Serum Lipids in Cholelithiasis: Effect of Chenodeoxycholic Acid Therapy

Hypercholesterolaemia has been predicted as a possible complication of chenodeoxycholic acid treatment for gall stones. To exclude this, fasting serum lipids were measured in patients with stones before and at monthly intervals for six months after starting chenodeoxycholic acid. Before treatment half of a group of 36 patients with presumed cholesterol gall stones had serum cholesterol levels exceeding 260 mg/100 ml or serum triglyceride values greater than 160 mg/100 ml or both; these lipid levels were significantly greater than those in control subjects matched for age and sex. Treatment with chenodeoxycholic acid (0·5-1·5 g/day by mouth) did not change serum cholesterol levels but did significantly reduce serum triglyceride concentrations from a pretreatment level of 118 (± S.E. of mean 11·7) mg/100 ml to 95 (± 7·2) mg/100 ml after six months of therapy. The mechanism of this triglyceride-lowering action of chenodeoxycholic acid is not known, but it may have therapeutic value in patients with hypertriglyceridaemia.     

Relation between Plasma Lignocaine Levels and Induced Haemodynamic Changes

Intravenous lignocaine (1 mg./kg. body weight) was found to produce insignificant haemodynamic changes, and in particular no reduction in myocardial contractility. A rate of 2 mg./minute infused intravenously is suggested for therapeutic purposes.In anaesthetized dogs an infusion of 13·5 mg./minute caused moderate haemodynamic depression and a maximum plasma level of 7 μg./ml. Massive injections of 200 and 400 mg. of lignocaine produced a maximum plasma level of 13·8 and 27·8 μg./ml., respectively, and in the latter failure of myocardial contraction in the presence of a normal E.C.G. ensued (“pump failure”). Lignocaine appears to alter the uptake of calcium by myocardial sarcoplasmic reticulum, and this may explain the negative inotropic effect of large doses.     

Studies on the congenitally goitrous sheep. The iodinated compounds of serum, and circulating thyroid-stimulating hormone

1. A group of normal and congenitally goitrous Merino sheep were investigated to identify the metabolic defect present in the abnormal animals. 2. Protein-bound iodine concentrations of serum from goitrous animals (average 5·7μg./100ml.) were higher than normal (average 4·2μg./100ml.; P 0·001), but the hormonal iodine measured as butanol-extractable ¹³¹I was low in the serum of goitrous (average 40·3% of protein-bound ¹³¹I) compared with that of normal (84·2%; P 0·02) sheep. The non-hormonal iodine of the serum of goitrous sheep appeared to include iodotyrosines and iodinated protein. 3. Starch-gel-electrophoretic separations of sera from normal and goitrous sheep after ¹³¹I injection (100–500μc) showed no qualitative differences in the radioactivity of protein components. No significant differences in thyroxine-binding in vitro by serum proteins of normal and goitrous sheep were observed. 4. The clearance rates of ¹³¹I-labelled iodotyrosines (t_½ 1·2–2·9hr.) and iodothyronines (t_½ 33·5–47·4hr.) were similar in normal and goitrous sheep. 5. The concentration of circulating thyroid-stimulating hormone was significantly higher (P<0·01 in three sheep, P<0·05 in one sheep) in goitrous sheep. 6. The congenital goitre appears to be due to compensatory hypertrophy of the gland resulting from an inability to synthesize an adequate supply of thyroid hormone.     

Metabolic Effects of Oestrogen Treatment in Patients with Carcinoma of Prostate: A Comparison of Stilboestrol and Conjugated Equine Oestrogens

Serum cholesterol and triglyceride levels were estimated and oral glucose tolerance tests performed on 16 patients with carcinoma of the prostate before treatment and while receiving stilboestrol in doses of 1 mg, 7·5 mg, and 15 mg daily and conjugated equine oestrogens (Premarin) 15 mg daily. Serum triglyceride levels were greater than 170 mg/100 ml in nearly all the patients while receiving Premarin or stilboestrol 7·5 mg and 15 mg daily. In six out of 10 patients who were given stilboestrol 1 mg daily the serum triglycerides remained within the normal range. No significant effects on serum cholesterol levels or glucose tolerance tests were observed with the various oestrogen regimens. The results support previous suggestions that a daily dose of 1 mg of stilboestrol should be regularly used in the treatment of carcinoma of the prostate.     

