Biomedical subjects

D Todd

Publications and source records attributed to D Todd.

At least 109 records · Page 6Linked to original sources

PubMed1992

Cytogenetic analysis of hematologic malignancies in Hong Kong. A study of 98 cases.

The karyotypes of 98 patients between the ages of 8 and 81 years with acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), and chronic myeloid leukemia (CML) are presented. Although the well-described cytogenetic abnormalities associated with particular FAB subtypes in the West were observed, certain important local differences were noted. In ALL, hyperdiploidy was rarely observed, whereas the Philadelphia chromosome was observed in 50% of abnormal karyotypes. In AML, the t(8;21) was infrequently observed in M2 case, whereas trisomy 4 and 6, rarely reported elsewhere, formed 12% of the abnormal cases. In MDS, the incidence of -5/5q- and/or -7/7q- was 83% of cases with aberrant cytogenetic findings. Neither i(17q) nor an extra Ph was seen in 26 cases of CML including 9 cases of accelerated phase/blast crisis. In addition, previously unreported cytogenetic abnormalities occurring as single cases are presented. These findings are discussed in the context of geographical heterogeneity of chromosomal abnormalities in leukemia and emphasize the importance of continued epidemiologic studies of cytogenetics in hematologic malignancies.

Adolescent↗

PubMed1992

Detection and differentiation of chicken anemia virus isolates by using the polymerase chain reaction.

Complementary oligonucleotide primers which flank a 675-bp DNA fragment encompassing part of the putative gene for the capsid protein of chicken anemia virus (CAV) were used for the enzymatic amplification of CAV DNA by the polymerase chain reaction (PCR). Application of a dot blot hybridization assay by using a 32P-labeled cloned CAV DNA probe allowed PCR product amplified from as little as 0.1 fg of the target DNA sequence to be detected. When it was used for PCR amplification, DNA extracted from thymus tissue by a guanidine isothiocyanate-based method proved to be more efficient than that extracted by methods involving phenol or boiling. DNAs specified by 14 CAV isolates originating in the United Kingdom, Ireland, Germany, Sweden, the United States, Japan, and Australia were amplified. Restriction endonuclease analysis of the PCR-amplified DNAs with the enzymes HaeIII, HinfI, and HpaII indicated that the 14 CAV isolates can be assigned to seven groups, with isolates from different countries usually exhibiting the greatest number of restriction site differences.

Anemia↗

PubMed1991

Detection of immunoglobulin gene rearrangement in acute and chronic lymphoid leukemias of B-cell lineage by polymerase chain reaction gene amplification.

Polymerase chain reaction (PCR) was used to amplify the DNA fragments of the complementarity determining region 3 of the immunoglobulin (Ig) gene heavy chain from the leukemic cell specimens of patients with acute and chronic lymphoid leukemias of B-cell lineage. Two different pairs of primers were tested. Fourteen of the 17 (82%) cases of acute lymphoblastic leukemia (ALL), and all 15 cases (100%) of B-cell chronic lymphocytic leukemia, who had rearrangement of the Ig gene heavy chain by Southern analysis, were positive by PCR with either one or both pairs of primers. This technique was able to detect leukemic cells at the level of 0.1%. Applying it to study the remission marrow specimens following induction chemotherapy was more useful than morphology alone in predicting early relapse of the leukemia.

Burkitt Lymphoma↗

PubMed1991

Salvage chemotherapy containing moderate-dose cytosine arabinoside and mitoxantrone for relapsed and resistant acute myeloid leukaemia.

A total of 29 evaluable patients with acute myeloid leukaemia (AML) either in relapse or resistant to initial induction daunorubicin-containing chemotherapy were given a salvage regimen consisting of moderate-dose cytosine arabinoside and mitoxantrone. There were 8 (28%) complete responders (CRs), 4 (14%) partial responders (PRs), and 17 (52%) nonresponders. The duration of CRs was 2+, 2+, 3+, 3, 4+, 4, 5 and 6 months respectively. Two of the eight CR patients were refractory to initial daunorubicin-containing induction therapy and another two had achieved a previous CR lasting less than 6 months. Four of the eight CR patients had received an amsacrine-containing salvage regimen (ATA) prior to administration of the present moderate-dose cytosine arabinoside and mitoxantrone regimen; this indicates the lack of absolute clinical cross-resistance between the present combination and the daunorubicin- or amsacrine-containing regimens. However, the duration of CRs achieved by these patients remains very short and should, if possible, be followed by allogeneic or autologous bone marrow transplantation.

