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Biomedical subjects

R J Berry

Publications and source records attributed to R J Berry.

At least 55 records · Page 3Linked to original sources

High dose cisplatin compared with high dose cyclophosphamide in the management of advanced epithelial ovarian cancer (FIGO stages III and IV): report from the North Thames Cooperative Group.

A randomised study comparing cisplatin 120 mg intravenously with cyclophosphamide 2 g intravenously, each drug being given every month for six months followed by a low dose regimen for a further six months in responding patients, was carried out in 86 patients with advanced epithelial ovarian carcinoma (FIGO stages III and IV). Patients given cisplatin were found to have a longer median survival time than those given cyclophosphamide (19 months compared with 12 months) and a longer median duration of complete clinical response (18 months compared with eight months). The difference in disease free survival was statistically significant even after factors such as age, stage of disease, and the completeness of initial surgery had been taken into account. This study suggests that cisplatin is a more effective chemotherapeutic agent than cyclophosphamide for advanced ovarian cancer and should be the agent of choice in future trials comparing combination chemotherapy with a single agent.

Adult↗

N-methyl-N-nitrosourea induces dysplasia and cell surface markers of neoplasia in long-term rat bladder organ cultures.

Untreated organ cultures of normal rat bladder can be maintained for long periods, up to 160 days, in a supplemented Waymouth's medium MB 752/1. During that time, the urothelium retains a similar appearance to that seen in vivo, namely a three-cell thick epithelium with specialised superficial cells whose characteristic surface features are identifiable by scanning electron microscopy. These superficial cells cover the major part of the explants, but the surface features of basal and intermediate cells can be observed on the cut edges and re-epithelialising surfaces of the explant. These are described and illustrated. When normal cultures are treated with the direct-acting carcinogen, N-methyl-N-nitrosourea (MNU), the in vitro response of the urothelium resembles to a certain extent the in vivo response to MNU instilled directly into the bladder. A histological progression is seen through mild to severe dysplasia which resembles carcinoma in situ. However, no marked changes in growth pattern, such as the development of papillary or nodular hyperplasia are seen. It is suggested that this is related to the failure of the vascular and stromal elements of the explants to respond to MNU treatment in vitro. The development of urothelial dysplasia is reflected by marked changes in cell surface differentiation, including development of pleomorphic microvilli, which closely resemble those seen following MNU treatment in vivo. These changes appeared earlier and were far more severe in vitro than in vivo. The significance of pleomorphic microvilli in bladder cultures is considered. A few were seen in control cultures but primarily on epithelial outgrowths onto the Millipore filter support, suggesting a relationship to the distance of the urothelium from viable stromal support. In the MNU-treated cultures, they were numerous and found on the surface of cells covering most of the explants. They were not solely related to the proliferative state of the urothelium in these cultures. This in vitro culture system provides a useful model with which to study the effects on the urothelium of various known and suspect carcinogens.

Animals↗

Invasive bladder cancer treated by radical external radiotherapy.

Fifty-three consecutive, unselected patients with invasive bladder cancer, Stage T2 to T3, treated by radical radiotherapy have been reviewed. Cystectomy was reserved for patients with significant worsening of disease during treatment, histologically confirmed persistent or recurrent invasive tumour after treatment, or patients with intolerable symptoms due to radiation cystitis. In 64% of our patients a favourable tumour response to radiotherapy was seen, while a further 31% showed disease progression either during or on completion of radiotherapy. Cystectomy was performed on 22% of patients, mainly for radiation cystitis, and was not associated with a significant operative mortality rate. The crude 5-year survival rate was 42%. We conclude that radical radiotherapy is as effective as other forms of treatment for invasive bladder cancer, but that there remains a need to identify those bladder tumours destined to respond poorly to radiotherapy at an earlier stage.

Adult↗

Oral rehydration fluids used in the treatment of diarrhoea. Analysis of the osmolalities, and sodium, potassium and sugar contents of commercial and home-made products.

Analysis of 91 commercial dietary "clear" fluids, including carbonated beverages, cordials, powdered drinks, jellies, fruit juices, fruit juice drinks, syrups, and soups showed a range of zero to 175 mmol/L of sodium, zero to 52.1 mmol/L of potassium, zero to 839 mmol/L of reducing sugars and an osmolality of 50 to 914 mmol/kg water. Home-made oral rehydration solutions prepared by a group of mothers and medical staff members also showed unacceptably wide variability in their composition. The composition of products specifically indicated for the treatment of diarrhoea was also remarkably diverse, with a range of 24 to 100 mmol/L of sodium, 14.2 to 21.0 mmol/L of potassium, 45 to 326 mmol/L of glucose, and 170 to 460 mmol/kg water osmolality. On the basis of our current knowledge of water and electrolyte absorption, neither the commercial dietary "clear" fluids nor the home-made solutions can be recommended for the treatment of diarrhoea. Of the therapeutic products, only "Unicef Oral Rehydration Salts" has been subjected to clinical trails and found safe and effective. However, the formulation of Diolyte appears appropriate for the treatment of mild diarrhoeal dehydration.

Adult↗

The subcellular basis of damage to the human urinary bladder induced by irradiation.

