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Biomedical subjects

G Nichols

Publications and source records attributed to G Nichols.

At least 37 records · Page 2Linked to original sources
PubMed2000

Cyclospora infections in England and Wales: 1993 to 1998.

The coccidian protozoon Cyclospora cayetanensis is a treatable cause of prolonged, watery diarrhoea in humans. Microbiology laboratories in England and Wales often restrict testing to those who have recently travelled abroad. Only 44 to 66 laboratory reports of C. cayetanensis are made in England and Wales each year and a large proportion are found to have visited developing countries. Large foodborne outbreaks of infection have arisen in North America among people who have not travelled abroad but no such outbreaks have been identified in the United Kingdom. Public health laboratories in England and Wales were surveyed in 1998 to investigate their procedures for identifying C. cayetanensis. Sixty-eight per cent actively looked for the protozoon, but only half used a recommended method of direct microscopy of formol ether concentrates. National external quality assurance results for all participating UK laboratories were reviewed to assess laboratory proficiency in identification. C. cayetanensis was correctly identified in a wet preparation by 58% of laboratories, the lowest rate for specimens containing a single parasite species. Cyclosporiasis could be acquired in the UK from imported food, but current laboratory procedures might fail to identify it. Ascertainment must improve and awareness needs to be raised among food handlers, public and environmental health workers, laboratory staff, and general practitioners. We recommend that laboratories test all patients with watery diarrhoea for > 1 week for cyclospora, use formol ether concentration and microscopy with a calibrated eyepiece graticule, and confirm diagnoses with the help of a reference laboratory.

Animals↗
PubMed2000

Foodborne outbreaks of cyclosporiasis have arisen in North America. Is the United Kingdom at risk?

Cyclospora cayetanensis is a parasitic protozoon that causes prolonged watery diarrhoea. It is endemic in some developing countries, and recent foreign travel is often used as a selection criterion for screening in the United Kingdom (UK). Epidemiological investigations of outbreaks of cyclosporiasis among people in the United States and Canada who had not travelled abroad showed the infection to be foodborne and often associated with foods eaten raw. These included raspberries imported from Guatemala, and pesto (made with basil) and lettuce from other sources. Such foods are also being imported in increasing amounts to the UK, but no outbreaks have been documented, perhaps because none has occurred or because of poor ascertainment. This paper reviews the outbreaks reported from North America, evaluates the risks to the UK population, and suggests how surveillance could be improved.

Animals↗
PubMed1998

Basic fibroblast growth factor downregulates Bcl-2 and promotes apoptosis in MCF-7 human breast cancer cells.

Basic fibroblast growth factor (bFGF) is a mitogen and a survival factor in fibroblasts and endothelial cells. It acts as an angiogenesis factor in breast cancer, but paradoxically inhibits proliferation in several breast cancer cell lines. In this study, we investigated the effects of bFGF on the survival of MCF-7 human breast cancer cells in order to determine if these effects were also opposite to those in fibroblasts. Incubation of NIH 3T3 cells with bFGF for 24 h caused an approximately 30% increase in day 12 +/- 2 adherent colonies while causing an approximately 50% decrease in MCF-7 colony formation. Incubation of NIH 3T3 cells with bFGF prior to etoposide or 5-fluorouracil treatment caused a proportionally smaller decrease in colony forming efficiency as a result of drug treatment, while preincubation of MCF-7 cells with bFGF caused a similar but opposite additive increase in drug-induced diminution of colony forming efficiency. These effects on MCF-7 cells were observed at variable times of incubation and doses of etoposide to 1 microM and 5-fluorouracil to 200 microM and at variable times of incubation and concentrations of bFGF to 1 ng/ml. Incubating with bFGF after drug exposure had similar effects on the reduction of cloning efficiency. The effects of bFGF were similar on programmed cell death, as determined by morphologic characteristics of apoptosis on 400 cell counts and FITC-dUTP 3'-OH DNA end labeling. Basic FGF promoted apoptosis and increased the rate of drug-induced cell death with both etoposide and 5-fluorouracil. While recombinant bFGF affected Bcl-2 protein and mRNA levels in NIH 3T3 cells only marginally and variably and had no discernible effects on Bax protein levels, it markedly downregulated Bcl-2 mRNA and protein levels in MCF-7 cells and caused an increase in Bax protein levels. These changes resulted in a decreased association of Bcl-2 with immunoprecipitable Bax and an increased association of Bax with immunoprecipitable Bcl-2 in MCF-7 cells treated with bFGF. These data suggest that bFGF may cause different phenotypic responses in breast cancer cells from those in surrounding cells and offer one possible mechanism through opposite regulation of Bcl-2 and Bax. Inhibition of colony formation by bFGF was observed in several breast cancer cells lines, demonstrating that this effect demonstrated in MCF-7 cells was more universal.

