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Biomedical subjects

M Morgan

Publications and source records attributed to M Morgan.

At least 55 records · Page 3Linked to original sources
PubMed2001

Biodegradable block copolymers for delivery of proteins and water-insoluble drugs.

Release of several drugs from new ABA-type biodegradable thermal gels, ReGel, including proteins and conventional molecules, are presented. These are biodegradable, biocompatible polymers that demonstrate reverse thermal gelation properties. Organic solvents are not used in the synthesis, purification, or formulation of these polymers. The unique characteristics of ReGel hinge on the following two key properties: (1) ReGel is a water soluble, biodegradable polymer at temperatures below the gel transition temperature; (2) ReGel forms a water-insoluble gel once injected. This is consistent with a hydrophobically bonded gel state where all interactions are physical, with no covalent crosslinking. An increase in viscosity of approximately 4 orders of magnitude accompanies the sol--gel transition. The gel forms a controlled release drug depot with delivery times ranging from 1 to 6 weeks. ReGel's inherent ability to solubilize (400 to >2000-fold) and stabilize poorly soluble and sensitive drugs, including proteins is a substantial benefit. The gel provided excellent control of the release of paclitaxel for approximately 50 days. Direct intratumoral injection of ReGel/paclitaxel (OncoGel) results in a slow clearance of paclitaxel from the injection site with minimal distribution into any organ. Efficacies equivalent to maximum tolerated systemic dosing were observed at OncoGel doses that were 10-fold lower. Data on protein release (pGH, G-CSF, insulin, rHbsAg) and polymer biocompatibility are discussed.

Drug Delivery Systems↗
PubMed2001

Female preproenkephalin-knockout mice display altered emotional responses.

The endogenous opioid system has been implicated in sexual behavior, palatable intake, fear, and anxiety. The present study examined whether ovariectomized female transgenic preproenkephalin-knockout (PPEKO) mice and their wild-type and heterozygous controls displayed alterations in fear and anxiety paradigms, sucrose intake, and lordotic behavior. To examine stability of responding, three squads of the genotypes were tested across seasons over a 20-month period. In a fear-conditioning paradigm, PPEKO mice significantly increased freezing to both fear and fear + shock stimuli relative to controls. In the open field, PPEKO mice spent significantly less time and traversed significantly less distance in the center of an open field than wild-type controls. Further, PPEKO mice spent significantly less time and tended to be less active on the light side of a dark-light chamber than controls, indicating that deletion of the enkephalin gene resulted in exaggerated responses to fear or anxiety-provoking environments. These selective deficits were observed consistently across testing squads spanning 20 months and different seasons. In contrast, PPEKO mice failed to differ from corresponding controls in sucrose, chow, or water intake across a range (0.0001-20%) of sucrose concentrations and failed to differ in either lordotic or female approach to male behaviors when primed with estradiol and progesterone, thereby arguing strongly for the selectivity of a fear and anxiety deficit which was not caused by generalized and nonspecific debilitation. These transgenic data strongly suggest that opioids, and particularly enkephalin gene products, are acting naturally to inhibit fear and anxiety.

Animals↗
PubMed2001

Effect of vancomycin and rifampicin on meticillin-resistant Staphylococcus aureus biofilms.

Decolonisation of patients with urinary catheter colonisation by meticillin-resistant Staphylococcus aureus (MRSA) is often difficult. Replacement of the catheter after prophylactic vancomycin administration has been one approach that is often unsuccessful in clinical practice. We suspected that formation of MRSA biofilms might account for the persistence of infection, and our study confirms this, also showing that MRSA is able to colonise a silastic rubber surface even in the presence of prophylactic vancomycin or rifampicin.

Anti-Bacterial Agents↗
PubMed2001

Statistical analysis of measures of arousal in ovariectomized female mice.

