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Biomedical subjects

J E Payne

Publications and source records attributed to J E Payne.

At least 19 recordsLinked to original sources
PubMed1992

Six week safety study of 2% MK-927 administered twice daily to ocular hypertensive volunteers.

Ocular hypertensive patients were enrolled in a 6-week double-masked safety study of 2% MK-927 (27 patients), a topically active carbonic anhydrase inhibitor, administered bilaterally b.i.d.; 9 additional patients received 0.5% timolol as the control agent. Intraocular pressure (IOP) was measured weekly prior to a.m. drug administration; twelve hour diurnal curves were performed prestudy and at 3 and 6 weeks. The mean reduction of IOP prior to a.m. drug administration ranged from 1.2 +/- 4.4 mm Hg (SD) to 3.0 +/- 4.2 mm Hg with MK-927 and from 4.7 +/- 3.9 mm Hg to 8.8 +/- 0.6 mm Hg with timolol. Mean outflow facility measured tonographically prestudy and on days 33 to 42 four hours after a.m. drug administration was unchanged in both groups. Corneal sensitivity (Cochet-Bonnet), corneal thickness (ultrasound pachymetry), Schirmer tear testing, and extensive ophthalmologic and medical examinations, and hematologic studies were not substantially altered throughout the study. In this longest chronic administration study to date, MK-927 did not cause adverse ocular or systemic side effects.

Adult↗
PubMed1992

Carnitine deficiency associated with long-term pivampicillin treatment: the effect of a replacement therapy regime.

A 51 year old female developed a skeletal muscle myopathy after 3 months of pivampicillin therapy. Pivampicillin can cause carnitine deficiency due to the pivalic acid side group. Plasma carnitine content and the patients symptoms failed to improve significantly on discontinuing the drug. Oral carnitine replacement therapy was administered for 6 weeks but the patient's plasma carnitine levels responded only slowly to this treatment. It is suggested that pivampicillin inhibits uptake of carnitine from the gut and may either directly or indirectly depress endogenous carnitine synthesis. In such cases a more aggressive carnitine replacement regime is indicated and pivampicillin should be avoided in patients requiring long-term antibiotic administration.

Carnitine↗
PubMed1991

Effects of Furegrelate (Upjohn 63557A) on patency and platelet deposition after canine carotid endarterectomy.

Platelet deposition upon endarterectomy sites is a likely cause for early postoperative thrombosis, embolism and restenosis. Platelets aggregate by the thromboxane-prostacycline mechanism. Thromboxane synthetase inhibitors which have been safely administered to humans should reduce platelet deposition after surgical therapy and therefore reduce peri-operative mortality and the prevalence of stroke. A randomized prospective controlled trial was designed to determine vessel patency and platelet deposition associated with the use of 3 mg/kg and 30 mg/kg of Furegrelate (Upjohn U63557A) daily in dogs, who were to have carotid endarterectomy. The 46 treated and 46 control dogs had total carotid patency of 96% and 76% respectively (P less than 0.01). Fourteen dogs treated with 30 mg/kg Furegrelate had no occlusions, compared with a 19% prevalence in 13 controls (P less than 0.02). Furegrelate 10 mg/kg significantly lowered platelet aggregation. Platelet deposition was not significantly changed, however. The reason for this disparity was a probable persistence of vessel wall factors which promoted platelet deposition. This approach might therefore lower rates of peri-operative thrombosis but it would be very unlikely to alter the incidence of restenosis or embolism. Further research could be directed towards modifying the stimuli for platelet deposition upon the endarterectomy site.

Animals↗
PubMed1990

Colorectal carcinogenesis.

It is generally accepted that genetic and environmental factors combine in the aetiology of bowel cancer. Epidemiological studies have shown that the environmental factors effects are shown more clearly in the left colon, and that they are related to living in western societies whose diets contain high levels of protein, fat and energy. There has been recent awareness that consumption of alcoholic beverages, particularly beer, may be causally related to cancers of the left colon and rectum. This review attempts to relate the general epidemiological data to more specific mechanisms of colorectal carcinogenesis. Dimethylhydrazine (DMH) and N-nitroso chemicals are potent colorectal carcinogens in animals. They have not been thought very relevant to humans because their existence in appropriate forms in the environment has been debatable and analytical methods for the specific detection of non-volatile nitrosamines and nitrosamides have not been available. Recently, however, relevant alkylating activity has been detected in foods incubated in quasi-gastric conditions, and several epidemiological studies have shown a protective effect for Vitamin C, which may inhibit the development of rectal cancer through beer consumption. As Vitamin C prevents nitrosation and as precursors of nitrosamides are present in prepared foods, further dietary studies with hypotheses based on N-nitroso carcinogenesis are required. Unfortunately, these studies will probably not show clear dose-response relationships. Many of the complex reasons for this are discussed; however, one of the most important could be related to an interplay between inherited and environmental factors. The inherited factors demonstrated by chromosomal analysis in cancer and polyposis syndromes are a reminder that other genetic (oncogenetic) changes may occur in sporadic colorectal cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

Carcinogens↗
PubMed1989

International colorectal carcinoma staging and grading.

