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Biomedical subjects

M Craig

Publications and source records attributed to M Craig.

At least 19 recordsLinked to original sources
PubMed2003

Temperature-suitability maps for schistosomiasis in South Africa.

The results of parasitological surveys have shown that both urinary and intestinal schistosomiasis occur widely among the human residents of South Africa. The national data on both diseases have now been incorporated into a geographical information system, to develop new maps based on defined temperature constraints. The disease data, obtained from a 'hard-copy' atlas of schistosomiasis, were used as a template to select temperature regimes that were (1) suitable and (2) unsuitable for the transmission of schistosomes to humans in South Africa. The regimes were derived from the published results of investigations in which the biology of larval schistosomes (i.e. schistosome transmission) was related to temperature in South Africa. Those regimes that were based on the estimated temperature minima for transmission corresponded more closely to the disease-distribution data than those based on the corresponding maxima. An estimate of the number of children living in the climate-suitable areas was made but, within the context of the spatial methodology used and the limitations of the available disease data, it was not possible to predict the prevalences of schistosomiasis.

Adolescent↗
PubMed2002

CCR5 genotyping in an Australian and New Zealand type 1 diabetes cohort.

Infiltration of pancreatic tissue by autoreactive T-cells involves secretion of multiple cytokines and chemokine receptor expression. Genetically determined variation in cell surface expression of the chemokine receptor CCR5 may result in differences in inflammatory cell migration in response to relevant chemokines. Adolescents with type 1 diabetes (T1D) from Australia and New Zealand were genotyped for CCR5-delta32 (n = 626). The allele frequency was compared with that of 253 non-diabetic Australian adolescents and with that of 92 adults with systemic lupus erythematosus. A reduced allele frequency was seen in T1D compared with controls (0.092 vs. 0.123, p = 0.05). This difference was not seen for the cohort of patients with SLE (freq = 0.114). A reduction in the number of CCR5-delta32/delta32 homozygotes, who lack CCR5, in the T1D cohort was also seen and while not statistically significant (2 observed compared to 5.25 expected; p = 0.12) is interesting. These results suggest a partial protection from T1D for CCR5-delta32 homozygous individuals is possible and that CCR5 has a potential role in the pathogenesis of T1D.

Adolescent↗
PubMed2002

Implant-related fractures of the femur following hip fracture surgery.

BACKGROUND: Most hip fractures are treated surgically, with use of either internal fixation or prosthetic replacement of the femoral head. The presence of these implants increases the risk of a later femoral fracture in susceptible osteoporotic patients. The purpose of this study was to analyze the incidence of and risk factors for implant-related fractures of the femur after previous hip fracture surgery. METHODS: Over a ten-year period from January 1988 to December 1997, 6230 patients (median age, eighty-two years; male:female ratio, 1247:4983) who sustained a total of 6696 hip fractures were admitted to the Edinburgh Orthopaedic Trauma Unit. Demographic information on the patients and details of the original treatment of the hip fracture were prospectively coded and entered into a trauma database. All subsequent readmissions due to a femoral fracture related to the implant were prospectively audited and extracted for the purposes of this study. RESULTS: One hundred and forty-one patients sustained an ipsilateral fracture of the femur at a median of twenty-four weeks following the original hip fracture surgery. Survivorship analysis of the hip fracture population revealed an overall rate of subsequent femoral fracture of 2.9% at five years, which increased to 5.1% at ten years. The median age and gender distribution of the patients who sustained a subsequent femoral fracture were similar to those of the hip fracture population as a whole. Two-thirds of the fractures propagated from the tip of the implant. Analysis of the subsequent fractures according to the type of implant used to treat the original fracture revealed considerable differences in incidence. The incidence was relatively high in the patients initially treated with a Gamma nail (18.74 fractures per 1000 person-years) or a cementless hemiarthroplasty (11.72 per 1000 person-years) and was relatively low in those treated with a compression hip screw (4.46 per 1000 person-years), cannulated screws (4.50 per 1000 person-years), or a primary arthroplasty with cement (6.2 per 1000 person-years). The highest incidence of fracture was seen in the patients who had required an arthroplasty with cement as a revision procedure following failure of a primary implant (22.39 per 1000 person-years). CONCLUSIONS: Implant-related fractures following hip fracture surgery are more common than has previously been appreciated. The risk of later ipsilateral femoral fracture is increased by the use of a Gamma nail or a cementless hemiarthroplasty to treat the original hip fracture.

Aged↗
PubMed2002

Psychiatric morbidity among patients with recurrent miscarriage.