In preparation for evaluating hormone effects and hormone receptor gene influences on fundamental processes of behavioral arousal, we subjected 48 ovariectomized female mice to a rigid protocol of several tests bearing on arousal concepts. The central hypothesis was that results would organize themselves according to capacities for sensory alertness, motor activity, and emotional reactivity. The large table of across-mouse correlation was subjected to factor analysis and cluster analysis. Results provided evidence for a general arousal (one-factor solution) which, however, accounted for only 29.72% of the variance. Four-factor (72.03%) matched four-cluster and six-factor (84.38%) matched six-cluster lineups of behavior components quite well, but did not conform to the main hypothesis; e.g., home cage exploration frequency and duration variables did not covary, and locomotor wheel activity grouped with fear indices. Besides providing a baseline for ongoing estrogen/thyroid and related genetic experiments, this statistical approach should be useful for a variety of hormonal studies of complex behaviors in mice.

Animals↗
PubMed2001

Benign keratosis with a spectrum of follicular differentiation: a case series and investigation of a potential role of human papilloma virus.

BACKGROUND: A variety of dermatopathologic entities are histologically defined by the presence of follicular differentiation. Follicular differentiation confined to the epidermis may follow induction from dermal mesenchymal proliferations, as in a nevus sebaceus of Jadassohn, or represent endogenous proliferations such as the tumor of the follicular infundibulum or trichilemmoma. METHODS: We report on five cases of a histologically distinct form of benign keratosis showing variable follicular differentiation. Clinicopathologic correlation and analysis of a potential human papilloma virus pathogenesis was investigated. RESULTS: Each of the cases arose on the trunk or extremities of three men and two women with a mean age at presentation of 66.6 years. All of the lesions showed variable follicular differentiation, with germinative basaloid cells, matrical cells with matrical keratinization, inner root sheath with trichohyalin granules, or glycogenated lower outer root sheath. Immunohistochemical staining for human papilloma virus was negative in each case. CONCLUSIONS: There exists a distinct entity, histologically defined as a keratosis with variable follicular differentiation, which has not been previously described. These lesions do not appear to be pathogenically related to human papilloma virus infection.

Aged↗
PubMed2001

Compulsory averaging of crowded orientation signals in human vision.

A shape can be more difficult to identify when other shapes are near it. For example, when several grating patches are viewed parafoveally, observers are unable to report the orientation of the central patch. This phenomenon, known as 'crowding,' has historically been confused with lateral masking, in which one stimulus attenuates signals generated by another stimulus. Here we show that despite their inability to report the orientation of an individual patch, observers can reliably estimate the average orientation, demonstrating that the local orientation signals are combined rather than lost. Our results imply that crowding is distinct from ordinary masking, and is perhaps related to texture perception. Under crowded conditions, the orientation signals in primary visual cortex are pooled before they reach consciousness.

Algorithms↗
PubMed2001

Patient satisfaction with teledermatology is related to perceived quality of life.

BACKGROUND: There is a lack of good data about patient satisfaction with teledermatology and about its potential interaction with quality-of-life factors. OBJECTIVES: To assess the association between perceived skin-related quality of life and patient satisfaction with a nurse-led teledermatology service. METHODS: In a mobile nurse-led teledermatology clinic located in four inner city general practices in Manchester, the teledermatology service used digital cameras to capture and store images of skin conditions for remote diagnosis by dermatologists. One hundred and twenty-three adult patients, non-urgent dermatology referrals from primary care, completed the Dermatology Life Quality Index (DLQI) and a 15-item patient satisfaction questionnaire. RESULTS: In common with other studies of patient satisfaction, subjects reported highly favourable views of 'hotel' aspects of the service (93%) and found it 'convenient' (86%). However, 40% of patients would have preferred to have had a conventional face-to-face consultation with a dermatologist, and 17% felt unable to speak freely about their condition. Patient satisfaction with the service was related to quality of life. Patients reporting lower quality of life as measured by the DLQI were more likely to prefer a face-to-face encounter with a dermatologist (r = 0.216, P < 0.05), and to evince anxiety about being photographed (r = 0.223, P < 0.05). CONCLUSIONS: Patient acceptance and satisfaction with telemedicine services is complicated by patients' subjective health status. Telehealthcare providers need to recognize that patients with poor quality of life may want and benefit from face-to-face interaction with expert clinicians.