Pathologic (Dukes) and clinicopathologic staging systems (Australian and TNM) are all used for the staging of colorectal cancer. Many modifications of the systems, with different standards of evidence, are currently used for a variety of purposes. It is not yet possible to readily exchange data from one staging system to another because of the lack of uniform anatomic and pathologic subdivisions. It would also be an advantage if staging systems more confidently predicted potential for cure. It is proposed that the TNM based system be modified to satisfy these requirements. Modifications identify common ground between the various systems, use prognostic variables shown to be significant by multivariate analyses, and introduce an abbreviated form of tumor grading. Grading improves prediction of cure and allows standardization of the composition of stages and substages because distant metastatic potential is shown to be related to the presence of high grade. The modifications are considered necessary and appropriate for epidemiologic and clinical studies.

Colorectal Neoplasms↗
PubMed1989

Reduction in amputation stump infection by antiseptic pre-operative preparation.

The prevalence of ischaemic or infective delayed wound healing in amputations for peripheral vascular disease may vary from 18 to 40%. A prospective trial to test the efficacy of 12 h pre-operative preparation with 10% povidone-iodine was performed in a 1-year period, during which time 80 consecutive amputations were performed on 73 patients. Accrual to the treatment arm was incomplete and was principally due to extreme nursing shortages. Failure of randomization resulted in the study being analysed as if it were retrospective. Infection occurred in 14 (23%) of unprepared limbs but was not found in any of the 19 prepared limbs (P less than 0.05). Infection occurred in 11 of 34 unprepared limbs which had distal ulcers or moist gangrenous lesions; however, 15 prepared limbs which had similar distal lesions had no infection (P less than 0.025). The reduction of wound breakdown and infection resulted in a significant reduction in hospitalization prior to commencement of prosthetic fitting (P less than 0.001). Pre-operative antiseptic preparation played an important role in the reduction of infection following amputation for peripheral vascular disease, particularly for those patients whose amputation was required because of contaminated peripheral ischaemic lesions. However, these preliminary results should be confirmed by further study.

Aged↗
PubMed1987

The cost of resection for colorectal cancer.

The aim of this study was to determine the average total cost and component costs of the surgical management of colorectal cancer (CRC) in a large teaching hospital and to examine the relationships between cost and several characteristics of the patients. Data were compiled for 97 consecutive patients undergoing resection for CRC at Concord Hospital in 1979. The cost of the following components was calculated for each patient: (a) pre- and postoperative bed occupancy; (b) investigations; (c) operation; (d) anaesthetic; (e) prescribed drugs; (f) allied health services. The cost of bed occupancy was by far the largest item in the average total cost (72%), followed by the cost of investigations (11%). There was no correlation between pre- and postoperative bed occupancy and no patient characteristic had a statistically significant effect on pre-operative stay. Several factors were associated with prolonged postoperative stay including the number of clinical problems, operation for rectal as opposed to colonic cancer, having a two-stage procedure, surgical complications and wound infection. By far the greatest reduction in total cost could be achieved by reducing the length of postoperative stay.

Adult↗
PubMed1986

Surgery for large bowel cancer in people aged 75 years and older.

Three hundred ten predominantly male patients who were 75 years of age or older and had surgery for colorectal carcinoma had a hospital mortality rate of 9 percent and a cancer-related five-year survival of 50 percent. These results and a detailed analysis of the causes of complications and mortality were compared with the outcome of 710 patients who were treated concurrently and who were younger than 75 years. Tumors in older patients had a tendency to occur on the right side and were more locally advanced. Increased mortality was particularly attributable to sepsis and cardiovascular causes. Increased morbidity was due principally to respiratory and urinary problems. There were no significant differences, however, in wound or anastomotic complications, nor was therapy for the older patients more costly. The indications for surgical resection for colorectal cancer in patients aged 75 years and older should be the same as those for any younger group.

Adenocarcinoma↗
PubMed1986

Gland to gland heterogeneity in histologically normal mucosa of colon cancer patients demonstrated by monoclonal antibodies to tissue-specific antigens.

