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Biomedical subjects

C Todd

Publications and source records attributed to C Todd.

At least 73 records · Page 4Linked to original sources
PubMed1996

The expression of the c-kit receptor by epidermal melanocytes may be reduced in vitiligo.

The proto-oncogene c-kit encodes the transmembrane tyrosine kinase receptor that has a role in the growth regulation of various cell types including melanocytes. In the present study we have examined the expression of the c-kit protein in the skin of seven patients with vitiligo. Melanocytes positive for c-kit protein were observed in the basal layer in non-lesional skin and the mean number of 25.8 +/- 5.2 (per 200 basal cells) compared with that of 21.8 +/- 3.5 from six control subjects. In perilesional skin there was a reduction in the numbers of c-kit positive melanocytes (6.7 +/- 2.6) and this was especially noticeable in six of the seven patients. Such a reduction was less obvious following staining with MEL-5 and in only two subjects were the numbers of melanocytes below the normal range. This suggests that the reduction in c-kit staining was the result of decreased expression of the protein rather than a loss of melanocytes. No melanocytes, positive for c-kit protein, or after staining with MEL-5, were identified in lesional skin although isolated tyrosinase-positive melanocytes were seen in one subject. There was no apparent change in the numbers of mast cells expressing c-kit protein and the intensity of staining in the dermis even in lesional skin was similar to that in the controls. These results demonstrate that c-kit protein is present on melanocytes in adult human skin and that in perilesional skin of some vitiligo patients there is a reduction in the numbers of melanocytes expressing this receptor. Whether this may contribute to the defective melanocyte growth and/or survival that occurs in vitiligo or whether it is a consequence of melanocyte damage remains to be seen.

Adult↗
PubMed1995

Eumelanin and phaeomelanin contents of human epidermis and cultured melanocytes.

There are two chemically distinct types of melanin: the red-yellow phaeomelanins and the brown-black eumelanins. While both melanins have been detected in human epidermis and cultured melanocytes, it is unknown how the phaeomelanin/eumelanin ratio in human melanocytes maintained in vitro relates to that in the epidermis from which they were isolated. This study uses high-performance liquid chromatography to quantify the eumelanin and phaeomelanin contents of epidermis and/or cultured melanocytes from 12 Europeans with lightly pigmented skin and 9 non-Europeans with more deeply pigmented skin. Epidermis from non-Europeans contained the highest levels of both eumelanin and phaeomelanin and had the lowest phaeomelanin/eumelanin ratios. In contrast, while cultured melanocytes from non-Europeans also had higher levels of eumelanin and phaeomelanin than melanocytes from Europeans, there was no difference in the phaeomelanin/eumelanin ratios in the two groups. However, the phaeomelanin/eumelanin ratios were higher in the cultured melanocytes than in the corresponding epidermis so that while eumelanin was the predominant melanin in these epidermis, phaeomelanin was the major melanin in the cultured melanocytes. These observations may have important implications for the use of cultured human melanocytes in the study of melanogenesis in man.

Adult↗
PubMed1995

Fall frequency and incidence of distal forearm fracture in the UK.

STUDY OBJECTIVE: This analysis aimed to determine the frequency of falls in men and women aged 50 years and over and to explore whether age variation in fall frequency may explain variation in the incidence of distal forearm fracture in women. DESIGN: This was a cross sectional survey. SETTING: Primary care based registers in four UK areas. PARTICIPANTS: Altogether 501 men and 702 women age 50-79 years participated. MAIN RESULTS: A total of 131 (26.1%) men and 181 (25.8%) women reported falling in the previous year. In women, the frequency of falls rose with age (chi 2 test for trend 4.33; p = 0.04), with no obvious early post-menopausal peak or subsequent decline. Men aged 50-54 years had a significantly increased risk of falls compared with women of this same age group, (odds ratio (OR) = 2.4; 95% confidence interval (CI) 1.3, 4.6), though above this age, the risk of falling was greater in women (OR = 1.2; 95% CI 0.9, 1.5). CONCLUSION: There are important differences in the frequency of falls in relation to age and sex. The data suggest that variation in fall frequency per se does not explain age variation in the incidence of distal forearm fracture in women.

Accidental Falls↗
PubMed1994

A set of ninety-seven overlapping yeast artificial chromosome clones spanning the human Y chromosome euchromatin.