Adolescent↗
PubMed2001

Haemodynamics of arteriovenous malformations of the brain and consequences of resection: a review.

The physiological manifestations of arteriovenous fistulae in humans have been studied since the 18th century. However, confusion regarding concepts of cerebral 'steal', 'normal perfusion breakthrough', and 'congestive hyperaemia' continue. Although the advent of more accurate monitoring of pressures and flows within the brain has provided useful information to help understand some of these proposed pathological hypotheses, disagreement still exists. The purpose of this review is to examine the current physiological data in attempt to explain the clinicopathological manifestations of arteriovenous malformations of the brain and the consequences of their removal.

Cerebrovascular Circulation↗
PubMed2001

Ethnic differences in behavioural risk factors for stroke: implications for health promotion.

OBJECTIVES: Ethnic minority groups are at a higher risk of stroke and heart disease. However, designing effective prevention strategies requires responding to the needs of different ethnic groups. The aims of this study were to estimate the prevalence of four behavioural risk factors (smoking, drinking, exercise and weight) for stroke among Black Caribbeans, Black Africans and Whites, and also to examined reported willingness to change these behaviours. DESIGN: A random sample of 311 Black Caribbean, 300 White, and 105 Black Africans aged 45-74 registered with 16 practices in south London were surveyed in 1995. Information was obtained on smoking, drinking and exercise patterns, body mass index and perceptions of being at risk of stroke, and willingness to change risk behaviour. RESULTS: White respondents (31% age and sex standardised prevalence) were more likely to smoke than Black Caribbeans (23%) and Black Africans (10%) (p < 0.001). Self reported rates of drinking were higher than the government's 'sensible drinking levels' for 19% of Whites, 11% of Black Caribbeans and 4% Black Africans (p < 0.001). In contrast, fewer Whites (51%) were overweight (BMI > 27) than Black Caribbeans (60%) and Black Africans (68%) (p = 0.001). A high proportion of smokers wished to give up (89% Black African; 83% Black Caribbean; 74% White). A higher proportion of Black Caribbeans (35%) reported a willingness to reduce their alcohol intake compared to only 15% of Whites (p = 0.040). There was a difference between groups in attitudes to weight reduction with 69% Black Caribbean women expressing a desire to be thinner compared to 86% Whites and 82% Black Africans (p = 0.051). CONCLUSION: Strategies to reduce behavioural risk factors for heart attack and stroke need to emphasise different risk foctors among ethnic groups, especially in relation to alcohol use in the White population and weight in the Black Caribbean population. Influencing the change of these behaviours requires working in partnership with local community' groups.

Africa↗
PubMed2001

Oral contraceptives, other methods of contraception, and risk reduction for ovarian cancer.

Oral contraceptives reduce the risk of ovarian cancer, but the impact of other methods of contraception has not been fully explored. This population-based, case-control study involved women 20-69 years of age who had ever had intercourse. We compared cases with a recent diagnosis of ovarian cancer (N = 727) with community controls (N = 1,360). All methods of contraception evaluated were associated with a reduced risk for ovarian cancer. After adjustment for age, race, pregnancies, and family history of ovarian cancer, the odds ratios for ever-use of each method as compared with never-use were: oral contraceptives for contraception, 0.6 (95% confidence interval = 0.5-0.8); intrauterine device, 0.8 (95% confidence interval = 0.6-1.0); barrier methods, 0.8 (95% confidence interval = 0.6-0.9); tubal ligation, 0.5 (95% confidence interval 0.4-0.7); and vasectomy, 0.8 (95% confidence interval = 0.6-1.1). Nulligravid women were not protected by any of these contraceptive methods. Multigravid women, however, were protected by all methods. We conclude that various methods of contraception reduce ovarian cancer risk. This effect does not appear to result from contraceptive use being a nonspecific marker of fertility. The results imply mechanisms other than hormonal or ovulatory by which ovarian cancer risk is reduced.

Adult↗
PubMed2001

Impact of illness and its treatment on workplace costs: regulatory and measurement issues.

