113 results on '"Whitehouse JM"'
Search Results
2. Involved field radiotherapy or chemotherapy in the management of stage I nodal intermediate grade non-Hodgkin's lymphoma
- Author
-
Jeffery, GM, primary, Mead, GM, additional, Whitehouse, JM, additional, and Ryall, RDH, additional
- Published
- 1991
- Full Text
- View/download PDF
3. COMPARATIVE EFFECTS OF ATROPINE AND METHYLATROPINE ON MAZE ACQUISITION AND EATING
- Author
-
Whitehouse Jm, Lloyd Aj, and Fifer Sa
- Subjects
Atropine ,Pharmacology ,Food intake ,business.industry ,media_common.quotation_subject ,Research ,Appetite ,Brain ,General Medicine ,Methylatropine ,Rats ,chemistry.chemical_compound ,Eating ,chemistry ,Anesthesia ,Medicine ,Learning ,Atropine Derivatives ,business ,media_common ,medicine.drug - Published
- 1964
4. Darobactin B Stabilises a Lateral-Closed Conformation of the BAM Complex in E. coli Cells.
- Author
-
Haysom SF, Machin J, Whitehouse JM, Horne JE, Fenn K, Ma Y, El Mkami H, Böhringer N, Schäberle TF, Ranson NA, Radford SE, and Pliotas C
- Abstract
The β-barrel assembly machinery (BAM complex) is essential for outer membrane protein (OMP) folding in Gram-negative bacteria, and represents a promising antimicrobial target. Several conformational states of BAM have been reported, but all have been obtained under conditions which lack the unique features and complexity of the outer membrane (OM). Here, we use Pulsed Electron-Electron Double Resonance (PELDOR, or DEER) spectroscopy distance measurements to interrogate the conformational ensemble of the BAM complex in E. coli cells. We show that BAM adopts a broad ensemble of conformations in the OM, while in the presence of the antibiotic darobactin B (DAR-B), BAM's conformational equilibrium shifts to a restricted ensemble consistent with the lateral closed state. Our in-cell PELDOR findings are supported by new cryoEM structures of BAM in the presence and absence of DAR-B. This work demonstrates the utility of PELDOR to map conformational changes in BAM within its native cellular environment., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors. Angewandte Chemie published by Wiley-VCH GmbH.)
- Published
- 2023
- Full Text
- View/download PDF
5. The role of membrane destabilisation and protein dynamics in BAM catalysed OMP folding.
- Author
-
White P, Haysom SF, Iadanza MG, Higgins AJ, Machin JM, Whitehouse JM, Horne JE, Schiffrin B, Carpenter-Platt C, Calabrese AN, Storek KM, Rutherford ST, Brockwell DJ, Ranson NA, and Radford SE
- Subjects
- Bacterial Outer Membrane Proteins genetics, Bacterial Outer Membrane Proteins isolation & purification, Bacterial Outer Membrane Proteins ultrastructure, Cryoelectron Microscopy, Dynamic Light Scattering, Escherichia coli Proteins genetics, Escherichia coli Proteins isolation & purification, Escherichia coli Proteins ultrastructure, Hydrolases genetics, Hydrolases isolation & purification, Hydrolases ultrastructure, Lipid Metabolism, Liposomes ultrastructure, Molecular Dynamics Simulation, Protein Conformation, beta-Strand, Proteolipids metabolism, Proteolipids ultrastructure, Recombinant Proteins genetics, Recombinant Proteins isolation & purification, Recombinant Proteins metabolism, Recombinant Proteins ultrastructure, Bacterial Outer Membrane Proteins metabolism, Escherichia coli Proteins metabolism, Hydrolases metabolism, Liposomes metabolism, Protein Folding
- Abstract
The folding of β-barrel outer membrane proteins (OMPs) in Gram-negative bacteria is catalysed by the β-barrel assembly machinery (BAM). How lateral opening in the β-barrel of the major subunit BamA assists in OMP folding, and the contribution of membrane disruption to BAM catalysis remain unresolved. Here, we use an anti-BamA monoclonal antibody fragment (Fab1) and two disulphide-crosslinked BAM variants (lid-locked (LL), and POTRA-5-locked (P5L)) to dissect these roles. Despite being lethal in vivo, we show that all complexes catalyse folding in vitro, albeit less efficiently than wild-type BAM. CryoEM reveals that while Fab1 and BAM-P5L trap an open-barrel state, BAM-LL contains a mixture of closed and contorted, partially-open structures. Finally, all three complexes globally destabilise the lipid bilayer, while BamA does not, revealing that the BAM lipoproteins are required for this function. Together the results provide insights into the role of BAM structure and lipid dynamics in OMP folding.
- Published
- 2021
- Full Text
- View/download PDF
6. Bitters: Time for a New Paradigm.
- Author
-
McMullen MK, Whitehouse JM, and Towell A
- Abstract
In plant-based medical systems, bitter tasting plants play a key role in managing dyspepsia. Yet when it comes to defining their mechanism of activity, herbalists and pharmacologists are split between two theories: one involves cephalic elicited vagal responses while the other comprises purely local responses. Recent studies indicate that bitters elicit a range of cephalic responses which alter postprandial gastric phase haemodynamics. Caffeine and regular coffee (Coffea arabica semen, L.) increase heart rate whereas gentian (Gentiana lutea radix, L.) and wormwood (Artemisia absinthium herba L.) increase tonus in the vascular resistance vessels. Following meals increased cardiac activity acts to support postprandial hyperaemia and maintain systemic blood pressure. The increased vascular tonus acts in parallel with the increased cardiac activity and in normal adults this additional pressor effect results in a reduced cardiac workload. The vascular response is a sympathetic reflex, evident after 5 minutes and dose dependent. Thus gentian and wormwood elicit cephalic responses which facilitate rather than stimulate digestive activity when postprandial hyperaemia is inadequate. Encapsulated caffeine elicits cardiovascular responses indicating that gastrointestinal bitter receptors are functionally active in humans. However, neither encapsulated gentian nor wormwood elicited cardiovascular responses during the gastric phase. These findings provide the platform for a new evidence-based paradigm.
- Published
- 2015
- Full Text
- View/download PDF
7. Bitter tastants alter gastric-phase postprandial haemodynamics.
- Author
-
McMullen MK, Whitehouse JM, Whitton PA, and Towell A
- Subjects
- Adult, Blood Pressure drug effects, Female, Gastric Mucosa metabolism, Humans, Middle Aged, Postprandial Period, Taste drug effects, Young Adult, Artemisia absinthium chemistry, Digestion drug effects, Gentiana chemistry, Hemodynamics drug effects, Plant Roots chemistry, Stomach drug effects, Taste physiology
- Abstract
Ethnopharmacological Relevance: Since Greco-Roman times bitter tastants have been used in Europe to treat digestive disorders, yet no pharmacological mechanism has been identified which can account for this practice. This study investigates whether the bitter tastants, gentian root (Gentian lutea L.) and wormwood herb (Artemisia absinthium L.), stimulate cephalic and/or gut receptors to alter postprandial haemodynamics during the gastric-phase of digestion., Materials and Methods: Normal participants ingested (1) 100 mL water plus capsules containing either cellulose (placebo-control) or 1000 mg of each tastant (n=14); or (2) 100mL of water flavoured with 500 or 1500 mg of each tastant (a) gentian (n=12) and (b) wormwood (n=12). A single beat-to-beat cardiovascular recording was obtained for the entire session. Pre/post-ingestion contrasts with the control were analysed for (1) the encapsulated tastants, in the "10 to 15" minute post-ingestion period, and (2) the flavoured water in the "5 to 10" minute post-ingestion period., Results: Water, the placebo-control, increased cardiac contraction force and blood pressure notwithstanding heart rate decreases. Encapsulated tastants did not further alter postprandial haemodynamics. In contrast gentian (500 and 1500 mg) and wormwood (1500 mg) flavoured water elicited increased peripheral vascular resistance and decreased cardiac output, primarily by reducing stroke volume rather than heart rate., Conclusions: Drinking 100mL water elicits a pressor effect during the gastric-phase of digestion due to increased cardiac contraction force. The addition of bitter tastants to water elicits an additional and parallel pressor effect due to increased peripheral vascular resistance; yet the extent of the post-prandial blood pressure increases are unchanged, presumably due to baroreflex buffering. The vascular response elicited by bitter tastants can be categorised as a sympathetically-mediated cephalic-phase response. A possible mechanism by which bitter tastants could positively influence digestion is altering gastric-phase postprandial haemodynamics and supporting postprandial hyperaemia., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2014
