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Biomedical subjects

M A Kelly

Publications and source records attributed to M A Kelly.

At least 73 records · Page 4Linked to original sources
PubMed1996

Instrumentation of the patellar osteotomy in total knee arthroplasty. The relationship of patellar thickness and lateral retinacular release.

This study investigates the influence of patellar thickness in total knee arthroplasty (TKA) with routine patellar resurfacing on the rate of lateral retinacular release. A study group comprised of 121 TKAs using surgical instrumentation allowing a measured resection of the patella was compared with a control group comprised of 100 TKAs using an "eye-ball" technique for patellar resurfacing without particular attention to patellar thickness. A composite without patellar thickness equal to or slightly less than the original patella was attempted in the study group. The average thickness difference of the patella in the study group was -1.58 mm. Lateral retinacular release for patellar maltracking was performed in 12.4% of knees in the study group compared with 55% of knees in the control group. The variation in patellar thickness in this series often led to a residual bone thickness < 15 mm. No clinical problems have been observed to date.

Aged↗
PubMed1995

Application of chemometric experimental designs in capillary electrophoresis: a review.

Various chemometric experimental designs have been employed for the optimisation of capillary electrophoresis (CE) methods. Similar designs have been utilised in the assessment of the robustness of CE methods. The designs employed include central composites, fractional factorials, Plackett-Burman, simplex and overlapping-resolution mapping. Optimisation studies have largely concentrated on the use of these designs on selection of the optimal electrolyte composition. The robustness testing studies performed have involved the use of screening designs to identify the critical parameters affecting responses such as migration times and resolution. Further designs such as central composites have then been employed to set method limits following robustness studies. It is concluded that the use of experimental designs and statistical data evaluation in conjunction with personal computer-controlled CE autosamplers and instruments are of great benefit in the optimisation and robustness evaluation of CE methods.

Electrophoresis, Capillary↗
PubMed1995

Fetal acidemia associated with regional anesthesia for elective cesarean delivery.

OBJECTIVE: To determine the prevalence, magnitude, and type of fetal acidemia associated with contemporary obstetric anesthetic techniques. METHODS: Umbilical artery blood gases were obtained in 1601 singleton pregnancies delivered by elective cesarean. RESULTS: General anesthesia was used in 371 (23%) women, epidural in 286 (18%), combined spinal-epidural in 659 (41%), and spinal in 231 (14%). Approximately 18% of infants exposed to regional anesthetics had umbilical artery blood pH values 7.19 or less, 42 (3%) infants had pH values less than 7.10, and nine (1%) had values 6.99 or less. The incidence of fetal acidemia was greater in spinal and combined spinal-epidural procedures compared to epidural anesthetics. Fetal acidemia was predominantly respiratory in type because carbon dioxide pressure was abnormally increased when fetal acidemia was diagnosed. CONCLUSIONS: Regional anesthesia is associated with fetal acidemia, occasionally severe, and has features of an acute respiratory type of acidemia. Fetal acidemia is less frequent with epidural anesthesia compared to subarachnoid techniques.

Adult↗
PubMed1995

Genetic susceptibility to multiple sclerosis in a Shanghai Chinese population. The role of the HLA class II genes.

The association of MS with the HLA class II loci DR and DQ was investigated in subjects of Shanghai Chinese and British Caucasian origin. Our aim was to determine whether common alleles predispose to the disease in both races. In the Caucasian population MS was significantly positively associated with the putative haplotype DRB1*1501, DQA1*0102, DQB1*0602. In contrast, HLA class II alleles were not found to predispose to the disease in the Shanghai Chinese, suggesting that this haplotype is unlikely to be a universal susceptibility determinant. The absence of a disease association with the HLA-DR and -DQ genes in the Chinese population has a number of possible explanations. Our study suggests that other genetic and/or environmental components may be more important in determining susceptibility to MS in this race.

Asian People↗
PubMed1995

Validated capillary electrophoresis method for the assay of a range of basic drugs.

A capillary electrophoresis method has been developed and validated for the analysis of a wide range of basic drugs. Acceptable precision was obtained by employing an internal standard. Optimal sensitivity was obtained using low UV wavelengths. An experimentally designed study showed the method to be robust. The method has advantages over HPLC in terms of simplicity, speed and cost. The method is now in routine use for identity confirmation and assay of both drug substance and formulations.

Buffers↗
PubMed1995

An investigation of HLA-encoded genetic susceptibility to multiple sclerosis in subjects of Asian Indian and Afro-Caribbean ethnic origin.

