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Biomedical subjects

C R Newton

Publications and source records attributed to C R Newton.

At least 19 recordsLinked to original sources
PubMed2006

Gender differences in how men and women who are referred for IVF cope with infertility stress.

BACKGROUND: Men and women use a variety of coping strategies to manage stress associated with infertility. Although previous research has helped us understand these coping processes, questions remain about gender differences in coping and the nature of the relationship between coping and specific types of infertility stress. METHODS: This study examined the coping behaviours of 1026 (520 women, 506 men) consecutively referred patients at a University-affiliated teaching hospital. Participants completed the Ways of Coping Questionnaire, Fertility Problem Inventory and the Dyadic Adjustment Scale. RESULTS: Women used proportionately greater amounts of confrontative coping, accepting responsibility, seeking social support and escape/avoidance when compared with men, whereas men used proportionately greater amounts of distancing, self-controlling and planful problem-solving. For men and women, infertility stress was positively related to escape/avoidance and accepting responsibility and negatively related to seeking social support, planful problem-solving and distancing. CONCLUSIONS: By analysing relative coping scores, this study identified key gender differences in how men and women cope with infertility. This was particularly true for men's coping processes that had previously remained hidden because of less frequent use of coping strategies when compared with women.

Adaptation, Psychological↗
PubMed2001

High-performance liquid chromatographic determination of diazepam in plasma of children with severe malaria.

A sensitive, selective and reproducible reversed-phase HPLC method with ultraviolet detection was developed for the quantification of diazepam in small plasma samples from children with severe malaria. The method involves plasma deproteinization with acetonitrile, followed by liquid-liquid extraction with ethyl acetate-n-hexane. Diazepam was eluted at ambient temperatures from a reversed-phase C18 column with an acidic (pH 3.5) aqueous mobile phase (10 mM KH2PO4-acetonitrile, 69:31, v/v). Calibration curves in spiked plasma were linear from 10 to 200 ng (r2 > or = 0.99). The limit of detection was 5.0 ng/ml, and relative recoveries at 25 and 180 ng were >87%. Intra- and inter-assay relative standard deviations were <15%. There was no interference from drugs commonly administered to children with severe malaria (phenobarbitone, phenytoin, chloroquine, quinine, sulfadoxine, pyrimethamine, halofantrine, cycloguanil, chlorcycloguanil, acetaminophen and salicylate). This method has been used for monitoring plasma diazepam concentrations in children with seizures associated with severe malaria.

Anticonvulsants↗
PubMed2001

Diagnosis of acute bacterial meningitis in children at a district hospital in sub-Saharan Africa.

BACKGROUND: The diagnosis of acute bacterial meningitis in children is difficult in sub-Saharan Africa, because the clinical features overlap with those of other common diseases, and laboratory facilities are inadequate in many areas. We have assessed the value of non-laboratory tests and incomplete laboratory data in diagnosing childhood acute bacterial meningitis in this setting. METHODS: We prospectively studied 905 children undergoing lumbar puncture at a rural district hospital in Kenya over 1 year. We related microbiological findings and cerebrospinal-fluid (CSF) laboratory measurements to tests that would typically be available at such a hospital. FINDINGS: Acute bacterial meningitis was proven in 45 children (5.0% [95% CI 3.7-6.6]) and probable in 26 (2.9% [1.9-4.2]). 21 of the 71 cases of proven or probable acute bacterial meningitis had neither neck stiffness nor turbid CSF. In eight of 45 children with proven disease the CSF leucocyte count was less than 10x10(6)/L or leucocyte counting was not possible because of blood-staining. The presence of either a leucocyte count of 50x10(6)/L or more or a CSF/blood glucose ratio of 0.10 or less detected all but two of the 45 children with proven acute bacterial meningitis; these two samples were grossly blood-stained. INTERPRETATION: The diagnosis of childhood acute bacterial meningitis is likely to be missed in a third of cases at district hospitals in sub-Saharan Africa without adequate and reliable laboratory resources. CSF culture facilities are expensive and difficult to maintain, and greater gains could be achieved with facilities for accurate leucocyte counting and glucose measurement.

Acute Disease↗
PubMed2001

Oxidative stress and erythrocyte damage in Kenyan children with severe Plasmodium falciparum malaria.

Anaemia causes significant morbidity in children with Plasmodium falciparum malaria, but the mechanism(s) are unclear. During malarial infection, increased reactive oxygen species (ROS) are generated that may contribute to erythrocyte damage and anaemia. This study measured the concentrations of alpha-tocopherol in plasma and erythrocyte membranes, and the percentage polyunsaturated fatty acid composition (%PUFA) (an indirect marker of ROS damage) in erythrocyte membranes in children with severe P. falciparum malaria from Kilifi, Kenya, and asymptomatic children from the same district. Malarial subjects were stratified into complicated malaria and malaria anaemia. Results demonstrated significant reductions in erythrocyte membrane alpha-tocopherol concentration (1.63 +/- 0.16 versus 3.38 +/- 0.18 micromol/mg protein; P < 0.001) and total %PUFA (30.7 +/- 0.49 versus 32.8 +/- 0.44% P < 0.005) for the malarial subjects (non-stratified) compared with controls. Malarial subjects showed a significant positive correlation between membrane alpha-tocopherol and haemoglobin concentrations (P < 0.005 r = 0.63 complicated malaria group; P < 0.05 r = 0.36 non-stratified data). There were no significant differences in plasma alpha-tocopherol concentration between malaria patients and controls. In conclusion, malarial infection may be associated with oxidative damage and reduced alpha-tocopherol reserve in the erythrocyte membrane, suggesting that local antioxidant depletion may contribute to erythrocyte loss in severe malaria. Erythrocyte membrane alpha-tocopherol appeared a better indicator of ROS exposure than plasma.

