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W Mills

Publications and source records attributed to W Mills.

At least 19 recordsLinked to original sources
PubMed1995

Generation of a human X-derived minichromosome using telomere-associated chromosome fragmentation.

A linear mammalian artificial chromosome vector will require at least three functional elements: a centromere, two telomeres and replication origins. One route to generate such a vector is by the fragmentation of an existing chromosome. We have previously described the use of cloned telomeric DNA to generate and stably rescue truncated derivatives of a human X chromosome in a somatic cell hybrid. Further rounds of telomere-associated chromosome fragmentation have now been used to engineer a human X-derived minichromosome. This minichromosome is estimated to be < 10 Mb in size. In situ hybridization and molecular analysis reveal that the minichromosome has a linear structure, with two introduced telomere constructs flanking a 2.5 Mb alpha-satellite array. The highly truncated chromosome also retains some chromosome-specific DNA, originating from Xp11.21. There is no significant change in the mitotic stability of the minichromosome as compared with the X chromosome from which it was derived.

Animals↗
PubMed1995

Hepatic artery chemoembolization therapy for hepatic tumors.

Patients with hepatocellular carcinomas who undergo chemoembolization therapies require skilled perioperative nursing care that addresses their knowledge deficits about chemoembolization techniques, their anxieties related to chemoembolization procedures and adverse effects, and their impaired mobility resulting from the presence of arterial lines and the progression of the cancer. Perioperative nursing participation in chemoembolization procedures is an example of the expanded role of today's OR nurse.

Carcinoma, Hepatocellular↗
PubMed1995

BEAM chemotherapy and autologous bone marrow transplantation for patients with relapsed or refractory non-Hodgkin's lymphoma.

PURPOSE: To evaluate the outcome of patients with relapsed or resistant non-Hodgkin's lymphoma (NHL) undergoing high-dose chemotherapy and autologous bone marrow transplantation (ABMT) and to determine the main prognostic factors. PATIENTS AND METHODS: One hundred seven patients with relapsed or resistant intermediate-/high-grade NHL underwent high-dose carmustine, etoposide, cytarabine, and melphalan (BEAM) chemotherapy and ABMT at University College Hospitals between September 1981 and February 1993. The minimum follow-up duration of all patients is 6 months. RESULTS: At 3 months, the overall response rate to BEAM and ABMT was 73% (41% complete response and 32% partial response). The 5-year actuarial overall survival and progression-free survival rates were 41% and 35%, respectively. The early procedure-related mortality rate was 7% (eight of 107 patients). On multivariate analysis, the main prognostic factor was disease status at the time of ABMT. Patients with chemosensitive disease had an actuarial 5-year survival rate of 49% at 5 years compared with 13% for those with chemoresistant disease (P < .001). For patients considered to have chemosensitive disease at the time of transplantation, there is a significant difference in the actuarial progression-free survival rates for those who received high-dose therapy after attaining a partial response to first-line therapy (69% at 5 years) as compared with those with sensitive but relapsed disease (32% at 5 years) (P = .003). CONCLUSION: Patients with chemosensitive disease benefit most from high-dose chemotherapy, and those who receive such therapy early after achieving a partial response to first-line therapy have a high rate of cure.

Adolescent↗
PubMed1995

Dose intensification of etoposide in the BEAM ABMT protocol for malignant lymphoma.

