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Biomedical subjects

C J O'Callaghan

Publications and source records attributed to C J O'Callaghan.

At least 37 records · Page 2Linked to original sources
PubMed2000

Comparison of cryotherapy with curettage in the treatment of Bowen's disease: a prospective study.

BACKGROUND: In our departments, curettage and cautery (C&C) and liquid nitrogen cryotherapy are the preferred methods of treatment for Bowen's disease (BD). OBJECTIVES: We aimed to compare these two treatments with regard to efficacy, time to heal, morbidity and recurrence rate. METHODS: Cryotherapy was performed using a liquid nitrogen spray giving two freeze-thaw cycles, each freeze cycle being maintained for 5-10 s after the formation of an ice ball to the intended margin. Curettage was performed with a conventional disposable curette under local anaesthesia, and electrocautery was then used for haemostasis. RESULTS: Eighty lesions in 67 patients (55 female) were analysed. The mean age of the patients was 74 years (range 46-89). The most frequent site was the lower leg, below the knee (n = 59, 74%). The average time taken for complete healing after the procedure was 60 days. The mean size of the lesions was 336 mm(2) (range 30-1890). The patients were followed up for a mean of 22 months (range 6-24, median 2 years). In the cryotherapy group (n = 36 lesions), the median time to complete healing was 46 days (range 14-210; mean 69). Twelve lesions took more than 90 days to heal. Infection requiring antibiotics developed in four patients. Thirteen of the treated lesions had recurred by 24 months. In the C&C group (n = 44 lesions), the median time to healing was 35 days (range 14-330; mean 53). Six of the lesions took more than 90 days to heal. Infection developed in two patients. Recurrence occurred in four lesions over the follow-up period. Considering BD on the lower legs separately, lesions took on average 90 days to heal in the cryotherapy group (n = 23), whereas in the C&C group (n = 36) they took 39 days to heal (P < 0.001). During the procedure and the subsequent 24 h, patients were 10.4 times more likely to report pain of any degree for lesions treated by cryotherapy than by C&C (P < 0.001). CONCLUSIONS: This study suggests a superiority of C&C over cryotherapy in the treatment of BD, especially for lesions on the lower leg. Curettage of lesions of BD is associated with a significantly shorter healing time, less pain, fewer complications and a lower recurrence rate when compared with cryotherapy.

Aged↗
PubMed2000

Mechanical strain-induced extracellular matrix production by human vascular smooth muscle cells: role of TGF-beta(1).

Elevated blood pressure imposes increased mechanical stress on the vascular wall, and mechanical strain is a mitogenic stimulus for vascular smooth muscle (VSM) cells. The role of mechanical forces in regulating the production of noncellular material by VSM cells for VSM cells of human origin remains undefined. We thus investigated the effects of chronic cyclical mechanical strain on extracellular matrix (ECM) protein production by cultured human VSM cells. To simulate a blood pressure of 120/80 mm Hg, human VSM cells were repetitively stretched and relaxed by 10% to 16% of their original length with the Flexercell apparatus. Fibronectin and collagen protein concentrations, matrix metalloproteinase (MMP) activity, and transforming growth factor-beta(1) (TGF-beta(1)) mRNA expression by human VSM cells were measured in response to mechanical strain. Exposing human VSM cells to 5 days of chronic cyclical mechanical strain increased fibronectin (+48%, P:<0.01) and collagen (+50%, P:<0.001) concentrations when compared with cells grown in static conditions. Mechanical strain also increased MMP-2 activity, the predominant matrix-degrading isoform (+11%, P:<0.05) in human VSM cells, thus strain-induced ECM accumulation was not due to inhibition of ECM protein degradation. Strain also increased TGF-beta(1) mRNA expression and the production of a soluble factor that increased ECM protein production. Moreover, a TGF-beta-blocking antibody inhibited the effect of strain-conditioned media on matrix production by human VSM cells. These results suggest that chronic cyclical mechanical strain can directly modulate the fibrogenic activity of human VSM cells by inducing ECM protein synthesis and MMP activity. This occurs, at least in part, through mechanical strain-induced TGF-beta(1) production, a mechanism that could explain the increased vascular ECM deposition in hypertension.

