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Biomedical subjects

R L Knowles

Publications and source records attributed to R L Knowles.

9 recordsLinked to original sources
PubMed1995

The association between typhoid carriage, typhoid infection and subsequent cancer at a number of sites.

It has been demonstrated that bacteria can produce the very potent carcinogens (N-nitroso compounds), from nitrite and suitable amines. It has been hypothesized that this can happen whenever a body site which is normally sterile becomes colonized by bacteria. If this is so then such chronic infections should result in an increased incidence of local cancers and also of cancers at some distant sites. To test this we studied the risk of cancer at various sites in a cohort of chronic carriers of Salmonella typhi/paratyphi. We have observed a greatly increased risk of cancers of the biliary tract and also of cancers of the colorectum, pancreas, lung and all sites. The results are discussed in terms of the hypothesis being tested.

Adolescent↗
PubMed1994

Near-ultraviolet mutagenesis in superoxide dismutase-deficient strains of Escherichia coli.

We compared mutagenic spectra induced by polychromatic near-ultraviolet radiation (near-UV; 300-400 nm) with superoxide anion (O2-) -dependent mutagenesis using a set of Escherichia coli tester strains. Near-UV radiation produced increased frequencies of G:C to A:T transitions, G:C to T:A and A:T to T:A transversions, and small increases in frameshift mutations in wild-type cells. Tester strains lacking superoxide dismutase (SOD) activity (sodAsodB double mutants) demonstrated high spontaneous mutation frequencies and increased near-UV sensitivity. The double mutants also showed increased mutations induced by near-UV compared to either isogenic wild type, sodA or sodB single mutants. Furthermore, these mutants had an unusual spontaneous mutation spectrum, with a predominance of A:T to T:A transversions, followed by G:C to T:A transversions and frameshifts generated in runs of adenines in both the +1 and -1 direction. Other frameshifts were detected to a lesser degree. The oxygen dependency and the type of mutations spontaneously induced in SOD-deficient cells indicated that this mutagenic spectrum was caused by oxidative DNA damage. However, no apparent synergistic action between near-UV radiation and an increased flux of O2- could be detected. From the frequency and types of mutations induced by the two agents, we speculate that near-UV-induced mutagenesis and O2--dependent mutagenesis involve, in part, different lesion(s) and/or mechanism(s). The nature and possible mutagenic pathways of each are discussed.

Bacterial Proteins↗
PubMed1991

Increased risk of cancer mortality after vagotomy for peptic ulcer: a preliminary analysis.

Patients (1,643) undergoing vagotomy for peptic ulcer at York District Hospital were traced through the Office of Populations Censuses and Surveys (OPCS) and cause of mortality obtained for the 577 who had died. Expected mortality for the cohort was calculated using a years at risk calculation in 5 year bands. There was an excess risk of mortality from cancer of all sites (1.5-fold), stomach (1.6-fold), colorectum (1.7-fold), biliary tract (4.1-fold) and lung (1.6-fold). There was no excess risk or mortality from cancer of the oesophagus, pancreas and female breast. The numbers of deaths have been too few and length of follow-up too short to investigate latency. The findings are consistent with the production of carcinogens as a result of the hypoacidity following vagotomy.

Biliary Tract Neoplasms↗
PubMed1991

Patient equipment management: integrating a flexible alternative to purchase or lease.

As hospital CSS and OR departments work together to manage patient equipment, alternatives to purchase are available that can provide them with needed flexibility and responsiveness. A rental equipment provider that can meet the standards demanded for quality health care can become a valuable asset when developing and refining a hospitalwide equipment management program. But in order to receive the level of quality and service they should expect, hospitals must continually communicate their changing needs while holding their providers accountable to established standards.

Central Supply, Hospital↗
PubMed1990

Occupational and socioeconomic factors associated with peptic ulcer and with cancers following consequent gastric surgery.

Over 3000 patients, treated surgically for peptic ulcers, were assigned to a Social Class and Occupation Group using information obtained either from their death certificates or from their hospital notes. An analysis of the relationship of socioeconomic status and occupation with the site of original ulcer and the risk of cancer is reported. The major observations were: (a) an association of gastric ulcer with manual and of duodenal ulcer with non-manual Social Class; (b) an association of gastric cancer with dusty occupation and colorectal cancer with professional and managerial workers; and (c) no association between post-surgery gastric cancer risk and social class. This implies that the early stages of gastric carcinogenesis are related to poor socioeconomic conditions but the progression from the precursor lesion (in this case gastric ulcer) to gastric cancer is not, and is consistent with the multistage hypothesis of gastric carcinogenesis proposed by Correa [Diet and Human Carcinogenesis (Edited by Joosens, J. V., Hill, M. J. and Geboers, J.), pp. 109-115. Excerpta Medica, Amsterdam (1985)].

Colorectal Neoplasms↗
PubMed1984

Treatment of poorly controlled non-insulin-dependent diabetic patients with Acarbose.

Acarbose, 300 mg/day, was administered over one month in a cross-over trial to 18 hyperglycemic patients aged 41-66 years with non-insulin-dependent diabetes mellitus (NIDDM). All showed "normal" or exaggerated insulin release after a glucose challenge and remained in poor control (random glucose levels greater than or equal to 13 mmol/l) despite involvement in a diabetes intervention programme and prior use of oral hypoglycemic agents. During the one month treatment with Acarbose, fasting glucose and % HbAl concentrations were not different from those observed during placebo therapy. Furthermore, glucose tolerance was unchanged by Acarbose treatment. Glucose concentrations after a 1.6 MJ test meal were reduced by Acarbose from peak values of 17.3 +/- 1.0 to 15.0 +/- 1.1 mmol/l and were associated with lower post-prandial C-peptide (CPR) and insulin responses. Nevertheless, daily insulin production, as assessed by CPR excretion rates and plasma CPR and insulin concentrations, was not reduced by Acarbose. In fact, fasting plasma insulin and CPR levels were significantly higher during Acarbose then placebo therapy. Acarbose (100-400 mg/day) was continued for six months in 12 of these patients. During treatment, post-prandial glucose levels remained lower but monthly MBG values, determined by self-measurement of blood glucose, were unchanged except for small reductions in the 4th and 5th treatment months. % HbAl levels did not change. These data show that Acarbose treatment of a defined group of patients with poorly controlled NIDDM: resulted in small but sustained reductions of post-prandial glucose levels but without improving glucose tolerance, and reduced the circulating concentrations of insulin and CPR postprandially, but overall did not reduce daily production.

Acarbose↗