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Biomedical subjects

G Standen

Publications and source records attributed to G Standen.

At least 19 recordsLinked to original sources
PubMed2004

A case of monocytic leukaemia cutis in a patient with myelodysplastic syndrome transforming to acute myeloid leukaemia.

A 49-year-old woman presented with a 1-year-history of a widespread eruption which proved to be due to leukaemia cutis. Subsequently, she developed pancytopaenia and a bone marrow biopsy revealed refractory anaemia with excess blasts in transformation (RAEB-T) with a high monoblastic component. This transformed into acute myeloid leukaemia. Leukaemia cutis in this context is well described but in this patient it became manifest 1 year prior to referral to the dermatologist. When occurring with a myelodysplastic syndrome, leukaemia cutis often heralds malignant transformation to acute myeloid leukaemia. Prompt diagnosis in this situation may identify a group of high-risk patients with myelodysplastic syndrome for whom chemotherapy and allogenic bone marrow transplantation, rather than the more conventional approach of supportive treatment, could be a more appropriate management strategy.

Anemia, Refractory, with Excess of Blasts↗
PubMed2003

Should we monitor vitamin B12 levels in patients who have had end-ileostomy for inflammatory bowel disease?

BACKGROUND AND AIMS: We examined whether vitamin B12 levels are low following surgery in those patients who have had end-ileostomy for inflammatory bowel disease. PATIENTS AND METHODS: This prospective observational study used the database of a university teaching hospital to identify patients with inflammatory bowel disease with an end-ileostomy constructed more than 30 months previously. Precise diagnosis, disease distribution and details of their surgery were collected from case notes of the 39 eligible patients (18 Crohn's disease, 17 ulcerative colitis, 4 indeterminate colitis). Mean duration since ileostomy formation was 12.53 years. Patients found to be vitamin B12 deficient underwent further investigations to ascertain the cause of their vitamin B12 deficiency (<150 ng/l). RESULTS: There was no significant difference between serum vitamin B12 levels in patients with Crohn's disease and those in patients with ulcerative colitis following end ileostomy formation. Two patients (5.1%) were identified as having vitamin B12 deficiency. One of these had had a panproctocolectomy for Crohn's disease, followed by subsequent resection for ileal obstruction and ongoing small intestinal disease. The other had had colectomy for ulcerative colitis, in whom no cause other than the ileostomy was found for the vitamin B12 deficiency. There was no significant correlation between serum vitamin B12 levels and duration of ileostomy overall or in the disease subgroups. CONCLUSION: We do not recommend routine screening for vitamin B12 deficiency in this group of patients unless they have undergone additional small bowel resection or have ongoing small bowel inflammation.

Adult↗
PubMed1999

A large bruise.

Explore the source record for details and available documents.

Aged↗
PubMed1999

Prenatal diagnosis in factor XIII-A deficiency.

Congenital factor XIII deficiency is a severe bleeding disorder that is inherited as an autosomal recessive trait. The condition is commonly due to absence of the factor XIII-A subunit protein in the plasma. The case of a baby is reported who showed typical clinical features of factor XIII-A deficiency, including recurrent bleeding from the umbilical stump and a life threatening haemorrhage after circumcision. Family studies were performed and molecular analysis, using a Short Tandem Repeat (STR) marker closely linked to the A subunit gene, allowed antenatal exclusion diagnosis to be undertaken in a subsequent pregnancy. The case highlights the importance of seeking a family history of bleeding disorders before surgery in the neonatal period, particularly if the parents are consanguineous.

Consanguinity↗
PubMed1998

Rapid genotypic diagnosis of type 2A von Willebrand's disease by heteroduplex analysis.

We have previously reported a rapid heteroduplex-based technique which is able to identify at least 10 recurrent mutations associated with type 2A von Willebrand's disease. Thirteen patients with this disorder were genotyped by this method and a specific mutation was identified in nine cases. This simple DNA based approach can provide useful information to support data derived from phenotype tests in the initial assessment of such patients.

DNA↗
PubMed1997

Rapid mutation screening in type 2A von Willebrand's disease using universal heteroduplex generators.

Patients with type 2A von Willebrand's disease (VWD) commonly have missense mutations in the A2 domain of the von Willebrand factor (VWF) protein. This domain is encoded by the 3' region of VWF gene exon 2 8 and the large majority of patients have heterozygous mutations clustered in the sequence between codons 742 and 909. We describe a DNA-based diagnostic technique which enables at least 10 previously described mutations to be rapidly identified. The method involves polymerase chain reaction (PCR) amplification of two exon 28 gene segments between codons 717-788 and 803-893, respectively. Each fragment is then hybridized with a synthetic complementary DNA molecule of similar size, termed a Universal Heteroduplex Generator (UHG). The UHG contains base deletions contiguous to the sites of known mutations and, following hybridization, allele-specific heteroduplexes are generated which can be detected by simple polyacrylamide gel electrophoresis and ethidium bromide staining. A small panel of UHG molecules covering the 3' region of exon 28 should enable the large majority of type 2A VWD patients to be rapidly diagnosed by genotype.