3T3 Cells↗
PubMed1998

Physicochemical characterization of the orthorhombic polymorph of paracetamol crystallized from solution.

This paper describes a method for the laboratory-scale crystallization of the orthorhombic polymorph (form II) of paracetamol (acetaminophen) from solution. Its structure has been determined by single-crystal X-ray crystallography at 298 K (to confirm the results of data published in 1974) and at 123 K (to improve the overall accuracy of the structure determination). Despite considerable effort by many investigators, the crystallization of form II from solution, using the method given in the 1974 structure report, has been elusive. The incentive for this effort is that form II, unlike commercial paracetamol (form I), undergoes plastic deformation and is suitable for direct compression. Consequently, the ability to produce form II in quantity has attracted much interest because of the potential commercial benefits to be gained by not using binders during the manufacture of tablets. However, until now, the only method that has been reported for the bulk preparation of form II has been to grow it as polycrystalline material from fused form I. This study also compares the solid-state properties of form II with those of form I, with particular emphasis on the crystallography (both X-ray and optical), crystal morphology, thermal behavior, and compaction properties.

Acetaminophen↗
PubMed1998

The contamination of pâté with Listeria monocytogenes--results from the 1994 European Community-Coordinated Food Control Program for England and Wales.

The Listeria monocytogenes contamination of 3,065 pâté products sampled at the point of retail sale in England and Wales was examined. Ninety-seven percent of samples were free of contamination with L. monocytogenes, 2.0% (60) had levels of less than 200 CFU/g, and 0.6% (18) had levels of 200 CFU/g or more. Fish and seafood pâté were significantly more commonly contaminated by L. monocytogenes than other pâté types (chi 2 test, P = 0.001). Pâté obtained from small retail shops was significantly more likely to be contaminated at levels of > or = 200 CFU/g (chi 2 tests, P < 0.0005) than that obtained from supermarkets. L. monocytogenes was isolated significantly more often (chi 2 tests, P < 0.00002) from packs of pâté that were open at the time of collection (3.8%) than those that were sold prepacked (1.2%). There were also significantly more samples (chi 2 test, P = 0.0009) where L. monocytogenes was recovered at higher levels (> or = 200 CFU/g) in opened, as compared to prepacked, samples. There was a significant difference in the rates and levels of contamination of opened samples between shops and supermarkets (chi 2 tests, P < 0.0025). Evidence from this study shows that most of the pâté sold in England and Wales is not contaminated with L. monocytogenes, and we suggest that the main areas of concern are cross-contamination and the length of display of pâté sold from opened packs.

Animals↗
PubMed1997

General outbreaks of infectious intestinal disease associated with milk and dairy products in England and Wales: 1992 to 1996.

Twenty general outbreaks of food poisoning in England and Wales associated with the consumption of milk and dairy products were reported to the PHLS Communicable Disease Surveillance Centre between 1992 and 1996. A total of 600 people were ill and at least 45 people were admitted to hospital but no deaths were reported. Salmonella species were responsible for 11 outbreaks, Campylobacter species for five, Vero cytotoxin producing Escherichia coli O157 (VTEC) for three, and Cryptosporidium parvum for one. Outbreaks were associated with hotels (2 outbreaks), a psychogeriatric hospital, schools (3), a Royal Air Force base, a farm visit, an outdoor festival (2), and community outbreaks associated with milk supplied direct from farms (8). Milk was implicated in 16 outbreaks; 10 of which were associated with unpasteurised milk. Two outbreaks were associated with eating contaminated ice cream, and two with eating contaminated cheese. All these outbreaks could have been prevented by pasteurisation and simple hygienic measures.

Adult↗
PubMed1995

Differentiation of immortal cells inhibits telomerase activity.

Telomerase, a ribonucleic acid-protein complex, adds hexameric repeats of 5'-TTAGGG-3' to the ends of mammalian chromosomal DNA (telomeres) to compensate for the progressive loss that occurs with successive rounds of DNA replication. Although somatic cells do not express telomerase, germ cells and immortalized cells, including neoplastic cells, express this activity. To determine whether the phenotypic differentiation of immortalized cells is linked to the regulation of telomerase activity, terminal differentiation was induced in leukemic cell lines by diverse agents. A pronounced downregulation of telomerase activity was produced as a consequence of the differentiated status. The differentiation-inducing agents did not directly inhibit telomerase activity, suggesting that the inhibition of telomerase activity is in response to induction of differentiation. The loss of telomerase activity was not due to the production of an inhibitor, since extracts from differentiated cells did not cause inhibition of telomerase activity. By using additional cell lineages including epithelial and embryonal stem cells, down-regulation of telomerase activity was found to be a general response to the induction of differentiation. These findings provide the first direct link between telomerase activity and terminal differentiation and may provide a model to study regulation of telomerase activity.

