Search PubMed⌕ Search

Biomedical subjects

D Harvey

Publications and source records attributed to D Harvey.

At least 55 records · Page 3Linked to original sources
PubMed1998

A high-resolution genetic map of the nervous locus on mouse chromosome 8.

The nervous (nr) mutant mouse displays two gross recessive traits: both an exaggeration of juvenile hyperactivity and a pronounced ataxia become apparent during the third and fourth postnatal weeks. Using an intersubspecific intercross, we have established a high-resolution map of a segment of mouse chromosome 8 that places the nr locus in a genomic segment defined by D8Rck1 on the centromeric end and D8Mit3 on the telomeric end. This map position places the nr locus within the BALB/cGr congenic region of the C3HeB/ FeJ-nr strain, confirming the accuracy of our study. We used this map position to identify and evaluate three genes-ankyrin 1, cortexin, and farnesyltransferase-as candidates for the nr gene. These three genes were eliminated from consideration but allowed us to establish the conservation of synteny between the region containing the nr locus and a segment of the short arm of human chromosome 8 (8p21-p11.2). Finally, the incomplete penetrance of the nr phenotype led us to perform a screen for modifier loci, and we present evidence that such a nervous modifier locus may exist on mouse chromosome 5.

Adjuvants, Immunologic↗
PubMed1998

Childhood immunisation in the European Union. Confederation of European Specialists in Paediatrics (CESP).

Harmonisation of working conditions is one of the major aims of the European Union. The Confederation of European Specialists in Paediatrics has elaborated documents on the harmonisation of immunisations in 1987 and 1992. The new and completely updated version focuses on the variations of immunisation practices and schedules and gives criteria for minimal agreement of immunisation schedules among the member countries. Catch-up vaccinations and false contra-indications are especially stressed.

Adolescent↗
PubMed1998

Double data entry: what value, what price?

We challenge the notion that double data entry is either sufficient or necessary to ensure good-quality data in clinical trials. Although we do not completely reject that notion, we quantify some of the effects that poor quality data have on final study results in terms of estimation, significance testing, and power. By introducing digit errors into simulated blood pressure measurements we demonstrate that simple range checks allow us to detect (and therefore correct) the main errors that impact the final study results and conclusions. The errors that cannot easily be detected by such range checks, although possibly numerous, are shown to be of little importance in drawing the correct conclusions from the statistical analysis of data. Exploratory data analysis cannot identify all errors that a second data entry would detect, but on the other hand, not all errors that are found by exploratory data analysis are detectable by double data entry. Double data entry is concerned solely with ensuring, to a high degree of certainty, that what is recorded on the case record form is transcribed into the database. Exploratory data analysis looks beyond the case record form to challenge the plausibility of the written data. In this sense, the second entering of data has some benefit, but the use of exploratory data analysis methods, either as data entry is ongoing or at the end of data entry and as the first stage in an analysis strategy, should always be mandatory.

Algorithms↗
PubMed1998

Assessment of the flexibility of elite athletes using the modified Thomas test.

AIM: To analyse the modified Thomas test and obtain measures of flexibility for the iliopsoas, quadriceps and tensor fascia lata/iliotibial band. METHOD: The modified Thomas test was used to determine the range of flexibility of 117 elite athletes in tennis, basketball, rowing, and running. RESULTS AND CONCLUSION: The study has provided objective data for a clinical test measuring flexibility of the iliopsoas, quadriceps, and tensor fascia lata/iliotibial band. It is recommended that sufficient flexibility is obtained to perform a specific sport and that asymmetries between limbs are addressed.

Biomechanical Phenomena↗
PubMed1998

Hemoglobin Old Dominion/Burton-upon-Trent, beta 143 (H21) His-->Tyr, codon 143 CAC-->TAC--a variant with altered oxygen affinity that compromises measurement of glycated hemoglobin in diabetes mellitus: structure, function, and DNA sequence.

