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Biomedical subjects

D Todd

Publications and source records attributed to D Todd.

At least 127 records · Page 7Linked to original sources

Histologic subtypes and survival of Chinese patients with non-Hodgkin's lymphomas.

The histologic subtypes and survival of 840 Chinese patients with non-Hodgkin's lymphoma (NHL) were reviewed. All cases were classified according to the Rappaport and Kiel systems and the Working Formulation (WF). A low incidence of nodular/follicular lymphomas (12%) was observed. The most common histologic subtypes were diffuse histiocytic, diffuse centroblastic, and diffuse large cell lymphomas, according to Rappaport, Kiel, and the WF, respectively. A high proportion (24%) of the cases were unclassifiable, according to Kiel, because of the precise terms of the classification. The "favorable"-prognosis NHL, according to Rappaport, or the low-grade NHL, according to Kiel and the WF, had a more indolent clinical course. However, except for the nodular mixed (Rappaport) or follicular mixed (WF) lymphomas which appeared to behave like the more aggressive NHL, a plateau was not seen in the survival curves of our patients with other kinds of favorable-prognosis or low-grade NHL, indicating the lack of curative potential of these tumors. The lymphoplasmacytoid lymphoma, according to Kiel, also appeared to have a more aggressive clinical course. A plateau was seen in most of the other survival curves of patients with the more aggressive tumors, indicating the prospect of cure. However, the prognosis of the very aggressive tumors such as the diffuse lymphoblastic and diffuse small noncleaved cell lymphomas, according to the WF, remains very poor with a median survival of less than 10 months.

Adolescent↗

Etoposide in acute nonlymphocytic leukemia. Australian Leukemia Study Group.

Previously untreated patients with acute nonlymphocytic leukemia (ANLL) aged 15 to 70 years were randomized to either cytosine arabinoside 100 mg/m2/d continuous intravenous (IV) infusion days 1 through 7, daunorubicin 50 mg/m2/d IV days 1 through 3 (7-3), or the same drugs intensified with etoposide 75 mg/m2/d IV days 1 through 7 (7-3-7) as induction therapy. Patients achieving complete remission (CR) received two courses of consolidation therapy (5-2 or 5-2-5) followed by maintenance therapy. Of 264 eligible patients, CR occurred in 56% of 7-3 and 59% of 7-3-7 patients; 7-3-7 significantly improved remission duration (P = .01). The median remission duration was 12 months for 7-3 and 18 months for 7-3-7. Survival was similar when the two arms were compared overall. Subset analysis performed to identify patients with the most benefit showed that etoposide significantly prolonged remission duration in younger patients (less than 55 years) with a median of 12 months for 7-3 and 27 months for 7-3-7 (P = .01). Survival appeared to be prolonged with 7-3-7 in patients aged less than 55 years, with a median of 9 months for 7-3 as compared with 17 months for 7-3-7 (P = .03). In older patients (aged greater than or equal to 55 years), 7-3-7 was more toxic, with significantly more severe [World Health Organization (WHO) grade 3 or 4] stomatitis (P = .02) and no additional clinical benefit. Hematologic toxicity for induction courses was similar, with granulocytopenia less than 0.5 x 10(9)/L for a median of 16 days per course for 7-3 and 15 days for 7-3-7. Hematologic toxicity was more severe for 5-2-5 consolidation courses (P = .003). Induction and consolidation therapy intensified with etoposide resulted in significantly improved remission duration but not survival.

Adolescent↗

Induction chemotherapy for newly diagnosed acute myeloid leukaemia using a regime containing cytosine arabinoside, daunorubicin and etoposide.

A total of 46 patients with previously untreated acute myeloid leukaemia were treated with an induction regimen consisting of 100 mg/m2 cytosine arabinoside given daily by 18-h i.v. infusion for 7 days, 50 mg/m2 daunorubicin given daily by i.v. bolus injection for 3 days and 75 mg/m2 etoposide given daily by 1-h i.v. infusion for 7 days. In all, 30 patients (67%) went into complete remission and were given further consolidation and maintenance chemotherapy. Of the 31 complete responders, 15 (48%) relapsed. The median disease-free survival of the 31 complete responders and the median overall survival of all 46 patients were 25 and 14 months, respectively. None of the clinical characteristics, which included sex, age, FAB morphology, extramedullary disease and initial WBC count, predicted the clinical response. Myelosuppression was the major toxicity and non-haematological side effects were acceptable. The regimen appeared to have acceptable toxicity, and its efficacy was comparable with that of standard regimens.

Adolescent↗

Polymorphic reticulosis and conventional lymphomas of the nose and upper aerodigestive tract: a clinicopathologic study of 70 cases, and immunophenotypic studies of 16 cases.

