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PubMed1990

Early activation of endogenous pp60src kinase activity during neuronal differentiation of cultured human neuroblastoma cells.

The proto-oncogene product pp60c-src is a tyrosine-specific kinase with a still unresolved cellular function. High levels of pp60c-src in neurons and the existence of a neuronal pp60c-src variant, pp60c-srcN, suggest participation in the progress or maintenance of the differentiated phenotype of neurons. We have previously reported that phorbol esters, e.g., 12-O-tetradecanoylphorbol-13-acetate (TPA), stimulate human SH-SY5Y neuroblastoma cells to neuronal differentiation, as monitored by morphological, biochemical, and functional differentiation markers. In this report, we describe activation of the pp60src (pp60c-src and pp60c-srcN) kinase activity observed at 6 h after induction of SH-SY5Y cells with TPA. This phenomenon coincides in time with neurite outgrowth, formation of growth cone-like structures, and an increase of GAP43 mRNA expression, which are the earliest indications of neuronal differentiation in these cells. The highest specific src kinase activity (a three- to fourfold increase 4 days after induction) was noted in cells treated with 16 nM TPA; this concentration is optimal for development of the TPA-induced neuronal phenotype. During differentiation, there was no alteration in the 1:1 ratio of pp60c-src to pp60c-srcN found in untreated SH-SY5Y cells. V8 protease and trypsin phosphopeptide mapping of pp60src from in vivo 32P-labeled cells showed that the overall phosphorylation of pp60src was higher in differentiated than in untreated cells, mainly because of an intense serine 12 phosphorylation. Tyrosine 416 phosphorylation was not detectable in either cell type, and no change during differentiation in tyrosine 527 phosphorylation was observed.

Cell Differentiation↗
PubMed1991

Is religion a help around the time of death?

Based on reports from relatives and other associates about a random sample of adults who had recently died, the data suggest that three-fifths of the people who died were perceived as having some sort of religious faith that had been helpful to them in the time before they died. Acceptance of death was seen as more common among those thought to have had a strong religious faith, but was not related to believing or not believing in some sort of life after death. It was less frequent among those thought to be uncertain about this. The majority of relatives who said they had a religious faith felt it had been helpful to them over their bereavement, but religious faith was not related to whether or not they felt they had come to terms with the person's death. Those with a religious faith were more likely than others to describe their relationship with the person who died as having been 'very good'. The data can be interpreted in various ways and it is not possible to say with certainty that a religious faith is helpful around the time of death.

Aged↗
PubMed2003

Occupational exposure to electromagnetic fields and acute leukaemia: analysis of a case-control study.

AIMS: To investigate whether the risk of acute leukaemia among adults is associated with occupational exposure to electromagnetic fields. METHODS: Probable occupational exposure to electromagnetic fields at higher than typical residential levels was investigated among 764 patients diagnosed with acute leukaemia during 1991-96 and 1510 sex and age matched controls. A job exposure matrix was applied to the self reported employment histories to determine whether or not a subject was exposed to electromagnetic fields. Risks were assessed using conditional logistic regression for a matched analysis. RESULTS: Study subjects considered probably ever exposed to electromagnetic fields at work were not at increased risk of acute leukaemia compared to those considered never exposed. Generally, no associations were observed on stratification by sex, leukaemia subtype, number of years since exposure stopped, or occupation; there was no evidence of a dose-response effect using increasing number of years exposed. However, relative to women considered never exposed, a significant excess of acute lymphoblastic leukaemia was observed among women probably exposed to electromagnetic fields at work that remained increased irrespective of time prior to diagnosis or job ever held. CONCLUSION: This large population based case-control study found little evidence to support an association between occupational exposure to electromagnetic fields and acute leukaemia. While an excess of acute lymphoblastic leukaemia among women was observed, it is unlikely that occupational exposure to electromagnetic fields was responsible, given that increased risks remained during periods when exposure above background levels was improbable.

Adolescent↗
PubMedDate not supplied

Management of patients with anti-Cartwright (Yta).

