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Biomedical subjects

A G Prentice

Publications and source records attributed to A G Prentice.

At least 55 records · Page 3Linked to original sources
PubMed1994

Multiple dose pharmacokinetics of an oral solution of itraconazole in autologous bone marrow transplant recipients.

The pharmacokinetics of itraconazole oral solution were measured in seven patients receiving chemotherapy followed by autologous bone marrow transplantation for leukaemia or lymphoma. Patients received 5 mg/kg/day itraconazole either as a once or twice daily dose. Drug concentrations reached steady state by day 15, in both groups. The mean pre-dose itraconazole serum concentration at hour 0, day 8 was 385 ng/mL in the od group and 394 ng/mL in the bd group, rising to 762 and 845 ng/mL by day 15, respectively. The mean AUCs for 0-24 h on day 8, 15 and 22 were 17,310 and 13,302 ng/mL/h, 24,476 and 25,154 and 22,621 and 21,423, for the od and bd groups, respectively. Thus serum concentrations of itraconazole suitable for antifungal prophylaxis can be attained in neutropenic patients, with the administration of an oral solution in a dosage of 5 mg/kg as either an od or bd schedule, following pre-autograft high-dose cytotoxic chemotherapy.

Adult↗
PubMed1994

Avascular necrosis of bone following intensified steroid therapy for acute lymphoblastic leukaemia and high-grade malignant lymphoma.

Five out of nine adults (55%) with lymphoblastic disease developed severe avascular necrosis of bone (AVN) when treated with a Berlin-Frankfurt-Munster (BFM) ALL protocol similar to the current joint MRC-ECOG ALL trial (UKALL XII). The principal purpose of these intensified regimens is to improve long-term disease-free survival without necessarily increasing toxicity and secondary morbidity. The presentation of all five was non-specific bone pain occurring after the re-intensification block of chemotherapy containing high doses of dexamethasone. Three types of diagnostic imaging were performed and magnetic resonance imaging (MRI) proved superior in demonstrating AVN and showed it at an earlier stage than plain radiographs or isotopic scans. We believe that the dose of corticosteroids was the major factor in the development of AVN. The five men in our series all remain in first remission with a median disease-free survival of 3.5 years (range 2-8 years) but with varying degrees of disability due to AVN. Clinicians involved in UKALL XII and similar trials should be aware of this debilitating and potentially crippling complication when using high-dose steroid-containing regimens, perform MRI scan early and modify treatment if necessary.

Adolescent↗
PubMed1994

HLA-DR typing for kidney transplants: advantage of polymerase chain reaction with sequence specific primers in a routine hospital laboratory.

AIMS: To determine whether the polymerase chain reaction with sequence specific primers (PCR-SSP) can assign HLA-DR type more accurately than serology in a routine hospital laboratory. METHODS: The 93 patients currently awaiting kidney transplants have been DR typed by serology over the past 14 years, 82% within the past five years. They have now been retyped using the PCR-SSP method described by Bein et al. Where the two results differed, PCR-SSP was repeated, once by the same method and once using the primer set of Olerup and Zetterquist. RESULTS: There were 13 (14%) discrepancies between the results. Of these, two were PCR-SSP failures, later overcome: three were failure to detect DRB1*0103 by serology; five assignment of other alleles by PCR-SSP to serological "blanks"; and three alleles were differently assigned by serology and PCR. The serological typing of the final patient when repeated for this study was at variance with the original findings (14 years ago), but in agreement with PCR. In the remaining patients, serology had not determined the split of 36 DR3 alleles (all DR17 by PCR-SSP) or 13 DR6 alleles (12 DR13 and one DR14 by PCR-SSP). One patient in each case had their antigen splits of DR2 and DR5 assigned by PCR-SSP (DR15 and DR11, respectively) but not by serology. CONCLUSIONS: PCR-SSP provides more reliable and detailed information on HLA-DR polymorphism than serology, and does so within a routine tissue typing laboratory.

HLA-DR Antigens↗
PubMed1994

Mitoxantrone, chlorambucil and prednisolone in the treatment of non-Hodgkin's lymphoma.