In this study 81 women with recurrent miscarriages completed questionnaires designed to assess depression, anxiety and general health. This data was matched with data from their medical notes to ascertain demographic and reproductive variables. The results indicated that 33% of patients could be classified as depressed with 9.9% of women being moderately depressed and 7.4% suffering from severe depression. Twenty-one percent of patients had levels of anxiety that were equal or higher to a typical psychiatric outpatient population. Neither age, cigarette consumption, alcohol intake, previous live birth, number of miscarriages, lateness of miscarriage nor length of time since last miscarriage were found to affect the degree of psychiatric morbidity. These findings add to our understanding of the degree to which recurrent miscarriage can affect mental health.

Abortion, Habitual↗
PubMed2001

Drugs in pregnancy. Prescribing for psychiatric disorders in pregnancy and lactation.

The most recent Confidential Enquiry into the causes of maternal deaths during the perinatal period in England and Wales (1994-1996) revealed that psychological illness was at least as important as hypertensive disorders. It is therefore important for obstetricians to be aware of a variety of psychiatric conditions as well as the psychotropic medication prescribed and sequelae of continuation or withdrawal of these drugs. Best management, of this particularly vulnerable group of women, requires close liaison with the psychiatric team. This chapter considers four groups of women most likely to be prescribed psychoactive drugs during the perinatal period: (i) women with mental illness wishing to conceive, (ii) women with mental illness who conceive while taking medication, (iii) those who become mentally ill while pregnant, and (iv) those who become unwell postnatally. Guidelines for treatment are discussed.

Antipsychotic Agents↗
PubMed2000

Distribution of African malaria mosquitoes belonging to the Anopheles gambiae complex.

The distribution of malaria vector mosquitoes, especially those belonging to species complexes that contain non-vector species, is important for strategic planning of malaria control programmes. Geographical information systems have allowed researchers to visualize distribution data on maps together with environmental parameters, such as rainfall and temperature. Here, Maureen Coetzee, Marlies Craig and David le Sueur review our current knowledge on the distribution of the members of the Anopheles gambiae complex.

Africa South of the Sahara↗
PubMed2000

Extended daily dialysis: A new approach to renal replacement for acute renal failure in the intensive care unit.

Continuous venovenous hemofiltration (CVVH) is an effective form of renal replacement therapy for acute renal failure (ARF) that offers greater hemodynamic stability and better volume control than conventional hemodialysis in the critically ill, hypotensive patient. However, the application of CVVH in the intensive care unit (ICU) has several disadvantages, including intensive nursing requirements, continuous anticoagulation, patient immobility, and expense. We describe a new approach to the treatment of ARF in the ICU, which we have termed extended daily dialysis (EDD). In this study, EDD was compared with CVVH in 42 patients: 25 patients were treated with EDD for a total of 367 treatment days, and 17 patients were treated with CVVH for a total of 113 days. Median treatment time per day was 7.5 hours for EDD (range, 6 to 8 hours, 25th to 75th percentile) versus 19.5 hours for CVVH (range, 13.4 to 24 hours; P < 0.001). Mean arterial blood pressures (MAPs) did not differ significantly for patients treated with EDD when measured predialysis (median MAP, 70 versus 67 mm Hg for CVVH; P = 0.078), midway through daily treatment (70 versus 68 mm Hg for CVVH; P = 0.083), or at the end of treatment (71 versus 69 mm Hg for CVVH; P = 0.07). Net daily ultrafiltration was similar for the two treatment modalities (EDD, median, 3,000 mL/d; range, 1,763 to 4,445 mL/d; CVVH, 3,028 mL/d; range, 1,785 to 4,707 mL/d; P = 0.514). Anticoagulation requirements were significantly less for patients treated with EDD (median dose of heparin, 4,000 U/d; range, 0 to 5,800 U/d versus 21,100 U/d; range, 8,825 to 31,275 U/d for patients treated with CVVH; P < 0.001). We found that EDD eliminated the need for constant supervision of the dialysis machine by a subspecialty dialysis nurse, allowing one nurse to manage more than one treatment. Overall, EDD was well tolerated by the majority of patients, offered many of the same benefits provided by CVVH, and was technically easier to perform.

Acute Kidney Injury↗
PubMed2000

A spatial statistical approach to malaria mapping.