- Full Text
- View/download PDF
8. Caffeine in hot drinks elicits cephalic phase responses involving cardiac activity.
- Author
-
McMullen MK, Whitehouse JM, Shine G, Whitton PA, and Towell A
- Subjects
- Adult, Baroreflex drug effects, Blood Pressure drug effects, Double-Blind Method, Female, Humans, Middle Aged, Regression Analysis, Taste physiology, Tea, Young Adult, Caffeine blood, Coffee chemistry, Heart Rate drug effects, Taste Buds metabolism
- Abstract
Caffeine stimulates both oropharyngeal and gut bitter taste receptors (hTAS2Rs) and so has the potential to elicit reflex autonomic responses. Coffee containing 130 mg caffeine has been reported to increase heart rate for 30 min post-ingestion. Whereas added-caffeine, in doses of 25 to 200 mg, ingested with decaffeinated coffee/tea decreases heart rate 10 to 30 min post-ingestion. This study aimed to clarify caffeine's chemosensory impact. Double-espresso coffees were compared to a placebo-control capsule in a double-blind between-measures design. Coffees tested were regular coffee (130 mg caffeine) and decaffeinated coffee with added-caffeine (0, 67 and 134 mg). Cardiovascular measures from three post-ingestion phases: 1) 0 to 5; 2) 10 to 15; and 3) 25 to 30 min; were compared to pre-ingestion measures. Participants comprised 11 women in the control group and 10 women in the test group. Decaffeinated coffee elicited no changes. Decaffeinated coffee with 67 mg caffeine: decreased dp/dt in Phase 1. Decaffeinated coffee with 134 mg caffeine: increased heart rate in Phases 1 and 2; decreased spontaneous baroreflex sensitivity in Phase 1; and increased diastolic pressure in Phases 2 and 3. Regular coffee: increased heart rate in Phases 1 and 2; decreased dp/dt in all phases; and decreased systolic pressure in Phase 1. Caffeine is the substance in regular coffee which elicits chemosensory autonomic reflex responses, which involves heart activity and the baroreflex. Compared to the caffeine in regular coffee, added-caffeine elicits somewhat different chemosensory responses including a more pronounced pressor effect and resetting of the baroreflex. Caffeine in commonly consumed amounts, as well as modulating body processes by blocking adenosine receptors, can elicit reflex autonomic responses during the ingestion of caffeinated drinks. It is plausible that caffeine stimulates hTAS2Rs, during the ingestion of coffee, eliciting cephalic phase responses. These cephalic phase responses likely result from vagal withdrawal and it is uncertain whether they enhance digestion or not.
- Published
- 2012
- Full Text
- View/download PDF
9. Respiratory and non-respiratory sinus arrhythmia: implications for heart rate variability.
- Author
-
McMullen MK, Whitehouse JM, Shine G, and Towell A
- Subjects
- Adult, Female, Humans, Male, Middle Aged, Posture, Reference Values, Stroke Volume physiology, Young Adult, Arrhythmia, Sinus physiopathology, Heart Rate physiology, Respiration
- Abstract
The quantity of blood arriving at the left side of the heart oscillates throughout the breathing cycle due to the mechanics of breathing. Neurally regulated fluctuations in the length of the heart period act to dampen oscillations of the left ventricular stroke volume entering the aorta. We have reported that stroke volume oscillations but not spectral frequency variability stroke volume measures can be used to estimate the breathing frequency. This study investigated with the same recordings whether heart period oscillations or spectral heart rate variability measures could function as estimators of breathing frequency. Continuous 270 s cardiovascular recordings were obtained from 22 healthy adult volunteers in the supine and upright postures. Breathing was recorded simultaneously. Breathing frequency and heart period oscillation frequency were calculated manually, while heart rate variability spectral maximums were obtained using heart rate variability software. These estimates were compared to the breathing frequency using the Bland-Altman agreement procedure. Estimates were required to be < ±10% (95% levels of agreement). The 95% levels of agreement measures for the heart period oscillation frequency (supine: -27.7 to 52.0%, upright: -37.8 to 45.9%) and the heart rate variability spectral maximum estimates (supine: -48.7 to 26.5% and -56.4 to 62.7%, upright: -37.8 to 39.3%) exceeded 10%. Multiple heart period oscillations were observed to occur during breathing cycles. Both respiratory and non-respiratory sinus arrhythmia was observed amongst healthy adults. This observation at least partly explains why heart period parameters and heart rate variability parameters are not reliable estimators of breathing frequency. In determining the validity of spectral heart rate variability measurements we suggest that it is the position of the spectral peaks and not the breathing frequency that should be the basis of decision making.
- Published
- 2012
- Full Text
- View/download PDF
10. The immediate and short-term chemosensory impacts of coffee and caffeine on cardiovascular activity.
- Author
-
McMullen MK, Whitehouse JM, Shine G, Whitton PA, and Towell A
- Subjects
- Adult, Blood Pressure drug effects, Caffeine administration & dosage, Cardiovascular System drug effects, Female, Heart Rate drug effects, Humans, Intestines drug effects, Intestines physiology, Middle Aged, Sensory Receptor Cells drug effects, Sensory Receptor Cells physiology, Caffeine pharmacology, Coffee, Hemodynamics drug effects
- Abstract
Unlabelled: The immediate and short-term chemosensory impacts of coffee and caffeine on cardiovascular activity., Introduction: Caffeine is detected by 5 of the 25 gustatory bitter taste receptors (hTAS2Rs) as well as by intestinal STC-1 cell lines. Thus there is a possibility that caffeine may elicit reflex autonomic responses via chemosensory stimulation., Methods: The cardiovascular impacts of double-espresso coffee, regular (130 mg caffeine) and decaffeinated, and encapsulated caffeine (134 mg) were compared with a placebo-control capsule. Measures of four post-ingestion phases were extracted from a continuous recording of cardiovascular parameters and contrasted with pre-ingestion measures. Participants (12 women) were seated in all but the last phase when they were standing., Results: Both coffees increased heart rate immediately after ingestion by decreasing both the diastolic interval and ejection time. The increases in heart rate following the ingestion of regular coffee extended for 30 min. Encapsulated caffeine decreased arterial compliance and increased diastolic pressure when present in the gut and later in the standing posture., Discussion: These divergent findings indicate that during ingestion the caffeine in coffee can elicit autonomic arousal via the chemosensory stimulation of the gustatory receptors which extends for at least 30 min. In contrast, encapsulated caffeine can stimulate gastrointestinal receptors and elicit vascular responses involving digestion., Conclusion: Research findings on caffeine are not directly applicable to coffee and vice versa. The increase of heart rate resulting from coffee drinking is a plausible pharmacological explanation for the observation that coffee increases risk for coronary heart disease in the hour after ingestion., (This journal is © The Royal Society of Chemistry 2011)
- Published
- 2011
- Full Text
- View/download PDF
11. Habitual coffee and tea drinkers experienced increases in blood pressure after consuming low to moderate doses of caffeine; these increases were larger upright than in the supine posture.
- Author
-
McMullen MK, Whitehouse JM, Shine G, and Towell A
- Subjects
- Adult, Cardiovascular System drug effects, Coffee, Dose-Response Relationship, Drug, Double-Blind Method, Female, Humans, London, Male, Middle Aged, Supine Position, Tea, Blood Pressure drug effects, Caffeine administration & dosage, Feeding Behavior, Posture
- Abstract
Caffeine users have been encouraged to consume caffeine regularly to maintain their caffeine tolerance and so avoid caffeine's acute pressor effects. In controlled conditions complete caffeine tolerance to intervention doses of 250 mg develops rapidly following several days of caffeine ingestion, nevertheless, complete tolerance is not evident for lower intervention doses. Similarly complete caffeine tolerance to 250 mg intervention doses has been demonstrated in habitual coffee and tea drinkers' but for lower intervention doses complete tolerance is not evident. This study investigated a group of habitual caffeine users following their self-determined consumption pattern involving two to six servings daily. Cardiovascular responses following the ingestion of low to moderate amounts caffeine (67, 133 and 200 mg) were compared with placebo in a double-blind, randomised design without caffeine abstinence. Pre-intervention and post-intervention (30 and 60 min) 90 s continuous cardiovascular recordings were obtained with the Finometer in both the supine and upright postures. Participants were 12 healthy habitual coffee and tea drinkers (10 female, mean age 36). Doses of 67 and 133 mg increased systolic pressure in both postures while in the upright posture diastolic pressure and aortic impedance increased while arterial compliance decreased. These vascular changes were larger upright than supine for 133 mg caffeine. Additionally 67 mg caffeine increased dp/dt and indexed peripheral resistance in the upright posture. For 200 mg caffeine there was complete caffeine tolerance. Cardiovascular responses to caffeine appear to be associated with the size of the intervention dose. Habitual tea and coffee drinking does not generate complete tolerance to caffeine as has been previously suggested. Both the type and the extent of caffeine induced cardiovascular changes were influenced by posture.
