Search PubMed⌕ Search

Biomedical subjects

K Williams

Publications and source records attributed to K Williams.

At least 541 records · Page 30Linked to original sources
PubMedDate not supplied

A two-dimensional electrophoresis database of human breast epithelial cell proteins.

As sequencing of the human genome progresses, attention is turning to when and where specific genes are being expressed and how that expression is regulated. The human breast, with the highly specific, but transient, function of milk production (lactation), exemplifies human gene regulation. The molecular mechanisms for the dramatic structural and functional changes involved in shifting from lactation-capable to lactation-incapable tissue are poorly understood, as are the mechanisms that result in deviation from normal breast cell growth into different types of breast neoplasms. We are using quantitative two-dimensional electrophoresis (2-DE) to determine which proteins are present in different types of human breast cells (milk-producing and -nonproducing, estrogen-receptor-positive and -negative, normal and malignant) and which proteins change in abundance in response to stimuli that trigger cell differentiation, growth, or death. A composite map of proteins found in human breast cells is being generated and used as an index of human genes that are differentially expressed, both qualitatively and quantitatively. Proteins found in 15 different types of human breast cells, two from healthy tissue (from milk and reduction mammoplasty tissue) and 13 from tumor tissue, are now included in the composite map. Copies of the human breast epithelial cell protein map are available on the World Wide Web (URL: http:(/)/www.anl.gov/CMB/PMG/ projects/index_hbreast.html) with links to quantitative data and identifications for proteins found to be differentially expressed in these epithelial cells. Links to the Swiss-Prot and enzyme metabolic pathway databases are also provided. The World Wide Web presentation is designed to allow public access to the available 2-DE data together with logical connections to databases providing genome-related information.

Breast↗
PubMedDate not supplied

Substrate effects on sarcolemmal permeability in the normoxic and hypoxic perfused rat heart.

OBJECTIVES: Based on the hypothesis that provision of glucose is good and fatty acids are bad for the ischaemic myocardium, the aims of this study were to determine i) the effects of different substrates on sarcolemmal permeability during normoxia, low-flow hypoxia (HLF) and reperfusion, ii) whether increased membrane permeability is associated with ultrastructural damage and increased influx of Ca2+ into cells and iii) whether changes in membrane permeability correlate with myocardial function and high energy phosphate metabolism. METHODS: The isolated rat heart subjected to HLF was used as model of global ischaemia, and sarcolemmal permeability assessed by release of LDH from and influx of lanthanum and Ca2+ into myocardial tissue. Myocyte structural injury was also evaluated quantitatively, and mechanical activity was monitored throughout the experimental protocol. RESULTS: Regardless of the substrate used, HLF caused a 80-90% and 20-40% reduction in myocardial oxygen uptake and coronary flow rate, respectively. Palmitate (0.5 mM conjugated to 0.1 mM albumin) or substrate-free perfusion caused ultrastructural damage and loss of normal sarcolemmal integrity during both normoxia and HLF. Although reperfusion reversed injury in some cells, in general, myocytes exhibited myofibrillar contracture, while membrane integrity recovered to some extent, as indicated by reduced lanthanum influx. Intracellular Ca2+ increased significantly upon reperfusion. Mechanical function as well as tissue high energy phosphates were significantly depressed during both HLF and reperfusion. Glucose, on the other hand, protected against ischaemia-induced structural damage and loss of sarcolemmal integrity. Reperfusion in these experiments resulted in almost complete recovery of normal morphology, ultrastructure and sarcolemmal integrity, while intracellular Ca2+ remained unchanged. Mechanical function and tissue high energy phosphates were significantly higher in glucose-perfused hearts than in palmitate-perfused or substrate-free hearts. Glucose was also able to attenuate the harmful effects of palmitate on myocardial ultrastructure, membrane integrity, mechanical function, energy metabolism and prevented Ca2+ overloading during reperfusion. CONCLUSION: The results provide new evidence for the protective role of glucose during myocardial ischaemia and reperfusion. Although the exact mechanism of the beneficial actions of glucose remains to be established, the results suggest that glycolytic flux and thus glycolytically derived ATP protect against ischaemic damage via preservation of membrane integrity.

Adenine Nucleotides↗
PubMedDate not supplied

Caffeine fatality: a case report.

A case of fatal caffeine toxicity due to suicidal ingestion of a "look-alike" illicit drug is reported. Caffeine concentrations were determined by high pressure liquid chromatography (HPLC) with the brain having the highest level reported in the literature to date. Also, the blood concentration of caffeine was one of the highest among the cases reported. A literature review of caffeine fatalities is presented.

Adult↗
PubMedDate not supplied

Human fetal pancreas transplants.

