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Biomedical subjects

S Heath

Publications and source records attributed to S Heath.

At least 19 recordsLinked to original sources
PubMed2000

Monitoring Piscirickettsia salmonis by denaturant gel electrophoresis and competitive PCR.

Reported strains of Piscirickettsia salmonis, a pathogen of salmonid fishes, were analyzed by amplifying part of the internal transcribed spacer (ITS) of the ribosomal RNA (rRNA) operon followed by denaturing gradient gel electrophoresis (DGGE) of the amplicons. All amplified fragments differing in sequence were distinguished by migration during DGGE. A simpler format, constant denaturant gel electrophoresis (CDGE), allowed the same diagnostic distinctions among strains. Sampling during 1997 and 1998 of salmonids from 5 different sites on and near Chiloé Island in southern Chile displaying piscirickettsiosis revealed only P. salmonis resembling LF-89, the type strain first isolated in 1989. These observations are encouraging for control strategies, which might otherwise be compromised by unpredictable shifts of P. salmonis types in salmon farms. A competitive PCR assay offered insight about the power of PCR for quantification and about specific tissue invasiveness by this intracellular pathogen. This approach revealed that the PCR could amplify approximately 1 to 10 P. salmonis genome equivalents against a background of > 99.9% salmonid DNA. It also raised the possibility that the salmonid brain is an important site for P. salmonis survival, with its bacterial load in 1 individual having been about 100 times the loads observed in liver and kidney. Pathogen detection by competitive PCR in a surface seawater sample from a netpen in use indicated a density of about 3000 to 4000 P. salmonis cells (or their DNA remnants) 1(-1). Such quantitative estimates should aid decisions about disease prevention and management as, for example, choice of netpen sites following fallow periods and certification of ova, which are known conduits of infection.

Animals↗
PubMed2000

Treatment of separation anxiety in dogs with clomipramine: results from a prospective, randomized, double-blind, placebo-controlled, parallel-group, multicenter clinical trial.

The efficacy and tolerability of clomipramine in the treatment of separation anxiety in dogs was tested in a prospective, randomized, double-blind, placebo-controlled, parallel-group, international multicenter clinical trial. For a diagnosis of separation anxiety, dogs had to exhibit at least one of the following signs in the absence of their owner: destruction, defecation, urination and/or vocalization, as well as the behaviour suggestive of "hyper-attachment" to their owner. A total of 95 dogs were randomized to receive one of the three treatments for 2-3 months: "standard-dose" clomipramine (1 to <2 mg/kg, PO, q. 12 h); "low-dose" clomipramine (0.5 to <1 mg/kg, PO, q. 12 h); and placebo (PO, q. 12 h). All dogs received behavioural therapy. Dogs were examined at four time points (days 0, 28, 56 and 84) after the initiation of therapy. Improvement in each dog's behaviour at days 28, 56 and 84 was evaluated in comparison to its behaviour at day 0.The results showed that, compared to placebo, dogs receiving standard-dose clomipramine were rated improved at least three times faster for the signs destruction, defecation and urination. At most time points, more dogs in the standard-dose clomipramine group were rated improved for the signs destruction, defecation and urination, and in an owner's global assessment of the dog's overall behaviour (p<0.05 at certain time points). However, there were no statistically significant differences at any time point between the standard dose and the placebo groups in the sign vocalization. The low-dose clomipramine group produced no statistically significant effect when compared with placebo. Mild and transient vomiting was noted as a side effect of clomipramine in a small number of dogs.It is concluded that addition of standard-dose (1 to <2 mg/kg, PO, q. 12 h) clomipramine to conventional behavioural therapy for 2-3 months ameliorated the signs of separation anxiety in dogs.

Journal Article↗
PubMed1999

Transgene expression and repression in transgenic rats bearing the phosphoenolpyruvate carboxykinase-simian virus 40 T antigen or the phosphoenolpyruvate carboxykinase-transforming growth factor-alpha constructs.

