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H Roberts

Publications and source records attributed to H Roberts.

At least 19 recordsLinked to original sources
PubMed2001

Loss of p16(INK4a) expression correlates with decreased survival in pediatric osteosarcomas.

Abnormalities of the G1 cell-cycle checkpoint are commonly reported in cancers at various anatomic sites. pRB, p16(INK4a) and cyclin D1 are critical G1-checkpoint proteins responsible for maintaining the balance of cellular proliferation. We examined a series of 38 pediatric osteosarcomas for abnormal expression of pRB, p16(INK4a) and cyclin D1 by immunohistochemical analysis of archival biopsy specimens. Overall, 17/38 (45%) osteosarcomas showed evidence of G1-checkpoint abrogation, including 11/38 (29%) with loss of pRB expression and 6/38 (16%) with loss of p16(INK4a) expression. Cyclin D1 over-expression was not detected. There was an inverse correlation between loss of pRB and p16(INK4a) expression (p = 0.07). pRB and p16(INK4a) abnormalities were independent of site of disease, presence of metastasis at diagnosis and percentage of tumor necrosis in the resection specimen. Clinical follow-up was available on all patients (median 31.6 months, range 5.9-116 months). Absence of p16(INK4a) expression significantly correlated with decreased survival in univariate analysis (p = 0.03), while loss of pRB expression did not affect survival. Immunohistochemical analysis of p16(INK4a) expression in pediatric osteosarcomas may be a useful adjunctive marker of prognosis.

Adolescent↗
PubMed2001

Combined oral contraceptive pill (OCP) as treatment for primary dysmenorrhoea.

BACKGROUND: Dysmenorrhoea refers to the occurrence of painful menstrual cramps and is a common gynaecological complaint. Research as early as 1937 has shown that dysmenorrhoea responds favourably to ovulation inhibition, and that the synthetic hormones in the combined oral contraceptive pill can be used to treat dysmenorrhoea. These hormones act by suppressing ovulation and lessening the endometrial lining of the uterus. Therefore, menstrual fluid volume decreases along with the amount of prostaglandins produced, in turn effectively reducing dysmenorrhoea by decreasing uterine motility, and thus uterine cramping. The use of combined oral contraceptive pills (OCP) has been advocated as a treatment for primary dysmenorrhoea since their introduction for general use in 1960. There is evidence from epidemiological studies of general populations that combined OCPs can effectively treat dysmenorrhoea. OBJECTIVES: The objective of this review is to determine the efficacy of combined oral contraceptive pills for the treatment of primary dysmenorrhoea. SEARCH STRATEGY: Electronic searches for relevant randomised controlled trials (RCTs) of the Cochrane Menstrual Disorders and Subfertility Group Register of controlled trials, CCTR, MEDLINE, EMBASE, and CINAHL, were performed. Attempts were also made to identify trials from the National Research Register, the Clinical Trials Register and the citation lists of review articles and included trials. SELECTION CRITERIA: The inclusion criteria were RCTs that compared all types of combined oral contraceptives (oestrogen/progestogen) with other combined oral contraceptives, placebo, no treatment, or treatment with nonsteriodal anti-inflammatory drugs (NSAIDs) in the treatment of primary dysmenorrhoea. The main outcome measures were pain relief, adverse effects, additional analgesics required and time off work or school. DATA COLLECTION AND ANALYSIS: Nine trials were identified that appeared to fulfil the initial criteria for this review. Of these nine trials, four were excluded, two at further investigation revealed a lack of randomisation and two included combined oral contraceptives that are now discontinued due to very high oestrogen content. Of the remaining five RCTs, four were included in the meta-analysis (Buttram 1969; Cullberg 1972; GPRG 1968; Nakano 1971). The results of the other trial (Matthews 1968) were included in the text of the review for discussion because data were not available in a form that allowed it to be combined in a meta-analysis. Data for all outcomes were in dichotomous form and the Peto odds ratio was used in the meta-analysis for all comparisons. MAIN RESULTS: Combined OCPs with medium dose oestrogen (>35 mcg) and 1st/2nd generation progestogens were shown to be more effective than placebo for pain relief. However, there was significant heterogeneity in the results from different studies and when data were analysed with a random effects model, the confidence intervals increased and the results became statistically non-significant. For the other outcomes, there was a significant difference in favour of OCPs when compared to placebo for the outcome of absence from work or school, and there was no difference between the treatment groups and placebo in the number of adverse effects experienced. REVIEWER'S CONCLUSIONS: No conclusions can be made about the efficacy of commonly used modern lower dose combined oral contraceptives for dysmenorrhoea. While there is some evidence from four RCTs that combined OCPs with medium dose oestrogen and 1st/2nd generation progestogens are more effective than placebo it should be emphasised that the studies were small, of poor quality and all included much higher doses of hormones that those commonly prescribed today. Therefore no recommendations can be made regarding the efficacy of modern combined oral contraceptives.

