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Biomedical subjects

M Hjelm

Publications and source records attributed to M Hjelm.

At least 37 records · Page 2Linked to original sources

Use of anonymous newborn serosurveys to evaluate antenatal HIV screening programmes.

OBJECTIVE: To evaluate the extent to which antenatal HIV screening programmes identify HIV infected women who go to term. DESIGN: Comparison of results of two surveillance systems. An anonymous neonatal HIV serosurvey was used to estimate the numbers of HIV infected women giving birth; reporting by obstetricians was used to assess the proportion who had been identified. SETTING: Three Thames regions. RESULTS: 729,105 neonatal blood samples were tested, of which 484 were HIV seropositive. Newborn HIV seroprevalence is increasing, at different rates, in inner London, suburban London, and in non-metropolitan districts. During the past four years the proportion of infected women who have been identified before delivery is 16.9%, but less than half of these were diagnosed during pregnancy. In 1993 only five of the 128 (4%) previously undiagnosed infected women delivering babies were identified by antenatal screening. CONCLUSION: Despite increased emphasis on antenatal testing for HIV in areas of higher prevalence the number of undiagnosed women delivering babies continues to increase. Consideration should be given to alternative strategies for offering antenatal HIV testing. Antenatal screening programmes should be monitored continuously by comparing anonymous neonatal seroprevalence with clinical reports from obstetricians.

Confidence Intervals↗

Maternal prevalence of Toxoplasma antibody based on anonymous neonatal serosurvey: a geographical analysis.

A total of 12,902 neonatal samples collected on absorbent paper for routine metabolic screening were tested anonymously for antibodies to toxoplasma. Seroprevalence varied from 19.5% in inner London, to 11.6% in suburban London, and 7.6% in non-metropolitan districts. Much of this variation appeared to be associated with the proportions of livebirths in each district to women born outside the UK. However, additional geographical variation remained and seroprevalence in UK-born women was estimated to be 12.7% in inner London, 7.5% in suburban London, and 5.5% in non-metropolitan areas. These estimates are considerably lower than any previously reported in antenatal sera in the UK. The wide geographical variation highlights a need for further research to determine the relative importance of different routes of transmission.

Antibodies, Protozoan↗

A quality manual for the clinical laboratory including the elements of a quality system. Proposed guidelines.

Development of quality manuals is a means for the promotion of quality in clinical laboratories by describing the total quality system. It also provides opportunity of checking whether the quality system is implemented in reality and demonstrates to the hospital administration and the clinicians that the laboratory is committed to quality. The intention of these guidelines is to describe the elements of the quality system for a large clinical laboratory, and to present such a system in the form of a quality manual. The proposed guidelines comply, where relevant, with ISO/IEC guide 25 'General requirements for the technical competence of testing laboratories' and EN 45001 'General criteria for the operation of testing laboratories'. The document may be used as an aid for laboratories wishing to be accredited according to EN 45001, or intending to apply for formal certification of their quality systems, according to ISO 9001 'Quality systems--Model for quality assurance in design/development, production, installation, and servicing' utilizing ISO 9004 'Quality management and quality system elements--guidelines; Part 2 Guidelines for service'. However, information about the minimum requirements for official recognition should be obtained from the particular accreditation or certification body concerned.

Chemistry, Clinical↗

Study of the relationship between estimates of enzyme kinetic parameters.

Previous indications of an intrinsic relationship between estimates of Km and Vmax calculated from the Michaelis-Menten equation have been explored further. A mathematically linear relationship could be established for the estimates of the two parameters. The relationship--the trend line--holds whether or not the experimental error is linked to the rate of reaction, the substrate concentration or both, provided that the distribution of errors is symmetrical. The practical implication is that enzyme variants with low values of Km and Vmax may not be distinguishable from those with high values of Km and Vmax.

Enzymes↗

Two methods for assessing the risk-factor composition of the HIV-1 epidemic in heterosexual women: southeast England, 1988-1991.