Acute Disease↗

PubMed1991

Intensive chemotherapy for adult lymphoblastic lymphomas.

A total of 20 adults patients presenting with previously untreated lymphoblastic lymphoma underwent an intensive chemotherapy protocol. Either the BACOP or the m-BACOD regimen was used for induction. If the patients achieved a complete clinical remission (CR) after three courses, they were given intensive consolidation and maintenance chemotherapy based on a protocol that was modified from the L10/L17M regimen of the Memorial Sloan-Kettering group for acute lymphoblastic leukaemia and lymphoblastic lymphoma. Patients exhibiting localised areas of bulky disease were given additional involved-field radiotherapy. In all, 15 (75%) men and 5 (25%) women were entered in this study. Their median age was 28 years (mean, 30 years; range, 12-64 years). Overall, 3 (15%) had stage II disease, 3 (15%) had stage III disease and 14 (70%) had stage IV disease; 7 (35%) patients exhibited B symptoms and 4 (20%) had bulky disease. The overall (CR) rate was 10/20 (20%), and that following BACOP and m-BACOD therapy was 4/8 (50%) and 6/12 (50%), respectively. In all, 7 of the 10 complete responders (70%) relapsed. The disease-free survival of the ten who achieved a CR was 23% at 3 years. The overall survival of all 20 patients at 3 years was only 37%, and there were very few long-term survivors. More effective treatment for adult lymphoblastic lymphoma is required.

Adult↗

PubMed1991

Chemotherapy for early-stage gastrointestinal lymphoma.

A total of 176 patients with gastrointestinal lymphomas were reviewed. According to a modified staging classification, 51 of them had stage I/II disease and the remaining 125 had stage III/IV disease. In most cases (68%), the histology was intermediate-grade according to the NIH working formulation, and the B-cell immunophenotype was involved in 89% of the 45 cases with a known immunophenotype. The primary site was the stomach in 56% of cases and the bowel in 44%. A significantly higher proportion (P = 0.001) of those with bowel lymphomas had stage III/IV disease (88% vs 57%). The primary gastrointestinal lesion was resected in 122 patients, including all 51 cases of stage I/II disease. In all, 8 stage I/II patients were given radiotherapy alone following surgery and the other 43 underwent chemotherapy; of the latter, 19 received additional radiotherapy following chemotherapy. Chemotherapy was also given to 112 stage III/IV patients, 42 of whom underwent additional radiotherapy. Factors associated with a poorer prognosis included advanced disease, bowel lymphoma and advanced age. Although the complete response (CR) rate according to disease stage was similar, stage I/II patients receiving chemotherapy showed a significantly lower relapse rate, better disease-free survival following CR and improved survival as compared with those receiving radiotherapy alone. However, additional radiotherapy following chemotherapy did not further improve the clinical outcome.

Adolescent↗

PubMed1991

m-BACOD chemotherapy for intermediate- and high-grade non-Hodgkin's lymphoma.

A total of 92 patients with previously untreated intermediate- or high-grade non-Hodgkin's lymphoma attending the University Department of Medicine, Queen Mary Hospital, Hong Kong, were treated with the m-BACOD chemotherapy regimen (methotrexate, bleomycin, doxorubicin, cyclophosphamide, vincristine and dexamethasone). Additional involved-field radiotherapy was given to 32 (35%) patients. Myelosuppression was the major toxicity, and 5 (5%) treatment-related deaths occurred due to pneumonia, bleomycin sensitivity, doxorubicin cardiotoxicity and reactivation of hepatitis B infection. The overall complete response (CR) rate was 65/92 (71%) and the relapse rate was 22/65 (34%). The disease-free survival of the 65 CR patients at 2 years was 52% and the overall survival of all 92 patients at 3 years was 56%. The CR rate of stage I and II patients was significantly better than that of those with stage III and IV disease (87% vs 59%; P = 0.01), and the CR rate of stage III patients was superior to that of those with stage IV disease (86% vs 50%; P = 0.05). The overall survival of stage III and IV patients was significantly worse than that of subjects with stage I and II disease (31% vs 73%; P = 0.02). Multivariate analysis revealed that the independent prognostic variables significantly determining the CR rate and survival included the clinical stage and the serum lactate dehydrogenase level. From this study, the results of treatment with the m-BACOD regimen in patients with advance disease appeared to be similar to those obtained using the conventional CHOP regimen (cyclophosphamide, doxorubicin, vincristine and prednisone).