The management of low grade lymphoma, both de novo and relapsed disease, is a contentious area in which there has been little real progress in recent years. Regimens which increase the intensity of treatment may accelerate the response but are inevitably associated with greater toxicity. This cannot be justified in a disease whose median survival is between 4 and 10 years and where the median age at presentation is 57. We have assessed the response of 144 patients treated with a combination of mitoxantrone, chlorambucil and prednisolone in a heterogeneous group with lymphoma, both de novo and relapsed disease. In the subgroup with low grade relapsed/refractory disease our results suggest that this combination is clinically effective, low in toxicity and suitable for the outpatient management of this usually elderly patient population.

Adult↗
PubMed1993

Inaccurate haemoglobin estimation in Waldenström's macroglobulinaemia: unusual reaction with monomeric IgM paraprotein.

Automated blood counts from a patient with Waldenström's macroglobulinaemia repeatedly failed critical limit standards set for mean cell haemoglobin concentration and mean cell haemoglobin. Haemoglobin estimation was higher than that suggested by clinical examination, symptoms, and the spun haematocrit. This was found to be due to an interaction between the Coulter lysing agent and monomeric IgM paraprotein in the patient's plasma, creating a precipitate which was optically dense at 525 nm.

Diagnostic Errors↗
PubMed1992

Acquired factor XI inhibitor in chronic lymphocytic leukaemia.

A 71 year old man with chronic lymphocytic leukaemia (CLL) experienced excessive bleeding following transurethral resection of the prostate. Investigations showed a prolonged kaolin cephalin clotting time (KCCT) with low concentrations of factor XI. The prolonged KCCT was largely corrected by mixing with normal plasma but this correction was lost on incubation, confirming the presence of an inhibitor. He was treated with pulsed methylprednisolone and chlorambucil which resulted in the resolution of the bleeding problem and the loss of detectable circulating inhibitor.

Aged↗
PubMed1991

Haematological toxicity compromises MOPP/ABVD chemotherapy in Hodgkin's disease.

A total of 23 patients with previously untreated Hodgkin's disease received MOPP/ABVD hybrid chemotherapy and response to treatment and toxicity were assessed. Of these 14 (61% (95% confidence limits 38.5%-80%] achieved complete remission with chemotherapy alone, six (26% (10.2%-48.4%)) achieved partial remission and there were three treatment failures (13%). Toxicity was mainly haematological resulting in treatment delays and dose reductions. Those in partial remission after chemotherapy achieved complete remission with additional radiotherapy. So far five of the 20 who remitted (25%) have relapsed. We conclude that the haematological toxicity from this regimen compromises dose intensity. The results from using this hybrid regimen are not superior to those using MOPP or ABVD alone in our experience.

Adolescent↗
PubMed1991

Comparison of the multiple dose pharmacokinetics of two formulations of itraconazole during remission induction for acute myeloblastic leukaemia.

This double-blind cross-over study compares the serum pharmacokinetics of a polyethylene glycol formulation of itraconazole (ITRA-PEG; 4 x 50 mg once daily) with a new pelleted formulation (ITRA-PEL; 2 x 100 mg once daily) during remission induction for acute myeloblastic leukaemia. Each formulation was administered for 28 days with a seven day washout period. Five of eight patients (median age 52 years, range 18-65) entering completed both arms of the study. At day 7 for ITRA-PEL (n = 8) the mean +/- one standard deviation and median maximum concentrations (Cmax) were 307 +/- 155 ng/mL and 275 ng/mL respectively and for ITRA-PEG (n = 6) 272 +/- 212 ng/mL and 193 ng/mL. At day 14 for ITRA-PEL (n = 8) the mean +/- S.D. and median Cmax were 412 +/- 227 ng/mL and 375 ng/mL respectively and for ITRA-PEG (n = 5), 315 +/- 177 ng/mL and 327 ng/mL. The Cmax mean and median values were therefore greater with ITRA-PEL but the differences between the two formulations were not statistically significant. Adequate therapeutic levels of itraconazole can be achieved in this clinical setting. However, the wide variation within and between patients suggests that an ITRA-PEL dosage of 400 mg/day may ensure earlier and more consistent therapeutic levels. Measurement of serum levels may be indicated in suspected failure of prophylaxis or treatment.

Adolescent↗
PubMed1991

Alopecia totalis and vitiligo in common variable immunodeficiency.

Three cases of severe and irreversible alopecia occurring in patients with common variable immunodeficiency are described. In all three cases, hair loss developed after the diagnosis of immune deficiency; one of the patients also had extensive vitiligo. A fourth patient had vitiligo in the absence of alopecia. No change in the alopecia or vitiligo was noted in any patient as a result of immunoglobulin replacement therapy.