BACKGROUND: Good maps of malaria risk have long been recognized as an important tool for malaria control. The production of such maps relies on modelling to predict the risk for most of the map, with actual observations of malaria prevalence usually only known at a limited number of specific locations. Estimation is complicated by the fact that there is often local variation of risk that cannot be accounted for by the known covariates and because data points of measured malaria prevalence are not evenly or randomly spread across the area to be mapped. METHOD: We describe, by way of an example, a simple two-stage procedure for producing maps of predicted risk: we use logistic regression modelling to determine approximate risk on a larger scale and we employ geo-statistical ('kriging') approaches to improve prediction at a local level. Malaria prevalence in children under 10 was modelled using climatic, population and topographic variables as potential predictors. After the regression analysis, spatial dependence of the model residuals was investigated. Kriging on the residuals was used to model local variation in malaria risk over and above that which is predicted by the regression model. RESULTS: The method is illustrated by a map showing the improvement of risk prediction brought about by the second stage. The advantages and shortcomings of this approach are discussed in the context of the need for further development of methodology and software.

Child↗
PubMed1999

Estimating mortality, morbidity and disability due to malaria among Africa's non-pregnant population.

The contribution of malaria to morbidity and mortality among people in Africa has been a subject of academic interest, political advocacy, and speculation. National statistics for much of sub-Saharan Africa have proved to be an unreliable source of disease-specific morbidity and mortality data. Credible estimates of disease-specific burdens are required for setting global and national priorities for health in order to rationalize the use of limited resources and lobby for financial support. We have taken an empirical approach to defining the limits of Plasmodium falciparum transmission across the continent and interpolated the distributions of projected populations in 1995. By combining a review of the literature on malaria in Africa and models of acquired functional immunity, we have estimated the age-structured rates of the fatal, morbid and disabling sequelae following exposure to malaria infection under different epidemiological conditions.

Adolescent↗
PubMed1997

Bispecific monoclonal antibody complexes facilitate erythrocyte binding and liver clearance of a prototype particulate pathogen in a monkey model.

We used Anger camera imaging in a monkey model to investigate the organ localization of a prototype particulate pathogen, 131I-labeled bacteriophage phi X174, after it was bound to the primate erythrocyte complement receptor and then cleared from the circulation. This 131I-labeled phi X174 was infused into the circulation of an immunized monkey, and the nascently formed immune complexes showed rapid and quantitative binding to erythrocytes via the immune adherence reaction (complement-mediated binding). Alternatively, phi X174 was infused into the circulation of a naive animal, and then cross-linked bispecific mAb complexes (heteropolymers, anti-CR1 x anti-phi X174) were infused into the circulation. The infused heteropolymers also facilitated rapid and quantitative binding of phi X174 to erythrocytes. In both cases, after a short lag period, the erythrocyte-bound phi X174 was rapidly cleared from the circulation, and the vast majority of the radiolabel was cleared to the liver, with a small amount clearing to the spleen. Further liver imaging confirmed that within 24 h most of the bacteriophage previously cleared to the liver via the heteropolymer system was phagocytosed and destroyed. The findings in this model system provide additional evidence for the potential utility of heteropolymers to facilitate the safe and rapid clearance of blood-borne pathogens as a potential treatment for infectious diseases.

Animals↗
PubMed1997

14C-labeled microcystin-LR administered to Atlantic salmon via intraperitoneal injection provides in vivo evidence for covalent binding of microcystin-LR in salmon livers.

The tissue distribution and clearance of radiolabeled microcystin-LR administered to Atlantic salmon via i.p. injection has been re-examined using uniformly 14C-labeled toxin. Significant differences were found to exist between these results and those obtained when fish received an i.p. injection of tritium-labeled dihydromicrocystin-LR. In addition, MeOH liver extracts were assayed by both phosphatase assay and 14C counts and the results compared with the total levels of incorporation determined by digestion and subsequent 14C counting of the same live tissues. An attempt to investigate the metabolism and to document the putative products was also undertaken. It was found that microcystin-LR was extensively metabolized to compounds that are more polar than the parent compound.

Animals↗
PubMed1997

Bioaccumulation and clearance of microcystins from salt water mussels, Mytilus edulis, and in vivo evidence for covalently bound microcystins in mussel tissues.