- Published
- 2011
- Full Text
- View/download PDF
12. The Finometer can function as a standalone instrument in blood pressure variability studies and does not require support equipment to determine breathing frequency.
- Author
-
McMullen MK, Whitehouse JM, Shine G, and Towell A
- Subjects
- Adult, Blood Pressure physiology, Blood Pressure Determination methods, Female, Humans, Male, Middle Aged, Posture physiology, Stroke Volume physiology, Supine Position physiology, Blood Pressure Determination instrumentation, Plethysmography methods, Respiration
- Abstract
Objective: The Finometer records the beat-to-beat finger pulse contour and has been recommended for research studies assessing short-term changes of blood pressure and its variability. Variability measured in the frequency domain using spectral analysis requires the impact of breathing be restricted to high frequency spectra (>0.15 Hz) so that the data from participants need to be excluded when the breathing impact occurs in the low frequency spectra (0.04-0.15 Hz). This study tested whether breathing frequency can be estimated from standard Finometer recordings using either stroke volume oscillation frequency or spectral stroke volume variability maximum scores., Methods: Twenty-two healthy volunteers were tested for 270 s in the supine and upright positions. Finometer recorded the finger pulse contour and a respiratory transducer recorded breathing. Stoke volume oscillation frequency was calculated manually whereas the stroke volume spectral maximums were obtained using the software Cardiovascular Parameter Analysis. These estimates were compared with the breathing frequency using the Bland-Altman procedures., Results: Stroke volume oscillation frequency estimated breathing frequency to less than +/-10% and 95% levels of agreement in both supine (-7.7 to 7.0%) and upright (-6.7 to 5.4%) postures. Stroke volume variability maximum scores did not accurately estimate breathing frequency., Conclusion: Breathing frequency can be accurately derived from standard Finometer recordings using stroke volume oscillations for healthy individuals in both supine and upright postures. The Finometer can function as a standalone instrument in blood pressure variability studies and does not require support equipment to determine the breathing frequency.
- Published
- 2010
- Full Text
- View/download PDF
13. The clinical utility of the Revised European-American Lymphoma (R.E.A.L.) Classification: preliminary results of a prospective study in patients with non-Hodgkin's lymphoma from a single centre.
- Author
-
Sweetenham JW, Smartt PF, Wilkins BS, Pellatt JC, Smith JL, Ramsay A, and Whitehouse JM
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Biopsy, Female, Guidelines as Topic, Histology classification, Humans, Lymphoma, B-Cell classification, Lymphoma, B-Cell diagnosis, Lymphoma, B-Cell pathology, Lymphoma, Non-Hodgkin pathology, Lymphoma, T-Cell classification, Lymphoma, T-Cell diagnosis, Lymphoma, T-Cell pathology, Male, Middle Aged, Prospective Studies, Lymphoma, Non-Hodgkin classification, Lymphoma, Non-Hodgkin diagnosis
- Abstract
Background: The clinical applicability of the Revised European-American Lymphoma (R.E.A.L.) Classification has been demonstrated in several retrospective studies. The present, ongoing study was initiated to evaluate the clinical and pathological utility of the R.E.A.L. Classification compared with the Working Formulation (WF) in a prospective fashion, in an unselected patient population treated at a single institution., Patients and Methods: Prospective data were collected on 596 biopsies from 557 patients referred with an initial diagnosis of lymphoma. After initial histologic review, 465 biopsies from 441 patients were confirmed as non-Hodgkin's lyphoma (NHL), 412 of which could be classified in R.E.A.L. and WF., Results: According to WF criteria, 25% were low grade, 58% intermediate grade and 2% high grade, 14% could not be allocated to a WF subtype. According to R.E.A.L., 46% were diffuse large B cell, 19% follicle centre lymphoma, 6% marginal zone, 6% small lymphocytic, 4% mantle cell, and 3% T-cell anaplastic large cell. For those with B-cell NHL, 7% were unclassifiable in WF compared with 1% in R.E.A.L. Corresponding figures for T-cell NHL were 68% and 3%, respectively., Conclusions: Preliminary results confirm the clinical utility of the R.E.A.L. Classification in a single institution setting, demonstrating that cases were more readily sub-typed in R.E.A.L. compared with WF. Frequencies are comparable with I.L.S.G. data. Further follow up with large patient numbers is on-going to analyse survival data with reference to clinical prognostic factors.
- Published
- 1999
- Full Text
- View/download PDF
14. More money is needed to care for patients with cancer.
- Author
-
Leonard RC, Smith IE, Coleman RE, Malpas JS, Nicolson M, Cassidy J, Jones A, McIllmurray MB, Stuart NS, Woll PJ, and Whitehouse JM
- Subjects
- State Medicine economics, United Kingdom, Cancer Care Facilities economics, Financing, Government
- Published
- 1997
15. Lymphadenopathy due to amyloid deposition in non-Hodgkin's lymphoma.
- Author
-
Simmonds PD, Cottrell BJ, Mead GM, Wright DH, and Whitehouse JM
- Subjects
- Humans, Lymphatic Diseases etiology, Lymphoma, Non-Hodgkin complications, Male, Middle Aged, Amyloid metabolism, Bone Marrow metabolism, Lymph Nodes metabolism, Lymphatic Diseases metabolism, Lymphoma, Non-Hodgkin metabolism
- Abstract
Background: Amyloidosis is a rare complication of non-Hodgkin's lymphoma. Most of the reported patients have had systemic amyloidosis and have died as a result of complications of this disease., Materials and Methods: The clinical cases of two patients with lymphoplasmacytic non-Hodgkin's lymphoma who presented with lymphadenopathy due to localised amyloid deposition are reviewed. Immunohistochemical studies were performed on the amyloid deposits and adjacent lymphoma., Results: The amyloid deposits in both patients were derived from monoclonal light chains of the same isotype as those expressed by the lymphoma cells and were localised to areas adjacent to the lymphoma despite the presence of circulating light chains. Both patients had an indolent clinical course and treatment appeared to have little influence on the amyloid deposition., Conclusions: Non-Hodgkin's lymphoma may be associated with localised amyloidosis secondary to local production and deposition of amyloid from monoclonal light chains synthesised by the lymphoma cells. This is a rare cause of lymphadenopathy which does not respond to treatment of the underlying lymphoma.
- Published
- 1997
- Full Text
- View/download PDF
16. PACE BOM chemotherapy: a 12-week regimen for advanced Hodgkin's disease.
- Author
-
Simmonds PD, Mead GM, Sweetenham JW, O'Callaghan A, Smartt P, Kerr J, Hamilton CR, Golding PF, Milne AE, and Whitehouse JM
- Subjects
- Adolescent, Adult, Aged, Antineoplastic Combined Chemotherapy Protocols adverse effects, Bleomycin administration & dosage, Combined Modality Therapy, Cyclophosphamide administration & dosage, Disease Progression, Dose-Response Relationship, Drug, Doxorubicin administration & dosage, Drug Administration Schedule, Etoposide administration & dosage, Female, Fertility drug effects, Follow-Up Studies, Hematologic Diseases chemically induced, Hodgkin Disease pathology, Humans, Male, Methotrexate administration & dosage, Middle Aged, Neoplasm Staging, Prednisolone administration & dosage, Retreatment, Treatment Outcome, Vincristine administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Hodgkin Disease drug therapy
- Abstract
Background: This study was designed to evaluate the efficacy and toxicity of a 12-week alternating weekly chemotherapy regimen for advanced Hodgkin's disease. Consolidative irradiation of residual masses was used in selected cases., Patients and Methods: Eighty-three patients with newly diagnosed advanced Hodgkin's disease (bulky stage IIA, stage IIB-IVB) or with progressive disease after extended field radiotherapy for early stage disease were included in this study. The patients were treated for 12 weeks with PACE BOM comprising oral prednisolone together with intravenous doxorubicin, cyclophosphamide and etoposide alternating weekly with intravenous bleomycin, vincristine and methotrexate. Limited field adjuvant radiotherapy was also given to 21 patients with localised persistent radiological abnormalities visible on chest X-ray after chemotherapy. The study end points were overall survival, failure free survival (FFS) and toxicity, particularly with respect to reproductive function., Results: With a median post treatment follow up of 52 months the actuarial 5-year overall survival is 90% (confidence interval 81%-95%) and FFS is 64% (52%-74%). This treatment was well tolerated and fertility was maintained in a high proportion of young adults., Conclusions: The brief duration PACE BOM regimen with or without radiotherapy appears to be comparable in efficacy to other doxorubicin containing regimens, with a favourable toxicity profile. Randomised clinical trials are now needed to evaluate the role of this and comparable initial treatment approaches to advanced Hodgkin's disease.