Animals↗
PubMed1995

Hypercalcaemia and increased serum interleukin-6 levels induced by all-trans retinoic acid in patients with multiple myeloma.

All-trans retinoic acid (ATRA) inhibits human myeloma cell growth in vitro, presumably through the down-regulation of interleukin 6 receptors (IL-6R). Based on these and other studies, we initiated a phase II clinical trial using ATRA in patients with advanced refractory multiple myeloma (MM). We report that three out of six treated patients developed severe hypercalcaemia following administration of ATRA, which was accompanied by a significant rise in serum IL-6 levels. Normal calcium levels were restored after the discontinuation of the drug and the administration of standard anti-hypercalcaemic care. We suspect that down-regulation of IL-6R resulted in increased serum IL-6 levels, leading to advanced bone resorption and hypercalcaemia. We conclude that the use of ATRA in patients with advanced MM is not warranted.

Humans↗
PubMed1989

Umbilical cord occlusion but not increased plasma T3 or norepinephrine stimulate brown adipose tissue thermogenesis in the fetal sheep.

Nonshivering thermogenesis is normally inactive in utero but increases with supplemental oxygenation and again after occlusion of the umbilical cord. To test the hypothesis that brown fat responses are triggered by the surge in triiodothyronine (T3) which occurs at birth, we studied 7 fetal sheep at 132-143 days gestation. Fetuses were first cooled 2-3 degrees C by circulating cold water through an external coil in the amniotic fluid and then ventilated with oxygen in utero to raise arterial PO2 to 109 +/- 10 (SEM) mmHg. An hour later T3 was infused intravenously to elevate and maintain plasma levels at 39.8 +/- 6.1 nmol/l, some 40-50 times basal levels. Indices of brown heat production did not rise during the next 30 min. Following snaring of the umbilical cord, however, plasma free fatty acid levels increased 400% to 423 +/- 91 mEq/l, plasma glycerol rose 350% to 766 +/- 168 mmol/1, and the temperature difference between brown fat and body core widened to 0.59 +/- 0.13 degrees C during the next 30 min. Whole body oxygen consumption peaked at 23.1 +/- 2.8 ml.min-1.kg-1 body weight. These responses to cord occlusion were similar with and without T3 administration. Changes in plasma catecholamines during these experiments did not correlate with the onset of nonshivering thermogenesis. We conclude that the rise in T3 or the changes in plasma catecholamines which occurs at birth are not causally related to the onset of nonshivering thermogenesis.

Adipose Tissue, Brown↗
PubMed1988

Progressive isoinertial lifting evaluation. I. A standardized protocol and normative database.

Dynamic tests of trunk strength and lifting capacity have become more popular in recent years, offering certain advantages over static isometric tests in measuring patient progress in functional restoration programs for spinal disorders. However, equipment for performing such tests is expensive to buy, complex to run, and requires technical expertise and clinical volume unavailable in most physician offices. In this study, a new dynamic test known as Progressive Isoinertial Lifting Evaluation (PILE) is described, which draws upon prior psychophysical and isoinertial methods. An industrial sample of 61 male and 31 female incumbent workers were tested using the PILE, and a variety of anthropometric normalizing factors were evaluated. The isolation of an "Adjusted Weight" (AW) normalizing factor is documented, after which normative data are presented for male and female workers utilizing lumbar (0-30 inches) and cervical (30-54 inches) dynamic protocols.

Adult↗
PubMed1988

Progressive isoinertial lifting evaluation. II. A comparison with isokinetic lifting in a disabled chronic low-back pain industrial population.

The Progressive Isoinertial Lifting Evaluation (PILE), as described in Part I of this series of articles, is a simplified test combining psychophysical and isoinertial protocols to provide an unconstrained lifting assessment. In the second part of this study, 100 chronically disabled low-back pain patients (57 men and 43 women) were studied at two points: 1) at initial evaluation, when referred for possible entry into a comprehensive Functional Restoration treatment program; and 2) at the conclusion of the treatment (an average 7 weeks later). Results of simultaneous lumbar PILE and Cybex Liftask (Lumex, Ronkonkoma, NY) tests are presented, showing that patients may frequently double or triple initial lifting capacity after undergoing the functional restoration training program, achieving lifting levels at or above normal for incumbent industrial workers. Overall, results demonstrate that the PILE test can be an effective baseline screening test for lifting capacity under certain circumstances. Although several drawbacks affecting the PILE as an isolated test are discussed, its usefulness as part of a battery of physical capacity tests making up a quantitative functional evaluation is clearly demonstrated. Finally, the potential use of PILE as a safe, inexpensive, simple, and relevant screening test for frequent lifting capacity in worker selection is discussed.

