Cell proliferation in human tumours measured by in-vivo labelling with bromodeoxyuridine.
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Aged↗
Biomedical subjects
M H Bennett
Publications and source records attributed to M H Bennett.
Epispinal stimulation of the spinal cord: a proposed method of operative monitoring.
By monitoring spinal cord function during surgical procedures in and around the spinal cord, vital information can be obtained regarding the integrity of this structure. However, the techniques currently used have several limitations. This paper describes a system of monitoring in the cat, whereby, using electrodes placed outside the spine for stimulation of the cord, reproducible responses can be recorded from a midline electrode tapped into the calvarium overlying the sensorimotor cortex. The levels of activation of the spinal cord achieved by direct stimulation of the cord through epidural electrodes and by the epispinal method were found to be similar. By studying the effects of various lesions on the epispinal evoked response, components in the recorded response were identified that were carried in all three funiculi of the cord; the changes produced by these lesions in the epispinal evoked response were immediate. In addition, the sensitivities of the epispinal evoked response and of the somatosensory evoked response to the lesions were compared. When the dorsal blood supply was interrupted, it became evident that, unlike the somatosensory evoked response, which monitors only the dorsal blood supply, the epispinal evoked response monitors both the dorsal and ventral blood supply. By evaluating the recorded response obtained using this method of monitoring, it was possible to identify the particular quadrant of spinal cord injury.
Animals↗
Systemic disturbance in Hodgkin's disease and its relation to histopathology and prognosis (BNLI report No. 30).
Systemic disturbances in Hodgkin's disease at presentation are not only manifested by 'B' symptoms (weight loss, fever, and night sweats), but are also mirrored in the peripheral blood as raised sedimentation rate, low haemoglobin, low albumin, and abnormal lymphocyte counts. Such systemic disturbance is more common than consideration of classical 'B' symptoms alone would suggest. In a series of 840 patients, 88% had some form of systemic disturbance on these criteria. Survival after treatment was found to be closely and inversely related to the degree of systemic disturbance present before treatment. Patients with no evidence of such disturbance had an almost 100% survival at 10 years. In the absence of 'B' symptoms the sedimentation rate was the most useful prognostic blood parameter, enabling about one third of the patients to be identified as having an excellent chance of survival, and identifying a further 12% as having a survival almost identical to that of patients with 'B' symptoms. The latter patients were those with a sedimentation rate of 60 mm/h or greater, and it is suggested that the term 'Systemic Symptoms' should be broadened to include a sedimentation rate of this magnitude. The degree of malignancy of the tumour, as reflected by histopathology, plays a dominant role in determining the amount of systemic disturbance in the host. However, the amount of disturbance varies amongst individual patients with the same histopathological subtype, reflecting either differences in the malignancy of the tumour within such subtypes, or differences in the constitution of the host.
Blood Sedimentation↗
Non-Hodgkin's lymphoma of the thyroid.
Twenty-eight patients with non-Hodgkin's lymphoma of the thyroid were treated between 1954 and 1981. The duration of follow-up ranged from 39 to 176 months. The overall 5 year survival was 51%. Twenty deaths have been recorded of which 12 were attributed to non-Hodgkin's lymphoma. Eight patients relapsed following initial treatment. Of these, two patients are long term survivors and the remainder had a mean survival of 14.5 months. The histology was reviewed by one histopathologist, with 88% of the cases being classified as grade 2 non-Hodgkin's lymphoma. The presence of Hashimoto's thyroiditis was identified in 56% of the 25 assessable specimens.
Adult↗
Gastrointestinal non-Hodgkin's lymphoma.
Seventy-two patients with gastrointestinal non-Hodgkin's lymphoma treated between 1952 and 1980 are reviewed. The small intestine was involved in 49% of cases and the stomach in 29%. Surgical resection of the tumour was performed whenever feasible. Radiotherapy was used either adjuvantly or for incompletely excised tumours and chemotherapy was more often reserved for advanced, unresected disease. The overall 5 year survival was 36% and the 5 year relapse free survival was 22%. Forty-one (57%) patients relapsed of whom 33 (80%) subsequently died of non-Hodgkin's lymphoma. The histology in each case was reviewed using the British National Lymphoma Investigation criteria and 94% of cases were reclassified as Grade 2 non-Hodgkin's lymphoma.
Adolescent↗
Non-Hodgkin's lymphoma of the tonsil. Experience of treatment over a 27-year period.
Over the 27-year period from 1954-1981, 51 patients with non-Hodgkin's lymphoma arising in the tonsil were treated at the Regional Radiotherapy Centre, Mount Vernon Hospital. The original biopsy material was reviewed in each case and reclassified using the British National Lymphoma Investigation criteria. Grade 2 non-Hodgkin's lymphoma was reported in 80 per cent of cases. Ninety per cent of patients presented in stages IE or IIE and were treated with radical local radiotherapy. A 5-year survival of 51 per cent was achieved and a 5-year relapse-free survival of 35 per cent. Stage IE patients had a statistically significant survival advantage compared to stage IIE. Sixty-one per cent of patients relapsed, of whom 74 per cent died from active lymphoma. The abdomen was the most frequent site for relapse with involvement of both nodal and extranodal sites.