Analysis of Variance↗
PubMed1999

Predicting the effect of vaccination on the transmission dynamics of heartwater (Cowdria ruminantium infection).

We used a mathematical description of the transmission dynamics of the tick-borne infection Cowdria ruminantium in commercial beef enterprises in Zimbabwe to consider the potential impact of a candidate vaccine to prevent heartwater. The important characteristics of the vaccine were (1) a delay in development of full protection, (2) prevention of clinical disease but not of infection and (3) a waning period of protection in the absence of challenge. We considered three different scenarios in which the vaccine might be used: prophylactically in susceptible cattle prior to the introduction of infection into a herd; in susceptible cattle in the face of an epidemic (i.e., when the infection is introduced and disease is first noticed); and at equilibrium (i.e., when parasite, vector and host have been co-existing for some time). The epidemic rise in infection was modelled assuming two different patterns (i.e., resulting from slow and fast increases in tick challenge). Vaccination (administered both in the face of an epidemic and prophylactically) reduced and delayed the peak of the epidemic. With insufficiently frequent revaccination, this can result in the epidemic occurring during a period of susceptibility, so that the benefit derived from a more-efficacious vaccine is lower than that from a less-efficacious vaccine. A vaccine of only 30% or 50% efficacy (if given to the whole herd) can have important effects on both morbidity and mortality if administered with sufficient frequency. However, a highly efficacious vaccine (e.g., 90%) can have only minimal effect if revaccination occurs too infrequently - especially if the epidemic of disease occurs when tick challenge is high and vaccination-related immunity has waned. There was a fairly consistent pattern of decreasing returns on increasing protection, although this was reversed in the situation of annual vaccination undertaken prophylactically combined with an epidemic of infection that occurred when the tick challenge was relatively low. Vaccination in equilibrium situations was most beneficial at low and intermediate tick challenges. There was very little effect of vaccination in high-transmission areas regardless of vaccine efficacy and/or frequency of revaccination because most animals were infected during periods of innate or maternally derived immunity (i.e., under endemic stability). Our results suggest that where relatively high tick challenge can be achieved and consistently maintained, vaccination may be used in susceptible herds to minimise losses in a policy of transition to endemic stability.

Animals↗
PubMed1999

Cowdria ruminantium infection in ticks in the Kruger National Park.

Adult Amblyomma hebraeum ticks, the principle vector of heartwater (cowdriosis) of domestic ruminants in southern Africa, were collected in pheromone traps placed in Kruger National Park, an exclusively wildlife sanctuary in South Africa. These ticks transmitted Cowdria ruminantium, the rickettsial agent causing heartwater, to a susceptible goat, resulting in acute, fatal disease. C ruminantium was isolated in bovine endothelial cell culture from the plasma of this animal during the febrile stage of the disease and transmitted to susceptible goats, causing fatal heartwater. The prevalence of C ruminantium infection in 292 ticks was determined by polymerase chain reaction (PCR) analysis to be 1.7 per cent (95 per cent confidence interval 0.71 to 4.0 per cent). A DNA probe analysis, which is less sensitive than PCR, detected infection in three of the five PCR-positive ticks. The remaining infections were below the detection limit of the DNA probe, which is approximately 70,000 organisms. This is the first evidence that a vector-wildlife cycle of transmission of C ruminantium can be maintained independently of domestic ruminants.

Animals↗
PubMed1999

An assessment of the economic impact of heartwater (Cowdria ruminantium infection) and its control in Zimbabwe.

