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Biomedical subjects

A G Robertson

Publications and source records attributed to A G Robertson.

At least 19 recordsLinked to original sources

Identification of the histidine residue in Escherichia coli isocitrate lyase that reacts with diethylpyrocarbonate.

Escherichia coli isocitrate lyase was inactivated by diethylpyrocarbonate in a pseudo-first-order process. The enzyme was completely inactivated by modification of a single histidine residue, but slower modification of further residues also occurred. The substrate, isocitrate, and products, glyoxylate and succinate, protected against inactivation by diethylpyrocarbonate but this was not simply due to binding at the active site. Treatment of the inactivated enzyme with hydroxylamine led to only partial recovery of activity. Diethylpyrocarbonate also reacted with sulphydryl groups in isocitrate lyase, as judged by titrations with Nbs2, but this reaction was not responsible for the failure of hydroxylamine to reactivate the enzyme fully. The reactivity of isocitrate lyase to diethylpyrocarbonate declined with pH, following a titration curve for a group of pKa 6.1. Isolation and sequencing of ethoxyformylated peptides showed that the major site of modification by diethylpyrocarbonate was histidine residue 306.

Amino Acid Sequence

An evaluation of functional outcome after surgery and radiotherapy for intraoral cancer.

Two hundred and fifty five patients undergoing treatment for oral cancer were studied. Tumour site, classification and treatment modality were recorded and an assessment of their ability to swallow was made postoperatively. Patients were graded into one of three groups depending on dietary consistency. Pre- and postoperative dental examinations were made and patients were weighted pre- and postoperatively. Postoperative functional problems are outlined. The results indicated that 21% of the sample reported difficulty with swallowing solid foods and 46% were limited to semi-solid or liquid diets postoperatively; 16% were unable to wear upper or lower dentures postoperatively and 15% of edentulous patients were able to wear an upper denture only; 65% of the patients who had surgery and radiotherapy were unable to regain their preoperative weight after 6 months. Patients with T1 tumours who did not progress to radiotherapy faired much better postoperatively and were more likely to return to normal diet and regain their preoperative weight.

Adult

The management of tumours arising in the maxillary antrum.

Eighty-eight cases of tumours arising in the maxillary antrum undergoing treatment between 1967 and 1989 are reported. The series comprised 34 females and 54 males. Sixty-two patients had squamous cell carcinoma (SCC). Forty of those with SCC were treated by XRT only, four cases by surgery only, while the remaining 18 patients had surgery and post-operative XRT as a combined modality treatment. Early SCC (T2N0) was adequately controlled by radical radiotherapy alone with a 5-year survival of 69.1%. In more advanced SCC (T3N0 and (T4N0) radical radiotherapy alone was less successful with the 5-year survival falling to 19%. Combined modality treatment comprising radical surgery followed by radical postoperative radiotherapy improved 5-year survival in advanced SCC to 61%. It is therefore recommended that if patients are treated for cure, major surgery followed by radical postoperative radiotherapy is preferable in advanced squamous tumours ((T3/T4) of the maxillary antrum.

Adult

Effect of radiation dose on the development of mixed haemopoietic chimerism following T cell-depleted allogeneic bone marrow transplantation.

The presence of mixed haemopoietic chimerism (MXC) was evaluated by cytogenetic and molecular analysis in 48 patients undergoing T cell-depleted BMT. The dose of total body irradiation (TBI) prescribed to all patients (14.4 Gy) was calculated to compensate for the absence of T cells in the graft. The actual midline dose of TBI received, however, differed significantly depending on the method of TBI administration. Thus, 35 adult patients received an average midline dose of 14.3 Gy, while 13 children received a lower dose of 13 Gy. The incidence of MXC in the adult group, who had received very close to 14.4 Gy to the midline, was 34% (12/35), which is lower than in most reported T cell-depleted series. During follow-up, chimerism remained relatively stable with time but varied between haemopoietic lineages. There was no relationship with relapse. MXC in the 13 children who had received a lower midline TBI dose was significantly higher at 69% (9/13) (p < 0.05) and increased to 90% (9/10) if patients who received additional chemotherapy in their conditioning were excluded (p = 0.001). This suggests that, in terms of marrow ablation, relatively small changes in the dose of TBI may be biologically significant, at least at this dose range. Again, in the lower TBI group MXC was not predictive of relapse.

Adolescent

Subclinical pulmonary function defects following autologous and allogeneic bone marrow transplantation: relationship to total body irradiation and graft-versus-host disease.