Base Sequence↗
PubMed1996

Preliminary observations on possible premalignant changes in bone marrow adjacent to worn total hip arthroplasty implants.

Previous epidemiologic studies have suggested that there may be a risk of malignancy, especially lymphoma and leukemia, after joint replacement, but the followup has been relatively short. This is a preliminary study to see if there is any biologic basis for such a risk. Blood and bone marrow samples from 71 patients at revision arthroplasty of a loose or worn prosthesis and 30 control patients at primary arthroplasty were analyzed with cytogenetic techniques and molecular biology. There was a higher chromosomal aberration rate in cells adjacent to the prosthesis at revision surgery compared with iliac crest marrow from the same patients or with femoral bone marrow at primary arthroplasty. Clonal expansion of lymphocytes without a serum paraprotein was seen in 2 of 21 patients at revision arthroplasty performed more than 10 years after primary arthroplasty. The results of this preliminary study suggest that future epidemiologic studies should concentrate on patients with longer postoperative intervals to see if there is any risk that would be pertinent to a young patient at primary arthroplasty.

Aged↗
PubMed1995

Optimisation and properties of a UHG for genotyping of hemoglobins S and C.

The use of universal heteroduplex generators (UHG) as an effective means of screening for specific mutations has been previously reported. Here, we report the optimisation of a UHG system used for the rapid and simple detection of sickle cell hemoglobinopathies, HbS and HbC. The test involves heteroduplex formation between between polymerase chain reaction (PCR)-amplified beta-globin gene first exon sequences, and a UHG. The UHG is a synthetic DNA molecule homologous to HbA but which contains a small deletion adjacent to the HbS and HbC mutation sites in codons 5 and 6. Heteroduplexes are resolved on nondenaturing polyacrylamide minigels and are diagnostic of HbS and HbC in homozygous and heterozygous individuals. A blind trial of UHG genotyping involving eleven previously sequenced DNAs showed complete concordance between methods. In addition, we identified a characteristic heteroduplex banding pattern for the H2H silent mutation (CAC-->CAT) in codon 2.

Anemia, Sickle Cell↗
PubMed1990

Family studies and prenatal diagnosis in severe von Willebrand disease by polymerase chain reaction amplification of a variable number tandem repeat region of the von Willebrand factor gene.

We have previously demonstrated within intron 40 of the von Willebrand factor (vWF) gene a region of ATCT repeats that was shown to vary in length between two different DNA clones from unrelated individuals. The polymerase chain reaction (PCR) was used to examine the variability in length of this variable number tandem repeat (VNTR) in 53 normal individuals, using primers to DNA sequence flanking the repeat region. Overall, eight different length allelic bands were seen. These were individually sequenced and shown to contain from 6 to 14 ATCT repeats (a nine-repeat band was not seen). Seventy-five percent of individuals were shown to be heterozygous for this vWF.VNTR, and family studies showed Mendelian inheritance with allelic frequencies from 1% (vWF.VNTR [8] and vWF.VNTR [14]) to 39% (vWF.VNTR [7]). In the family of a patient with type III severe von Willebrand disease (vWD), vWF.VNTR results mirrored the phenotypic data and results with previously reported intragenic vWF restriction fragment length polymorphisms (RFLP). The patient was shown to be a compound heterozygote. In a family with a child with severe type III vWD, prenatal diagnosis by vWF.VNTR analysis on DNA obtained by chorionic villus sampling at 10 weeks gestation during a subsequent pregnancy indicated a severely affected fetus. This diagnosis was confirmed by fetal blood sampling at 18 weeks.

DNA↗
PubMed1990

Severe type III von Willebrand's disease caused by deletion of exon 42 of the von Willebrand factor gene: family studies that identify carriers of the condition and a compound heterozygous individual.

Southern blotting was performed with cDNA probes for the human von Willebrand factor (vWF) gene on six patients with severe type III von Willebrand's disease (vWD). A partial deletion in the 3' end of the vWF gene was demonstrated in one individual whose parents were related and who had an alloantibody inhibitor to vWF. A resulting novel 2.0-kilobase (kb) EcoRI fragment was used for carrier detection within the patient's family, and seven carriers of this recessive trait were identified. Of the six tested, five had normal or only slightly reduced levels of vWF antigen, but with generally higher levels of factor VIII. The sixth carrier had moderately severe vWD and it is proposed that this patient is heterozygous for the defective vWF gene and a second recessive vWF defect. The novel 2.0-kb EcoRI restriction fragment was cloned and sequenced, and compared with that of the corresponding normal 4.2-kb EcoRI fragment that includes exons 41 and 42 of the vWF gene. A deletion of 2,320 base pairs (bp) which included exon 42, was identified and a novel 182-bp insert was found between the breakpoints. This insert was detected by polymerase chain reaction amplification both in the patient's DNA and in his carrier relatives.