OBJECTIVE: To determine the nature and characteristics of a unique hemoglobin variant that causes a spurious increase in glycated hemoglobin (HbA1c). MATERIAL AND METHODS: Blood specimens from four unrelated persons with this hemoglobin variant were examined by conventional laboratory methods, including electrophoresis, high-performance ion-exchange chromatography, and isoelectric focusing; by amino acid sequence analysis, polymerase chain reaction-based DNA sequence analysis, and electrospray ionization mass spectrometry, to establish the molecular structure; and by studies of oxygen affinity under varied conditions, to define the functional characteristics of the hemoglobin variant. RESULTS: The unique hemoglobin variant observed in these four cases is due to the mutation CAC-->TAC, at beta-globin gene codon 143, corresponding to beta 143 (H21) His-->Tyr. This amino acid substitution affects an important 2,3-diphosphoglycerate binding site and slightly increases the oxygen affinity of the hemoglobin variant. CONCLUSION: A hitherto unrecognized hemoglobin variant, encountered in four unrelated persons of Irish or Scots-Irish ancestry, hemoglobin Old Dominion/Burton-upon-Trent, beta 143 (H21) His-->Tyr, has now been characterized at the molecular, structural, and functional levels. Although it is associated with a slight increase in oxygen affinity, it is without hematologic effect, and its only clinical significance is that it coelutes with HbA1c on ion-exchange chromatography and thereby causes a spurious increase in HbA1c and compromises the use of this analyte to monitor the treatment of diabetes mellitus.

Adult↗
PubMed1997

The myelotoxicity of chloramphenicol: in vitro and in vivo studies: I. In vitro effects on cells in culture.

1 Chloramphenicol is used extensively in non-industrialized countries for the treatment of life-threatening infections because it is cheap and effective, despite its known hemotoxicity and linkage to fatal aplastic anaemia. It is important to define the mechanism of toxicity so that means can be devised to ameliorate the toxic effects in order to produce safer usage. 2 Chloramphenicol, at concentrations from 5 mM to 2 mM initiated apoptosis in dividing cells from a monkey kidney-derived cell line and in haematopoietic progenitor cells from human neonatal cord blood. 3 Growth of progenitor cells was suppressed at concentrations of chloramphenicol which would be considered less than therapeutic during patient treatment. 4 These effects could be ameliorated in progenitor cells by co-culture with the antioxidant mercaptoethylamine and in monkey kidney cells by co-culture with vitamin C. 5 This is the first report of apoptosis in chloramphenicol toxicity and suggests a possible link between a metabolic event i.e. the production of free radicals; a morphological effect, apoptosis; and a clinical effect, bone marrow suppression and aplastic anaemia.

Animals↗
PubMed1997

The presence and significance of the Pi class glutathione S-transferase isoenzyme in cerebrospinal fluid during the course of meningitis in children.

A rise in the concentration of the Pi class isoenzyme of glutathione S-transferase (GST) in the cerebrospinal fluid (CSF) during meningitis may be an early indicator of inflammation and cell damage. Pi class GST concentrations were measured in 48 samples of CSF from 46 children with proven or suspected meningitis using a commercially available immunoassay. Forty-four fetal brain samples were assayed by isoelectric focusing to determine the nature and number of isoenzymes likely to be released. Twenty-four percent of children had measurable amounts of the isoenzyme in their CSF during the initial stages of the disease. One child, for whom CSF samples were taken pre-, mid-, and post-antibiotic treatment, had measurable Pi class GST in the CSF only in the mid-treatment sample, when bacterial lysis and inflammation are likely to be at their peak. Where follow-up data were available, two of three children with measurable Pi class GST in their CSF at the initial stages had recordable disabilities at 5 y of age compared with 4 of 11 of those in whom no Pi class GST was detected. Two proteins analogous to Pi class GST were detected in frozen brain tissue, but only one was active with a known substrate; only the active protein was seen in fresh tissue. We conclude that 1) initial high levels of CSF Pi class GST may be an indicator of the severity of inflammation and thus of prognostic significance and 2) only one Pi class GST occurs in brain tissue.