Secretory IgA in Urinary Tract Infections

Secretory IgA, measured by radial immunodiffusion, was compared in the urine of children with chronic and recurrent non-obstructive urinary tract infections with that in normal children. IgA, IgG, and IgM were also measured. Absent and low levels of IgA(s) were found in both groups; however, the mean levels of IgA(s) were significantly higher in the infected group compared with normals—3·3 to 0·78 mg./24 hours, respectively. Secretory IgA was found to be locally produced in the bladder. It is suggested that IgA(s) levels reflect an antibody response to infection.     

Serum and Urinary Folate in Liver Disease

During the active phase of viral hepatitis urinary folate loss was found to be 8·0 to 48·3 (mean 31·1) μg./day, compared with a normal urinary folate excretion of 0·1 to 18·0 (mean 9·5) μg./day. In cirrhosis and cardiac failure with congestive hepatomegaly the corresponding values were 25·8 to 55·0 (mean 35·7) μg./day and 2·5 to 61·6 (mean 26·9) μg./day, respectively. Urinary folate loss may be a significant factor in the aetiology of folate deficiency of chronic liver disease, particularly when dietary intake is poor.After prolonged dialysis in Visking casing urinary folate was almost totally dialysable, but an appreciable fraction of serum folate was not, even after 72 hours. The dialysable (free) folate fraction of serum and urine disappeared maximally during the first six hours'' dialysis, and was virtually cleared after 24 hours'' dialysis; clearance curves in normal individuals and in liver disease were comparable. The non-dialysable serum folate fraction was of similar magnitude in all subjects studied, in spite of marked variation in total folate, and probably represented protein-bound folate.     

Switching Patients with Non-Dialysis Chronic Kidney Disease from Oral Iron to Intravenous Ferric Carboxymaltose: Effects on Erythropoiesis-Stimulating Agent Requirements,Costs, Hemoglobin and Iron Status

Background

Patients with non-dialysis-dependent chronic kidney disease (ND-CKD) often receive an erythropoiesis-stimulating agent (ESA) and oral iron treatment. This study evaluated whether a switch from oral iron to intravenous ferric carboxymaltose can reduce ESA requirements and improve iron status and hemoglobin in patients with ND-CKD.

Methods

This prospective, single arm and single-center study included adult patients with ND-CKD (creatinine clearance ≤40 mL/min), hemoglobin 11–12 g/dL and iron deficiency (ferritin <100 μg/L or transferrin saturation <20%), who were regularly treated with oral iron and ESA during 6 months prior to inclusion. Study patients received an intravenous ferric carboxymaltose dose of 1,000 mg iron, followed by a 6-months ESA/ ferric carboxymaltose maintenance regimen (target: hemoglobin 12 g/dL, transferrin saturation >20%). Outcome measures were ESA dose requirements during the observation period after initial ferric carboxymaltose treatment (primary endpoint); number of hospitalizations and transfusions, renal function before and after ferric carboxymaltose administration, number of adverse reactions (secondary endpoints). Hemoglobin, mean corpuscular volume, ferritin and transferrin saturation were measured monthly from baseline until end of study. Creatinine clearance, proteinuria, C-reactive protein, aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase bimonthly from baseline until end of study.

Results

Thirty patients were enrolled (age 70.1±11.4 years; mean±SD). Mean ESA consumption was significantly reduced by 83.2±10.9% (from 41,839±3,668 IU/patient to 6,879±4,271 IU/patient; p<0.01). Hemoglobin increased by 0.7±0.3 g/dL, ferritin by 196.0±38.7 μg/L and transferrin saturation by 5.3±2.9% (month 6 vs. baseline; all p<0.01). No ferric carboxymaltose-related adverse events were reported and no patient withdrew or required transfusions during the study.

Conclusion

Among patients with ND-CKD and stable normal or borderline hemoglobin, switching from oral iron to intravenous ferric carboxymaltose was associated with significant improvements in hematological and iron parameters and a significant reduction in ESA dose requirements in this single-center pilot study.

Trial Registration

ClinicalTrials.gov NCT02232906     

Serum Transferrin of Pregnant Mothers Related to Birth Weight of their Infants

In a study of 81 pregnant mothers and their newborn infants the maternal serum transferrin concentration at about 24 weeks of gestation was shown to have a low but significant correlation with infant birth weight (r=0·33; P<0·01). Maternal undernutrition is suggested as a possible cause of low serum transferrin levels.     

