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Biomedical subjects

D Phil

Publications and source records attributed to D Phil.

17 recordsLinked to original sources
PubMed2006

Problems associated with scuba diving are not evenly distributed across a menstrual cycle.

The problems encountered during scuba diving may be a contributing factor in an episode of decompression illness (DCI). Evidence exists that there may be a relationship between the position in the menstrual cycle and the occurrence of DCI. We examined, by prospective observation in female recreational scuba divers, any interaction between reported problems during diving (RPDD) and the position in the menstrual cycle. A total of 533 women, aged between 14 and 57 years, returned diaries for >6 months, with 61% returning diaries for 3 consecutive years. A total of 34,625 dives were reported within 11,461 menstrual cycles between 21 and 40 days in length, with 65% of women reporting at least one RPDD. Logistic regression showed a significant non-linear relationship between the position in the menstrual cycle and RPDD (p = 0.004). RPDD were not evenly distributed over the menstrual cycle; the rate per 1,000 dives varied from 39.2 at start of the cycle to 19.7 during week 3, and 31.9 in week 4. We concluded these field data suggest a possible correlation between the incidence of RPDD and the position in which they occurred in the menstrual cycle.

Adolescent↗
PubMed2004

Incidence of inflammatory bowel disease is rising and abdominal tuberculosis is falling in Bangladeshis in East London, United Kingdom.

OBJECTIVES: Ulcerative colitis (UC) and Crohn's disease (CD) were previously thought to be uncommon and abdominal tuberculosis (TB) common in patients from Bangladesh. We have reevaluated their incidence in Bangladeshis resident in East London. METHODS: Bangladeshis resident in Tower Hamlets presenting between 1997 and 2001 were identified from pathology, endoscopy, and medical records. Demographic, clinical, and management details were recorded. Incidences were calculated and compared with those from 1981 to 1989. RESULTS: Sixteen Bangladeshi patients with UC, 19 with CD, and 5 with abdominal TB were identified. Between 1997 and 2001, the age-standardized incidence of UC was 8.2/10(5)/yr (95% CI 2.5-13.9) compared with 2.4 (95% CI 0.8-3.8) in 1981-1989, and that of CD was 7.3/10(5)/yr (95% CI 2.0-12.6) (2.3, 95% CI 0.7-3.7 in 1981-1989). The standardized ratios for the incidences of UC and CD in recent periods compared with previous periods were 2.1 (95% CI 0.9-3.9) and 2.5 (1.2-4.6), respectively. There was a significant increase in the number of Bangladeshis developing CD by age <20 yr between the earlier and more recent periods (p < 0.02). The standardized incidence of abdominal TB was 2.5/10(5)/yr (95% CI 0.2-4.8) in 1997-2001, and 7.4 (95% CI 2.1-12.7) in 1985-1989 (p < 0.05). The standardized ratio for the incidence of TB in the two periods was 0.22 (95% CI 0.07-0.53). CONCLUSIONS: In Bangladeshis in East London, the incidence of IBD has increased and of abdominal TB has fallen over the last decade; CD has become a more likely diagnosis than abdominal TB. Clinicians in the Western world need to be aware of the changing incidences of IBD and abdominal TB in South Asians.

Adolescent↗
PubMed2000

Sensitivity and power deposition in a high-field imaging experiment.

Image signal-to-noise ratio and power dissipation are investigated theoretically up to 400 MHz. While the text is mathematical, the figures give insights into predictions. Hertz potential is introduced for probe modeling where charge separation cannot be ignored. Using a spherical geometry, the potential from current loops that would produce a homogeneous static B1 field is calculated; at high frequency it is shown to create an unnecessarily inhomogeneous field. However, a totally homogeneous field is shown to be unattainable. Boundary conditions are solved for circularly polarized fields, and strategies for limited shimming of the sample B1 field are then presented. A distinction is drawn between dielectric resonance and spatial field focusing. At high frequency, the region of maximum specific absorption is shown to move inside the sample and decrease. From the fields in both rotating frames, the signal-to-noise ratio is derived and compared with the traditional, low-frequency formulation. On average, it is mostly found to be slightly larger at high frequency. Nevertheless, the free induction decay is sometimes found to be annulled.

Electromagnetic Fields↗
PubMed2000

Phage therapy: the peculiar kinetics of self-replicating pharmaceuticals.

The specter of antibiotic-resistant bacteria has provoked renewed interest in the possible use of bacteriophages to control bacterial infections. We argue that clinical application of phage therapy has been held back by a failure to appreciate the extent to which the pharmacokinetics of self-replicating agents differ from those of normal drugs. For self-replicating pharmaceutical agents, treatment outcome depends critically on various density-dependent thresholds, often with apparently paradoxical consequences. An ability to predict these thresholds and associated critical time points is a necessity if phage therapy is to become clinically practicable.