Pulmonary function results pre- and post-transplant, to a maximum of 4 years, were analyzed in 98 patients with haematological disorders undergoing allogeneic (N = 53) or autologous bone marrow transplantation (N = 45) between 1982 and 1988. All received similar total body irradiation based regimens ranging from 9.5 Gy as a single fraction to 14.4 Gy fractionated. FEV1/FVC as a measure of airway obstruction showed little deterioration except in patients experiencing graft-versus-host disease in whom statistically significant obstructive ventilatory defects were evident by 6 months post-transplant (p less than 0.01). These defects appeared to be permanent. Restrictive ventilatory defects, as measured by reduction in TLC, and defects in diffusing capacity (DLCO and KCO) were also maximal at 6 months post-transplant (p less than 0.01). Both were related, at least in part, to the presence of GVHD (p less than 0.01) or use of single fraction TBI with absorbed lung dose of 8.0 Gy (p less than 0.05). Fractionated TBI resulted in less marked restricted ventilation and impaired gas exchange, which reverted to normal by 2 years, even when the lung dose was increased from 11.0 Gy to between 12.0 and 13.5 Gy. After exclusion of patients with GVHD (30% allografts) there was no significant difference in pulmonary function abnormalities between autograft and allograft recipients.

Adolescent

Stomal recurrence: a separate entity?

Uncertainty exists concerning the exact aetiology of stomal recurrence following laryngectomy, although it is generally agreed that, when present, the prognosis is very poor. Fourteen cases of stomal recurrence were compared with 15 cases of other types of aggressive recurrence in the neck, for factors implicated in stomal recurrence. Similarities exist between the two groups and, although stomal recurrence has a greater association with subglottic tumour, this difference is not statistically significant. The possible mechanisms of recurrence are discussed, particularly in relation to aggressiveness, and it is concluded that factors involved in aggressive recurrences are similar. Stomal recurrence can be considered part of a group of aggressive neck recurrences associated with more advanced disease prior to laryngectomy.

Carcinoma, Squamous Cell

Phase II trial of carboplatin and vinblastine in advanced squamous-cell carcinoma of the head and neck.

A chemotherapy regimen consisting of carboplatin and vinblastine was given to 30 patients with recurrent or previously untreated, locally advanced squamous carcinoma of the head and neck region. The main aim of the study was to assess the toxicity of this regimen, the feasibility of its outpatient administration and the tumour response. A total of ten patients (33%) achieved an objective response, including two who achieved a complete response. The combination offered useful palliation for patients with recurrent disease; it was well tolerated and can be given on an outpatient basis. This regimen could be combined with other active agents such as methotrexate or bleomycin.

Adult

Assessment of factors influencing the outcome of radiotherapy for bladder cancer.

The results of treatment of 709 patients with carcinoma of the bladder are reported. Inclusion of the pelvic lymph nodes in the treatment volume failed to lead to any improvement in survival. The factors influencing survival were stage, tumour histology and differentiation. The presence of tumour at follow-up cystoscopy at 3 months was of great prognostic significance.

Aged

Functional implications of major surgery for intraoral cancer.

A group of 41 patients were questioned about functional problems and concern for appearance, experienced following major surgery for intraoral malignancy. Twenty-five per cent of the group reported significant difficulties. Spouses reported a higher incidence of problems. The effects of primary tumour site and type of reconstruction on functional outcome are discussed.

Adenocarcinoma

Psychological distress at follow-up after major surgery for intra-oral cancer.

A cohort of patients who had received major intra-oral surgery, up to 10 yr (mean 3.5 yr) prior to this study were reviewed and assessed for evidence of current psychological disturbance. Forty-one per cent of patients were found to have significant levels of psychological distress comprising mood disorder, social dysfunction or both types of difficulty. Prevalence of clinical anxiety and depression per se was within the range 22-32%, but few patients were receiving any form of active therapy for these problems. Investigation of predictors revealed that females and younger people were more at risk to psychological distress. Tentative evidence for variability in psychological outcome in relation to tumour site is also reported. Results are discussed with reference to service provision needs and further research priorities.

Adult

Improving prognosis of Hodgkin's disease in Scotland.

