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Biomedical subjects

N Paul

Publications and source records attributed to N Paul.

At least 19 recordsLinked to original sources

Effects of cultivar, fruit number and reflected photosynthetically active radiation on Fragaria x ananassa productivity and fruit ellagic acid and ascorbic acid concentrations.

BACKGROUND AND AIMS: A number of strawberry varieties were surveyed for their total ellagic acid concentration, and attempts were made to determine if ellagic acid and ascorbic acid concentrations of two strawberry cultivars could be increased by polythene reflective mulches. METHODS: After adjusting crop yields and cultivation using polythene mulches with two different PAR reflective capacities, field- and polytunnel-grown strawberries were analysed for ellagic acid and ascorbic acid concentrations by HPLC. Comparative measurements of yield and fruit quality were determined along with plant developmental changes. KEY RESULTS: Ellagic acid concentration varied widely with strawberry cultivar (60-341 microg g(-1) frozen weight), as did the ratio of conjugated ellagic acid : free ellagic acid. Also, there was significant year-to-year variation in total ellagic acid concentration with some cultivars. Mulches with different reflective capacities impacted on strawberry production; highly reflective mulches significantly increased growth and yield, the latter due to increases in fruit size and number. CONCLUSIONS: Highly reflective mulches significantly increased total concentrations of ellagic acid and ascorbic acid relative to control in fruit of different cultivars. The potential of agronomic practices to enhance the concentration and amounts of these important dietary bioactive compounds is discussed.

Ascorbic Acid↗

A HIPS-mimic.

Explore the source record for details and available documents.

AIDS-Related Opportunistic Infections↗

Decay of intestinal enterococci concentrations in high-energy estuarine and coastal waters: towards real-time T90 values for modelling faecal indicators in recreational waters.

Intestinal enterococci are the principal 'health-evidence-based' parameter recommended by WHO for the assessment of marine recreational water compliance. Understanding the survival characteristics of these organisms in nearshore waters is central to public health protection using robust modelling to effect real-time prediction of water quality at recreation sites as recently suggested by WHO and the Commission of the European Communities Previous models have more often focused on the coliform parameters and assumed two static day-time and night-time T90 values to characterise the decay process. The principal driver for enterococci survival is the received dose of irradiance from sunlight. In the water column, transmission of irradiance is determined by turbidity produced by suspended material. This paper reports the results of irradiated microcosm experiments using simulated sunlight to investigate the decay of intestinal enterococci in relatively turbid estuarine and coastal waters collected from the Severn Estuary and Bristol Channel, UK. High-turbidity estuarine waters produced a T90 value of 39.5 h. Low-turbidity coastal waters produced a much shorter T90 value of 6.6 h. In experiments receiving no irradiation, high-turbidity estuarine waters also produced a longer T90 of 65.1 h compared with corresponding low-turbidity coastal waters, T90 24.8 h. Irradiated T90 values were correlated with salinity, turbidity and suspended solids (r>0.8, p<0.001). The results suggest that enterococci decay in irradiated experiments with turbidity >200 NTU is similar to decay observed under dark conditions. Most significantly, these results suggest that modelling turbidity and or suspended solids offers a potential means of predicting T90 values in 'real-time' for discrete cells of a hydrodynamic model.

Dose-Response Relationship, Radiation↗

Radiation induced mucositis: co-ordinating a research agenda.

AIMS: A one-day workshop was hosted by the Symptom Control Committee of the National Cancer Institute of Canada, Clinical Trials Group (NCIC-CTG), in conjunction with the October 2002 annual meeting of the Canadian Association of Radiation Oncologists in Toronto, Ontario. The primary intention of the workshop was to direct the future research agenda of the Symptom Control Committee. Large group presentations were held initially to review the contemporary research issues of four selected areas of interest: fatigue, brain metastasis, bone metastasis and radiation-induced mucositis. Panel members were then charged with the identification of specific research proposals that could be considered for further development. Research questions were to be clinically relevant and currently appropriate. Any additional information needed before the launch of any potential trial was also requested. In this paper, we will review and summarise the outcomes from the radiation-induced mucositis sessions. MATERIALS AND METHODS: Thirty-four participants participated in the large group sessions and contributed to one of four panel discussions on selected supportive care issues relevant to radiation oncologists. RESULTS: Three potential and non-overlapping research questions were identified; two involving mucositis management in patients receiving radical radiation for head and neck cancer, and a third for patients with advanced lung cancer undergoing combined radiation and chemotherapy and at risk for the development of symptomatic oesophagitis. CONCLUSION: The workshop successfully identified three potential research questions. The large group and the smaller panel discussions successfully established consensus on important aspects of future study designs. The current 'standard of care', appropriate experimental treatments, primary outcomes of interest and study population parameters were each important issues that were discussed. The importance of developing meaningful biological assays was reviewed, as was the need to ensure the appropriate storage of biological samples from patients for future study.