Acute Disease↗
PubMed2001

Brain damage after neonatal tetanus in a rural Kenyan hospital.

OBJECTIVE: Neonatal tetanus (NNT) is an important cause of mortality in resource poor countries, particularly sub-Saharan Africa. There are no reports of the long-term outcome of children who survive NNT in African hospitals. DESIGN: In a retrospective study of children discharged from Kilifi District Hospital (KDH), Kenya with NNT, each child was linked with a comparative child (CC) in the community matched for age, sex and locality. PARTICIPANTS: A total of 123 patients were admitted with NNT between 1992 and 1996, of whom 68% died. Twenty-three (59%) of the 39 survivors were traced in the community, 10 had moved away, six had died. OUTCOME MEASURES: NNT survivors underwent a neurological and developmental examination and a questionnaire was administered to the parents about the behaviour of the child. A verbal autopsy was used to determine the cause of death in children who had died after discharge. RESULTS: The head circumference of NNT survivors was significantly smaller than that of CC (P=0.037); eight children had microcephaly compared with one CC (P=0.011). NNT survivors had more problems with hand-eye co-ordination tasks (P=0.035), a lower summated developmental score (P=0.023) and more mild neurological abnormalities (P=0.008) than CC. Parents of NNT survivors reported more behavioural problems (P=0.02) than parents of CC. CONCLUSIONS: Children who survive NNT have evidence of brain damage that manifests as microcephaly, mild neurological abnormalities, developmental impairment - particularly fine motor difficulties - and behaviour problems.

Brain Damage, Chronic↗
PubMed2000

Arginine vasopressin secretion in Kenyan children with severe malaria.

Hyponatraemia is common in African children with severe malaria, but the cause is unknown. We measured plasma sodium (p[Na]) and arginine vasopressin concentrations (p[AVP]) in 30 consecutive children with severe malaria (19 had cerebral malaria), on admission, at 48 and 96 h after admission. Hyponatraemia (p[Na] < 130 mmol/l) occurred in 53 per cent of the children and was unrelated to peripheral parasite density, dehydration or abnormal renal function. The highest p[AVP] were seen in patients with cerebral malaria. Overall, p[AVP] declined 96 h after treatment. In children with hyponatraemia (cerebral and non-cerebral), p[AVP] levels were not suppressed and in 67 per cent of cases they were deemed inappropriate. Inappropriate AVP secretion is common in children with severe malaria and may influence fluid therapy after correction of initial dehydration.

Arginine Vasopressin↗
PubMed2000

Cerebral malaria.

Cerebral malaria may be the most common non-traumatic encephalopathy in the world. The pathogenesis is heterogeneous and the neurological complications are often part of a multisystem dysfunction. The clinical presentation and pathophysiology differs between adults and children. Recent studies have elucidated the molecular mechanisms of pathogenesis and raised possible interventions. Antimalarial drugs, however, remain the only intervention that unequivocally affects outcome, although increasing resistance to the established antimalarial drugs is of grave concern. Artemisinin derivatives have made an impact on treatment, but other drugs may be required. With appropriate antimalarial drugs, the prognosis of cerebral malaria often depends on the management of other complications-for example, renal failure and acidosis. Neurological sequelae are increasingly recognised, but further research on the pathogenesis of coma and neurological damage is required to develop other ancillary treatments.

Adult↗
PubMed1999

The Fertility Problem Inventory: measuring perceived infertility-related stress.

OBJECTIVE: To develop a reliable, valid instrument to evaluate perceived infertility-related stress. DESIGN: Prospective study. SETTING: University-affiliated teaching hospital. PATIENT(S): Consecutively referred patients (1,153 women and 1,149 men) seen for infertility treatment. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Participants' infertility-related stress was assessed by written questionnaire using the Fertility Problem Inventory. Current levels of anxiety, depression, and marital satisfaction also were determined. RESULT(S): Women described greater global stress than men and higher specific stress in terms of social concerns, sexual concerns, and need for parenthood. Both men and women facing male infertility reported higher global stress and more social and sexual concerns than men and women experiencing female infertility. Social, sexual, and relationship concerns related to infertility were more effective predictors of depression and marital dissatisfaction than expressed needs for parenthood or attitudes toward child-free living. CONCLUSION(S): The Fertility Problem Inventory provides a reliable measure of perceived infertility-related stress and specific information on five separate domains of patient concern. Patterns of infertility-related stress differed depending on gender, fertility history, and infertility diagnosis. Among patients receiving treatment, social, sexual, and relationship concerns appear central to current distress. Counseling interventions that target these domains appear likely to offer maximal therapeutic benefit.

