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Biomedical subjects

S Ratnaike

Publications and source records attributed to S Ratnaike.

At least 19 recordsLinked to original sources
PubMed1997

A novel form of hereditary sideroblastic anaemia with macrocytosis.

We describe a pedigree with maternally inherited sideroblastic anaemia in which the red cells are dimorphic with a raised MCV. To our knowledge, this form of hereditary sideroblastic anaemia (HSA) has not been reported previously. 16 members of the family were investigated, revealing eight affected members. Two further family members were not tested but were presumed affected on the histories available. The proband, born in 1967, presented during pregnancy with a macrocytic anaemia (Hb 7.0 g/dl, MCV 106 fl) and a dimorphic red cell picture. Post partum, a bone marrow biopsy showed hypercellularity, mild dyserythropoiesis and ring sideroblasts. Cytogenetics were normal. Other causes of macrocytosis were excluded. Six other family members (three female, three male) have similar findings. There is no evidence of paternal transmission. An additional female relative who presented in 1992 with refractory anaemia with excess blasts in transformation and a dimorphic blood film, died from progression to AML. Affected members show a raised metal-free red cell protoporphyrin level suggestive of a defect at the level of Fe2+ incorporation into protoporphyrin. We propose that this form of HSA is due to a mitochondrial mutation. A search for deletions or point mutations in the mitochondrial DNA is currently underway.

Adult↗
PubMed1996

Five new mutations in the uroporphyrinogen decarboxylase gene identified in families with cutaneous porphyria.

We describe five new mutations in the uroporphyrinogen decarboxylase (UROD) gene. All mutations were observed in conjunction with decreased erythrocyte UROD and clinical familial porphyria cutanea tarda (fPCT), (four families) or hepatoerythropoietic porphyria (HEP), (one family). The fPCT mutations included three point mutations that resulted in amino acid substitutions: a lysine to glutamine at amino acid position 253 (exon 7); a glycine to arginine at position 318 (exon 10); an isoleucine to threonine at position 334 (exon 10). The lysine to glutamine at amino acid position 253 was found in conjunction with a single C nucleotide deletion in exon 8 on the same allele of the UROD gene in the same family. This deletion resulted in a shift in the reading frame and the introduction of a premature stop codon 8 amino acids downstream. In the fourth family, a 31-bp deletion (nucleotides 828-858: exon 8) of the coding region, resulted in a frameshift and the introduction of a stop codon 19 amino acids downstream. A point mutation was observed in an individual diagnosed with HEP, resulting in an alanine to glycine change at amino acid position 80 and was present on both alleles. All mutations were confirmed in at least one other family member. The impact of these mutations on the function of the UROD protein was examined using in vitro protein expression and with activity assessed using pentacarboxylic acid porphyrinogen I as a substrate for UROD. Although three mutations reduced UROD activity to < 15% of normal, one resulted in a UROD protein with 50% functional activity and the other had near normal activity. These results indicate that many different genetic lesions of the UROD gene are associated with fPCT.

Family↗
PubMed1995

The 75 g oral glucose tolerance in pregnancy.

A 75 g oral glucose tolerance test was performed between 26 and 32 weeks gestation in 1371 women attending an ante-natal clinic in Melbourne. Gestational diabetes according to various criteria was present in 4.2% (2 h plasma glucose > or = 8.0 mmol/l), 5.2% (2 h plasma glucose > or = 7.8 mmol/l) and 5.5% by the proposed Australian criteria (fasting plasma glucose > or = 5.5 mmol/l and/or 2 h plasma glucose > or = 8.0 mmol/l). The long-term implications of gestational diabetes in the development of diabetes and metabolic abnormalities for both the mother and her child in addition to related infant morbidity emphasise the urgent need for an agreed definition of this condition.

Administration, Oral↗
PubMed1995

The diagnosis and follow-up of porphyria.