Transgenic Sprague-Dawley rats expressing either human transforming growth factor-alpha (TGFalpha) or simian virus 40 large and small T antigen (TAg), each under the control of the phosphoenolpyruvate carboxykinase (PEPCK) promoter, were developed as an approach to the study of the promotion of hepatocarcinogenesis in the presence of a transgene regulatable by diet and/or hormones. Five lines of PEPCK-TGFalpha transgenic rats were established, each genetic line containing from one to several copies of the transgene per haploid genome. Two PEPCK-TAg transgenic founder rats were obtained, each with multiple copies of the transgene. Expression of the transgene was undetectable in the TGFalpha transgenic rats and could not be induced when the animals were placed on a high-protein, low-carbohydrate diet. The transgene was found to be highly methylated in all of these lines. No pathological alterations in the liver and intestine were observed at any time (up to 2 years) during the lives of these rats. One line of transgenic rats expressing the PEPCK-TAg transgene developed pancreatic islet cell hyperplasias and carcinomas, with few normal islets evident in the pancreas. This transgene is integrated as a hypomethylated tandem array of 10 to 12 copies on chromosome 8q11. Expression of large T antigen is highest in pancreatic neoplasms, but is also detectable in the normal brain, kidney, and liver. Mortality is most rapid in males, starting at 5 months of age and reaching 100% by 8 months. Morphologically, islet cell differentiation in the tumors ranges from poor to well differentiated, with regions of necrosis and fibrosis. Spontaneous metastasis of TAg-positive tumor cells to regional lymph nodes was observed. These studies indicate the importance of DNA methylation in the repression of specific transgenes in the rat. However, the expression of the PEPCK-TAg induces neoplastic transformation in islet cells, probably late in neuroendocrine cell differentiation. T antigen expression during neoplastic development may result in a pervasive change in the islet cell growth properties with selection of a transformed phenotype as a possible requirement for cell viability.

Animals↗
PubMed1999

Helminth parasites of the wild rabbit Oryctolagus cuniculus near Malham Tarn, Yorkshire, UK.

Between 1992 and 1996, 95 rabbits from the immediate locality of Malham Tarn, North Yorkshire, UK were examined for the presence of helminth parasites. All the examinations took place in late September or October. Three species of nematodes, Graphidium strigosum, Passalurus ambiguus and Trichostrongylus retortaeformis and two species of cestodes, Taenia pisiformis and Cittotaenia pectinata were identified. There were no associations between helminth species richness and year of sampling, host weight or sex. A logistic model was fitted to the prevalence data from these helminths as was an over-dispersed Poisson model to the worm burden data. Graphidium strigosum was the most frequently identified species with an average prevalence of 78%. The mean prevalence and intensity of Graphidium infection were significantly effected by sampling year. The lower than normal rainfall recorded at the Tarn during the years 1995 and 1996 may have be one reason for this pattern. The worm burden of G. strigosum was significantly positively associated with rabbit body weight. The intensity of infection with P. ambiguus was significantly higher in female rabbits. There was a significant non-linear relationship between P. ambiguus worm burden and rabbit weight (P = 0.002) with worm burdens being highest in the 1000 g to 1499 g weight cohort. Trichostrongylus retortaeformis was only identified in 1994 and male rabbits harboured significantly higher worm burdens than females (48 vs. 7, P = 0.022). Over the five years, the average Taenia pisiformis prevalence was 31% and there was a significant positive association between worm burden and rabbit weight (P = 0.001). Cittotaenia pectinata had a prevalence of 37% over the whole study period with no interactions between prevalence or intensity and body weight, year of sampling or rabbit sex. All five helminths showed an overdispersed distribution with k values less than 1.

Animals↗
PubMed1998

The mechanism of thioacetamide-induced apoptosis in the L37 albumin-SV40 T-antigen transgenic rat hepatocyte-derived cell line occurs without DNA fragmentation.