Five patients with anti-Cartwright (Yta) in their serum were observed during a 14-month period. One of the patients in whom a 51Cr-labeled donor red cell survival study was done showed increased destruction of infused Yta-positive red cells while three other patients tested showed a survival of greater than 85 percent at 1 hour. None of the antibodies potentiated interaction between sensitized red cells and heterologous activated mononuclear cells. The fifth patient received many transfusions of Yta-positive red cells without any adverse reaction. Performance of a 1-hour red cell survival with 51Cr-labeled Yta-positive cells is recommended when time permits to determine whether patients with anti-Yta can receive Yta-positive red cells or, alternatively, whether they must receive Yta-negative red cells. This approach not only is the safest for the patient, but allows conservation of Yta-negative blood. Such an approach also should be used in patients with antibodies against other high-incidence antigens.

Aged↗
PubMed2005

Simplified mons plasty: a new technique to improve cosmesis in females with the exstrophy-epispadias complex.

PURPOSE: Long-term data suggest that a significant number of women with the exstrophy-epispadias complex (EEC) report dissatisfaction with the cosmetic appearance of the genitalia. We developed a new technique of mons plasty in an attempt to improve the overall cosmetic appearance of the external genitalia in females with EEC. MATERIALS AND METHODS: Nine consecutive females with a mean age of 6.4 years (range 2 days to 12.2 years) previously diagnosed with EEC underwent simplified mons plasty concomitantly with various other urological reconstructive procedures. Briefly, a simplified mons plasty was performed by approximating the bifid hemiclitoris and subsequently incising the lateral sulci between the labia majora and minora, which allowed the superomedial rotation of the labia majora and underlying peripubic adipose tissue, thus, recreating the mons. RESULTS: There were no perioperative complications. With a mean followup of 6 months (range 4 to 12) all patients had improved cosmesis with respect to a more prominent mons, more appropriately situated labia and adequately recessed introitus. CONCLUSIONS: Simplified mons plasty improves cosmesis in females with external genital abnormalities secondary to EEC. Although our followup is admittedly short, we believe that this technique should be considered in the armamentarium of the reconstructive surgeon during the operative treatment of this complex group of patients.

Abdominal Wall↗
PubMed2000

Risk factors for Hodgkin's disease by Epstein-Barr virus (EBV) status: prior infection by EBV and other agents.

A UK population-based case-control study of Hodgkin's disease (HD) in young adults (16-24 years) included 118 cases and 237 controls matched on year of birth, gender and county of residence. The majority (103) of the cases were classified by Epstein-Barr virus (EBV) status (EBV present in Reed-Stenberg cells), with 19 being EBV-positive. Analyses using conditional logistic regression are presented of subject reports of prior infectious disease (infectious mononucleosis (IM), chicken pox, measles, mumps, pertussis and rubella). In these analyses HD cases are compared with matched controls, EBV-positive cases and EBV-negative cases are compared separately with their controls and formal tests of differences of association by EBV status are applied. A prior history of IM was positively associated with HD (odds ratio (OR) = 2.43, 95% confidence interval (CI) = 1.10-5.33) and with EBV-positive HD (OR = 9.16, 95% CI = 1.07-78.31) and the difference between EBV-positive and EBV-negative HD was statistically significant (P = 0.013). The remaining infectious illnesses (combined) were negatively associated with HD, EBV-positive HD and EBV-negative HD (in the total series, for > or =2 episodes compared with < or =1, OR = 0.45, 95% CI = 0.25-0.83). These results support previous evidence that early exposure to infection protects against HD and that IM increases subsequent risk; the comparisons of EBV-positive and EBV-negative HD are new and generate hypotheses for further study.

Adolescent↗
PubMed1994

Why don't more young men in the UK become fathers?

OBJECTIVE: This paper aims to show that, compared with young women, there is an apparent discrepancy in the reported sexual behaviour of young men and records of their fatherhood. DESIGN: The data come from four studies of the sexual behaviour of young people in various parts of Britain between 1960 and 1990 and from statistics published by the Office of Population Censuses and Surveys. MAIN RESULTS: More of the young men than the young women had been sexually active, and the men had had more sexual partners. Relatively few men under 20, however, are identified as fathers. In 1991 there were 52,396 live births to women under 20 years, but only 12,959 births were attributed to men under 20, and if all those to women under 20 for which the father was not identified are added to this, the total is still only 28,208--54% of the number of births to women of that age. Seven possible reasons for the discrepancy are discussed. Data suggest that the two most probable explanations are that there are different patterns of intercourse among young men and women and that the data obtained in surveys are to some extent inaccurate or biased. CONCLUSIONS: Differing behaviours indicate a double standard for men and women. Imperfect information affects predictions about a potential heterosexual HIV epidemic.