The association of multiple sclerosis (MS) with the HLA class II loci DR and DQ was investigated in populations of Asian Indian and Afro-Caribbean ethnic origin, resident in the United Kingdom. The putative haplotype, DRB1*1501.DQA1*0102.DQB1*0602, was weakly positively associated with MS in both races. The overall contribution to disease susceptibility of this marker was small. Over 80% of the MS patients in both racial groups did not possess this haplotype. The data suggest that other genetic and/or environmental factors may be more important in predisposing to MS in these two races. Our study also raises the possibility that genetically distinct forms of the disease may be expressed in white Caucasian and non-Caucasian populations.

Black People↗
PubMed1995

Bilateral simultaneous optic neuropathy in adults: clinical, imaging, serological, and genetic studies.

To elucidate the cause(s) of acute or subacute bilateral simultaneous optic neuropathy (BSON) in adult life, a follow up study of 23 patients was performed with clinical assessment, brain MRI, HLA typing, and mitochondrial DNA analysis. The results of CSF electrophoresis were available from previous investigations in 11 patients. At follow up, five (22%) had developed clinically definite multiple sclerosis, four (17%) had mitochondrial DNA point mutations indicating a diagnosis of Leber's hereditary optic neuropathy (LHON). The remaining 14 patients (61%) still had clinically isolated BSON a mean of 50 months after the onset of visual symptoms: three of 14 (21%) had multiple MRI white matter lesions compatible with multiple sclerosis, three of 14 (21%) had the multiple sclerosis associated HLA-DR15/DQw6 haplotype, and one of seven tested had CSF oligoclonal IgG bands; in total only five (36%) had one or more of these risk factors. The low frequency of risk factors for the development of multiple sclerosis in these 14 patients suggests that few will develop multiple sclerosis with more prolonged follow up. It is concluded that: (a) about 20% of cases of BSON without affected relatives are due to LHON; (b) multiple sclerosis develops after BSON in at least 20% of cases, but the long term conversion rate is likely to be considerably less than the rate of over 70% seen after an episode of acute unilateral optic neuritis in adult life.

Adolescent↗
PubMed1995

Genetic susceptibility to multiple sclerosis in the Shanghai Chinese is not linked to the myelin basic protein gene microsatellite.

Aim-To investigate the role of myelin basic protein (MBP) gene polymorphisms in determining susceptibility to multiple sclerosis in a Shanghai Chinese population.Methods-Forty seven unrelated patients with multiple sclerosis and 94 healthy control subjects were included in the study. Genomic DNA was extracted from peripheral blood lymphocytes and amplified using the polymerase chain reaction to characterise two adjacent tetranucleotide repeats ([ATGG](12) and [TGGA](9)) located 5' to exon 1 of the MBP gene.Results-Two polymorphic loci were identified: locus A, comprising both repeats, and locus B, comprising the [ATGG](12) repeat only. Nine allelic variants were identified at locus A and six at locus B, ranging from 212 to 244 and 122 to 146 base pairs, respectively. The 244 base pair allele at locus A has not been reported before. The allele frequencies observed in the controls differed from those seen in normal white populations.Conclusions-The present study demonstrates a race specific pattern of allelic distribution within the tetranucleotide repeat of the MBP gene. Further studies are needed to fully elucidate the role of the MBP gene in inherited susceptibility to multiple sclerosis.

Journal Article↗
PubMed1994

Optimization by mass spectrometry of a tryptophan-specific protein cleavage reaction.

Mass spectrometry has been used to define the reaction of BNPS-skatole (3-bromo-3-methyl-2-(o-nitrophenylsulfenyl)indolenine) with selected proteins and peptides, confirming the cleavage of the protein chain at tryptophan residues, characterizing the products, and identifying the side reactions. A short procedure for carrying out the cleavage reaction with minimal side reactions is presented.

Alkylation↗
PubMed1994

Analysis of a Chinese population suggests that the TNFB gene is not a susceptibility gene for Graves' disease.