Animals↗
PubMed1999

Temporomandibular Joint Arthroplasty Using Metal-on-Metal and Acrylic-on-Metal Configurations : Wear In Laboratory Tests and In Retrievals.

In the long-term performance ofthe temporomaridibular joint (TMJ) implant, wear must be considered. Thus retrieved and laboratory test implants were examined both optically and in a scanning electron microscope (SEM). In laboratory testing, the volumetric wear of metal-on-metal was about an order of magnitude less than that of acrylic-on-metal TMJ implants. This metal-on-metal wear was also about half of that reported in the literature for a laboratory test of polyethylene-on-metal TMJ implants, The retrieved TMJ implants showed some abrasive wear occurred during multi-directional articulation with smaller wear zones for the metal-on-metal compared to the acrylic-on-metal configuration. Further efforts to characterize and minimize wear were recommended as prudent in the continuing development of TMJ arthroplasty.

Journal Article↗
PubMed1998

Prefrontal glucose deficits in murderers lacking psychosocial deprivation.

Previous research has suggested that links between autonomic nervous system functioning and violence are strongest in those who come from benign home backgrounds, but there appears to be no similar research using brain-imaging measures of central nervous system functioning. It was hypothesized that murderers who had no early psychosocial deprivation (e.g., no childhood abuse, family neglect) would demonstrate lower prefrontal glucose metabolism than murderers with early psychosocial deprivation and a group of normal controls. Murderers from a previous study, which showed prefrontal deficits in murderers, were assessed for psychosocial deprivation and divided into those with and without deprivation. Murderers without any clear psychosocial deficits were significantly lower on prefrontal glucose metabolism than murderers with psychosocial deficits and controls. These results suggest that murderers lacking psychosocial deficits are characterized by prefrontal deficits. It is argued that among violent offenders without deprived home backgrounds, the "social push" to violence is minimized, and consequently, brain abnormalities provide a relatively stronger predisposition to violence in this group.

Adult↗
PubMed1997

Current concepts in the pathogenesis of Alzheimer's disease.

Alzheimer's disease (AD) affects a large proportion of the increasingly aging population of this country, with prevalence rates as high as 47% for those >85 years old and a total annual cost approaching $70 billion. There is no currently validated test for detection of dementia of the Alzheimer type (DAT). Because of this and the insidious onset of the disease, the diagnosis may be missed by primary care physicians. Cerebral extracellular beta-amyloid deposition as senile plaques and intraneuronal neurofibrillary tangles appear to represent critical processes in the development of AD; however, whether and the extent to which these may also occur in nondemented aging is uncertain. Tangles occur primarily in medial temporal lobe structures (hippocampus, entorhinal cortex, and amygdala), and tangle density correlates with dementia severity. Plaques are diffusely distributed throughout the cerebral cortex, and are the neuropathologic hallmark of the disease. Aging is the primary risk factor for AD. After controlling for differential life expectancy, female sex still appears to be an additional risk factor. There may be a genetic component, in some cases based on family and twin studies. Allelic variation in the apolipoprotein E (Apo E) gene located on chromosome 19 represents another important risk factor. However, the diversity of gene mutations apparently responsible for the various forms of AD suggest that the disease is genetically heterogeneous. AD may be conceptualized as an imbalance between neuronal injury and repair. Oxygen free radicals may be involved in the cross-linking process of beta-amyloid aggregation, and antioxidants may represent a potential intervention. There may be a role for heavy metals in the pathogenesis of AD, but this remains controversial. Work continues toward possibly a cure or prevention, but more likely palliation, of AD, and the results of trials of anti-inflammatory agents, estrogen, and antioxidant therapy are anticipated in the near future.

Aging↗
PubMed1996

Effect of methylation on the electrophoretic mobility of chromosomal DNA in pulsed-field agarose gels.

Factors other than molecular weight are known to affect DNA electrophoretic mobility. DNA methylation has been found to affect the curvature of DNA, causing anomalous mobility in polyacrylamide gels; the effect of methylation on the mobility of large DNA molecules in agarose gels was unknown. Chromosomal DNA from Mycoplasma capricolum, a wall-less prokaryote which has a low intrinsic methylation rate, was methylated in agarose blocks by SssI methylase, a de novo methylase with a CpG recognition sequence. (A surprising finding was that SssI methylase altered the structure of InCert, but not SeaKem Gold, agarose.) Restriction enzyme analysis was used to estimate the extent of CpG methylation. DNA methylation was found to have no effect on the electrophoretic mobility of full-length chromosomal DNA (1,120 kbp) in agarose gels. Therefore, methylation is not a source of error in PFGE-based size estimation for chromosomal DNA molecules less than 1.12 Mbp in agarose gels.