Human fetal pancreatic islet tissue has several advantages as a transplant source for the amelioration of insulin deficiency in patients with Type I diabetes mellitus. It is now possible to obtain viable tissue, store and ship the tissue without adverse effects on the insulin secretory capacity, and transplant either minced tissue or isolated islet-like cell clusters following digestion and culture into animal models or man. A number of centers have undertaken studies of human fetal pancreatic allografts in man. Optimal results have occurred when pooled tissue from six to 20 donors has been implanted and a number of sites have been studied. The author's own experience in four recipients who did not receive immunosuppression has documented insulin secretion for up to 1 year in the absence of an anticytoplasmic islet cell antibody response on the part of the recipients. Nevertheless, the procedure has not resulted in insulin independence for the recipients and the implanted tissue has not secreted insulin in response to a glucose-amino acid challenge in a normal physiologic pattern. Thus, human fetal pancreatic transplantation for the treatment of Type I diabetes remains an experimental approach.

Animals↗
PubMedDate not supplied

Studies of human fetal pancreatic allografts in diabetic recipients without immunosuppression.

Four Type I insulin-dependent diabetic men received minced tissue from 6-12 pooled fetal pancreata cultured for 48 hours. Immunosuppressive therapy was not given. The tissue was transplanted under local anesthesia into the brachioradialis muscle of the nondominant arm or below the subcutaneous adipose tissue of the left lower quadrant of the abdominal wall. An increase in C-peptide secretion was documented following each procedure. Detectable C-peptide secretory capacity has persisted for 1 year in three cases. The total insulin requirement showed a drop of 71-100% at the time of maximum C-peptide secretion. No increase in anticytoplasmic islet cell antibody titer was detected during the year of observation following transplantation. These studies document that transplantation of functioning fetal pancreatic insulin-secreting tissue can be performed with minimal operative or immunologic risk to the recipient. Significant insulin secretory capacity persists for 1 year following implantation. Further studies are warranted in order to optimize insulin secretion following fetal pancreatic islet transplantation.

Adult↗
PubMedDate not supplied

Results from a new renal transplantation unit.

158 kidneys, 9 from living related donors and 149 from cadavers, have been transplanted in the first 42 months of the establishment of a transplant unit at Oxford. Patients' ages ranged from 11 to 56 (mean 35) years. Azathioprine and prednisolone alone were used for immunosuppression, and a minimum-transfusion policy was in operation throughout. After cadaveric transplantation actuarial patient-survival is 70% and 68%, respectively, at the same intervals. 85% of patients who had a functioning graft are fully rehabilitated. Matching for HLA-DR, pregraft blood-transfusions, and the finding that a transplant could be performed in the presence of a positive B-cell crossmatch have proved to be the most significant of the many factors examined both prospectively and retrospectively. The function of the unit is based on dialysis and transplantation for all patients in end-stage renal failure, with transplantation being considered the first line of treatment for patients under the age of 56. The results of transplantation reported here, which have been achieved with conventional immunosuppressive therapy and minimum-transfusion policy, might be considered a standard against which modifications of the practice of renal transplantation can be compared.

Adolescent↗
PubMedDate not supplied

Medicare managed care: policy concerns.

This paper briefly reviews the extent of current drug coverage for Medicare beneficiaries and describes the most important issues faced by aged beneficiaries who receive or seek drug coverage through a Medicare managed care plan. Changes in payment rates to these plans as a result of the Balanced Budget Act of 1997 may result in plans reducing or eliminating drug coverage. Under current law beneficiaries in these plans will have severely limited options for replacing drug coverage; as a result, many will not be able to obtain this coverage either through Medigap or previous retiree coverage. In the absence of any change in current law, one approach to addressing these issues is to refocus Medicare managed care plans on managing the total cost of caring for patients over time and across settings. Only through such an integrated approach will Medicare managed care plans have the tools to function within the new payment rates and realize the value of the pharmaceutical benefit to the plan and the patients.

Aged↗
PubMedDate not supplied

Correlates of specific childhood feeding problems.

OBJECTIVE: The correlates of specific childhood feeding problems are described to further examine possible predisposing factors for feeding problems. We report our experience with 349 participants evaluated by an interdisciplinary feeding team. METHODS: A review of records was conducted and each participant was identified as having one or more of five functionally defined feeding problems: food refusal, food selectivity by type, food selectivity by texture, oral motor delays, or dysphagia. The prevalence of predisposing factors for these feeding problems was examined. Predisposing factors included developmental disabilities, gastrointestinal problems, cardiopulmonary problems, neurological problems, renal disease and anatomical anomalies. RESULTS: The frequencies of predisposing factors varied by feeding problem. Differences were found in the prevalence of the five feeding problems among children with three different developmental disabilities: autism, Down syndrome and cerebral palsy. Gastro-oesophageal reflux was the most prevalent condition found among all children in the sample and was the factor most often associated with food refusal. Neurological conditions and anatomical anomalies were highly associated with skill deficits, such as oral motor delays and dysphagia. CONCLUSIONS: Specific medical conditions and developmental disabilities are often associated with certain feeding problems. Information concerning predisposing factors of feeding problems can help providers employ appropriate primary, secondary and tertiary prevention measures to decrease the frequency or severity of some feeding problems.