OBJECTIVE: The prevalence of HIV-1 in the heterosexual population in southeast England between 1988 and 1991 was examined using two methods. DESIGN AND METHODS: First, district neonatal seroprevalence was compared on a geographical basis to social and demographic variables reflecting risk-factor prevalence. Second, over the same period eight children who developed AIDS within the first 12 months of life were born. RESULTS: The differences in seroprevalence between districts could be explained by the proportion of livebirths to women born in parts of Africa. An estimated 92% of neonatal seropositives could be associated with this demographic variable. The proportions of livebirths to women born in other countries, the prevalence of notified injecting drug use, and area measures of social deprivation, were only poorly related to HIV seroprevalence, and had no additional explanatory value. Seven of the eight (87.5%) children who developed AIDS in the first year were born to black women from Africa. CONCLUSIONS: Both methods suggest that a high proportion of heterosexually transmitted HIV in southeast England has been imported.

Adult↗

Prevalence of maternal HIV-1 infection in Thames regions: results from anonymous unlinked neonatal testing.

To monitor the spread of human immunodeficiency virus (HIV) in the heterosexual population, residues of blood samples collected routinely on absorbent paper for neonatal screening (Guthrie cards) in NE, NW, and SW Thames Regions in England have been tested for antibodies to HIV-1 since June, 1988. 323,369 dried blood spots were analysed to end March, 1991. Prevalence of anti-HIV-1 in newborn babies has remained stable in outer London and non-metropolitan districts whereas prevalence in inner London has increased from 1 in 2000 in the 12 months beginning June, 1988, to 1 in 500 in the first 3 months of 1991. Either exponential or linear growth in the numbers of new seropositives could account for the results. That obstetricians were aware of maternal HIV infection in only 20% of infected pregnancies, indicates the extent to which HIV infection goes unrecognised in the heterosexual community.

Confidentiality↗

Phenylalanine in whole blood and plasma--a candidate reference method.

A method for the quantification of phenylalanine in whole blood and plasma by isotope dilution gas chromatography-mass spectrometry is presented. The use of an uncommon derivative allows a simple extraction procedure and the most basic mass spectrometer. The relative standard deviation was found to be 1.3% within-batch and 2.1% between-batch under optimum conditions, and the detection limit was found to be 7 pmol injected. The ruggedness of the procedure and sample handling conditions were also examined.

Gas Chromatography-Mass Spectrometry↗

Prevalence of maternal HIV infection based on unlinked anonymous testing of newborn babies.

This pilot study established that unlinked anonymous testing of dried blood spots routinely collected on Guthrie cards for neonatal screening is a feasible method for monitoring HIV prevalence in women at the time of delivery. The method was sensitive, specific, and less expensive than more conventional ELISAs. 114,515 dried blood spots taken from cards collected in three Thames regions were tested for antibody to HIV-1. 28 samples were confirmed to be antibody positive by western blot (seroprevalence 0.24 per 1000). Unlinked anonymous screening of newborn babies should be extended to monitor the spread of HIV infection in the heterosexual population and to target preventive strategies and provision of health care.

Agglutination Tests↗

The urea cycle in the Rett syndrome.

The in vivo functioning of the urea cycle in the Rett syndrome (RS) was investigated using alanine load test. The test was carried out in girls with RS and their mothers. These results were compared with those on normal females, males and obligate carriers for ornithine carbamoyltransferase deficiency. Post load hyperammonaemia was not seen in any of the RS girls who were not on medication (valproate). Increased orotate excretion was found in some of the RS girls and mothers. The pattern of urinary excretion of orotate in RS girls and their mothers after a standardised alanine load was similar to that found in female carriers of OCT deficiency. This finding can be explained by a mutant OCT, subject to the Lyon effect, and linked to the gene abnormality in RS or by the presence of an abnormal X-linked mitochondrial protein synthesised in cytoplasma and positioned in close proximity to OCT. Such a protein abnormality could also affect mitochondrial functions in other cells, e.g. in the developing brain.

Adult↗

Age dependency of the lactase persistence and lactase restriction phenotypes among children in Sri Lanka and Britain.

