bluuebunny/crossref_metadata_2025 huggingface dataset:
Body composition and adipose tissue cellularity before and after jejuno‐ileostomy in severely obese subjects
Authors: KRAL J. G. , BJÖRNTORP P. , SCHERSTÉN T. , SJÖSTRÖM L.
Published: March 2008

Abstract. In severe obesity with adipose tissue hyperplasia it is difficult to achieve and sustain weight decrease by conventional therapy. Fifteen severely obese patients (mean body weight 135 kg) with hyperplastic obesity had a jejuno‐ileostomy according to Payne to induce weight reduction by controlled malabsorption. Body composition, adipose tissue cellularity, and glucose tolerance were studied before and after the operation when the patients had reached a new stable weight (WS) a mean 21 months after surgery.

Preoperative fat cell number was unchanged at follow‐up, in contrast to all other variables of body composition. Reductions in fat cell size were evenly distributed in different major subcutaneous regions. Body potassium was determined immediately after operation and at 6 months intervals until WS. The postoperative decrease stopped at 6 months, thus differing from the decrease in body weight.

Significant positive correlations between the postoperative decrease in body weight or body fat, and preoperative body weight, body fat and body cell mass were analysed by multiple stepwise regression. Preoperative body weight and body fat were shown to predict postoperative weight loss at a level of P 0.005. A positive correlation between body fat decrease and fat cell number could be explained hypothetically by an increased caloric demand in hyperplastic obesity.
Ethanol‐induced hypoglycaemia in man: its suppression by the alcohol dehydrogenase inhibitor 4‐methylpyrazole
Authors: SALASPURO M. P. , PIKKARAINEN P. , LINDROS K.
Published: March 2008

Abstract. Infusion of ethanol (0.6 g/kg body wt) caused marked hypoglycaemia in subjects fasted for 36 h. Previous administration of the alcohol dehydrogenase (ADH) inhibitor 4‐methylpyrazole (4‐MP, 7 mg/kg body wt i.v.) strongly suppressed the ethanol‐induced hypoglycaemia. The rate of ethanol elimination was 84.6 mg/kg per hour. 4‐MP at the dose used caused a 21% reduction of ethanol elimination, but had no significant effect on blood acetaldehyde levels. 4‐MP also significantly suppressed the ethanol‐induced elevation of blood lactate and almost completely prevented the increase in the 3‐hydroxy‐butyrate/acetoacetate ratio, but had only a slight effect on the lactate/pyruvate ratio of venous blood. The results demonstrate that the hypoglycaemia and lactacidaemia produced by the oxidation of alcohol can be prevented by a dose of 4‐MP that diminishes or prevents the ethanol‐induced shift in the NAD‐coupled redox state of the liver.
Serum immunoreactive prolyl hydroxylase in liver disease
Authors: TUDERMAN LEENA , RISTELI JUHA , MIETTINEN TATU A. , KIVIRIKKO KARI I.
Published: March 2008

Abstract. The concentration of serum immunoreactive prolyl hydroxylase (SIRPH) was measured in thirty patients with chronic active hepatitis, thirteen with primary biliary cirrhosis, four with alcoholic or idiopathic cirrhosis, and four with acute hepatitis; the values were compared with those in twenty‐three control subjects. Increases in SIRPH were found in all the groups with liver diseases, individual values being highest in primary biliary cirrhosis in which about two‐thirds of patients had values more than two standard deviations above the mean value in the control subjects. No correlation was found between SIRPH and other tests of liver function or some routine laboratory tests. SIRPH may reflect some hitherto unknown or unmeasured process in the diseased hepatic cells.
Relationship among the concentrations of serum lipoproteins and changes in their chemical composition in patients with untreated nephrotic syndrome
Authors: GHERARDI E. , ROTA E. , CALANDRA S. , GENOVA R. , TAMBORINO A.
Published: March 2008

Abstract. The quantitative and qualitative changes of serum lipoproteins have been studied in twelve patients with untreated uncomplicated nephrotic syndrome. The lipoprotein disorders found in these patients were characterized by an elevation of VLDL (d < 1.006 g ml‐1), LDL (d 1.006–1.019 g ml‐1) and LDL2 (d 1.019–1.063 g ml‐1) and a diminution of HDL2 (d 1.063–1.125 g ml‐1). These changes were strictly correlated with the concentration of serum albumin and were more pronounced in the patients with serum albumin < 20 g l‐1.

The study of the relationship among the concentrations of the various lipoprotein classes indicated that (i) the levels of VLDL and LDL1 were reciprocally related to that of the high density lipoproteins and (ii) the level of LDL2 rose with the moderately increased VLDL and LDL1 but at the high concentrations of VLDL and LDL1 observed in the severe nephrotic syndrome it did not show any further increase, suggesting a defect in the conversion of VLDL to LDL2.

The nephrotic syndrome was associated with marked changes in the composition of all lipoprotein fractions which were found to contain more phospholipid but less protein than normal. Major changes in composition were observed in VLDL and LDL1 which were rich in esterified cholesterol and phopholipids and had an esterified cholesterol: triglyceride molar ratio (CE/TG) higher than the corresponding fractions of the control subjects. Furthermore, CE/TG ratio in these fractions increased as their serum concentration increased.

