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Biomedical subjects

H G Prentice

Publications and source records attributed to H G Prentice.

At least 271 records · Page 15Linked to original sources
PubMed1983

Acyclovir prophylaxis against herpes virus infections in severely immunocompromised patients: randomised double blind trial.

Twenty patients undergoing allogeneic bone marrow transplantation and 39 patients receiving remission induction chemotherapy for acute leukaemia were entered into a double blind, placebo controlled stratified trial of acyclovir prophylaxis against herpes group virus infections. Within the transplant group intravenous acyclovir 5 mg/kg twice daily given throughout the period of granulocytopenia completely prevented oropharyngeal herpes simplex virus infection compared with a 50% incidence in the placebo arm (p = 0.033). The acyclovir group also had fewer days of fever during the trial and a shorter duration of leukopenia, possibly because of the prevention of herpes simplex virus infections. There was a high incidence of herpes infections after the trial in patients who received either acyclovir or placebo. In the non-transplant group there was also a significant reduction of herpes simplex virus infection in the oropharynx and oesophagus (two out of 19 patients as compared with 10 out of 20; p = 0.018). Herpes simplex virus was isolated in the acyclovir arm within a day after starting the trial in one patient, and the other failure was due to a virus with reduced sensitivity to acyclovir in a patient who had had several previous courses of the drug. The incidence of herpes infections after stopping treatment was low. The influence of acyclovir on excretion of Epstein-Barr virus in saliva in either group was inconclusive. One patient (transplant group) developed a cytomegalovirus infection while receiving acyclovir. Acyclovir provides effective prophylaxis against oropharyngeal and oesophageal herpes simplex virus infection in severely immunocompromised seropositive (greater than or equal to 1/8) patients. In patients given bone marrow transplants this may have the additional benefit of reducing the time to recovery of an adequate blood count and the number of days of fever.

Acyclovir↗
PubMed1983

Sequential studies on the role of mitoxantrone in the treatment of acute leukaemia.

Mitoxantrone, a synthetic and newly available intercalating agent, was shown to have activity in relapsed or refractory acute leukaemia, which is apparently schedule dependent. A 5-day treatment programme demonstrated impressive activity, with a 50% response rate and 24% complete remissions. Toxicity in these preliminary studies was limited compared to that expected with the anthracycline antibiotics. Mitoxantrone is an active and relatively non-toxic agent which merits further assessment prior to its incorporation in first-line therapy of acute leukaemia.

Acute Disease↗
PubMed1983

Prophylactic studies against herpes infections in severely immunocompromised patients with acyclovir.

A total of 59 patients, including 20 undergoing bone marrow transplantation (BMT) and 39 who were receiving cytotoxic chemotherapy (CT), were included in a placebo-controlled trial of intravenous acyclovir as a prophylactic against herpes simplex virus infections. Fifty per cent of the patients (both BMT and CT) receiving placebo developed herpes simplex virus infections; in those receiving acyclovir, none of the BMT group and 10 per cent of the CT group became infected with herpes simplex. Prevention of herpes infections in the immunosuppressed is clearly both desirable and, in the case of herpes simplex virus, attainable.

Acyclovir↗
PubMed1983

Use of acyclovir for prophylaxis of herpes infections in severely immunocompromised patients.