This review details an approach to the biochemical diagnosis and follow-up of porphyria. We discuss the problems of diagnosis of both symptomatic patients suspected of porphyria and patients being investigated because of a family history of porphyria. High performance liquid chromatography plays a major role in the investigation of these patients. Molecular biology is emerging as a useful tool in further defining this group of diseases.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Complex pattern of alternative splicing in the normal uroporphyrinogen decarboxylase gene: implications for diagnosis of familial porphyria cutanea tarda.

We describe multiple alternative transcripts of uroporphyrinogen decarboxylase mRNA in normal individuals and patients with familial porphyria cutanea tarda. mRNA was reverse-transcribed, subjected to the polymerase chain reaction, and analyzed for nucleotide sequence. Seven different transcripts were characterized, and a cryptic splice acceptor site was identified in intron 1. In all mRNAs the exons abutted at previously defined exon boundaries. Characterization of the splice junctions in the genomic DNA showed that splice donor and acceptor sequences complied with the consensus sequences for these sites except for the splice acceptor sequences of exons 3 and 10. THese deviations were present in two normal individuals and one patient with familial porphyria cutanea tarda and were thus unable to explain the multiple aberrant uroporphyrinogen decarboxylase transcripts. We conclude that apparent deletions observed in transcripts derived from the uroporphyrinogen decarboxylase gene in patients with familial porphyria cutanea tarda should be interpreted with caution.

Alternative Splicing↗
PubMed1993

The investigation of chest pain: audit and intervention.

OBJECTIVE: To examine the patterns of tests requested for patients admitted with chest pain, and to monitor the effects on those patterns of issuing a set of guidelines formulated by an expert panel. SETTING: Tertiary referral hospital (teaching). DESIGN: A retrospective audit of the patterns of testing of patients with chest pain compared with testing recommended by an expert panel, followed by comparison with patterns of testing after guidelines were issued. INTERVENTION: Practice guidelines, based on the expert committee's recommendations, were drawn up for use in the cardiology unit. OUTCOME MEASURES: Tests per admission, bed days per admission, emergency readmission rate. PATIENTS: Sixty-seven patients with diagnosis at the time of admission of chest pain and a discharge diagnosis of "intermediate coronary syndrome". RESULTS: The major finding of the audit was the excessive use of "biochemistry test profiles" instead of targeted tests as recommended by the expert committee. Intervention led to a decrease in the number of tests per admission in the cardiology unit from an average of 22.9 tests in the six months before intervention to 9.7 in the six months after (P < 0.001). There was no effect on bed days per admission or emergency readmission rates. CONCLUSION: Audit and intervention in a specialised unit of patients with a specified diagnosis led to more cost effective use of the resources of the Royal Melbourne Hospital Department of Biochemistry.

Adult↗
PubMed1993

Albuminuria in aborigines and Europids of south-eastern Australia.

OBJECTIVE: To determine the prevalence of albuminuria in Aborigines and Australians of European descent (Europids), as part of an epidemiological study of glucose intolerance and cardiovascular risk factors based in country towns of south-eastern Australia. DESIGN: Population-based cross-sectional study, with Aborigines and Europids of south-eastern Australia as the reference populations. METHOD: Random urine samples were collected from people aged > or = 35 years, and tested with Albuscreen (a test kit sensitive to urinary albumin concentrations of 0.03 g/L) and two other methods in the field. The samples were later analysed for the calculation of urinary albumin:creatinine ratios, which were then categorised according to cut-off points for abnormal renal function that have been proposed in the literature. RESULTS: Three hundred and six Aborigines and 553 Europids participated, with response rates of 90% and 94% respectively. According to Albuscreen, albuminuria was more common in Aborigines than in Europids. In men, 36% (95% confidence interval [CI], 20%-52%) of Aborigines exceeded the albumin concentration of 0.03 g/L, compared with 14% (CI, 9%-19%) of Europids (P < 0.01); in women, 39% (CI, 27%-51%) of Aborigines exceeded 0.03 g/L, compared with 18% (CI, 12%-24%) of Europids (P < 0.01). Sixty-one per cent (CI, 44%-78%) of Aboriginal men had a urinary albumin:creatinine ratio of > or = 1.30 mg/mmol, compared with 12% (CI, 7%-17%) of Europid men (P < 0.01); 56% (CI, 44%-68%) of Aboriginal women exceeded this cut-off point, compared with 23% (CI, 16%-30%) of Europid women (P < 0.01). CONCLUSION: A higher prevalence of renal disease in the Aboriginal population of south-eastern Australia is expected. Risk factors for renal disease in Aborigines throughout Australia require elucidation.

