Excessive calcium ingestion leading to milk-alkali syndrome.

This report describes the presentation and clinical course of a 40-year-old woman who had an emergency admission for eclampsia. During routine investigations, she was found to have profound hypercalcaemia, the cause of which was identified as milk-alkali syndrome, caused by self-medication with antacid tablets for dyspepsia. Treatment with aggressive rehydration, bisphosphonates and discontinuation of antacid tablets restored normocalcaemia. The patient made a full recovery with no long-term side-effects. Her male infant was safely delivered with no deleterious effects of exposure to high calcium concentrations in utero.

Natriuretic peptides and the heart: current and future implications for clinical biochemistry.

The measurement of B-type natriuretic peptides in plasma is under intense promotion as a method of screening for heart failure. This article provides a historical context for this contention, and attempts to highlight what practical problems may be encountered in establishing a screening service from a clinical biochemistry standpoint. B-type natriuretic peptide measurements may also prove, in future, to have a significant role in the objective monitoring of treatment for heart failure, and to be a valuable prognostic indicator in patients suffering from acute coronary syndrome.

The prevalence of iron deficiency among patients presenting with colorectal cancer.

OBJECTIVES: To examine prospectively the prevalence of iron deficiency among new patients presenting with colorectal cancer and to compare transferrin saturation and serum ferritin as markers of iron deficiency in this group of patients. PATIENTS AND METHODS: Data were gathered on all patients presenting with a new diagnosis of colorectal cancer over a 12-month period. Iron status was estimated and, when possible, confirmed by measurement of serum ferritin concentration and transferrin saturation. Iron status was further examined in relation to tumour site and Dukes' stage. RESULTS: During the study 157 patients presented with a new colorectal cancer. Of these, 130 could be evaluated and 78[60%] had evidence of iron deficiency. Transferrin saturation was below the reference range in 55 patients, but serum ferritin was below in only 18 patients. Among the 49 patients with right-sided cancers, 39[80%] were iron deficient. Iron deficiency was significantly more likely in patients with right sided cancers compared with those with cancers at or distal to the splenic flexure (chi2 = 13, P < 0.001). CONCLUSION: The majority of patients with a new diagnosis of colorectal cancer are iron deficient at presentation. In such patients transferrin saturation measurement is a more sensitive marker of iron deficiency than serum ferritin. The potential role of measuring serum transferrin saturation as an adjunct to faecal occult blood screening should be explored further.

Postnatal urinary conductance measurement in preterm infants.

UNLABELLED: The aim of this study was to determine whether serial urinary conductance measurements can be used to estimate reliably the end of the transition period of negative sodium balance in preterm infants. The relationship between urine conductance, measured by a conductance meter, and urine sodium concentration was determined in 109 pooled samples of urine obtained from 14 preterm infants during the transitional period of fluid balance. It was shown by linear regression analysis that urine sodium concentration (mmol l(-1)) = 0.78 x urine conductance - 1.25. Urine sodium concentrations derived from the above formula were concordant with urine sodium measured directly when used to calculate daily sodium balance in all 14 infants. CONCLUSION: Urine conductance can be accurately measured at the cotside by neonatal nurses and used to identify the timing of the postnatal transition from negative to positive sodium balance in preterm infants. These findings can help in making decisions on the introduction of postnatal sodium administration to preterm infants.

Simplified detection of a mutation causing familial hypercholesterolaemia throughout Britain: evidence for an origin in a common distant ancestor.

