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Biomedical subjects

W M Ross

Publications and source records attributed to W M Ross.

At least 37 records · Page 2Linked to original sources
PubMed1986

The long-term effects of megavoltage radiotherapy as sole or combined therapy for large prolactinomas: studies with high definition computerized tomography.

The long-term sequelae of external pituitary irradiation alone or in combination with surgery and/or bromocriptine therapy have been studied in 14 patients with large prolactinomas over an observation period of 6-22 years (mean 13 years). Galactorrhoea was abolished in four of the five females with this symptom, but menstrual disturbance persisted in five of six patients. Sexual function was normal without sex hormone replacement in only one of the eight males after treatment. Neurological deficits were abolished or improved by treatment in all 9 patients with this presentation. Serum prolactin levels declined after treatment (P less than 0.001) and fell to within the normal range off bromocriptine therapy in six of the 14 patients at a mean of 9 years (range 5-17 years) after radiotherapy. All patients had anterior pituitary deficiency of some degree at reassessment, and 13 required replacement treatment. Serial skull radiographs revealed remineralization of the fossa floor in five patients and a decrease in fossa size in three. All five patients who did not also have surgery had evidence of tumour shrinkage without bromocriptine treatment (on CT scan or metrizamide cisternography). Fourth generation CT scans on completion of the study revealed a decrease in tumour mass in all patients, with varying degrees of empty sella in 13 and a cystic intrasellar tumour in the remaining one. Residual tumour was demonstrated in 10 patients, three of whom had normal serum prolactin levels, while one patient without visible tumour had persistent hyperprolactinaemia. Radiotherapy, alone or in combination with surgery and bromocriptine, effectively decreases prolactin secretion and tumour size in patients with large prolactinomas at the expense of other anterior pituitary function. Circulating prolactin levels are a poor marker of residual tumour volume.

Adolescent↗
PubMed1986

Radioprotection conferred by dextran sulfate given before irradiation in mice.

Dextran sulfate (DS) has been observed to cause mobilization (fivefold) of hemopoietic stem cells (HSC) and leukocytes, primarily lymphocytes, into the peripheral blood of mice within 2-3 h after intraperitoneal (i.p.) injection. This effect was dose dependent and was prolonged for several hours when the high-molecular-weight version DS500 (500,000 daltons) was used. When DS500 was given 1-3 days before irradiation, hemopoietic recovery was markedly enhanced. Postirradiation injection was ineffective. By ten days after irradiation (7.0 Gy), the number of endogenous spleen colonies (CFUs) and the splenic mass were much larger if DS pretreatment had been given. This effect was dependent on the dose of DS500 and on the time administered, 60 mg/kg producing a maximal effect when given three days before irradiation. DS500 caused a transient anaphylactoid shock, however, in most mice--mild at low doses but potentially lethal at doses above 40 mg/kg (10% mortality within 1-3 days after 60 mg/kg). The following results were obtained with 50 mg/kg, a compromise dose causing minimal mortality (3%) given three days before irradiation. Reticulocyte reappearance was earlier in irradiated mice given DS500, indicating earlier erythropoietic recovery. Some of these reticulocytes were resistant to lysing agents, so their appearance could be detected using the Coulter electronic cell counter, as well as in stained blood smears. The 30-day mortality due to bone marrow failure after irradiation was significantly decreased in DS-treated mice below 9.5 Gy, and the LD50/30 was increased by 0.5 Gy. This study shows that dextran sulfate exerts a radioprotective influence on the hemopoietic system and hence survival when administered prophylactically.

Animals↗
PubMed1985

Modelling cortical cataractogenesis VII: Effects of vitamin E treatment on galactose-induced cataracts.

