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Biomedical subjects

P Cooper

Publications and source records attributed to P Cooper.

At least 73 records · Page 4Linked to original sources
PubMed1997

Protein C and protein S in homozygous sickle cell disease: does hepatic dysfunction contribute to low levels?

The aim of this study was to confirm reports of low protein C (PC) and S (PS) concentrations in steady-state patients with homozygous sickle cell (SS) disease when compared to a racially matched normal haemoglobin (AA) control group and to examine the mechanisms of this reduction with respect to hepatic function, coagulation activation and haematological indices. In 36 SS patients and 35 AA race-matched controls PC (functional and immunoreactive), PS (free and total) were measured. C4B binding protein (C4B) was assessed by immunoelectrophoresis and D-dimer by ELISA. Hepatic function was assessed by prothrombin (PT) time (49 SS, 64 AA), factor V (34 SS, 36 AA) and factor VII concentrations (28 SS, 29 AA). Proteins induced in vitamin K absence or antagonism (PIVKA) were sought in 12 SS's. The relationship between PC, PS and total bilirubin, haemoglobin (Hb) F and reticulocyte count was also assessed. PC, PS and C4B were lower in SS disease. SS patients had longer PT times, and lower factor V and VII concentrations in comparison to AA controls. PC (functional and immuno-reactive) and free PS correlated with PT. Within SS genotype PT correlated negatively with factor V and factor VII. Factor V and VII were positively correlated. PIVKAs were not detected. There was no correlation between PC, PS and D-dimer, haemolytic rate or Hb F concentration. Prolongation of PT time, low factor V and VII suggest that hepatic dysfunction, rather than coagulation activation or haemolytic rate, accounts for the reduced concentrations of PC and PS in steady-state SS disease. The absence of PIVKAs suggests a hepatocellular problem.

Anemia, Sickle Cell↗
PubMed1997

In vivo coagulation activation following infusion of highly purified factor XI concentrate.

The use of factor XI concentrates has been associated with thrombosis. Plasma markers of coagulation activation were measured before and 30, 60, 120 and 240 min after six infusions of the BPL factor XI concentrate. Five studies were completed before surgical intervention, one was undertaken in a patient with an intracerebral haemorrhage. Significant elevation of levels of fibrinopeptide A (FpA) (P < 0.05) and thrombin-antithrombin (TAT) were demonstrated following six infusions and prothrombin fragment F1.2 following four. Levels of all three markers had risen 60 min following concentrate administration and FpA levels remained elevated throughout the study period. Levels of D-dimer rose in four patients at 240 min. These results indicate significant thrombin generation by 60 min and subsequent plasmin generation consistent with coagulation activation by the factor XI concentrate. The greatest elevation of activation markers was seen in those subjects with pre-existing coagulation activation. We advise caution in the use of these products and awareness of the risks in patients who may already have activated coagulation states.

Adult↗
PubMed1997

Activated protein C resistance in homozygous sickle cell disease.

The activated protein C resistance (APC-R) ratios in 50 patients with steady state homozygous sickle cell (SS) disease and 59 healthy AA controls was measured. There was a significant reduction in median APC-R ratio in sickle cell disease compared to controls. This reduction in APC-R ratio was not explained by (1) the presence of the factor V Leiden, found in only one of 165 patients with SS disease including those tested for APC-R, or (2) the presence of lupus anticoagulants. However, the raised levels of factor VIIIC in SS patients in this study may be contributing to increased resistance to APC, which in turn may contribute to the vaso-occlusive complications of SS disease.

Adolescent↗
PubMed1997

Changing incidence of invasive adenocarcinoma of the uterine cervix in East Anglia.