Graves' disease is associated with different HLA genes in different races. The TNFB gene lies between the class I and class II HLA genes and has two alleles, TNFB*1 and TNFB*2. Studies in Caucasians have suggested that the TNFB gene might be a susceptibility gene for Graves' disease. To investigate further the role of TNFB in predisposition to Graves' disease, we determined whether the TNFB disease associations in the Chinese were similar to those in Caucasians. A total of 57 patients with Graves' disease (32 male) were studied. A TNFB gene fragment was amplified from genomic DNA by using the polymerase chain reaction and digested with Nco I to distinguish the TNFB alleles (TNFB*1 and TNFB*2). Genotype frequencies were compared with those in a racially matched group of 92 controls. TNFB*1 homozygosity occurred in 15 (26%) Graves' and 22 (24%) control subjects. TNFB*1/TNFB*2 heterozygosity occurred in 29 (51%) and 48 (52%) and TNFB*2 homozygosity in 13 (23%) and 22 (24%), respectively (NS). There were gender differences in the frequencies of TNFB*1 homozygosity (13 male [41%], 2 female [8%]). TNFB*1/TNFB*2 heterozygosity (13 male [41%], 16 female [64%]) (chi 2 = 7.3, p = 0.02), and TNFB*2 frequency (19 male [59%], 23 female [92%]; pc = 0.04) in Graves' patients. We conclude that the TNFB associations with Graves' disease in the Hong Kong Chinese differ between the genders and from those described in Caucasians. The TNFB gene is not a susceptibility gene for Graves' disease.

Asian People↗
PubMed1994

The HLA association with Graves' disease is sex-specific in Hong Kong Chinese subjects.

OBJECTIVE: Graves' disease is associated with different HLA genes in Caucasians and the Chinese, in whom the HLA associations may be stronger in males than females. Common HLA-associated susceptibility in both races may occur at the HLA-DQ loci. The aims of this study were to examine the HLA-A, B, DR and DQ associations with Graves' disease in a Hong Kong Chinese population and to determine whether the HLA associations differ between the sexes and between subjects with and without thyrotoxic periodic paralysis. DESIGN: HLA-A, B and DR types were determined by serological typing and DQA1 and DQB1 alleles by oligonucleotide probing of the respective enzymatically amplified gene. PATIENTS: Ninety-seven Chinese patients with Graves' disease (31 males with, 35 males without and 31 females without thyrotoxic periodic paralysis) and 105 racially matched healthy controls. MEASUREMENTS: Frequencies of HLA types/alleles at each locus were compared between patients and controls and between the Graves' subgroups using the chi 2-test. RESULTS: HLA-B46, DR9 and DQB1*0303 were associated with Graves' disease in males only; these associations were weaker in males with thyrotoxic periodic paralysis. DR12, DQA1*0401 and DQB1*0301 were protective, regardless of sex or the presence of thyrotoxic periodic paralysis. The positive HLA associations in the Hong Kong Chinese were distinct from those in Caucasians whereas the protective haplotype was similar to that described in Caucasians. CONCLUSIONS: These findings call in question the role of HLA genes in disease susceptibility but suggest a role for HLA in protection from Graves' disease.

Adult↗
PubMed1994

Development and trial of a bovine herpesvirus 1-thymidine kinase deletion virus as a vaccine.

An Australian bovine herpesvirus 1 (BHV1) isolate with a defined (427 base pair) deletion in the protein coding region of the thymidine kinase gene was obtained by standard marker rescue procedures. After selection in the presence of the nucleotide analogue 5'-iodo-deoxy-uridine the virus was analysed by hybridisation with three differential oligonucleotide probes, restriction endonuclease profile studies and DNA sequence analysis. The virus elicited an immune response in recipient animals after either intramuscular or intravenous administration and produced no significant deleterious side-effects when administered at a dose sufficient to stimulate the host immune response. The safety and immunogenicity of the recombinant BHV1 virus 39B1 were similar to those reported for other registered BHV1 vaccines and the virus would appear to be suitable for the production of a vaccine seed lot and more exhaustive field trials as a prelude to commercial vaccine production and registration.

Animals↗
PubMed1994

The Bgl II RFLP associated with type 1 diabetes in DR3-positive subjects is not due to a DQA1 promoter region polymorphism.

Type 1 (insulin-dependent) diabetes is strongly associated with the HLA genes encoding DR3 and DR4 and their associated DQ alleles. While 70% of all Caucasian diabetic patients carry the DR3-associated allele DQA1*0501, this allele also occurs in up to 40% of the healthy population. A DQA1 Bgl II 7.2 kb RFLP has been shown to identify a disease-associated subset of DR3-positive subjects. We examined the frequency of this RFLP pattern in 43 diabetic and 25 control DR3-positive subjects and found it to be present in 27 (65%) and 5 (20%) respectively (p = 0.0012). The promoter of the DR3-associated DQA1*0501 allele was amplified in four diabetic subjects who were positive, and four control subjects who were negative, for the 7.2 kb band. The promoter was digested with Bgl II to determine whether polymorphism within the promoter created a disease-associated Bgl II restriction site, which might influence disease susceptibility by an effect on gene transcription. No amplified promoter fragment contained a Bgl II restriction site, suggesting that the disease-associated 7.2 kb band does not result from DQA1 promoter region polymorphism but may be due to polymorphism elsewhere on the DR3 haplotype.