These observations indicate that in severe, untreated uncomplicated nephrotic syndrome there is a progressive accumulation of d < 1.019 g ml‐1 lipoproteins rich in esterified cholesterol. Chemically these resemble VLDL and chylomicron remnants and are possibly related to some defect in the conversion of VLDL to LDL2.
The effects of administrations of HCI, NH4CI and NH4HCO3 on the excretion of urea and ammonium in man
Authors: FINE ADRIAN , CARLYLE J. E. , BOURKE E.
Published: March 2008

Abstract. In man, HCl acidosis reduces blood and urinary urea with a concomitant rise in ammonium (NH+4) excretion. Significantly less urea is excreted following NH4Cl administration than following equimolar ingestion of NH4 HCO3. The results of these alterations in nitrogen excretion are interpreted in terms of bicarbonate utilization and production.
Measurement of serum apolipoprotein B by radioimmunoassay
Authors: KARLIN JOAN B. , JUHN DAWN J. , SCANU ANGELO M. , RUBENSTEIN ARTHUR H.
Published: March 2008

Abstract. A sensitive and specific double antibody radioimmunoassay for the major apolipoprotein (apo B) of human serum very low density lipoprotein (VLDL) and low density lipoprotein (LDL) is described. Using anti‐LDL and anti‐apo B antibodies the immunoreactivity of LDL and apo B were compared. Human LDL and its isolated apo B were not immunologically identical when each antiserum was used with its homologous label; a population of antibodies was selected which reacted with antigenic sites unique to the antigen itself as well as to those which were common to the closely related protein. When the heterologous label was used with either antiserum, a population of antibodies directed against antigenic sites shared by the LDL and apo B molecules was selected.

Apo B in sera samples can be measured using either anti‐LDL or anti‐apo B antibodies provided that intact LDL was used for preparation of the iodinated tracer and standard. Serum apo B levels in healthy normolipi‐daemic males and females were 0.93 ±0.25 g/l (range 0.58–1.39) and 0.90 ± 0.15 g/l (range 0.58–1.12), respectively. The total cholesterol and apo B, and phos‐pholipid and apo B concentrations for both males and females were significantly correlated (P<0.05). In another normolipidaemic population (n= 52), total serum apo B values correlated positively with LDL cholesterol (r= 0.92, P< 0.001).

Apo B was measured in sera from patients with abetalipoproteinaemia, familial hypercholesterolaemia and Tangiers disease. Apo B was not detected in the serum of subjects with abetalipoproteinaemia, while the apo B level in the familial hypercholesterolaemic subjects was significantly elevated (range 3.26–4.94 g/l) compared to normals (P<0.001). Serum apo B (0.80 g/l) of the subject with Tangier disease was within the normal range.
Thyroid function after subtotal resection for hyper‐thyroidism: a prospective study
Authors: LUNDSTRÖM B. , GILLQUIST J. , KARLBERG B. , TEGLER L.
Published: March 2008

B.KÅGEDAL1

Abstract. Eight‐seven patients treated for thyrotoxicosis by subtotal thyroidectomy were examined 6 weeks, 6 months and 12 months after surgery. Thirty‐six of the patients were also examined 24 months after surgery.

The patients were divided into two groups according to serum concentration of thyrotrophin (TSH) 6 weeks after surgery. Group I contained fifty‐five patients with a normal serum TSH, of whom three developed recurrent hyperthyroidism during the observation period. The remaining fifty‐two patients were clinically euthyroid during the entire observation period but had rather low serum thyroxine (T4) levels and normal serum triiodothyronine (T3) levels 6 weeks after surgery. Most patients had a normal TSH response to thyro‐trophin‐releasing hormone (TRH). T4 levels rose significantly within 6 months after surgery and then remained almost unchanged.

Group II contained thirty‐two patients with a serum TSH above 5 mU/1 6 weeks after surgery. Seven of these patients developed hypothyroidism within 1 year of surgery. The twenty‐five remaining patients had low serum T4 with normal serum T3 levels at 6 weeks. TSH response to TRH was pathologically raised. Basal TSH level remained raised during the observation period but serum T4 levels approached those in group I within 12 months.

These investigations show that patients with a raised basal serum TSH are at risk of developing hypothyroidism. Normal serum concentrations of thyroid hormones are reached sooner by patients with normal TSH levels than by patients with raised TSH levels. The basal serum TSH level seems to be a better indicator of risk of hypothyroidism than the serum T4 level, which is low in most patients 6 weeks after surgery.
Relation between triglycerides in human skeletal muscle and serum and the fractional elimination rate of exogenous plasma triglycerides
Authors: FRÖBERG S. O. , RÖSSNER S. , ERICSSON M.
Published: March 2008

Abstract. Muscle triglycerides, serum lipid and lipo‐protein concentrations and an intravenous fat tolerance test were determined on thirteen survivors of myocardial infarction and on fourteen subjects referred to a Lipid Clinic but without myocardial infarction.

The mean concentration of triglycerides in muscle and the fractional removal rate k2 of intravenous injected Intralipid were similar in patients with and without MI. In seventeen of these subjects type IV hyperlipoproteinaemia was found.

In type IV patients the muscle triglyceride concentration was twice that found in patients without hyper‐triglyceridaemia. A negative correlation between muscle triglyceride concentration and the k2 value was found for all subjects with a correlation coefficient of —0.62 (P< 0.001). No independent correlations were found between muscle triglyceride and serum triglyceride concentration or the triglyceride concentrations of the major lipoproteins.
Lowering of serum 3,3‘,5‐triiodothyronine thyroxine ratio in patients with myocardial infarction; relationship with extent of tissue injury
Authors: SMITH S. J. , BOS G. , GERBRANDY J. , DOCTER R. , VISSER T. J. , HENNEMANN G.
Published: March 2008