Head and Neck Neoplasms↗

Gemcitabine, dexamethasone and cisplatin is an active and non-toxic chemotherapy regimen in relapsed or refractory Hodgkin's disease: a phase II study by the National Cancer Institute of Canada Clinical Trials Group.

BACKGROUND: Gemcitabine (difluorodeoxycytidine) is active as a single agent in Hodgkin's disease and has been used successfully in combination with cisplatin to treat a variety of solid tumors. PATIENTS AND METHODS: We evaluated the combination of gemcitabine/dexamethasone/cisplatin (GDP) as salvage chemotherapy in 23 patients with relapsed or refractory Hodgkin's disease (median age 36 years, range 19-57). Treatment consisted of gemcitabine 1000 mg/m(2) intravenously on days 1 and 8, dexamethasone 40 mg orally days 1-4 and cisplatin 75 mg/m(2) on day 1, every 21 days as an outpatient. Response was assessed following two cycles of treatment. RESULTS: There were four complete responses and 12 partial responses for a response rate of 69.5% (95% confidence interval 52% to 87%); the remaining seven patients had stable disease and no patient progressed on treatment. All patients had successful stem cell mobilization and underwent transplantation with a median 10.6 x 10(6) CD34+ cells/kg. Hematological toxicity from GDP was mild (grade 3 neutropenia 8.6%, grade 3 thrombocytopenia 13%). CONCLUSIONS: In summary, GDP is an active regimen for patients with relapsed or refractory Hodgkin's disease. The response rate is similar to the rates of other current salvage regimens, it can be given to outpatients with tolerable toxicity and it does not inhibit the mobilization of autologous stem cells.

Administration, Oral↗

["Health is a Crossroad"--Nature and society, individual and community, in safeguarding public health].

Any person actively engaged in the sphere of Public Health who refers to "molecular medicine" is bound to arouse suspicion. Nevertheless, neither Public Health nor public health protection or the health sciences in general can afford to ignore medicine and biology. This fundamental fact is explored in a historical and subsequently in an anthropological context. The connections between molecular medicine and public health are discussed at length. Accordingly, health on an individual as well as on a social level is essentially bound to the knowledge of genetically determined dispositions. We may expect that this molecular-genetic reality will become as "true" in future as the hygienic-bacteriological reality has become "true" today. The medicalisation of all human realities will be continued by their "molecularisation". It is important to fundamentally understand the actual effects of this transformation, which is the subject of a wider public discussion. This is the only way to rationally estimate both the opportunities offered by molecular medicine and the involved risks. It is essential for a debate of this kind within public health care institutions that the public health movement addresses the current developments of molecular medicine in a critical but constructive manner. "Nature", and with it the medicine and biology of public health, is an essential aspect of protecting public health. This is the only way to clarify the sphere of activity of public health protection in general, to appreciate its dynamics and to develop adequate measures: "Health is a crossroad" according to Julio Frenk: "It is where biological and social factors, the individual and the community, and social economic policy all converge".

Forecasting↗

Peptide nucleic acid-DNA duplexes containing the universal base 3-nitropyrrole.

A peptide nucleic acid (PNA) monomer containing the universal base 3-nitropyrrole was synthesized by coupling 1-carboxymethyl-3-nitropyrrole to ethyl N-[2-(tert-butoxycarbonylamino)ethyl]glycinate. The PNA sequence H-TGTACGTXACAACTA-NH2 (X = 3-nitropyrrole and C) and DNA sequence 5'-TGTACGTXACAACTA-3' were synthesized and thermal melting studies with the complementary DNA sequence 5'-TAGTTGTYACGTACA-3' (Y = A,C, G, T) compared. The T(m) data show that 3-nitropyrrole pairs indiscriminately with all four natural nucleobases as a constituent of either DNA or PNA. However, 3-nitropyrrole-containing PNA-DNA (average T(m) value = 51.1 degrees C) is significantly more thermally stable than 3-nitropyrrole-containing DNA-DNA (average T(m) value = 39.6 degrees C). From circular dichroism measurements, it is apparent that 3-nitropyrrole in the PNA strand causes a significant change in duplex structure.

Amino Acid Sequence↗

Antibacterial activity of Vitex trifolia.