The possibility that vitamin E or other antioxidants might prevent cataracts was tested by incubating rat lenses in vitro in galactose-enriched medium or by treating rats fed a diet containing 50% galactose (w/w). The vitamin E was added to the medium at 2.4 microM, and to the diet at a level of 5 g kg-1 diet. In vitro, lenses incubated with 55.6 mM galactose underwent globular degeneration, which was partially prevented by addition of vitamin E (2.4 microM). Even in such vitamin E-protected lenses, which appeared clear, many small globules could be seen in the region of interdigitation at the 'corners' where hexagonal cells intersected. In vivo, in dietary experiments, a dense nuclear opacity of the lens was observed after approximately 5 weeks; unlike diabetic cataracts, this was not prevented by the addition of vitamin E to the diet. The extensive globular degeneration observed was typical of that found in long-term (21-week diabetic) cataracts. Although no significant difference in cataract incidence was observed, the extent of damage in vitamin E-treated rat lenses appeared to be less. The difference in effectiveness of vitamin E in galactose-induced cataracts, as compared to diabetic cataracts, is tentatively ascribed to (1) the more severe osmotic stress expected from the products of the aldose reductase pathway for galactose and (2) the greater depletion of reduced pyridine nucleotides (NADPH + NADH) expected of galactose as compared to glucose.

Animals↗
PubMed1985

Prognostic factors in malignant melanoma: a retrospective analysis of 182 patients.

The records of 182 patients with malignant melanoma, referred to the Regional Radiotherapy Centre, Newcastle upon Tyne, between January 1975 and December 1980, have been reviewed to determine the influence of site of disease, age and sex of the patient, Clark's levels and stage of disease on the prognosis. Site and age were found to have no influence on the survival rate. The difference in the survival rates of males and females was almost entirely accounted for by the difference in their disease at the time of presentation. Survival was found to be highly significantly affected by the Clark's levels (p less than 0.0001) and by the stage of disease (p less than 0.0001).

Adult↗
PubMed1985

Pituitary function following megavoltage therapy for Cushing's disease: long term follow up.

Eight patients who had received megavoltage therapy for Cushing's disease 5-12 years previously have been reviewed. The long term response to this therapy was assessed with respect to efficacy of treatment in inducing continued remission and disturbance of hypothalamic-pituitary function. One patient showed clear evidence of relapse of Cushing's disease. One patient had unequivocal hypopituitarism. Basal levels of growth hormone (GH), TSH, LH, and FSH were not statistically different from controls, but provocative testing revealed significant abnormalities of response of cortisol/ACTH, GH, prolactin and LH. Six out of eight patients had absent diurnal cortisol variation and five patients had elevated serum prolactin levels. Thus, in this group of patients normal pituitary-adrenal function has not been satisfactorily restored. It is clear that significant disturbances of hypothalamic-pituitary function follow mega-voltage therapy and these may progress to overt hypopituitarism.

Adult↗
PubMed1984

Ablative radioiodine therapy for hyperthyroidism: long term follow up study.

A total of 225 patients were treated for hyperthyroidism with 555 MBq (15 mCi) radioiodine to ablate the thyroid and induce early hypothyroidism. The efficacy of this treatment in eradicating hyperthyroidism and problems of follow up were assessed one to six years later from case records and questionnaires. Information was received from 197 out of 219 live patients (90%) and from 160 doctors concerning 207 patients (92%). Only three patients were not traced and six had died since treatment. The modal time to hypothyroidism was three months, and 64% of patients were hypothyroid at one year; 5.6% had failed to become euthyroid within one year. Ninety five per cent of patients had been seen by the doctor and 82% had had a thyroid test done within the past two years. Most doctors preferred patients to be returned to their care once thyroxine treatment was stabilised. An ablative dose of 131I is recommended as an effective means of treatment which has clear advantages over conventional methods. Good communications and effective follow up should ensure success.

Adult↗
PubMed1984

Cytogenetic studies in dogs after total body irradiation and allogeneic transfusion with cryopreserved blood mononuclear cells: observations in long-term chimeras.

Cytogenetic studies were performed on two dog groups after total body irradiation and allogeneic transfusion with cryopreserved blood mononuclear cells. The first group of dogs was transfused with unseparated leukocytes and suffered from graft-versus-host disease (GvHD). Cytogenetic studies demonstrated only cells of donor origin in all dogs of this group. The second group of animals was transfused with fraction 2 of a discontinuous albumin gradient. The dogs of this group did not develop GvHD, and the cytogenetic studies showed the presence of a mosaic of cells from donor and recipient origin in all of them. These results suggest that the GvHD may suppress autochthonous regeneration.

Animals↗
PubMed1984

Management of malignant melanoma: a retrospective analysis of 182 patients.

