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Biomedical subjects

D Todd

Publications and source records attributed to D Todd.

At least 145 records · Page 8Linked to original sources

Subclinical Aujeszky's disease virus infection in a pig herd and the characterisation of the strain of virus isolated.

The spread of antibody to Aujeszky's disease virus through a susceptible pig herd was monitored after the probable introduction of infection by a recently purchased boar. The infection spread slowly through the herd but no clinical signs of Aujeszky's disease were seen. The strain of virus isolated was designated NIA-6. It has been characterised by a series of experimental infections and extends the known range of virulence of isolates of Aujeszky's disease virus made in Northern Ireland. The strain caused no disease in four-week-old piglets and is therefore less virulent than other isolates from Northern Ireland pigs. However, it killed rabbits and a proportion of experimentally infected two-week-old piglets, which differentiates it from the avirulent bovine isolate (NIA-4).

Animals↗

Restriction fragment length polymorphism in the interzeta hypervariable region for prenatal diagnosis of non-deletion alpha thalassemia.

A Bam HI restriction fragment length polymorphism in the interzeta hypervariable region (IZ HVR) of the zeta-alpha gene cluster was used for the prenatal diagnosis of a pregnancy at risk for Hb H hydrops fetalis. The parents had zeta-alpha thalassemia 1 and non-deletion alpha thalassemia, respectively, and a previous hydrops was missed using the conventional method of gene detection. In this prenatal diagnosis, linkage to IZ HVR was used to exclude non-deletion alpha thalassemia, and the numbers of zeta and alpha genes in the fetus were quantitated to predict the exact genotype. Confirmation was made by analysis of cord blood at delivery.

Amniocentesis↗

HOAP-Bleo as salvage therapy for diffuse aggressive non-Hodgkin's lymphoma.

A total of 30 patients with recurrent or unresponsive diffuse, aggressive non-Hodgkin's lymphoma, who had previously received doxorubicin, cyclophosphamide, vincristine, and prednisone with or without bleomycin were treated with a combination of doxorubicin, vincristine, ara C, prednisone, and bleomycin (HOAP-Bleo). Complete remissions were achieved in 33.3% of the patients and partial remissions in 13.3%. Four of the ten complete responders relapsed at 4, 10, 11, and 18 months. Myelosuppression was the major toxicity and nonhematological toxicities were acceptable. Their median survival from the date of first relapse was only 4-5 months.

Adult↗

Chemotherapy for relapsed and resistant acute nonlymphoblastic leukemia. Effect of ATA, an amsacrine-containing regime.

Twenty-nine evaluable patients with acute nonlymphoblastic leukemia (ANLL), either in relapse or resistant to initial induction therapy (ara C, daunorubicin + etoposide), received the ATA regime consisting of 100 mg/m2 per day Ara C by i.v. infusion for 4-5 days, 100 mg/m2 per day thioguanine orally for 4-5 days, and 100 mg/m2 per day amsacrine i.v. for 2-5 days. Each patient received 1-6 courses (median, 2) of the regime. There were 7 (24%) complete responders, and their duration of responses were 2, 2, 2, 5, 9+, 19, and 24+ months. The complete remission (CR) rate of patients who had a previous CR beyond 6 months (6/13, 46%) was significantly better (X2 = 4.25, p less than 0.05) than that of those who had previously relapsed within 6 months or were refractory to primary induction chemotherapy (1/16, 6%). The two groups of patients had similar patterns of treatment failure. Myelosuppression was the major toxic side effect, and nonhematological toxicities were mild and acceptable.

Acute Disease↗

Imipenem/cilastatin as initial therapy for febrile neutropenic patients.

Imipenem 2 g daily was administered intravenously to 40 evaluable patients with neutropenia and fever. Twenty-three patients had acute leukaemia and 17 malignant lymphoma. The overall response rate was 70.0%. Of the 14 patients with documented infection, 9 (64.3%) responded. Poorer responses were observed in patients with pneumonia (40%) or pseudomonal infection (50%). The response rate was significantly higher among patients with increasing neutrophil counts during therapy (P less than 0.02). Fungal infection was a common cause of treatment failure. Gastrointestinal side effects and skin rashes were occasionally seen. No patient developed central nervous system toxicity. Imipenem is a practical alternative to antibiotic combinations for management of neutropenic infection. However, careful monitoring is essential in the subgroups of patients with pneumonia or pseudomonal infections, who may require modifications of therapy.

Agranulocytosis↗

Different forms of Hb H disease in the Chinese.