Heartwater, caused by the rickettsial organism Cowdria ruminantium, is a serious constraint to livestock development in much of sub-Saharan Africa. Traditionally, the disease has been controlled by the use of chemical acaricides to control the vector tick. The University of Florida/USAID-supported heartwater research project (based in Zimbabwe) is developing a new inactivated vaccine to control the disease. In order that the vaccine is used effectively, the project has been studying the epidemiology of the disease in different livestock production systems of Zimbabwe, and evaluating the economic impact of the disease and of its future control using a vaccine such as the one under development. Initially, field studies were conducted to characterise the communal and commercial livestock-productions systems at risk from heartwater and to understand the epidemiology of the disease. The data from these studies were then applied to an infection-dynamics model of heartwater, which was used to provide estimates of disease incidence and impact under various scenarios over a period of 10 yr. Two principal outputs of the epidemiological model (cumulative annual heartwater incidence and infection-fatality proportion) were key inputs into an economics model. The estimated total annual national losses amount to Z$ 61.3 million (US$ 5.6 million) in discounted value terms over 10 yr. Annual economic losses per animal in the commercial production system (Z$ 56 discounted values) are 25 times greater than the losses in the communal system (Z$ 2.2). The greatest component of economic loss is acaricide cost (76%), followed by milk loss (18%) and treatment cost (5%). Losses in outputs other than milk (beef, traction and manure) appear to be minimal. A new vaccine has the promise of a benefit: cost ratio of about 2.4:1 in the communal and 7.6:1 in the commercial system. A control strategy based on a new vaccine would yield additional non-financial benefits to farmers and the government resulting from reductions in the use of chemical acaricides.

Animals↗
PubMed1999

Epidemiology and genetic variability of two species of nematodes (Heligmosomoides polygyrus and Syphacia stroma) of Apodemus spp.

The epidemiology and genetic variability of 2 parasitic nematodes Heligmosomoides polygyrus and Syphacia stroma of Apodemus spp. were investigated. Both are parasites of the same host, exhibit a direct life-cycle and are dioecious. However, H. polygyrus has a diploid and S. stroma a haplodiploid mode of reproduction. Haplodiploidy may lead to a more female biased sex ratio and reduced genetic variability. Levels of genetic diversity were analysed using both isoenzyme electrophoresis and RAPDs (random amplified polymorphic DNA). Both parasites showed a female biased sex ratio with a stronger bias for the haplodiploid parasite. Results showed significantly fewer genetic polymorphisms as measured by RAPDs for the haplodiploid parasite S. stroma in comparison with H. polygyrus. Despite the observed female biased sex ratio this could not be explained by a significant amount of inbreeding. Heterozygote deficiency for individual allozyme loci--which could indicate inbreeding--was not found in either parasite species. Other features of the particular life-history of these species are likely to have an impact on the sex ratio and genetic variability too.

Animals↗
PubMed1999

Intestinal parasites in swine in the Nordic countries: multilevel modelling of Ascaris suum infections in relation to production factors.

In Denmark, Finland, Iceland, Norway and Sweden, 413 sow herds were randomly selected for sampling. Faeces from pigs of 7 age groups/categories were examined for helminth eggs (11,233 individual samples), and an accompanying questionnaire was completed at each visit. In total, 1138 pigs on 230 farms were found to be positive for Ascaris suum. Considerable differences in the occurrence of A. suum could be observed directly for several of 20 independent variables at the herd or category level. However, given that univariate analyses may be severely affected by confounding of covariates resulting in spurious inference, additional multivariate analyses were undertaken. An ordinary logistic regression on Ascaris positive/negative farms showed that Denmark had the highest frequency of infected herds, while Iceland and Finland had the lowest frequencies and that herds using 'late weaning' and 'Class 2' drugs (pyrantel, levamisole) were most often infected. Because many herds were found to be totally negative for A. suum, mixed hierarchical logistic-normal regression models (both the penalized quasi-likelihood and the Markov Chain Monte Carlo methods) were developed for both a full (all herds) and a reduced (the 230 infected herds) data set using either a cut-off of > 0 eggs per gram (epg) or > 200 epg to counter for false-positive egg counts. Estimates for identical models, but where the animal level variance was constrained to the binomial assumption, were also calculated. Significant covariates were robust to model development with 'Age group', 'Country', 'Weaning age', 'Water system' and simple interactions between the latter two and 'Age group' being significantly associated with the occurrence of A. suum, while all variables concerning anthelmintic drug, anthelmintic strategy, floor type, bedding, dung removal, washing and disinfection were not. These findings are discussed in the light of the complex relationship between A. suum and its pig host.

Age Factors↗
PubMed1999

Prevalence of Cowdria ruminantium infection in Amblyomma hebraeum ticks from heartwater-endemic areas of Zimbabwe.

