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1.  A randomized trial comparing methotrexate and vinblastine (MV) with cisplatin, methotrexate and vinblastine (CMV) in advanced transitional cell carcinoma: results and a report on prognostic factors in a Medical Research Council study. MRC Advanced Bladder Cancer Working Party. 
British Journal of Cancer  1998;78(8):1067-1075.
Transitional cell carcinomas may arise at any site within the urinary tract and are a source of considerable morbidity and mortality. In particular, patients with metastatic disease have a poor prognosis, with less than 5% alive at 5 years. A multicentre randomized trial comparing methotrexate and vinblastine (MV) with cisplatin, methotrexate and vinblastine (CMV) in advanced or metastatic transitional cell carcinoma was conducted in the UK. From April 1991 to June 1995, 214 patients were entered by 16 centres, 108 randomized to CMV and 106 to MV. A total of 204 patients have died. The hazard ratio (relative risk of dying) was 0.68 (95% CI 0.51-0.90, P-value = 0.0065) in favour of CMV. This translates to an absolute improvement in 1-year survival of 13%, 16% in MV and 29% in CMV. The median survival for CMV and MV was 7 months and 4.5 months respectively. Two hundred and eight patients objectively progressed or died. The hazard ratio was 0.55 (95% CI 0.41-0.73, P-value = 0.0001) in favour of CMV. Two hundred and nine patients symptomatically progressed or died. The hazard ratio was 0.48 (95% CI 0.36-0.64, P-value = 0.0001) in favour of CMV. The most important pretreatment factors influencing overall survival were WHO performance status and extent of disease. These two factors were used to derive a prognostic index which could be used to categorize patients into three prognostic groups. We conclude that the addition of cisplatin to methotrexate and vinblastine should be considered in patients with transitional cell carcinoma, taking into account the increased toxicity.
PMCID: PMC2063167  PMID: 9792152
2.  Survival of patients with advanced urothelial cancer treated with cisplatin-based chemotherapy. 
British Journal of Cancer  1996;74(10):1655-1659.
The aim of the present retrospective study was to assess long-term survival after cisplatin-based chemotherapy in 398 patients with advanced urothelial transitional cell carcinoma (TCC) treated at seven international oncological units. Various combinations of cisplatin, methotrexate, vinblastine (or vincristine) and doxorubicin were used. The complete response rate according to the WHO criteria was 17%. Partial responses were obtained in 42% of the patients. The overall cancer-related 2 year and 5 year survival rates were 21% and 11% respectively. Based on multivariate analyses, a good prognosis group could be identified comprising patients with a good performance status with disease confined to lymph nodes (14%) or patients with T4b disease only. These patients had a 28% 5 year survival rate, which, in part, has to be related to post-chemotherapy consolidation treatment in patients with pelvis-confined disease (radiotherapy, 26%; total cystectomy, 11%). Fifteen patients died of chemotherapy-related complications and in 16% of the patients toxicity led to discontinuation of treatment. Modern cisplatin-based chemotherapy leads to long-term survival and cure of selected patients with advanced urothelial transitional cancer. In routine clinical practice, chemotherapy should be offered to good prognosis patients; those presenting with a good performance status and a non-metastasising T4b tumour or with metastases confined to lymph nodes. Post-chemotherapy consolidation treatment by surgery or radiotherapy should always be considered. Such chemotherapy requires oncological expertise in order to avoid unnecessary toxicity.
PMCID: PMC2074866  PMID: 8932351
3.  A phase II study of oral piritrexim in recurrent high-grade (III, IV) glioma. 
British Journal of Cancer  1995;72(3):766-768.
Piritrexim is a lipid-soluble drug which is as effective an inhibitor of dihydrofolate reductase as methotrexate. Phase I and II studies have indicated activity in some tumour types. Because of its lipophilicity we have conducted a phase II study in recurrent high-grade malignant glioma (grades III and IV). Twenty-seven patients were treated with 25 mg p.o. three times daily for five consecutive days, repeated weekly, with provision for dose escalation or reduction according to toxicity. Five patients received less than 4 weeks' treatment because of disease progression or death. Twenty-two patients were evaluable for response. One complete and one partial response was seen (duration 262+ and 241+ weeks) and 13 patients had static disease for a median duration of 13 weeks (range 7-35). The major toxicity was myelosuppression. This response rate of 9% of evaluable patients is much lower than that seen for some conventionally used drugs and we conclude that piritrexim is unlikely to be of value in the management of high-grade gliomas.
PMCID: PMC2033879  PMID: 7669591
4.  Intravenous infusions of ifosfamide/mesna and perturbation of warfarin anticoagulant control. 
Postgraduate Medical Journal  1990;66(780):860-861.
We report three patients who had serious disturbance of anticoagulant control while receiving ifosfamide/mesna-containing cytotoxic chemotherapy in association with warfarin. In view of the likely biological potentiation of warfarin by ifosfamide/mesna, close monitoring of anticoagulant control should be performed during the co-administration of these drugs.
