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Biomedical subjects

A J Bellingham

Publications and source records attributed to A J Bellingham.

At least 19 recordsLinked to original sources
PubMed1996

Prenatal diagnosis of triosephosphate isomerase deficiency.

First-trimester prenatal diagnosis was undertaken by chorionic villus DNA analysis in two unrelated families with the inherited glycolytic disorder triosephosphate isomerase (TPI) deficiency. The propositus in each family was shown to be homozygous for a missense mutation (GAG --> GAC) at codon 104 of the TPI gene. In the first case the fetus was heterozygous for the codon 104 mutation and therefore clinically unaffected. Prenatal diagnosis in the second case showed the fetus to be homozygous for the codon 104 mutation and thus affected by TPI deficiency. This represents the first molecular diagnosis during early pregnancy of a human glycolytic enzyme disorder.

Base Sequence↗
PubMed1995

Hereditary red cell enzymopathies.

The hereditary red cell enzymopathies are an uncommon but important cause of chronic haemolytic anaemia. Their clinical diversity is mirrored by increasingly evident heterogeneity at the molecular level. The structure, function, and expression of the genes encoding red cell enzymes and the nature of the gene defects in the deficient state are examined.

Amino Acid Sequence↗
PubMed1994

Salmonella bacteraemia in sickle cell disease at King's College Hospital: 1976-1991.

A review of all blood culture isolates for the 16 years from 1976 were collated with prospective laboratory and clinical records of 620 sickle cell patients treated at King's College Hospital. Over half of all salmonella bacteraemias diagnosed in the clinical laboratory occurred in sickle cell disease (SCD) patients. Of 21 bacteraemias in SCD patients, 11 (52.3%) were due to Salmonella spp. compared with 23 (0.4%) of 4884 bacteraemias in patients without SCD (P = < 0.00001). In SCD, Gram-negative bacilli were responsible for 16 (76.2%) bacteraemias, of which 11 (68.8%) were due to Salmonella spp. but there were no cases of S. typhi or S. paratyphi. An increase in the number of salmonella infections over the past 5 years were noted in the SCD and non-SCD patients, nine and 16 cases respectively, compared with two and seven cases in the previous decade. However, the recent increase of S. enteritidis phage type 4 in the UK was not evident in SCD patients. These findings have important preventative and therapeutic implications for the management of SCD patients.

Anemia, Sickle Cell↗
PubMed1994

Screening for ophthalmic manifestations of sickle cell disease in the United Kingdom.

There are marked variations in the manifestations of sickle disease in different populations. The ocular complications of this condition amongst the Afro-Caribbeans living in the United Kingdom have not previously been reported. We present the preliminary results of an ophthalmic screening programme at King's College Hospital, London. One hundred eyes of 50 patients with sickle cell disease were assessed. Full ocular examination was performed including fundus fluorescein angiography. We have looked at the haematological and clinical profile of the patients involved as well as the number of days spent in hospital during the year preceding the eye examination. The incidence of grade II retinopathy was found to be significantly higher than grade I in SC disease. This concurs with the results of the Jamaican screening and confirms that these patients are at higher risk of visual impairment than those with SS disease. Our results also agree with the Jamaican experience which suggest that visual morbidity is mostly due to complications of proliferative sickle retinopathy (PSR). However, the findings in patients without proliferative changes are different; in particular, angioid streaks leading to disciforms are an important cause of visual loss in Jamaica, but were not seen in any of the 98 eyes examined in this study. No correlation was found between the grade of retinopathy and age, sex, systemic complications and various haematological parameters except for the percentage of haemoglobin F, which was significantly higher in patients with grade I (7.6) compared with grade II (4.2) retinopathy (p = 0.0127).

Adolescent↗
PubMed1994

Pathology.

In summary, the College is a long way forward in the preparation for the implementation of Calman and the unified training grade. It has identified a number of problems that could hinder its implementation and is anxious to develop, along with its sister Colleges, a unified approach to these problems to ensure that the doctors of tomorrow have an effective and satisfying training experience for the benefit of all the patients for whom we care.

Curriculum↗
PubMed1991

The osteodystrophy of congenital erythropoietic porphyria.