Abstract. Serial measurements of haematocrit (Ht), plasma thyroxine (T4), triiodothyronine (T3) and α‐hydroxybutyrate dehydroxygenase (α‐HBDH) were performed in patients following myocardial infarction (MI). Infarct size was estimated by mathematical analysis of the change in plasma α‐HBDH activity with time. After an initial small increase Ht decreased 12% until day 9 and remained constant thereafter. Serum T4 did not change during the entire study. Serum T3 decreased to 66% at day 9 and then returned to normal within 2 months. These figures are expressed relative to determinations in the first blood sample obtained within 12 h after MI. A significant correlation between the lowest serum T3/T4 ratio and infarct size was observed. These observations suggest that in these patients the peripheral conversion of T4 into T3 is reduced. This was accompanied by an increased production of reverse T3 as evidenced by observations in one patient.
Metabolism of apolipoproteins A‐I and A‐ll and its influence on the high density lipoprotein subfraction distribution in males and females
Authors: SHEPHERD JAMES , PACKARD CHRISTOPHER J. , PATSCH JOSEF R. , GOTTO ANTONIO M. , TAUNTON O. DAVID
Published: March 2008

Abstract. Rate zonal ultracentrifugation of plasma samples from ten healthy age‐matched volunteers (five males, five females) indicated that the high density lipoprotein subfraction ratio (HDL2:HDL3) in females was significantly higher than in males. The cause of this phenomenon was investigated by simultaneous examination of the metabolism of the major HDL apoproteins (apoA‐I and apoA‐II) in both groups. The results show that there is no significant sex‐related difference in the plasma pool size, fractional catabolic rate, or synthetic rate of either apoprotein. We conclude that the increased HDL2:HDL3 ratio in females versus males does not derive from measurable differences in the metabolic handling of either apoprotein.
The Tromsø Heart Study: Serum apolipoprotein Al concentration in relation to future coronary heart disease
Authors: ISHIKAWA T. , FIDGE N. , THELLE D. S. , FØRDE O. H. , MILLER N. E.
Published: March 2008

Abstract. The concentrations of apolipoprotein AI, a major peptide of high density lipoprotein (HDL), have been measured by immunoelectrophoresis in samples of serum from twelve subjects who subsequently developed a coronary event during 2 years of follow‐up and compared with those in serum from sixteen matched control subjects. The mean apolipoprotein AI concentration in the cases was significantly lower than that in the controls, independently of the serum total cholesterol and triglyceride concentrations. There was no significant difference between the cases and controls in mean HDL cholesterol:apolipoprotein AI ratio. Within several case‐control pairs, however, the difference in apolipoprotein AI concentration was proportionately much less than that in HDL cholesterol. On discriminant function analysis, apolipoprotein AI concentration was a less powerful predictor of coronary heart disease than was HDL cholesterol.
Turnover of radiolabelled plasminogen and prothrombin in cirrhosis of the liver
Authors: COLLEN D. , ROUVIER J. , CHAMONE D. A. F. , VERSTRAETE M.
Published: March 2008

Abstract. The turnover of purified radiolabelled plasminogen was studied in four patients with cirrhosis of the liver, and that of radiolabelled prothrombin in six patients with cirrhosis of the liver. The cirrhotic patients showed an increased fractional catabolic rate and a decreased synthetic rate, resulting in subnormal plasma levels of plasminogen and prothrombin. The plasma concentration of the two proteins correlated with the synthetic rate, but not with the fractional catabolic rate. Heparin infusion prolonged the shortened half‐life of plasminogen in two cirrhotics from 1.25 to 2.10 days and from 1.45 to 1.90 days, and the half‐life of prothrombin in three cirrhotics from 2.25 to 2.70 days, from 2.35 to 2.80 days and from 2.40 to 3.70 days. These results indicate that the abnormal turnover of labelled plasminogen and prothrombin in cirrhosis of the liver is due to two mechanisms: increased breakdown, reversible by heparin administration, and impaired synthesis. The decreased plasma levels are, however, mainly caused by decreased synthesis.
Influence of chenodeoxycholic acid on the kinetics of endogenous triglyceride transport in man*
Authors: BEGEMANN F.
Published: March 2008

Abstract. Plasma lipids and triglyceride kinetics were studied in ten subjects before and after 6–8 weeks treatment with 1 g/day chenodeoxycholic acid for radio‐lucent gallstones. Plasma triglyceride concentration fell by 20% and phospholipid concentration rose by 5% on average; there was no change in cholesterol or free fatty acids. Body weight remained constant. Triglyceride kinetics, studied by a precursor‐labelling technique, revealed a reduction both of triglyceride plasma pool and turnover rate, accompanied by a decline of more than 35% both of plasma triglyceride precursor pool and of incorporation of plasma free fatty acids into newly synthesized plasma triglycerides. Fractional turnover rates in both pools remained unaltered. The appearance‐time for newly synthesized plasma triglycerides after injection of label did not change. These results indicate that chenodeoxycholic acid lowers plasma triglyceride by reducing its synthesis, thereby precluding alternative, and possibly undesired, modes of action, such as impaired secretion or increased peripheral catabolism of endogenous triglyceride. Several biochemical mechanisms may be responsible for this effect, among which stimulation of phospholipid synthesis by bile acids could play a role.
Hepatic and extrahepatic triglyceride lipase activity in uraemic patients on chronic haemodialysis
Authors: BOLZANO K. , KREMPLER F. , SANDHOFER F.
Published: March 2008

Abstract. In eleven patients with chronic renal insufficiency treated by intermittent haemodialysis and in ten normal subjects, hepatic and extrahepatic triglyceride lipase activity of post heparin plasma was selectively measured, utilizing the different sensitivity of both enzymes to inhibition by protamine sulphate. In uraemic patients, hepatic triglyceride lipase activity was significantly decreased and extrahepatic triglyceride lipase activity was normal when compared with the control group.