Child↗
PubMedDate not supplied

Childhood psoriasis: a clinical review of 1262 cases.

Our aim was to describe the types of psoriasis seen in a large series of patients presenting to a tertiary referral pediatric dermatology department using a classification system combining conventional terminology and additional categories based on the site and characteristics of the rash. A total of 1262 patients seen consecutively in the dermatology department of the Royal Alexandra Hospital for Children, Sydney, Australia, between 1981 and 1995 are described and classified according to the pattern of psoriasis at the time of presentation. Additional information recorded included family history, facial involvement, and history of a psoriatic type of diaper rash in infancy. The ages of the children ranged from 1 month to 15 years. There was an equal gender distribution and a high rate of positive family history at 71%. Twenty-six percent of children had a history of a psoriatic diaper rash and facial involvement occurred in 38% of children. Plaque psoriasis was the most common type overall, affecting 430 patients (34%). Three hundred forty-five children were less than 2 years of age, and this is the largest series of children with psoriasis in this age group presented to date. An entity defined by us as psoriatic diaper rash with dissemination was the most common type of psoriasis in the less than 2-year age group, affecting 155 (45%) patients. This large series offers information on the manifestations of psoriasis in childhood, but is particularly useful in examining the previously less well-described infant age group. The classification used is proposed as a practical way to describe psoriasis in children, particularly with respect to future descriptive studies.

Adolescent↗
PubMedDate not supplied

Early Years Centres for pre-school children with primary language difficulties: what do they cost, and are they cost-effective?

BACKGROUND: High levels of early language difficulties raise practical issues about the efficient and effective means of meeting children's needs. Persistent language difficulties place significant financial pressures on health and education services. This has led to large investment in intervention in the early years; yet, little is known about the actual and relative costs of early years provision. AIMS: To profile the different costs incurred by two Early Years Centres (EYCs) partially funded by the charity I CAN and children receiving what might be termed 'routine' NHS speech therapy to provide an analysis of cost efficiency and equity. METHODS & PROCEDURES: Costings for service provision for 91 children (mean age 2;9) were collected. The activity of staff at each site and the cost of staff allocated to services were computed. Data on other resources were also collected. OUTCOMES & RESULTS: The cost per child per session was on average 12 pounds. Despite the longer course of intervention in the first centre (10 compared with 6 weeks), the cost of the course per child was of the same order (245 pounds compared with 253 pounds). The annual cost of the early years provision per child was higher relative to the costs of the NHS provision, 645 pounds compared with 181 pounds in one EYC (A) and 462 pounds compared with 173 pounds in the other (B). When the cost of standard nursery provision was factored in, the difference in annual costs was rather less, with 5298 pounds for the early years provision (EYC A) relative to 4276 pounds in the comparison group. By contrast, the annual cost of early provision rises to 5926 pounds relative to 8861 pounds in the comparison group (EYC B). CONCLUSIONS: The cost of the EYCs is relatively low and given the positive outcomes reported in the study of which this economic evaluation is a part, there is a good case for saying that they represent an efficient use of resources. The strengths and limitations of the economic evaluation are considered and the need for long-term evaluations is highlighted.

Child Health Services↗
PubMedDate not supplied

Responses of neurologic complications of AIDS to 3'-azido-3'-deoxythymidine and 9-(1,3-dihydroxy-2-propoxymethyl) guanine. I. Clinical features.

Fourteen patients with AIDS were treated for 23 neurologic complications: four episodes of acute meningoencephalitis; eight episodes of subacute encephalopathy; two cases of progressive multifocal leukoencephalopathy; and nine cases of polyneuropathy. Nine patients were treated with 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG), one with 3'-azido-3'-deoxythymidine (AZT), and four initially with DHPG directed against cytomegalovirus (CMV) retinitis or encephalitis and subsequently with AZT against human immunodeficiency virus (HIV) encephalopathy. CMV retinitis was a helpful clinical observation indicating neurologic involvement. DHPG produced improvement in two of three cases of acute meningoencephalitis but was ineffective in cases of subacute encephalopathy or neuropathy. AZT therapy resulted in resolution in both of the two treated cases of acute confusional state and in two of the four treated cases of polyradiculoneuropathy with paraparesis but was ineffective in the late stage of subacute encephalopathy. These results suggest that CMV is important in some cases of acute meningoencephalitis, whereas HIV is a dominant pathogen in subacute dementia and polyneuropathy in patients with AIDS. DHPG may be beneficial in the former, whereas AZT appears to be effective in the latter complications.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

Neonatal exposure to potent and environmental oestrogens and abnormalities of the male reproductive system in the rat: evidence for importance of the androgen-oestrogen balance and assessment of the relevance to man.

