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Biomedical subjects

D L Barnard

Publications and source records attributed to D L Barnard.

68 records · Page 4Linked to original sources

Ifosfamide and mitoxantrone (I-M) in relapsed and refractory high grade non-Hodgkin's lymphoma and Hodgkin's disease.

Fifty-five patients, initially diagnosed as having advanced high grade non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD) refractory to first-line treatment or in relapse, were treated with ifosfamide 6 g/m2, infused over 48 h, followed by mitoxantrone 12 mg/m2. The regimen repeated at three-weekly intervals. Of 32 patients with NHL evaluable for response, 10 (31 per cent) achieved complete remission and five partial remission, giving an overall response rate of 47 per cent. Two patients subsequently went on to bone marrow transplant (BMT)--one allogeneic and the other autologous. Of 17 patients with HD evaluable for response, six (35 per cent) achieved complete remission and six partial remission, giving an overall response rate of 71 per cent. Two of this group also went on to BMT (both autografts). The principal toxicity was neutropenia, though central nervous system changes were observed in 10 patients. Given the need to offer alternative treatment of patients in these categories, this combination (I-M) is clearly of value in relapsed patients especially where therapeutic options are limited because of previous multi-drug treatment.

Adolescent↗

Twin-track studies of ifosfamide and mitoxantrone (I-M) in recurrent high grade non-Hodgkin's lymphoma and Hodgkin's disease. Yorkshire Regional Lymphoma and Central Lymphoma Groups.

Fifty-seven patients, initially diagnosed as having advanced high grade non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD) refractory to first-line treatment or in relapse, were treated with ifosfamide 6 g/m2, infused over 48 h, followed by mitoxantrone 12 mg/m2. The regimen repeated at three-weekly intervals. Of 33 patients with NHL evaluable for response, 10 (30 per cent) achieved complete remission and six partial remission, giving an overall response rate of 48 per cent. Two patients subsequently went on to bone marrow transplant (BMT)--one allogeneic and the other autologous. Of 18 patients with HD evaluable for response, seven (39 per cent) achieved complete remission and six partial remission, giving an overall response rate of 72 per cent. Two of this group also went on to BMT (both autografts). The principal toxicity was neutropenia, though central nervous system changes were observed in 10 patients. The possibility of increasing the safety of the regimen by increasing the time of infusion to 72 h is discussed. Given the need to offer alternative treatment to patients in these categories, this combination (I-M) is of value in relapsed patients, especially where options are limited because of previous multi-drug treatment. Remissions may not be prolonged but allow the effective application of additional intensive treatment including bone marrow transplantation.

Adolescent↗

A pilot study of ChlOPhEPP-B--a weekly regimen for patients with untreated advanced or recurrent Hodgkin's disease.

Twenty-five patients with either previously untreated advanced Hodgkin's disease (HD) or with relapsed disease were treated with an intensive weekly chemotherapy regimen (ChlOPhEPP-B) in which the myelosuppressive combinations of epirubicin and chlorambucil, and procarbazine and etoposide alternated at two-week intervals, interspersed with vincristine and prednisolone and then vincristine, prednisolone and bleomycin in a four-week cycle. Of the previously untreated patients (n = 14), 12 (86 per cent) showed a complete response (CR); in the previously treated patients (n = 11), CR was achieved in five (46 per cent). Toxicity was predictable and not evidently more severe than with more standard regimens. Neutropenia leading to treatment delay and/or dose reduction was seen in 11 patients (44 per cent) but severe neutropenia (WHO grade 4) was documented in only six patients (24 per cent) for a cumulative total of nine treatment weeks (1.8 per cent of the total treatment time). Dose reductions for neutropenia were applied in relation to 11 of the 379 weekly treatment points (2.9 per cent). Delays in treatment, for any reason, averaged 3.65 weeks per patient. The study demonstrated the feasibility of a more intensive weekly multidrug schedule. This approach may be applicable in the treatment of advanced HD and represents a further option in the strategy of treating relapsed disease.