Adult↗
Selective peripheral blood eosinophilia associated with survival advantage in Hodgkin's disease (BNLI Report No 31). British National Lymphoma Investigation.
A peripheral blood eosinophilia was found at presentation in 193 of 1260 (15%) patients with Hodgkin's disease who had been entered into clinical studies by the British National Lymphoma Investigation (BNLI). Eosinophilia as a component of a general leucocytosis conferred no survival advantage. Eosinophilia without a general leucocytosis was present in 95 patients, and this selective eosinophilia was associated with a clear survival advantage. The association of selective eosinophilia and improved survival was limited to patients with mixed cellularity and grade I nodular sclerosis histology. Selective eosinophilia was found to be a good prognostic indicator both in local and generalised disease. Its survival advantage seemed to lie in the response to second line treatment following relapse.
Eosinophilia↗
Lymphomas of salivary glands.
Primary lymphomas arising in salivary glands are very uncommon. The histologic classification of 40 cases of lymphomas in salivary gland tissue submitted to the British Salivary Gland Tumour Panel is reported, and, for 30 of the patients for whom adequate information was available, the clinical presentation, management, and outcome have been analyzed. Lymphomas in salivary glands represented 1.7% of all reported salivary neoplasms. The majority developed in the parotid glands of patients aged between 50 and 70 years. Only four cases gave a premorbid history compatible with sicca syndrome. In this series, non-Hodgkin's lymphomas predominated; 23 were Grade I, and 13 were Grade II. Treatment regimens were not uniform, but are outlined. Survival ranged from 5 to 111 months. Median survival for the group was 49 months. Prognosis was not influenced by the clinical stage of disease at presentation. Four cases of lymphoma arising in benign lymphoepithelial lesions are included. None had clinical symptoms of sicca complex. Prognosis for this group was found to be as favorable as the others.
Actuarial Analysis↗
Concentrations achieved in human tumors after administration of misonidazole, SR-2508 and Ro 03-8799.
Misonidazole, SR-2508 and Ro 03-8799 have been given in sequence to patients before tumor sampling. Tumor concentrations of the three drugs have been measured and it has been possible to make prediction as to the likely advantage of the newer drugs over misonidazole. Based upon the three cases described here and 13 others given two drug combination, we suggest that in multifraction radiotherapy, both are likely to prove more than five times more efficient than misonidazole.
Aged↗
Non-Hodgkin's lymphoma following radiotherapy for Hodgkin's disease.
Two patients successfully treated for Hodgkin's disease with radiotherapy alone subsequently developed a non-Hodgkin's lymphoma. One patient presented with a pleural effusion and a paraprotein band, the second with recurrent lymphadenopathy. Their case histories are compared with the five others previously reported. Full investigation including biopsy is essential when recurrent lymphoma is suspected, as the results may influence management.
Adult↗
Cardiovascular and electroencephalographic effects of laudanosine in "nephrectomized" cats.
We studied a cat model simulating laudanosine accumulation in the "anephric" patient. Cardiovascular effects were seen only with the bolus doses of laudanosine 2 mg kg-1, and at plasma laudanosine concentrations unlikely to be achieved clinically. Similarly, EEG and power spectra analysis showed no evidence of epileptiform activity at all plasma laudanosine concentrations achieved. The non-specific EEG/power spectra changes observed may reflect a direct CNS activity with neurodepression, since laudanosine was shown by its presence in CSF to cross the blood-brain barrier. These EEG changes were observed at plasma concentrations eight to 10 times those observed in humans during infusion of atracurium. Thus, laudanosine accumulation and related CNS or cardiovascular toxicity seem unlikely following atracurium administration in the anephric patient.
Animals↗
The oocytic origin of dysgerminoma.
An early dysgerminoma, found by chance in a grossly normal ovary, was completely blocked and multiply sectioned. It was found to have a mainly cortical location, being densest in the subtunical and adjacent zones where primordial follicles are normally most numerous, and to be associated with a reduction of the oocyte count in tumor-involved areas. An oocytic origin of the tumor is inferred from these findings and from other data, including the age incidence, available in the literature.
Adolescent↗
Benign lymphoepithelial lesion: a less than benign disease.