Familial hypercholesterolaemia (FH) is an inherited autosomal codominant disorder caused by many different mutations in the low-density lipoprotein receptor (LDLR) gene. The one described most frequently in patients with FH from England, arises from a G-->A transition at the first nucleotide of codon 80, resulting in the substitution of lysine for glutamic acid at residue 80 of the mature protein, FH E80K. We describe a simple method to detect this mutation in genomic DNA using the polymerase chain reaction (PCR). A 69 base pair (bp) fragment of exon 3 of the LDLR gene is amplified using a mutagenic upstream PCR primer. This substitutes a T for an A residue in the amplified product, 2 bp upstream from the mutant site, generating a restriction site for the endonuclease Taq I, in normal, but not in mutant DNA. Following digestion of amplified DNA with Taq I, normal but not mutant DNA is cut into two fragments of 29 and 40 bp, which are readily identified by polyacrylamide gel electrophoresis. Using this method, 410 patients with clinically diagnosed FH, attending lipid clinics in Edinburgh (72), Newport (158), Walsall (30) and Southampton (150), were screened for the mutation. Five individuals tested positive as heterozygotes, one from Edinburgh, three from Newport and one from Southampton. This finding was confirmed by DNA sequence analysis. We conclude that FH due to this mutation occurs in individuals throughout Great Britain and that it can be detected accurately using this simple technique. DNA from these and other individuals previously identified to be heterozygous for FH E80K, was then studied using PCR of highly informative microsatellite markers flanking the LDLR gene. Sixteen of 17 apparently unrelated individuals heterozygous for FH E80K also were heterozygous for an identical size (239 nucleotide) allele, of polymorphic microsatellite D19S394, located approximately 250 kb away from the LDLR gene. This supports the hypothesis that FH E80K in these 16 individuals arose from a single ancestor less than 1000 years ago.

Familial ligand-defective apolipoprotein B-100: detection, biochemical features and haplotype analysis of the R3531C mutation in the UK.

Familial ligand-defective apolipoprotein (apo) B-100 (FDB) is an autosomal codominant disorder which may give rise to hypercholesterolaemia. It is caused by the substitution of glutamine for arginine at codon 3500 of the apo B gene (apo B R3500Q), resulting in decreased binding of low density lipoprotein (LDL) to the LDL receptor. In order to search for other mutations in this region of the apo B gene, we have screened genomic DNA, obtained from 412 hypercholesterolaemic individuals, using heteroduplex analysis. Additional heteroduplex bands were observed following analysis of DNA from 11 individuals, nine of whom were heterozygous for apo B R3500Q. The two remaining individuals, both of Celtic origin, were shown by DNA sequencing to be heterozygous for a C-->T transition at nucleotide 10800 of the apo B gene, resulting in the substitution of cysteine for arginine at codon 3531 (apo B R3531C). Both had a strong family history of atherosclerosis and family studies revealed a further four individuals heterozygous for the mutation, three of whom were hypercholesterolaemic. Individuals heterozygous for apo B R3531C and R3500Q had mean +/- S.E.M. cholesterol concentrations of 7.82 +/- 0.68 and 8.53 +/- 0.31 mmol/l, respectively. These values were significantly higher than the value of 5.51 +/- 0.23 mmol/l observed in their unaffected relatives. These findings suggest that apo B R3531C is both less common in the UK and gives rise to a less severe form of hypercholesterolaemia than the classical 3500 mutation. In one of the families, the R3531C mutation occurred on a haplotype, compatible with that previously assigned to the mutation in a North American family also of Celtic origin. This is consistent with the mutation having been inherited from a common distant ancestor in individuals of Celtic origin.

Familial defective apolipoprotein B-100: a study of patients from lipid clinics in Scotland and Wales.

Familial defective apolipoprotein (apo) B-100 (FDB) is an autosomal codominant disorder, which may be associated with hypercholesterolaemia. The defect is caused by the substitution of glutamine for arginine at amino acid residue 3500 of apo B-100. A total of 357 hypercholesterolaemic patients, 48 with a clinical diagnosis of familial hypercholesterolaemia attending lipid clinics in Scotland and Wales, were screened for the presence of FDB. Seven unrelated individuals, five of whom had a family history of coronary heart disease, and a further 11 first-degree relatives, were shown to be heterozygous for the mutation. Pedigree analysis demonstrated the mutation to be present on a single haplotype, suggesting that in Britain it is inherited from a common ancestor. Treatment of 11 heterozygous individuals with lipid-lowering medication showed falls in total and low density lipoprotein cholesterol ranging from 11.6 to 38.8% and 5.3 to 49.5%, respectively. In view of the condition's association with coronary heart disease and hypercholester-olaemia, it may be worthwhile identifying carriers attending lipid clinics, so that affected siblings can be offered cholesterol-lowering treatment where necessary.