Adolescent↗
PubMed1996

An outbreak of viral gastroenteritis on a cruise ship.

Three hundred and seventy-eight passengers reported gastroenteritis during four cruises in the western Mediterranean on consecutive weeks of 1995. The rate at which cases were reported each day increased on the fourth cruise. The ship's owner commissioned an epidemiological investigation from the PHLS Communicable Disease Surveillance Centre. Cases reported explosive vomiting and diarrhoea, which lasted from 24 hours to five days, and were suggestive of viral gastroenteritis. No food handlers reported illness, but enquiries suggested that some had been ill and treated themselves. No bacterial pathogens were isolated from faecal specimens provided by cases or from water, food, and environmental samples taken from the galley. Small round structured viruses (SRSV) were identified by reverse transcriptase polymerase chain reaction in two faecal specimens and one specimen of vomit from people who became ill during the fourth cruise. SRSV was also identified in one faecal specimen by electron microscopy. Environmental inspection revealed inappropriate food handling, hygiene, and storage. During one 24 hour period no chlorine was detectable in the water. A case control study conducted on the fourth cruise sought details of exposure to various foodstuffs, unbottled water, and various parts of the ship. No significant associations were found between illness and any exposures. The evidence strongly suggested a continuing outbreak of SRSV infection transmitted from person to person. Some passengers remained on board for a second week and could have transmitted their infection to new arrivals. The ship was cleared and disinfected at the end of the fourth cruise in order to interrupt transmission. Fewer than 10 cases presented in each of the fifth and sixth cruises.

Adolescent↗
PubMed1994

Development and evaluation of a rapid and simple procedure for detection of Pneumocystis carinii by PCR.

We report the development of a simplified PCR-based assay for the detection of Pneumocystis carinii DNA in clinical specimens. The adoption of a rapid DNA extraction procedure and the introduction of a type of enzyme-linked immunosorbent assay for PCR product detection enabled this procedure to be carried out in a single working day in a clinical microbiology laboratory. The PCR assay was prospectively compared with an immunofluorescent-antibody (FA) staining method for the detection of P. carinii in induced sputum and bronchoalveolar lavage (BAL) specimens. The results of the study showed that, for induced sputum specimens, FA staining had a sensitivity of 78% (32 of 41 specimens) and a specificity of 100% (166 of 166 specimens); PCR was 100% (41 of 41 specimens) sensitive and 98% (162 of 166 specimens) specific. For BAL specimens, FA staining was 100% sensitive (21 of 21 specimens) and 100% specific (133 of 133 specimens), and PCR had a sensitivity of 100% (21 of 21 specimens) and a specificity of 99% (132 of 133 specimens). These results strongly suggest that use of our PCR-based assay could effect clinically useful improvements in the sensitivity of induced sputum specimens for the detection of P. carinii.

Bronchoalveolar Lavage Fluid↗
PubMed2005

Symptom experiences of residents dying in assisted living.

OBJECTIVES: To identify the end-of-life symptom experiences of residents who died in assisted living, to describe family satisfaction with the end-of-life care, and to compare end-of-life symptom distress across 4 settings: assisted living, private home, nursing home, and hospital. DESIGN: In-person interviews with family members of people aged 65 or older who had died 2 to 4 months earlier in an assisted-living facility. Symptom distress reports were compared with data from prior studies in other settings. SETTING: A mixed urban-rural community in the Northwest. PARTICIPANTS: Twenty-five family members who self-identified as closely involved in the care or decision making for a relative who died in an assisted-living facility. MEASUREMENTS: A 28-item interview guide composed of demographic questions, the modified Family Memorial Symptom Assessment Scale-Global Distress Index (FMSAS-GDI), and open-ended items describing the decedent's last days and family satisfaction with care and symptom management. RESULTS: Symptoms experienced by at least 75% of decedents were lack of energy, loss of appetite, dry mouth, drowsiness, and pain. Symptom experiences in assisted living were comparable to those in other settings. Families overall were satisfied with end-of-life care in assisted living, but had concerns about communication among providers, inadequate monitoring of their decedent, and lack of staff knowledge specific to symptom management. CONCLUSION: Residents dying in assisted-living settings have similar symptom distress experiences as people dying in other, more studied settings. As residents and families alike overwhelmingly support resident deaths in their assisted living "home," policies, structures, and processes are needed to ensure that end-of-life care needs are met.

