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Biomedical subjects

F A Riordan

Publications and source records attributed to F A Riordan.

36 records · Page 2Linked to original sources

Co-ordinated downregulation of bcl-2 and bax expression during granulocytic and macrophage-like differentiation of the HL60 promyelocytic leukaemia cell line.

The bcl-2 protein suppresses apoptosis and the bax protein opposes the cytoprotective effect of bcl-2. A decrease in bcl-2 levels has been implicated in the induction of apoptosis during the terminal differentiation of HL60 myeloid leukaemia cells. We show here that bax protein also declined with a time course similar to the downregulation of bcl-2 following treatment of HL60 with phorbol myristate acetate (PMA), dimethyl sulphoxide (DMSO) or retinoic acid (RA). Decreased bcl-2 protein expression in induced cells was associated with down-regulation of its mRNA. By contrast, the decrease in bax occurred by a post-transcriptional mechanism. Co-ordinate downregulation of bcl-2 and bax proteins may fine-tune the induction of apoptosis during cellular differentiation.

Apoptosis↗

Aspergillus endocarditis in chronic granulomatous disease.

We report the first case, to our knowledge, of Aspergillus endocarditis in chronic granulomatous disease in a patient who also had an atrial septal defect. A diagnosis was made on culture of the organism from the mass despite extensive prior investigation. The presence of distinctive skin lesions as a diagnostic clue of fungaemia is highlighted. Possible advances in diagnosis by detection of fungal cell wall components and in prophylaxis by use of itraconazole are referred to. We conclude that fungal endocarditis should be considered in this condition, especially in the presence of a structural heart defect.

Aspergillosis↗

Proinflammatory and anti-inflammatory cytokines in meningococcal disease.

Interleukin-10 (IL-10), an anti-inflammatory cytokine, was measured in 131 children with meningococcal disease. IL-10 concentrations were significantly higher in children who died and correlated positively with proinflammatory cytokines. Children who die from meningococcal disease have high IL-10 concentrations, which do not suppress proinflammatory cytokines.

Adolescent↗

The changing presentations of meningococcal disease.

UNLABELLED: Meningococcal disease (MCD) can present as meningitis, meningitis plus septicaemia or septicaemia alone. This 17-year retrospective study sought to determine if the proportion of cases presenting as septicaemia alone was increasing. Four hundred and forty-nine children with MCD were admitted between 1977 and 1993, 50 children died (11%). The proportion of cases with septicaemia alone increased from 7% in 1977-1985 to 36% in 1990-1993 (P < 0.0005). Mortality was highest in children with septicaemia alone (19%). Despite the increase in septicaemia, overall mortality did not alter over the 17 years. CONCLUSION: MCD should not be thought of as "meningitis", since 33% of cases now present as septicaemia alone. Nearly one in five children with septicaemia alone die. Information and publicity about MCD should focus on septicaemia, characterised by a petechial rash, as the life-threatening presentation.

Bacteremia↗

Urgent full blood count in children over 3 months of age with bacterial meningitis.

Children with bacterial meningitis often have a full blood count (FBC) measured urgently on admission. We investigated whether urgent FBC gave results that aided immediate management or predicted outcome in children with meningitis. FBCs were measured on admission during 190 episodes of bacterial meningitis in children admitted between 1984 and 1991. Significant anaemia was found in seven children, but immediate transfusion was only necessary in the three subjects who were in the Paediatric Intensive Care Unit (PICU). A white blood count of less than 5 x 10(9) L-1 was significantly associated with death (P < 0.02), but a Glasgow Coma Score of less than 8 predicted death more accurately (positive predictive value of 40%). FBC yielded immediately useful information only in the 15% of children who were admitted to PICU. Conscious level was a better predictor of outcome than FBC. We recommend that urgent FBC should be performed in children with meningitis admitted to a PICU; in other children with meningitis FBC can be analysed during normal laboratory hours.

Age Factors↗

Bacterial meningitis in the first three months of life.

A retrospective study of infants with bacterial meningitis admitted to our hospital during 1949-52, highlighted the lack of 'classical' signs of meningitis in these infants. We carried out a similar review of 44 infants aged less than three months, admitted during 1982-91. We also determined the causative organisms and their antibiotic sensitivities. Symptoms and signs were similar in the two series. Forty infants in the later series were either febrile, irritable or had seizures on the day of admission. Overall mortality fell from 30% to 11%. Between 1982 and 1991 Group B Streptocococcus and Neisseria meningitidis were the commonest causes of meningitis. All organisms, except one, were sensitive to ampicillin and/or cefotaxime. Bacterial meningitis should be suspected in young infants who are febrile, irritable or having seizures. Initial treatment with ampicillin and cefotaxime is appropriate.