The uraemic subjects showed a moderate hypertri‐glyceridaemia; their serum cholesterol level, however, was normal. The high triglyceride concentration was due to an increase of very low density lipoproteins and low density lipoproteins of the density between 1.006 and 1.019g/ml (LDL1) The concentration of low density lipoproteins of the density between 1.019 and 1.063g/ml (LDL2) was decreased. LDL2 were relatively rich in triglycerides when compared with LDL2 from the control group.
Skin polyamine levels in psoriasis: the effect of dithranol therapy*
Authors: BÖHLEN P. , GROVE J. , BEYA M. F. , KOCH‐WESER J. , HENRY M. H. , GROSSHANS E.
Published: March 2008

Abstract. Concentrations of putrescine, spermidine and spermine were determined in biopsies of skin of eight control subjects and of uninvolved skin and skin lesions of eight psoriatic patients before and after topical therapy with dithranol. Mean spermidine and spermine concentrations in uninvolved skin of psoriatic patients were normal, but putrescine concentration was elevated. In psoriatic skin lesions all three mines were significantly elevated. Chemotherapy effectively reduced polyamine concentrations in involved skin towards normal. This decrease in polyamine levels correlated with reduction of the proliferative activity of the epidermis and with clinical improvement of the patients.
Polymorphic acetylation and aminopyrine demethylation in Gilbert's syndrome
Authors: PLATZER R. , KÜPFER A. , BIRCHER J. , PREISIG R.
Published: March 2008

Abstract. Polymorphic acetylation was investigated in twenty‐seven patients with Gilbert's syndrome using the sulphadimidine test. Whereas the finding of 51% slow acetylators in seventy‐eight control persons agreed well with the expected frequency in a continental European population, the prevalence of slow acetylators in Gilbert's syndrome was increased to 78% (P<0.03, Woolfs G‐test). After oral administration of 14C‐aminopyrine there was no significant difference between seventeen patients with Gilbert's syndrome and twenty‐seven normal controls in total plasma clearance of aminopyrine (280 ± SD 100 and 270 ± 60 ml/min) and in the disappearance curve of 14CO2 in breath (0.23 ± 0.04 and 0.22 ± 0.03 h‐1 respectively). Thus, whereas aminopyrine metabolism appears unaffected in the examined patients, the data documents a new association between slow acetylator status and Gilbert's syndrome.
Quantitative changes of serum lipoprotein‐X after cholestyramine administration in infants with cholestatic biliary tract and liver disease
Authors: POLEY J. R. , CAPLAN D. B. , MAGNANI H. N. , ALAUPOVIC P. , SMITH E. I. , CAMPBELL D. P. , BHATIA M. , BURDELSKI M. , BOJANOVSKI D.
Published: March 2008

5Department of Pediatrics, Medizinische Hochschule Hannover, GFR

Abstract. Lipoprotein‐X (LP‐X) was determined before and after the administration of cholestyramine in fifty‐five infants with persistent cholestatic jaundice to differentiate between intra‐ and extrahepatic disease.

In twenty‐seven infants with biliary atresia, serum LP‐X prior to cholestyramine ranged from 0.87 to 11.42 g/1 (mean: 3.43 g/l); the average concentration was significantly lower (P < 0.001) in males. After cholestyramine, LP‐X rose in twenty‐three, remained the same in two, and decreased slightly in two infants.

Serum LP‐X was present in twenty of the twenty‐eight infants with intrahepatic cholestasis prior to cholestyramine in concentrations from 0.84 to 14.19 g/l (mean: 3.13 g/l). After cholestyramine, LP‐X decreased in all by an average of 78% (P< 0.005). The other eight infants did not have LP‐X before or after cholestyramine.

This study shows that LP‐X in the serum of infants with cholestatic jaundice indicates severe cholestasis, but is not itself diagnostic of biliary atresia. The differentiation of biliary atresia from other diseases is readily achieved, as the administration of cholestyramine for 2–3 weeks causes a marked decrease of serum LP‐X in patients with patent extrahepatic bile ducts. The absence of serum LP‐X excludes biliary atresia.
Increased excretion of two sialic acid‐containing trisaccharides in the urine of patients with rheumatoid arthritis
Authors: MAURY PETER
Published: March 2008

Abstract. The urinary excretion of sialic acid‐containing trisaccharides in patients with active rheumatoid arthritis was studied. Sialyl‐lactose and sialyl‐N‐acetyl‐lactosamine were identified and their excretion patterns studied by thin layer and gas chromatography. The urinary output of sialyl‐lactose was greater in patients with active rheumatoid arthritis (48.2 ± 6.1 nig/24 h, SEM, n = 6) than in healthy subjects (19.8 ± 3.7 mg/24 h, SEM, n = 5; P< 0.01). The excretion of sialyl‐N‐acetyllactosaniine was also higher in the rheumatoid group (18.5 ± 2.1 mg/24 h, SEM, n= 6) than in the controls (11.1 ± 1.2 mg/24 h, SEM, n= 5; P< 0.05). The qualitative excretion patterns of the sialyl‐oligo‐saccharide fraction were similar for the two groups as judged from the thin layer chromatograms. Correlating the results with the clinical state of the patients with rheumatoid arthritis suggests that the urinary level of the sialyl‐oligosaccharides reflects the activity of the disease. A proposed mechanism for the increased excretion of sialic acidcontaining trisaccharides in rheumatoid arthritis is presented.
Effect of continuously increasing concentrations of plasma ketone bodies on the uptake and oxidation of glucose by muscle in man
Authors: WICKLMAYR M. , DIETZE III G.
Published: March 2008