The precise clinical correlate of the benign lymphoepithelial lesion is unclear. Thirty-six cases of benign lymphoepithelial lesions (BLL), reported to the British Salivary Gland Tumour Panel between 1971 and 1984, have been reviewed. Eighty per cent arose in the parotid gland and 20% were bilateral; 83% were in females and the mean age at presentation was 55.26 years. Only 50% presented with, or developed, symptoms of sicca complex, Sjogren's syndrome or related autoimmune disease. Two cases of BLL had, or went on to develop, extra salivary lymphomas and 5 cases of BLL had lymphomatous change in the initial biopsy. A further case had carcinoma within the benign lymphoepithelial lesion. None of those who developed lymphoma had sicca or Sjogren's syndrome but 3 of them had rheumatoid arthritis. The incidence of lymphomas (salivary or extra-salivary) in this series is very much higher than that reported in Sjogren's patients and amounted to 20% overall.
Adult↗
A comparison of the tumour concentrations obtainable with misonidazole and Ro 03-8799.
Both Ro 03-8799 and misonidazole were administered to six patients before tumour sampling. Using similar doses, tumour concentrations of Ro 03-8799 were approximately double those of misonidazole. Examination of the data with regard to the relative sensitising efficiencies of these two compounds gives us, as a conservative estimate, a factor of 1.6 in favour of Ro 03-8799. From these observations it is predicted that, when given with radiotherapy in a 25-fraction course Ro 03-8799, is likely to be at least five times more effective as a hypoxic cell sensitiser than misonidazole.
Adult↗
Review of British National Lymphoma Investigation studies of Hodgkin's disease and development of prognostic index.
A review of data from the British National Lymphoma Investigation (BNLI) studies of Hodgkin's disease (HD) done over the past 14 years shows (i) that systemic chemotherapy is appropriate for all clinical stages except I and IIA, and that MOPP (mustine, vincristine, procarbazine, and prednisone) courses are substantially more effective than MOP (the same without prednisone) but no better than the less toxic LOPP combinations (where chlorambucil replaces mustine); (ii) that local involved-field irradiation in stages I and IIA HD is as effective as wide-field in terms of both overall and recurrence-free survival; and (iii) that, histologically, nodular sclerosing HD can be divided into grades 1 and 2, the latter containing areas of lymphocyte depletion or numerous pleomorphic Hodgkin's cells. A multivariate analysis of factors influencing prognosis in clinical stages I and IIA disease shows that laparotomy has no significant effect but that age, sex, erythrocyte sedimentation (ESR), the presence or absence of mediastinal involvement and, especially, pathological grade are the most important factors influencing overall survival, while ESR, pathological grade, and stage of disease (I or II) correlate with recurrence-free time. A prognostic "survival" index was developed; an index of greater than 7.5 indicated a poor prognosis and that chemotherapy was perhaps more appropriate than local radiation. Laparotomy is no longer justified as a routine procedure in staging HD, although it may still be useful in special circumstances and in some research investigations.
Adult↗
Experimental trigeminal glycerol injection. Electrophysiologic and morphologic effects.
The mechanism by which glycerol abolishes the pain of tic douloureux with minimal trigeminal deafferentation remains unknown. To study the action of glycerol, ten cats underwent unilateral retrogasserian injection of anhydrous glycerol. The contralateral (control) side was injected with saline. Glycerol injection increased the average latencies and reduced the average amplitudes of trigeminal brain-stem evoked potentials. Histopathologic examination disclosed focal demyelination, axonal swelling, endoneurial fibrosis, and neuronal loss. Evoked potentials were severely altered or abolished in cats with axonal damage in the maxillary portion of the postganglionic nerve. Glycerol injection into the trigeminal nerve damages axons and myelin sheaths. We believe that relief of tic douloureux after glycerol injection most likely results from further destruction of the abnormally myelinated fibers implicated in the etiology of trigeminal neuralgia.
Animals↗
Primary tumor control after radiotherapy for carcinoma of the bronchus.
The primary tumor control and the appearance of distant metastasis was observed closely in 62 patients entered into a randomized controlled trial of the radiosensitizing drug, misonidazole, in carcinoma of the bronchus. Sixty-one of the 62 patients are now dead; an autopsy examination was carried out in 42 (69%). Although survival was comparable to that observed in similar studies, tumor persisted or recurred at the primary site in 95% (58/61) while 39% (24/61) showed no evidence for distant metastasis. In these patients, improvement in the primary tumor control would be important in extending survival.
Bronchial Neoplasms↗
The clinical testing of Ro 03-8799--pharmacokinetics, toxicology, tissue and tumor concentrations.
Ro 03-8799, a lipophilic nitroimidazole with a basic side chain, has now been administered intravenously to 69 patients. The elimination half-life in plasma was 5.1 hr and the plasma concentration at 30 min was 14.8 micrograms/ml standardized to a dose of 1 g per square meter of surface area. Immediate symptoms of malaise, heat, sweating and disorientation limit the amount of the drug which may be given on any one occasion. However, a dose of 750 mg per square meter of surface area may be given combined with daily radiotherapy. Our data suggest that when given with a 20 fraction course of radiotherapy, sensitization of hypoxic cells may be achieved equal to a 10-fold increase in the dose of misonidazole above that presently permitted.
Drug Evaluation↗