PMCID: PMC2429713  PMID: 2129174
5.  Oral piritrexim, an effective treatment for metastatic urothelial cancer. 
British Journal of Cancer  1993;67(2):388-390.
Piritrexim is a lipid-soluble inhibitor of dihydrofolate reductase (DHFR) that enters tumour cells rapidly by passive diffusion, cannot be polyglutamated, and is as effective as methotrexate in inhibiting DHFR. Bioavailability after oral dosing is approximately 75%. We performed a phase II study with oral piritrexim in non-chemotherapy pretreated patients with metastatic urothelial cancer. Thirty-three patients were treated with 25 mg three times daily for 5 consecutive days, repeated weekly, with provision for dose escalation or reduction according to the toxicity observed. Of 29 evaluable patients, one patient achieved a complete response of 19+ weeks duration, and ten patients achieved a partial response with a median duration of 22 weeks (range 16-48), for a total response rate of 38%. Piritrexim was generally well tolerated, with myelosuppression as the major toxicity, that frequently required dose modification. We conclude that piritrexim appears to be an active agent in patients with metastatic urothelial cancer when administered as a 5-day, low-dose oral schedule. It would be attractive to investigate the combination of piritrexim and cisplatin.
PMCID: PMC1968166  PMID: 8431372
6.  Cutaneous vasculitis. 
In this paper the current concepts of cutaneous vasculitis are reviewed, with emphasis on clinical patterns, strict pathologic criteria and mechanisms of injury. A plea is made to classify vasculitis not as syndromes but (a) according to organ involvement (limited cutaneous or complicated multisystem), (b) by cause, (c) by pathologic description and (d) by anatomic depth and type of vessel involvement.
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PMCID: PMC1880353  PMID: 757382
7.  Postsplenectomy sepsis due to influenzal viremia and pneumococcemia. 
A 31-year-old man, who had undergone splenectomy 18 months previously because of hereditary spherocytosis, suddenly became ill, with fever, vomiting, epigastric pain and shock, and died 10 hours after the onset of his symptoms. Autopsy showed influenzal viremia, pneumococcemia and bilateral adrenal hemorrhage. The rapid course of the patient's illness emphasizes the serious risk of sepsis for individuals who have had a splenectomy. Anti-influenza immunization in such patients should be considered.
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PMCID: PMC1878716  PMID: 8205
8.  Clinical trial of combination chemotherapy and specific active immunotherapy in disseminated melanoma. 
British Journal of Cancer  1976;34(2):174-179.
Fifty-six patients with disseminated malignant melanoma were randomly allocated to two treatment groups. The first group C received combination chemotherapy consisting of DTIC and ICRF 159. The second group (C+I) received the same chemotherapy but were also immunized with 2 X 10(7) irradiated allogeneic melanoma cells mixed with 50 mug of percutaneous BCG. The survival rates in both treatment groups C and (C+I) were not significantly different, and only minor enhancement of the chemotherapy was found in the (C+I) group. A similar pattern of tissue response was observed in both groups: lymph node, skin and, to some extent liver metastases, respond better than other sites.
PMCID: PMC2025153  PMID: 962994
9.  Amino acid imbalance in cystinuria 
Journal of Clinical Pathology  1974;27(6):500-504.
After oral ingestion of a free amino acid mixture by three cystinuric patients, plasma increments of lysine and arginine were lower and those of many other amino acids were significantly higher than those found in control subjects.
Similar results were obtained in control subjects after amino acid imbalance had been artificially induced by the omission of cystine, lysine, and arginine from the amino acid mixture. Especially high increments of alanine and proline provided the best evidence of amino acid imbalance caused by a temporary lysine and, to a lesser extent, arginine and cystine deficit.
No such amino acid imbalance was found to occur in the cystinuric patients after ingestion of whole protein, indicating that absorption of oligopeptides produced by protein digestion provided a balanced physiological serum amino acid increment. This is considered to explain the lack of any unequivocal nutritional deficit in cystinuric patients despite poor absorption of the essential free amino acid, lysine.
PMCID: PMC478164  PMID: 4411931
11.  Coagulation studies in massive pulmonary haemorrhage of the newborn 
Journal of Clinical Pathology  1966;19(4):334-338.
Coagulation studies were performed on two newborn infants with fatal massive pulmonary haemorrhage. The first showed a reduced level of plasma fibrinogen with defective thrombin-fibrinogen reaction, corrected by protamine, and defective thromboplastin generation. In the second case, a premature infant, the fibrinogen level was normal but there was a severe defect in thromboplastin generation with evidence of an inhibitor. A relationship between the pulmonary haemorrhage and coagulation defects is suggested but not established.
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PMCID: PMC473278  PMID: 5929334
12.  Localization of plasminogen activator in neonatal lung in the presence of hyaline membrane disease 
Journal of Clinical Pathology  1965;18(5):586-587.
A case is described in which Todd's method (1959) for the histological localization of plasminogen activator was applied to neonatal lung tissue obtained at (unsuccessful) open cardiac massage. This was localized around small pulmonary veins, usually at some distance from the hyaline membrane.
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PMCID: PMC473003  PMID: 5835439

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