The records of 182 patients, referred to the Regional Radiotherapy Centre, Newcastle upon Tyne between January 1975 and December 1980, have been reviewed to evaluate the results of different modes of treatment. Fifty-two patients were managed for Stage 1, 83 for Stage 2 and 47 for Stage 3 disease. Fifty-seven patients with 95 sites of disease were given chemotherapy. The overall response rate was 35% (complete response (CR) 14%, partial response (PR) 21%) (median duration of remission = 4 months). Sixty-three patients with 74 sites of disease were treated by radiotherapy. The overall response rate was 73% (CR 47%, PR 26%) (median duration of remission = 7 months). In Stage 2 disease, no significant difference in the disease-free or overall survival was found between four different treatment groups. In disseminated disease, chemotherapy had little impact on the survival of patients with visceral metastases, while those with skin and lymph node metastases had significantly better survival. Radiotherapy was tolerated better and had lower morbidity than chemotherapy. The role of both modes in the management of advanced disease is discussed.

Adolescent↗
PubMed1983

Stimulation of extramedullary hemopoiesis by dextran sulfate.

The spleen of normal dogs (beagles) shows only slight hemopoietic activity, characterized by the presence of megakaryocytes in mitosis and small groups of erythroblasts scattered throughout the red pulp of the organ. Repeated intravenous injection of dextran sulfate, at a dose of 15 mg per kg body weight, produced markedly enhanced erythropoietic and megakaryocytopoietic activity in the splenic red pulp, without concomitant increase in splenic granulopoiesis. The probable existence of a micro-environment adequate for erythro- and megakaryocytopoietic differentiation of stem cells is discussed.

Animals↗
PubMed1983

Radiation cataract formation diminished by vitamin E in rat lenses in vitro.

Eye lens cataract is a late effect of exposure to ionizing radiation. Depending on the dose and quality of radiation impinging on the lens, the development of a clinically discernible cataract usually takes several months in animal models, when the lens is irradiated in situ. However, we have developed a rapid in vitro assay with the isolated intact rat lens to study the effect of radiation and influence of antioxidants as protective agents. After only 24 hr of post-irradiation incubation at 35.5 degrees C in complete medium 199 + 10% foetal calf serum, damage in the form of globular degeneration subcapsularly and 'holes' in the cortical fibre cells is detectable. Doses as low as 0.10 Gy seem to be capable of causing some damage, and vitamin E (2.4 microns) in the medium confers some protection to the irradiated lens.

Animals↗
PubMed1983

Modelling cortical cataractogenesis: VI. Induction by glucose in vitro or in diabetic rats: prevention and reversal by glutathione.

Cataractogenesis can be induced by glucose in the rat lens in vitro and in vivo. In vitro, this is done by increasing the amount of glucose in the medium surrounding the isolated lens; within 48 hr considerable globular degeneration is seen subcapsularly, deeper in the equatorial region. In vivo, it is achieved by making the rat diabetic by injecting streptozotocin i.v., which selectively destroys the beta-cells of the pancreas; the blood serum glucose level increases markedly, and thence the aqueous humour level and, in turn, the lens concentration. Globular degeneration occurs as in vitro, but not until 6 weeks is a degree of damage observed comparable to that seen in the lenses incubated in vitro for only 48 hr. Lenticular sorbitol and fructose are also markedly elevated as a result of the high glucose levels. If glutathione (GSH) is present in the medium (0.1 mM) or injected s.c. daily into the diabetic rats, there is no evidence of subcapsular globular degeneration of the cortical fiber cells, even though the lenticular levels of glucose, sorbitol and fructose are the same as when GSH was not given; this is true for either the in vitro or in vivo situation, although individual values in the two situations do differ somewhat from one another. When rats were given GSH beginning several weeks after the diabetic state had been induced, the damage subsequently observed was much less than if the rats had been diabetic without GSH for the same total length of time; it was also much less than damage which should have occurred by the time GSH treatment was instituted. It would thus appear that a certain amount of reversal of the globular degeneration is possible, although damage in the equatorial region (wedge-shaped) seems less amenable to rescue by glutathione. The data indicate that glutathione can prevent or diminish the severity of sugar cataractogenesis, and that there would appear to be more steps in sugar cataractogenesis than simply osmotic damage, although this may be the primary event.