All neonates are born with intestinal lactase activity. In most of them the intestinal lactase activity is lost during childhood (lactase restriction phenotype). In a minority of children normal intestinal lactase activity is retained (lactase persistence phenotype). In this study the progression of the lactase restriction phenotypes has been studied in 94 Sri Lankan children by oral lactose loads and 162 British children by intestinal lactase estimation (adult Sri Lankans and British predominantly belong to the lactase restriction and lactase persistence phenotypes, respectively). Lactase was present in infancy at birth in all Sri Lankan children and declined around the age of eight years, the majority (59 per cent) of the 10-15-year-olds belonging to the lactase restriction phenotype. In contrast the majority of the British children (95 per cent of all the British children studied) demonstrated the lactase persistence phenotype. The low prevalence rate of the restriction phenotype found among British children was largely contributed by children of African and Asian origin.

Age Factors↗

Temperature effects on the estimation of free levels of phenytoin carbamazepine and phenobarbitone.

Serum samples from patients on phenytoin (PHT), carbamazepine (CBZ), or phenobarbitone (PB) monotherapy were filtered at 15, 25, and 37 degrees C and the free concentrations measured by high-performance liquid chromatography. The mean apparent dissociation constants at each temperature were calculated, and were used to predict free drug levels from a further series of patients' samples in which total drug and albumin concentrations only were known. The correlation coefficients (r) between these predicted free levels and experimental results obtained by analysis of the same samples for PHT, CBZ, or PB were 0.977, 0.968, and 0.998, respectively, at 25 degrees C; at 37 degrees C, the corresponding values of r were 0.975, 0.961, and 0.997, respectively. We then determined free fractions (alpha) of PHT, CBZ, and PB at 25 and 37 degrees C and used these values to derive theoretical target ranges for free levels for each of the three drugs. We discuss the implication of these results for patient care, with special reference to the need to specify temperature and quote the appropriate target range when analyses of free levels of AEDs are carried out.

Blood Proteins↗

A micromethod for the estimation of free levels of anticonvulsant drugs in serum.

A micromethod for estimating free levels of phenobarbitone, phenytoin and carbamazepine in patients' sera is described. Serum samples are subjected to a process of ultrafiltration, the filtrates treated with acetonitrile and the drug concentration quantified using high performance liquid chromatography. The stability of free levels in specimens before and after storage is investigated. The method is reproducible and mean recovery exceeds 98.5% showing that there is no significant absorption of drug onto the filters used. There is no interference from other substances normally present in patients' sera and there is a good correlation between results obtained by this method and a fluorescence polarisation immunoassay with correlation coefficient between 0.975 and 0.999. Serum samples can be stored for a lengthy period before ultrafiltration without adverse effects. The relevance of the method to patient care is discussed.

Carbamazepine↗

Hemorrhagic shock and encephalopathy: clinical, pathologic, and biochemical features.

To further define the clinical, pathologic, and biochemical features of hemorrhagic shock and encephalopathy syndrome, we studied 25 affected children (aged 3 months to 14 years) admitted to a single center between 1982 and 1985. A prodromal illness comprising vomiting, diarrhea, listlessness, and fever was present in 84% of the cases. Acute onset of shock, convulsions and coma, bleeding (or laboratory evidence of disseminated intravascular coagulation), elevated plasma activity of hepatic enzymes, acidosis, and impaired renal function was present in every case. Twenty patients died, and all the survivors are neurologically damaged. At postmortem examination, intravascular microthrombi coexisting with hemorrhages and petechiae were found in most organs. Centrilobular liver necrosis and cerebral edema were prominent features. No microbiologic cause for the disorder was identified, but decreased plasma levels of the protease inhibitors alpha 1-antitrypsin and alpha 2-macroglobulin, together with increased levels of circulating proteolytic enzymes, were frequently present. An overrepresentation of the uncommon variant phenotypes of alpha 1-antitrypsin was found in first-degree relatives of affected patients (four had the MZ phenotype, and one each the MS or MC phenotype, of 19 relatives studied). Abnormal accumulation of alpha 1-antitrypsin was detected immunohistochemically in the livers of six of the patients. Defective protease inhibitor production or release may be involved in the pathogenesis of the disorder.

Adolescent↗