Two of three monoclonal antibodies to tissue-specific antigens of isolated colonic glands revealed gland to gland heterogeneity of antigen expression in sections of the histologically normal colonic mucosa from patients with colorectal adenocarcinoma or various nonmalignant conditions. A colon-specific goblet cell antigen (designated 3NM) was absent from rare, solitary glands randomly distributed among the otherwise strongly stained glands of distal colon. These 3NM-negative glands stained normally for the other two antigens studied and appeared morphologically and histochemically normal. They occurred in 11 of 13 cancer patients and in each of the five patients with benign conditions with median incidences of 2.2 and 0.4 per 1000 glands, respectively. Gland heterogeneity was also demonstrated in both patient groups for a cell membrane antigen (designated 6NM). In cecum and ascending colon, glands staining strongly and weakly for 6NM were found intermixed. The weakly stained glands tended to predominate in cecum and first part of ascending colon, but they were completely replaced by strongly stained glands in more distal colon. The heterogeneity shown by both 3NM and 6NM appeared due to phenotypically distinct cell clones. Our observations indicate that histologically normal colonic mucosa contains antigenically diverse gland populations.

Antibodies, Monoclonal↗
PubMed1986

Antigen expression in normal and neoplastic colonic mucosa: three tissue-specific antigens using monoclonal antibodies to isolated colonic glands.

Monoclonal antibodies to normal colonic glands were used to localize three tissue-specific antigens in sections of 40 hyperplastic polyps, 29 adenomas, 43 colorectal adenocarcinomas, and blocks or rolls of histologically normal large bowel mucosa. Two antibodies identified antigens (designated 3NM and 17NM) associated with the mucin vacuole of goblet cells and the third antibody identified a cell membrane antigen (designated 6NM). Antigen 3NM was absent from virtually all carcinoma cells and from all, or most, cells of hyperplastic polyps. Antigen 17NM was absent from 21 carcinomas, with some antigen-positive cells present in the others. Antigen 6NM content was unchanged compared to normal mucosa in 12 carcinomas, decreased somewhat in another 20, and either absent or markedly depleted in 11. Antigen 6NM increased in 22 hyperplastic polyps. Three cancer patients synthesized 6NM in their normal mucosa but the cellular distribution was abnormal. Antigens decreased in most adenomas, with heterogeneity of expression seen in glands and cells of some adenomas. Low concentrations of one or more antigens in normal mucosa were significantly more frequent (P less than 0.05) in patients with metastases than in those with stage A or B tumors.

Adenoma↗
PubMed1985

Patient selection for adjuvant therapy trials in colorectal carcinoma.

The aim of this research was to determine how to improve the efficiency of study design in adjuvant therapy trials of colorectal carcinoma. Survival analysis related to pathological variables was performed on 1020 patients who had resections for colorectal carcinoma during an 11 year complete follow-up. It was felt that the median survival of B stage patients was too long to justify their inclusion in survival trials. Practical multi-centre trials could be undertaken with patients who were found to have clinicopathological stage C. Fifty per cent of the total number of stage C patients had primary tumours with either high grade or venous invasion of mural and extra-mural veins. They had a highly significantly (P = 0.0004) poorer prognosis (median survival 27 months) than those with low or average grade and no venous invasion (median survival 49 months). The most efficient trial would select patients whose primary tumours showed lymph node involvement and high grade and venous invasion.

Clinical Trials as Topic↗
PubMed1979

A pattern of local recurrence following resection of colorectal cancer.

Twenty patients (10%) developed a local recurrence following 200 consecutive curative resections for colorectal carcinoma. Analysis of the pathology of the primary tumours suggests that invasion of adjacent tissues, and lymph node involvement, were more important presection on the mucosa. The average time interval between resection and diagnosis of local recurrence was 17 months. The average survival time following diagnosis was 10 months. Nineteen out of 20 of these patients developed evidence of disseminated disease subsequent to the diagnosis of local recurrence. The most effective palliation occurred in patients in whom the local recurrence could be resected.

Colonic Neoplasms↗
PubMed1978

Decompression sickness in the goat: nature of brain and spinal cord lesions at 48 hours.

An investigation was undertaken to determine whether permanent damage to the central nervous system (CNS) is associated with transient decompression sickness in the goat. Twelve goats were compressed in air at 100 fsw for one hour. After decompression over a period of 2.5 min, seven animals showed signs of decompression sickness and four of these were treated by recompression in oxygen. Residual clinical signs after 12 h were present in one animal only. The seven affected goats were killed 48 h after decompression. Lesions in the CNS (other than hemorrhage) were confined to the spinal cord of three animals that had shown paralysis, and consisted of infarction of white matter with occasional microthrombi and perivascular proteinaceous edema of the gray matter. In all seven animals, there was hemorrhage in the spinal cord and in four, hemorrhage in the brain. Infarction of the spinal cord was not present in the four animals that had shown only slight clinical signs (limping); one of these goats had been treated by recompression in oxygen.

Animals↗