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Biomedical subjects

L Pickering

Publications and source records attributed to L Pickering.

16 recordsLinked to original sources
PubMed2004

The longer term outcome of children born to mothers with epilepsy.

OBJECTIVES: To determine the prevalence of cognitive delay and possible associated dysmorphic features in children exposed to antiepileptic drugs (AEDs) in utero. DESIGN: Retrospective study of children born to mothers with epilepsy. SETTING: Regional epilepsy clinics in Liverpool and Manchester, UK. PARTICIPANTS: Children aged between 6 months and 16 years born to mothers with epilepsy. MAIN OUTCOME MEASURES: Structured interviews, hospital records, clinical examination, and psychometric tests (Wechsler) were used to assess exposure and intelligence quotient (IQ). Blinded assessment of photographs was used to score children with characteristic dysmorphic features. RESULTS: A total of 249 children aged 6 and over were studied: 41 were exposed to sodium valproate, 52 to carbamazepine, 21 to phenytoin, 49 to polytherapy, and 80 were unexposed. Mean verbal IQ was significantly lower in the valproate group compared to unexposed and other monotherapy groups. Multiple regression analysis showed that both valproate exposure and frequent tonic-clonic seizures in pregnancy were significantly associated with a lower verbal IQ despite adjusting for other confounding factors. There was a significant negative correlation between dysmorphic features and verbal IQ in children exposed to valproate. CONCLUSIONS: This study identifies valproate as a drug carrying potential risks for developmental delay and cognitive impairment and is the first to suggest that frequent tonic-clonic seizures have a similar effect. Our results need to be interpreted with caution given their retrospective nature. Women with epilepsy need careful counselling about individual risk benefit of AED treatment before pregnancy.

Abnormalities, Drug-Induced↗
PubMed2001

Attitudes, practices, and preferences of pediatricians regarding initiation of hepatitis B immunization at birth.

OBJECTIVES: To explore practices and attitudes of pediatricians toward administration of the first dose of hepatitis B vaccine to infants, and to identify factors influencing the decision of pediatricians to initiate immunization at birth versus at 1 to 2 months of age. METHODS: A random sample of 600 pediatricians obtained from the American Academy of Pediatrics membership database was surveyed by mail. RESULTS: Three hundred eighty (68%) of the 563 pediatricians who were located responded to the survey. Of these 380 pediatricians, 279 provided routine immunizations to children. Of the 270 pediatricians who vaccinated children with hepatitis B vaccine and indicated their practice regarding the birth dose, 50% offered the first dose of hepatitis B vaccine at birth to all infants; the rest either offered the vaccine at birth only to infants of hepatitis B surface antigen-positive mothers and mothers whose serostatus is unknown, or did not offer the birth dose to any infants at all. Practicing in the inner city, working for a medical school or government hospital, and living in a state with universal immunization supply policies were associated with the respondent giving the birth dose. The strongest perceived barriers to giving the birth dose in the hospital were the difficulty tracking these vaccines (39%), the increased cost (27%), and the lack of reimbursement from insurance companies (26%). If a combination vaccine that includes hepatitis B; diphtheria, tetanus, pertussis (diphtheria and tetanus toxoids and acellular pertussis vaccine); and polio (inactivated poliovirus vaccine) antigens become available in the near future, then 38% of physicians who currently give the birth dose to all infants would prefer to wait until 2 months of age to initiate hepatitis B immunization. CONCLUSIONS: Efforts to achieve high implementation of hepatitis B birth dose administration may falter once a hepatitis B-containing pentavalent combination vaccine becomes available. Programmatic efforts should ensure prevention of perinatal hepatitis B virus transmission through universal prenatal hepatitis B surface antigen screening and immunoprophylaxis of high-risk newborn infants.

Health Knowledge, Attitudes, Practice↗
PubMed2001

Human milk oligosaccharides: a novel method provides insight into human genetics.