Congenital erythropoietic porphyria (CEP) is a rare disorder of heme biosynthesis that results in the production of large quantities of photoactive porphyrins. The clinical syndrome is dominated by extreme photosensitivity with mutilation of light exposed extremities and hemolytic anemia. Bone disease has been occasionally noted, but is not well characterised. We describe a man with CEP who developed bone pain and spinal crush fractures at the age of 22. Skeletal radiographs revealed features typical of other severe hemolytic anemias, but in addition there was loss of the terminal phalanges of the hand as a result of photomutilation. Spinal bone density (assessed by DPA) was reduced and at the hip bone density was at the lower limit of normal. The metacarpal cortical bone density was 2.9 standard deviations below normal. Biochemical and histological studies accelerated bone turnover. Although the serum 250H vitamin D concentration was very low (because of light avoidance) there was no evidence that the bone disease was a consequence of this. Treatment for one year with clodronate and a high transfusion regime was associated with small reductions in serum alkaline phosphatase and urine hydroxyproline excretion, but there was no improvement in bone mineral density. We conclude that CEP has a distinctive osteodystrophy comprising osteolysis of light-exposed extremities and a high turnover type of osteoporosis. Privational vitamin D deficiency may also occur. The effect upon bone of the new therapies for CEP should be considered.

Alkaline Phosphatase↗
PubMed1991

Neonatal screening for haemoglobin variants using filter paper-dried blood specimens.

Neonatal screening for haemoglobinopathies utilizing cord blood samples is well established, although it has a high miss rate and has the inherent problem of possible misdiagnosis from maternal contamination of the sample. The use of dried Guthrie card samples which are taken at six days of age avoids these problems and has the advantage of using an established system of sample collection. Controversy exists as to the method of choice for analysis of dried samples, this study of 2406 samples found that Iso-electric focusing (IEF) analysis of dried specimens gives excellent correlation when compared with cellulose acetate/citrate agar electrophoresis of liquid cord blood samples. The IEF results were clear and relatively simple to interpret even when the samples had been stored at room temperature for 4 weeks. The commercial enzyme linked immunosorbent assay (ELISA) screening test JOSHUA reliably determines the presence or absence of haemoglobin S in dried specimens. It could therefore be used as a relatively cheap and simple method for the confirmation of sickle cell trait in neonatal screening programmes based on dried specimens.

Electrophoresis↗
PubMed1991

Anticardiolipin antibodies in patients from Malaysia with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is highly prevalent in Malaysia, which has a mixed population of Malays, Chinese, and Indians. A quantitative enzyme linked immunosorbent assay (ELISA) was used to determine anticardiolipin antibody (aCL) levels (total immunoglobulin, IgG, and IgM) in 200 patients with SLE (164 Chinese, 26 Malay, and 10 Indian) attending the University Hospital of Kuala Lumpur, Malaysia, and 103 matched controls. Only 33 (16.5%) of the patients had raised aCL levels; 26 had raised IgG aCL, five IgM aCL, and two both IgG and IgM aCL. There was a low prevalence of raised levels of aCL in the population studied, which was seen in conjunction with a rare occurrence of thrombosis. The classical association of high aCL levels with thrombocytopenia and recurrent abortions was noted, though not with cerebral disease. The low prevalence of aCL in this study population of mixed racial origin contrasts with findings in European patients with SLE and lends support to the influence of local factors, be they genetic or environmental, on the clinical manifestations of this disease.

Abortion, Habitual↗
PubMed1991

Current problems in haematology. 2: Hereditary spherocytosis.

Hereditary spherocytosis is a relatively common haematological disorder and will be encountered by all haematologists. The abundance of new information, dealing principally with molecular and genetic aspects of pathophysiology, is beginning to have implications for its investigation and management. While these advances have not yet exerted a large influence at therapeutic level, the promise of such advents as prenatal diagnosis make this an exciting field to watch.

Erythrocyte Membrane↗
PubMed1990

Differential expression of transferrin receptor in duodenal mucosa in iron overload. Evidence for a site-specific defect in genetic hemochromatosis.

In genetic hemochromatosis, metabolic studies have demonstrated inappropriately increased iron absorption by cells of the duodenal mucosa. It is not clear whether this reflects an intrinsic abnormality of iron homeostasis at this site or is a consequence of a more generalized defect in cellular iron metabolism particularly involving the liver. We have previously used the expression of iron-related proteins as markers of iron homeostasis and have demonstrated normal regulation of the transferrin receptor and ferritin in the liver in this condition. In the present study we used immunohistochemical techniques to study transferrin-receptor expression in the gastrointestinal epithelium in normal subjects and patients with iron overload. In untreated genetic hemochromatosis and normal subjects, villus epithelial cells expressed receptor in the basolateral, subnuclear region. In contrast, in patients with secondary iron overload, receptor staining was absent in villus epithelial cells. The cells in the duodenal crypts showed intense staining for the transferrin receptor in all subjects investigated, a finding consistent with the known behavior of this receptor in proliferating cells. Given that body iron stores in both types of iron overload were comparable, these findings indicating a failure of down-regulation of the villus enterocyte transferrin receptor in genetic hemochromatosis may reflect the presence of a regulatory defect associated with the inability to control iron absorption in this condition.