The effects of x-irradiation on the subcellular structure of the human urinary bladder were investigated by electron microscopic examination of biopsies taken during check cystoscopies from 25 patients between 1 month and 22 years after completion of a course of therapeutic radiation. All tissues of the bladder wall were damaged to some extent by the treatment. In the urothelium this was reflected by the development of more than the usual numbers of lysosomes and autophagic vacuoles in all cell layers. In the bladder wall, large often binucleate or multinucleate fibroblasts were prominent and persistent in all specimens and were associated with the development of progressive fibrosis. The vasculature and the muscle coats of the bladder wall were also damaged. In the blood vessels many endothelial cells were oedematous or necrotic and some intravascular coagulation was also observed. Smooth muscle cells became oedematous soon after irradiation, and after longer time intervals there was focal death and loss of individual muscle cells. The observed degeneration and extensive necrosis of the bladder wall, which involved severe destruction and disorganization of the muscular layers, is sufficient to explain the clinical sequelae of bladder irradiation, namely loss of elasticity, reduced capacity and incomplete micturition with residual urine.

Adult↗

Evaluation of the role of computed tomography in radiotherapy treatment planning.

The role of computed tomography (CT) in radiotherapy treatment planning was assessed in a series of 231 patients in whom treatment was planned with radical intent. For each patient, a treatment plan was produced by the best conventional techniques in use at the Middlesex Hospital. Each patient then underwent a CT scan in which the treatment conditions were closely simulated. As a result of the CT scan images, alteration was made to the planned treatment in 47% of 198 assessable patients. Large differences were seen in the usefulness of CT treatment planning for tumours in different sites, with the greatest contribution made to treatment of tumours of the sinuses and nasopharynx and of the bladder. Although its unit cost is high, computed tomography can be a very useful tool in radiotherapy treatment planning and can contribute uniquely to improved patient management for adequately selected patients.

Bronchial Neoplasms↗

A modified infant mouse assay for bacterial enterotoxins.

The reproducibility of the infant mouse assay for Escherichia coli ST and heat-labile enterotoxins of Aeromonas spp. is improved if both intestinal weight to remaining body weight ratio (IW/RBW) and the amount of diarrhoea produced are considered as criteria for classifying enterotoxigenic strains. Animals with profuse diarrhoea may have IW/RBW ratios below the widely accepted critical value for a positive test. Using pools of supernatants from broth cultures of three different strains of E. coli, 15% of ST producers would have been regarded as negative using IW/RBW ratio as the only criterion of a positive test. In testing single supernatants, 25% of ST producing E. coli would not have been correctly classified using IW/RBW alone. A scoring system which incorporates IW/RBW ratios and the amount of diarrhoea produced improves the usefulness of the test by allowing clear separation of positive and negative strains. The scoring system is also applicable to older mice for assay of E. coli ST so that a wider age range of mice can be used allowing increased use of animal facilities.

Aeromonas↗

Studies on enterotoxigenic Escherichia coli isolated from persons without diarrhoea in Western Australia.

The epidemiology of enterotoxigenic Escherichia coli (ETEC) was studied in children without diarrhoea in two remote Aboriginal communities in tropical north-western Australia. Serial surveys of the same individuals during different seasons showed that isolations were much more frequent in the wet monsoonal summer than in the dry winter. All E. coli were isolated from symptomless children aged 5 years or less; in addition, clearance of ETEC carriage without treatment was observed in all individuals within 3 months of isolation. Of the 58 ETEC strains isolated, 40 had either an H32 or an O126 antigen. Five O antigens which have never been associated with ETEC (O2, O41, O71, O77 and O157) were found. A recently proposed system to detect ETEC, using groups of polyvalent antisera, would have detected only 3 out of these 58 ETEC strains.

Antigens, Bacterial↗

Examination of vocal fold movement by ultra-short pulse X radiography.

Antero-posterior radiographs of the larynx lack spatial and temporal resolution, due to the movement of the vocal folds during phonation. By utilising the electrolaryngograph to monitor vocal fold movement, single X-ray pulses of 30 nanoseconds duration have been triggered at pre-determined points during the cycle of vocal fold movement to visualise these in normal phonation.

Female↗

Long-term organ culture of normal human bladder.

Normal adult human bladder obtained at cystoscopy has been maintained in long-term organ culture. Several media were tested for their ability to maintain viability and normal tissue morphology. The optimum medium was Ham's F-12 nutrient mixture, supplemented with 10% fetal calf serum, hydrocortisone (1 microgram/ml), and FeSO4, (0.45 microgram/ml). During the first 28 days in vitro, epithelial damage incurred at biopsy and during preparation of the cultures was repaired, and epithelialization of cut stromal surfaces occurred. A wave of cell proliferation was identified by [3H]thymidine autoradiography, 24-h labeling indices rising to a peak of up to 50% on the cut sides of the cultures between 7 and 21 days and falling to 0 to 5% by 21 to 28 days. The regenerating epithelium showed all the normal features of urothelial cell differentiation when examined by scanning and transmission electron microscopy. From 28 days, histology and scanning and transmission electron microscopy showed the cultured urothelium in most cultures to resemble closely that in the normal bladder in vivo, and in this mature state cultures were maintained for 100 days. Urothelium derived from certain patients, although showing normal surface maturation, developed enlarged intercellular spaces or intraepithelial mucin-containing acini. A study of the cytology of cells shed into the medium at different stages in culture showed that culture viability and epithelial differentiation could be monitored easily in long-term culture by this nondestructive means.

Adult↗