Abstract. Muscle metabolism in man was studied by measuring the arterial and deepvenous concentrations of glucose, lactate, pyruvate, free fatty acids, β‐hydroxy‐butyrate and acetoacetate, and forearm blood flow. After the subjects had fasted overnight, their arterial free fatty acid and ketone levels rose continuously during a period of 90 min, leading to increased ketone body uptake by muscle. Hence, for each subject, a relation was obtained between arterial concentrations and arterial‐deepvenous differences of P‐hydroxybutyrate and acetoacetate. As the ketone body utilization increased, the release of lactate rose as well. In spite of these alterations the uptake of glucose remained unchanged. These findings underline the current notion that accelerated ketone uptake reduces pyruvate oxidation but not glucose uptake by muscle.
Bile acid profiles in urine of patients with liver diseases
Authors: BREMMELGAARD A. , SJÖVALL J.
Published: March 2008

Abstract. Quantitative gas chromatography‐mass spectrometry was used to study the metabolic profiles of unconjugated, conjugated and sulphated bile acids in urine of patients with intermittent intrahepatic cholestasis of unknown aetiology, cirrhosis of the liver, primary biliary cirrhosis, viral and toxic hepatitis and extrahepatic cholestasis.

A large number of bile acids was present which can broadly be classified into four groups: cholic and chenodeoxycholic acids constituted between 49·4% and 77·9% of the total bile acids (mean values of the groups); deoxycholic and other 3,12‐disubstituted bile acids between 1·3% and 12·3%, monohydroxy bile acids between 6·7% and 14·4% and bile acids hydroxylated at C‐1 or C‐6 between 4·6% and 14·6%. The high proportion of bile acids from the latter group, and the presence of tetrahydroxylated bile acids, clearly distinguished hepatic disease from the normal state. The metabolic profiles were very variable and there were few consistent differences between the groups of diseases studied. Norcholic acid constituted a significantly higher percentage of the total bile acids in cirrhotic patients (6·2 ± 6·8%) than in non‐cirrhotic patients (1·3±1·8%, P<0·001). With this exception, no profile was specific for any type of intra‐ or extra‐hepatic cholestasis.

The excretion rates of the major l‐hydroxylated bile acids were positively correlated to each other. The same was true for the major 6‐hydroxylated bile acids. This may indicate that cholic, chenodeoxycholic and deoxycholic acids act as substrates for common 1‐ and 6‐hydroxylating enzymes. Possibly the taurine conjugates are preferred substrates since 1‐hydroxylated bile acids and hyocholic acid were found mainly in this fraction. A positive correlation between the excretion of sulphated 3β‐hydroxy‐5‐cholenoic acid and 3β,12α‐dihydroxy‐5‐cholenoic acid indicates a direct metabolic relationship between these compounds.

Confirming previous data, a high proportion of bile acids was sulphated. The degree of sulphation increased with decreasing number of hydroxyl groups, reaching 100% for the monohydroxy and most of the dihydroxy acids. Tetrahydroxycholanoates were not sulphated, and sulphation of trihydroxycholanoates was positively correlated to the renal bile acid excretion rate.

Bile from patients with intermittent intrahepatic cholestasis did not contain the tetrahydroxylated bile acids present in urine. Hyocholic acid was a very minor, mainly taurine conjugated, bile acid. Monohydroxy bile acids were usually below the detection limit. These data do not support the hypothesis that lithocholic acid participates in the initiation or perpetuation of intermittent intrahepatic cholestasis of unknown aetiology.
HLA B27 and defects in the T‐cell system in Whipple's disease
Authors: FEURLE GERHARD E. , DÖRKEN BERND , SCHÖPF ERWIN , LENHARD VOLKER
Published: March 2008

Abstract. The cellular immune system was tested in nine patients with Whipples' disease. Three patients had active disease, and six had been in remission for up to 10 years. Intradermal delayed hypersensitivity reactions to candidin, trichophytin, tuberculin and varidase, T‐cell counts as determined by E‐rosettes, allogeneic stimulation of lymphocytes in the mixed lymphocyte culture, and mitogenic activation of lymphocytes by concanavalin A, phytohaemagglutinin and by pokeweed mitogen, were tested in the patients and compared with control subjects. HLA typing was performed in all patients. The reaction to tuberculin and varidase, the T‐cell counts and the activation of lymphocytes by concanavalin A were significantly reduced in patients with active disease and in patients during remission. The reaction to candidin and trichophytin was poor even in the controls. The mean results of the mixed lymphocyte culture, phytohaemagglutinin, and pokeweed mitogen activation tests were not significantly different from the controls. In patients with active disease the mixed lymphocyte culture reaction and the T‐cell counts were less than in patients in remission. The results suggest a persistent defect of T‐cells in patients with Whipple's disease, a defect that is more severe in patients with active disease. The finding of HLA B27 in four of the nine patients supports the hypothesis of primary rather than secondary impairment of the cellular immune system in Whipple's disease.
On the contribution of prostaglandin‐like substances to the action of bradykinin on intestinal motility and blood flow in canine jejunal loop in situ
Authors: PYTKOWSKI BOHDAN
Published: March 2008

Abstract. Blood flow and motility were studied in a canine jejunal loop in situ with intact innervation.

Bradykinin was administered into a side branch of the supplying artery and indomethacin was infused intravenously I h before experiments. In the control group without indomethacin infusion, bradykinin 1–10 nmol/l gradually increased blood flow without significantly altering motility. Higher concentrations of bradykinin (20–100 nmol/l) augmented rhythmic contractions of the intestine. Phasic blood flow decreased during contraction and increased after relaxation, and mean blood flow increased. Bradykinin (0·2–1·0 μmol/l) caused tonic intestinal contractions. Blood flow initially increased but was soon impeded in proportion to the amplitude and duration of the tonic contractions. With intestinal muscle relaxation, blood flow increased to values markedly higher than control. In the group pretreated with indomethacin, blood flow did not increase after bradykinin administration. However, administration of PGE2 produced significant increase in flow, similar to that observed after bradykinin. Acetylcholine or isoprenaline also markedly increased blood flow.