Brain↗
PubMed1997

Decrease in CD4 lymphocyte counts with rest; implications for the monitoring of HIV infection.

Measurement of the CD4 lymphocyte count is widely used as a prognostic marker and guide for the institution of antiretroviral therapy in patients infected with HIV (human immunodeficiency virus). CD4 counts are known to fluctuate with strenuous physical activity and diurnal variation but there is no information on the effects of rest or normal daily activity. We investigated the effects of rest on the absolute CD4 lymphocyte count in 20 healthy laboratory workers. Blood samples were obtained in 20 subjects upon arrival in the laboratory (CD4 0), following 30 and 60 min rest (CD4 30 and CD4 60 respectively) and 8 h into a normal working day (CD4 8). A significant decrease in the CD4 lymphocyte count was observed following 60 min rest; mean CD4 count at 0 min 1060 x 10(6)/L, mean CD4 count at 60 min 660 x 10(6)/L (P = 0.0017). These results demonstrate a significant effect of rest on CD4 lymphocyte counts in healthy volunteers. This biological variation may be important in HIV-infected patients and needs to be addressed by further studies.

Activities of Daily Living↗
PubMed1997

FLAG is a useful regimen for poor prognosis adult myeloid leukaemias and myelodysplastic syndromes.

Forty patients, with mainly poor risk haematological malignancies, were given the new regimen FLAG, comprising fludarabine, arabinosyl cytosine and G-CSF. Twenty four patients had acute myeloid leukaemia (AML), 8 patients myelodysplastic syndrome (MDS) and a further 8 patients had a variety of other haematological malignancies. The response rates for 19 relapsed and 4 refractory AML patients were 68% and 100% respectively and comparable to those attained using other regimens, although the numbers are small. Of 8 patients with MDS, 7 showed some response with 4 remaining in an improved disease status 5-12 months after FLAG. Follow-up has been too short thus far to provide any survival data in both patient groups. In general, the other smaller group of 8 patients (3 transformed chronic myeloid leukaemia (CML), 3 acute lymphoblastic leukaemia (ALL), 2 granulocytic sarcoma (GS) did poorly with response shown in 1 only. The regimen was well tolerated with 4 procedure-related neutropenic deaths. The neutropenic and thrombocytopenic periods are generally short when compared with those from current protocols. The overall modest toxicity may encourage combination with other anti-leukaemic agents and be of particular use in the aged or heavily pre-treated patients. Preliminary results may favour the setting up of controlled trials to properly evaluate the benefit of FLAG.

Adolescent↗
PubMed1997

Unravelling the genetics of deafness.

Hearing-impaired mouse mutants not only are good models for human hereditary deafness, but also are extremely useful for understanding the molecular basis of the cochlear defect. We describe here how we identified the gene responsible for the deafness and vestibular defects in the shaker-1 mouse mutant as a myosin VII gene. Three different mutations, all causing the same phenotype in different lines of mouse, were found, providing good evidence that we had, indeed, found the correct gene. The same gene was subsequently found to be involved in Usher's syndrome type 1B, which features deafness, vestibular dysfunction, and progressive retinitis pigmentosa. The myosin VII gene is expressed in sensory hair cells, but not in supporting cells or neurons. We are investigating the role of myosin VII in hair cell development and function. Analysis of the different mutant stocks suggests it has at least two functions. First it is involved in the development and maintenance of the stereocilia bundle. Second, it has a role in inner hair cell function. No evidence of retinal degeneration like that in Usher's syndrome has been found in the shaker-1 mutants so far studied. The benefits of understanding the function of the gene for families with Usher's type 1B are discussed. This gene is the first to be identified as causing the most common type of disorder in human hearing impairment, neuroepithelial abnormalities, and suggests a new class of candidate genes for involvement in such defects.

Animals↗
PubMed1996

Macrophages and apoptotic cells in human colorectal tumours.