- Published
- 1997
- Full Text
- View/download PDF
17. A complicated case of metastatic teratoma. Growing teratoma syndrome and cerebral metastasis.
- Author
-
Simmonds PD, Mead GM, and Whitehouse JM
- Subjects
- Antineoplastic Combined Chemotherapy Protocols therapeutic use, Biomarkers, Tumor blood, Bleomycin administration & dosage, Brain Neoplasms drug therapy, Brain Neoplasms radiotherapy, Cisplatin administration & dosage, Combined Modality Therapy, Cranial Irradiation, Etoposide administration & dosage, Humans, Ifosfamide administration & dosage, Lung Neoplasms drug therapy, Lung Neoplasms surgery, Lymph Node Excision, Lymphatic Metastasis, Male, Middle Aged, Orchiectomy, Remission Induction, Teratocarcinoma drug therapy, Teratocarcinoma pathology, Teratocarcinoma surgery, Thoracotomy, Vincristine administration & dosage, Brain Neoplasms secondary, Lung Neoplasms secondary, Occipital Lobe, Teratocarcinoma secondary, Testicular Neoplasms drug therapy, Testicular Neoplasms surgery
- Abstract
All patients presenting with metastatic teratoma should be regarded as potentially curable and this case demonstrates the multiple treatment modalities which are often needed in the management of such patients. Increasing experience with cisplatin based combination chemotherapy has led to the development of prognostic factors which are used to determine the intensity of treatment given to individual patients. Surgical intervention plays a very important role in the management of residual disease at the completion of chemotherapy. Recognition of the growing teratoma syndrome and the importance of early surgical excision is illustrated by this case. Isolated CNS relapse may occur because the CNS may act as a sanctuary site in patients receiving systemic chemotherapy, but does not preclude long term disease free survival.
- Published
- 1995
- Full Text
- View/download PDF
18. Immuno-, lectin-, and enzyme-histochemical characterization of human bone marrow endothelium.
- Author
-
Masek LC, Sweetenham JW, Whitehouse JM, and Schumacher U
- Subjects
- Alkaline Phosphatase analysis, Alkaline Phosphatase antagonists & inhibitors, Antibodies, Monoclonal, Arsenates pharmacology, Bone Marrow chemistry, Edetic Acid pharmacology, Endothelium, Vascular chemistry, Endothelium, Vascular cytology, Histocytochemistry, Humans, Immunoenzyme Techniques, Immunohistochemistry, Lectins, Levamisole pharmacology, Lysine pharmacology, Oligopeptides pharmacology, von Willebrand Factor analysis, Bone Marrow blood supply, Plant Lectins
- Abstract
"Homing" of hematopoietic progenitor cells to the bone marrow occurs during the clinical practice of bone marrow transplantation. Its mechanism is unknown, although adhesive interactions between hematopoietic cells and sinusoidal endothelium in the bone marrow may be implicated. Studies of human bone marrow endothelial cells have previously been limited by the lack of markers for these cells. In this report, we describe positive staining of bone marrow endothelial cells from human bone marrow trephine biopsies with antibody to factor VIII-related antigen (FVIIIR-Ag) (Dako, High Wycombe, UK), the plant lectin Ulex europaeus agglutinin-I (UEA-I), and two mouse monoclonal antibodies, BMA120 and QBEND/10. In addition, alkaline phosphatase could be demonstrated in the majority of marrow endothelial cells using a novel enzyme histochemical technique. These studies defined the marker profile of human marrow endothelium. The results of this study will facilitate the isolation and culture of human marrow endothelial cells for in vitro studies of their roles in hematopoietic stem cell homing.
- Published
- 1994
19. CAPE/PALE salvage chemotherapy for Hodgkin's disease patients relapsing within 1 year of ChlVPP chemotherapy.
- Author
-
Fairey AF, Mead GM, Jones HW, Sweetenham JW, and Whitehouse JM
- Subjects
- Adult, Aged, Antineoplastic Combined Chemotherapy Protocols adverse effects, Chlorambucil administration & dosage, Cyclophosphamide administration & dosage, Doxorubicin administration & dosage, Etoposide administration & dosage, Female, Follow-Up Studies, Hodgkin Disease mortality, Hodgkin Disease pathology, Humans, Lomustine administration & dosage, Male, Middle Aged, Neoplasm Staging, Prednisolone administration & dosage, Procarbazine administration & dosage, Prognosis, Remission Induction, Survival Rate, Vinblastine administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Hodgkin Disease drug therapy, Salvage Therapy
- Abstract
Background: Patients with advanced Hodgkin's disease failing to achieve complete remission with chemotherapy or developing disease progression within 1 year have a poor prognosis with salvage chemotherapy., Patients and Methods: Twenty-five patients fulfilling the above criteria after failing treatment with ChlVPP (chlorambucil, vinblastine, procarbazine and prednisolone) or its variant were treated with a new salvage regimen CAPE/PALE (cyclophosphamide, adriamycin, prednisolone, etoposide and lomustine), given for 6 courses at three weekly intervals., Results: Thirteen of the 25 patients (52%) achieved complete remission. After a minimum follow-up period of 38 months five of these patients remained free from disease progression. This regimen was very well tolerated., Conclusions: CAPE/PALE produces results comparable to other salvage regimens in Hodgkin's disease. New strategies are however required for this patient group.
- Published
- 1993
- Full Text
- View/download PDF
20. Prednisolone, cytosine arabinoside, lomustine (CCNU), etoposide and thioguanine (PACET) combination chemotherapy for relapsed or refractory non-Hodgkin lymphoma.
- Author
-
Sweetenham JW, McKendrick JJ, Mead GM, and Whitehouse JM
- Subjects
- Adult, Aged, Antineoplastic Combined Chemotherapy Protocols adverse effects, Cytarabine administration & dosage, Etoposide administration & dosage, Female, Humans, Lomustine administration & dosage, Male, Middle Aged, Neutropenia chemically induced, Prednisolone administration & dosage, Prognosis, Prospective Studies, Thioguanine administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Lymphoma, Non-Hodgkin drug therapy
- Abstract
27 patients with relapsed/refractory non-Hodgkin lymphoma (NHL) received combination chemotherapy with prednisolone, cytosine arabinoside, lomustine (CCNU), etoposide and thioguanine (PACET). 25 patients are evaluable for response. 7 (26%) obtained a complete response and one (4%) a partial response. The median survival for the entire group was 6 months. 2 patients are currently alive without disease, 1 of whom has received further therapy. The regimen was intensely myelosuppressive, but was well tolerated. The complete response rate and median survival figures are comparable to previous studies of salvage therapy confirming the poor prognosis for relapsed NHL and emphasising the need for prospective randomised studies.
- Published
- 1993
- Full Text
- View/download PDF
21. Adult lymphoblastic lymphoma: high incidence of central nervous system relapse in patients treated with the Stanford University protocol.
- Author
-
Sweetenham JW, Mead GM, and Whitehouse JM
- Subjects
- Adolescent, Adult, Asparaginase therapeutic use, Cyclophosphamide therapeutic use, Doxorubicin therapeutic use, Humans, Methotrexate therapeutic use, Middle Aged, Prednisolone therapeutic use, Recurrence, Remission Induction, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Brain Neoplasms secondary, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy
- Abstract
Twelve adult patients with non-leukaemic lymphoblastic lymphoma were treated with combination chemotherapy and central nervous system prophylaxis according to the protocol developed at Stanford University. Despite strict adherence to the Stanford protocol, 4 of 12 patients relapsed in the CNS, all with meningeal disease. Only four of the 12 patients are in continuing complete remission 6 to 88 months from the completion of induction therapy. These results are inferior to those previously reported for this regimen, and fail to confirm the high rate of control of CNS disease.