Increased intestinal motility caused by bradykinin mechanically impeded blood flow through the intestine, thus masking its direct vasodilating action. The action of bradykinin on the intestinal vascular bed is probably mediated or modulated by endogenous prostaglandin‐like substances.
Lactate elimination in man: effects of lactate concentration and hepatic dysfunction
Authors: WOLL P. J. , RECORD C. O.
Published: March 2008

Abstract. Lactate elimination was studied in twenty‐six healthy volunteers during primed constant lactate infusion or multiple lactate injection tests, at blood lactate concentrations of 1–8 mmol‐1. Although lactate elimination fitted a single exponential curve over a 30 min period, a significant correlation between the rate removal constant (KL) and the peak blood lactate concentration (Lø) was demonstrated:

logeKL= ‐ 2·43 ‐ 0.132 Lø (P= 0·003, r= 0·63, n= 20)

This suggests that lactate removal does not follow first order kinetics over a wide concentration range but becomes saturated at relatively low blood lactate concentrations. Estimates of the lactate distribution volume did not differ significantly at different dosage levels, but remained in the range 270–300 ml kg‐1. Skeletal muscle uptake accounted for about 26% of the infused lactate load.

Seven patients with well‐compensated hepatic cirrhosis were compared with a group of six control subjects during primed constant infusion tests. Fasting and steady state blood lactate concentrations achieved were similar in both groups. A significant prolongation in lactate half‐life was demonstrated in the cirrhotics (18·8 ± 1·4 min (mean ± SEM) compared to 14·7 ± 2·2 min; P < 0·02). Since peripheral uptake of lactate in the forearm was similar in the two groups, this suggests that hepatic lactate uptake was impaired, due either to hepatocyte dysfunction or portal diversion.
Mechanism of regulation of 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase activity by low density lipoprotein in human lymphocytes
Authors: KRONE W. , BETTERIDGE D. J. , GALTON D. J.
Published: March 2008

Abstract. The mechanism of action of low density lipoprotein (LDL) on the rate of sterol synthesis and on the activity of its rate‐determining enzyme 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase‐(HMG‐CoA reductase) was studied in lymphocytes freshly isolated from normal subjects and patients heterozygous for familial hypercholesterolaemia.

Incubation of normal cells in lipid‐depleted serum led to a substantial rise in the rate of sterol synthesis from [14C]acetate. Addition of cycloheximide (20 μg/ml), a translational inhibitor, reduced sterol synthesis; addition of LDL (100 μg LDL‐cholesterol/ml) had a similar effect as cycloheximide in reducing sterol synthesis with a half‐life of about 3 h.

Cordycepin (50 μg/ml) inhibited messenger RNA synthesis by more than 50% but had no inhibitory effect on the induction of sterol synthesis suggesting that the induction of the pathway is independent of newly synthesized messenger RNA.

Lymphocytes from patients heterozygous for familial hypercholesterolaemia behaved similarly to cells from normal subjects in that cycloheximide reduced the incorporation of [14C]acetate into sterols, while cordycepin had no effect on the induction of sterol synthesis mediated by lipid‐depleted serum.

Since sterol synthesis from [14C]acetate can be taken as a measure of HMG‐CoA reductase activity under our experimental conditions, the results suggest that: (i) the increase HMG‐CoA reductase activity in cells incubated in the presence of lipid‐depleted serum is due to increased de novo synthesis of the enzyme which can rapidly be inhibited by the addition of LDL, and (ii) in lymphocytes from normal subjects and patients heterozygous for familial hypercholesterolaemia the induction of HMG‐CoA reductase by lipid‐depleted serum and, by implication, the subsequent repression of the enzyme by LDL cannot be accounted for by a corresponding increase or decrease in the synthesis of messenger RNA.
Urinary bile acids during development of recurrent cholestasis of pregnancy
Authors: THOMASSEN PETER A.
Published: March 2008

Abstract. The pregnancies of two patients with mild intrahepatic cholestasis of pregnancy (RCP) were followed with detailed analyses of bile acids in urine. About twenty‐five different bile acids were determined by GC/MS following separation according to mode of conjugation. The results were collated with the clinical course of the disease.

The first detectable change in bile acid excretion was the appearance of tetrahydroxylated bile acids at about the 30th gestational week. Somewhat later and concomitant with the rise in urinary oestriol, the total bile acid excretion started to increase. In one of the patients, who had a maximum total excretion of 84 μmol/24 h, deoxycholic acid was a major constitutent, comprising about 40% of the total. The same patient had only slightly elevated levels of tetrahydroxylated bile acids and serum amino‐transferases. The possible effect of low‐fat diet on these results is discussed.

Monohydroxylated bile acids were present throughout the pregnancies in small amounts and their role as aetiological factors is discussed. The care of RCP patients is outlined, and the need for simple, specific and quantitative methods for following the course of RCP is pointed out.
Urinary bile acids in late pregnancy and in recurrent cholestasis of pregnancy
Authors: THOMASSEN PETER A.
Published: March 2008

Abstract. The metabolic profiles of urinary bile acids in pregnant women in the last trimester and patients with recurrent intrahepatic cholestasis of pregnancy (RCP) were studied. Following separation according to mode of conjugation, about thirty different bile acids were quantitatively analysed by gas chromatography‐mass spectrometry. In all patients the sulphate fraction comprised 50–90% of the total bile acids. In RCP a shift from glycine to taurine conjugation was noted together with a slight relative increase in sulphation.

