Mutation detection rate and spectrum in familial hypercholesterolaemia patients in the UK pilot cascade project.

Cascade testing using DNA-mutation information is now recommended in the UK for patients with familial hypercholesterolaemia (FH). We compared the detection rate and mutation spectrum in FH patients with a clinical diagnosis of definite (DFH) and possible (PFH) FH. Six hundred and thirty-five probands from six UK centres were tested for 18 low-density lipoprotein receptor gene (LDLR) mutations, APOB p.

Long-term improvement in homocysteine levels and arterial endothelial function after 1-year folic acid supplementation.

Purpose: Hyperhomocysteinemia, a risk factor for atherosclerosis, is associated with endothelial dysfunction that can be improved with short-term folic acid supplementation. The current study aimed to assess whether folic acid supplementation could produce longer-term improvements in homocysteine levels and arterial endothelial function.

Subjects And Methods: Twenty-nine healthy adults with hyperhomocysteinemia were selected from 89 volunteers enrolled in a community-based atherosclerosis screening project.

Folic acid improves arterial endothelial function in adults with hyperhomocystinemia.

Objectives: To evaluate whether oral folic acid supplementation might improve endothelial function in the arteries of asymptomatic adults with hyperhomocystinemia.

Background: Hyperhomocystinemia is an independent risk factor for endothelial dysfunction and occlusive vascular disease. Folic acid supplementation can lower homocystine levels in subjects with hyperhomocystinemia; however, the effect of this on arterial physiology is not known.

Hyperhomocyst(e)inemia is a risk factor for arterial endothelial dysfunction in humans.

Background: Hyperhomocyst(e)inemia is associated with premature peripheral vascular, cerebrovascular, and coronary artery disease. Because homocysteine has been found to be damaging to endothelial cells in animal and cell culture studies, we evaluated the association between hyperhomocysteinemia and arterial endothelial dysfunction (a marker of early atherosclerosis) in asymptomatic adult subjects.

Methods And Results: Using high-resolution ultrasound, we measured endothelium-dependent flow-mediated dilation (EDD) and endothelium-independent nitroglycerin-induced dilation (GTN) of the brachial artery in 14 prospectively defined hyperhomocysteinemic (mean plasma homocysteine, 34.

Monoclonal gammopathy of unknown significance and malignant paraproteinemia in Hong Kong.

The incidence of multiple myeloma is lower in Southeast Asia than in the West. However, there are few reports on the overall incidence of paraproteinemia and its disease-associations in the Chinese. Therefore, the authors have correlated the laboratory features with the eventual clinical diagnosis in patients with paraproteinemia in a Hong Kong general/teaching hospital.

Hyperhomocysteinaemia and premature coronary artery disease in the Chinese.

Objectives: To examine the prevalence of hyperhomocysteinaemia and compare it with the classic risk factors and vitamin status in Hong Kong Chinese patients with premature atherosclerotic coronary artery disease.

Design: Case-control study.

Setting: General hospital and community.

Fatal acute hepatorenal failure following potassium permanganate ingestion.

Potassium permanganate (KMnO4), a powerful oxidizing agent, is readily available without prescription. Tissue contact produces coagulation necrosis and the lethal consequences of oral ingestion are well described, with most deaths because of airway oedema and obstruction or circulatory collapse. Whilst systemic toxicity is reported, its mechanism is unclear.

Water and sodium disorders following surgical excision of pituitary region tumours.

A prospective observational study of the pathophysiology of sodium and water disorders in patients with pituitary region tumours after surgical excision was carried out in 20 patients. Serial pre-operative and post-operative fluid and sodium balance, plasma and urine elctrolyte biochemistry and their derived parameters, and circulating hormones associated with fluid balance, atrial natriureic peptide (ANP) and antidiuretic hormone (ADH) were documented to correlate with the patients' clinical conditions. Ten out of these twenty cases developed diabetes insipidus (DI) requiring ADH replacement therapy, although in the majority (6 cases), this way only a transient event.

Alpha-1-antitrypsin phenotypes and associated disease patterns in neurological patients.

Introduction: Alpha-1-antitrypsin (AAT) deficiency is usually associated with lung or liver disease. It is often detected as a qualitative reduction of the alpha-1 band on the serum protein electrophoretic pattern.

Material And Methods: We examined the protein electrophoretic pattern in sera of 22980 unselected consecutive patients with neurological disorders and noted a reduced alpha-1 band in 88.

Antiepileptic drug pharmacokinetics and neuropharmacokinetics in individual rats by repetitive withdrawal of blood and cerebrospinal fluid: phenytoin.

The temporal pharmacokinetic (blood) and neuropharmacokinetic (cerebrospinal fluid, CSF) interrelationship of phenytoin was studied after acute and during chronic (up to 5 days) intraperitoneal administration of phenytoin (30, 50 or 100 mg/kg) using a new freely behaving rat model. After administration, phenytoin rapidly appeared in both serum (Tmax mean range 0.15-0.

IgD multiple myeloma with thoracic spine compression due to epidural extra-osseous tumour spread.

On initial presentation of a patient with IgD multiple myeloma there were no features to suggest an unusual variant. Two months later she developed spinal cord compression due to an IgD plasmacytoma. This complication of IgD myeloma has rarely been reported.