Animals↗
PubMed1982

Quantitative aspects of granulocytic progenitor cell (CFUc) mobilization from extravascular sites in dogs using dextran sulphate (DS).

The relationship between the increase in the blood CFUc concentration after intravenous injection of dextran sulphate (DS) and the pre-existing levels of spontaneously circulating CFUc was studied in dogs. After 15 mg DS/kg body weight the CFUc numbers per ml blood rose by a factor of 3.7 over the pre-injection values, from 78 +/- 11 (SEM) to 359 +/- 50, in normal dogs, and increased by a factor of 3.9 in 0.84-Gy-r-irradiated animals which had a reduced initial CFUc concentration per ml, from 35 +/- 8 to 116 +/- 43. The injection of 20 mg DS/kg body weight into unirradiated dogs caused an increase, by a factor of 11.5, of the pre-injection CFUc concentration, from 101 +/- 20 to 921 +/- 106. On the basis of the mobilization curves for individual dogs, a significant correlation was found between the normal blood CFUc value and the number of CFUc mobilized by DS for both dose levels. From the descending part of the mobilization curves obtained after 15 mg DS/kg body weight, kinetic parameters of canine circulating CFUc were derived. The mean blood transit time (t) was 1.4 +/- 0.5 hr and the half time (T/2) was 1.0 +/- 0.4 hr.

Animals↗
PubMed1982

Cyclic GMP in urine to monitor the response to ovarian cancer to therapy.

Guanosine 3':5'-phosphate (cycle GMP) in urine has been used to monitor the response of patients with ovarian cancer to treatment. Changes in the cyclic GMP level appear to correlate well with clinical status in that the disappearance of clinically detectable tumour is associated with a drop in the level whereas a tumour recurrence is associated with an elevation. Serially measured cyclic GMP is valuable for detecting a recurrence of tumour growth in patients in clinical remission and can predate any clinical signs by as much as 10 months. In patients who show no response to treatment, cyclic GMP levels in urine are elevated in the majority of specimens collected.

Creatinine↗
PubMed1982

Urine cyclic nucleotide concentrations in cancer and other conditions; cyclic GMP: a potential marker for cancer treatment.

Cyclic guanosine 3',5' monophosphate (cyclic GMP) and cyclic adenosine 3',5' monophosphate (cyclic AMP) have been determined in random urine specimens from 95 healthy individuals, 60 patients with non-cancerous conditions, 52 patients with benign tumours, and 74 patients with malignant tumours. Concentrations of cyclic GMP have also been determined in a number of other groups, including some undergoing cancer treatment. Ninety-three per cent of cancer patients had raised urinary cyclic GMP concentrations compared to the reference range for healthy subjects. For the non-cancerous and benign groups, 33% and 42% respectively had raised concentrations. The urine cyclic AMP concentrations were similar in all groups. Urine cyclic GMP appeared to rise early in the onset of malignant growth. Successful cancer treatment was accompanied by a dramatic fall in the urine cyclic GMP concentrations, whereas if the treatment was unsuccessful the level did not change. It is concluded that urine cyclic GMP may have important applications in the monitoring of cancer treatment.

Adolescent↗
PubMed1982

Levels of adenosine 3',5' cyclic monophosphate and guanosine 3',5' cyclic monophosphate in single urine specimens collected from a large population of healthy subjects.

The levels of adenosine 3',5' cyclic monophosphate and guanosine 3',5' cyclic monophosphate have been measured in random urine specimens provided by 95 healthy volunteers with a view to assessing the importance of the effects of certain physiological factors on the cyclic nucleotide levels in this type of specimen, and to establish suitable reference ranges for future patient monitoring studies. Of the factors investigated, only the stage of the menstrual cycle was found to have a significant effect; even this variation was still within the overall normal reference range. Measurements of urine cyclic nucleotides were also made in relation to the method of specimen collection, handling, and storage. From these studies it was concluded that if the specimen is placed in a refrigerator within a few hours of collection and then transferred to a deep-freeze within 48 hours, these factors do not present any major problems for the subsequent assay of the cyclic nucleotides.

Adult↗