Seventy patients with malignant lymphomas, including the entity known as polymorphic reticulosis (PR), involving the nose, nasal sinuses, nasopharynx, oropharynx (excluding tonsil), and larynx were studied. There were 26 cases of PR, 19 cases of lymphoma with features of PR (ML[PR]) and 25 cases of conventional lymphomas. Fourteen of the 25 conventional lymphomas were due to dissemination from distant sites. For all histologic types of primary lymphoma, the presenting symptoms were similar, and the nasal cavity was more commonly involved than the nasopharynx. Patients with PR were younger, had a higher male:female ratio, and had a better overall survival rate than patients with conventional lymphomas. Cryostat section immunohistochemistry performed on 17 samples from 16 patients showed only one B lymphoma out of 11 primary lesions; the other 10 cases and three recurrent tumors at distant sites showed phenotypic markers of T lymphocytes and natural killer cells. All three secondary tumors were of B-cell type. Of eight patients with sequential biopsies, progression to a more malignant histopathologic type was found in six. In the PR and ML[PR] biopsies, angiocentricity was detected in 11%, and angioinvasion in 22%. We could not confirm identity of PR with other angiocentric immunoproliferative lesions.

Humans↗

Purification and biochemical characterization of chicken anaemia agent.

Chicken anaemia agent (CAA) was purified using differential centrifugation and successive cycles of equilibrium density gradient centrifugation using sucrose and CsCl. The purification method was dependent on the use of an antigen-detecting ELISA based on a CAA-specific monoclonal antibody. Virus particles banded at a density of 1.33 to 1.34 g/ml in CsCl and measured 23.5 +/- 0.8 nm in diameter. Purified preparations contained one major polypeptide (Mr 50,000) and a single-stranded, circular DNA (2.3 kb). CAA shares some of the biochemical characteristics possessed by porcine circovirus and the virus associated with psittacine beak and feather disease.

Animals↗

Risk factors in progression beyond stage 2 retinopathy of prematurity.

Of the 96 babies born at less than 30 weeks gestation at Westmead Hospital between January 1986 and December 1987, 91 were studied. Of these 37 developed some form of retinopathy of prematurity (ROP), with eight babies having stage 3 or worse. We compared the clinical features of these eight babies to a control group of eight babies with stage 2 ROP, having matched for gestational age. Factors of statistical significance in progression beyond stage 2 were male sex and number of days of assisted ventilation. The presence of a patent ductus arteriosus, although not statistically significant, is a factor which we consider to be clinically important. The development of Plus disease is associated with a poor prognosis.

Australia↗

Ofloxacin versus co-trimoxazole for prevention of infection in neutropenic patients following cytotoxic chemotherapy.

The efficacy of ofloxacin in preventing infection in neutropenic patients following cytotoxic chemotherapy was evaluated and was compared with that of co-trimoxazole. A total of 102 patients with hematological malignancies were randomly selected to receive either co-trimoxazole or ofloxacin. All patients were monitored for compliance, occurrence of infection, and drug-related side effects. A surveillance culture of a rectal swab was performed regularly. A total of 25 of the 52 patients (48%) who received co-trimoxazole and 11 of the 50 patients (22%) who received ofloxacin developed fever during the study period (P less than 0.025). Gram-negative bacteremia occurred in nine patients in the co-trimoxazole group (17%) but in only one patient (2%) in the ofloxacin group (P less than 0.05). No patient in either group had documented gram-positive bacterial or Pneumocystis carinii infection. Poor performance status was the only identifiable factor associated with an increased incidence of bacteremia. The surveillance study showed that significantly fewer bacterial strains were resistant to ofloxacin than to co-trimoxazole and that acquisition of resistance to co-trimoxazole was more commonly observed than was acquisition of resistance to ofloxacin. Significantly more patients had skin rashes following co-trimoxazole than ofloxacin treatment (P less than 0.05). Ofloxacin was superior to co-trimoxazole in preventing infection in this population of neutropenic patients.

Adolescent↗

Ceftazidime versus imipenem-cilastatin as initial monotherapy for febrile neutropenic patients.

One hundred febrile episodes in 89 neutropenic patients after cytotoxic chemotherapy were randomized to be treated with either ceftazidime or imipenem as initial monotherapy. The clinical characteristics of the two groups of patients were comparable. The response of the fever in patients who received imipenem was significantly better than that in those who received ceftazidime (77 versus 56%, respectively; P = 0.04), especially in those with microbiologically documented infection (81 versus 33%, respectively; P = 0.02). The in vitro susceptibilities and the clinical responses suggested that, with the possible exception of Pseudomonas spp., imipenem was more effective than ceftazidime in treating neutropenic infections caused by both gram-positive and -negative organisms. An additional 23 and 21% of the patients in the ceftazidime and imipenem groups, respectively, responded to the addition of cloxacillin and amikacin following failure of monotherapy. The majority of the treatment failures, relapses, and superinfections were related to resistant infective organisms such as methicillin-resistant Staphylococcus spp. and Pseudomonas spp. or disseminated fungal infections.