The hepatotoxicant thioacetamide (TH) has classically been used as a model to study hepatic necrosis; however, recent studies have shown that TH can also induce apoptosis. In this report we demonstrate that 2.68+/-0.54% of the albumin-SV40 T-antigen transgenic rat hepatocytes undergo TH-induced apoptosis, a level comparable to other in vivo models of liver apoptosis. In addition, TH could induce apoptosis and necrosis in the L37 albumin-SV40 T-antigen transgenic rat liver-derived cell line. Examination of dying L37 cells treated with 100 mM TH by electron microscopy revealed distinct morphological characteristics that could be attributed to apoptosis. Quantitation of apoptosis by FACS analysis 24 h after treatment with 100 mM TH revealed that 81.3+/-1.6% of the cells were undergoing apoptosis. In contrast, when L37 cells were treated with 250 mM TH, cells exhibited characteristics consistent with necrotic cell death. DNA fragmentation ladders were produced by growth factor withdrawal-induced apoptosis; however, in 100 mM TH-induced apoptosis, DNA fragmentation ladders were not observed. Analysis of endonuclease activity in L37 cells revealed that the enzymes were not inactivated in the presence of 100 mM TH. The data presented in this report indicate that the L37 cell line could be used to study the mechanism of TH-induced apoptosis that was not mediated through a mechanism requiring DNA fragmentation.

Albumins↗
PubMed1997

Differential behavioral responses to dopaminergic stimulation of nucleus accumbens subregions in the rat.

The following experiments investigated the behavioral response to local microinfusion of dopamine (DA) and selective DA agonists into the core and shell subregions of the nucleus accumbens. Rats were implanted with chronic indwelling cannulae aimed at these subregions. Two experiments were conducted. In experiment 1, the response to DA (0, 2, 5, 10 microg/0.5 microl/side), the D-1 agonist SKF-82598 (0, 0.1, 1.0 microg), the D-2/3 agonist quinpirole (0, 1, 5, 15 microg) and the D-3 preferring agonist pramipexole (0.1, 1.0, 10.0 microg) was examined in photocell activity cages. Locomotor (horizontal) and rearing (vertical) activities were measured. DA and SKF-82958 induced relatively greater increases in activity following stimulation of the shell as compared with the core. Quinpirole induced a dose-dependent suppression of activity after infusion into both sites, although the core was more sensitive to the suppressive effect than the shell. Pramipexole induced time-dependent, biphasic effects that were small in magnitude and did not differentiate between site. In experiment 2, an observation procedure was used to record behaviors (locomotion, rearing, feeding, drinking). Dopamine (0, 2, 10 microg) elicited greater increases in rearing and feeding behavior in the shell than in the core. SKF-82958 (0, 0.75 microg) enhanced locomotion and rearing to a similar extent in both subregions in this test, whereas a mixture of a low dose (0.25 microg) of the D-1 and D-2 agonists selectively induced behavioral activation in the shell. In contrast to the results in the activity cage test, quinpirole (0, 1, 5 microg) increased motor activity at the lower dose when infused into the shell but not into the core. No alterations in feeding were observed following infusion of selective agonists, and no changes in drinking were found with any of the treatments. In summary, the shell appears to be relatively more sensitive to the motor activating effects of DA agonists than the core. Moreover, circuits associated with shell may be preferentially involved in feeding.

Animals↗
PubMed1996

Pseudomeningocele/CSF fistula in a patient with lumbar spinal implants treated with epidural blood patch and a brief course of closed subarachnoid drainage. A case report.

STUDY DESIGN: This case report illustrates the development of a cerebrospinal fluid fistula and pseudomeningocele in a patient after lumbar discectomy and fusion with instrumentation. OBJECTIVE: The patient is treated successfully with a combined treatment protocol of epidural blood patch and brief course of spinal drainage. SUMMARY OF BACKGROUND DATA: Many surgeons advocate a trial of cerebrospinal fluid diversion for postoperative cerebrospinal fluid fistula. This treatment may be problematic in patients with spinal implants because a trial of cerebrospinal fluid diversion may not obliterate the extradural anatomic dead space that is created by instrumentation procedures and increases the rist of infection. A few case reports indicate that epidural blood patch also may be an effective management technique. A combined treatment protocol that may offer some advantages to either treatment alone is described METHODS: The patient was brought to the radiology department, and a lumbar spinal drain was placed at the L2-L3 interspace under fluoroscopic guidance with the patient in the prone position. A Tuohy needle was inserted into the pseudomeningocele, and the collection was drained. Thirty milliters of blood drawn from an antecubital vein was injected into the epidural space over the laminectomy site. Spinal drainage was continued for 4 days. RESULTS: The treatment protocol resulted in resolution of cerebrospinal fluid leakage in the patient. This result was confirmed by myelogram. CONCLUSIONS: Postoperative pseudomeningocele and cerebrospinal fluid fistula in patients with spinal instrumentation can be treated successfully with epidural blood patch and a brief course (4 days) of spinal drainage. This combined treatment protocol may have some advantages to treatment with 7 days of cerebrospinal fluid diversion or to percutaneous epidural blood patch alone.