We have previously demonstrated a dose response relationship in Hodgkin's disease for the combination of BCNU, VP16, Ara C and Melphalan, with the superior efficacy of the BEAM regimen requiring haemopoietic support, compared with miniBEAM. To further exploit this, we have attempted to escalate the VP16 dose in BEAM. The standard etoposide dose is 200 mg/m2 IV for four days. Thirty seven patients with refractory lymphoma received 400 mg/m2/day of etoposide, and 13 patients 600 mg/m2/day, in addition to BCNU, cytarabine, and melphalan. Toxicity and outcome parameters were compared in the preceding 40 patients, who received 200 mg/m2/day etoposide. The toxic mortality with 400 mg/m2/day of etoposide (3%) was identical to that for the standard BEAM regimen (5%). Two procedure related deaths occurred in the highest VP16 dose group (15%). The morbidity of the lower etoposide dose regimens was comparable, but 600 mg/m2/day induced significantly greater gastrointestinal toxicity. Twelve of the 13 patients receiving this dose suffered grade II-IV mucositis, with stomatitis, dysphagia and prolonged diarrhoea; 5 haemodynamically significant gastrointestinal haemorrhage, and 1 fatal toxic colitis. Granulocyte colony stimulating factor did not influence the nonhaematological toxicity. The three month response rates were similar (91%) in all dose cohorts. The maximum tolerable etoposide dose within the BEAM regimen is thus 400 mg/m2 for four days.

Adolescent↗
PubMed1994

Liposomal amphotericin B in the treatment of fungal infections in neutropenic patients: a single-centre experience of 133 episodes in 116 patients.

Liposomal amphotericin B (AmBisome) was used for suspected or confirmed fungal infection complicating 133 neutropenic episodes in 116 patients not tolerating, or not responding to, conventional amphotericin. Adverse effects were infrequent and no significant renal impairment resulted. Acute reactions occurred in five patients, reversible hepatic dysfunction in 23, and hypernatraemia in 17. The putative mycosis resolved with AmBisome treatment in 81 episodes (61%) and progressed with fatal outcome in 25 (19%), but the diagnosis was equivocal in most, and in 27 episodes (20%) evidence indicating nonfungal pathogenesis emerged. Treatment efficacy is, however, evaluable in those with proven aspergillosis. 13/17 patients with confirmed invasive aspergillosis responded to AmBisome (77%), conventional amphotericin having failed in 11. Treatment was successfully discontinued when the neutrophil count was < 1 x 10(9)/l in eight responders (61%). In four further patients treated for suspected aspergillosis, disseminated infection was documented at post-mortem, but the true incidence is unknown. This analysis confirms that AmBisome is well tolerated and effective against invasive mycoses in neutropenic patients, and may salvage patients when conventional amphotericin proves excessively toxic or ineffective.

Adolescent↗
PubMed1994

Detection and significance of bone marrow infiltration at the time of autologous bone marrow transplantation in Hodgkin's disease.

Bilateral iliac crest biopsies were performed at the time of bone marrow (BM) harvest in patients with poor-risk Hodgkin's disease (HD) undergoing autologous bone marrow transplantation (ABMT). 67 consecutive patients with normal trephine biopsies (58 unilateral; nine bilateral) taken 2 weeks prior to harvest were studied. Nine (13%) of patients had BM infiltration with HD on the harvest biopsies. These patients had all previously had only unilateral biopsies. Three patients did not proceed to ABMT because disease progression became clinically apparent, but the remaining six patients were infused with involved marrow. One patient died 6 weeks post ABMT, with no evidence of disease at post-mortem. One patient showed no response to ABMT and four patients either had a partial or complete response to ABMT. Of the responders, three patients are now in complete remission at 53, 39 and 33 months past ABMT.

Adolescent↗
PubMed1994

Development of a simplified single-apheresis approach for peripheral-blood progenitor-cell transplantation in previously treated patients with lymphoma.