Glucose metabolism in the superovulated rat ovary in vitro. Effects of luteinizing hormone and the role of glucose metabolism in steroidogenesis

1. Superovulated rat ovary slices from rats treated with 20μg. of luteininzing hormone/100g. body wt. 2hr. before death and from control animals have been incubated in vitro. Output of Δ⁴-3-oxo steroids (0·2μmole/g. wet wt./hr. in control tissue) was linear for 4hr., and was increased by approx. 70% in slices from luteinizing hormone-treated rats. Rate of oxygen consumption (90·0±4·6μmoles/g. wet wt./hr.) was linear for 3hr. and unaltered by luteinizing hormone treatment or addition of glucose (1mg./ml.) to the medium. 2. In slices from control animals, steady-state rate of glucose uptake was 78·0±2·9μg. atoms of carbon/g. wet wt./hr.; steady-state rates of lactate output, pyruvate output and incorporation of [U-¹⁴C]-glucose carbon atoms into carbon dioxide and total lipid extract were 60·7±0·9, 2·4±0·1, 18·0±1·1 and 0·7±0·1μg. atom of carbon/g. wet wt./hr. and accounted for 104·5±1·9% of the glucose uptake. In slices from luteinizing hormone-treated rats, glucose uptake and outputs of lactate, pyruvate and [¹⁴C]carbon dioxide were increased by approx. 25%, and 108·4±3·2% of the glucose uptake could be accounted for. 3. The total lipid extract was separated by thin-layer chromatography and saponification. Of the ¹⁴C incorporated into this fraction during incubation with [U-¹⁴C]glucose 97% was found in the fractions containing glyceride glycerol and less than 3% in the fractions containing sterols, steroids or fatty acids. Appreciable quantities of ¹⁴C were incorporated into these lipid fractions from [1-¹⁴C]acetate. 4. From a consideration of the tissue glycogen content, the specific activities of [¹⁴C]lactate and glucose 6-phosphate (C-1) derived from [1-¹⁴C]-, [6-¹⁴C]- and [U-¹⁴C]-glucose, and the ratio of [¹⁴C]carbon dioxide yields from [1-¹⁴C]glucose and [6-¹⁴C]glucose, it was concluded that there was no appreciable glycogenolysis or flow through the pentose phosphate cycle. 5. In ovary slices from both control and luteinizing hormone-treated animals, glucose in vitro raised the incorporation rate of ¹⁴C from [1-¹⁴C]acetate into sterols and steroids. Luteinizing hormone in vivo stimulated the incorporation rate in vitro but only in the presence of glucose. 6. In slices incubated in medium containing [³H]water, [¹⁴C]sorbitol and glucose (1mg./ml.), the total water space (865±7·1μl./g.) and the extracellular water space (581±22μl./g.) were unchanged by luteinizing hormone treatment in vivo but the glucose space was raised from 540±23·6μl./g. to 639±31·3μl./g. 7. Luteinizing hormone treatment was found to lower the tissue concentration of the hexose monophosphates and to increase the total activity of hexokinase, glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase and possibly of phosphofructokinase. 8. The kinetic properties of a partially purified preparation of phosphofructokinase were found to be qualitatively similar to those from other mammalian tissues. 9. The results are discussed with reference to both the role of glucose metabolism in steroidogenesis and the mechanism by which luteinizing hormone increases the rate of glucose uptake.     

Effect of manganese on calcification of bone

1. Young mice were maintained on a basal diet composed of meat, which is poor in both manganese and calcium. 2. The addition of small amounts (2·5–5·0mg./kg. of meat) of manganese improved weight gain and calcification of bone and decreased incorporation of injected radiocalcium into bone. 3. Prolonged treatment with larger amounts (10·0–25·0mg./kg. of meat) of manganese depressed growth, induced defective calcification of bone and increased incorporation of radiocalcium into bone.     

Variation in Plasma Calcium with Induced Changes in Plasma Specific Gravity,Total Protein,and Albumin

The relationship of plasma calcium levels to changes in plasma specific gravity, total protein, and albumin induced by venous stasis was investigated. Factors were derived for adjusting calcium results to offset the effects of variation in protein concentration and thus to make them of increased discriminatory value to the clinician. The validity of an existing specific gravity correction has been substantiated, but a more exact adjustment of 0·23 mg/100 ml of calcium for every 0·001 change in specific gravity is proposed. We recommend for automated laboratories that the factor based on albumin be used: 0·09 mg/100 ml of calcium should be subtracted from the total calcium value for every increase of 0·1 g in albumin above 4·6 g/100 ml, and a corresponding addition should be made for values of albumin below 4·6 g/100 ml.Using a calcium specific electrode, it has been shown that the ionized calcium concentration does not alter with prolonged venous stasis.     