Adolescent↗

PubMed1991

Comparison of three animal viruses with circular single-stranded DNA genomes.

No common antigenic determinants and no DNA sequence homologies were detected when three animal viruses, chicken anaemia agent (CAA), porcine circovirus (PCV), and psittacine beak and feather disease virus (PBFDV), all of which possess circular single-stranded DNA genomes, were compared. Negative contrast electron microscopy showed that PCV and PBFDV particles were 30% smaller than CAA particles and lacked the surface structure of CAA.

Animals↗

PubMed1991

Reactivation of hepatitis B virus replication in patients receiving cytotoxic therapy. Report of a prospective study.

One hundred Chinese patients who received induction cytotoxic therapy for malignant lymphoma were prospectively studied to determine the incidence, morbidity, mortality, and predisposing factors for reactivation of hepatitis B virus replication during cytotoxic therapy. In 18 (67%) hepatitis B surface antigen-positive and 10 (14%) hepatitis B surface antigen-negative patients, hepatitis developed during cytotoxic therapy (P less than 0.0001). Hepatitis could be attributed to exacerbation or reactivation of chronic hepatitis B in 13 (72%) hepatitis B surface antigen-positive patients but in only 2 (20%) hepatitis B surface antigen-negative patients (P less than 0.0001). Sudden increase or reactivation of hepatitis B virus replication gave rise to icteric hepatitis, nonfatal hepatic failure, and death in 22.3%, 3.7%, and 3.7% of patients who were positive for hepatitis B surface antigen; in 2%, 2%, and 0% of those positive for hepatitis B antibodies; and in none of those who were seronegative. Among the hepatitis B surface antigen-positive patients, male sex was the only factor that was associated with an increased risk of reactivation of hepatitis B virus replication. We recommend that hepatitis B surface antigen-positive patients with malignancies receiving cytotoxic therapy be closely monitored.

Adolescent↗

PubMed1991

Comparison of reporter molecules for viral in situ hybridization.

A number of streptavidin-linked reporter molecules at the endpoint of a five-step detection protocol for viral in situ hybridization using biotinylated probes were examined. DNA-DNA and RNA-RNA model systems were used. Streptavidin linked to either peroxidase or fluorescein was found to be optimal in terms of sensitivity and resolution within individual cells. All other reporter molecules labelled similar numbers of cells with low background reaction. However, streptavidin-5 nm gold followed by silver enhancement gave very high background staining making interpretation of positive signals very difficult.

Alkaline Phosphatase↗

PubMed1991

Chemotherapy versus radiotherapy for stage I-II intermediate grade non-Hodgkin's lymphomas.

The clinical outcome of 149 patients with Stage I-II intermediate grade non-Hodgkin's lymphomas was analysed. There were 77 (52%) males and 72 (48%) females. Their median age was 58 years. Eighty patients (54%) had Stage I disease and 69 (46%) Stage II. Twenty-nine (20%) of them received radiotherapy only, 75 (50%) doxorubicin-containing chemotherapeutic regimens and 45 (30%) other less intensive chemotherapy. Sixty-two patients had additional radiotherapy following chemotherapy. Patients receiving other less intensive chemotherapy were significantly older (P = 0.0001) and those receiving radiotherapy alone had a significantly higher proportion of Stage I disease (P = 0.007). Patients receiving less intensive chemotherapy had a significantly low complete response (CR) rate. Patients receiving radiotherapy alone had a significantly high relapse rate and low disease-free survival following CR. However, there was no significant difference in overall survival regardless of the mode of therapy. This lack of survival advantage might be related to the effective salvage chemotherapy in some of the radiotherapy failures and the occasional chemotherapy-related mortality. Additional radiotherapy following chemotherapy did not appear to give further benefit.

Adolescent↗

PubMed1991

A comparison of expression of surface-bound immunoglobulin E on antigen-presenting cells in cutaneous tissue between patients with allergic, irritant and atopic dermatitis.