A freely moving and behaving rat model for the chronic and simultaneous study of drug pharmacokinetics (blood) and neuropharmacokinetics (cerebrospinal fluid): hematological and biochemical characterization and kinetic evaluation using carbamazepine.

A freely moving and behaving rat model for the chronic and simultaneous study of drug pharmacokinetics (blood) and neuropharmacokinetics [cerebrospinal fluid (CSF)] is described. The blood (jugular vein) and CSF (cisterna magna) catheters employed are simple, reliable, and inexpensive. The blood catheter was made of soft and flexible Silastic tubing and sealed with heparin.

Value of urinary copper excretion after penicillamine challenge in the diagnosis of Wilson's disease.

To investigate the diagnostic value of 24-hr urinary copper excretion testing after penicillamine challenge in the diagnosis of Wilson's disease, 75 consecutive children referred for a variety of liver problems and in whom parameters of copper metabolism had been investigated were analyzed retrospectively. Seventeen had Wilson's disease, 22 had autoimmune chronic active hepatitis, 6 had primary sclerosing cholangitis, 12 had chronic liver disease of various etiologies, 4 had cryptogenic acute liver failure, 6 had acute hepatitic illnesses and 8 had a variety of disorders featuring normal liver histological appearance. Serum ceruloplasmin and total copper levels were significantly lower in Wilson's disease patients compared with all other groups, but three children with Wilson's disease had normal ceruloplasmin levels and seven had normal total copper levels.

Hyponatraemia in neurosurgical patients: diagnosis using derived parameters of sodium and water homeostasis.

Seventeen unselected, consecutive patients with intracranial disease and accompanying hyponatraemia were studied. All would previously have been diagnosed as having the syndrome of inappropriate antidiuretic hormone (ADH) secretion on the basis of spot plasma/urinary electrolyte testing with the application to them of existing standard laboratory criteria. Timed urinary collections and matching plasma samples were available in all but three cases for the derivation of creatinine, osmotic and free-water clearances, tubular reabsorbed water, and fractional water and sodium excretions.

Cerebral neoplastic angioendotheleosis complicated by hypercalcaemia.

This is a case report of a 67 year old man who presented with a fluctuating level of consciousness and myoclonic jerks caused in part by hypercalcaemia. The diagnosis of cerebral neoplastic angioendotheleosis was only made later on brain biopsy and is the first report of the occurrence of hypercalcaemia in neoplastic angioendotheleosis.

Transient nephrotic syndrome after anaesthesia resulting from a familial cryofibrinogen precipitating at 35 degrees C.

Transient nephrotic syndrome, haematuria, and cryofibrinogenuria in a child after anaesthesia were found in association with a plasma cryofibrinogen that precipitated at 35 degrees C. Investigation of the family showed this to be a familial trait probably with dominant inheritance.

Chronic neurological toxicity associated with exposure to volatile substances.

1. The main neurological disorders associated with chronic VSA are peripheral neuropathy, cerebellar disease, chronic encephalopathy and dementia. Apart from peripheral neuropathy, the clinical features are non-specific, evidence for solvent-related toxicity is in most cases circumstantial and there is no clear dose/response relationship.

An intra-erythrocytic low molecular weight lead-binding protein in acute and chronic lead exposure and its possible protective role in lead toxicity.

A low-molecular-weight protein was measured in erythrocytes from workers with chronic and recent lead exposure, with and without clinical lead toxicity, and from a group of control subjects not exposed to undue environmental lead. The protein was detected in all the workers, but in significantly smaller amounts in those with symptoms, and was absent from controls. The synthesis of the protein is induced at blood lead concentrations above 1.

Cerebral depression due to propylene glycol in a patient with chronic epilepsy--the value of the plasma osmolal gap in diagnosis.

A case of propylene glycol poisoning is described in a 39 year old woman which resulted in her admission to hospital in status epilepticus. She had had a long-standing history of uncontrollable epilepsy. The diagnosis of propylene glycol poisoning resulted directly from the finding of a high plasma osmolal gap on admission.

Concurrent monitoring of central carbamazepine and transmitter amine metabolism and motor activity in individual unrestrained rats using repetitive withdrawal of cerebrospinal fluid.

A method for repeated withdrawal of cerebrospinal fluid (CSF) from the cisterna magna was used in a pharmacokinetic and behavioural study of conscious, freely-moving rats, given the antiepileptic drug carbamazepine (35 mg/kg i.p.).

The effect of moderate blood alcohol levels on T1 and T2 relaxation times in the brains of normal volunteers.

T1 and T2 measurements of the brains of six human volunteers did not change in the presence of moderate blood alcohol levels.

delta-Aminolaevulinic acid dehydratase as an index of the presence and severity of lead poisoning in acute and chronic lead exposure.

The activity of delta-aminolaevulinic acid dehydratase (ALA-D; porphobilinogen synthase) was measured in whole blood from a group of workers with acute exposure to lead and with low blood lead levels, a group of workers with chronic lead exposure and high blood lead levels, and a group of people without undue environmental lead exposure. The activity of ALA-D was reduced significantly at low blood lead levels only if undue exposure to lead had occurred, and was thus a reflection of low level lead poisoning. In chronic lead exposure the enzyme was not invariably reactivated fully with dithiothreitol, indicating more severe enzyme poisoning.