OBJECTIVE: To determine trends in incidence of invasive adenocarcinoma of the uterine cervix in East Anglia. METHODS: Cervical cancer incidence data for both squamous cell carcinomas and adenocarcinomas were obtained from the East Anglian Cancer Registry for the period 1971-94. Similar data were obtained for England and Wales. European age standardised rates (ASRs) were used for comparisons. RESULTS: The mean incidence (ASR) of cervical adenocarcinoma was 0.85 per 10(5) in 1971-76, rising to 2.54 per 10(5) in 1989-94. There has been a marked age shift, with the main increase in incidence occurring in younger women aged 30-39. The mean incidence (ASR) of squamous cell carcinoma of the cervix has decreased from 9.78 to 8.74 per 10(5) over the periods 1971-76 and 1989-94. Again there has been an age shift, moving from a single incidence peak in the 45-59 age band in earlier years to incidence peaks in both the 30-39 and 55-69 age bands in more recent years. Similar trends were noted when data for England and Wales were analysed. Birth cohort analyses show that both tumours are occurring progressively earlier (about five years earlier in each five year birth cohort). CONCLUSION: Although the overall incidence of cervical carcinoma is declining, this study has shown an increased incidence of cervical adenocarcinoma, particularly in the younger age groups. In future it would seem advisable to publish separate incidence and mortality data for squamous cell carcinoma and adenocarcinoma of the uterine cervix. All practitioners involved in the cervical cancer screening programme would then be aware of the very real significance of this tumour.

Adenocarcinoma↗
PubMed1996

Infant growth in the context of maternal eating disorders and maternal depression: a comparative study.

There is evidence of growth faltering in infants of mothers with eating disorders. The aim of the current study was to examine whether this is a specific relationship. Thus, the infants of mothers with eating disorders were compared with infants of mothers with post-natal depression and a large comparison group. This study also aimed to explore possible mechanisms whereby growth disturbance comes about. It was found that the infants of mothers with eating disorders were smaller, both in terms of weight for length and weight for age, than either comparison group infants or infants of mothers with post-natal depression. There was little evidence, however, that mothers with eating disorders preferred smaller children or were dissatisfied with their children's shape or that they misperceived their children's size. On the contrary these mothers seemed highly sensitive to their children's shape and, compared with the other two groups, were more likely to judge their children's size accurately. None of these maternal measures significantly predicted the child's growth. The mechanism whereby growth disturbance arises in the context of eating disorders does not appear to be by means of a direct extension of the maternal psychopathology to the infant.

Adolescent↗
PubMed1996

Demographic, psychosocial, and objective risk factors related to perceived risk of skin cancer.

BACKGROUND AND METHODS: The present study examined the ways in which demographic, psychosocial, and objective risk factors were related to perceived risk of skin cancer among 384 hospital employees who participated in a screening program. It was hypothesized that pyschosocial risk factors would account for a significant portion of the variance in risk perception beyond that accounted for by the other risk factors. RESULTS: The risk factors accounted for approximately 44% of the variance in risk perception. Psychosocial risk factors accounted for a statistically significant portion of the variance in risk perception beyond that accounted for by other risk factors. Worry, family history of skin cancer, and race/ethnicity were most strongly related to perceived risk. CONCLUSIONS: Results are discussed in terms of the need for educational programs that emphasize the relationship between level of risk and skin cancer and provide specific information regarding steps that can be taken to prevent skin cancer.

Adult↗
PubMed1996

Mutations revealed by sequencing the 5' half of the gene for ataxia telangiectasia.

Ataxia telangiectasia is a recessive disorder in which patients show a progressive cerebellar degeneration leading to ataxia, abnormal eye movements and deterioration of speech. Other features include ocular telangiectasia, high serum AFP levels, immunodeficiency, growth retardation and an increased predisposition to some tumours, particularly T cell leukaemia and lymphoma. We report the 1348 amino acid sequence of the N-terminal half of the A-T gene product which, together with the previously published C-terminal half, completes the sequence of the A-T protein. No homologies with other genes have been found within the N-terminal half of the A-T protein. We have also identified six mutations affecting the N-terminal half of the protein. One of these mutations was found to be associated with a haplotype that is common to four apparently unrelated families of Irish descent. All the patients so far examined for both A-T alleles were shown to be compound heterozygotes. None of these mutations affected a putative promoter region which may direct divergent transcription of both the A-T gene and a novel gene E14. The ability to recognise mutations across the entire coding sequence of the A-T gene provides a practical advantage to A-T families since a DNA based prenatal diagnosis will be possible in families where the mutations are identified irrespective of the level of radiosensitivity in these families.