Human milk is a unique reservoir of oligosaccharides. The presence of many of these oligosaccharides is determined genetically and is related to the Lewis blood group and secretor antigen status of each donor. A method to quantitate neutral human milk oligosaccharides was developed. Sample preparation was based on a single centrifugation-filtration step that yields oligosaccharide extracts. These extracts first were fractionated to remove a significant portion of their lactose content and were analyzed using high-pH anion-exchange chromatography. Oligosaccharide profiles from 386 milk samples obtained in this fashion generated quantitative information on lactose, the neutral cores lacto-N-tetraose (LNT) and lacto-N-neotetraose (LNneoT), and the key fucosylated oligosaccharides. Additionally, the profiles provided genetic footprints of the Lewis and secretor status of the donors. Furthermore, unusual profiles that could not have been predicted from known genotypes were found. For this reason, milk glycoproteins were studied using carbohydrate-binding probes. Results confirm that oligosaccharides are an accurate predictor of the Lewis blood group status of the donor, and that glycosyltransferases have exquisite specificities. The data obtained in this study corroborate that Lewis-related antigens are tissue specific. This attribute of immunodominant carbohydrate sequences has significant implications for epidemiological studies of breast-fed infants.

Anions↗
PubMed2000

An epidemic without illness. Using dna markers to model infection.

PURPOSE: Combining molecular biology with infection control interventions can increase compliance and allow objective measurement of effectiveness. We developed a group of PCR detectable non-infectious DNA markers that can be used to model infection and provide immediate feedback on hygiene practices in institutional settings. In previous studies, we illustrated that the markers were spread in the environment in the same manner as infectious particles.METHODS: We are conducting a prospective study in 10 child care centers in order to 1) confirm that the DNA markers are valid surrogates for bacteria and viruses; 2) identify specific foci of contamination and modes of transmission; 3) illustrate the effectiveness of infection control programs utilizing the DNA markers. Centers are randomized to receive an interactive educational infection control intervention or a standard immunization intervention. The DNA markers are introduced into the center and the rate of dispersion of the DNA markers is compared with directly observed changes in hygiene behavior among the staff.RESULTS: Initial results indicate that the markers can be removed mechanically by hand washing and that common over-the-counter cleaners are effective in inactivating the markers. Toys, countertops and doorknobs appear to be more important as infectious reservoirs than brief casual contact. Data from the prospective study will be available prior to September, 2000.CONCLUSIONS: This novel approach utilizing an objective measurement will be used to identify the interaction between behavior and environmental reservoirs of infection and drive future strategies for infection control.

Journal Article↗
PubMed1995

4'-Aza-sugar nucleosides.

From readily available starting materials, the preparation and characterization of a variety of pyrimidine 2', 3'-dideoxyribo-, 2'-deoxyribo-, 3'-deoxyribo- and ribo- N-protected 4'-aza nucleosides is reported. None was found to possess any significant antiviral activity.

Aza Compounds↗
PubMed1992

T-cell receptor beta-chain gene usage in the T-cell recognition of Mycobacterium leprae antigens in one tuberculoid leprosy patient.

The beta chain of the T-cell antigen receptor present on 20 T-cell clones isolated from a tuberculoid leprosy patient was studied by gene rearrangement and PCR analysis. These T-cell clones all responded to Mycobacterium leprae-encoded protein antigens, and 8 of them specifically recognized peptides of the mycobacterial 65-kDa heat shock polypeptide (65hsp). All T-cell clones studied were HLA-DR-restricted (DR2 or -3). In the DR3-restricted group, 7 of 10 used a beta-chain variable region V beta 5 gene family member, whereas in the DR2-restricted group, 2 of 10 T-cell clones used a V beta 5 gene segment and 5 used the V beta 18 gene segment. The deduced amino acid sequences of the beta chain from 8 T-cell clones have revealed that 3 of 4 DR3-restricted T-cell clones expressed the V beta 5.1 gene segment whereas the fourth DR3-restricted T-cell clone employed a V beta 5 family member not previously described. The V beta 5.1-positive T-cell clones all recognized the same 65hsp peptide from residues 2 to 12. The N-D-N segment (where D is diversity) of the junctional region of these T-cell clones was very similar, despite different beta-chain joining gene segments. Of the 4 DR2-restricted T-cell clones investigated, 3 used the V beta 18 gene segment and recognized the 65hsp peptide from residues 418 to 427. In conclusion, within this panel of M. leprae-reactive T-cell clones, the DR3-restricted T-cell clones mainly used a V beta 5 gene segment, whereas the DR2-restricted clones employed preferentially the V beta 18 gene segment.

Amino Acid Sequence↗
PubMed1992

Detection of rotaviruses in the day care environment by reverse transcriptase polymerase chain reaction.