- Published
- 1992
- Full Text
- View/download PDF
22. Intensive weekly combination chemotherapy for patients with intermediate-grade and high-grade non-Hodgkin's lymphoma.
- Author
-
Sweetenham JW, Mead GM, and Whitehouse JM
- Subjects
- Adult, Aged, Antineoplastic Combined Chemotherapy Protocols adverse effects, Bleomycin administration & dosage, Central Nervous System Neoplasms prevention & control, Cyclophosphamide administration & dosage, Doxorubicin administration & dosage, Drug Administration Schedule, Etoposide adverse effects, Female, Humans, Leucovorin administration & dosage, Male, Methotrexate administration & dosage, Middle Aged, Neoplasm Staging, Prednisone administration & dosage, Survival Analysis, Vincristine administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Etoposide administration & dosage, Lymphoma, Non-Hodgkin drug therapy
- Abstract
High response and overall survival rates have been reported for second- and third-generation combination chemotherapy regimens used in the treatment of advanced intermediate- and high-grade non-Hodgkin's lymphoma (NHL). Results with methotrexate with leucovorin, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B) chemotherapy have been particularly impressive, although this regimen produces considerable toxicity. We have devised a similar regimen, which differs from previously reported weekly regimens in that it includes etoposide given at 14-day intervals. The doses of methotrexate and prednisolone were lower in our regimen than those used in MACOP-B. Alternating cycles of cyclophosphamide, doxorubicin, and etoposide (week 1) and methotrexate, bleomycin, and vincristine (week 2) were given for a total of 12 weeks, with continuous oral prednisolone and prophylactic antibiotics. We report here the first 61 patients entered onto this study. The overall response rate is 84% (57% complete remission [CR], 27% partial remission [PR]). With a median follow-up of 32 months for surviving patients, the actuarial overall survival at 3 years is 47%, and the failure-free survival is 45%. The dose-limiting toxicity of this regimen was mucositis. Five deaths occurred during chemotherapy, two of which were due to sepsis. The dose intensities of cyclophosphamide and doxorubicin in this regimen are considerably lower than those in MACOP-B. However, because of the inclusion of etoposide, the projected average relative dose intensity for our regimen is higher than that for MACOP-B. Our regimen has produced inferior results to those reported for MACOP-B. This may be because the addition of etoposide has failed to compensate for the lower doses of doxorubicin and cyclophosphamide. Alternatively, it may reflect differences in the presenting features of the patient populations.
- Published
- 1991
- Full Text
- View/download PDF
23. Life-threatening airway obstruction at the presentation of Hodgkin's disease.
- Author
-
Jeffery GM, Mead GM, and Whitehouse JM
- Subjects
- Adult, Female, Hodgkin Disease diagnosis, Hodgkin Disease therapy, Humans, Male, Airway Obstruction etiology, Hodgkin Disease complications
- Abstract
Mediastinal involvement from Hodgkin's disease is common. Significant symptoms resulting from disease at this site are less common and only rarely does severe airway obstruction occur. The authors report six cases of Hodgkin's disease in which life-threatening airway obstruction was a major feature of the clinical presentation and early clinical course. The literature describing this complication is reviewed. General anesthesia with endobronchial intubation should be avoided if at all possible in patients with airway obstruction and alternative methods of diagnosis and management are discussed.
- Published
- 1991
- Full Text
- View/download PDF
24. Results of the first ESMO examination in medical oncology, London 1989.
- Author
-
Alberto P, Mermillod B, Cocconi PG, Schneider M, Seeber S, Wagener DJ, Whitehouse JM, and Cortes-Funes H
- Subjects
- Europe, London, Certification, Educational Measurement, Medical Oncology
- Abstract
Since 1989, a Certification in Medical Oncology is offered to ESMO members on the basis of their professional curriculum vitae and of their scores in a multiple choice examination. The first session took place in London, U.K., in September 1989, during ECCO 5. One hundred and twenty-five ESMO members were evaluated by means of 60 multiple choice questions covering various aspects of medical oncology, such as tumor diagnosis, prognosis and treatment, drug pharmacology and toxicity, histology and cytology, epidemiology, carcinogenesis and tumor biology. The mean percent of correct answers was 77.4. The best results were obtained with questions dealing with chemotherapy. Scores of 40% or less were obtained in 8 questions, including 2 questions on AIDS related tumors. A similar examination is available in 1990 and will be prepared yearly in the future. It is hoped that this European ESMO Certification will contribute to lessen the professional discrepancies between oncologists of European countries and improve the level of oncological training in Europe.
- Published
- 1991
- Full Text
- View/download PDF
25. Tactile detection of slip: surface microgeometry and peripheral neural codes.
- Author
-
Srinivasan MA, Whitehouse JM, and LaMotte RH
- Subjects
- Animals, Humans, Macaca fascicularis, Mathematics, Psychophysics, Fingers, Motion Perception physiology, Peripheral Nerves physiology, Skin anatomy & histology, Touch physiology
- Abstract
1. The role of the microgeometry of planar surfaces in the detection of sliding of the surfaces on human and monkey fingerpads was investigated. By the use of a servo-controlled tactile stimulator to press and stroke glass plates on passive fingerpads of human subjects, the ability of humans to discriminate the direction of skin stretch caused by friction and to detect the sliding motion (slip) of the plates with or without micrometer-sized surface features was determined. To identify the associated peripheral neural codes, evoked responses to the same stimuli were recorded from single, low-threshold mechanoreceptive afferent fibers innervating the fingerpads of anesthetized macaque monkeys. 2. Humans could not detect the slip of a smooth glass plate on the fingerpad. However, the direction of skin stretch was perceived based on the information conveyed by the slowly adapting afferents that respond differentially to the stretch directions. Whereas the direction of skin stretch signaled the direction of impending slip, the perception of relative motion between the plate and the finger required the existence of detectable surface features. 3. Barely detectable micrometer-sized protrusions on smooth surfaces led to the detection of slip of these surfaces, because of the exclusive activation of rapidly adapting fibers of either the Meissner (RA) or the Pacinian (PC) type to specific geometries of the microfeatures. The motion of a smooth plate with a very small single raised dot (4 microns high, 550 microns diam) caused the sequential activation of neighboring RAs along the dot path, thus providing a reliable spatiotemporal code. The stroking of the plate with a fine homogeneous texture composed of a matrix of dots (1 microns high, 50 microns diam, and spaced at 100 microns center-to-center) induced vibrations in the fingerpad that activated only the PCs and resulted in an intensive code. 4. The results show that surprisingly small features on smooth surfaces are detected by humans and lead to the detection of slip of these surfaces, with the geometry of the microfeatures governing the associated neural codes. When the surface features are of sizes greater than the response thresholds of all the receptors, redundant spatiotemporal and intensive information is available for the detection of slip.
- Published
- 1990
- Full Text
- View/download PDF
26. High dose intensity combination chemotherapy for advanced epithelial ovarian carcinoma: results of a pilot study.
- Author
-
Sweetenham JW, McKendrick JJ, Jones DH, Whitehouse JM, and Williams CJ
- Subjects
- Adult, Aged, Antineoplastic Combined Chemotherapy Protocols adverse effects, Cisplatin administration & dosage, Creatinine urine, Cyclophosphamide administration & dosage, Female, Humans, Middle Aged, Neutropenia chemically induced, Peripheral Nervous System Diseases chemically induced, Randomized Controlled Trials as Topic, Retrospective Studies, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Ovarian Neoplasms drug therapy
- Abstract
Retrospective studies have recently demonstrated a significant correlation between dose intensity of chemotherapy and response rates and survival in various diseases including epithelial ovarian carcinoma. As part of a proposed randomised trial to assess the effect of dose intensity on outcome in ovarian carcinoma, a pilot study has been undertaken to determine the toxicity and efficacy of the high intensity therapy. Nineteen patients with advanced ovarian carcinoma received initial treatment with cisplatin 120 mg m-2 i.v. day 1, and cyclophosphamide 1,000 mg-2 i.v. day 1, given at 21-day intervals for six cycles. The average relative dose intensity of this therapy is 1.14 when compared with the CHAP regimen. Severe toxicity was experienced by most patients. The median received average relative dose intensity was 0.90, with only one patient receiving treatment to the proposed intensity. Randomised studies of the effect of dose intensity in ovarian carcinoma are essential, but an initial step must be to assess whether the proposed high dose treatment can be delivered.