Aged, 80 and over↗
PubMed1992

Residential proximity of children with leukaemia and non-Hodgkin's lymphoma in three areas of northern England.

A retrospective population-based case-control interview study has been conducted in three distinct areas in the north of England where local excesses of children with leukaemia have been reported. A total of 109 cases of childhood (0-14 years at diagnosis) leukaemia and non-Hodgkin's lymphoma who were born in one of the study areas and diagnosed there between 1974 and 1988 were included in the study. One control per case was matched on sex, date-of-birth and health district of birth. The objective was to compare residential histories of cases and controls and in particular to determine whether case children had lived in the same place at the same time more often than controls. The residential distance between two children was taken to be the smallest geographical distance between homes they had 'occupied' simultaneously for a period of at least 6 months between conception and diagnosis. Case children were more likely than expected to have other cases as their nearest neighbours by residential distance (observed = 69, expected = 54.5, P = 0.006). A detailed examination of the nearest neighbour pattern permits the generation of further specific hypotheses. These suggest that persistent infection established in utero or early infancy may be involved in the development of some cases of childhood leukaemia. Horizontal transmission of the agent(s) within small communities may occur but there is no evidence of direct contact between cases.

Case-Control Studies↗
PubMed2001

Genetic influences on craniofacial outcome in an avian model of prenatal alcohol exposure.

BACKGROUND: Understanding the basis for ethanol's teratogenic effects may inform the etiology of fetal alcohol syndrome. Here we investigate how genetic background and susceptibility to ethanol-induced neural crest apoptosis contribute to the distinctive craniofacial phenotype observed after prenatal alcohol exposure. METHODS: Nine different chick strains were exposed to ethanol at gastrulation. The sensitivity of these embryos to ethanol-induced neural crest apoptosis was reported elsewhere (Debelak and Smith, 2000). Here, these embryos were permitted to develop until embryonic day 10, when facial morphogenesis was largely complete, and cephalometric measurements were made on cleared skulls. Shifts in facial growth were correlated against the severity of ethanol-induced apoptosis in facial precursors. RESULTS: The facial shape produced by ethanol exposure was a function of the embryos' genetic strain. Three general responses were observed: apparent midfacial flattening (Babcock B300 x Hampshire Red, ISA-Babcock, HyLine W98, and HyLine W36 strains), overall facial expansion (Spafas and Babcock B300 strains), or overall facial hypoplasia (DeKalb strains). When dose and timing of exposure were held constant, the embryo's genetic background predicted the facial outcome. For ethanol-sensitive strains, apoptosis of facial precursor populations was required to produce the facial defects. That some strains had essentially normal faces despite extensive cell death indicated a capacity to recover from the earlier neural crest losses. CONCLUSIONS: We propose that ethanol's effects on craniofacial development are multifactoral, and these influences may include susceptibility to apoptosis, regenerative capacity, and compensatory outgrowth of the facial primordia. The embryo's genetic background may modulate these events. The high and low responder chick strains are useful tools to dissect these contributions.

Animals↗
PubMed1993

Cancer in Cumbria and in the vicinity of the Sellafield nuclear installation, 1963-90.