Adult↗
PubMed1999

Molecular characterization of a new alpha-1-antitrypsin M variant allele, Mwhitstable: implications for DNA-based diagnosis.

The mother and second child from a family, already with one PI ZZ child, were typed PI MZ by isoelectric focusing and unexpectedly as PI ZZ using a commercial alpha-1-antitrypsin genotyping kit. Both methods typed the father and first child as PI MZ and PI ZZ, respectively. DNA sequence analysis identified a 26-base pair (bp) deletion and 2-bp insertion in intron IV of the normal PI*M allele from both the mother and second child. The majority of the binding site for an amplification primer of the genotyping kit was absent in the variant deletion-insertion allele. The apparent PI*Z/PI*Z genotype of the mother and second child therefore arose from amplification of the PI*Z allele alone. Two hundred random DNA samples were subsequently examined and 5 of these were found to be heterozygous for the same deletion-insertion allele. The authors have designated the previously undescribed PI*M allele that harbors this benign polymorphism PI*Mwhitstable. The genotyping kit has been redesigned and revalidated, and its performance is not affected by the presence of the PI*Mwhitstable allele. The Gen Bank accession number for the nucleotide sequence described is AF159454.

Alleles↗
PubMed1999

Fibrocalculous pancreatic diabetes in a child: case report.

A case of fibrocalculous pancreatic diabetes in a 12-year old boy is described. A medline literature search back to 1966 revealed that no cases had been reported from East Africa. We reviewed the literature and suggest that the condition is probably under-reported.

Abdominal Pain↗
PubMed1998

Neurological manifestations of falciparum malaria.

Plasmodium falciparum remains one of the most common causes of central nervous system infection worldwide. Recently, differences between the pathophysiology of cerebral malaria in African children and nonimmune adults have been discovered, new syndromes occurring after malaria infection described, and mechanisms for the pathogenesis proposed. In addition, new antimalarial agents have been examined worldwide and initial studies on supportive studies conducted. This paper reviews these new advances, putting them into the perspective of the more established knowledge.

Adult↗
PubMed1998

Severe falciparum malaria in children: current understanding of pathophysiology and supportive treatment.

Severe falciparum malaria is one of the most lethal parasitic infections in the world and is responsible for more than one million deaths in African children per year. Changes to management over the last 40 years have not improved survival. A reduction in the mortality and morbidity may only come about by a better understanding of the pathophysiological processes that are responsible for severe disease and that determine the outcome before antimalarials have had time to work. This review discusses potential adjunctive therapies for severe malaria that are under development following such detailed clinical and pathophysiological studies.

Animals↗
PubMed1998

Advances in approaches to DNA-based diagnostics.

The most tangible advances in DNA diagnostics during the past year have been in enhancing existing techniques to simplify their use and improve throughput. This has led to simplified genotyping methods using homogeneous analysis coupled with spectral data output. Miniaturisation and increased throughput have also been achieved through improvements in DNA chip technology.

Biotechnology↗
PubMed1998

The detection of K-ras mutations in colorectal cancer using the amplification-refractory mutation system.

A total of 301 colorectal carcinoma (CRC) archival samples were analysed using the amplification-refractory mutation system (ARMS). Each sample was examined to determine the mutation status of codons 12 and 13 of the K-ras oncogene. The results from direct DNA sequence analysis carried out on 30 of the samples differed from the ARMS result in almost 50% of the cases as a result of the relative excess of wild-type to mutated DNA sequences. To assess the validity of the ARMS data, the polymerase chain reaction (PCR) was used to generate an amplicon from K-ras exon 1 from 23 of the samples. The PCR amplicons were cloned and sequenced, and the DNA sequence analysis of the cloned material was in agreement with the ARMS results in all but one case. This case represented a tumour that exhibited a five-nucleotide reversed inversion. The cloned sequence data confirm the sensitivity and specificity of the individual ARMS reactions and that it is possible in certain cases to detect additional, more complex, sequence variations.

Adenoma↗
PubMed1998

Amplification refractory mutation system linear extension: a novel, gel-free, enzyme-linked immunoassay method for DNA genotyping.

A single synthesis cycle of the amplification refractory mutation system (ARMS) was applied to the analysis of K-ras alleles amplified by polymerase chain reaction and immobilized in streptavidin-coated microtiter plates. The ARMS cycle provided the specificity and molecular switch characteristics of a conventional ARMS assay. This allowed linear extension from an allele-specific primer and the incorporation of digoxigenin-labeled deoxyuridine monophosphate from digoxigenin-11-deoxyuridine triphosphate in the presence of the appropriate K-ras allele. Any digoxigenin-labeled deoxyuridine monophosphate substitution was then demonstrated by enzyme-linked immunoassay with colorimetric endpoint. This method is capable of detecting underrepresented acquired mutations, and this has been shown by the unambiguous detection of specific K-ras mutations in cell line DNA/normal human genomic DNA admixtures. The characterization of K-ras mutations in frozen colorectal tumor samples and histologic material is also described.

Alleles↗