- Published
- 1990
- Full Text
- View/download PDF
27. ChlVPP chemotherapy in advanced Hodgkin's disease.
- Author
-
McKendrick JJ, Mead GM, Sweetenham J, Jones DH, Williams CJ, Ryall R, and Whitehouse JM
- Subjects
- Adult, Antineoplastic Combined Chemotherapy Protocols adverse effects, Chlorambucil administration & dosage, Chlorambucil adverse effects, Female, Humans, Male, Prednisolone administration & dosage, Prednisolone adverse effects, Procarbazine administration & dosage, Procarbazine adverse effects, Vinblastine administration & dosage, Vinblastine adverse effects, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Hodgkin Disease drug therapy
- Abstract
Between March 1978 and January 1987 54 patients with advanced Hodgkin's disease (HD) or relapse following radiotherapy (RT) for Hodgkin's disease have been treated with combination chemotherapy consisting of chlorambucil, vinblastine, procarbazine and prednisolone (ChlVPP). A subgroup of five patients with bulky mediastinal disease received mantle RT in addition to ChlVPP chemotherapy. Forty-two patients (77.8%) entered complete remission with 33 (61.0%) remaining in unmaintained remission and 44 (81.5%) alive at a median follow up of 51 months (range: 22-103). The treatment was generally well tolerated with minimal toxicity. ChlVPP is effective first-line treatment for Hodgkin's disease with results which may be comparable to those achieved for MOPP but with significantly less toxicity.
- Published
- 1989
- Full Text
- View/download PDF
28. Antitubulin antibody in healthy adults and patients with infectious mononucleosis and its relationship to smooth muscle antibody (SMA).
- Author
-
Mead GM, Cowin P, and Whitehouse JM
- Subjects
- Adolescent, Adult, Aged, Animals, Child, Child, Preschool, Chromatography, Affinity, Electrophoresis, Polyacrylamide Gel, Fluorescent Antibody Technique, Humans, Immunoglobulin G immunology, Immunoglobulin M immunology, Middle Aged, Radioimmunoassay, Rats, Antibodies analysis, Infectious Mononucleosis immunology, Muscle, Smooth immunology, Tubulin immunology
- Abstract
Antibody to tubulin in man has been studied using a specific radioimmunoassay, affinity chromatography radioimmunoassay but markedly increased levels were noted in patients with infectious mononucleosis where the antibody was predominantly IgM in type. This finding was confirmed on fluorescence microscopy. Affinity chromatography purified antibody produced characteristic microtubular staining of fixed 3T3 cells, but in addition, produced weak staining of cryostat sections of rat tissue, similar in distribution to that of smooth muscle antibody. Our studies indicate that the IgM smooth muscle antibody found in infectious mononucleosis by IF techniques is at least in part due to an antitubulin antibody.
- Published
- 1980
29. Combination chemotherapy using high or low dose methotrexate for small cell carcinoma of the lung--a randomised trial.
- Author
-
Arnold AM, Williams CJ, Mead GM, Buchanan RB, Green JA, Macbeth FM, and Whitehouse JM
- Subjects
- Aged, Antineoplastic Combined Chemotherapy Protocols adverse effects, Clinical Trials as Topic, Female, Humans, Male, Middle Aged, Random Allocation, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Carcinoma, Small Cell drug therapy, Lung Neoplasms drug therapy, Methotrexate administration & dosage
- Abstract
Eighty-three patients with histologically proven small cell carcinoma of the lung were entered into a prospective randomised clinical trial to evaluate two induction regimes. A 'low' dose methotrexate regime which employed three cycles of etoposide, adriamycin and methotrexate given at conventional dosage was compared with a regime which employed three cycles of etoposide and adriamycin together with five courses of high dose methotrexate and folinic acid rescue. All patients achieving a complete response (CR) received prophylactic cranial irradiation. Patients with limited disease who achieved a CR received additional radiotherapy to the primary site. An alternative four drug regime (procarbazine, vincristine, cyclophosphamide and CCNU) was evaluated in patients failing to achieve or subsequently relapsing from a complete response. Response rates for the low dose and high dose methotrexate arms were 54 and 55% respectively with median survivals of 8.6 and 9.7 months. Median survival for complete and partial responders was 20.2 and 11 months respectively. The alternative four drug regime showed limited activity in patients failing to achieve a complete response after primary therapy. We conclude that high dose methotrexate as used in this study has no role in small cell lung cancer. The 'low' dose regime was well tolerated by outpatients, is effective and is suitable for generalised use in the palliation of small cell lung cancer.
- Published
- 1984
- Full Text
- View/download PDF
30. Cytotoxic drugs for non-neoplastic disease.
- Author
-
Whitehouse JM
- Subjects
- Antineoplastic Agents adverse effects, Arthritis, Rheumatoid drug therapy, Bone Marrow Diseases chemically induced, Humans, Neoplasms chemically induced, Psoriasis drug therapy, Antineoplastic Agents therapeutic use
- Published
- 1983
- Full Text
- View/download PDF
31. Hypoplastic acute myelogenous leukaemia.
- Author
-
Beard ME, Bateman CJ, Crowther DC, Wrigley PF, Whitehouse JM, Fairley GH, and Scott RB
- Subjects
- Adult, Aged, Cytarabine therapeutic use, Daunorubicin therapeutic use, Female, Humans, Immunotherapy, Leukemia, Myeloid, Acute blood, Leukemia, Myeloid, Acute therapy, Male, Middle Aged, Remission, Spontaneous, Leukemia, Myeloid, Acute pathology
- Abstract
The clinical course, diagnosis and management of nine cases of hypoplastic acute myelogenous leukaemia are described. Such cases may follow a slowly progressive course and should not receive anti-leukaemic chemotherapy unless the disease is advancing rapidly or unless some specific complication develops. If chemotherapy has to be given, usually because of severe and recurrent infections, then prompt and prolonged remission of disease may occur.
- Published
- 1975
- Full Text
- View/download PDF
32. Interaction of VP16-213 with the DNA repair antagonist chloroquine.
- Author
-
Arnold AM and Whitehouse JM
- Subjects
- Animals, Chloroquine toxicity, Drug Interactions, Etoposide toxicity, Female, Lymphoma metabolism, Mice, Mice, Inbred CBA, Neoplasms, Experimental metabolism, Vincristine metabolism, Chloroquine pharmacology, DNA Repair drug effects, Etoposide pharmacology, Podophyllotoxin analogs & derivatives
- Published
- 1982
- Full Text
- View/download PDF
33. Treating ovarian cancer.
- Author
-
Sweetenham JW, Mead GM, Whitehouse JM, and Williams CJ
- Subjects
- Carboplatin, Female, Humans, Antineoplastic Agents therapeutic use, Cisplatin therapeutic use, Organoplatinum Compounds therapeutic use, Ovarian Neoplasms drug therapy
- Published
- 1986
- Full Text
- View/download PDF
34. Comparison of combined and single-agent chemotherapy in non-Hodgkin's lymphoma of favourable histological type.
- Author
-
Lister TA, Cullen MH, Beard ME, Brearley RL, Whitehouse JM, Wrigley PF, Stansfeld AG, Sutcliffe SB, Malpas JS, and Crowther D
- Subjects
- Adult, Aged, Antineoplastic Agents therapeutic use, Chlorambucil therapeutic use, Cyclophosphamide therapeutic use, Drug Therapy, Combination, Female, Humans, Lymphoma mortality, Lymphoma pathology, Male, Middle Aged, Neoplasm Staging, Prednisolone therapeutic use, Remission, Spontaneous, Vincristine therapeutic use, Antineoplastic Agents administration & dosage, Lymphoma drug therapy
- Abstract
Sixty-six untreated patients with advanced non-Hodgkin's lymphoma of favourable histological type were allocated alternately to initial treatment with cyclophosphamide, vincristine, and prednisolone or with chlorambucil. The complete remission rate was higher in the group receiving combination chemotherapy, but the overall response rate was the same for both groups. The mean duration of complete remission was the same as that of good partial remission, and was the same for both treatments. The duration of remission was influenced by histological type and extent of disease at presentation, but not age. Those who responded to the initial treatment (whether with complete or with good partial remission) survived significantly longer than did non-responders. It is concluded that neither treatment is satisfactory and that new treatment programmes are needed for patients with a favourable prognosis, especially young patients with extensive disease.