Analysis of the transmission dynamics of Cowdria ruminantium, the tick-borne rickettsial agent of heartwater in ruminants, requires accurate measures of infection in vector populations. To obtain these, Amblomnia hebraeum ticks were collected at two heartwater-endemic locations in the lowveld and highveld regions of Zimbabwe and assessed for C. ruminantium infection with specific polymerase chain reaction (PCR) and DNA probe detection assays. At the lowveld site, 11.2% (50/446) of adult ticks and 8.5% (23/271) of nymphs carried C. ruminantium, as detected by PCR. At the highveld site, the prevalence of infection in adult ticks was 10.2% (40/392). DNA probe analysis revealed that most infections at both sites were of low intensity; only 9% and 23% of all nymph and adult tick infections, respectively, were greater than 70000 organisms, the detection limit of the DNA probe. However, the majority (70%) of probe-detectable adult tick infections were high, between 10(7) and 10(9) organisms/tick, while those within nymphs were lower, between 10(5) and 10(6) organisms/tick.

Animals↗
PubMed1999

Hypotensive effect of low-fat, high-carbohydrate diet can be independent of changes in plasma insulin concentrations.

To examine the relationship between diet, blood pressure, and plasma insulin concentrations, we studied 14 healthy males who were prescribed low-fat and high-fat diets. The low-fat diet contained 25% (of energy intake) fat and 54% carbohydrate; the high-fat diet was 45% fat (predominantly saturated fat) and 36% carbohydrate. The diets were consumed over consecutive 2-week periods in random sequence, separated by a 2-week washout period. Resting supine systolic and diastolic blood pressures decreased significantly by 7 and 3 mm Hg, respectively, and plasma total cholesterol, LDL cholesterol, and HDL cholesterol concentrations all fell (by 21.6%, 25.7%, and 18.0%, respectively; all P<0.001) on the low-fat compared with the high-fat diet. Fasting glucose and the glucose area under the curve during the frequently sampled intravenous glucose tolerance test (300 mg/kg glucose load with blood sampling for 180 minutes) were significantly lower, and the glucose disappearance rate tended to be faster after the low-fat diet. In contrast, fasting insulin concentrations and the insulin response (insulin area under the curve) to glucose challenge were unchanged. Insulin sensitivity (defined as the rate of glucose disappearance per unit of insulin increase during the period 0 to 40 minutes after the glucose load) was significantly higher on the low-fat diet. These results suggest that the hypotensive effects of a low-fat, high-carbohydrate diet, although associated with an improvement in insulin sensitivity, are not mediated by changes in plasma insulin concentration.

Adult↗
PubMed1999

Free leptin, bound leptin, and soluble leptin receptor in normal and diabetic pregnancies.

We measured serum levels of free leptin, bound leptin, and soluble leptin receptor by specific RIA methods in 20 normal and 19 insulin-dependent diabetes mellitus subjects at 20 and 30 weeks gestation and postpartum, and analyzed the data using hierarchical statistical models. Total leptin levels rise from 20-30 weeks gestation (688 +/- 58 to 785 +/- 62 pmol/L, mean +/- SEM; P = 0.009). There is a significant postpartum fall to 445 +/- 47 pmol/L (P < 0.001). This rise is caused by the rise in the bound leptin levels, as there is no significant change in free leptin levels between 20 and 30 weeks (P = 0.17). There is a significant postpartum fall in free leptin levels (P < 0.001). Insulin requirements rise in the third trimester, but despite this there was no significant difference in free or bound leptin levels between the normal and diabetic subjects at any stage [free leptin, 223 +/- 35 and 266 +/- 24, 237 +/- 45 and 223 +/- 27, and 109 +/- 16 and 104 +/- 24 (P = 0.34); bound leptin, 410 +/- 73 and 428 +/- 54, 501 +/- 78 and 562 +/- 71, and 330 +/- 47 and 271 +/- 46 (P = 0.84); for normals and diabetics at 20 and 30 weeks gestation and postpartum, respectively]. Diabetic subjects, however, had significantly higher soluble leptin receptor levels at all stages (P << 0.001), which rose further in the third trimester from 3742 +/- 268 (mean +/- SEM) to 4134 +/- 239 pmol/L, whereas in the normal group there was a fall from 3149 +/- 169 to 2712 +/- 123 (P = 0.05). There is a linear relationship between the soluble leptin receptor levels and the body mass index in the diabetic group only. We conclude that there is no significant difference in free or bound leptin levels between the normal and insulin-dependent diabetic subjects either during pregnancy or postpartum, but female insulin-dependent diabetic subjects have significantly higher soluble leptin receptor levels. We speculate that high soluble leptin receptor levels might be implicated in the development of the leptin resistance in this group.