Disturbance of peripheral microvascular fluid permeability by the onset of atrioventricular asynchrony in patients with programmable pacemakers.

BACKGROUND: In vitro and in vivo evidence suggests that atrial natriuretic peptide can enhance fluid flux from intravascular to extravascular compartments. The relevance of this to human pathophysiology remains unclear. OBJECTIVES: To determine whether a central haemodynamic change associated with increased plasma concentrations of atrial natriuretic peptide produces detectable change in the capillary filtration coefficient in a peripheral microvascular bed. PATIENTS: 12 patients with programmable dual chamber permanent pacemakers. METHODS: Calf capillary filtration coefficient (using a modified plethysmographic technique) and plasma atrial natriuretic peptide concentrations were measured during atrioventricular synchronous and ventricular pacing. RESULTS: Atrioventricular asynchrony was associated with higher mean (SD) concentrations of atrial natriuretic peptide (231.9 (123.1) v 53.5 (38.8) pg/ml) and an increased mean (SD) calf capillary filtration coefficient (4.2 (1.1) v 3.6 (1.1) ml/min.mm Hg.100 ml x 10(-3)), but there was no correlation between the magnitude of the change in these variables in individual patients. CONCLUSIONS: The peripheral capillary filtration coefficient may change in response to altered central haemodynamics. Atrial natriuretic peptide remains one potential candidate mechanism, but other factors are also likely to be involved.

An open, in-patient incremental safety and efficacy study of desmopressin in women with multiple sclerosis and nocturia.

OBJECTIVES: To examine the safety and efficacy of desmopressin in three doses given to women with multiple sclerosis to treat nocturia with or without enuresis. PATIENTS AND METHODS: Eight women with clinically confirmed multiple sclerosis and nocturia with or without enuresis were entered as in-patients into an open, nonrandomized, placebo-controlled study of incremental doses of 20, 40 and 60 micrograms desmopressin. Urinary and serum sodium, plasma arginine vasopressin and urine osmolality were monitored every 4 h for 24 h. A single dose of placebo or desmopressin was given during each of four 24-h periods. RESULTS: There was a significant decrease in nocturnal urinary volumes and a significant increase in nocturnal urinary osmolalities in patients taking desmopressin when compared with those taking a placebo, but there was no difference among the desmopressin doses. There was no significant difference in serum sodium level between the desmopressin doses. However, at the end of the 24-h period with the 60 micrograms dose, serum sodium was decreased significantly. CONCLUSIONS: Neither a significant decrease in nocturnal urinary volumes nor an increase in urinary osmolality was achieved by doses of desmopressin > 20 micrograms. A dose of 60 g was associated with a decreased serum sodium level at the end of the 24-h period but there was no biochemical hyponatraemia. Because there were no benefits and a possibility of clinical hyponatraemia with higher doses, doses of > 20 micrograms desmopressin cannot be recommended.

Biochemical diagnosis of myocardial infarction within the thrombolytic time window.

A demonstrated temporal change in the total activity of creatine kinase or mass measurement of the cardio-specific isoenzyme creatine kinase MB is currently used as the biochemical diagnosis of myocardial infarction. The isoforms of creatine kinase MB may provide an earlier diagnostic marker of myocardial infarction than the currently available biochemical markers. We compare the sensitivity and specificity of total creatine kinase activity, creatine kinase MB mass measurement and the muscle and heart specific isoforms of creatine kinase in the early diagnosis of myocardial infarction. Using current methodologies, neither CK isoform offered any advantage over CK mass measurement as an early marker of ischaemic myocardial damage.