Contiguous arrays of yeast artificial chromosomes (YACs) extending from proximal heterochromatic Yq into the pseudoautosomal portion of the Y chromosome and separated by a small interval at the centromere have been constructed. A total of 97 YACs have been aligned along the Y chromosome by STS content analysis using 222 sequence tagged sites (STSs) that detect 263 loci. Forty-five of the STSs used are novel. Their inclusion provides a significant improvement over previously available maps on the density of STS coverage along the Y chromosome, reducing the average spacing to 120 kb assuming a length of 30 Mb for the euchromatin. The average size of 61 YACs determined by pulsed-field gel electrophoresis analysis was at least 0.9 Mb. Minor differences noted between the ordering of STSs on this map compared with those previously reported may be attributed to inherent polymorphism between the Y chromosomes used to construct the YAC libraries.

Base Sequence↗
PubMed1994

A 6.5-Mb yeast artificial chromosome contig incorporating 33 DNA markers on the human X chromosome at Xq22.

The Xq22 region of the human X chromosome contains genes for a number of inherited disorders. Sixty-nine yeast artificial chromosome clones have been isolated and assembled into a 6.5-Mb contig that contains 33 DNA markers localized to this region. This contig extends distally from DXS366 to beyond DXS87 and includes the genes involved in X-linked agammaglobulinemia (btk), Fabry disease (GLA), and Pelizaeus-Merzbacher disease (PLP). The order of markers in this contig is consistent with the known genetic and physical mapping information of Xq22. This cloned material provides a source from which to isolate other genes located in this part of the X chromosome.

Adult↗
PubMed1994

The 12-hour shift: the views of nurse educators and students.

Interest in 12-hour nursing shifts has been renewed in response to demands for improved cost-effectiveness in the UK National Health Service. But the effects of the shift on nursing education are unclear. We report surveys of the attitudes of student nurses and nurse educators towards 12-hour shifts. Learners are reasonably positive about 12-hour shifts, but this preference is based on social rather than professional benefits. A reported effect of fatigue on home study is evident. Very negative views about the 12-hour shift are held by the group of educators. Their criticisms appear to be primarily organizational, but they are unequivocal that learning is detrimentally affected. Thus, even if students appear to like this shift pattern, serious concerns are raised by these findings about the impact of the shift on nursing education.

Adult↗
PubMed1994

Cultured human melanocytes respond to MSH peptides and ACTH.

Although the administration of melanocyte-stimulating hormone (MSH) peptides results in skin darkening in man, cultured human melanocytes have been reported to be unresponsive to these peptides. This may be a consequence of the conditions under which the cells were maintained in vitro, particularly the use of phorbol esters and cholera toxin as melanocyte mitogens. By culturing the cells in the absence of these additives, we demonstrate that alpha-MSH and its synthetic analogue Nle4DPhe7 alpha-MSH (NDP-MSH) induce dose-related increases in melanin content and tyrosinase activity and affect cell morphology in the majority of human melanocyte cultures. In addition, NDP-MSH induces increases in tyrosinase mRNA and tyrosinase-related protein-1 (TRP-1) mRNA. The dose-response curves for the MSH peptides are sigmoidal and the two peptides are equipotent in their effects on human melanocytes. Adrenocorticotropic hormone (ACTH) also affects morphology and stimulates melanogenesis and tyrosinase activity in human melanocytes. However, the dose-response curves for ACTH are biphasic, and the melanocytes respond to lower concentrations of ACTH than MSH peptides, similar to those normally present in human plasma. These findings may be important in understanding the role of these pro-opiomelanocortin peptides in human skin pigmentation.

Adrenocorticotropic Hormone↗
PubMed1994

Age and sex influences on fall characteristics.