Over a period of 3 days saltwater mussels, Mytilus edulis, were fed a cyanobacteria, Microcystis aeruginosa, that contained a high concentration of microcystins. The mussels were killed on a periodic basis over the course of 2 months. Mussels were also collected at two sites were high levels of microcystins in tissues had been noted. A strategy based on the chemically unique nature of the C20 beta-amino acid, (2S,3S,8S,9S)-3-amino-9-methoxy-2,6,8-trimethyl-10-phenyldeca-4,6- dienoic acid (Adda), portion of the microcystins was used in conjunction with a protein phosphatase (PPase) assay to analyse for both covalently bound microcystins and free microcystins in the mussel tissues. The mussel PPase assay results were compared with the Lemieux oxidation gas chromatography-mass spectrometry (GCMS) analysis. Less than 0.1% of the total microcystin burden in the mussel tissue was found to be extractable with MeOH. Thus, direct evidence was provided for the existence of covalently bound microcystins in mussel tissues in vivo. The mussels rapidly cleared the covalently bound microcystins when transferred to untreated seawater. Within 4 days the total microcystin burden dropped from a high of 336.9 (+/- 45.8) micrograms/g wet tissue to 11.3 (+/- 2.6) micrograms/g. After 4 days postexposure until completion of the experiment the total levels remained below the detection limits of the GCMS method. The levels of free microcystins, extracted with MeOH and detected by the PPase assay, fell from 204 ng/g wet tissue to a residual 14 ng/g over a 53 day postexposure period. Presumably the bound microcystin present in the mussel tissue exists as a covalent complex with the PP-1 and PP-2A enzymes. We conclude that in any shellfish monitoring program it is the total tissue microcystin burden that needs to be considered.

Animals↗
PubMed1997

Evidence for a covalently bound form of microcystin-LR in salmon liver and Dungeness crab larvae.

The chemically unique nature of the C20 beta-amino acid (2S,3S,8S,9S)-3-amino-9-methoxy-2,6,8-trimethyl-10-phenyldeca-4,6- dienoic acid (Adda) portion of the microcystins has been exploited to develop a strategy to analyze for the total microcystin-LR (1; see Figure 1) burden in salmon liver and crab larvae tissues. Lemieux oxidation of microcystin-LR (1) gives 2-methyl-3-methoxy-4-phenylbutanoic acid (2), a unique marker for the presence of microcystins. The butanoic acid 2 can be isolated and detected by GC/MS from the livers of Atlantic salmon that received an ip injection of microcystin-LR (1) and from tissues of wild-caught crab larvae. The Lemieux oxidation-GC/MS results are compared with those from MeOH extraction-PPase analysis. Only approximately 24% of the total microcystin-LR (1) burden in salmon liver tissue is found to be extractable with MeOH. Similarly, the Lemieux oxidation-GC/MS method detected 10,000-fold greater microcystin concentrations in Cypress Island Dungeness crab larvae than did the MeOH extraction-PPase method. The disparity in microcystin concentrations measured by the two methods is taken as direct evidence for the existence of covalently bound microcystins in vivo.

Animals↗
PubMed1996

Molecular mechanisms underlying he interaction of motuporin and microcystins with type-1 and type-2A protein phosphatases.

Heptapeptide microcystin and pentapeptide motuporin (nodularin-V) are equipotent inhibitors of type-1 and type-2A protein phosphatase catalytic subunits (PP-1c and PP-2Ac). Herein we describe elucidation of the molecular mechanisms involved in the interaction of these structurally similar hepatotoxins with PP-1c/PP-2Ac and identification of an important functional difference between their mode of interaction with these enzymes. Microcystin-LR, microcystin-LA, and microcystin-LL were found to interact with PP-2Ac and PP-1c by a two-step mechanism involving rapid binding and inactivation of the protein phosphatase (PPase) catalytic subunit, followed by a slower covalent interaction (within hours). Covalent adducts comprising PPase-toxin complexes were separated from free PPase by C-18 reverse-phase liquid chromatography, thus allowing the time course of covalent adduct formation to be quantitated. In contrast to microcystins, motuporin (nodularin-V) and nodularin-R were unable to form covalent complexes with either PP-1c or PP-2Ac even after 96 h incubation. Specific reduction of microcystin-LA to dihydromicrocystin-LA abolished the ability of the toxin to form a covalent adduct with PP-2Ac. Specific methyl esterification of the single Glu residue in microcystin-LR rendered this toxin inactive as a PPase inhibitor and abolished subsequent formation of a covalent adduct. Our data indicate that inactivation of PP-2Ac/PP-1c by microcystins precedes covalent modification of the PPases via a Michael addition reaction between a nucleophilic phosphatase residue and Mdha in the heptapeptide toxin. In contrast, following rapid inactivation of PP-2Ac/PP-1c by motuporin, the equivalent N-methyldehydrobutyrine residue in this toxin is unreactive and does not form a covalent bond with the PPases. These results are consistent with structural data for (i) the NMR solution structures of microcystin-LR and motuporin, which indicate a striking difference in the relative positions of their corresponding dehydroamino acids in the toxin peptide backbone, and (ii) X-ray crystallographic data on an inactive complex between PP-1c and microcystin-LR, which show a covalent bond between Cys-273 and the bound toxin.

Enzyme Inhibitors↗