Adolescent↗

Immunoglobulin gene rearrangement in the peripheral blood and bone marrow of patients with lymphomas of the mucosa-associated lymphoid tissues.

The theory of 'homing' mechanism has been proposed to explain the association of malignant lymphoma involving multiple sites of mucosa-associated lymphoid tissue (MALT). DNA rearrangement in the peripheral blood and bone marrow specimens of 20 patients with MALT lymphoma were studied utilizing JH and C beta gene probes, aiming to detect circulating lymphoma cells and unrecognized bone marrow involvement. Our search for malignant cells in the peripheral blood was unrewarding and the 'homing' theory remained unproven. However, the study of DNA rearrangement showed to be useful in determining the malignant nature of abnormal lymphoid aggregates found in the bone marrow of these patients.

Adult↗

Wilson's disease: 35 years' experience.

Thirty-seven Chinese patients fulfilling the criteria for Wilson's disease seen during a 35-year period were reviewed. Males and females were equally affected. Twenty-two patients were symptomatic and 15 asymptomatic; most of them presented before the third decade. Thirty-one per cent of the relatives screened showed evidence of disease, and parents were rarely affected (13 per cent). Half of the adult symptomatic females presented with primary amenorrhoea. Liver laboratory tests were abnormal in only 50 per cent of patients, with gamma-glutamyltranspeptidase being the most sensitive index. Renal disease was infrequent. Serum caeruloplasmin level was the single biochemical parameter of prognostic significance (p = 0.0001). Seventy per cent of the symptomatic patients showed an improvement after treatment with penicillamine.

Adolescent↗

Treatment of adult acute lymphoblastic leukaemia using an intensive chemotherapy protocol.

A total of 25 evaluable adult patients with acute lymphoblastic leukaemia (ALL) were treated with an intensive chemotherapy regime modified from the L17/L17M protocol of the Sloan-Kettering Hospital. There were 18 men and 7 women; their median age was 36 years (range, 13-78). Seven cases had L1 morphology and 18, L2. The immunophenotype was common-ALL in 10, null-ALL in 9, T-ALL in 4 and B-ALL in 1. Of the 25 patients, 14 (56%) achieved a complete remission (CR). The causes of induction failure were partial remission (PR) only in 7 (28%) and hypoplastic death in 4 (16%). Of the 14 CR patients, 11 (78.6%) relapsed. Five patients developed CNS disease. The median disease-free survival and overall survival were only 9 and 13 months, respectively. As the follow-up periods of the surviving patients were short, late relapses may still occur and the overall treatment result is likely to be worse on longer follow-up. The possible causes of this disappointing result are discussed.

Adult↗

Central nervous system involvement in non-Hodgkin's lymphoma.

Fifty-eight Hong Kong Chinese patients with CNS lymphoma were reviewed (primary seven, secondary 51). The incidence of secondary CNS lymphoma in patients with non-Hodgkin's lymphoma was estimated to be 9.4%. The Working Formulation separated subtypes which had a special propensity to involve the CNS. Significant proportions of our patients with secondary CNS lymphoma had other features which were known to be associated with a high risk of CNS disease including stage IV (48/51, 91.4%), bone marrow (26/51, 50.9%), peripheral blood (7.51, 13.7%), nasal (7/51, 13.7%), orbital (3/51, 5.9%), testicular (2/51, 3.9%) and bulky retroperitoneal (6/51, 11.8%) disease. 82% of patients with secondary CNS lymphoma had concurrent systemic disease and a further 12% had systemic relapse shortly afterward. CNS lymphoma is associated with poor prognosis and only 29% and 14% of the patients with primary and secondary CNS lymphoma respectively survived beyond 1 year. Patients responding to therapy had significantly better survival. 69.9% of the deaths were related to progressive systemic disease.

Adolescent↗

Acute lymphoblastic leukemia in Chinese adults in Hong Kong.

