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Biomedical subjects

G Nichols

Publications and source records attributed to G Nichols.

At least 19 recordsLinked to original sources
PubMed2002

Phase II trial of sequential high-dose chemotherapy with paclitaxel, melphalan and cyclophosphamide, thiotepa and carboplatin with peripheral blood progenitor support in women with responding metastatic breast cancer.

A single high-dose cycle of chemotherapy can produce response rates in excess of 50%. However, disease-free survival (DFS) is 15-20% at 5 years. The single most important predictor of prolonged DFS is achieving a complete response (CR). Increasing the proportion of patients who achieve a complete response may improve disease-free survival. Women with metastatic breast cancer and at least a partial response (PR) to induction chemotherapy received three separate high-dose cycles of chemotherapy with peripheral blood progenitor support and G-CSF. The first intensification was paclitaxel (825 mg/m(2)), the second melphalan (180 mg/m(2)) and the third consisted of cyclophosphamide 6000 mg/m(2) (1500 mg/m(2)/day x 4), thiotepa 500 mg/m(2) (125 mg/m(2)/day x 4) and carboplatin 800 mg/m(2) (200 mg/m(2)/day x 4) (CTCb). Sixty-one women were enrolled and 60 completed all three cycles. Following the paclitaxel infusion most patients developed a reversible, predominantly sensory polyneuropathy. Of the 30 patients with measurable disease, 12 converted to CR, nine converted to a PR*, and five had a further PR, giving an overall response rate of 87%. The toxic death rate was 5%. No patient progressed on study. Thirty percent are progression-free with a median follow-up of 31 months (range 1-43 months) and overall survival is 61%. Three sequential high-dose cycles of chemotherapy are feasible and resulted in a high response rate. The challenge continues to be maintenance of response and provides the opportunity to evaluate strategies for eliminating minimal residual disease.

Adolescent↗
PubMed2002

Therapy-related myelodysplastic syndrome after autologous stem cell transplantation for breast cancer.

Therapy-related myelodysplastic syndrome and acute myelogenous leukemia (t-MDS/AML) are serious complications of chemotherapy and radiotherapy for cancer. High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) may be associated with an increased incidence of these complications. The frequency of t-MDS/AML after ASCT for breast cancer is uncertain. We reviewed our database of 379 consecutive breast cancer ASCT patients treated with alkylator-based chemotherapy, followed for a median of 1.52 years (range 0-8.97), with a median survival of 6.16 years. Three patients have developed tMDS/AML. The probability of developing this complication at 5 years is 0.032 in our series. We have used pathologic, cytogenetic and molecular methods to evaluate which portions of therapy may have predisposed to the development of this complication. Cytogenetic abnormalities were not found in the stem cell harvests of these patients by metaphase analysis or by fluorescence in situ hybridization (FISH). One patient demonstrated a clonal X chromosome inactivation pattern in her stem cell harvest, indicating pre-transplant chemotherapy may have been responsible for the development of her leukemia. As two of our patients developed this complication at greater than 4 years post-transplant, the number of cases may increase with longer follow-up. While the incidence appears to be low, further prospective and retrospective analysis will be necessary to determine which portions of therapy predispose to the development of t-MDS/AML in patients undergoing ASCT for treatment of breast cancer.

Acute Disease↗
PubMed2001

Reduction of paclitaxel-induced peripheral neuropathy with glutamine.

PURPOSE: Dose-limiting toxicity of many newer chemotherapeutic agents is peripheral neuropathy. Prior attempts to reduce this side effect have been unsuccessful. We report on the possible successful reduction of peripheral neuropathy with glutamine administration after high-dose paclitaxel. EXPERIMENTAL DESIGN: Patients entered a high-dose chemotherapy protocol in which the first high-dose cycle was paclitaxel at 825 mg/m(2) given over 24 h. The first cohort of patients did not receive glutamine, and the second cohort of patients received glutamine at 10 g orally three times a day for 4 days starting 24 h after completion of paclitaxel. Neurological assessment was performed at baseline, and at least 2 weeks after paclitaxel, and consisted of a complete neurological exam and nerve conduction studies. RESULTS: There were paired pre- and post-paclitaxel evaluations on 33 patients who did not receive glutamine and 12 patients who did. The median interval between pre- and post-exams was 32 days. For patients who received glutamine, there was a statistically significant reduction in the severity of peripheral neuropathy as measured by development of moderate to severe dysesthesias and numbness in the fingers and toes (P < 0.05). The degree and incidence of motor weakness was reduced (56 versus 25%; P = 0.04) as well as deterioration in gait (85 versus 45%; P = 0.016) and interference with activities of daily living (85 versus 27%; P = 0.001). Moderate to severe paresthesias in the fingers and toes were also reduced (55 versus 42% and 64 versus 50%, respectively), although this value was not statistically significant. All of these toxicities were reversible over time. CONCLUSIONS: Glutamine may reduce the severity of peripheral neuropathy associated with high-dose paclitaxel; however, results from randomized, placebo-controlled clinical trials will be needed to fully assess its impact, if any. Trials are currently ongoing to assess its efficacy for standard-dose paclitaxel in breast cancer and other tumors for which peripheral neuropathy is the dose-limiting toxicity.