Amino Acid Sequence↗
PubMed1996

The cognitive development of 5-year-old children of postnatally depressed mothers.

As part of a longitudinal study of the influence of postnatal depression on child development, the cognitive functioning of index and control children was assessed at age 5 years. There was no evidence of an adverse effect of postnatal depression, even amongst sub-groups of children suggested to be vulnerable (boys and children from low SES families). However, early experience of insensitive maternal interactions predicted the persistence of poorer cognitive functioning. A number of factors in the child's current environment, including stimulation at home, social class and, for boys, the experience of schooling, contributed to cognitive performance. The findings are considered in relation to the ongoing debate on sensitive periods.

Child of Impaired Parents↗
PubMed1996

Direct in situ nucleic acid amplification: control of artefact and use of labelled primers.

Aims-To evaluate factors which ameliorate false positive artefacts with direct in situ PCR using labelled dNTPs; to investigate the use of labelled primers to overcome this artefact whilst maintaining sensitivity.Methods-Sections of measles (RNA virus) infected Vero cells with cytoplasmic signal or cytomegalovirus (DNA virus) infected fibroblasts with nuclear signal were collected. In situ PCR (or in situ RT-PCR) was carried out by methods permitting evaporation. Reagents or conditions which may control false positive artefacts using labelled dNTPs were investigated systematically. Labelled primers were tested to overcome artefacts, with adjuncts which improve sensitivity.Results-No reagent nor condition investigated was able to control the artefact with labelled dNTPs. Excessive digestion and incomplete DNAse treatments exacerbated the artefact, whereas novobiocin decreased both specific signal and artefact. However, the artefact was controlled by labelled primers, albeit with relatively low sensitivity. Sensitivity using labelled primers could be increased using alcohol fixation, albumin or Perfectmatch.Conclusions-A repair process is implicated for the artefact using labelled dNTPs. Excessive digestion or DNAse treatment may exacerbate DNA damage by disrupting histones or the DNA, respectively. Labelled primers control this artefact, albeit with reduced sensitivity, which may be improved by precipitation fixatives (alcohol) and reagents which enhance specific reaction.

Journal Article↗
PubMed1996

Pitfalls in interpreting prostate specific antigen velocity.

PURPOSE: The concept of prostate specific antigen (PSA) velocity as an improved marker for prostate cancer detection is intriguing. However, before this concept is applied to individual patients several confounding parameters must be addressed. We determined the variability of serum PSA levels in men without prostate cancer. MATERIALS AND METHODS: We reviewed data from a prostate cancer screening program, and determined inter-assay and individual variability of the serum PSA values for a 2-year followup period in 265 men clinically free of prostate cancer. RESULTS: Our average inter-assay coefficient of variation was 7.5%. Therefore, we considered only PSA changes exceeding +/- 15% as significant. Fluctuations in serum PSA occurred in 78% of the men during the observation period, and 12.5% had at least a single PSA increase exceeding 0.75 ng/ml. per year. Fluctuations were noted throughout the entire range of serum PSA levels but became progressively larger with an increasing mean PSA. CONCLUSIONS: The inter-assay variability must be considered when interpreting PSA velocity. Individual fluctuations in serum PSA dictate an observation period of at least 2 years before PSA velocity is considered abnormal.

Adult↗
PubMed1996

Nebulized budesonide is as effective as nebulized adrenaline in moderately severe croup.