The effects on reproductive tract development in male rats, of neonatal exposure to potent (reference) oestrogens, diethylstilboestrol (DES) and ethinyl oestradiol (EE), with those of two environmental oestrogens, octylphenol and hisphenol A were systematically compared. Other treatments, such as administration of a gonadotrophin-releasing hormone antagonist (GnRHa) or the anti-oestrogen tamoxifen or the anti-androgen flutamide, were used to aid interpretation of the pathways involved. All treatments were administered in the neonatal period before onset of puberty. The cellular sites of expression of androgen receptors (AR) and of oestrogen receptor-alpha (ERalpha) and ERbeta were also established throughout development of the reproductive system. The main findings were as follows: (i) all cell types that express AR also express one or both ERs at all stages of development; (ii) Sertoli cell expression of ERbeta occurs considerably earlier in development than does expression of AR; (iii) most germ cells, including fetal gonocytes, express ERbeta but not AR; (iv) treatment with high, but not low, doses of potent oestrogens such as DES and EE, induces widespread structural and cellular abnormalities of the testis and reproductive tract before puberty; (v) the latter changes are associated with loss of immunoexpression of AR in all affected tissues and a reduction in Leydig cell volume per testis; (vi) none of the effects in (iv) and (v) can be duplicated by treating with high-dose octylphenol or bisphenol A; (vi) none of the reproductive tract changes in (iv) and (v) can be induced by simply suppressing androgen production (GnRHa treatment) or action (flutamide treatment); and (vii) the adverse changes induced by high-dose DES (iv and v) can be largely prevented by co-administration of testosterone. Thus, it is suggested that many of the adverse changes to the testis and reproductive tract induced by exposure to oestrogens result from a combination of high oestrogen and low androgen action. High oestrogen action or low androgen action on their own are unable to induce the same changes.

Abnormalities, Drug-Induced↗
PubMedDate not supplied

Universal, developmental, and variable aspects of young children's play: a cross-cultural comparison of pretending at home.

Using longitudinal data from five Irish American families in the United States and nine Chinese families in Taiwan, in conjunction with an emerging body of evidence in the cultural psychology literature, we propose universal, culturally variable, and developmental dimensions of young children's pretend play. Possible universal dimensions include the use of objects, and the predominantly social nature of pretend play. Developmental dimensions include increases in the proportion of social pretend play initiated by the child, the proportion of partner initiations elaborated upon by the child, and caregivers' use of pretend play initiations to serve other, nonplay social functions. Culturally variable dimensions include the centrality of objects, the participation of specific play partners, the extent of child initiations of social pretend play with caregivers, the various functions of social pretend play in interaction, and specific themes. These findings raise the theoretical issue of how universal and variable dimensions of pretend play interact in specific communities to create distinctive development pathways.

Child Development↗
PubMedDate not supplied

Bandages: indications for use and Drug Tariff status.

Community nurses need to have an up-to-date knowledge of which bandages are available on NHS prescription (i.e. on Drug Tariff) so that they can select the most appropriate bandage for their patient from those currently available. It seems that, for many years, both doctors and nurses have selected bandages for their patients without any clear knowledge of how the materials in the bandage will perform or what effect they will have (McCollum, 1992). Ideally, the nurse would first carry out an accurate assessment of the wound and then use this information to select an appropriate bandage, based on a full knowledge of its components, indications for use, and correct application technique. A bandage that is applied incorrectly can cause serious tissue damage. This article presents an up-to-date guide to the bandages currently available on Drug Tariff. However, since the Drug Tariff status of wound care products is constantly changing, community nurses need to keep up to date with the changes if they are to provide optimum care for their patients.

Bandages↗
PubMedDate not supplied

Triggers that prompt people with urinary symptoms to seek help.

Urinary symptoms are fairly common among the adult population yet only a small percentage report them as bothersome. There are many reasons why people do not seek help for urinary symptoms, e.g. the embarrassment felt by those experiencing them. Little research, however, has looked at the reasons why some people seek healthcare professional help for urinary symptoms. This article describes a study aimed to identify the triggers that prompt a person with urinary symptoms to seek help. The findings suggest that health promotion campaigns play an important role in both raising awareness and demand for services. Furthermore, this study highlights the personal and social reasons why people seek help for urinary symptoms. It is important, therefore, that healthcare professionals take these personal and social circumstances into account when carrying out any assessment to ensure that a successful management of symptoms is achieved.

Activities of Daily Living↗