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Biomedical subjects

L Blackwood

Publications and source records attributed to L Blackwood.

At least 19 recordsLinked to original sources
PubMed2006

Long-term survival after combination chemotherapy for bilateral renal malignant lymphoma in a dog.

CASE HISTORY: A 6-year-old, entire male Flat-coated Retriever was presented with a history of lethargy, polydipsia and seizures. Clinical chemistry had shown marked azotaemia. CLINICAL FINDINGS AND DIAGNOSIS: Radiography and ultrasonography revealed bilateral renomegaly, and cytology of fine needle aspirates from the kidneys was diagnostic of malignant lymphoma. The dog was treated with a modified high-dose cyclophosphamide-, vincristine-, and prednisolone-based chemotherapy protocol, achieved remission, and returned to normal quality of life. Survival time was 346 days from the time of diagnosis. CLINICAL RELEVANCE: Malignant lymphoma in the kidneys of dogs has been considered to carry a uniformly poor prognosis. Long-term remission after medical treatment has not previously been reported. The favourable outcome in this case illustrates the limitations of clinical staging in determining the outcome for individual patients.

Animals↗
PubMed2005

Somatic mutations of the thyroid-stimulating hormone receptor gene in feline hyperthyroidism: parallels with human hyperthyroidism.

Hyperthyroidism is the most common endocrinopathy in cats, and is both clinically and histopathologically very similar to human toxic nodular goitre (TNG). Molecular studies on human TNG have revealed the presence of mis-sense mutations in the thyroid-stimulating hormone receptor (TSHR) gene, most frequently in exon 10. Our hypothesis was that similar mutations exist in hyperthyroid cats. Genomic DNA was extracted from 134 hyperplastic/adenomatous nodules (from 50 hyperthyroid cats), and analysed for the presence of mutations in exon 10 of the TSHR gene. 11 different mutations were detected, one silent and 10 mis-sense, of which nine were somatic mutations. 28 of the 50 cats (67/134 nodules) had at least one mis-sense mutation. The mis-sense mutations were Met-452-->Thr in 17 cats (35 nodules), Ser-504-->Arg (two different mutational forms) in two cats (two nodules), Val-508-->Arg in one cat (three nodules), Arg-530-->Gln in one cat (two nodules), Val-557-->Leu in 13 cats (36 nodules), Thr-631-->Ala or Thr-631-->Phe (each mutation seen in one nodule of one cat), Asp-632-->Tyr in six cats (10 nodules) and Asp-632-->His in one cat (one nodule). Five of these mutations have been associated previously with human hyperthyroidism. Of the 41 cats for which more than one nodule was available, 14 had nodules with different mutations. The identification of a potential genetic basis for feline hyperthyroidism is novel, increases our understanding of the pathogenesis of this significant feline disease, and confirms its similarity to TNG.

Animals↗
PubMed2004

Glucose self-monitoring in primary care: a survey of current practice.

BACKGROUND: The role of long-term glycaemic control in minimizing long-term complications of diabetes mellitus is evidence-based and national guidelines recommend a target glycosylated haemoglobin level of approximately 7%. Although the role of self-monitoring blood and urine glucose is less well defined, this activity consumes vast National Health Service (NHS) resources. AIMS: The aims of this study were to (i) determine the current practice of glucose self-monitoring in primary care, (ii) determine any changes to therapy made as a result and (iii) compare monitoring and frequency of monitoring in those patients using insulin with those patients taking oral hypoglycaemic agents. METHODS: Postal questionnaire to 311 patients using insulin or oral hypoglycaemic agents identified from three general practices. RESULTS: The response rate was 59.8% (186/311), with the majority of responding patients (n = 158, 87.3%) performing self-monitoring. The patients using insulin were more likely to be self-monitoring than those taking oral therapy (chi(2), P < 0.001, d.f. = 1). The majority of patients who self-monitored and were using insulin (n = 45, 61.1%) altered the dose of insulin if a reading was beyond their target range. However, the majority of patients who self-monitored and were taking oral therapy (n = 48, 68.6%) took no action at all. CONCLUSIONS: Blood glucose self-monitoring was common in those treated with insulin or oral hypoglycaemics, although those using insulin were more likely to self-monitor. Notably many patients, particularly those on oral therapy, took no action based on the results of self-monitoring.

Administration, Oral↗
PubMed2004

Multicentric lymphoma in a dog after cyclosporine therapy.

An 11-year-old, neutered male German shepherd dog was presented with perianal ulceration and fistulas. A clinical diagnosis of anal furunculosis was made, and the dog was treated with cyclosporine and ketoconazole. The perianal lesions resolved. However, after four weeks of therapy the dog developed multicentric lymphoma. Complete remission was achieved with combination chemotherapy (Wisconsin-Madison protocol). Cyclosporine administration is associated with an increased risk of development of lymphoma in humans and a similar increased risk might be expected in dogs. Although a causative relationship between cyclosporine administration and the development of lymphoma cannot be proven in this case, it is possible that cyclosporine therapy may have contributed to lymphomagenesis. As the use of cyclosporine in small animals is increasing, further work is required to substantiate and quantify the proposed increased risk.