Activities of Daily Living↗
PubMed2000

Characterisation of the influence of micronisation on the crystallinity and physical stability of revatropate hydrobromide.

Micronised particles of revatropate hydrobromide were observed to agglomerate when stored in uncontrolled conditions. Dynamic vapour sorption (DVS), isothermal microcalorimetry, microscopy and particle size measurement by laser diffraction have been used to study micronised revatropate hydrobromide. The rate and extent of agglomeration were dependent on the energy of the micronisation process, the sampling point for bulk within the mill and the humidity during storage. The agglomeration was attributed to the recrystallisation of disordered regions on the particles of revatropate hydrobromide generated during micronisation. This recrystallisation was assessed qualitatively and quantitatively, compared against spray-dried amorphous material, using DVS and isothermal microcalorimetry, respectively. A correlation was established between the energy of micronisation and the level of disorder within the micronised powder. A comparison of the DVS profiles of freshly prepared and aged micronised revatropate hydrobromide suggests an increased physical stability for the aged material.

Adsorption↗
PubMed2000

The microbiological quality of ice used to cool drinks and ready-to-eat food from retail and catering premises in the United Kingdom.

A survey of 4,346 samples of ice from retail and catering premises examined 3,528 samples (81%) used to cool drinks and 144 samples (3%) from food displays. For 674 samples (15%), the origin was not recorded. Most samples of ice used to cool drinks or ready-to-eat food on displays did not contain coliforms, Escherichia coli, or enterococci. Of the ice used to cool drinks, 9% contained coliforms, 1% E. coli, and 1% enterococci in excess of 10(2) CFU/100 ml, and 11% had an aerobic plate count at 37 degrees C in excess of 10(3) CFU/ml. The microbiological quality of ice used to cool drinks was poorer when melt water was present in the ice buckets. Ice used in food displays was more contaminated than ice used to cool drinks, with 23% containing coliforms, 5% E. coli, and 8% enterococci at 10(2) CFU/100 ml or more. Twenty-nine percent of samples had an aerobic plate count greater than 10(3) CFU/ml. Ice that had been used to cool shellfish was of a lower microbiological quality than samples used to cool ready-to-eat fish, salads, or dairy produce. Samples of ice produced in commercial production facilities were of higher microbiological quality than samples of ice that were not. The microbiological quality of ice was dependent on the type of use, the type of premises, and the type and place of production. Although most ice samples were of acceptable microbiological quality, evidence from this study suggests that the microbiological quality of ice prepared and used at certain premises in the UK is a cause for concern.

Colony-Forming Units Assay↗
PubMed2000

Microbiological standards for water and their relationship to health risk.

Maintenance of the microbiological quality of water has been used as an important means of preventing waterborne disease throughout the twentieth century. The commonest microbiological tests done on water are for coliforms and Escherichia coli (or faecal coliform). This paper reviews the legislative and other guidance for microbial standards in drinking and bathing waters and considers evidence for the relationship between the microbiological quality of water and risk to human health. In the past measures of the microbiological quality of water correlated well with risks of acquiring gastrointestinal disease. More recent work suggests that gastrointestinal disease is more strongly associated with the presence of enterococci than of E. coli. New diseases such as cryptosporidiosis have been shown to cause outbreaks of waterborne disease when levels of conventional microbiological parameters are satisfactory. In response to this, and because of failure of prosecution in one outbreak, the United Kingdom (UK) Government has introduced new legislation that requires water providers to perform a risk assessment on their water treatment facilities and to implement continuous monitoring for cryptosporidium. A new European directive on drinking water has been introduced and legislation on cryptosporidium in drinking water has been proposed in the UK.

Animals↗
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↗