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Biomedical subjects

B A McVerry

Publications and source records attributed to B A McVerry.

At least 19 recordsLinked to original sources

The development of targeted chemotherapy for CNS lymphoma-a pilot study of the IDARAM regimen.

PURPOSE: We have developed and evaluated a CNS-targeted chemotherapy regimen based on the pharmacokinetic properties of the individual drugs in the combination. PATIENTS AND METHODS: In a twin-track study, 16 patients with secondary CNS lymphoma (SCNSL) and 8 with primary CNS lymphoma (PCNSL) were treated with IDARAM which comprised idarubicin 10 mg/m(2) i.v., days 1 and 2; dexamethasone 100 mg, 12-h infusion, days 1, 2 and 3; cytosine arabinoside (ARA-C) 1.0 g/m(2), 1-h infusion, days 1 and 2; methotrexate 2.0 g/m(2), 6-h infusion, day 3 (with folinic acid rescue); and cytosine arabinoside 70 mg plus methotrexate 12 mg, intrathecally, days 1 and 8. Two cycles were delivered at 3-weekly intervals. After response assessment, patients received adjuvant cranial radiotherapy (40 Gy over 20 fractions). RESULTS: The series comprised 24 patients, 11 male and 13 female. Their median age was 53 years (range 21 to 73 years). Grade 4 neutropenia and thrombocytopenia occurred in the majority of patients treated. Of the eight PCNSL patients, seven achieved complete remission (CR). Four remained in CR at the time of this report with a median duration of follow-up of 25 months (range 11 to 42 months). Of the 16 SCNSL patients, 12 achieved CR. Seven patients remained in CR at the time of this report with a median duration of follow-up of 24 months (range 18 to 57 months). CONCLUSION: This study suggests that IDARAM is an effective regimen in both PCNSL and SCNSL and is suitable for further development and evaluation.

Adult↗

Term delivery in a woman with severe congenital neutropenia, treated with growth colony stimulating factor.

The patient was diagnosed in childhood as having severe congenital neutropenia and had recurrent admissions with severe infections. In 1987, prior to getting married, she was sterilized. She continued to require i.v. antibiotics when she contracted a severe infection. On one occasion, she was treated with growth colony stimulating factor (G-CSF). Her increased neutrophil count was sustained following this treatment. In June 1993, she wished to start a family and underwent in-vitro fertilization (IVF) treatment. G-CSF was given prior to oocyte retrieval. She conceived on her first cycle and an ultrasound scan revealed a singleton pregnancy. Throughout the course of the pregnancy, her white cell count was monitored closely and remained at <1.0x10(9)/l. The pregnancy progressed uneventfully and at 37 weeks gestation she was admitted for G-CSF injections. At 38 weeks she was delivered of a boy weighing 3350 g, by elective Caesarean section. His white cell count was normal. This is the first case of G-CSF being used before conception and during pregnancy in a patient with congenital neutropenia. It shows that advances in cytokine therapy and close interdisciplinary liaison can lead to a successful outcome and help patients, who would otherwise remain childless, to achieve a family.

Adult↗

An assessment of the comparative utility of functional and molecular level analyses in the investigation of patients with thrombophilia.

Aim-To determine the relation of the low anticoagulant response phenotype with the Factor V Q506 (Leiden) mutation in a cohort of patients with thrombophilia.Methods-Fifty four patients with either a personal or family history of deep vein thrombosis were investigated both for their anticoagulant response by the activated protein C resistance test (APCR) and their genetic status in respect of the Leiden mutation by means of a PCR-RFLP method.Results-Low APCR ratios do not necessarily predict possession of the Leiden mutation. Conversely, normal ratios do not exclude the mutation. Of 14 individuals with low APCR ratios, the Leiden mutation was absent in five. Of the remainder, three were heterozygous and six homozygous. Of nine heterozygote individuals, only three had low APCR ratios. All patients homozygous for the defect had low APCR ratios.Conclusions-These results lend further weight to the hypothesis that the APC resistant phenotype results from more than one genetic defect and indicate the value of combined functional and molecular investigations in all patients with thrombophilia.

Journal Article↗

Prognostic indicators for the development of AIDS in HIV antibody positive haemophiliac patients: results of a three-year longitudinal study.