Forty-four previously untreated Chinese adult patients with acute lymphoblastic leukemia (ALL) were treated with vincristine, adriamycin and prednisone with or without L-asparaginase. The clinical features and prognostic factors were similar to those reported in Caucasian series. Overall complete remission (CR) rate was 52%. Duration of first remission and overall median survival were nine and 12 months respectively. The addition of L-asparaginase did not improve CR rate or duration of remission and was associated with clotting dysfunction and other adverse reactions. Factors associated with a higher CR rate include age less than 40 years, blast count less than 10 x 10(9)/l and CALLA + phenotype at presentation. Sex, platelet count and FAB morphology did not affect CR rate. Bone marrow relapse occurred in 11 patients and was associated with short survival after relapse (median two months; mean two months; range 0.5-7 months). Central nervous system relapse occurred in four patients and was compatible with relatively long survival after relapse (median 13 months; mean 12 months; range 6-12 + months). The poor CR rate and short median survival in this study could not be adequately explained by an increase in risk factors and is likely to be due to what is currently regarded as suboptimal chemotherapy.

Adolescent↗

Hypogonadotropic hypogonadism in severe beta-thalassemia: effect of chelation and pulsatile gonadotropin-releasing hormone therapy.

We studied pituitary-gonadal function in 11 male and 5 female patients, aged 12-30 yr, with severe beta-thalassemia and chronic iron overload. All had normal basal serum cortisol, T4, and PRL concentrations and normal serum cortisol and GH responses to insulin-induced hypoglycemia and TSH responses to TRH. Of the 11 male patients (all over 17 yr of age), only 3 attained full pubertal development and 4 had subnormal serum LH and FSH responses to GnRH. As a group, their mean basal serum testosterone (T) level was low [11.7 +/- 4.9 (+/- SE) nmol/L; normal, 10-40 nmol/L], and 9 of the 11 male patients responded to hCG with a rise in serum T. Two of the 3 female patients over 17 yr of age were prepubertal with undetectable serum estradiol (E2) levels and absent serum LH and FSH responses to GnRH; the other female patient had regular menstrual cycles and normal serum E2 levels and LH and FSH responses to GnRH. Six of the prepubertal patients (4 males and 2 females, aged 17-30 yr) were studied serially for 3 yr after the start of chelation therapy. Despite a fall of median serum ferritin from 11,910 to 1,303 pmol/L, there was no progression of puberty, and their basal and GnRH-stimulated serum LH and FSH and serum T or E2 levels did not change. Three of these patients (1 male and 2 female) then received pulsatile sc GnRH therapy in addition to chelation therapy for 6 months with no improvement. We conclude that chronic iron overload in patients with severe thalassemia leads to variable degrees of hypogonadotropic hypogonadism, which do not respond to chelation therapy given late in the course of the disease. The hypogonadism in most patients was due to pituitary hyporesponsiveness to GnRH.

Adolescent↗

Measurement of circulating immune complexes containing IgG, IgM, IgA and IgE by flow cytometry: correlation with disease activity in patients with systemic lupus erythematosus.

The immunoglobulin (Ig) class of the antibody component of circulating immune complexes (IC) may be an important determinant of their pathogenicity. This study reports the development of a fluorometric immunoassay, using Raji cells as solid phase component and detection by flow cytometry, for the measurement of IC containing IgG, IgM, IgA and IgE. Analytic specificity of the method was established and diagnostic sensitivity determined in groups of patients with various disorders. In a detailed study of 44 patients with systemic lupus erythematosus (SLE), elevated levels of IC were observed in the majority of patients, the prevalence of the respective Ig subclasses within the patient group being IgG-IC (93%); IgM-IC (77%); IgA-IC (59%); IgE-IC (52%). Raised levels of IC (of all classes) correlated with disease activity. Longitudinal study of a patient with acute cerebral SLE revealed elevated IC levels of all four Ig classes at presentation which fell during treatment, coincident with normalization of complement values. The biological consequences of IC of various Ig subclasses is discussed with particular reference to a possible mechanism of IgE-IC mediated tissue damage.

Adult↗

Fatal reactivation of chronic hepatitis B virus infection following withdrawal of chemotherapy in lymphoma patients.

Four Chinese patients with non-Hodgkin's lymphoma and asymptomatic chronic hepatitis B infection developed fulminant hepatitis three to four weeks after two to five courses of chemotherapy. One was initially positive for hepatitis B e antigen and three were positive for antibody to HBeAg. They had normal initial serum aminotransferase levels. In all four patients, the hepatic illness appeared to be caused by reactivation of hepatitis B virus replication as evidenced by the appearance of HBV DNA in serum at the onset of hepatitis, seroreversion from anti-HBe to HBeAg positivity, and the absence of other incriminating drugs or viral markers. All died within three weeks after the onset of jaundice. Serum HBV DNA level dropped to undetectable level as the hepatitis progressed. We postulate that potent cytotoxic therapy reactivated HBV replication and permitted widespread infection of hepatocytes. Upon withdrawal of chemotherapy, the immunologic rebound resulted in rapid destruction of infected hepatocytes and massive liver necrosis. Several methods for the prevention of such hepatic reactivation are discussed.

Adult↗