Amino Acid Sequence↗
PubMed1982

Phagocytosing neutrophils rapidly release a factor which inhibits granulopoiesis in vitro.

Phagocytosis of the heat-killed opsonised yeast, Candida guilliermondii, by human neutrophils resulted in the rapid release of a potent factor which suppressed granulopoiesis in vitro. The factor has been shown to act on monocytes and macrophages by inhibiting the production and release of colony-stimulating factor (CSF) which is the specific stimulator of granulocytic colony-forming cell (CFUc) proliferation in vitro. When added directly to target cells containing CFUc, the inhibitory factor had no effect on colony growth. The absence of detectable inhibitor in media conditioned for short periods with resting neutrophils or neutrophils challenged with unopsonised Candida which are not phagocytosed confirmed that active phagocytosis was the stimulus for inhibitor release. In further experiments, addition of endotoxin to the cultures was shown to suppress the inhibitory effect. We suggest that feedback inhibition of CSF production in vivo may be mediated by products derived from phagocytosing neutrophils.

Candida↗
PubMed1981

Failure of chronic-granulocytic-leukaemia leucocytes to release an inhibition of granulopoiesis.

Phagocytosing, but not resting, neutrophils normally release an inhibitor of in-vitro granulopoiesis which suppresses the production or release of colony-stimulating factor by monocytes and macrophages. Neutrophils from 12 patients with chronic granulocytic leukaemia (CGL) were found to contain the inhibitor, but in 11 of the 12 patients there was failure to release significant amounts during phagocytosis. It is suggested that such a defect in the feedback control of granulopoiesis could lead to the progressive inappropriate accumulation of morphologically normal granulocytes, as seen in CGL.

Candida↗
PubMed1980

The effects of surgical trauma on human granulopoiesis.

Marked changes in the concentration and proliferative state of circulating granulocytic progenitor cells (colony forming units in culture; CFUc) were observed in female patients following surgical trauma. Within one day of an abdominal hysterectomy there was an abrupt fall in the number of blood CFUc to between 10% and 20% of normal and an increase in the proportion synthesizing DNA which coincided with the maximum neutrophilia. Subsequently, as the neutrophil count declined, the CFUc concentration increased to supranormal values and the proliferative response persisted, both parameters returning to normal 2 weeks after surgery. These results suggest that, following surgical trauma, the increased demand for neutrophils is rapidly met by increased CFUc proliferation.

Cell Division↗
PubMed1980

The proliferative state of granulocytic progenitor cells in human blood and marrow.

A double layer agar technique was used to investigate the proliferative state of granulocytic progenitor cells (Colony Forming Units in Culture; CFUc) in human peripheral blood and bone marrow. The sensitivity of the progenitor cells to the S-phase specific agent, hydroxyurea, was used as an index of the proportion of cells engaged in DNA synthesis. In the presence of low concentrations of colony stimulating factor (CSF) the CFUc were found to be virtually insensitive to the drug. However, when cultured in the presence of increasing concentrations of CSF the proportion of CFUc apparently killed by hydroxyurea increased to a maximum of 23% for those cells in the blood and 39% for those in the marrow. The results indicate that CFUc which are slowly proliferating are sensitive to low concentrations of CSF. In contrast, those CFUc which are proliferating more rapidly require high concentrations of CSF before they will form colonies in culture. A model has been devised which suggests that as CFUc mature, their cell cycle time shortens and their sensitivity to CSF decreases.

Blood Cells↗
PubMed1979

Reduced number of peripheral blood granulocytic progenitor cells in patients with Down's syndrome.

The number of granulocytic progenitor cells (colony forming units in culture: CFUc) in the blood of patients with Down's syndrome was found to be reduced by 73.2% when compared to a group of age and sex matched controls. However, the blood CFUc of the Down's syndrome patients and the controls showed similar sensitivity to hydroxyurea which suggests that the low number of progenitor cells in Down's syndrome is not compensated by a marked increase in their cellular proliferation. The colony size distributions were similar for both the patients and the controls and, in addition, repeated assays at various intervals revealed no marked fluctuation in the number of blood CFUc in either group. The significance of the reduced number of circulating CFUc in Down's syndrome in relation to the known susceptibility of such patients to leukaemia is discussed.

Adolescent↗