OBJECTIVE: To investigate age and sex influences on fall characteristics. METHODS: A total of 1243 subjects (517 males and 726 females) aged 50 years and over and drawn from population based sampling frames were invited to complete an interviewer administered questionnaire concerning descriptive characteristics of falls experienced in the previous four months. Information collected included details about the part of the body to strike the ground, direction of the fall, level of trauma and whether or not injury or fracture was sustained. RESULTS: One hundred and seventy two subjects reported a fall in the previous four months. Restricting analysis to the 142 subjects who fell from a standing height or less, females aged 50-64 years were more than twice as likely to fall onto their hand compared with older females (odds ratio (OR) = 2.2; 95% confidence interval (CI) 0.8 to 6.2) and at all ages (50+) were more than three times as likely to fall on their hip compared with males (OR = 3.4; 95% CI 1.0 to 11.5). Compared with older males, males aged 50-64 were more likely to fall sideways (OR = 5.1; 95% CI 1.5 to 17.4) and less likely to fall forwards (OR = 0.4; 95% CI 0.1 to 1.1). CONCLUSION: There is a potentially clinically important variation in fall type by age and sex. In particular, this variation might explain patterns of occurrence of hip and Colles' fracture.

Accidental Falls↗
PubMed1994

Alpha-melanocyte stimulating hormone and its analogue Nle4DPhe7 alpha-MSH affect morphology, tyrosinase activity and melanogenesis in cultured human melanocytes.

Although melanocyte stimulating hormone (MSH) peptides are known to stimulate pigmentation in man, previous reports suggest that human melanocytes are relatively unresponsive to these peptides in vitro. This may be related to the conditions under which the melanocytes were cultured. Thus, we have re-investigated the in vitro effects of MSH peptides using human melanocytes cultured in the absence of artificial mitogens. Human melanocytes were incubated with alpha-MSH or its potent analogue Nle4Dphe7 alpha-MSH for 3 days. After 18 hours, melanocyte morphology had evolved from mainly bipolar to dendritic in approximately 66% of cultures. Nle4DPhe7 alpha-MSH produced dose-related increases in both tyrosinase activity and melanin content although the degree of response was variable and tyrosinase activity was the relatively more responsive to the peptide. Similar results were obtained with alpha-MSH, but, although the effect on melanin content was similar to that of Nle4DPhe7 alpha-MSH, the effect on tyrosinase activity was less marked. The preliminary EC50 values for the actions of the MSH peptides suggest that they may be equipotent in their actions on human melanocytes. In addition, we have demonstrated that the common melanocyte mitogens 12-O-tetradecanoyl phorbol-13-acetate (TPA) and cholera toxin affect basal melanogenesis and modulate the effects of the MSH peptides. However, not all melanocyte cultures showed melanogenic responses to the MSH peptides. Ability to respond was unrelated to basal levels of tyrosinase activity or melanin content. In at least some cultures, morphological and melanogenic responses appear to be independent of one another.(ABSTRACT TRUNCATED AT 250 WORDS)

Cells, Cultured↗
PubMed1994

ACTH stimulates melanogenesis in cultured human melanocytes.

While ACTH is known to induce skin pigmentation in man, its effects on cultured human melanocytes have not been investigated. Using a culture system free of artificial mitogens, we report for the first time that ACTH stimulates melanogenesis in cultured human melanocytes. While ACTH, alpha-MSH and the synthetic alpha-MSH analogue Nle4DPhe7 alpha-MSH all stimulate the activity of tyrosinase, the rate limiting enzyme in melanogenesis, and all produce a 50% increase in the melanin content of the cells at a concentration of 10(-8)-10(-7) mol/l, the shapes of the dose response curves differ: those for the MSH peptides are sigmoidal while those for ACTH are biphasic. In addition, human melanocytes are able to respond to concentrations of ACTH comparable with physiological plasma levels. We suggest that ACTH may be relatively more important than alpha-MSH as a pigmentary hormone in man and could have a physiological role in skin pigmentation.

Adrenocorticotropic Hormone↗
PubMed1993

Cost analysis of early discharge after hip fracture.

OBJECTIVE: To ascertain the economic impact of an early discharge scheme for hip fracture patients. DESIGN: Population based study comparing costs of care for patients who had "hospital at home" as an option for rehabilitation and those who had no early discharge service available in their area of residence. SETTING: District hospital orthopaedic and rehabilitation wards and community hospital at home scheme. PATIENTS: 1104 consecutively admitted patients with fractured neck of femur. 24 patients from outside the district were excluded. MAIN OUTCOME MEASURES: Cost per patient episode and number of bed days spent in hospital. RESULTS: Patients with the hospital at home option spent significantly less time as inpatients (mean of 32.5 v 41.7 days; p < 0.001). Those patients who were discharged early spent a mean of 11.5 days under hospital at home care. The total direct cost to the health service was significantly less for those patients with access to early discharge than those with no early discharge option (4884 pounds v 5606 pounds; p = 0.048). CONCLUSIONS: About 40% of patients with fractured neck of femur are suitable for early discharge to a scheme such as hospital at home. The availability of such a scheme leads to lower direct costs of rehabilitative care despite higher readmission costs. These savings accrue largely from shorter stays in orthopaedic and geriatric wards.