In an attempt to document a broader spectrum of the benefits of their pharmaceutical products, drug companies increasingly seek to include productivity claims in their promotional campaigns. We describe the existing regulatory framework of the Food and Drug Administration (FDA) for considering productivity claims, distinguishing between the traditional "substantial evidence" standard and the "competent and reliable scientific evidence" standard. But the notion of competent and reliable scientific evidence may itself be problematic, even when it is the appropriate regulatory standard, because there exists no consistent measurement approach across diseases, workplaces, jobs, and worker capabilities that is widely accepted in this emerging area of health outcomes research. We examine the various measurement approaches that have been used to quantify the impact of illness and its treatment on workplace productivity, and we describe some of the shortcomings associated with each alternative. This discussion highlights the possible difficulties faced by the FDA in reviewing productivity-based promotional claims. Finally, we suggest possible strategies for furthering this field of investigation.

Absenteeism↗
PubMed2001

Use of a portable bladder scanner to reduce the incidence of bladder catheterisation prior to laparoscopy.

The aim of this study was to evaluate the usefulness of estimating bladder volume with a dedicated portable ultrasound device immediately prior to gynaecological laparoscopy. Catheterisation was performed if the estimated volume was greater than 100 ml. Forty consecutive women were studied prospectively. Twenty-six women did not require catheterisation. The procedure was quick and effective in safely reducing the frequency of pre-operative catheterisation.

Ambulatory Surgical Procedures↗
PubMed2001

Candida lusitaniae as an unusual cause of recurrent vaginitis and its successful treatment with intravaginal boric acid.

Increasing use of short-course antifungal therapies in patients with recurrent vulvovaginitis may enable the emergence of less-common, more resistant yeast strains as vaginal pathogens. We report the case of a patient with chronically symptomatic and repeatedly treated vaginal candidiasis whose infection was attributable to Candida lusitaniae, a previously unreported cause of candidal vaginitis.

Administration, Intravaginal↗
PubMed2001

Patient satisfaction with store-and-forward teledermatology.

We assessed patient satisfaction with a nurse-led store-and-forward teledermatology service in Manchester. A teledermatology nurse obtained the patient's history, took digital photographs of the patient's skin lesion and then sent the information to a hospital dermatologist, who responded with management advice the following week. Of 141 patients who attended their teledermatology appointment, 123 (50 male, 73 female) completed the study questionnaire (87%). The average age of respondents was 42 years (SD 17, range 18-90 years). Ninety-three per cent reported that they were happy with the teleconsultation while 86% reported that it was more convenient than going to the outpatient clinic. Forty per cent agreed that they would feel more comfortable seeing the dermatologist in person while only 58% were comfortable with not speaking to the dermatologist about their skin condition. The absence of interaction with the dermatologist and the delay in receiving management advice may have contributed to the somewhat low satisfaction rates.

Adolescent↗
PubMed2000

Estrogens, brain and behavior: studies in fundamental neurobiology and observations related to women's health.

Mechanisms and consequences of the effects of estrogen on the brain have been studied both at the fundamental level and with therapeutic applications in mind. Estrogenic hormones binding in particular neurons in a limbic-hypothalamic system and their effects on the electrophysiology and molecular biology of medial hypothalamic neurons were central in establishing the first circuit for a mammalian behavior, the female-typical mating behavior, lordosis. Notably, the ability of estradiol to facilitate transcription from six genes whose products are important for lordosis behavior proved that hormones can turn on genes in specific neurons at specific times, with sensible behavioral consequences. The use of a gene knockout for estrogen receptor alpha (ERalpha) revealed that homozygous mutant females simply would not do lordosis behavior and instead were extremely aggressive, thus identifying a specific gene as essential for a mammalian social behavior. In dramatic contrast, ERbeta knockout females can exhibit normal lordosis behavior. With the understanding, in considerable mechanistic detail, of how the behavior is produced, now we are also studying brain mechanisms for the biologically adaptive influences which constrain reproductive behavior. With respect to cold temperatures and other environmental or metabolic circumstances which are not consistent with successful reproduction, we are interested in thyroid hormone effects in the brain. Competitive relations between two types of transcription factors - thyroid hormone receptors and estrogen receptors have the potential of subserving the blocking effects of inappropriate environmental circumstances on female reproductive behaviors. TRs can compete with ERalpha both for DNA binding to consensus and physiological EREs and for nuclear coactivators. In the presence of both TRs and ERs, in transfection studies, thyroid hormone coadministration can reduce estrogen-stimulated transcription. These competitive relations apparently have behavioral consequences, as thyroid hormones will reduce lordosis, and a TRbeta gene knockout will increase it. In sum, we not only know several genes that participate in the selective control of this sex behavior, but also, for two genes, we know the causal routes. Estrogenic hormones are also the foci of widespread attention for their potential therapeutic effects improving, for example, certain aspects of mood and cognition. The former has an efficient animal analog, demonstrated by the positive effects of estrogen in the Porsolt forced swim test. The latter almost certainly depends upon trophic actions of estrogen on several fundamental features of nerve cell survival and growth. The hypothesis is raised that the synaptic effects of estrogens are secondary to the trophic actions of this type of hormone in the nucleus and nerve cell body.