Contraceptives, Oral, Combined↗
PubMed2001

Immunohistochemical [corrected] detection of the alternate INK4a-encoded tumor suppressor protein p14(ARF) in archival human cancers and cell lines using commercial antibodies: correlation with p16(INK4a) expression.

The INK4a locus encodes two structurally unrelated tumor suppressor proteins, p16(INK4a) and p14(ARF). Although the former is one of the most common targets for inactivation in human neoplasia, the frequency of p14(ARF) abrogation is not established. We have developed an immunohistochemical assay that allows the evaluation of p14(ARF) expression in formalin-fixed, paraffin-embedded tissues, using commercially available antibodies. p14(ARF) positive cells showed nuclear/nucleolar staining, which was absent in all cell lines and tumors with homozygous deletions of the INK4a gene. The assay was applied to 34 paraffin-embedded cell buttons, 30 non-small cell lung cancers and 28 pancreatic carcinomas, and the staining results were correlated with p16(INK4a) expression. Loss of p14(ARF) expression was common but less frequent than down-regulation of p16(INK4a) (53% versus 76% of all specimens). The p14(ARF) and p16(INK4a) expression pattern was concordant in 65 of 92 cases (71%). Significantly, 24 cases were p16(INK4a)-/p14(ARF)+, while the opposite staining pattern was observed in three cases, consistent with the notion that the two proteins have nonredundant functions. The immunohistochemical assay described here may facilitate studies on the prevalence and significance of aberrant p14(ARF) expression in human tumors.

Adenocarcinoma↗
PubMed2001

Aberrant expression of tumor suppressor proteins in the Ewing family of tumors.

BACKGROUND: Deregulation of tumor suppressor gene function and abrogation of cell cycle control are common features of malignant neoplasms, but corresponding data on Ewing sarcomas and primitive neuroectodermal tumors are relatively scarce. We studied the expression of 4 tumor suppressor proteins in the Ewing family of tumors (EFTs). DESIGN: We examined a series of 20 pediatric EFTs for abnormal expression of p16(INK4a), p14(ARF), p21(WAF1), and pRB by immunohistochemical analysis of pretreatment, nondecalcified archival specimens. Clinical follow up was available in all cases (median, 21 months; range, 5-103 months). Five patients presented with metastatic disease, 8 had no evidence of disease at last follow up, and 12 had an adverse outcome (death or progressive tumor posttherapy). RESULTS: Twelve cases (60%) demonstrated abnormal expression of at least one tumor suppressor protein. There were 11 cases (55%) with loss of p21(WAF1) expression, 4 (20%) with down-regulation of p16(INK4a), 2 (10%) with absence of pRB, and one case (5%) with loss of p14(ARF) expression. Loss of p16(INK4a) expression correlated with metastatic disease at presentation (P =.026), and showed a trend toward shortened survival (P =.20). The p21(WAF1), p14(ARF), and pRB status was not significantly correlated with either metastatic disease at presentation or outcome. CONCLUSION: Abrogation of the G1 checkpoint was common in this series of EFTs, and down-regulation of p21(WAF1) and p16(INK4a) were the most frequent findings. Loss of p16(INK4a) expression may identify a subset of cases with a more aggressive phenotype.

Adolescent↗
PubMed2000

Deuterium in the Galactic Centre as a result of recent infall of low-metallicity gas.