Adult↗
PubMed1990

A logical approach to the investigation of red cell enzymopathies.

This relatively rare group of disorders may cause quite marked morbidity and occasionally be life-threatening. As their inheritance is largely known accurate information in one family member has obvious benefits to other family members as well as the patient. The identification of the defect is dependent on an accurate clinical story which can be used to guide both the use and the interpretation of the various laboratory tests available. From the clinical aspect the enzymopathies can be divided into various broad groups. First, those involving the main glycolysis which produces the red cell's energy requirements in the form of ATP. Defects of this pathway generally cause a non-spherocytic haemolytic anaemia. Second, those involving the pentose phosphate shunt which maintains the redox potential of the cell necessary for its protection against oxidant stress. The commonest enzyme deficiency world wide, G6PD, is in this pathway and is characterized by stress-induced haemolytic crises. Third, defects of the various linked reactions. The most important of these are the methaemoglobin reductases which catalyse the reduction of methaemoglobin to functional haemoglobin and the enzymes in the Rapoport-Luebering shunt which can modulate the 2,3-DPG level. Whilst defects of these metabolic pathways make up the majority of cases associated with haemolysis, defects of other enzymes, on the whole less critical to the red cell's survival, must occasionally be considered. The red cell, because of its relatively easy availability, can be used as a 'biopsy tool' in the diagnosis of some systemic disorders in which the red cell enzymopathy is not the main feature of the disease. Such considerations are particularly important owing to the technological advances that have occurred in the last 10-15 years which have enabled correct assignment of an increased number of difficult cases. Not only is it possible to characterise the variant enzymes more accurately but it is now possible to have a 'metabolic window' on the red cell and examine it for the derangements of metabolism that characterise the various enzyme deficiencies.

Erythrocytes↗
PubMed1990

Clinicopathological features of acute undifferentiated leukaemia with a stem cell phenotype.

Over a 4 1/2-year period, 141 patients with acute leukaemia had morphologic, immunophenotypic and cytochemical studies performed at King's College Hospital. Seven cases were noted to have blast cells which did not express myeloid or lymphoid antigens or cytochemical staining indicative of differentiation but were HLA DR and CD 34 positive. Based on these criteria we have used the term stem cell acute leukaemia to denote these patients. There were five women and two men with a median age of 61 years (16-86). Presentation marrows were heavily infiltrated with blasts (greater than 95% in 6/7) which were usually pleomorphic. Type 2 blasts. Auer rods and dysplastic features were absent. Two of six cases studied showed clonal karyotypic abnormalities. Four patients were treated with high dose chemotherapy. Three of these achieved a complete remission but relapsed at 3, 6 and 7 months respectively. The median survival of the group was 7 months (2-12). We conclude that the stem cell acute leukaemias are a distinct clinicomorphological group which appear to have a poor prognosis with conventional chemotherapy.

Acute Disease↗
PubMed1990

Lead poisoning: clinical, biochemical, and haematological aspects of a recent outbreak.

The clinical, biochemical, and haematological aspects of a recent outbreak of lead poisoning, in which exposure was related to the oxyacetylene cutting of red lead painted ironwork, were investigated. Initial suspicion was raised when a blood film showed punctate basophilia which remains a simple and useful method of picking up lead toxicity. Estimations of blood lead concentration and conventional laboratory data confirmed the diagnosis. Although there was prominent punctate basophilia, spectrophotometric analysis showed only negligible accumulation of pyrimidine-5'-nucleotides despite severe suppression of pyrimidine-5'-nucleotidase activity. The pattern of the red cell glycolytic intermediates, investigated for the first time, suggested that lead may also affect glycolysis at the hexokinase step. Once the diagnosis was made intravenous chelation treatment was begun with a rapid improvement in symptoms. Long term follow up is required to assess any sequelae of intoxication. These cases emphasise the classic features of lead poisoning, and despite the currently available diagnostic tests, lead intoxication may still go unrecognised unless a thorough occupational history is taken.

5'-Nucleotidase↗
PubMed1989

Prenatal diagnosis of a red-cell enzymopathy: triose phosphate isomerase deficiency.

A child with triose phosphate isomerase deficiency was born to nonconsanguineous parents, and died at 13 months of age. The parents were both found to be heterozygous for this enzyme deficiency. At a subsequent pregnancy, analysis of fetal red blood cells obtained by cordocentesis at 19 weeks' gestation enabled prenatal diagnosis of the heterozygous state. This technique may allow diagnosis of other red-cell enzymopathies during the second trimester.

Carbohydrate Epimerases↗