Time trends in mortality from Hodgkin's disease have been studied in Great Britain for the 70-year period, 1911-1980, and incidence in Scotland since 1959. In both Scotland and England and Wales, in each sex, mortality from Hodgkin's disease rose steadily from 1911 until 1970 and thereafter dropped substantially; the greatest fall was apparent in Scottish males. While mortality rates continue to decline in Scotland the incidence has remained fairly constant over the last 25 years suggesting a major change in prognosis for this disease. The introduction of effective chemotherapy and improved techniques of radiotherapy appear to have improved prognosis sufficiently, and to have been made adequately widely available, as to influence overall mortality rates at a national level as well as at the level of the clinical trial. No such improvement in prognosis, however, explains the declines observed in mortality rates among children of each sex in both areas which have taken place since the 1930s. In view of the current knowledge of the aetiology of Hodgkin's disease this fall may have been brought about by changes in socioeconomic factors.

Age Factors

The effect of chlorhexidine and benzydamine mouthwashes on mucositis induced by therapeutic irradiation.

A variety of mouthwashes are frequently used in the management of irradiation-induced mucositis. Benzydamine has recently been introduced for alleviating this condition. Its efficacy as a mouthwash was compared with chlorhexidine in two groups of patients receiving radiotherapy for oral carcinoma. Mucositis and pain were recorded over a 6 week period and oral carriage of Candida species, coliforms and Staphylococcus aureus was assessed using an oral rinse technique. There was no significant difference in the mucositis scores, overall pain scores or the yeast and bacterial species isolated between the two treatment groups. However, 58% (7 out of 12) and 92% (12 out of 13) patients reported oral discomfort when rinsing the mouth with chlorhexidine and benzydamine, respectively. In both groups, the most common coliform isolated was Klebsiella pneumoniae and the carriage of yeasts was significantly greater than that of coliforms. These results indicate that, although the individual patient acceptance of chlorhexidine is better than benzydamine, there is little difference between the two mouthwashes both in controlling pain and mucositis or in the oral carriage of the micro-organisms studied.

Aged

Central nervous system decompression sickness: latency of 1070 human cases.

Many aspects of central nervous system (CNS) decompression sickness (DCS) are poorly understood, including the temporal pattern of its presentation and the pathogenic mechanisms involved in the development of the disease. Using case histories and clinical series published in the literature and retrieved from treatment center records, this study is an attempt to define the interval between surfacing from a hyperbaric exposure and the onset of symptoms of CNS DCS. The results of 1070 cases of human CNS DCS were included in the study. The results show that the disease generally occurs rapidly: over 50% became symptomatic within 10 min of returning to 1 ATA, and in only 15% of cases was the onset of symptoms delayed for more than 1 h. Cerebral DCS had a more rapid onset than spinal cord disease: 50% of cerebral cases became apparent within about 3 min and a similar proportion of spinal cord cases within about 9 min from surfacing. The influence of these results on the diagnosis and treatment of dysbaric illness, on the safety of certain diving practices, and on possible pathogenic mechanisms is discussed.

Central Nervous System Diseases

Prevention of graft-versus-host disease by ex vivo T cell depletion: reduction in graft failure with augmented total body irradiation.

Graft-versus-host disease prevention was attempted in 35 consecutive patients with hematological malignancy who received bone marrow from an HLA match sibling donor who was depleted of T cells ex vivo. Five of the first 8 patients who received cyclophosphamide 60 mg/kg on 2 consecutive days followed by fractionated total body irradiation (TBI) (6 x 2 Gy) had graft failure. The subsequent 27 patients had received an extra fraction of TBI (7 x 2 Gy), and only one failed to have stable engraftment. There were no differences in nucleated cell dose, granulocyte-macrophage colony-forming units, or T cell numbers given to the two groups. Neutrophil but not platelet regeneration of those patients who successfully grafted was slower than in a group of historical controls receiving unmanipulated marrow. Significant graft-versus-host disease was prevented with no increase in relapse rate. We suggest that engraftment can be reliably achieved by augmenting the TBI conditioning in recipients of T cell-depleted matched allogeneic bone marrow.

Adolescent

Carcinoma of the larynx.

Six hundred sixty-eight patients with tumours of the larynx were treated by radiotherapy. The patients had stage T1 N0 M0 to T4 N3 M0 disease. Patients with T1 N0 M0 disease (273) had an excellent long-term survival (90%) as did those with T2 N0 M0 disease (142), whose 5-year survival was 70%. Patients with more advanced disease but no nodal spread did not respond as readily to radiotherapy; the 5-year survival was 40%. All patients were treated using a parallel pair set-up 6 X 6 cm lateral neck fields. A more aggressive radiotherapy regime to a larger tissue volume to include microscopic spread to lymph nodes may improve survival of locally advanced disease.

Adult