummaryAmmonia is produced by some organs and removed by others. Glucose may influence ammonia formation. The contribution of the pancreas to ammonia metabolism is unknown. This study compares pancreatic and duodenal venous ammonia to arterial ammonia in dogs. Pancreatic venous ammonia exceeds arterial ammonia by a factor of 2.8 (range 1.3–9.3); and duodenal ammonia by a factor of 1.1 (range 0.9–2.8). Duodenal venous exceeds arterial ammonia by a factor of 2.4 (range 0.8–5.8). High-dose glucose infusion decreased pancreatic venous ammonia by approximately one-third and duodenal venous ammonia by approximately one quarter, but left arterial ammonia virtually unaltered. The mechanism of pancreatic ammonia production is unknown. We postulate that it may be related to pancreatic bicarbonate synthesis, binding the hydrogen ions which are liberated during this process.