- Published
- 1978
- Full Text
- View/download PDF
35. Chemotherapy and immunotherapy for acute myelogenous leukemia.
- Author
-
Lister TA, Whitehouse JM, Oliver RT, Bell R, Johnson SA, Wrigley PF, Ford JM, Cullen MH, Gregory W, Paxton AM, and Malpas JS
- Subjects
- Adolescent, Adult, BCG Vaccine therapeutic use, Blood Transfusion, Child, Drug Therapy, Combination, Female, Humans, Immunotherapy, Lymphocyte Transfusion, Male, Middle Aged, Prognosis, Leukemia, Myeloid, Acute immunology, Leukemia, Myeloid, Acute therapy
- Abstract
Eighty-six consecutive untreated adults with acute myelogenous leukemia were treated with a combination of Adriamycin, vincristine, prednisolone, Cytosine Arabinoside, and BCG. Complete remission was achieved in 39 (45%) patients; these patients were then allocated on an alternate basis to receive BCG and monthly chemotherapy with or without weekly irradiated allogeneic blast cells. The median duration of remission was eight months and was the same for both groups. The median survival of those achieving complete remission was 19 months compared with two months for those not achieving complete remission. Nine patients are still alive without relapse and five of these patients have been disease free for more than three years.
- Published
- 1980
- Full Text
- View/download PDF
36. Immunotherapy for acute myelogenous leukaemia: a controlled clinical study 2 1/2 years after entry of the last patient.
- Author
-
Powles RL, Russell J, Lister TA, Oliver T, Whitehouse JM, Malpas J, Chapuis B, Crowther D, and Alexander P
- Subjects
- Adolescent, Adult, Aged, Clinical Trials as Topic, Female, Humans, Leukemia, Myeloid, Acute drug therapy, Leukemia, Myeloid, Acute immunology, Male, Middle Aged, Prognosis, Remission, Spontaneous, Time Factors, BCG Vaccine therapeutic use, Leukemia, Myeloid, Acute therapy
- Abstract
One hundred and thirty-nine untreated patients with acute myelogenous leukaemia (AML) were admitted between August 1970 and December 1973 and allocated into two remission treatment regimens: one to receive chemotherapy alone and the other chemotherapy with immunotherapy. Of the patients who attained remission. 22 were in the chemotherapy group and in September 1975 2 remained alive, the median survival time being 270 days and after relapse 75 days. Twenty-eight patients received immunotherapy during remission, and 5 remained alive; the median survival time of the group being 510 days and after relapse 165 days. Ongoing acturial analysis precisely predicted early in the study the median survival of the two groups, but it took a 2-year follow-up after entry of the last patient before it became clear that there were very few long-term survivors. The increase in survival time produced by the immunotherapy is apparently made up of two components: prolongation of the first remission and length of survival after the first relapse. It must be notted that the chemotherapy for this study was devised 6 years ago and the results of the control arm (chemotherapy alone) may be poorer than those obtained in contemporary studies.
- Published
- 1977
- Full Text
- View/download PDF
37. Cisplatin, adriamycin and cyclophosphamide (PACe) combination chemotherapy in patients with ovarian carcinoma resistant to chlorambucil.
- Author
-
Mead GM, Williams CJ, and Whitehouse JM
- Subjects
- Alopecia chemically induced, Antineoplastic Combined Chemotherapy Protocols adverse effects, Cisplatin administration & dosage, Cyclophosphamide administration & dosage, Doxorubicin administration & dosage, Drug Resistance, Female, Fever chemically induced, Hematologic Diseases chemically induced, Humans, Middle Aged, Nausea chemically induced, Neoplasm Staging, Ovarian Neoplasms pathology, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Chlorambucil therapeutic use, Ovarian Neoplasms drug therapy
- Abstract
Twenty patients with stage III or IV ovarian carcinoma refractory to chlorambucil were treated with IV cisplatin, adriamycin and cyclophosphamide. Two patients achieved CR and four PR, giving an overall response rate of 30%. All patients have since died at 0-18 (median 8) months. Use of this region was associated with marked toxicity, including three drug-related deaths. Second-time drug combinations should be regarded as experimental, and they should probably only be used in selected patients outside of clinical trials.
- Published
- 1985
- Full Text
- View/download PDF
38. Second malignancy after cisplatin, vinblastine, and bleomycin (PVB) chemotherapy: a case report.
- Author
-
Mead GM, Green JA, Macbeth FR, Williams CJ, Whitehouse JM, and Buchanan R
- Subjects
- Adult, Drug Therapy, Combination, Humans, Male, Antineoplastic Combined Chemotherapy Protocols, Bleomycin administration & dosage, Carcinoma, Transitional Cell, Cisplatin administration & dosage, Neoplasms, Multiple Primary, Teratoma drug therapy, Testicular Neoplasms drug therapy, Urinary Bladder Neoplasms, Vinblastine administration & dosage
- Published
- 1983
39. Antiemetics for patients treated with antitumor chemotherapy.
- Author
-
Williams CJ, Bolton A, de Pemberton R, and Whitehouse JM
- Subjects
- Adolescent, Adult, Aged, Cyclizine administration & dosage, Dronabinol administration & dosage, Dronabinol analogs & derivatives, Drug Therapy, Combination, Female, Humans, Male, Metoclopramide administration & dosage, Middle Aged, Nausea chemically induced, Nausea drug therapy, Neoplasms drug therapy, Pilot Projects, Vomiting chemically induced, Antiemetics administration & dosage, Cisplatin adverse effects, Vomiting drug therapy
- Abstract
The clinical efficacy of antiemetic drugs was tested in cancer patients who were given a placebo and two antiemetic drugs alone and in combination according to random sequences. The method of investigation allowed assessment of the antiemetic effect and side effects of each drug or combination of drugs using a minimum number of patients. The trial design takes into account carry-over effects and biased selection and is potentially useful in the study of drug side effects. Fifteen patients received cyclizine, metoclopramide, cyclizine and metoclopramide, or placebo in a random sequence without evidence that the drugs tested were better than the placebo. A combination of Nabilone and metoclopramide was used in an unrandomized pilot study (prior to the withdrawal of Nabilone from clinical use); these patients recorded better scores for nausea and vomiting and patient acceptability than those in the randomized study. Present antiemetics remain inadequate and although cannabinol derivatives show an improved antiemetic effect, they cause moderate side effects themselves.
- Published
- 1980
40. Auto-antibodies in malignant disease.
- Author
-
Whitehouse JM and Fairley G
- Subjects
- Adenocarcinoma immunology, Antigens, Antigens, Neoplasm, Breast Neoplasms immunology, Bronchial Neoplasms immunology, Carcinoma immunology, Female, Fetus immunology, Fluorescent Antibody Technique, Humans, Immunoglobulin G, Immunoglobulin M, Lung immunology, Melanoma immunology, Neuroblastoma immunology, Ovarian Neoplasms immunology, Antibodies, Neoplasm, Autoantibodies, Neoplasms immunology
- Published
- 1973
41. Hodgkin's disease occurring during acute leukaemia in remission.
- Author
-
Woodruff RK, Lister TA, Brearley RL, Stansfeld, Whitehouse JM, Malpas JS, Sutcliffe SB, Thompson EI, and Aur RJ
- Subjects
- Adolescent, Adult, Child, Female, Hodgkin Disease pathology, Humans, Immunosuppression Therapy adverse effects, Leukemia, Lymphoid therapy, Lymph Nodes pathology, Remission, Spontaneous, Hodgkin Disease etiology, Leukemia, Lymphoid complications
- Abstract
Three patients with acute lymphoblastic leukaemia are reported in whom Hodgkin's disease developed during chemotherapy-maintained remission. This association has been reported only once before. The pathogenesis of the Hodgkin's disease in these patients is discussed, including the possible role of anti-leukaemic therapy.