A ten‐ to hundred‐fold increase in cholic and chenodeoxycholic acids was seen in RCP, the increase being mainly in the sulphate fraction. Tetrahydroxylated bile acids, tentatively regarded as 1‐ and 6‐hydroxylated products of cholic acid, were quantitatively important in patients with RCP. The relative amounts of the secondary bile acids, deoxycholic and lithocholic acids, decreased with increasing cholestasis. Metabolites hydroxylated at C‐6 were common, and the excretion of hyocholic acid was positively correlated to that of chenodeoxycholic acid. An increase in the excretion of 5α‐configurated bile acids in RCP was noted.

A positive correlation between the excretion of 3β‐hydroxy‐5‐cholenoic acid and 3β,12α‐dihydroxy‐5‐cholenoic acid indicates a metabolic relationship between the two compounds. Because of the relatively small amounts of lithocholic and 3β‐hydroxy‐5‐cholenoic acids in patients with RCP, these compounds do not seem to be of pathogenetic importance in this type of cholestasis.
Transport of vitamin D sterols in human plasma: effect of excess vitamin D, 25 hydroxyvitamin D and 1,25 dihydroxyvitamin D
Authors: SILVER JUSTIN , FAINARU MENAHEM
Published: March 2008

Abstract. Vitamin D and its more active metabolites, 25 hydroxyvitamin D (25‐OH‐D) and 1,25‐dihydroxy‐vitamin D (1,25‐(OH)2‐D), are transported in human plasma on a specific binding protein (DBP), which has been shown to have an α‐globulin electrophoretic mobility. Since the concentration of DBP in normal human plasma is approximately 5 μmol/l, whereas that of all the vitamin D metabolites is less than 0·2 μmol/l, DBP is less than 3% saturated under physiological conditions. We have studied the transport of the above‐mentioned metabolites in human plasma in vitro at normal and saturating concentrations. Human plasma was incubated with increasing amounts of vitamin D metabolites together with their radiolabelled tracers. Ultracentrifugation was used to isolate plasma lipoproteins (density, d < 1·21 g/ml) and agarose gel electrophoresis of lipoprotein‐free plasma (d > 1·21 g/ml) to separate DBP (α globulin) from albumin. The recovery of the tracer in plasma proteins was always more than 80%. At physiological concentrations [3H]25‐OH‐D bound almost exclusively to DBP (98%), [3H]vitamin D or [14C]vitamin D bound both to DBP and to lipoproteins (40%), and [3H]1,25‐(OH)2‐D bound to DBP (62%), to lipoproteins (15%) and also to albumin (23%). When the concentration of vitamin D metabolites was increased, DBP became saturated. The binding capacity of DBP was similar for all three sterols, about 5 μmol/l plasma, or one mole of sterol per mole of protein, but the saturating concentration was different for the three sterols (vitamin D > 1,25‐(OH)2‐D > 25‐OH‐D). 25‐OH‐D had the greatest affinity for DBP, and it completely displaced both vitamin D and 1,25(OH)2‐D from DBP at higher concentrations. All sterols bound to both plasma lipoproteins and albumin: vitamin D preferentially to lipoproteins and both 25‐OH‐D and 1,25‐(OH)2‐D to albumin. A similar binding pattern for vitamin D in plasma was observed previously by us in a child with vitamin D toxicity. The increased binding of vitamin D to lipoproteins and especially to albumin may help explain the pathogenesis of toxicity in hypervitaminosis D, where the plasma levels of the more active metabolites are insufficient to account for the clinical signs.
Influence of meal frequency on diurnal lipid, glucose and insulin levels in normal subjects on a high fat diet; comparison with data obtained on a high carbohydrate diet
Authors: GENT C. M. VAN , MIRANI‐OOSTDIJK C. PAGANO , REINE P. H. VAN , FRÖLICH M. , HESSEL L. W. , TERPSTRA J.
Published: March 2008

Abstract. Diurnal levels of serum triglyceride (TG) were measured in six normal persons consuming a fixed solid 65% fat diet under steady state conditions in a metabolic unit. The food was divided into either three or eight similar portions, differently spaced over the day and night.

The diurnal TG‐profiles on this diet were practically identical to those found under comparable conditions on a 65% carbohydrate diet [1]. Mean diurnal TG values did not significantly differ with varying meal frequency. Free fatty acid levels, however, were significantly higher on a high fat diet.

Post‐prandial glucose and insulin responses did not significantly differ whether a high fat diet or a high carbohydrate diet was consumed.

We conclude that the composition of the diet is of little importance in determining diurnal TG patterns when the diet consists of normal food stuffs, but that these patterns are dependent on meal frequency and distribution.
The significance of gross elevations of the erythrocyte sedimentation rate in a general medical unit
Authors: FORD M. J. , INNES J. A. , PARRISH FRANCES M. , ALLAN N. C. , HORN D. B. , MUNRO J. F.
Published: March 2008