Hypophosphataemia in Septicaemia: Higher Incidence in Gram-negative Than in Gram-positive Infections

Phosphataemia has been investigated in 54 patients with Gram-negative septicaemias; either absolute (serum phosphate <2 mg./100 ml.) or relative (P./B.U.N. 0·04) hypophosphataemia was found in 69% of all determinations. In 37 patients with Gram-positive septicaemias hypophosphataemia was present in only 24%, many of whom had additional Gram-negative bacteriuria and possible Gram-negative septicaemia suppressed by antibiotics. The mechanism of this phenomenon is not known. This new sign of Gram-negative septicaemia has some diagnostic importance.     

Blood Muramidase Activity in Colorectal Cancer

The serum muramidase levels were measured in 128 patients with primary or metastatic colorectal cancer, 166 tumour-free patients after resection of a colorectal cancer, and 172 controls. Muramidase levels over 10 μg/ml were detected in 30%-39% of the tumour-bearing patients, in 8·2% of the tumour free, and in only 1·7% of the controls (normal level 6·68 ± 1·42 μg/ml). Long-term follow up indicated that raised levels may occur as a transient phenomenon in recurrent or metastatic disease. The likely relation of abnormal serum muramidase activity and stimulation of the reticuloendothelial system is discussed.     

Acute Pancreatitis and Diabetic Ketoacidosis in Accidental Hypothermia and Hypothermic Myxoedema

Serial serum amylase and blood glucose levels were measured in 68 hypothermic (rectal temperature 35°C or less) patients, including 15 who had hypothermic myxoedema (serum protein bound iodine 3·5 μg/100 ml or less). Raised amylase levels were found in 34 patients and probably reflected a mild acute pancreatitis. The high amylase levels correlated with low arterial PO₂ levels and significantly with high arterial PCO₂ levels and the base deficit but not with the severity or duration of the hypothermia. The acute pancreatitis does not explain why hypothermic patients with myxoedema have a poorer prognosis than those who are euthyroid. The pancreatitis occasionally contributed to the development, sometimes delayed, of diabetic ketoacidosis, blood glucose levels of over 120 mg/100 ml being found in 20 patients. There was a significant correlation between the raised serum amylase levels and the hyperglycaemia. Hypoglycaemia, sometimes profound, was found in 12 patients.     

Effect of Vegetarianism and Smoking on Vitamin B12, Thiocyanate,and Folate Levels in the Blood of Normal Subjects

Vitamin B₁₂, thiocyanate, and folate levels in the blood were estimated in 69 apparently normal subjects, of whom 26 were non-vegetarian non-smokers, 19 non-vegetarian smokers, 15 vegetarian non-smokers, and nine vegetarian smokers. The serum total (cyanide-extracted) B₁₂ level (value A) ranged from 105 to 728 pg/ml, with a mean of 292 pg/ml. The highest values were found in non-vegetarian non-smokers and the lowest in vegetarian smokers. There was no significant difference in value A between smokers as a group and non-smokers as a group. On the other hand, in vegetarians value A was very significantly lower than in non-vegetarians regardless of their smoking habits.It is suggested that A may represent both the protein-bound and free forms of vitamin B₁₂ in the blood, and B mainly the free B₁₂, which may be the physiologically active form. The plasma thiocyanate level varied from 1·0 to 15 μmol/100 ml, being, as expected, much higher in smokers (mean 8·20 μmol/100 ml) than in non-smokers (mean 2·02 μmol/100 ml). There was a rough correlation between falling B₁₂ levels and rising thiocyanate levels. The serum folate level ranged from 2·75 to 15·75 ng/ml, and was slightly but significantly higher in vegetarians (mean 6·60 ng/ml) than in non-vegetarians (mean 4·79 ng/ml), reflecting the greater content of folate in a vegetarian diet.     