Adult↗
PubMed1996

Cancer rehabilitation for children: a model with potential.

The dramatic improvements in the treatment of children's cancers has lead to the identification of a growing need for the development of comprehensive rehabilitation programmes. These programmes should include help in learning to live with cancer, and maximize levels of independence for the child with cancer and their family. In this paper, the author will demonstrate the potential for childhood cancer rehabilitation, highlighting factors already in place and those areas that could benefit from development.

Activities of Daily Living↗
PubMed1995

The effects of calcitonin on serum calcium levels in immature brown trout, Salmo trutta.

Salmon calcitonin was administered intraperitoneally (0.1, 10, 1000 ng/100 g of fish) to freshwater-adapted, immature, female brown trout, Salmo trutta, and changes in serum calcium levels were determined. The lowest dose (0.1 ng) had an effect similar to injection of saline (control), but the higher doses produced hypercalcemia. These latter effects were associated with increased serum levels of calcitonin. Maintaining immature brown trout in waters containing 20 and 50 mM calcium chloride resulted in a significant lowering of serum calcitonin with time although serum calcium levels remained stable. The extent of the decrease in serum calcitonin increased with the higher levels of environmental calcium.

Aging↗
PubMed1993

A partial cDNA clone of trypomastigote decay-accelerating factor (T-DAF), a developmentally regulated complement inhibitor of Trypanosoma cruzi, has genetic and functional similarities to the human complement inhibitor DAF.

Resistance to complement-mediated lysis in Trypanosoma cruzi is due to the expression of complement-regulatory factors by the virulent developmental forms of this protozoan parasite. An 87- to 93-kDa molecule, which we have termed T-DAF (trypomastigote decay-accelerating factor), is present on the surface of the parasite and inhibits complement activation in a manner functionally similar to the mammalian complement regulatory component, decay-accelerating factor. In this report, we characterized monospecific polyclonal and monoclonal antibodies which were obtained from mice and rabbits immunized with fast protein liquid chromatography-purified T-DAF. These polyclonal antibodies were shown to inhibit T-DAF activity and were capable of inducing lysis of the parasites. Both the polyclonal and monoclonal antibodies were used to screen a cDNA expression library prepared from T. cruzi trypomastigote mRNA. From this library, we obtained a partial lambda gt11 cDNA clone which showed genetic and functional similarity to the human C3 convertase inhibitor DAF (A. Nicholson-Weller, J. Burge, D. T. Fearon, P. F. Weller, and K. F. Austen, J. Immunol. 129:184-189, 1982).

Amino Acid Sequence↗
PubMed1993

Attitudes of private general practitioners towards health care in South Africa.

The need for health care reform in South Africa is acknowledged by the government as well as by the non-governmental health sector. There is, however, no unanimity regarding the nature of the envisaged reform. A country-wide postal survey of 700 private sector general practitioners (GPs) from a commercial database of 5,000 was conducted to explore attitudes towards health care. A response rate of 67.4% was obtained. Respondents were mostly male (92%) and urban-based (64%). The median age was 42 years. Most respondents: (i) believed health care to be a right for all citizens; (ii) favoured private or a combination of private and public funding mechanisms with fee-for-service arrangements; (iii) opposed cost-containment measures imposed by funders, e.g. medical aids; and (iv) believed doctors should be responsible for primary care in under-served areas. After sex, age, location (urban versus rural) and GP postgraduate qualification had been controlled for by means of logistic regression techniques, the university at which a respondent's basic degree was obtained emerged as the only independent predictor of attitudes to the following: (i) comprehensive care as a right; (ii) integration of the public and private sectors; (iii) preferred funding source for a future health system; and (iv) preference for fee-for-service remuneration. Both university and gender independently predicted attitudes on GPs' income. Graduates of white, Afrikaans-medium universities were strongly in favour of a privately funded and fee-for-service orientated system. Those who qualified at black universities, on the other hand, favoured public funding with less emphasison fee-for-service.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Genes selectively expressed in the infectious (metacyclic) stage of Leishmania major promastigotes encode a potential basic-zipper structural motif.