Adult↗
PubMed1991

Duplex sonography in splenomegaly.

The aetiology of splenomegaly is seldom clear from either clinical or imaging assessment of the spleen. In the majority of cases sonographic assessment of the spleen produces a homogeneous enlargement of variable echodensity, but with very poor correlation with pathology. A study has been undertaken to assess the Doppler characteristics of the splenic artery in splenomegaly, excluding cases of portal hypertension in an attempt to provide further diagnostic information. Duplex assessment of 18 normal subjects and 10 patients with splenomegaly due to five different causes was undertaken. Analysis of waveform, peak frequency and pulsatility index were compared and failed to demonstrate any significant change. In the normal subject there is a broad systolic spectrum related to the tortuosity of the splenic artery, with persistence of forward flow throughout diastole, a reflection of the low peripheral resistance of the spleen. In splenomegaly the broad systolic spectrum is unchanged, since vessel tortuosity persists. Pathological and physiological assessment of the spleen in splenomegaly shows that a low resistance circulation persists, explaining maintenance of the diastolic flow pattern in splenomegaly. Increased blood flow to the spleen in splenomegaly occurs either as a result of an increase in vessel diameter or an increase in flow velocity, or a variable combination of the two which does not seem to be governed by specific pathology. An increase in peak frequency in some cases reflected some increase in flow velocity but provided no useful correlation. Analysis of the pulsatility index supported the above findings without adding further information.

Adolescent↗
PubMed1989

Prophylaxis of fungal infections with itraconazole during remission-induction therapy.

Deep fungal infections are an increasing problem in the treatment of acute leukemias and malignant lymphomas. Risk factors are known but unavoidable. Because of diagnostic difficulties most patients are treated empirically with intravenous amphotericin B. This drug's toxicity increases morbidity and mortality. An orally absorbable triazole derivative, itraconazole, may offer effective and safe prophylaxis against deep candidosis and aspergillosis in these patients. Such infections have been treated successfully with oral itraconazole even when resistant to intravenous amphotericin B. In retrospective comparative studies there are significantly less deep fungal infections in patients given itraconazole. The significance of the difference varies between studies. Pharmacokinetic data confirm therapeutic plasma levels of itraconazole but with wide variation within and between patients. The current large, multi-centre, randomised, double-blind, prospective trial of oral itraconazole versus placebo in the U.K. will test its prophylactic efficacy against deep fungal infections during treatment of haematological malignancies.

Adolescent↗
PubMed1989

Oral and gastrointestinal candidosis: prophylaxis during immunosuppressive therapy.

Patients with acute leukaemia and malignant lymphomas often are severely affected by fungal infections. There is in particular growing concern about disseminated candidosis. Oral, gastrointestinal and systemic candidosis seem to be closely linked. Predisposing factors are damaged mucosal barriers due to chemotherapy, protracted periods of neutropenia, and prolonged use of antibiotics and steroids. Oropharyngeal candidosis is very frequent. This can be prevented or controlled by the application of topical antifungals such as nystatin. The systemic application of antifungals is an alternative for patients who do not respond. Both oral ketoconazole and intravenous amphotericin B have been proven effective. Candida oesophagitis is also an important problem. Oral nystatin suspension can be helpful in mild cases. In others oral ketoconazole and intravenous amphotericin B have to be used. A whole range of measures has to be taken to prevent spread of the disease, i.e. H2-antagonists should be used only if definitely needed. Specific antifungal prophylaxis has also been discussed. Oral amphotericin B seems to be helpful. The azole itraconazole might be especially promising.

Antifungal Agents↗
PubMed1989

Lack of significant effect of therapeutic propranolol on measurable platelet function in healthy subjects.

Propranolol, a non-selective beta blocker, was administered orally in therapeutic doses. The effects of a single dose (160 mg) and one week's treatment (80 mg twice a day) on platelet function were compared in healthy young subjects. There were no significant changes in circulating platelet aggregates, template bleeding time, platelet factor 3 availability and thromboxane beta 2 (TX beta 2) generation. Platelet aggregation responses as assessed by angle of slope and maximal percentage aggregation (all agonists) and lag phase (collagen) showed no changes of biological importance, although minor changes reaching significance were observed with some agonists. These findings suggest that propranolol does not significantly affect platelet function when taken at doses commonly encountered in clinical practice.

Adolescent↗