The petroleum ether and ethanol extracts of Vitex trifolia leaves exhibited moderate inhibiting activity against both gram-positive and gram-negative bacteria.

Anti-Bacterial Agents↗

The effects of UVB and temperature on the survival of natural populations and pure cultures of Campylobacter jejuni, Camp. coli, Camp. lari and urease-positive thermophilic campylobacters (UPTC) in surface waters.

AIMS: To determine whether diurnal and seasonal variations in campylobacters in surface waters result from the effects of temperature and u.v. radiation, and whether natural populations of Campylobacter lari and urease-positive thermophilic campylobacters (UPTC) from birds survive better in surface waters than Camp. jejuni from sewage. METHODS AND RESULTS: Natural populations of Camp. lari and UPTC in sea water, and Camp. jejuni in river water, were exposed to artificial sunlight (equivalent to a sunny day in June). Both populations became non-culturable within 30 min, with T90s of 15 min and 25 min, respectively. Cultures of Camp. jejuni became non-culturable within 40 min and those of Camp. coli, Camp. lari and UPTC, within 60 min. In darkness, survival was temperature-dependent. Natural populations took 12 h at 37 degrees C and 5 days at 4 degrees C to become non-culturable in sea water, and slightly less in river water. Cultures of Camp. lari and UPTCs survived for significantly longer than Camp. jejuni and Camp. coli. Loss of culturability for all isolates was most rapid at 37 degrees C and slowest at 4 degrees C. Newly isolated strains from sea water and river water behaved in an almost identical manner to NCTC strains. CONCLUSION: Campylobacter lari and UPTCs survive for longer in surface waters than Camp. jejuni and Camp. coli, particularly in the dark. Low Campylobacter numbers in coastal waters in the summer, especially in the afternoon, are due to the combined effects of higher temperatures and higher levels of u.v. radiation. SIGNIFICANCE AND IMPACT OF THE STUDY: Campylobacter lari and UPTCs from birds predominate in bathing waters in Morecambe Bay because they are better able to survive; they also originate from closer to the shore than Camp. jejuni and Camp. coli in sewage effluent, which survive poorly and die before the incoming tide reaches the shore. The predominance of Camp. jejuni in river water results from its dominance of the inputs and not from its ability to survive.

Animals↗

Fiber type-specific expression of major proteolytic systems in fast- to slow-transforming rabbit muscle.

The present study investigates the role of two major proteolytic systems in transforming rabbit and rat muscles. The fast-to-slow transformation of rabbit muscle by chronic low-frequency stimulation (CLFS) induces fast-to-slow transitions of intact, mature fibers and replacement of degenerating fibers by newly formed slow fibers. Ubiquitination, an indicator of the ATP-dependent proteasome system, and calpain activity were measured in homogenates of control and stimulated extensor digitorum longus muscles. Calpain activity increased similarly (approximately 2-fold) in stimulated rat and rabbit muscles. CLFS had no effect on protein ubiquitination in rat muscle but led to elevations in ubiquitin protein conjugates in rabbit muscle. Immunohistochemistry was used to study the distribution of micro-calpain and m-calpain and of ubiquitinated proteins in myosin heavy chain-based fiber types. The findings suggest that both proteolytic systems are involved in fiber transformation and replacement. Transforming mature fibers displayed increases in micro-calpain and accumulation of ubiquitin protein conjugates. The majority of these fibers were identified as type IIA. Enhanced ubiquitination was also observed in degenerating and necrotic fibers. Such fibers additionally displayed elevated m-calpain levels. Conversely, p94, the skeletal muscle-specific calpain, decayed rapidly after stimulation onset and was hardly detectable after 4 days of CLFS.

Animals↗

Glutathione modulates the level of free radicals produced in UVA-irradiated cells.

We have developed an assay to detect reactive oxygen species (ROS) generated by UVA radiation utilising chemical probes which become fluorescent upon oxidation. Using a human bladder carcinoma cell line (MGH-U1) and spontaneously immortalised keratinocytes (HaCaT), we have shown a UVA (narrow band 365+/-5 nm) dose-dependent increase in fluorescence by flow cytometry following loading of the cells with either dihydrorhodamine 123 (DHR) or 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA). The UVA response of both DHR and DCFH was enhanced by elevation of intracellular levels of the photosensitiser protoporphyrin IX by incubation for 2.5 h with 5-aminolaevulinic acid. Depletion of the antioxidant glutathione (GSH) using the inhibitor D,L-buthionine-sulphoximine (BSO), resulted in an increase in the UVA-induced fluorescence of DCF but not of rhodamine 123. Conversely, raising intracellular GSH levels with N-acetyl cysteine (NAC) had relatively little protective effect in terms of degree of induced fluorescence.