Abstract. One hundred consecutive patients with an ESR of 100 mm or more in the first hour admitted to a general medical unit were studied. Their mean age was 67 years and forty‐seven were male. Three patients recovered without a satisfactory diagnosis. In thirty‐three of the remainder a single diagnosis was considered responsible for the elevation of the ESR, and in the others multiple diagnoses were found. Infection was found in 60% of patients, malignancy in 28% (including 7% with myelomatosis), rheumatoid disease in 20% and renal disease in 11%. 34% of patients died within 6 months of entry into the study. In the absence of rheumatoid disease or a paraproteinaemia, elevation of the ESR in excess of 60 mm in the first hour at 1 month or longer was associated with a particularly poor prognosis. This study has shown the diagnostic implications of an ESR of 100 mm or more in the first hour and the prognostic significance of a persistent elevation of the ESR.
Hereditary deficiency of triosephosphate isomerase in four unrelated families
Authors: EBER STEFAN W. , DÜNNWALD MANFRED , BELOHRADSKY BERND H. , BIDLINGMAIER FRANK , SCHIEVELBEIN HELMUT , WEINMANN HANS M. , KRIETSCH WOLFGANG K. G.
Published: March 2008

Abstract. Triosephosphate isomerase deficiencies in erythrocytes and leucocytes were discovered in three unrelated families by a heterozygote screening of 3000 blood samples. In addition, a family found by Schröter et al. [not published] was studied. In these four families, only heterozygote carriers were found. In the family described by Freycon et al. with hetero‐ and homozygote carriers of triosephosphate isomerase deficiency, the heterozygotes were reinvestigated. There was 51% of normal enzyme activity in three of the families. In the other two families the enzyme activity was 64% and 71% of normal. Two of the eleven heterozygotes, both children, were diseased, but it seems unlikely that the disorders resulted from the deficiencies.

The activities of thirteen enzymes, the Km of triosephosphate isomerase for glyceraldehyde phosphate and the concentrations of metabolites were normal. Antibody titration showed normal specific activities in four families and 50% of normal in one family. No electrophoretic variant was detected.

From the proved heredity, a heterozygous frequency of at least 1/1000 is indicated. A maximal frequency of 5/1000 is estimated by using further instances of triosephosphate isomerase deficiency where heredity has not yet been investigated. An explanation for the small number of known cases is that this enzyme is not routinely assayed.
Reduced high density lipoprotein in stroke: relationship with elevated triglyceride and hypertension
Authors: TAGGART H. , STOUT R. W.
Published: March 2008

Abstract. Lipids and lipoproteins were analysed in forty‐one survivors of stroke, aged less than 65 years, and the same number of age and sex matched controls without vascular disease. The stroke subjects had no evidence of coronary artery or peripheral vascular disease. High density lipoprotein cholesterol was significantly lower (1.19 ± 0.06 mmol/l) in the stroke subjects than the controls (1.47 ± 0.07 mmol/l). Triglyceride was also elevated in the stroke subjects, but this was confined to those who were taking antihypertensive treatment which included beta‐blockers and/or thiazides. The low levels of high density lipoprotein in stroke were independent of hypertension or its treatment. Thus low levels of high density lipoprotein appear to be associated with cerebrovascular disease, while elevated triglyceride is a complication of anti‐hypertensive therapy.
Uraemic sympathetic neuropathy after haemodialysis and transplantation
Authors: RÖCKEL A. , HENNEMANN H. , STERNAGEL‐HAASE A. , HEIDLAND A.
Published: March 2008

Abstract. Autonomic function in patients with uraemia treated conservatively, by haemodialysis, and by transplantation was evaluated by the pupillary reaction to tyramine, the Valsalva manoeuvre and a postural tolerance test.

The pupillary reaction to tyramine is diminished in haemodialysis patients compared with control subjects. Renal transplantation improves, but does not correct the pupillary reaction to tyramine. The frequency of the diminished response roughly correlates with the degree of renal insufficiency, with results of a Valsalva manoeuvre, and with postural tolerance tests. Our data show that uraemic autonomic dysfunction is improved by successful renal transplantation, but not by adequate haemodialysis.
Effects of chlorpromazine hydrochloride on bile salt synthesis, bile formation and biliary lipid secretion in the Rhesus monkey: a model for chlorpromazine‐induced cholestasis
Authors: ROS EMILIO , SMALL DONALD M. , CAREY MARTIN C.
Published: March 2008

Abstract. We studied the acute effects of intravenous infusions of chlorpromazine hydrochloride on bile salt synthesis, bile formation and biliary lipid secretion in the alert female Rhesus monkey prepared with a total biliary fistula and in a steady bile salt secretory state. In twelve studies (three animals), five doses of radio‐labelled chlorpromazine hydrochloride (1–10 mg = 2.8–28 μmol/kg) were infused intravenously for 1 h in random order. Cholestasis was induced within minutes in all experiments. The radiolabel appeared rapidly in bile, with similar recoveries in bile and urine and a 90% total cumulative output in 4 days. Both bile flow, bile salt and other biliary lipid outputs were inhibited in a dose related and reversible manner. The apparent bile salt independent bile flow was consistently abolished, and a prompt return to basal values occurred when biliary concentrations of the drug and metabolites fell below 1–2 mM. When chlorpromazine hydrochloride was infused at three doses (2.5, 5.0 and 10.0 mg = 7–28 μmol/kg) during constant intravenous infusion of 14C sodium taurocholate (300 μmol/h), bile flow, total bile salt output and 14C taurocholate output decreased within minutes. This was accompanied by a progressive rise in the serum 14C taurocholate concentration. After 90 min the taurocholate specific activity in bile increased significantly indicating that bile salt synthesis was inhibited. Secretion of retained bile salts and reversal of inhibition of bile salt synthesis occurred with time: the course of both events was correlated with the dose of the drug.

Thus, in monkeys, chlorpromazine hydrochloride induces reversible, dose related cholestasis involving suppression of the bile salt dependent and independent flow, inhibition of bile salt synthesis and impairment of biliary lipid secretion. We suggest that these effects are due to both bile salt‐chlorpromazine interactions and the effect of the latter on canalicular and other membranes.