Adult↗

Prognosis in low grade non-Hodgkin's lymphoma: relevance of the number of sites involved, absolute lymphocyte count and serum immunoglobulin level.

Eighty-eight patients with low grade non-Hodgkin's lymphoma were followed for a median period of 63 months. Sixty-eight per cent of the group were centrocytic/centroblastic B cell lymphomas by the updated Kiel classification. Fifty-one (58 per cent) of the patients were stage IV by the Ann Arbor classification. In 18 of these patients the bone marrow was the only site of extranodal involvement. Univariate survival analysis showed that the sum of involved sites was more discriminatory than Ann Arbor stage. Analysis by site of involvement showed that the liver and other intraabdominal sites were associated with worse survival than involvement of peripheral lymph nodes. Bone marrow and spleen involvement were not significantly associated with short survival. Increasing age at presentation was strongly associated with shorter survival and was also inversely correlated with serum albumin. Both low absolute lymphocyte count (< 1.0 x 10(9)/l), low serum IgG level (< 10 g/l) and low total immunoglobulins on presentation were significantly associated with short survival. Multivariate analysis showed that age, serum albumin and number of involved sites gave the best survival prediction. The sum of involved sites, immunoglobulin level and absolute lymphocyte count may be useful objective markers of prognosis in low-grade non-Hodgkin's lymphoma.

Adolescent↗

The anti-aging action of hypophysectomy in hypothalamic obese rats: effects on collagen aging, age-associated proteinuria development and renal histopathology.

Hypophysectomy in young male Wistar rats aged 70 days, like food restriction begun at the same age, retarded the life-long rate of collagen aging in tail tendon fibres and inhibited the development of age-associated proteinuria and renal histopathology. Hypothalamic lesions which increased the food intake of hypophysectomized rats from 7 g to 15 g/day and produced obesity did not alter the rate of either collagen aging or proteinuria development, nor reduce life expectancy, but increased the incidence of abnormal glomeruli. In the intact rats elevation of food intake from 7 g to 15 g/day increased the rate of proteinuria development, but did not affect the rate of collagen aging. Hypophysectomy was found to have a greater anti-collagen aging effect than food restriction, when food intakes were the same in both groups. These studies suggest a pituitary-hormonal effect on collagen aging and a food-pituitary-hormone-mediated effect on the development of age-associated proteinuria.

Adrenal Cortex Hormones↗

Antiherpesvirus activity and mode of action of SP-303, a novel plant flavonoid.

SP-303, a natural plant flavonoid polymer of molecular weight 2,100 daltons, was found to have antiviral activity against two strains of type 1 herpes-type simplex virus, including a thymidine-kinase-deficient strain, and a strain of type 2 herpes simplex virus. The 50% effective concentrations (EC50s) were 1-2 microM. Acyclovir, which was run in parallel, had values of 4-28 microM. Surprisingly, the compound was inactive against human cytomegalovirus. SP-303 was also virucidal at 50 microM. Interferon was not induced. The mode of antiviral action of this biopolymer was through inhibition of virus penetration into cells (EC50 = 2.1 +/- 0.2 microM). SP-303 also significantly reduced lesion formation in a mouse vaginal model when applied topically at 5-10%.

Animals↗

Mode of inhibition of respiratory syncytial virus by a plant flavonoid, SP-303.

A natural-product polyphenolic polymer of molecular weight 2,100 daltons designated SP-303, was found to have antiviral activity against respiratory syncytial virus (RSV) in the 2-10 microM range in plaque reduction assays and cytopathic-effect-inhibition assays. The material was also virucidal. The 50% effective concentration (EC50) for virucidal activity was 28 microM. Experiments were done to determine the mode(s) of RSV inhibition by SP-303. Interferon was not induced. SP-303 did not inhibit attachment at antiviral concentrations. However, the EC50 for inhibition of virus penetration by SP-303 was 0.48 +/- 0.19 microM. These data suggest that abolition of RSV penetration into host cells is one mechanism whereby SP-303 inhibits RSV replication.

Antiviral Agents↗