In February 1986, 40 out of 75 adult patients with haemophilia A attending St. James's University Hospital were human immunodeficiency virus (HIV) antibody positive. Over a three-year period these patients were prospectively studied with regard to possible prognostic indicators for the development of the acquired immune deficiency syndrome (AIDS). Using the Centres for Disease Control (CDC) classification of HIV infection, 17 patients (42.5%) developed group 4 disease during this time, giving an actuarial three-year progression rate of 44%, and 5 patients (12.5%) died. The following parameters measured at recruitment were found independently to predict progression to AIDS: a serum beta 2-m level of greater than 3.5 mg/l, (chi 2 = 15.95, P less than 0.001), a serum IgA level of greater than 4.5 milligram(s) (chi 2 = 6.08, P less than 0.02) and p24 antigenaemia (chi 2 = 5.7, P less than 0.05). The actuarial three-year progression rate in those patients abnormal by two or more of these parameters was 100% (n = 7), compared to only 7% in patients who were normal by all three values (n = 15). CD4+ lymphocyte counts and CD4+:CD8+ ratios were significantly lower in HIV positive compared with HIV negative patients (P less than 0.01), but did not predict the development of AIDS.

Acquired Immunodeficiency Syndrome↗

A longitudinal study of serum beta 2-microglobulin levels in haemophilia.

Serum beta 2-microglobulin (beta 2-m) levels were measured in 75 adults with haemophilia A. Beta 2-microglobulin was found to be significantly elevated in haemophiliacs compared with the non-haemophiliac population. There was a greater rise in beta 2-m in HIV antibody-positive haemophiliacs. No further significant increase occurred in the subgroup with HIV-related disease but all these patients had beta 2-m levels greater than or equal to 3 mg/l. Over the study period of 18 months no significant increase in beta 2-m was documented in either HIV antibody-negative or -positive groups. Beta 2-microglobulin was elevated in HIV antibody-negative subjects with raised transaminase levels. No correlation was found between beta 2-m and the amount of factor VIII concentrate infused, T-cell subsets, thrombocytopenia or age. It is concluded that probable reasons for elevated beta 2-m levels in haemophiliacs include infection with HIV and other viruses, chronic liver disease, and repeated antigenic challenge from multiple infusions of factor VIII. The role of serial measurement of beta 2-m in haemophiliacs with a view to predicting the onset of HIV-related disease warrants further study.

Adolescent↗

Elevated fibrinopeptide A levels in patients with clinically localised breast carcinoma.

58 patients with clinically localised breast carcinoma, treated by either mastectomy alone or lumpectomy plus local radiotherapy, have now been followed for up to 51 months (median 12 months). 21 of the 58 patients (36.2%) had a persistently elevated or rising fibrinopeptide A level after surgery and 11 of these patients (52%) to date have subsequently developed recurrent breast carcinoma up to 27 months after the fibrinopeptide A level became elevated (median 6 months). Conversely, only 2 (5.4%) of the 37 patients with persistently normal post-operative fibrinopeptide A levels have developed recurrent disease. Elevated fibrinopeptide A levels appear to be a marker of persistent tumour activity and precede clinical recurrence in certain patients with breast carcinoma, but normal values do not exclude recurrent or residual disease.

Adult↗

HTLV-III antibody and T-cell subset ratios in haemophiliacs and their spouses.

44% of 63 British patients with either haemophilia A or B were HTLV-III antibody positive (HTLV-VIII+). HTLV-III+ was more frequent in high factor VIII concentrate users and 75% of severely affected haemophilia A patients were HTLV-III+. All eight patients who were exposed to factor IX concentrate were HTLV-III-. 17 haemophilia A patients who received only British made factor VIII concentrate (average 12,000 units/year) were HTLV-III-. Two of 63 patients had evidence of a pre-AIDS type symptom complex and both were HTLV-III+. Information from a cohort of 21 Liverpool haemophiliacs suggests that HTLV-III was first introduced into this country in 1981. OKT4/T8 ratios were abnormal in 52% of 21 patients studied but this finding was not confined to either HTLV-III+ or HTLV-III- individuals. The spouses of 14 HTLV-III+ haemophiliacs were all HTLV-III-.

Adolescent↗

Elastase-alpha 1 antitrypsin complexes in acute leukaemia.

30 consecutive patients with acute leukaemia were studied prior to commencement of treatment in order to assess the incidence and significance of raised elastase (ELP) - alpha 1 antitrypsin complex level. In addition the reliability of detecting low factor XIII subunit levels as an indicator of in vivo release of ELP was evaluated. While 15 patients had raised levels of ELP alpha 1 antitrypsin complex levels, only 4 of these had reduced levels or factor XIII subunits A and S. In addition increased levels of ELP- alpha 1 antitrypsin complex were not associated with any marked disturbance of routine coagulation tests. Patients with raised ELP- alpha 1 antitrypsin complex levels had significantly higher circulating white cell and blast cell counts as compared to those patients with normal levels of this complex. In patients entering remission the levels of ELP- alpha 1 antitrypsin complex returned to normal.

Acute Disease↗