A marked genetic and clinical variability of the Hb H syndrome occurs because of the molecular heterogeneity of alpha-thalassemia (thal). The hallmark is the presence of excess beta chains forming Hb H (beta tetramer). In the Chinese, classical Hb H disease presents as "alpha-thalassemia intermedia" and is due to a double heterozygosity for two deletional forms of alpha-thal, alpha-thal-1 and alpha-thal-2. The majority of cases with an alpha-thal-1 defect have a deletion of at least 18.1 kb starting 3' to the zeta 1 gene which includes the psi alpha and the two alpha genes; it is similar to that described in Thais. However, two families had a deletion of the entire zeta-alpha gene cluster, i.e. zeta-alpha-thal-1. Of 33 alpha-thal-2 defects studied, 26 were the rightward deletion (alpha -3.7 kb, all type I defects) and seven the leftward deletion (alpha -4.2 kb); one of the latter was associated with Hb Q. About 10% of the alpha-thal defects belong to the nondeletion type, the most common form being Hb Constant Spring (CS). This anomaly, when coinherited with alpha-thal-1, produces Hb H-CS disease which has a most marked anemia and splenomegaly due to the instability of the alpha-CS chain. Hb Quong Sze produces an alpha-thal-2 because of the unstable alpha-Quong Sze chain. One patient who inherited classical Hb H disease and Hb New York (NY) [alpha 113(G15)Val----Glu] had severe anemia, and required frequent blood transfusions due to the deleterious effect of an increased alpha-NY chain turnover.(ABSTRACT TRUNCATED AT 250 WORDS)

Chromosome Deletion↗

Prenatal diagnosis of alpha- and beta-thalassemias: experience in Hong Kong.

The incidence of alpha-thalassemia trait (alpha-thal-1 and alpha-thal-2) among Southern Chinese in Hong Kong is about 3%. From June 1983 to September 1987, prenatal diagnosis for homozygous alpha-thal-1 was performed in 88 pregnancies at risk, using direct DNA analysis of amniotic fluid cells or chorionic villi. Twenty-one homozygous alpha-thal-1 fetuses were aborted and confirmed as Hb Bart's hydrops fetalis, and two were "Hb H" hydrops fetalis. Of 47 pregnancies delivered, 26 were alpha-thal-1 heterozygotes, 10 normal, eight alpha-thal-1/normal. Twenty-one pregnancies, diagnosed as alpha-thal-1/normal, await delivery. Based on a 6% incidence of beta-thalassemia minor among pregnant women in Hong Kong, the number of pregnancies at risk for beta-thalassemia major should be 288 per annum. However, since February 1984, only 25 diagnoses were performed. Comprehensive screening and education programs need to be implemented. The majority of beta-thalassemia defects in Southern Chinese are point mutations, single nucleotide insertions or minor deletions, not detectable by standard gene mapping techniques. With linkage analysis of the defective gene to polymorphic restriction sites, a definitive diagnosis can be obtained in 50% of the families, while in the remaining there is a 50% exclusion rate. We routinely use the Hind III-3' beta, Bam HI-3' beta, Ava II-beta, and Hinc II-psi beta sites for linkage analysis. For first pregnancies, the marked linkage disequilibrium of the Bam HI polymorphism can be applied in 29% of the cases. In nonconclusive cases, fetal blood beta/gamma globin chain synthetic ratio was used.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗

A novel beta-thalassemia frameshift mutation (codon 14/15), detectable by direct visualization of abnormal restriction fragment in amplified genomic DNA.

A new frameshift mutation due to an insertion of G between codon 14/15 of the beta-globin gene was found in two unrelated Chinese patients with Cooley's anemia. The first patient (W.S.) was homozygous for haplotype 5 (Chinese) and carried a codon 41/42 (four base pair deletion) mutant, while the second patient (C.K.) was homozygous for haplotype 2 (Chinese), and also had a codon 17 (A----T) nonsense mutation. Molecular cloning and M13 sequencing of the beta gene in patient W.S. revealed that the new mutant was found in a beta-globin gene framework type 3 (Asian). Direct sequencing was performed on polymerase chain reaction-amplified genomic DNA from patient C.K. With the new mutation, an additional BstNI or EcoRII recognition site is generated and the abnormal restriction fragment (134 basepair) can be directly visualized on polyacrylamide gel electrophoresis of the amplified genomic DNA.

Base Sequence↗

Application of DNA polymorphisms for prenatal diagnosis of beta thalassemia in Chinese.

Forty-seven Chinese suffering from beta thalassemia major and their parents were studied to establish linkage of the beta thal and beta A genes with 11 restriction site polymorphisms. There is marked linkage disequilibrium at the BamH I site 3' to the beta globin gene, such that, in 31% of pregnancies, absence of the site in the fetus can exclude beta thalassemia major. Using four restriction sites (Hinc II psi beta, Ava II beta, Hind III beta, and BamH I beta), prenatal diagnosis is feasible in all families. In 46% of all cases, a definitive diagnosis can be made, and in the remaining cases, a 50% chance of exclusion is possible. Fetal blood globin chain analysis would be required for the failures. Our experience in nine successive beta thalassemia prenatal diagnosis is also reported.