Failure of Glucagon Release in Infants of Diabetic Mothers

Two hours after birth 30 normal infants had a fall in blood glucose of 20·6 mg/100 ml and a rise of plasma pancreatic glucagon of 50·7 pg/ml. Fifteen infants of diabetic mothers treated with insulin had a much greater fall in blood glucose of 77·5 mg/100 ml and a smaller rise of glucagon of 20·9 pg/ml. By comparison 14 small-for-dates infants, who are also prone to hypoglycaemia, had a blood glucose fall of 32·8 mg/100 ml and a larger rise of pancreatic glucagon of 96·0 pg/ml. It is suggested that the impaired pancreatic glucagon rise in the infants of diabetic mothers may be a significant factor in their hypoglycaemia.     

The fluorimetric microdetermination of glyoxylic acid in blood, urine and bacterial extracts

1. A spectrophotofluorimetric method for the determination of glyoxylic acid in biological materials is described. 2. The method is based on the reaction between glyoxylic acid and resorcinol in acid solution, a fluorescent complex being obtained on the subsequent addition of alkali. 3. The reaction was found to be sensitive and highly specific, the minimum detectable amount of glyoxylic acid being 1·35×10⁻⁸ mole. 4. The urinary excretion of glyoxylic acid by ten normal adults ranged from 1·4 to 4·7mg./24hr. Small but measurable amounts of glyoxylic acid were found in cell-free extracts of Pseudomonas oxalaticus OX1 grown on oxalic acid as a source of carbon. No glyoxylic acid was detected in human serum.     

Iron Status and Systemic Inflammation,but Not Gut Inflammation,Strongly Predict Gender-Specific Concentrations of Serum Hepcidin in Infants in Rural Kenya

Hepcidin regulation by competing stimuli such as infection and iron deficiency has not been studied in infants and it’s yet unknown whether hepcidin regulatory pathways are fully functional in infants. In this cross-sectional study including 339 Kenyan infants aged 6.0±1.1 months (mean±SD), we assessed serum hepcidin-25, biomarkers of iron status and inflammation, and fecal calprotectin. Prevalence of inflammation, anemia, and iron deficiency was 31%, 71%, 26%, respectively. Geometric mean (±SD) serum hepcidin was 6.0 (±3.4) ng/mL, and was significantly lower in males than females. Inflammation (C-reactive protein and interleukin-6) and iron status (serum ferritin, zinc protoporphyrin and soluble transferrin receptor) were significant predictors of serum hepcidin, explaining nearly 60% of its variance. There were small, but significant differences in serum hepcidin comparing iron deficient anemic (IDA) infants without inflammation to iron-deficient anemic infants with inflammation (1.2 (±4.9) vs. 3.4 (±4.9) ng/mL; P<0.001). Fecal calprotectin correlated with blood/mucus in the stool but not with hepcidin. Similarly, the gut-linked cytokines IL-12 and IL-17 did not correlate with hepcidin. We conclude that hepcidin regulatory pathways are already functional in infancy, but serum hepcidin alone may not clearly discriminate between iron-deficient anemic infants with and without infection. We propose gender-specific reference values for serum hepcidin in iron-replete infants without inflammation.     

Folic Acid in Folate-deficient Patients with Epilepsy

A double-blind trial using folic acid 15 mg. daily and identical placebo was carried out in 51 epileptic patients having a serum folate level below 3·6 ng./ml. Treatment was for a minimum of six months and in 41 patients was for more than one year. There were no significant changes in the frequency of seizures, behaviour, and personality, or in a number of cognitive functions.     

The Effect on Serum Ionic Magnesium of Exchange Transfusion with Citrated as Opposed to Heparinized Blood

Serum Mg++ levels before, during, and after replacement transfusion were determined in 20 newborn infants. In 10 infants exchanged with acid-citrate-dextrose (ACD) blood, the level fell from 1.75 ± 0.16 mEq./l. to 0.99 ± 0.16 mEq./l. By contrast, levels in 10 infants exchanged with two types of heparinized blood were unchanged: the pre-exchange values were 1.59 ± 0.11, and the postexchange levels were 1.59 ± 0.08 mEq./l. Mean values for donor bloods were 0.42 ± 0.07 mEq./l. with ACD blood, and 1.45 ± 0.03 mEq./l. with heparinized blood. In vitro studies involving the addition of known amounts of citrate to standard Mg++ solutions demonstrated that the citrate caused a reduction of ionic magnesium. It is proposed that the fall in serum Mg++ when ACD blood is used for exchange transfusion is the combined result of Mg++ binding by the citrate, and the dilution effect of the relatively large proportion of anticoagulant to blood (1:3) used with the ACD mixture.