The Galactic Centre is the most active and heavily processed region of the Milky Way, so it can be used as a stringent test for the abundance of deuterium (a sensitive indicator of conditions in the first 1,000 seconds in the life of the Universe). As deuterium is destroyed in stellar interiors, chemical evolution models predict that its Galactic Centre abundance relative to hydrogen is D/H = 5 x 10(-12), unless there is a continuous source of deuterium from relatively primordial (low-metallicity) gas. Here we report the detection of deuterium (in the molecule DCN) in a molecular cloud only 10 parsecs from the Galactic Centre. Our data, when combined with a model of molecular abundances, indicate that D/H = (1.7 +/- 0.3) x 10(-6), five orders of magnitude larger than the predictions of evolutionary models with no continuous source of deuterium. The most probable explanation is recent infall of relatively unprocessed metal-poor gas into the Galactic Centre (at the rate inferred by Wakker). Our measured D/H is nine times less than the local interstellar value, and the lowest D/H observed in the Galaxy. We conclude that the observed Galactic Centre deuterium is cosmological, with an abundance reduced by stellar processing and mixing, and that there is no significant Galactic source of deuterium.

Astronomical Phenomena↗
PubMed2000

Hormone replacement therapy in postmenopausal women: endometrial hyperplasia and irregular bleeding.

BACKGROUND: The decline in circulating oestrogen around the time of the menopause often induces unacceptable symptoms that affect the health and well being of women. Hormone replacement therapy (both unopposed oestrogen and oestrogen and progestogen combinations) is an effective treatment for these symptoms. In women with an intact uterus, unopposed oestrogen may induce endometrial stimulation and increase the risk of endometrial hyperplasia and carcinoma. The addition of progestogen reduces this risk but may cause unacceptable symptoms, bleeding and spotting which can affect adherence to therapy. OBJECTIVES: The objective of this review is to assess which hormone replacement therapy regimens provide effective protection against the development of endometrial hyperplasia and/or carcinoma with a low rate of abnormal vaginal bleeding. SEARCH STRATEGY: Electronic searches for relevant randomised controlled trials of the Cochrane Menstrual Disorders and Subfertility Group Register of Trials, MEDLINE, EMBASE, PsychLIT, Current Contents, Biological Abstracts, Social Sciences Index and CINAHL were performed. Attempts were also made to identify trials from citation lists of review articles and drug companies were contacted for unpublished data. In most cases, the corresponding author of each included trial was contacted for additional information. SELECTION CRITERIA: The inclusion criteria were randomised comparisons of unopposed oestrogen therapy, combined continuous oestrogen-progestogen therapy and sequential oestrogen-progestogen therapy with each other and placebo administered over a minimum treatment period of six months. Trials had to assess which regimen was the most protective against the development of endometrial hyperplasia/carcinoma and/or caused the lowest rate of irregular bleeding. DATA COLLECTION AND ANALYSIS: Twenty three RCTs were identified and five were excluded. The reviewers assessed the eighteen included studies for quality, extracted the data independently and odds ratios for dichotomous outcomes were estimated. Outcomes analysed included frequency of endometrial hyperplasia or carcinoma, frequency of irregular bleeding and unscheduled biopsies or dilation and curettage, and adherence to therapy. MAIN RESULTS: Unopposed moderate or high dose oestrogen therapy was associated with a significant increase in rates of endometrial hyperplasia with increasing rates at longer duration of treatment and follow up. Odds ratios ranged from 5.4 (1. 4-20.9) for 6 months of treatment to 16.0 (9.3-27.5) for 36 months of treatment with moderate dose oestrogen (in the PEPI trial, 62% of those who took moderate dose oestrogen had some form of hyperplasia at 36 months compared to 2% of those who took placebo). Irregular bleeding and non adherence to treatment were also significantly more likely under these unopposed oestrogen regimens with greater effects with higher dose therapy. There was no evidence of increased hyperplasia rates, however, with low dose oestrogen. The addition of progestogens, either in continuous combined or sequential regimens, helped to prevent the development of endometrial hyperplasia and improved adherence to therapy (odds ratios of 3.7 for sequential therapy and 6.0 for continuous therapy). Irregular bleeding, however, was more likely under a continuous than a sequential oestrogen-progestogen regimen (OR = 2.3, 95% CI 2.1-2.5) but at longer duration of treatment, continuous therapy was more protective than sequential therapy in preventing endometrial hyperplasia (OR = 0.3, 95% CI 0.1-0.97). There was evidence of a higher incidence of hyperplasia under long cycle sequential therapy (progestogen given every 3 months) compared to monthly sequential therapy (progestogen given every month). No increase in endometrial cancer was seen in any of the treatment groups during the limited duration (maximum of 3 years) of these trials. (ABSTRACT TRUNCATED)

Endometrial Hyperplasia↗
PubMed2000

Temporal lobe epilepsy with and without psychosis: exploration of hippocampal pathology including that in subpopulations of neurons defined by their content of immunoreactive calcium-binding proteins.