China↗

Antigenically important proteins of Aujeszky's disease (pseudorabies) virus identified by immunoblotting.

Immunoblotting was used to identify those Aujeszky's disease virus proteins which elicited major antibody responses in naturally and experimentally infected pigs. Although some proteins comprising purified virus preparations reacted nonspecifically, proteins with mol. wts. of 120 K, 90 K, 71 K and 60 K were antigenically important. These corresponded in size to the virus glycoproteins identified by 3H-glucosamine labelling. Glycoproteins isolated by affinity chromatography from infected PK 15 cells solubilised by Triton X-100 (Triton-soluble glycoproteins) contained antigenic components similar in size to virus glycoproteins and produced minimal non-specific immunoblotting reactions. Antibody responses to the 120 K and 71 K proteins usually occurred together and were more pronounced than responses to other proteins especially at early times postinfection.

Animals↗

Peripheral T cell lymphoma.

Thirty-one Chinese patients with peripheral T cell lymphoma (PTCL) were reviewed. Using the modified Japanese Lymphoma Group classification, there were nine (29%) of the pleomorphic type, 16 (52%) immunoblastic lymphadenopathy (IBL)-like, two (7%) T-zone lymphoma, and one (3%) Lennert's lymphoepithelioid type. Three (9%) were not classifiable. All were positive for T11 (E rosette receptor antigen). Fifty-four percent (15 of 28) were positive predominantly for T4 (helper T cell) and 46% (13/28) for T8 (suppressor T cell). The median age of the patients was 57 years. They usually presented with advanced disease, and while extranodal involvement was common, CNS disease was not seen. The IBL-like type was associated with a positive Coombs' test and polyclonal hypergammaglobulinemia. Five of the nine pleomorphic type were checked for antibody to HTLV-I virus and all were negative. PTCL was associated with poor prognosis, which was not influenced by the histologic subtypes and the T4/T8 phenotypes. The complete response rate of 13 consecutive patients who received the BACOP (bleomycin, doxorubicin, cyclophosphamide, vincristine, and prednisone) L17M regimen was significantly better than the 16 historic controls who received other less-intensive regiments, 84% v 19% (P less than .01). The relapse rate was also significantly lower, 9% v 100% (P less than .001). There appeared to be an improvement in the disease-free survival (DFS) (80% v 0% at 18 months), as well as the overall survival (60% v 36% at 18 months), but the differences did not reach statistical significance due to small sample sizes.

Adult↗

Distribution of beta-thalassemia mutations in south China and their association with haplotypes.

DNA from 93 Chinese beta-thalassemia chromosomes were hybridized to eight different mutant oligomers to determine their specific mutation. Four mutations accounted for 87% of the chromosomes; in descending frequencies, these mutations were codon 41/42, IVS-2 nt654, codon 17, and -28. Since codon 41/42 mutation can be associated with multiple beta-thalassemia haplotypes, codon 41/42 is probably a hot spot for the 4-bp deletion. The distributions of these mutations were mapped to various regions in south China. These data are useful for the planning of prenatal diagnosis programs in other Chinese communities worldwide.

China↗

Continuing medical education.

With the rapid advances in medical science and increasing complexities of patient care, the need for continuing medical education (CME) is widely accepted by the profession. CME follows general and higher professional training, and should be a life long process. Teaching hospitals and postgraduate professional institutions play vital roles in organising, promoting, and monitoring this activity. CME directorates should be established. University authorities must recognise the important role of medical teachers in postgraduate and continuing medical education, and the staff establishment and terms of service should be held regularly. Medical libraries should have easy borrowing facilities. Self-assessment and audio-visual material are particularly helpful to the busy practitioner and inexpensive local or regional journals of quality can provide pertinent and up-to-date information. All charges for attending scientific meetings and educational material should be tax deductible or subsidized. The effectiveness of CME is difficult to assess and participation is almost impossible to enforce. Much depends on the standard of medical practice wanted by society. Recertification of general practitioners or specialists poses many problems. On the other hand, completion of self-assessment programmes, active participation at medical meetings, contributions to scientific literature, and membership of medical societies with built-in peer review could be monitored and regularly used to evaluate professional status.

Education, Medical, Continuing↗

Characteristics and distribution of beta thalassemia haplotypes in South China.

Eleven restriction site polymorphisms in the beta-globin gene cluster were determined in 48 Chinese with homozygous beta-thalassemia and their parents. Seven haplotypes were identified as associated with the beta thal chromosome and 25 with the beta A chromosome. The distribution of the various beta thal haplotypes in different regions of South China was mapped and discussed in relation to prenatal diagnosis and migration of the Chinese people.

China↗