OBJECTIVE: Nebulized budesonide and nebulized adrenaline have been shown to be effective in the treatment of moderately severe croup. However, there has been no direct comparison of these therapies. We undertook a multicenter, randomized, double-blind, parallel group study in 66 hospitalized children with viral or spasmodic croup. METHODS: Children 0.5 to 6 years of age were assessed using a validated croup symptom score (stridor, 0 through 4; cough, 0 through 3; retractions, 0 through 3; dyspnea, 0 through 3; and color, 0 through 4) at 0.5, 1, 1.5, 2, 12, and 24 hours after nebulization. Patients received either budesonide (2 mg/4 mL) or L-adrenaline (4 mg/4 mL) via nebulization. The primary outcome measure was change in the total croup symptom score. RESULTS: Thirty-five children received budesonide and 31 received adrenaline. There was no significant difference in baseline features, including croup score (mean [95% confidence interval]: budesonide, 7.1 [6.7-7.5]; adrenaline, 7.7 [7.3-8.1]). All patients had significant improvement from baseline, and there was not significant difference between the two treatments, as measured by change in croup scores, change in oxygen saturation, duration of hospitalization, number of subsequent treatments with systemic steroids or adrenaline, and adverse events. No child required intubation. CONCLUSION: This study does not show any difference in efficacy and safety between nebulized budesonide and nebulized adrenaline in the treatment of acute upper airway obstruction in patients with moderately severe croup.

Administration, Topical↗
PubMed1996

The impact of postnatal depression and associated adversity on early mother-infant interactions and later infant outcome.

The impact of maternal depression and adversity on mother-infant face-to-face interactions at 2 months, and on subsequent infant cognitive development and attachment, was examined in a low-risk sample of primiparous women and their infants. The severe disturbances in mother-infant engagement characteristic of depressed groups in disadvantaged populations were not evident in the context of postpartum mood disorder in the present study. However, compared to well women, depressed mothers were less sensitively attuned to their infants, and were less affirming and more negating of infant experience. Similar difficulties in maternal interactions were also evident in the context of social and personal adversity. Disturbances in early mother-infant interactions were found to be predictive of poorer infant cognitive outcome at 18 months. Infant attachment, by contrast, was not related to the quality of 2-month interactions, but was significantly associated with the occurrence of adversity, as well as postpartum depression.

Adult↗
PubMed1995

A new method for routine isolation of oral treponemes using U-tubes and pectin medium.

Determination of the composition of the oral microflora has traditionally been based on cultivation. Treponemes are prevalent in many oral infections but, unfortunately, are not regularly cultured. In this study a new method was established for routine isolation of oral treponemes from clinical samples. Bacterial samples from 47 periodontal pockets and 4 endodontic infections were incubated anaerobically under nitrogen atmosphere at 37 degrees C in U-tubes containing pectin medium. In the U-tube a 'bacterial sample side' and a 'sterile medium side' were established on separate sides of a membrane filter and an agar plug. Using this method we were able to isolate viable treponemes from all bacterial samples. This was in contrast to previously established methods such as the agar dilution technique, the technique involving the membrane filter placed on the surface of solid agar media and the well in agar plate technique. We believe that the 'U-tube method' is a valuable supplement to previously described techniques in routine isolation of treponemes from clinical samples.

Journal Article↗
PubMed1995

An examination of driving records in a dementia clinic.

The driving records of 249 persons referred to an outpatient dementia clinic were examined retrospectively to assess the specificity of the association between diagnosed dementia and increased traffic accidents. The clinic patients were divided into two groups: those who met criteria for dementia and those who did not. For each group, control subjects matched on age, gender, and location of residence were randomly selected from the records of all drivers in the province. The dementia sample had approximately 2.5 times the traffic crash rate of their matched control sample. The not-demented sample had approximately 2.2 times the traffic crash rate of their matched control sample. These individuals exhibited a variety of psychiatric, neurological, and medical conditions which could have affected their driving, and multiple medical problems were often present. Further clarification of the characteristics of "high risk" drivers is required if effective strategies for maximizing independence while minimizing the risk of traffic crashes are to be realized.

Accidents, Traffic↗