Animals↗
PubMed2002

Feline hyperthyroidism: advances towards novel molecular therapeutics.

Feline hyperthyroidism is the most common endocrine disorder of the elderly cat. Traditionally, the disease is treated by surgical thyroidectomy, medical management with antithyroid drugs or radiation therapy using iodine-131. However, none of these treatments is ideal and molecular therapeutics may offer novel methods of treating the disease. This article reviews the background of, and preliminary investigations into, the development of a transcriptionally targeted somatic gene therapy strategy for the treatment of this feline condition.

Animals↗
PubMed2001

Characterization of the feline thyroglobulin promoter.

The feline thyroglobulin promoter was identified by a combination of standard polymerase chain reaction (PCR) techniques, using primers designed according to regions of homology in published sequences from other species, then adaptor ligated PCR. A 310 bp fragment of the feline thyroglobulin promoter was generated, including 8 nucleotides of adaptor sequence at the 5' end and, based on the putative transcription start site, 36 nucleotides of the thyroglobulin mRNA (untranslated portion). The homology between the feline promoter sequence (from 193 bp upstream to the putative cap site) and canine, bovine and human sequences was 89%, 81% and 78%, respectively. Transient transfection studies, using reporter constructs in which the feline promoter controlled expression of chloramphenicol acetyl transferase, demonstrated promoter activity in thyroid cells, but no activity in non-thyroid cells. The data presented here demonstrate that the feline thyroglobulin promoter may provide a targeting mechanism for somatic gene therapy of feline thyroid disease.

Animals↗
PubMed2001

E. coli nitroreductase/CB1954: in vitro studies into a potential system for feline cancer gene therapy.

Investigations were carried out to identify a suitable prodrug activating system for feline gene therapy with the eventual aim of treating feline thyroid disease and feline neoplasia. The E. coli nitroreductase (NTR)/CB1954 prodrug activating system was evaluated in vitro in feline cells by transient transfection with a nitroreductase expressing construct and subsequent treatment with the prodrug CB1954. The feline cells successfully expressed E. coli nitroreductase, which was able to activate the prodrug CB1954 resulting in cytotoxicity to both transformed and adjacent cells (a bystander effect) in vitro. In the absence of nitroreductase, CB1954 was non-toxic to feline cells. In addition, the nitroreductase gene was expressed in rat thyroid cells under the control of the cell type specific feline thyroglobulin promoter. This paper demonstrates that the E. coli nitroreductase/CB1954 system may be suitable for in vivo feline gene therapy, and further investigations are warranted.

Animals↗
PubMed1997

Evidence for channeling of intermediates in the oxidative pentose phosphate pathway by soybean and pea nodule extracts, yeast extracts, and purified yeast enzymes.

Evidence is presented that intermediates of the oxidative pentose phosphate pathway (OPPP) are channeled from one pathway enzyme to the next. CO2 produced from [1-14C]glucose in the presence of unlabelled pathway intermediates contained much more radioactivity than predicted by a model in which pathway-produced intermediates are in equilibrium with identical molecules in the bulk phase. This was the case whether glucose 6-phosphate (Glc6P), 6-phosphogluconolactone, or 6-phosphogluconate was added. Assumptions involved in calculating the amount of 14CO2 predicted for free mixing of 14C-labelled and unlabelled intermediates are discussed, together with the following results. (a) 14CO2 production by pea nodules in the presence of 3 mM 6-phosphogluconate was higher than in its absence. (b) Apparent channeling of intermediates was much higher for purified yeast enzymes than for yeast extract. (c) 6-Phosphogluconate and 6-phosphogluconolactone were channeled between yeast Glc6P dehydrogenase and 6-phosphogluconate dehydrogenase despite the absence of 6-phosphogluconolactonase in the purified yeast enzyme mixture. (d) When purified yeast hexokinase was physically separated from Glc6P dehydrogenase and 6-phosphogluconate dehydrogenase by a dialysis membrane, there was no apparent channeling. (e) Poly(ethylene glycol), high salt and detergents had little effect on apparent channeling of OPPP intermediates, which is consistent with a stable complex of enzymes. On the other hand, density gradient centrifugation experiments suggested a more transient interaction between the enzymes. Taken together, the results support channeling of OPPP pathway intermediates.

Carbon Radioisotopes↗
PubMed1997

Radiographic abnormalities in canine multicentric lymphoma: a review of 84 cases.