Complementary DNA clones representing transcripts selectively expressed in the non-dividing, infective (metacyclic) stage of Leishmania major promastigotes (MP) were identified by differential and subtractive screening. The majority of the selected clones hybridized on Northern blots to a set of transcripts highly expressed by MP, but to a much lower extent in proliferating and stationary-phase attenuated promastigotes. Stationary, but not log-phase cultures, of each of 5 L. major strains showing a potential for differentiation to metacyclics, expressed these transcripts (MAT-1; MP-associated transcripts). From sequence analysis of full-length cDNA clones corresponding to the predominating MAT-1 species, an open reading frame encoding a 139 aa polypeptide (15.4 kDa) was predicted and supported by immunoprecipitation by kala-azar sera of reticulocyte extract translation products using in vitro transcribed RNA. Although no significant primary sequence homology to database nucleic acid and protein sequences was found, the sequence displays similarities to the basic-zipper families of transcription regulatory proteins.

Amino Acid Sequence↗
PubMed1991

Women doctors in South Africa. A survey of their experience and opinions.

The proportion of women entering medical school has increased at some faculties but remains at around 20% at others. A postal survey of 2,626 women on the Medical Register of the South African Medical and Dental Council was conducted to investigate aspects related to their work. Fifty-five per cent responded, with a possible bias towards older doctors and graduates from Afrikaans-language faculties. Although a significant majority (86.5%) are in practice, about one-third (33.4%) are employed part-time and nearly one-third (29.4%) reported that they had experienced an interruption of their careers for periods of more than 5 years. Major factors relating to this wastage of medical resources identified by this study were the women's dual responsibility at home and at work, the one-time joint taxation system and discrimination in the workplace, in particular with regard to housing loans. Few women find their way into specialist practice (10.8%) [corrected], although 68.2% indicated that they would have liked to specialise. Home responsibilities (48.2%) and the structure of the curriculum (31.5%) were the commonly reported difficulties experienced with further study. In addition, the lack of part-time training and the geographical location of such facilities also played a role.

Adult↗
PubMed1991

Characterization of a programmed alteration in an 18S ribosomal gene that accompanies the experimental induction of drug resistance in Schistosoma mansoni.

Stable resistance to the anthelmintic hycanthone can be produced in the human blood fluke Schistosoma mansoni by exposing immature parasites in mice to the drug. Within a single generation, genomic rearrangements, detected as rRNA-encoding DNA restriction fragment length polymorphisms (RFLPs), accompany the appearance of resistance in this model. One of these RFLPs, an approximately 3.6-kilobase BamHI fragment, was shown previously to associate consistently with resistance in independent generations of the JHU strain of S. mansoni. To characterize the genetic changes responsible for this RFLP, the fragment was cloned and sequenced. A comparison of the cloned fragment with a normal 18S rRNA gene demonstrated that the drug resistance-associated RFLP fragment arises through the addition of 732 base pairs into an 18S rRNA gene, 134 base pairs downstream of the junction of the intergenic spacer and the mature 18S rRNA gene. The mutation is nonrandom, targets one, or a few only, of the 100 or so copies of the ribosomal genes, and may represent the incomplete duplication of the gene since the inserted element is identical in sequence to the region contiguous to it. The sequence spanning the junction of the insertion and the original 18S rRNA gene was used as a specific primer for the BamHI RFLP in PCR experiments. The analysis conclusively demonstrated that the mutation is induced rather than selected by the drug since the junctional sequence was not detectable in the drug-sensitive parent population of schistosomes. In addition, analysis of four, independently derived, resistant lines indicated that the same region of the gene was mutated each time. Together, these data demonstrate that reproducible changes are induced during the acquisition of resistance in schistosomes and suggest that the resistant phenotype is induced rather than selected from preexisting forms.

Animals↗