Adult↗
PubMed1992

Stroke topography and outcome in relation to hyperglycaemia and diabetes.

In a prospective study to analyse stroke topography and outcome in diabetics and to determine the prognostic value of blood glucose and glycosylated haemoglobin estimation, we evaluated 176 patients with acute stroke. The patients were classified into four groups on the basis of history, fasting glucose, and glycosylated haemoglobin: euglycaemic patients with no history of diabetes, stress hyperglycaemia, newly diagnosed diabetics, and known diabetics. A high prevalence of undiagnosed diabetes was shown. No difference was found in the type or site of stroke between the four groups. No difference was found in the site of symptomatic or incidental lesions on computerised axial tomography. Patients with stress hyperglycaemia and known diabetics had more severe strokes. Mortality was higher in patients with stress hyperglycaemia, newly diagnosed diabetics, and the combined diabetes groups. This increased mortality was evident in the hyperglycaemic and diabetic groups, even after excluding patients with cerebral haemorrhage. Stroke severity and mortality also increased independently with blood glucose in the euglycaemic group. We conclude that there is a correlation between admission glucose concentration, diabetes, and poor stroke outcome, which may not be attributed to stroke type or location.

Adult↗
PubMed1992

Fecal coproporphyrin isomers in hereditary coproporphyria.

To see whether the fecal coproporphyrin III:coproporphyrin I (CIII:CI) ratio (determined by HPLC) would be suitable for screening patients at risk of hereditary coproporphyria (HC), we compared such ratios with the lymphocyte coproporphyrinogen oxidase (EC 1.3.3.3) activities (COOX) in 38 subjects from one large family and two smaller families with HC. The CIII:CI ratio was normal (less than 1.3) in adults with normal COOX (greater than 180 nmol/g of protein per hour) and high (greater than 2) in those with low COOX. Results were difficult to interpret in six of 10 children, who had borderline or low COOX but normal fecal CIII:CI ratios. Five subjects with low COOX and abnormal fecal CIII:CI ratios had normal fecal total porphyrin, indicating that the latter investigation alone is inadequate for family studies. The sample for determining the fecal CIII:CI ratio is easier to obtain and the assay is technically less demanding than COOX. We found the fecal CIII:CI ratio suitable for investigation of adults in a family study, but its usefulness in children needs to be established.

Adolescent↗
PubMed1991

Four cases of IgD multiple myeloma.

The pathological and clinical findings in 4 cases of IgD multiple myeloma are presented. Two patients presented with renal failure and 2 with bone pain and weight loss. Three had IgD lambda paraproteins and 1 an IgD kappa paraprotein. One patient also developed hypercalcemia and extraosseous spread of tumor to pleura, skin, and palate. There were no distinctive bone marrow or histological findings which suggested this unusual type of myeloma.

Aged↗
PubMed1991

Comparison of four methods for free thyroxin.

We performed a limited evaluation of four free thyroxin (FT4) reagent kits: the Amerlex-M (AFT4), the Amerlite (LFT4), the MagicLite (MFT4), and the GammaCoat two-step RIA (GFT4). FT4 was measured in specimens from 201 subjects: 19 healthy controls, 14 patients who were thyrotoxic, 13 who were hypothyroid, 59 who had a past history of thyroid disease, seven with thyroxin autoantibodies, seven who were taking amiodarone, and 82 who had no clinical indication of thyroid hormone abnormality. Of these 201 subjects, 78 had a low serum albumin (less than 35 g/L) and 27 had severe nonthyroidal illness. We also investigated 60 pregnant subjects. We found no correlation between thyroxin-binding globulin (TBG) and FT4 in any of the assays, and only the AFT4 method showed a significant correlation with albumin concentrations. The presence of autoantibodies to thyroxin affected the results of all methods except the GFT4 method. All methods showed a decrease in mean FT4 values in late pregnancy. Correlation of patients' clinical state and FT4 results suggested that the reference ranges published by the manufacturers need to be modified for our laboratory.