Bacterial Proteins↗
PubMed1994

Meconium: a 1990s perspective on an old obstetric hazard.

OBJECTIVE: To quantify the current perinatal consequences associated with intrapartum detection of meconium in the amniotic fluid (AF). METHODS: We compared retrospectively the outcomes in 8136 term singleton cephalic pregnancies with meconium and 34,573 similar pregnancies with clear AF. RESULTS: Virtually all measures of adverse fetal-neonatal outcomes were significantly increased with meconium. For example, perinatal mortality increased from 0.3 per 1000 births with clear AF to 1.5 deaths per 1000 with meconium (P < .001). Most of these deaths resulted from meconium aspiration. Other unwanted outcomes also increased; eg, severe fetal acidemia at birth (umbilical artery blood pH 7.00 or less) increased from three per 1000 to seven per 1000 when meconium was diagnosed (P < .001). Delivery by cesarean also increased with meconium, from 7 to 14% (P < .001). CONCLUSION: Meconium in the AF is an obstetric hazard with small but significantly increased risks of adverse fetal-neonatal outcomes.

Adolescent↗
PubMed1994

Ticlopidine: a new antiplatelet agent for the secondary prevention of stroke.

Ticlopidine hydrochloride, an inhibitor of platelet aggregation that has been approved for use in the United States for secondary stroke prevention, may be more effective than aspirin for the secondary prevention of stroke, but this advantage decreases greatly over time. The pharmacology, adverse effects, efficacy, drug interactions, and indications for ticlopidine are discussed here with summaries of various clinical trials. The drug is more costly than aspirin, and patients must have complete blood counts during the first 3 months of therapy. It is recommended for those who cannot take aspirin and may be more effective in certain groups--nonwhites, diabetics, and women and those with vertebrobasilar ischemia, intermittent claudication, unstable angina, and nonproliferative retinopathy.

Cerebrovascular Disorders↗
PubMed1993

Pigmentation phenotypes of variant extension locus alleles result from point mutations that alter MSH receptor function.

Coat colors in the chestnut horse, the yellow Labrador retriever, the red fox, and one type of yellow mouse are due to recessive alleles at the extension locus. Similarly, dominant alleles at this locus are often responsible for dark coat colors in mammals, such as the melanic form of the leopard, Panthera pardus. We show here that the murine extension locus encodes the melanocyte-stimulating hormone (MSH) receptor. In mice, the recessive yellow allele (e) results from a frameshift that produces a prematurely terminated, nonfunctioning receptor. The sombre (Eso and Eso-3J) and tobacco darkening (Etob) alleles, which both have dominant melanizing effects, results from point mutations that produce hyperactive MSH receptors. The Eso-3J receptor is constitutively activated, while the Etob receptor remains hormone responsive and produces a greater activation of its effector, adenylyl cyclase, than does the wild-type allele.

Alleles↗
PubMed1993

Both DQA1 and DQB1 genes are implicated in HLA-associated protection from type 1 (insulin-dependent) diabetes mellitus in a British Caucasian population.

Inherited susceptibility to Type 1 (insulin-dependent) diabetes mellitus is partly determined by HLA genes. It has been suggested that protection from disease may be conferred by HLA-DQB1 genes which encode molecules with aspartate at position 57. We investigated the contributions of HLA-DRB1, DQA1 and DQB1 genes to protection from disease. Restriction fragment length polymorphism and sequence specific oligonucleotide analysis in 156 British Caucasian Type 1 diabetic and 116 control subjects showed protection from disease was associated with DR2, DRw6 and DR7 haplotypes. The most protective DQA1 allele was DQA1*0102 which occurred on both DR2 and DRw6 haplotypes. The DQB1 alleles DQB1*0303, DQB1*0602 and DQB1*0603 were associated with protection, as was DQB1*0604, which encodes an Asp-57 negative DQ beta molecule. Heterozygosity for both protective and predisposing HLA markers was reduced in diabetic compared with control subjects. We conclude that both DQA1 and DQB1 genes are implicated in HLA-associated protection from Type 1 diabetes in this British Caucasian population. The overall structure of the DQ heterodimer is critical and DQ beta-Asp 57 is of secondary importance in determining protection from disease. The effect of protective HLA types may predominate over that of predisposing markers.

Adult↗