Back Pain↗
PubMed1987

Flow cytometric measurement of antiplatelet antibodies.

A flow cytometric technic was developed to detect platelet surface-bound immunoglobulin in patients with thrombocytopenia. Elevated platelet surface IgG and/or IgM was detected in 90.9% of patients with immune thrombocytopenia purpura (ITP). False positive results occurred in 9.3% of patients with nonimmune thrombocytopenia usually associated with sepsis. False negatives occurred most frequently in adults with chronic ITP. Measurement of platelet surface immunoglobulin with this flow cytometric technic helps differentiate immune from nonimmune thrombocytopenia.

Blood Platelets↗
PubMed1985

Studies on uptake and catabolism of vascular histamine in spontaneously hypertensive rats.

Reduced vascular histamine content is postulated to contribute to increased peripheral vascular resistance in experimental hypertension in rats. Experiments were conducted to examine histamine content, in vitro uptake ability and in vitro catabolism of histamine in blood vessels from 12-week-old spontaneously hypertensive rats (SHR) and age-matched normotensive controls. Histamine content of mesenteric artery and abdominal aorta from SHR was significantly reduced (P less than .05) when compared to Wistar-Kyoto normotensive controls. This finding confirms a similar observation of reduced vascular histamine content in deoxycorticosterone acetate salt hypertensive rats reported from our laboratory. This reduction in histamine content may be more prevalent in arteries because the decrease was not observed in the portal vein from SHR. Uptake of [14C]histamine into mesenteric artery and abdominal aorta was unchanged in SHR compared to Wistar-Kyoto controls. No significant differences between slopes for uptake regression lines were observed for either mesenteric artery or abdominal aorta. Mesenteric artery exhibited a greater capacity of [14C]histamine accumulation than aorta and significant reductions in accumulation of labeled histamine after 20 and 60 min were found in this vessel from SHR. Because metabolism of histamine was inhibited by aminoguanidine, this reduction may reflect diminished retention by histamine storage sites. In vitro I-[14C]histidine uptake was significantly increased in abdominal aorta and iliac artery but not mesenteric artery from SHR. These differences were also present at the later accumulation periods of 20 and 60 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

U.K. deep diving trials.

Using a breathing medium of 40 kPa oxygen, remainder helium, 18 volunteer subjects participated in a series of 15 exposures to pressures equivalent to depths of 180-540 m s.w. The time of exposure at these pressures was mostly 2 days, except for the 540 m s.w. exposure, when 6 days were spent at full pressure. Compression procedures, based upon placing 'stages' at 60 m s.w. intervals, evolved with experience and proved to be a highly successful way of achieving acceptable pressure-time courses. Decompression combined slow linear release of pressure with overnight halts for sleep. On one occasion a depth of 660 m s.w. was reached by breathing 40 kPa oxygen, 10% nitrogen, remainder helium. Throughout all exposures, teams of investigators followed the changes in cardiovascular, respiratory, haematological, neurophysiological and metabolic status, and mental performance of the volunteers. Some major findings were that the neurophysiological and behavioural changes could be assigned to the motor, or vestibular, or cerebral, or autonomic systems, and were mainly first observed during compression. The subjects suffered, apparently from severe nitrogen narcosis, when breathing 10% (by volume) nitrogen in oxygen-helium at 420 m s.w. Lung ventilation was remarkably adaptable to the oxygen requirements of exercise at all depths, but cardiac output was adversely affected at 540 m s.w., particularly for heavier workloads. Ventilatory responses to carbon dioxide were significantly elevated after diving. Thermal balance was seen to be precarious, but nevertheless it was achieved by the normal subjective assessments of comfort. Water loss was affected by diminished evaporation from the skin. Skin temperature sensitivity was changed and took many days after the dives to return to normal. Energy requirements increased for work purposes, but basal metabolic rate was undisturbed. Body chemistry altered at pressures in excess of 300 m s.w., for example thyroid hormone and nitrogen balances were affected. No decompression sickness was encountered until the pressures were low, but marked haematological changes could occur during decompression. Every change that occurred during these dives reverted to normal, mostly before the end of the decompression. It is concluded that diving with oxygen-helium breathing mixtures to depths as great as 540 m s.w. can be effective and safe. An attempt is made to assess the physiological significance of the principal findings.

Adult↗