Affect↗
PubMed2000

Risk of ovarian cancer in relation to estrogen and progestin dose and use characteristics of oral contraceptives. SHARE Study Group. Steroid Hormones and Reproductions.

Although past studies have shown that oral contraceptives with 50 microg or more of estrogen reduce the risk of ovarian cancer, it is not clear whether newer, lower-dose formulations do as well. We conducted a population-based, case-control study in the Delaware Valley to assess the impact of dose of oral contraception on risk of ovarian cancer. Cases aged 20-69 years with a diagnosis of epithelial ovarian cancer ascertained between May 1994 and July 1999 (n = 767) were compared with community controls (n = 1,367). Compared with never users, the adjusted risk of ovarian cancer was reduced by 40% for oral contraceptive users overall, with longer duration of use affording greater protection. The ovarian cancer risk reduction was similar for women who initiated oral contraception before 1972, when high-dose pills dominated the market; between 1972 and 1980; and after 1980, when newer, lower-dose pills dominated. Oral contraceptive estrogen and progestin content were compared for cases and controls after adjustment for current age, number of pregnancies, race, and family history of ovarian cancer. Use of low-estrogen/low-progestin pills afforded an estimated risk reduction (odds ratio = 0.5, 95% confidence interval: 0.3, 0.6) that was identical to that for high-estrogen/high-progestin pills (odds ratio = 0.5, 95% confidence interval: 0.3, 0.7).

Adult↗
PubMed2000

Fibronectin influences cellular proliferation and apoptosis similarly in LNCaP and PC-3 prostate cancer cell lines.

The mechanisms responsible for the emergence of clinically advanced prostate cancer (PC) are incompletely understood. Recent studies suggest that altered tumoral apoptosis with disordered cell proliferation sustains advanced disease and may account for the phenomena of anti-androgen therapeutic resistance. Previous inquiry has focused primarily on faulty intracellular mechanisms with limited scrutiny of the extracellular matrix including fibronectin and collagen type 4. We evaluated cell proliferation with Ki-67 immunoassay/image analysis and apoptosis by TUNEL staining and Bcl-2 immunoassay/image analysis in LNCaP and PC-3 human PC cell lines at baseline and following propagation on fibronectin and collagen type 4-coated coverslip substrate. Cell cultures showed differing proliferative and apoptosis characteristics at baseline, with the LNCaP cell line showing relatively higher proliferation and apoptosis rates than the PC-3 cell line. Cell proliferation and apoptosis were statistically significantly decreased in both cell lines following propagation on fibronectin. Bcl-2 expression was significantly increased among both cell lines following propagation on fibronectin. In contrast, cell proliferation, apoptosis, and Bcl-2 expression showed insignificant changes in both cell lines following uncoated coverslip and collagen type 4 matrix propagation. Our findings showed that fibronectin influences cell proliferation, apoptosis, and Bcl-2 expression similarly among LNCaP and PC-3 PC cell lines. It is likely that the altered rates are independent of the androgen status of the cell line and are mediated through a nonhormonal mechanism.

Journal Article↗