Two consecutive studies are reported. In study 1, 59 patients with acute leukaemia undergoing remission induction therapy or bone marrow transplantation were given either acyclovir (5 mg/kg) or placebo by intravenous infusion twice daily during the period of neutropenia. All patients were seropositive (greater than or equal to 1:8) for herpes simplex virus. Acyclovir provided total protection against herpes simplex virus infection in bone marrow transplant patients with 0/10 versus 5/10 infections in the placebo group (P = 0.033). For the remission induction therapy group 2/19 on acyclovir developed HSV versus 10/20 receiving placebo (P = 0.018). Only one episode of cytomegalovirus (CMV) infection was seen and this was in a patient on acyclovir. Epstein-Barr virus secretion studies were inconclusive. No varicella zoster virus (VZV) infections were seen. In Study 2, 20 consecutive HSV seropositive (greater than or equal to 1:8) bone marrow transplant recipients received oral acyclovir. Five (25%) developed HSV infections, one of which was in a non-compliant patient, who subsequently developed a fatal infection whilst receiving therapeutic (5 mg/kg 8 hourly) intravenous acyclovir for this HSV infection. Intravenous acyclovir is effective in preventing HSV infections in the immunocompromised host but it seems unlikely that CMV will be amenable to acyclovir in its present formulation.

Acyclovir↗
PubMed1983

Allogeneic bone marrow transplantation: the monitoring of granulocyte macrophage colonies following the collection of bone marrow mononuclear cells and after the subsequent in-vitro cytolysis of OKT3 positive lymphocytes.

Marrow nucleated cells from eight normal allogeneic donors was layered on Ficoll-Metrizoate to isolate the mononuclear cell fraction. The cells were then washed to remove Ficoll-Metrizoate and coagulation factors prior to resuspension in a balanced salt solution and the addition of the murine anti-human T-lymphocyte monoclonal antibody OKT3 and rabbit complement. The procedures were assessed for their effect on mononuclear cell viability (mean recovery 84.4%); the ability of the cells to proliferate granulocyte-macrophage colonies (mean recovery 57.4%); the in-vitro T-lymphocytolysis (mean 75.7%) and the removal of rabbit complement (greater than 99%). Following marrow transplantation with this treated mononuclear fraction the mean day to recovery of greater than or equal to 1.0 X 10(9)/l leucocytes was 20 d, with three patients developing greater than or equal to Grade II acute graft versus host disease (GvHD). Thus, treatment of donor marrow with OKT3 and complement in a large volume system was not detrimental to subsequent engraftment, nor effective in complete T-lymphocytolysis, nor in prevention of severe GvHD.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1983

A technique for the concentration of nucleated bone marrow cells for in vitro manipulation or cryopreservation using the IBM 2991 blood cell processor.

27 bone marrow aspirates were processed on the IBM 2991 Blood Cell Processor to achieve a reduction in volume (greater than 80%) and in red blood cell contamination (greater than 75%), without loss (less than 20%) of nucleated cells. The procedure was used to concentrate nucleated bone marrow cells either prior to cryopreservation for subsequent autologous transplantation, or prior to incubation with a murine monoclonal antibody (OKT3) for allogeneic transplantation. We conclude that the procedures used for the concentration, cryopreservation, thawing and infusion do not adversely affect the viability of cells as assessed by in vitro culture (CFU-GM). Of the marrows processed, 12 have been reinfused and resulted in successful engraftment.

Adolescent↗
PubMed1983

A review of the current status and techniques of allogeneic bone marrow transplantation for treatment of leukaemia.

Bone marrow transplantation is now an accepted component in the overall therapy of acute and chronic (myeloid) leukaemia for some selected patients. Some of the obstacles to success have been partially overcome. Many advances in supportive care have been made. Pneumocystis carinii and herpes simplex infections are preventable. Effective decontamination of the gastrointestinal tract for bacteria and fungi is now readily achievable and may have reduced the risk of serious systemic infections. New antibiotics which, in combination, are effective in life-threatening infections are under study. Recent developments in the prevention or amelioration of graft versus host disease (GvHD) have included T lymphocyte depletion in the donor marrow and the use of the fungal polypeptide cyclosporin A. Less than 10% of patients would now be expected to succumb to this complication. Outstanding problems remaining to be resolved are the improvement in the antileukaemic conditioning prior to transplantation and the prevention or treatment of cytomegalovirus infection in the seropositive recipient. This infection can cause pneumonitis and is currently the single most frequent transplant related cause of mortality.