Adult↗
PubMed1998

Investigating the epidemiology of heartwater (Cowdria ruminantium infection) by means of a transmission dynamics model.

A mathematical model of the transmission dynamics of Cowdria ruminantium by the ixodid tick Amblyomma hebraeum in the bovine host is developed and used to investigate the epidemiology of heartwater across a range of vector challenge. The processes described are supported by empirical data. The pattern of outcome measures (incidence, case-fatality and proportion of infected hosts) predicted agrees with those described anecdotally from field experience and empirical observation, and demonstrates the concept of endemic stability. The underlying theory is explored and it is shown that endemic stability may be due principally to the protection of calves against disease by either innate or maternally derived factors. The role of vertical infection in the establishment and maintenance of endemic stability is also investigated. Although increasing the vertical infection proportion results in endemic stability occurring at progressively lower levels of tick challenge, the concomitant reduction in incidence and case-fatality predictions across the range of tick challenge means the endemically stable state simultaneously becomes less discernible. Model limitations and future developments are discussed. The essential role of a transmission dynamics model in assessing the impact of new vaccines in conjunction with vector control programmes is highlighted.

Africa South of the Sahara↗
PubMed1998

Distributions of the vectors of heartwater, Amblyomma hebraeum and Amblyomma variegatum (Acari: Ixodidae), in Zimbabwe.

The tick vectors of heartwater (Cowdria ruminantium infection) in Zimbabwe, Amblyomma hebraeum and Amblyomma variegatum, historically were believed to be confined to the low-lying regions of the south and north-west of the country. However, country-wide surveys performed in 1975-1980 and 1988-1991 demonstrated that both species were also established in western parts of the highveld plateau and had started to encroach on the predominantly heartwater-free central and eastern highveld regions. To determine the current distributions of both the vectors and evaluate the potential threat of heartwater to animals in the highveld, a survey of ticks infesting cattle was performed in 1996 at 2994 locations in small-holder and large-scale commercial farming areas throughout Zimbabwe. Amblyomma hebraeum was collected at 1329 locations, A. variegatum at 72 locations and both A. hebraeum and A. variegatum at 13 locations. The results demonstrated that A. hebraeum was present, as previously recorded, throughout the southern half of the country and appeared to have undergone further limited spread into the central and eastern highveld regions. Only the northern-most region of the country appeared to be free of this species. Amblyomma variegatum was collected mainly in the north-west, as previously recorded, but was also found at isolated locations across the central highveld region and along the eastern border with Mozambique. This species was, however, still absent from the southern half and the northern-most regions of the country. An overlap of the distributions of the two species existed within a zone along the southern and eastern regions of the distribution of A. variegatum. These results suggest that the vectors of heartwater are spreading and threaten to introduce heartwater into intensive livestock-producing regions of the country.

Animals↗
PubMed1998

Systematic errors in estimating mean blood pressure from finger blood pressure measurements.