PURPOSE: The aims of this study were to develop a simplified, safe, and cost-effective peripheral-blood progenitor-cell (PBPC) mobilization protocol. PATIENTS AND METHODS: Twenty-six patients with relapsed or resistant lymphomas were entered onto a sequential cohort study in which schedules of various granulocyte colony-stimulating factor (G-CSF) were administered after cyclophosphamide 1.5 g/m2. Hematologic recovery after high-dose carmustine (BCNU) etoposide, cytarabine, and melphalan (BEAM) chemotherapy was compared with that of 46 patients who received autologous bone marrow transplantation (ABMT) without growth factors and 28 patients who received ABMT followed by G-CSF. RESULTS: When G-CSF (10 micrograms/kg/d) was administered from the day after the cyclophosphamide, neutropenia developed on day 8 followed by an abrupt increase in the WBC count. The optimal time for PBPC harvesting was the day on which the postnadir WBC count was greater than 8.0 x 10(9)/L, as shown by CD34+ cell counts and granulocytic-macrophage colony-forming cell (GM-CFC) assays. The reproducibility of the response was such that routine monitoring of CD34+ cell counts and GM-CFC was not necessary. A single leukapheresis on this day was adequate for prompt hematologic engraftment, and posttransplant G-CSF made little further impact on the rapid recovery. Compared with both control groups, the use of PBPC led to more rapid neutrophil recovery, markedly accelerated platelet recovery, less use of antimicrobial agents and parenteral nutrition, and more than 10 days earlier discharge from hospital. All of these differences were highly significant (P < .01). CONCLUSION: A simplified mobilization protocol is described that requires only one apheresis to achieve rapid hematologic engraftment.

Adult↗
PubMed1994

Autologous bone marrow transplantation in multiple myeloma: a single centre experience of 23 patients.

We report the complications and outcome of high-dose melphalan and TBI combined with ABMT used in the treatment of multiple myeloma at a single centre. Twenty-three patients, aged 65 years or less, who underwent the procedure are reviewed. All had chemosensitive disease. Response to ABMT assessed at 3 months showed 75% of evaluable patients to have further tumour cytoreduction of at least 50%, with 24% of patients who entered ABMT with residual disease eventually achieving CR. There was one toxic death. The overall survival is 60% and the progression-free survival is 49.8% at a median follow-up time of 17 months. Relapse or disease progression has occurred in 27% of patients, of whom half have died. No significant prognostic factors affecting survival were found although those patients with IgG myeloma had a better outcome. Patients transplanted in first plateau appeared to do significantly better if they had been resistant to their first-line chemotherapy but had then responded to further conventional chemotherapy (p = 0.029).

Adult↗
PubMed1994

Partial hypopituitarism following total body irradiation in adult patients with haematological malignancy.

We present the endocrine parameters of two adult patients with partial hypopituitarism documented at 6 and 8 months after chemotherapy, single fraction total body irradiation (10.5 Gy) and autologous bone marrow transplantation. The hormone profiles demonstrate severe somatotroph insufficiency and impaired adrenocorticotroph secretory capacity, despite sparing of the gonadotroph compartment. We recommend stimulatory testing of hypothalamic-pituitary function from 3 months post-transplant, as basal hormonal concentrations may be equivocal, and supplementation may significantly improve quality of life.

Adult↗
PubMed1994

Prospective study of pituitary-gonadal function to evaluate short-term effects of ablative chemotherapy or total body irradiation with autologous or allogenic marrow transplantation in post-menarcheal female patients.

Pituitary-gonadal (P-G) function was evaluated 0-3 months before and 3-4 months after bone marrow transplantation (BMT) in 15 post-menarcheal females aged 17-30 (21.6 +/- 0.34) years with haematological malignancies. All patients had evidence of gonadal insufficiency prior to BMT in that their basal and human menopausal gonadotrophin (HMG)-stimulated oestradiol (E2) levels were significantly lower than those of control subjects. The patients also had markedly higher basal FSH levels and exaggerated responses to 100 micrograms iv gonadotrophin release hormone bolus compared with those of control subjects. However, the conditioning regimens employed prior to BMT, i.e. cytotoxic chemotherapy (CT) and total body irradiation (TBI), acting either singly or in combination, caused further ovarian damage. As a result, their gonadotrophins rose further into the menopausal range. Their oestradiol secretion diminished and ovaries became almost unresponsive 3-4 months after BMT. Pelvic ultrasound undertaken in 5 patients before and after BMT demonstrated a reduction in ovarian size associated with follicular depletion. All patients developed menopausal symptoms and became amenorrhoeic during this period. Contrary to expectation, the hormonal changes occurring acutely were similar in patients undergoing radiation-based regimens and those conditioned with high-dose chemotherapy alone. Also, the severity of ovarian dysfunction appeared independent of age at transplantation, the nature of the conditioning-regimen or the type of transplant. Gonadotrophic, thyrotrophic, lactotrophic and adrenocorticotrophic secretions were unaffected. These data indicate that the ovary suffers an acute insult during short-term chemotherapy but the anterior pituitary gland retains its trophic hormone reserve and secretory capacity.