Adolescent↗
PubMed1983

T cell regeneration after allogeneic bone marrow transplantation.

Various T cell subsets were characterized by double immunofluorescent staining using monoclonal antibodies (MoAb) in blood, bone marrow (BM) and tissues of 29 patients after allogeneic BM transplantation (BMT). In an attempt to prevent graft versus host disease (GvHD), 15 patients received cyclosporin A (Cy A). In the remaining 14 patients the BM was pre-incubated with a MoAb, OKT3. The regeneration of T4+ subset was delayed and the level of T8+ cells was abnormally high even 1 year after engraftment. This did not have any predictive value for the appearance of complications such as GvHD or severe viral infections. The number of T8+ cells was lower in the group of patients who received Cy A than in the OKT3 group (0.7 +/- 0.2 vs 1.5 +/- 0.3 X 10(9)/1 at day 90). In contrast to normal individuals, the T4/T8 ratio in both blood and regenerating BM of BMT patients was less than 1. A sizeable subset of circulating T cells expressed the phenotype T8+, T10+, HNK-1+, DR+. Circulating cells of this phenotype were transiently very high (up to 50%) in patients with active GvHD or suffering from severe viral infection. This subpopulation of lymphocytes was not found in the epidermal infiltrate that accompanied GvHD where the predominant phenotype was T8+, T1-, T10-, HNK-1-, DR-. We conclude therefore that after BMT the number and phenotype of circulating T cells reflects the T cell distribution seen in the regenerating BM.

Adolescent↗
PubMed1983

Studies in the prophylaxis of herpes infections in severely immunocompromised patients using acyclovir.

That acyclovir is effective therapeutically in herpes simplex virus (HSV) and herpes zoster (VZV) infections in immunocompromised patients has been established [13]. This paper reviews our subsequent studies in prophylaxis of herpes group infections in a high risk group of patients suffering from acute leukaemia. In study 1 we randomised HSV seropositive (greater than or equal to 1:8) patients to receive intravenous acyclovir or placebo. In this stratified study bone marrow transplant (BMT) recipients were completely protected from HSV infections by acyclovir compared with a 50% failure rate for those on placebo. There was significant protection also in the non-BMT group [8]. In study 2 oral acyclovir prophylaxis failed to provide complete protection in BMT recipients despite the achievement of apparently adequate blood levels. In study 1 the secretion of EBV in saliva before and during the trial gave inconclusive results. In each of the first two studies one patient on "active" acyclovir developed a cytomegalovirus (CMV) infection. Thus, at the dosage of drug used, prophylaxis of CMV was unsuccessful suggesting that claims of therapeutic efficacy are unlikely to be supported in controlled trials. Study 3 is current and concerns the pharmacokinetics of an acyclovir prodrug (BW 134U) taken by mouth. This drug is near 100% absorbed and achieves approximately twice the level of active acyclovir in vivo, following conversion by adenosine deaminase (ADA), in normal volunteers.

Acyclovir↗
PubMed1983

Prolonged access to the venous system using the Hickman right atrial catheter.

Seventy-one Hickman catheters were inserted into 63 patients for prolonged access to the venous system. The mean catheter life was 98 days, but despite the long life in situ provided by these catheters only 5 (7%) had to be removed for septic complications. The technique of insertion is described and the subsequent management of these catheters discussed. The management of patients receiving parental nutrition, those undergoing bone marrow transplantation for acute leukaemia, and those having cytotoxic chemotherapy was greatly facilitated by the use of the catheter.

Cardiac Catheterization↗
PubMed1982

ABO-incompatible bone-marrow transplantation: removal of red blood cells from donor marrow avoiding recipient antibody depletion.