Group A rotavirus is an important cause of morbidity among infants and toddlers in day care centers. Transmission by the fecal-oral route is well established, but fomites and environmental surfaces may also play an important role in transmission. A highly sensitive polymerase chain reaction (PCR) assay was used to detect rotavirus RNA in day care environments. Areas sampled included floors, diaper change areas, toy balls, and other surfaces. In two centers undergoing outbreaks of rotavirus, 7 (39%) of 18 toy balls had detectable rotavirus as did 8 (21%) of 39 swabs from environmental surfaces. By comparison, only 1 (5%) of 21 toy balls and 1 (2%) of 44 environmental surface swabs had detectable rotavirus in centers without rotavirus outbreaks (P = .0001). Thus, rotaviruses are highly prevalent in day care centers during outbreaks of diarrhea. The monitoring of environments by sensitive nucleic acid amplification techniques may lead to strategies for the diminution of disease transmission within the day care environment.

Base Sequence↗
PubMed1989

Giemsa staining for cysts and trophozoites of Pneumocystis carinii.

Although Giemsa staining has been routinely used for the detection of trophozoites and intracystic bodies in smears of bronchoalveolar lavage fluid (BAL) from patients with Pneumocystis carinii pneumonia, it does not normally stain the cyst wall. For detection of the cysts other stains such as toluidine Blue 'O' and methenamine silver must be used as well. Sulphation of smears before staining with Giemsa allows cysts to be visualised, thus enabling a single stain to be used to show all the stages of BAL or sputum, which is particularly useful, considering the increase in the prevalence of P carinii pneumonia in conjunction with the spread of AIDS.

Animals↗
PubMed1986

Human T-cell receptor genes: organization, diversity, and polymorphism.

The analysis of 27 human beta cDNA clones has revealed striking insights as to the germ line, combinatorial, and somatic mechanisms that operate to diversify V beta gene segments. It appears that the repertoire of human V beta genes is limited to 60 or so functional gene segments. Deletional mapping together with the analysis of large DNA fragments by field inversion gel electrophoresis and the isolation of cosmid clones should permit us to map the entire human V beta gene family. The polymorphisms that are present in these V beta gene segments will facilitate a search for interesting disease associations. A detailed comparison of the mouse and human V beta loci should permit us to come to understand in more detail the evolutionary mechanisms that have created these fascinating gene families.

Base Sequence↗
PubMed1985

Two tissue-specific isozymes of creatine kinase have closely matched amino acid sequences.

Creatine kinase activity is associated with different isozyme species. We have examined two of these: the cytoplasmic brain (B) isozyme that is expressed in many tissues and is reported to be induced by estrogen and the developmentally regulated cytoplasmic muscle (M) isozyme that is found predominantly in differentiated muscle tissue. Recently, we cloned and sequenced the cDNA for the M isoenzyme of rabbit creatine kinase. We now report the isolation of B-isozyme cDNAs and the deduced primary structure of the polypeptide. The translated cDNA nucleotide sequence was cross-checked by fast-atom bombardment/mass spectrometry of tryptic fragments from the protein. The sequence is exactly colinear with the rabbit M isozyme and the two isozymes have 80% nucleotide and amino acid sequence identity. There are blocks of 36 and 41 amino acids where the amino acid sequence is conserved exactly. The colinearity of the two sequences and the extent of their identity makes it unlikely that either isozyme has unique polypeptide domains that account for specialized functions. The rationale for the existence of these creatine kinase isozymes, with distinct biological features, evidently is at the level of regulation of individual isozyme expression.

Amino Acid Sequence↗
PubMed1984

Rabbit muscle creatine phosphokinase. CDNA cloning, primary structure and detection of human homologues.

A cDNA library was constructed from rabbit muscle poly(A) RNA. Limited amino acid sequence information was obtained on rabbit muscle creatine phosphokinase and this was the basis for design and synthesis of two oligonucleotide probes complementary to a creatine kinase cDNA sequence which encodes a pentapeptide. Colony hybridizations with the probes and subsequent steps led to isolation of two clones, whose cDNA segments partially overlap and which together encode the entire protein. The primary structure was established from the sequence of two cDNA clones and from independently determined sequences of scattered portions of the polypeptide. The reactive cysteine has been located to position 282 within the 380 amino acid polypeptide. The rabbit cDNA hybridizes to digests of human chromosomal DNA. This reveals a restriction fragment length polymorphism associated with the human homologue(s) which hybridizes to the rabbit cDNA.

Amino Acid Sequence↗