Chromosomes, Bacterial↗
PubMed1994

Inhibitors of phosphatidylinositol signalling as antiproliferative agents.

Intracellular signalling pathways mediating the effects of oncogenes on cell growth and transformation offer novel targets for the development of anticancer drugs. With this approach it may be sufficient to target a component of the signalling pathway activated by the oncogene rather than the oncogene product itself. Phosphatidylinositol (PtdIns) is a key component of two growth factor signalling pathways. It acts as a substrate for PtdIns specific phospholipase C (PtdInsPLC) and for PtdIns-3-kinase. In this review the antiproliferative properties of some inhibitors of PtdInsPLC and PtdIns-3-kinase are considered. There are some compounds already in clinical trial as anticancer drugs that may act by inhibiting PtdIns signalling, as well as several compounds in preclinical development. Some problems that may be encountered in developing this new class of anticancer drugs are discussed.

Animals↗
PubMed1993

Recent advances in breast feeding.

Increasingly, epidemiological studies are showing the benefits of exclusive breast-feeding to infants in industrialized countries, as they have previously for those in developing countries. In this review we have focused on several recent developments, in particular on the interplay between infant behaviour and maternal physiology in regulating breast milk supply. This will illustrate that many past and current clinical problems concerning breast-feeding are likely to be of iatrogenic origin, the products of imposing arbitrary rules for breast-feeding management. In order for the protective benefits to be fully realized it is necessary to ensure that breast-feeding is free from prescriptive practices. We will illustrate the key role played by the infants' control of appetite in the hope of encouraging clinicians to empower infants to exercise more control over the feeding process.

Appetite Regulation↗
PubMed1992

NLA-1: a 2-nitroimidazole radiosensitizer targeted to DNA by intercalation.

Targeting of electron affinic radiosensitizers to DNA via reversible non-covalent intercalative binding has potential for increasing sensitizer concentrations locally at the DNA target while decreasing accessibility to reductases responsible for bioactivation and cytotoxicity. We have prepared an DNA-targeted acridine-linked 2-nitroimidazole (NLA-1) as an example of such a compound. NLA-1 binds reversibly to DNA with an affinity similar to 9-aminoacridine, and is approximately 1000 times more potent than MISO as a cytotoxin, despite a similar reduction potential. It shows less enhancement of cytotoxicity under hypoxia (5- to 6-fold) than does MISO (approximately 11-fold), but is a potent hypoxia-selective radiosensitizer in AA8 cells with a concentration for an enhancement ratio of 1.6 (C1.6) of 9 microM. The mean intracellular concentration at the C1.6 is 400 microM, on which basis its potency is about twice that of MISO. The in vitro therapeutic index (aerobic cytotoxic potency/hypoxic C1.6) of NLA-1 is approximately 6-fold lower than that for MISO. NLA-1 lacks radiosensitizing activity against SCCVII or EMT6 tumors in vivo at the maximum tolerated dose (MTD) of 100 mumol.kg-1.

Aminoacridines↗
PubMed1991

Sequential observation of pathomorphological alterations in liver of experimental murine schistosomiasis mansoni.

Fifty CFI female mice were experimentally infected with schistosomiasis mansoni (50 cercariae per mouse). This study was designed to follow the stages of structural changes that may take place in the liver of patients infected by this parasite. Histological examination of liver tissue samples were carried out weekly for ten weeks after infection with schistosomiasis mansoni cercariae. The present study suggests that the development of hepatic schistosomiasis mansoni in mice is biphasis with a first or granulomatous phase in which the morphological changes are mild and a second aggressive fibrotic phase, when hepatic collagen synthesis increases rapidly and leads to fibrotic morphological changes that are characteristic of this infection. Gross and microscopic portal fibrosis and portal vascular lesions resembled those in hepatosplenic schistosomiasis in man. The rapid production of severe hepatic fibrosis without the use of hepatotoxic compound makes this model of interest for the study of liver fibrosis and its therapy.

Animals↗
PubMed1987

A study of cytoplasmic and nuclear estrogen and progestin receptors in gynecologic neoplasms.

A rapid method for simultaneous preparation of cytosol and nuclear estrogen (E) and progestin (P) receptors and their in vitro determination is described. The method was applied to several uterine or ovarian surgical specimens to evaluate their steroid hormone "dependence". The results suggest that low cytoplasmic E receptor levels (ERc) are associated with higher nuclear E receptor (ERn) levels but no apparent correlation was observed between PRc and ERn levels. The method appeared to be suitable for screening steroid hormone receptor content in tumor tissues and may provide better estimation of steroid dependence since both cytoplasmic and nuclear compartments can be studied simultaneously.

Adult↗