The thoracic and abdominal radiographs of 84 dogs with multicentric lymphoma were examined to identify the radiological abnormalities. The frequency of occurrence of individual changes, role of radiography in diagnosis, relationship of radiographic changes to hypercalcaemia and prognostic relevance of radiographic findings were assessed. Multiple abnormalities were more commonly seen than solitary changes. No radiographic abnormalities were seen in approximately one quarter of thoracic radiographs and one fifth of abdominal radiographs. Lymphoma could not be diagnosed on the basis of radiographs alone. Many of the features of lymphoma were non-specific, having numerous possible causes. Cranial mediastinal disease was neither a prerequisite for, nor a disproportionately common finding in, hypercalcaemic patients. The absence of radiological abnormalities may be a positive prognostic indicator for the individual patient. The differential diagnoses for the radiographic abnormalities seen in lymphoma are discussed.

Abdomen↗
PubMed1996

Radiotherapy of oral malignant melanomas in dogs.

OBJECTIVE: To evaluate response to radiotherapy in dogs with oral malignant melanomas. DESIGN: Clinical trial. ANIMALS: 36 dogs with histologically confirmed oral malignant melanomas. PROCEDURE: The prescribed radiation dose was 36 Gy given in 4 fractions of 9 Gy at 7-day intervals. The primary radiation source was a linear accelerator. RESULTS: In 25 of 36 dogs, complete remission was achieved, and in 9 dogs, partial remission was achieved. Recurrence of the primary tumor was the cause of euthanasia of 4 dogs. Twenty-one dogs were euthanatized because of metastasis. CLINICAL IMPLICATIONS: Radiotherapy was an effective palliative treatment for the primary tumor in dogs with oral malignant melanomas. However, rapid development of metastatic disease remained a major challenge.

Animals↗
PubMed1991

Epitopes of human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins recognized by antibodies in the sera of HIV-1-infected individuals.

Sera from human immunodeficiency virus (HIV)-infected study subjects and controls were analyzed by enzyme-linked immunosorbent assay using 10 synthetic peptides to identify epitopes of HIV envelope glycoproteins (ENVgp) that were recognized by antibodies. Two epitopes of HIV ENVgp, ENVP466 (amino acids 466-481) and ENVP497 (amino acids 497-509), were recognized by antibodies in the sera of most HIV-infected individuals. The frequency of individuals with detectable serum antibodies to these two epitopes was not associated with the stage of HIV disease. Purified antibodies to ENV497 had only very weak neutralizing activity against infectious HIV. These data suggest that a particular dominant type of antibody response to HIV's ENVgp has minimal protective effects. These and other studies to identify and stimulate immune responses to selected epitopes of HIV antigens may be useful in the design of vaccines to prevent or treat HIV infections.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Latent variable models for the analysis of medical data with repeated measures of binary variables.

Consideration of within-subject dependencies is a key issue in modelling binary repeated measures medical data. Borrowing from recent developments in sociology and psychology, we demonstrate the applicability of a latent variable approach to the analysis of such data. In particular we present the Rasch model as a basic model for representing the relationship of subject and treatment parameters. The latent variable approach is useful in providing a theoretical framework for specifying dependencies exactly and also as a base for considering more complicated relationships between repeated measures variables.

Attitude to Health↗
PubMed1988

Effects of interleukin 2 and large envelope glycoprotein (gp 120) of human immunodeficiency virus (HIV) on lymphocyte proliferative responses to cytomegalovirus.

Lymphocytes from many HIV-infected asymptomatic individuals or patients with AIDS-related conditions (ARC) and from all AIDS patients were unable to proliferate in vitro in response to UV-inactivated cytomegalovirus (CMV). The addition of recombinant IL2 (rIL2) restored proliferative responses of lymphocytes from most HIV-infected asymptomatic individuals and ARC patients to levels similar to those of HIV-seronegative (HIV-) CMV-seropositive (CMV+) individuals. In contrast, rIL2 augmented CMV-specific lymphocyte proliferation of only 33% (6/18) of AIDS patients. Proliferative responses to CMV with or without rIL2 did not correlate well with the levels of CD4+ lymphocytes, HIV antigen levels or ratios of CD4+ and CD8+ lymphocytes. Proliferative responses to CMV were inhibited by relatively high concentrations (greater than or equal to 10 micrograms/ml) of recombinant HIV envelope glycoprotein (rgp120) and this immunosuppression was completely overcome by rIL2. These results indicate that defects in antigen-driven lymphocyte responses of HIV-infected individuals are not simply the result of reduced numbers of CD4+ lymphocytes but are influenced by defects in IL2 pathways and by immunosuppressive effects of HIV gp120.

Acquired Immunodeficiency Syndrome↗
PubMed1983

First aid.

Explore the source record for details and available documents.

Emergencies↗
PubMed1981

Epidemiology of gonorrhoea in native Alaskans.

Data on gonococcal infections confirmed by culture show that the native population of Alaska has an incidence rate many times higher than the other population groups; both sexes and all age groups are affected. In contrast to the remainder of the United States, where gonorrhoea occurs much more often in men, native Alaskan women are as likely to be infected as native Alaskan men.

Adolescent↗