Eight patients with acute leukaemia undergoing allogeneic bone-marrow transplantation from ABO-incompatible donors received red-cell-depleted donor marrow without any procedure to diminish their anti-ABO antibody titres. Successful marrow red-cell removal (mean 98.8%) was achieved by means of a large-volume separation technique on Ficoll-Metrizoate in the IBM 2991 blood-cell processor. Clinically significant ABO-haemolytic reaction was prevented in all patients, and there was neither failure of engraftment nor rejection. This approach used alone is satisfactory for most ABO-incompatible marrow-transplant recipients, although combining this with some method of recipient antibody depletion, such as plasma exchange, is recommended in the occasional patient with high anti-ABO titres.

ABO Blood-Group System↗
PubMed1982

Ketoconazole versus nystatin plus amphotericin B for fungal prophylaxis in severely immunocompromised patients.

72 patients severely immunocompromised by their underlying disease (marrow aplasia, acute leukaemia, or solid tumour) or by the treatment they were receiving, or both, were randomised to receive antifungal prophylaxis with either oral ketoconazole or conventional doses of oral amphotericin B and nystatin. All patients also had gut decontamination with non-absorbable antibiotics, skin antisepsis, sterile food, and oral cotrimoxazole. Protection against fungal infection was significantly superior with ketaconazole. When patients who had received allogeneic bone-marrow transplant were studied separately, there was no significant difference between the two treatments, probably because there was a fall-off in ketoconazole absorption from the end of the third week after the transplant. However, ketoconazole greatly reduced the likelihood of fungal infection in non-transplant patients.

Amphotericin B↗
PubMed1982

Use of anti-T-cell monoclonal antibody OKT3 to prevent acute graft-versus-host disease in allogeneic bone-marrow transplantation for acute leukaemia.

Seventeen patients who received allogeneic bone-marrow transplants from matched or slightly mismatched (in four patients) siblings were observed for at least 60 days or until acute graft-versus-host disease (GvHD) developed. All donor marrows after preliminary manipulation were incubated with 1 mg of the murine monoclonal antibody OKT3 before infusion in an attempt to deplete them of immunocompetent T lymphocytes (opsonisation). In three of the seventeen patients acute GvHD of grade II or greater developed. Two of these patients died, but they had disseminated cytomegalovirus infection as well as GvHD. Eleven patients showed no evidence of acute GvHD, and four had transient limited skin rashes (grade I GvHD). Opsonisation of T lymphocytes has reduced the incidence of severe acute GvHD in this unit from 79% in an earlier group of 14 patients to 18% when added to prophylactic methotrexate.

Acute Disease↗
PubMed1982

Hypoparathyroidism and hypocalcaemia during treatment for acute leukaemia.

Nine patients with acute leukaemia developed a complex syndrome of hypocalcaemia and hypomagnesaemia during treatment. These metabolic abnormalities developed rapidly in some patients and gave rise to acute symptoms. Immunoreactive parathormone concentrations in these patients were found to be either absolutely or inappropriately low. Hypomagnesaemia and the action of chemotherapeutic agents, especially adriamycin or cytarabine, or both may have contributed to the pathogenesis of this syndrome.

Adolescent↗
PubMed1982

5'nucleotidase, adenosine deaminase and purine nucleoside phosphorylase activities in acute leukaemia.

Three enzymes concerned in purine degradation, 5'nucleotidase (5'NT), adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) have been measured biochemically in the bone marrow or peripheral blood blasts from 75 patients with acute leukaemia, from 18 patients with blast crisis of chronic granulocytic leukaemia and in the bone marrow and peripheral blood lymphocytes from 14 normal donors. Characteristic patterns among the different sub-types of acute leukaemia have been detected, with high ADA, low 5'NT and PNP in Thy-ALL, high 5'NT and ADA in c-ALL, high PNP and low ADA in AML. The cells in CGL blast transformation resembled the enzymatic pattern of either AML or c-ALL respectively. However, no significant correlation was found between any pair of enzymes in any group of leukaemia, normal bone marrow or peripheral blood lymphocytes studied here.

Acute Disease↗