We have investigated relationships between hippocampal/temporal lobe neuropathology and psychosis in subjects with temporal lobe epilepsy, paying particular attention to possible differences in density of hippocampal neurons immunoreactive for calcium-binding proteins. There was a trend for a greater prevalence of left handedness in the psychotic (n = 6) than the non-psychotic (n = 26) cases (P = 0.0504). Psychotic cases also differed from non-psychotic ones in having: (1) more focal lesions outside the hippocampus (P = 0.006); (2) less severe CAI neuron loss (P = 0.015); and (3) a trend, after Bonferroni correction, for a higher density of calbindin-immunoreactive neurons in the CA4 (P = 0.022). An additional finding was that dentate granule cell dispersion was significantly associated with the presence of a reduced density of calretinin-immunoreactive neurons in CA4 (P = 0.002) and with a more severe loss of CA4 neurons visible with Nissl stain (P = 0.003). Thus, cases of temporal lobe epilepsy with psychosis were distinguishable on the basis of a higher density of calbindin-reactive neurons in CA4 as well as on more general aspects of their pathology.

Adolescent↗
PubMed2000

Personality in adolescents with chronic fatigue syndrome.

Our aim was to study the presence of personality traits and disorder in adolescents with Chronic Fatigue Syndrome (CFS). Personality was then compared to other measures of functioning such as presence of psychiatric disorder and rating on the Child Behavior Checklist 4-18 (CBCL) and in relation to CFS outcome. Twenty-five adolescents with CFS followed-up after contacts with tertiary paediatric/psychiatric clinics were compared with 15 matched healthy controls. Interviews and questionnaires from parents and youngsters included Personality Assessment Schedule (PAS), Kiddie-SADS Psychiatric Interview, Child Behavior Checklist. CFS subjects were significantly more likely than controls to have personality difficulty or disorder. Personality features significantly more common amongst them were conscientiousness, vulnerability, worthlessness and emotional lability. There was a nonsignificant association between personality disorder and worse CFS outcome. Personality difficulty or disorder was significantly associated with psychological symptoms and decreased social competence on the CBCL but it was distinguishable from episodic psychiatric disorder. Personality difficulty and disorder are increased in adolescents with a history of CFS. Personality disorder may be linked to poor CFS outcome.

Adolescent↗
PubMed2000

Smacking.

Explore the source record for details and available documents.

Humans↗
PubMed2000

Field evaluation of a semiautomated method for rapid and simple analysis of recreational water microbiological quality.

An early warning system using a rapid enzymatic semiautomated method suitable for fecal coliform detection in recreational waters within 8 h was developed further and evaluated in this study. This rapid method was compared to the standard method followed in the United Kingdom. We used 1,011 samples originating from 206 different locations in Wales. When we assessed the presence or absence of fecal coliforms, targeting very low levels of contamination, we obtained 83.9% agreement between the rapid method and the lauryl sulfate broth-membrane filtration technique, whereas direct confirmation of the samples processed by the rapid method showed 89. 3% agreement. Environmental enzymatic background activity was found to be the main limiting factor for this method. Owing to a specific and integrated handling of the results by the software of the instrument, the percentage of false-positive results (a consequence of enzymatic background) was successfully limited to 2.9% by the direct confirmation evaluation. However, 7.8% false-negative results due to "late-growers" had to be accepted in order to produce results within a working day. At present, the method can be used in a more conservative way to assess the environmental threshold of 100 CFU of fecal coliforms per 100 ml in recreational waters. The implications of our findings with regard to the applicability of rapid enzymatic methods are discussed.

Acinetobacter↗
PubMed2000

The course of severe chronic fatigue syndrome in childhood.

Little has been reported on prognostic indicators in children with chronic fatigue syndrome (CFS). We used interviews with children and parents, a mean of 45.5 months after illness onset, to follow up 25 cases of CFS referred to tertiary paediatric psychiatric clinics. At its worst, the illness had been markedly handicapping (prolonged bed-rest and school absence in two-thirds); mean time out of school was one academic year. Two-thirds, however, had recovered and resumed normal activities--mean duration of illness to recovery/assessment 38 months--and none had developed other medical conditions. Recovery was associated with specific physical triggers to the illness, with start of illness in the autumn school term and with higher socioeconomic status. Severe fatigue states in children can cause serious and longlasting handicap but most children recover.

Adolescent↗