The expression of surface-bound immunoglobulin E by dendritic cells within cutaneous tissue has been compared in atopic and contact dermatitis. 45 patients were recruited into 4 groups using clinical criteria and patch testing to a standard series of allergens: atopic (12 cases), allergic contact dermatitis (14 cases), irritant contact dermatitis (10 cases) and the control group (9 cases); using clinical criteria and patch testing to a standard series of allergens. Skin biopsies from each patient were analysed by the indirect immunofluorescence technique. This differentiated 3 patterns of cutaneous IgE distribution: (i) no detectable cutaneous IgE; (ii) detection of IgE solely within the dermis; (iii) detection of IgE within both epidermis and dermis. Detection of IgE within the epidermis was always associated with the presence of IgE within the dermis. In each case, IgE was surface-bound by dendritic cells. Immunoglobulin E was detected within both epidermis and dermis in skin biopsies from 8 (66.7%) atopic patients and 2 (20%) patients with irritant contact dermatitis. No other cases demonstrated IgE deposition within both the epidermis and dermis. Atopic patients were significantly more likely to have detectable IgE deposition, within both epidermis and dermis, than patients with contact dermatitis (allergic and irritant groups combined, p = 0.0011) or controls (p = 0.0049). This finding suggests that the demonstration of IgE within both epidermis and dermis supports a diagnosis of atopic dermatitis. It would therefore be of value in differentiating between atopic and contact dermatitis, where clinical diagnosis is in doubt.

Dendritic Cells↗

PubMed1991

Dot blot hybridization assay for chicken anemia agent using a cloned DNA probe.

A dot blot hybridization assay capable of detecting chicken anemia agent (CAA)-specific DNA in tissues from infected birds has been developed. The assay uses a 32P-labeled DNA probe prepared from cloned CAA-specific fragments representing the entire virus genome and has a sensitivity limit of between and 1 and 10 pg. DNAs from CAA isolates originating in the Federal Republic of Germany, Japan, the United States, the United Kingdom, and Australia were detected. Investigation of specimens from experimentally infected chicks indicated that virus-specific DNA was detected in the tissues of birds from 5 through 42 days after infection and that greater amounts were usually detected in the thymus than in the spleen, liver, feces, or blood. Tissues from specific-pathogen-free and broiler chicks which had become infected at an older age through contact with experimentally infected anemic chicks also contained CAA-specific DNA detectable by the assay. Thymuses from 1- to 2-week-old chicks from eight commercial broiler flocks which had been showing clinical signs characteristic of anemia-dermatitis syndrome were found positive by the hybridization technique, but thymuses from chicks obtained from broiler flocks which did not show such signs were found negative. Of the 35 positive samples (from 46 samples tested), 19 (54%) contained virus-specific DNA in sufficiently great amounts to permit 4-h autoradiography exposures and sample throughput times of 2 days. When compared with virus isolation, the CAA dot blot hybridization assay is time- and labor-saving.

Anemia↗

PubMed1991

Rearrangement of immunoglobulin and T cell receptor genes in acute and chronic leukaemias.

The pattern of immunoglobulin (Ig) and T cell receptor (TCR) gene rearrangements was determined in 87 patients with acute and chronic leukaemias and myelodysplastic syndromes by Southern blot hybridisation. All 31 cases of common, B cell and null cell acute lymphoblastic leukaemia, and B cell chronic lymphocytic leukaemia showed Ig heavy chain (JH) rearrangement, and TCR (beta-chain) rearrangement was seen in all 5 cases of T cell acute lymphoblastic leukaemia. Inappropriate JH and TCR (beta) rearrangements were present in some cases of T-ALL (60%) and common acute lymphoblastic leukaemia (18%), respectively. For the 19 patients with acute leukaemias following chronic myeloid leukaemia, blastic transformation, all 4 with lymphoid transformation and 3 of the 15 with myeloid transformation had JH rearrangement, and 3 CD10-positive lymphoid transformation and 2 myeloid transformation had their TCR (beta) genes rearranged. In conclusion, the pattern of Ig and TCR gene rearrangements correlated well with the cell lineage. However, cross-lineage rearrangements were more commonly seen in patients with acute leukaemias following chronic myeloid leukaemia blastic transformation, as compared to the de novo cases.