OBJECTIVE: To reappraise the epidemiological findings reported by the Black Advisory Group concerning a possible excess of malignant disease, particularly of childhood acute lymphoid leukaemia and non-Hodgkin lymphomas, in the vicinity of the Sellafield nuclear installation, and to determine whether any excess of malignant disease had occurred among people aged 0-24 years in the area in the years after the Black report--that is, from 1984 to 1990. DESIGN: Calculation of incidence of cancer using data from population based cancer registries and special surveys. SETTING: England and Wales; county of Cumbria; county districts Allerdale and Copeland within Cumbria; Seascale ward within Copeland. SUBJECTS: All residents under the age of 75 years in the above areas, but with particular reference to those aged 0-24 years. MAIN OUTCOME MEASURES: Numbers of cases and incidence particularly of lymphoid leukaemia and non-Hodgkin lymphomas in those aged 0-24 years, but including other cancers and age groups. RESULTS: Previous reports of an increased incidence of cancer, especially of leukaemia, among those aged 0-24 years in Seascale during the period up to and including 1983 are confirmed. During 1984-90 there was an excess of total cancer among those aged 0-24 years. This was based on four cases including two cases of non-Hodgkin lymphoma but none of leukaemia. There was an increased, but nonsignificant, incidence of other cancers, based on two cases (one pinealoma and one Hodgkin's disease) occurring among those aged 15-24 years during 1984-90. This was not observed in the younger age group or in previous years. For the immediately surrounding area--that is, the county districts of Allerdale and Copeland excluding Seascale and in the remainder of Cumbria--there was no evidence of an increased incidence of cancer among those aged 0-24 years in either period. CONCLUSIONS: During 1963-83 and 1984-90 the incidence of malignant disease, particularly lymphoid leukaemia and non-Hodgkin lymphomas, in young people aged 0-24 in Seascale was higher than would be expected on the basis of either national rates or those for the surrounding areas. Although this increased risk is unlikely to be due to chance, the reasons for it are still unknown.

Adolescent↗
PubMed1999

Patterns of care and survival for adolescents and young adults with acute leukaemia--a population-based study.

We report a population-based study of patterns of care and survival for people with acute leukaemia diagnosed at age 15-29 years during 1984-94 in regions of England and Wales covered by specialist leukaemia registries. There were 879 patients: 417 with acute lymphoblastic leukaemia (ALL) and 462 with acute myeloid leukaemia (AML). For ALL, actuarial survival rates were 43% at 5 years after diagnosis and 37% at 10 years. Survival improved significantly between 1984-88 and 1989-94 for those aged 15-19 at diagnosis. Patients entered in national clinical trials and those not entered had similar survival rates. Survival rates were similar at teaching and non-teaching hospitals and at hospitals treating different numbers of study patients per year. For AML, survival rates were 42% at 5 years after diagnosis and 39% at 10 years. Survival improved significantly between 1984-88 and 1989-94. Patients entered in the Medical Research Council AML10 trial had a higher survival rate than those who were in the earlier AML9 trial. Survival did not vary with category of hospital. We conclude that survival has improved for adolescents and young adults with acute leukaemia but that there is at present no evidence that centralized treatment results in a survival benefit for patients in this age group.

Adolescent↗
PubMed2002

The use of aerosolized fibrin glue in face-lift surgery.

The purpose of this study was to report the use of aerosolized fibrin glue in face-lift surgery. A prospective study was conducted of 48 patients undergoing face-lift surgery sequentially assigned into two groups. The first 24 patients underwent face lifts without glue and the next 24 patients with the use of aerosolized fibrin glue. One surgeon (J.P.F.) performed all the face lifts using the same technique. Drains were only used in those patients who did not receive fibrin glue. The amount of bruising and edema was compared in the two groups, as was the incidence of complications, such as hematomas. Operating time was also assessed in the two groups. The patients in whom glue was used had significantly less bruising and swelling (p < 0.0001), with a more rapid healing response. The risk of hematoma was also less with the use of glue (0 percent) than without glue (8.3 percent), but this was not statistically significant (p = 0.489). Another benefit was that drains were not needed when glue was used. Operating times were shorter by 13.3 minutes with the use of glue (p < 0.0001). Aerosolized fibrin glue has great promise in improving face-lift results, with excellent outcomes and fewer complications. The added cost of the glue is partially offset by an expedited patient recovery period without the need for drains.

Aerosols↗
PubMed1998

Mortality and cancer incidence in acromegaly: a retrospective cohort study. United Kingdom Acromegaly Study Group.