Adolescent↗
PubMed1994

Germ cell failure and Leydig cell insufficiency in post-pubertal males after autologous bone marrow transplantation with BEAM for lymphoma.

Thirteen post-pubertal male patients aged 17-25 years were assessed for pituitary-gonadal function 0-3 months prior to and 2-3 months post-bone marrow transplantation for haematological malignancy. All patients had multiagent cytotoxic treatment prior to transplantation and 30% were found to have germ cell dysfunction with abnormal semen parameters before high-dose therapy indicating damage to the germinal epithelium. They also had evidence of reduced Leydig cell reserve even before transplantation. During transplantation all patients sustained sustained gonadal injury, the effect on their germ cells being more pronounced than on the Leydig cells. Fifty per cent had reduction in testicular volume and all had azoospermia 2-3 months post-transplantation. Our results indicate that short-term chemoradiotherapy causes profound damage to the germ cell compartment of the testis, with less severe damage to the Leydig cells, but no overt injury to the anterior pituitary gland. The changes appeared to be identical in patients conditioned with total body irradiation-based protocols and those who received only high-dose chemotherapy prior to bone marrow transplantation.

Adolescent↗
PubMed1993

Five case reports of high grade non-Hodgkin's lymphoma in human immunodeficiency virus-1 negative homosexual men.

High grade non-Hodgkin's lymphoma accounts for only 5%-10% of all non-Hodgkin's lymphoma. Infection with the human immunodeficiency virus increases the risk of developing high grade, usually B-cell, lymphoma, which has been noted to occur more commonly in homosexual men. These lymphomas often have unusual clinical presentations. We report five cases of high grade non-Hodgkin's lymphoma in HIV negative homosexual men who presented to our hospital in a 13-month period. As a major centre for the treatment of the acquired immune deficiency syndrome, there may be a self-selected homosexual population attending for medical care, and thus a bias in the relative incidence of lymphoma seen in this group.

Adult↗
PubMed1993

Induction of ovarian function by using short-term human menopausal gonadotrophin in patients with ovarian failure following cytotoxic chemotherapy for haematological malignancy.

Currently no treatment has proved successful in inducing ovarian steroidogenic and/or gametogenic recovery in patients with haematological malignancies treated by cytotoxic chemotherapy once biochemical failure becomes manifest i.e., when FSH levels exceed 40 IU/L. This paper reports two such cases with classical biochemical ovarian failure in which ovarian function was induced by brief stimulation with Human Menopausal Gonadotrophin (HMG).

Adult↗
PubMed1993

Efficacy of delayed granulocyte colony-stimulating factor after autologous BMT.

Granulocyte colony-stimulating factor (G-CSF) has been shown to be effective in accelerating neutrophil recovery after BMT. In this single centre study, we have examined the effect of delaying the start of treatment with G-CSF (5 micrograms/kg) until 8 days after BM infusion in a cohort of 17 patients with malignant lymphomas undergoing autologous BMT. In comparison with historical controls, neutrophil recovery to > 0.5 x 10(9)/l was shortened from 22 to 14 days (p < 0.01). Patients receiving G-CSF required iv antibiotics for a median 13 days (control 17, p < 0.05) and were discharged a median 28 days post-ABMT (control 32.5, p = NS). Patients received G-CSF for a median of 10 days only. Although these results require confirmation in a randomised trial they suggest that G-CSF administration could be delayed until 8 days after BMT without compromising efficacy and with an accompanying reduction in treatment costs.

Adult↗