Ampicillin↗

Bacterial meningitis after MMR immunisation.

Two children developed bacterial meningitis within five days of measles-mumps-rubella (MMR) immunisation. Diagnosis was delayed because symptoms were attributed to the vaccine, although both had a raised C-reactive protein. Fever or rash within five days of MMR vaccination are unlikely to be due to the vaccine and a raised C-reactive protein suggests bacterial infection.

Diagnosis, Differential↗

Mortality from group C meningococcal disease: a case for a conjugate vaccine?

This 17-year retrospective review of children with meningococcal disease (MCD) has determined the mortality due to serogroup C, in order to assess the potential impact of a group C conjugate vaccine. Four hundred and forty-nine cases of MCD were admitted to our hospitals during 1977-1993; 78 due to group C, 11 of whom died. There was a significant increase in the proportion of cases due to group C from 1986 onwards (10% vs 21%), and an increase in the total number of cases of MCD (151 vs 298). The currently available group C polysaccharide vaccine has low efficacy below 2 years of age and could not have prevented 54 cases of group C disease. A conjugate group C vaccine administered between 2 and 4 months of age could have prevented 68 cases, including all fatal cases. The recent increase in MCD is partly due to an increase in group C disease. A meningococcal group C conjugate vaccine could prevent most cases of infection due to group C, and decrease the mortality from MCD by up to 30%.

Age Factors↗

Kinking of RNA helices by bulged bases, and the structure of the human immunodeficiency virus transactivator response element.

We have used gel electrophoresis to show that the pyrimidine bulge of the HIV-1 TAR sequence causes a local bending of the helical axis. The TAR bulge caused a retardation in electrophoretic mobility in polyacrylamide gels. When this was placed adjacent to an additional bulged sequence in a linear RNA fragment, the mobility of the molecule varied sinusoidally with the spacing between the two bulges. Electrophoretic mobilities suggested that the TAR sequence context of the pyrimidine bulge causes a greater degree of axial kinking than in an equivalent randomly chosen sequence. Experiments in which an A5 bulge was progressively opposed by adenine bases inserted in the opposite strand showed that even a single opposed adenine markedly reduced electrophoretic mobility, i.e. axial bending, and two adenine bases reduced the mobility virtually to that of a normal duplex. We suggest that the pronounced kinking resulting from an unopposed bulge provides a particularly recognizable feature in RNA, and that this is the basis of the interaction between the HIV Tat protein and the TAR sequence.

Base Sequence↗

Bloodspot 17 alpha-hydroxyprogesterone radioimmunoassay for diagnosis of congenital adrenal hyperplasia and home monitoring of corticosteroid replacement therapy.

A convenient and inexpensive radioimmunoassay for bloodspot 17 alpha-hydroxyprogesterone (17-OHP) has been evaluated in the screening of newborn infants for congenital adrenal hyperplasia (CAH) and for home monitoring of CAH patients on steroid replacement therapy. In the screening study, analysis of 491 bloodspots taken for routine screening programmes for phenylketonuria and hypothyroidism established the upper limit of normal for infants aged 5-10 days as 64 nmol 17-OHP/l blood (99.9 centile). Home monitoring of patients by examination of fingerprick bloodspot 17-OHP profiles taken by parents over Saturday and Sunday on consecutive weekends showed that changes in control occurred as a result of transition from inpatient to outpatient treatment or following adjustment of steroid replacement regimens. The method was found to be valuable in the diagnosis and management of children with CAH.

17-alpha-Hydroxyprogesterone↗

Recognition, treatment and complications of meningococcal disease.

Meningococcal disease remains a major cause of death in young children. A decrease in mortality requires recognition and treatment of the disease at a number of stages in the illness. Life-threatening meningococcal disease usually presents as septicaemia rather than meningitis. The cardinal feature of meningococcal septicaemia is the purpuric rash. Many parents recognise the rash and seek medical advice because of it. When primary care physicians recognise the rash, the administration of parenteral penicillin may decrease mortality. However, antibacterials are not given promptly if there is no rash or if the disease presents in an atypical form. In hospital, antibacterial therapy with a third-generation cephalosporin should be given. Disease severity needs to be assessed by a valid method, such as the Glasgow Meningococcal Septicaemia Prognostic Score (GMSPS). This can identify those patients who need intensive care and/or might benefit from new therapies. The 2 life-threatening complications are septic shock and meningoencephalitis with raised intracranial pressure. Despite numerous case reports of success with potential new treatments, none has been proven safe and/or effective by controlled trials. Although it is tempting to focus on new treatments, the early recognition of severe meningococcal disease by parents, primary care physicians and junior hospital doctors is equally, if not more, important as a potential means of decreasing mortality.

Child↗