Patients with acromegaly have a reduced life expectancy, with the accepted causes for premature death being vascular and respiratory disease. Increased mortality from malignant disease has also been reported. We, therefore, performed a multicenter retrospective cohort study of 1362 patients with acromegaly and investigated the relationships of mortality and cancer incidence with GH levels, duration of disease, and age at diagnosis. The overall cancer incidence rate [standardized incidence ratio, 0.76; 95% confidence interval (CI), 0.60-0.95] was lower than that in the general population of the United Kingdom, and there was no significant increase in site-specific cancer incidence rates. The overall cancer mortality rate was not increased, but the colon cancer mortality rate (standardized mortality ratio, 2.47; 95% CI, 1.31-4.22) was higher than expected. Mortality rates due to colon cancer, all malignant disease, cardiovascular disease and overall mortality were increased with higher posttreatment GH levels (P for trends, <0.02, <0.05, <0.02, and <0.0001). The overall mortality rate in patients with acromegaly with posttreatment GH levels less than 2.5 ng/mL (5 mU/L) was comparable to that in the general population of the United Kingdom (standardized mortality ratio, 1.10; 95% CI, 0.89-1.35). We conclude that high posttreatment GH levels are associated with an increased overall mortality rate and increased mortality rates due to colon cancer, cardiovascular disease, and all malignant disease. Posttreatment GH levels less than 2.5 ng/mL (5 mU/L) result in an overall mortality rate similar to that in the general population.

Acromegaly↗
PubMed1992

Human papillomavirus in women. A three-year experience in a county hospital colposcopy clinic.

The human papillomavirus (HPV) has been associated with cervical dysplasia and carcinoma. This report summarizes the authors' experience with HPV-related problems over three years, 1987-89, while managing 1,644 women at a county hospital colposcopy clinic. Probes for HPV DNA were not used, and the diagnoses were made with cytologic and histologic criteria alone. The percentage of patients referred to the clinic with HPV found on routine Papanicolaou smears rose significantly, from 3 in 1987 to 18 in 1989. Fifteen percent of those referred because of HPV on a Papanicolaou smear were found to have cervical intraepithelial neoplasia (CIN) grade II or III after they were evaluated at the clinic. Of the 367 cases of biopsy-proven cervical HPV, only 33 (9%) were recorded on Papanicolaou smears performed immediately before the biopsy, and 140 (38%) also had concomitant, biopsy-proven CIN, grade II or III. Of the 195 instances in which the colposcopic impression was simple HPV without CIN, 46 (24%) had high-grade CIN on biopsy. We conclude that the proportion of patients with HPV-associated problems is increasing, that the Papanicolaou smear is not sensitive in detecting cervical HPV infections, that patients with HPV changes found on Papanicolaou smears should be evaluated with colposcopy and that lesions that appear colposcopically to be simple HPV should undergo biopsy to rule out the presence of high-grade CIN.

Biopsy↗
PubMed1992

Characterization of the interaction of polyomavirus middle T antigen with type 2A protein phosphatase.

Two cellular proteins of 36 and 63 kDa which bind the small T and middle T antigens of polyomavirus recently have been identified as the catalytic and regulatory subunits of the phosphoserine/threonine-specific type 2A protein phosphatase (PP2A). We report here the presence of phosphoseryl phosphatase activity associated with polyomavirus small T and middle T antigens in immunoprecipitates prepared from virus-infected and transformed cells. Phosphatase activity was also found associated with middle T-antigen mutants, some of which had been defined previously to associate with 36- and 63-kDa cellular proteins. Middle T-antigen-associated phosphatase activity was sensitive to okadaic acid and microcystin-LR, inhibitors of PP2A, and insensitive to inhibitor 1 or 2, orthovanadate, or EDTA. Using antiserum specific for the catalytic subunit of PP2A, we found that unlike the majority of PP2A, middle T-antigen-bound PP2A was membrane associated. However, no gross change in the amount, activity, or localization of PP2A could be attributed to middle T-antigen expression in transformed cells. Anti-PP2A antibodies coprecipitated a 63-kDa protein from normal cells and in addition coprecipitated middle T antigen, 60- and 61-kDa proteins (identified as src family members), and an 81-kDa protein from middle T-antigen-transformed cells. Furthermore, we detected protein kinase activity in PP2A immunoprecipitates and protein phosphatase activity in src immune complexes from extracts of middle T-antigen-transformed, but not normal, cells. These results reinforce the notion that at least a portion of middle T antigen bridges a protein kinase with a protein phosphatase.

Animals↗