The mean blood pressure (BP) can be accurately estimated from indirect measurements of brachial artery pressure, i.e. mean BP = diastolic BP + 1/3 pulse pressure. Although this equation has been used as a surrogate of mean systemic pressure, it is unknown whether this approximation can be validly applied to distal vascular beds. Therefore we determined the accuracy of this method as an estimate of the mean pressure in distal arteries by measuring finger BP with the Finapres device in 16 normotensive and 12 hypertensive subjects. The "calculated" and measured values of mean BP were compared when subjects were resting and during manoeuvres which aimed to alter the shape of the pulse waveform. Although closely correlated with the measured value, the "calculated" resting mean BP was systematically greater (+2.7+/-0.7 mm Hg, p<0.001). Additionally, the rise in the mean pressure produced by infusion of phenylephrine, an alpha1-adrenoceptor stimulant (16.0+/-1.5 mm Hg) was underestimated by the calculation (13.1+/-1.5 mm Hg, p<0.05). Of even greater concern was that calculating the mean pressure during infusion of isoprenaline (a beta-adrenergic stimulant) suggested the mean pressure had increased by 5.8+/-1.6 mm Hg when it had actually fallen (-2.1+/-2.4 mm Hg, p<0.001 vs. the measured value). Thus, calculating the mean BP from Finapres measurements roughly approximates the measured value when subjects are at rest. However, this estimation becomes inaccurate when pulse wave dimensions are altered, and is probably unsuitable for assessing the acute effects of vasoactive drugs, in particular vasodilators, on BP.

Adrenergic beta-Agonists↗
PubMed1998

Acute effects of blood pressure elevation on insulin clearance in normotensive healthy subjects.

Reduced clearance of insulin from plasma contributes to the hyperinsulinemia associated with essential hypertension (EH); however, the association between impaired insulin clearance and EH remains unexplained. Whether elevated blood pressure (BP) affects insulin clearance is unknown; therefore, we used the hyperinsulinemic euglycemic clamp to determine the effects of BP elevation on insulin clearance and sensitivity in eight healthy volunteers. Placebo infusion increased mean BP by 2.6+/-1.6 mm Hg, which was significantly less than rises produced by phenylephrine, an alpha1-adrenoceptor agonist (+11+/-1.8 mmHg, P<.05), or by angiotensin II (+13+/-1.3 mmHg, P<.01). Although beta-adrenoceptor stimulation with isoproterenol did not change mean BP (+3.6 mm Hg, P=NS), it significantly increased systolic pressure (+23+/-2.8 mm Hg versus +2.3+/-4.6 mm Hg with placebo P<.01). Insulin secretion (ie, C-peptide concentrations) was not affected by any of the treatments; however, phenylephrine significantly reduced the metabolic clearance rate of insulin (MCRinsulin) (16.6+/-1.0 mL/kg per minute with placebo versus 13.6+/-0.7 mL/kg per minute with phenylephrine, P<.01) and thereby increased plasma insulin concentrations (66+/-5.1 microU/mL with placebo versus 79+/-4.1 microU/mL with phenylephrine, P<.05). Phenylephrine also increased glucose utilization (42+/-5.8 micromol/kg per minute during placebo versus 58+/-4.8 micromol/kg per minute during phenylephrine, P<.05); however, this was proportional to the increased insulin concentrations; therefore, insulin sensitivity was unchanged. MCRinsulin and plasma insulin concentrations were not affected by angiotensin II; however, glucose utilization increased to 51+/-2.7 micromol/kg per minute (P<.01 versus placebo), indicating insulin sensitivity was increased. MCRinsulin was unaffected by isoproterenol. Thus, alpha-adrenergic stimulation but not increased BP per se is a potent regulator of insulin clearance and plasma insulin concentrations.

Adrenergic alpha-Agonists↗
PubMed1998

The distribution of heartwater in the highveld of Zimbabwe, 1980-1997.

Heartwater, the tick-borne disease caused by the rickettsia Cowdria ruminantium has historically been confined to the southern and western lowvelds of Zimbabwe. Since 1986, however, cases of heartwater have been diagnosed with increasing frequency in the central and eastern regions of the previously heartwater-free highveld plateau. During the same period, collections of the two major tick vectors of heartwater in Zimbabwe, Amblyomma hebraeum and Amblyomma variegatum, were made for the first time in these areas, suggesting that spread of these ticks was responsible for the changed distribution of the disease. The factors associated with this spread have not been determined, but increased cattle and wildlife movement and reduced intensity of dipping undoubtedly play important roles. Currently, the distribution of heartwater and its vectors in the highveld is still largely restricted to the central and eastern regions. The northern regions of the highveld appear to be predominantly uninfected, though it is likely that, eventually, heartwater will spread further with considerable impact on livestock production in Zimbabwe.

Animals↗