Adolescent↗
PubMed1990

Cerebrospinal fluid biochemistry in the diagnosis of multiple sclerosis.

The Poser criteria for diagnosing multiple sclerosis (MS) includes clinical, paraclinical and laboratory information. We studied the influence of cerebrospinal fluid (CSF) biochemistry results on the categorisation of patients with suspected MS. A retrospective study was made of 138 patients who had CSF samples sent over a 1 year period to the laboratory for examination for oligoclonal bands. Using the Poser criteria, 23 patients were diagnosed as having definite MS and one patient as probable MS. Cerebrospinal fluid biochemistry upgraded the categorisation from probable to definite MS in 16 of these 24 patients (66%). In this study, we found oligoclonal bands to be more sensitive in the diagnosis of MS (96%) than either the concentration of IgG in the CSF (43.5%) or the IgG expressed as a percentage of the total protein in the CSF (71%). We conclude that CSF biochemistry is a valuable investigation in the evaluation of patients with suspected MS.

Adolescent↗
PubMed1989

Alpha-1-antitrypsin in liver disease.

Low alpha-1-antitrypsin (AAT) levels are known to be associated with liver disease. As AAT is also synthesised in the liver, we investigated whether liver disease itself may result in low AAT levels. AAT was measured in plasma from 100 patients with various liver diseases including hepatitis, cirrhosis, jaundice and liver failure. Twenty-eight patients had increased AAT values (greater than 3.1 g/L), 70 had normal AAT values (between 1.5 and 3.1 g/L) and 2 had decreased AAT levels (less than 1.5 g/L). The 2 patients with low AAT levels were found to be of the PiMZ phenotype. There was no significant correlation between any of the standard 'liver function tests' and the AAT level. Our findings suggest that in liver disease AAT levels are usually normal or increased. Low levels are uncommon and the possibility of an abnormal AAT phenotype being associated with the liver disease should be examined.

Adolescent↗
PubMed1989

Alpha 1-antitrypsin phenotypes in homosexual men.

The alpha 1-antitrypsin (AAT) phenotype was determined by isoelectric focusing in 215 male homosexuals and compared with those in 208 male heterosexuals. The incidence of abnormal phenotypes was 16.3% in the homosexual group which was significantly different (p less than 0.03) than the 8.7% in the heterosexual group. There was no difference in the phenotype distribution between homosexuals who were anti-human immunodeficiency virus reactive and those who were non-reactive. It suggests that investigation into the interplay of factors associated with homosexuality could include genetic as well as psychological and social factors.

HIV Seropositivity↗
PubMed1988

An assay of uroporphyrinogen decarboxylase in erythrocytes.

Measurement of uroporphyrinogen decarboxylase (UROD; EC 4.1.1.37) activity in erythrocytes is useful in distinguishing between familial porphyria cutanea tarda (PCT), in which UROD activities are low, and acquired PCT, in which UROD activity is normal. In this method for measuring UROD, pentacarboxylic acid porphyrinogen I (PPI) is used as substrate. A sample of the patient's whole blood is incubated with PPI at 37 degrees C for 30 min at pH 6.0. The reaction is stopped by adding trichloroacetic acid/dimethyl sulfoxide containing mesoporphyrin (internal standard). The coproporphyrin so produced is measured directly by high-performance liquid chromatography, with fluorescence detection. Our values by this method for healthy subjects and non-PCT patients ranged from 1.8 to 4.0 U/L. The CV for the assay was 10% at 1.1 U/L and 9% at 2.4 U/L. Twelve of 42 patients with PCT had low erythrocyte UROD activities. In each of six families of patients with low UROD activity we found at least one other family member with a low UROD activity in erythrocytes.

Adult↗