- Published
- 1977
- Full Text
- View/download PDF
42. Correlations between clonogenicity and prognostic factors in human breast cancer.
- Author
-
Smallwood JA, Morgan GR, Cooper A, Kirkham N, Williams CJ, Whitehouse JM, and Taylor I
- Subjects
- Breast Neoplasms metabolism, Clone Cells pathology, Female, Humans, Prognosis, Receptors, Estrogen analysis, Thymidine metabolism, Breast Neoplasms pathology
- Abstract
The pursuit of more effective systemic treatments in breast cancer has been limited by a failure to maintain or grow tumour cells in vitro. This study reports our experience in obtaining clonogenic growth in 54 primary breast cancers obtained at mastectomy. Of 47 assays free of infection, clonogenic growth was achieved in 22 (41 per cent). Only 5 of 23 oestrogen receptor positive tumours grew compared to 14 of 21 oestrogen receptor negative tumours chi 2 = 9.03; P less than 0.01). None of the 5 cytosolic receptor positive tumours contained a nuclear receptor for oestrogen. Growth was not related to tumour stage, menopausal status, age or histological grade. Receptor negative tumours had higher thymidine labelling indices, but these were no different to the tumours grown in the assay.
- Published
- 1984
- Full Text
- View/download PDF
43. Measurement of antibodies to tubulin by radioimmunoassay.
- Author
-
Mead GM, Cowin P, and Whitehouse JM
- Subjects
- Animals, Antibody Specificity, Binding Sites, Antibody, Binding, Competitive, Cattle, Humans, Immunoglobulin Fc Fragments immunology, Immunoglobulin gamma-Chains immunology, Immunoglobulin mu-Chains immunology, Radioimmunoassay, Sheep, Tubulin isolation & purification, Antibodies, Tubulin immunology
- Abstract
A solid-phase double antibody radioimmunoassay capable of measuring antibody to tubulin, the principal component of microtubules, is described. This assay is simple, combining sensitivity with specificity and also allowing determination of antibody subclasses.
- Published
- 1979
- Full Text
- View/download PDF
44. Small-cell lung cancer.
- Author
-
Mead GM, Arnold AM, Green JA, Williams CJ, and Whitehouse JM
- Subjects
- Evaluation Studies as Topic, Carcinoma, Small Cell drug therapy, Lung Neoplasms drug therapy
- Published
- 1980
- Full Text
- View/download PDF
45. Extensive stage small cell carcinoma of the bronchus. A randomised study of etoposide given orally by one-day or five-day schedule together with intravenous adriamycin and cyclophosphamide.
- Author
-
Mead GM, Thompson J, Sweetenham JW, Buchanan RB, Whitehouse JM, and Williams CJ
- Subjects
- Administration, Oral, Adult, Cyclophosphamide administration & dosage, Doxorubicin administration & dosage, Drug Administration Schedule, Etoposide administration & dosage, Female, Humans, Injections, Intravenous, Male, Middle Aged, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Bronchial Neoplasms drug therapy, Carcinoma, Small Cell drug therapy
- Abstract
Fifty-four patients whose disease had been staged as extensive small cell carcinoma of the bronchus were randomised to receive either CAV1 (cyclophosphamide 600 mg m-2 i.v., adriamycin 50 mg m-2 i.v., given on day 1, and etoposide 500 mg m-2 p.o. given on day 3) or CAV5 (cyclophosphamide and adriamycin given as for CAV1, etoposide 500 mg m-2 given in divided dose over days 3-7) on a 21-day schedule. The two regimens proved comparable (CR + PR 55% vs 56%), and the survival curves were virtually superimposable (median survival: CAV1, 8 months; CAV5, 9 months). Only five patients are still alive. The toxicity of the two treatments was similar. The scheduling of etoposide over 1 or 5 days seemed clinically unimportant in this study, perhaps because of concurrent use of other effective chemotherapy drugs.
- Published
- 1987
- Full Text
- View/download PDF
46. Combination chemotherapy for haematological relapse in adult acute lymphoblastic leukaemia (ALL).
- Author
-
Woodruff RK, Lister TA, Paxton AM, Whitehouse JM, and Malpas JS
- Subjects
- Adolescent, Adult, Drug Therapy, Combination, Female, Humans, Male, Recurrence, Asparaginase therapeutic use, Doxorubicin therapeutic use, Leukemia, Lymphoid drug therapy, Prednisolone therapeutic use, Vincristine therapeutic use
- Published
- 1978
- Full Text
- View/download PDF
47. Combination chemotherapy for acute lymphoblastic leukaemia in adults.
- Author
-
Lister TA, Whitehouse JM, Beard ME, Brearley RL, Wrigley PF, Oliver RT, Freeman JE, Woodruff RK, Malpas JS, Paxton AM, and Crowther D
- Subjects
- Adolescent, Adult, Aged, Asparaginase adverse effects, Asparaginase therapeutic use, Central Nervous System Diseases radiotherapy, Doxorubicin therapeutic use, Drug Therapy, Combination, Female, Humans, Male, Methotrexate therapeutic use, Middle Aged, Prednisolone therapeutic use, Remission, Spontaneous, Vincristine therapeutic use, Antineoplastic Agents therapeutic use, Leukemia, Lymphoid drug therapy
- Abstract
Fifty-one adults with acute lymphoblastic leukaemia were entered into a trial of intense initial chemotherapy and early "prophylaxis" of the central nervous system (CNS). Initial treatment with OPAL (Oncovin (vincristine), prednisolone, adriamycin (doxorubicin), and L-asparaginase (colaspase)) followed by craniospinal or cranial irradiation and intrathecal methotrexate produced remission in 36 patients (71%). Seventeen of these patients relapsed three to 18 months after the start of remission; the remainder had been in remission for 12 to 52 months by the end of the study. The predicted median duration of complete remission was 18.5 months. None of the four patients who initially had clinical evidence of CNS disease, three of whom also had leukaemic cells identical to those found in Burkitt's lymphoma, achieved remission. Those patients who initially had hepatomegaly or splenomegaly had a shorter remission than those without. The predicted median survival was 27 months in those who achieved complete remission, one month in those who did not, and 21 months overall. The addition of colaspase and doxorubicin to vincristine and prednisolone and the use of early CNS treatment clearly improved the remission rate among adults with acute lymphoblastic leukaemia, though the presence and length of remission was affected by the extent of disease at presentation. Burkitt-like leukaemia, which had a poor prognosis, is probably a separate disease and may benefit from a different therapeutic approach.
- Published
- 1978
- Full Text
- View/download PDF
48. Bilateral testicular germ cell tumours: an increasing incidence and prevention by chemotherapy.
- Author
-
Thompson J, Williams CJ, Whitehouse JM, and Mead GM
- Subjects
- Adult, Cisplatin administration & dosage, Dysgerminoma prevention & control, Humans, Male, Middle Aged, Neoplasm Metastasis, Neoplasms, Germ Cell and Embryonal epidemiology, Teratoma prevention & control, Testicular Neoplasms epidemiology, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Neoplasms, Germ Cell and Embryonal prevention & control, Testicular Neoplasms prevention & control
- Abstract
Of 120 patients with germ cell tumours of the testis, 6 (5%) developed contralateral tumours; 63 patients received cisplatin-based combination chemotherapy for metastatic disease and none developed contralateral disease. By contrast, of 57 patients treated with orchiectomy alone or abdominal radiotherapy, 5 (8.8%) developed contralateral disease.
- Published
- 1988
- Full Text
- View/download PDF
49. Burkitt's lymphoma in British adults: clinical features and response to chemotherapy.
- Author
-
Brearley RL, Lister TA, Whitehouse JM, and Stansfeld AG
- Subjects
- Adolescent, Adult, Age Factors, Burkitt Lymphoma diagnosis, Female, Humans, Male, United Kingdom, Burkitt Lymphoma therapy
- Abstract
Eight British adults with tumours histologically and cytochemically identical to African Burkitt's lymphoma are described. In each case there was an acute clinical onset and similar tumour distribution, with involvement of the intra-abdominal organs, bone marrow and central nervous system. Jaw tumours were only present in 3 cases, and were never gross. Four patients presented as acute leukaemia. Combination chemotherapy and cranial irradiation were used to eradicate disease, but complete remissions were obtained in only 3 patients, and survival of over 1 year in only 2. The remainder died with disease present, less than 5 months from diagnosis.
- Published
- 1977
- Full Text
- View/download PDF
50. Acute leukaemia in the elderly, remission induction versus palliative therapy.
- Author
-
Smith AG, Whitehouse JM, Roath OS, Williams CJ, and Mead GM
- Subjects
- Aged, Humans, Leukemia, Lymphoid mortality, Leukemia, Myeloid, Acute mortality, Middle Aged, Remission Induction, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Leukemia, Lymphoid drug therapy, Leukemia, Myeloid, Acute drug therapy, Palliative Care
- Published
- 1987
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.