The numerical relationship between tumour associated macrophages (TAM) and apoptotic cells in 12 human colorectal tumours was evaluated. TAM were labelled immunohistochemically and apoptotic cells were visualized by counterstaining with haematoxylin and eosin (H&E). The stereological techniques, Cavalieri's estimator of volume and the Disector were used to estimate both tumour volume and numerical density of both cell types. The occurrence of TAM per unit volume of tissue increased with increasing tumour volume to a maximum in a tumour of 110.5 cm3, after which numbers declined. Levels of apoptosis also increased with tumour volume though more erratically than levels of TAM and declined for tumour volumes greater than 80 cm3. This is the first report of an attempt to assess the relationship between apoptotic cells and TAM in human tumours.

Apoptosis↗
PubMed1996

The role of pregnenolone-metabolizing enzymes in the regulation of oestradiol biosynthesis during development of the first wave dominant follicle in the cow.

During the luteal phase in the cow, a first-wave dominant follicle grows to reach ovulatory size, but then ceases to grow, becomes no longer dominant and enters a phase of slow regression. During this growth transition, the concentration of oestradiol has been shown to decrease in follicular fluid. The objective of this study was to determine if follicular fluid oestradiol concentrations are regulated by the activity of three major steroidogenic enzymes, namely P450-aromatase (P450-arom), 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase (3 beta-HSD) and 17 alpha-hydroxylase C-17,20 lyase cytochrome P450 enzyme (P450-17 alpha) measured in granulosa and theca cells isolated from individual first-wave dominant follicles. Follicle growth and state of dominance was assessed by ultrasonography and follicles were classified as growing-dominant (GD, n = 6), non-growing-dominant (NGD, n = 8) or non-growing-non-dominant (NGD, n = 6). Mean follicular fluid concentrations of oestradiol were higher in GD than in NGD or NGND follicles (511 +/- 98 versus 136 +/- 16 and 20 +/- 11 nmol/l respectively). Oestradiol was not correlated with P450-arom in any of the three groups. In GD follicles, oestradiol was positively correlated with pregnenolone concentration but neither was correlated with granulosa or theca 3 beta-HSD activity or with theca P450-17 alpha activity. In NGD follicles, oestradiol was negatively correlated with theca 3 beta-HSD activity and pregnenolone was negatively correlated with granulosa 3 beta-HSD activity. In NGND follicles, oestradiol was positively correlated, and pregnenolone was negatively correlated with theca 3 beta-HSD and P450-17 alpha activities. These studies demonstrated that pregnenolone supply is the principal regulating factor of oestradiol output during follicle dominance and during the loss of dominance but that the levels of P450-17 alpha and 3 beta-HSD activity become rate-limiting when the follicle is no longer dominant.

3-Hydroxysteroid Dehydrogenases↗
PubMed1996

Continuous negative extrathoracic pressure in neonatal respiratory failure.

OBJECTIVE: In uncontrolled clinical trials, negative extrathoracic pressure has been shown to be an effective respiratory support. We aimed to assess its role in the context of current neonatal intensive care. DESIGN: A randomized controlled trial, with sequential analysis of matched pairs of infants. Matching was undertaken by stratified randomization from 15 groups divided according to gestational age, oxygen requirement, and whether patients were intubated at 4 hours of age. SETTING: Two neonatal intensive care units. PATIENTS: Two hundred forty-four patients (birth weight 1.53 +/- 0.69 kg (mean +/- SD); gestational age 30.4 +/- 3.5 weeks) with respiratory failure. INTERVENTIONS: Patients were randomized at 4 hours of age to receive either standard neonatal intensive care, or standard care plus continuous negative extrathoracic pressure (CNEP, -4 to -6 cmH2O) applied within a purpose-designed neonatal incubator. OUTCOME SCORES: Clinical scores were calculated for each infant at 56 days of age, or death if earlier. Scores included measures for mortality, respiratory outcome, the presence of cerebral ultrasound abnormalities, patent arterial duct, necrotizing enterocolitis, and retinopathy. The treatment given for the higher score for each pair was recorded and the cumulative net number of pairs favoring CNEP plotted in the sequential analysis to provide an ethical early termination strategy. Individual components of the outcome score and other secondary measurements were analyzed on completion of the trial. RESULTS: The sequential analysis reached a decision boundary after 122 out of a possible maximum of 124 pairs were completed. The overall outcome score showed an overall significant benefit for CNEP. Secondary analysis showed that the use of CNEP was associated with an increase in mortality, cranial ultrasound abnormalities, and pneumothoraces, which were not statistically significant. However, 5% fewer patients were intubated (95% confidence interval [CI], 0-10), and the total duration of oxygen therapy among surviving infants at 56 days was lower (20.5 days, compared with 38.9 in controls; difference 18.4 days, 95% CI 3.8 to 33.0). Among all infants, the mean total duration of oxygen therapy was 18.3 days among CNEP-treated infants compared with 33.6 days among the controls (difference -15.3 days, 95% CI -0.2 to -30.4). This reduction in mean levels is entirely attributable to substantially fewer patients requiring prolonged oxygen therapy, the median duration of treatment being very similar in the two groups. As a result, commensurately fewer surviving infants showed chronic lung disease of prematurity. CONCLUSIONS: The use of continuous negative pressure improves the respiratory outcome for neonates with respiratory failure.