Acetylcysteine↗

Intravenous urography in urinary tract surveillance in carcinoma of the bladder.

AIMS: The need for intravenous urography (IVU) in upper tract surveillance for primary transitional cell carcinoma (TCC) of the bladder is contentious. We reviewed our intensive screening policy in the follow-up of these patients to ascertain if such a policy is required and if specific groups could be identified to rationalise this protocol. METHODS: Review of the clinical and radiological data on 174 patients with a diagnosis of primary TCC of the bladder attending a teaching hospital urology department. RESULTS: Eight upper tract 'lesions' were identified: six TCC and two false-positive examinations using IVU. No link was demonstrable between upper tract recurrence and tumour stage, grade or multiplicity at diagnosis. All had recurrent bladder tumour but four of the six upper tract tumours occurred at 72 months or later. Twenty-nine patients over the study period developed either a dilated pelvi-calyceal system or a non-functioning kidney detected on IVU. CONCLUSIONS: Upper tract TCC can present late and patients with early bladder recurrence and those who do not show a reduction in bladder tumour number at follow-up cystoscopy are most at risk. IVU can probably be safely abandoned in those without local recurrence at 24 months. IVU is sensitive but not specific for upper tract tumour but also yields other relevant clinical information concerning the renal tract. Screening for upper tract metachronous disease should therefore be confined to those with recurrent transitional cell carcinoma of the bladder.

Adult↗

Exploratory studies on azole carboxamides as nucleobase analogs: thermal denaturation studies on oligodeoxyribonucleotide duplexes containing pyrrole-3-carboxamide.

In order to study base pairing properties of the amide group in DNA duplexes, a nucleoside analog, 1-(2'-deoxy-beta-D-ribofuranosyl)pyrrole-3-carboxamide, was synthesized by a new route from the ester, methyl 1-(2'-deoxy-3',5'-di-O-p -toluoyl-beta-D-erythro-pentofuranosyl)pyrrole-3-carboxylate, obtained from the coupling reaction between 1-chloro-2-deoxy-3,5-di-O -toluoyl-d-erythropentofuranose and methyl pyrrole-3-carboxylate by treatment with dimethylaluminum amide. 1-(2'-Deoxy-beta-D-ribofuranosyl)pyrrole-3-carboxamide was incorporated into a series of oligodeoxyribonucleotides by solid-phase phosphoramidite technology. The corresponding oligodeoxyribonucleotides with 3-nitropyrrole in the same position in the sequence were synthesized for UV comparison of helix-coil transitions. The thermal melting studies indicate that pyrrole-3-carboxamide, which could conceptually adopt either a dA-like or a dI-like hydrogen bond conformation, pairs with significantly higher affinity to T than to dC. Pyrrole-3-carboxamide further resembles dA in the relative order of its base pairing preferences (T >dG >dA >dC). Theoretical calculations on the model compound N-methylpyrrole-3-carboxamide using density functional theory show little difference in the preference for a syntau versus anti conformation about the bond from pyrrole C3 to the amide carbonyl. The amide groups in both the minimized antitau and syntau conformations are twisted out of the plane of the pyrrole ring by 6-14 degrees. This twist may be one source of destabilization when the amide group is placed in the helix. Another contribution to the difference in stability between the base pairs of pyrrole-3-carboxamide with T and pyrrole-3-carboxamide with C may be the presence of a hydrogen bond in the former involving an acidic proton (N3-H of T).

Azoles↗

Incurable suffering from the "hiatus theoreticus"? Some epistemological problems in modern medicine and the clinical relevance of philosophy of medicine.

Up to now neither the question, whether all theoretical medical knowledge can at least be described as scientific, nor the one how exactly access to the existing scientific and theoretical medical knowledge during clinical problem-solving is made, has been sufficiently answered. Scientific theories play an important role in controlling clinical practice and improving the quality of clinical care in modern medicine on the one hand, and making it vindicable on the other. Therefore, the vagueness of unexplicit interrelations between medicine's stock of knowledge and medical practice appears as a gap in the theoretical concept of modern medicine which can be described as "Hiatus theoreticus" in the anatomy of medicine. A central intention of the paper is to analyze the role of philosophy of medicine for the clarification of the theoretical basis of medical practice. Clinical relevance and normativity in the sense of modern theory of science are suggested as criteria to establish a differentiation between philosophy of medicine as a primary medical discipline and the application of general philosophy in medicine.

Decision Making↗