Adolescent↗

PubMed1991

Direct comparison of peripheral T-cell lymphomas with their B-cell counterpart.

The aim of this study was to determine the effect of immunophenotype on the clinical characteristics and prognosis of 144 adult Chinese patients with non-Hodgkin's lymphomas. Those entities with well-recognised immunophenotype and clinical characteristics were excluded. Significantly more patients with T-cell lymphomas had B symptoms (52 vs. 30%, p = 0.05) and fewer had bulky disease (7 vs. 25%, p = 0.04). Extranodal involvements of liver, spleen, marrow, nasal region and skin were significantly more common in T-cell lymphomas. On the other hand, gastro-intestinal involvement was more commonly seen in B-cell tumours. Induction chemotherapy of comparable intensity was used in treating these patients. The immunophenotype did not appear to affect significantly their prognosis.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1991

Combined chemotherapy and radiotherapy for lymphomas of Waldeyer's ring.

The management of 47 patients with stage I and II Waldeyer's ring lymphomas was reviewed. Twenty-one of them received radiotherapy only, and the other 26 received combined chemotherapy and radiotherapy. Patients with primary disease in the nasopharynx, high-grade histology or advanced age were associated with poorer survival. Although the complete response rates were similar, the patients receiving combined chemotherapy and radiotherapy had significantly fewer relapses and a better disease-free survival. However, their survivals were similar. The lack of improvement in the overall survival might be due to the effectiveness of salvage chemotherapy in treating some of the radiotherapy failures and the occasional chemotherapy-related mortality.

Adult↗

PubMed1990

Nasal lymphoma. A retrospective analysis of 60 cases.

Sixty cases of nasal lymphomas were reviewed. There were 42 men and 18 women. The median age was 49 years. The histologic types were low grade in four cases, intermediate grade in 33, high grade in seven, and unclassifiable in 16. Thirteen cases had features of polymorphic reticulosis. The immunophenotype was available in 18 cases and a majority of 67% of them were T-cell. Forty-one of them (68%) had clinically localized (Stage I and II) disease which often spread locally to neighboring tissues and they presented predominantly with nasal symptoms. Nasal lymphoma appeared to carry a poor prognosis. Although our patients with clinically localized disease had significantly better prognosis than those with advanced disease, the 5-year survival of Stage I and II patients was only 55%. Chemotherapy did not appear to be more effective than radiotherapy alone in preventing relapses but the patient number was too small to allow a firm conclusion to be made. Patients with advanced disease had even poorer prognosis with a 5-year survival of only 17%. Innovative therapy has to be developed for these patients.

Adolescent↗

PubMed1990

Rearrangement of immunoglobulin, T-cell receptor, and bcl-2 genes in malignant lymphomas in Hong Kong.

The pattern of malignant lymphomas in the Hong Kong Chinese population is characterized by a low incidence of Hodgkin's disease and follicular lymphomas. The authors studied the immunoglobulin (Ig), T-cell receptor (TCR), and bcl-2 gene rearrangement in 62 cases of malignant lymphoma in this population by Southern blot hybridization. Two cases of Hodgkin's disease showed no rearrangement of the Ig and TCR genes. All 42 cases of B-cell lymphoma had Ig heavy chain (JH) rearrangement with or without additional rearrangement of the light chains (C kappa and C lambda). One case of diffuse B-cell lymphoma had additional T-cell receptor beta-chain (C beta) rearrangement. Sixteen of 18 cases of T-cell lymphoma had C beta rearrangement, and one case of T-lymphoblastic lymphoma had additional JH rearrangement. Two of eight (25%) cases of follicular lymphoma but only one of the 34 (2.9%) cases of diffuse B-cell lymphoma had bcl-2 rearrangement that was detected by pFL-1 probe. None of the 62 cases showed bcl-2 rearrangement using the pFL-2 probe. In conclusion, the Ig and TCR gene rearrangement pattern of the lymphomas found in Hong Kong correlates well with the T-cell and B-cell lineage, which is similar to reports in the white population. However, the incidence of bcl-2 gene rearrangement in follicular B-cell lymphoma is lower than that reported in the US but comparable with that in Japan.

Chromosomes, Human, Pair 18↗