Aged↗
PubMed1993

Co-culture of human melanocytes and keratinocytes in a skin equivalent model: effect of ultraviolet radiation.

Melanocytes grown in pure monolayer culture lack the three-dimensional organization and many of the cellular interactions that exist in vivo. This can be partially overcome by growing melanocytes together with other epidermal cells in skin equivalent models. In this study skin equivalents were prepared by seeding mixtures of cultured human keratinocytes and melanocytes in various ratios onto de-epidermized dermis. They were cultured in DMEM/Ham's F12 (3:1) for 3 days and then lifted to the air-liquid interface and maintained for 11 days. Histological examination revealed a structure that closely resembled human interfollicular epidermis. Melanocytes, identified by their dendritic appearance, positive dopa reaction and positive staining with a melanocyte-specific antibody (MEL5), were located in the basal layer. Melanin was seen both in melanocytes and in neighbouring keratinocytes. Whilst the skin equivalent became more pigmented following UV irradiation (total UVB 4760 J/m2 over 3 days), the quantity and distribution of melanin at the light microscopic level appeared to be unchanged. However, the number and dendricity of melanocytes increased, as did their staining with dopa and MEL5. These results indicate that melanocytes are functional and capable of responding to UV irradiation.

Cell Count↗
PubMed1993

The quantity of nursing care on wards working 8- and 12-hour shifts.

Interest in 12-hour nursing shifts has been renewed in response to demands for improved cost-effectiveness in the NHS, but the effects of this shift on the delivery of patient care have been unclear. This paper describes the results of a repeated-measures study of 10 wards, using activity analysis to describe patterns of care under an 8-hour compared to a 12-hour shift system. Significant reductions in the amount of direct patient care were found under the 12-hour shift, with corresponding increases in unofficial work-breaks. It is suggested that these findings, which were consistent over all study wards and throughout the whole 12-hour day, demonstrate a "pacing" effect by nurses who face 12 hours on duty. Such a detrimental effect should be a major consideration when coming to any decision to implement a 12-hour shift.

Hospital Units↗
PubMed1993

Resolution by erythrocytapheresis of the exposure of an Rh-negative person to Rh-positive cells: an alternative treatment.

Acute trauma with severe bleeding caused the unavoidable transfusion of Rh-positive red cells (RBCs) to a young, childless, Rh-negative woman during surgery. Of the 10 units of RBCs given, 6 were Rh positive. An alternative treatment for large-volume exposure involves the removal of some of the Rh-positive cells transfused at a time when the patient's condition could not be jeopardized by the shortage of Rh-negative RBCs. It is believed that the combination of erythrocytapheresis followed by Rh immune globulin treatment was successful, when immunoprophylaxis alone might not have been. It is strongly recommended that partial RBC exchange for the removal of the unwanted RBCs be considered in addition to Rh immune globulin treatment in cases of large-volume exposure such as the one presented.

Adult↗
PubMed1993

General practitioners' strategies and tactics of communication with the terminally ill.

Interviews with 22 randomly selected general practitioners (GPs) investigated their communication with terminally ill patients. In interview analysis a conceptual distinction was drawn between objectives, strategies and tactics. When treating terminal patients, GPs expressed the objectives of keeping the patient comfortable, painfree, happy and maintaining dignity. A strategy is a plan and mode of approaching patients existing over an extended time period. Three strategies were described by GPs for use when interacting with terminally ill patients. These are characterized as 'try to disclose', 'let the patient decide' and 'avoid disclosing'. Tactics refer to behaviours used within a single consultation, as part of a strategy. Six tactics are described: evasion, denial, uncertainty, hints and prompts, euphemism and reassurance. Different strategies imply quite different forms of consultation. Thus to understand a consultation we must place it into the context of the series.

Attitude to Death↗