Female↗
PubMed1995

Cytoplasmic inhibition of carotenoid biosynthesis with virus-derived RNA.

The carotenoid biosynthetic pathway in higher plants was manipulated by using an RNA viral vector. A cDNA encoding phytoene synthase and a partial cDNA encoding phytoene desaturase (PDS) were placed under the transcriptional control of a tobamovirus subgenomic promoter. One to two weeks after inoculation, systemically infected Nicotiana benthamiana plants were analyzed for phytoene. Leaves from transfected plants expressing phytoene synthase developed a bright orange phenotype and accumulated high levels of phytoene. Cytoplasmic inhibition of plant gene expression by viral RNA was demonstrated with an antisense RNA transcript to a partial PDS cDNA derived from tomato. The leaves of the plants transfected with the antisense PDS sequence developed a white phenotype and also accumulated high levels of phytoene. A partial cDNA to the corresponding N. benthamiana PDS gene was isolated and found to share significant homology with the tomato antisense PDS transcript. This work demonstrates that an episomal RNA viral vector can be used to deliberately manipulate a major, eukaryotic biosynthetic pathway. In addition, our results indicate that an antisense transcript generated in the cytoplasm of a plant cell can turn off endogenous gene expression.

Amino Acid Sequence↗
PubMed1995

A reappraisal of chloramphenicol metabolism: detection and quantification of metabolites in the sera of children.

Seventy-four samples of serum from 27 children (age range: 26 weeks preterm to 12 y) treated with chloramphenicol for serious infections, were analyzed by high performance liquid chromatography (HPLC) for the presence of chloramphenicol metabolites. Five, including a previously unreported human metabolite--chloramphenicol aldehyde, were detected and identified by comparative HPLC, enzymic degradation or gas chromatography followed by mass spectrometry. The presence of these metabolites in the serum suggests that the biotransformation of chloramphenicol takes place by oxidation, reduction and conjugation and not by conjugation alone, as has been previously supposed. Sera from 84% of the patients contained one or more metabolites, however the presence of particular compounds did not correlate with toxicity in the four patients in whom this was observed.

Adolescent↗
PubMed1995

Should we estimate liver span in the right mid-clavicular line or the midline?

OBJECTIVE: Comparison was made between the accuracy of repeated measurements of liver projection below the costal margin in the right mid-clavicular line (RMCL) and in the midline (ML). METHODOLOGY: Clinical measurement of liver span was studied in 34 children under 5 years of age by five members of junior ward staff. Three patients were followed longitudinally by the same observers. RESULTS: The coefficient of reliability between different observers for measurement in the RMCL was 13 mm but for that in the ML was 7 mm. Estimates of liver size in the RMCL were particularly inaccurate when examining larger livers. CONCLUSION: More reliable sequential estimates of liver size are likely to be obtained using measurements both in the midline and in a well-defined and agreed point below the right costal margin.

Age Factors↗