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Biomedical subjects

J Griffiths

Publications and source records attributed to J Griffiths.

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

Attempts to establish experimental Cyclospora cayetanensis infection in laboratory animals.

Attempts were made to develop an animal model for Cyclospora cayetanensis to identify a practical laboratory host for studying human cyclosporiasis. Oocysts collected from stool of infected humans in the United States, Haiti, Guatemala, Peru, and Nepal were held in potassium dichromate solution to allow development of sporozoites. The following animal types were inoculated: 9 strains of mice, including adult and neonatal immunocompetent and immune-deficient inbred and outbred strains, rats, sandrats, chickens, ducks, rabbits, jirds, hamsters, ferrets, pigs, dogs, owl monkeys, rhesus monkeys, and cynomolgus monkeys. Most animals were inoculated by gavage, although some of the primates were fed oocysts on food items. The animals were examined for signs of infection, particularly diarrhea, and stool samples were examined for 4-6 wk after inoculation. None of the animals developed patent infections or signs of infection. We conclude that none of the animals tested is susceptible to infection with C. cayetanensis.

Animals↗
PubMed2000

Elevation of plasma homocysteine levels associated with acute myocardial infarction.

OBJECTIVE: To study the effect of acute myocardial infarction (AMI) on plasma homocystein (Hcy) levels, to determine the optimal time to measure this risk factor for coronary artery disease. DESIGN: A prospective case study. SETTING: The Division of Cardiac Sciences, Grey Nuns Hospital in Edmonton. PATIENTS: Sixty-two patients (40 men, 22 women) admitted to hospital with AMI. INTERVENTION: Measurement of Hcy levels within 48 to 72 hours of admission and at 6 weeks after discharge from the Coronary Care Unit. In a second group of 15 patients, the Hcy levels were measured on hospital days 1 and 3. MAIN OUTCOME MEASURE: Comparison of the Hcy levels measured at the time of AMI and after discharge. RESULTS: Mean (and standard error of the mean) Hcy level measured during the AMI (13.6 [0.98] micromol/L) was significantly higher (p < 0.05) than at 6 weeks (12.1 [1.01] micromol/L). Based on the 48- to 72-hour and 6-week determinations, 31 and 21 patients, respectively, had abnormal Hcy levels (greater than 12 micromol/L) (p < 0.001). In the separate group of 15 patients, the Hcy level measured on day 3 (9.7 [0.6] micromol/L) was noted to be significantly higher (p < 0.01) than on day 1 (7.7 [0.8] micromol/L). CONCLUSIONS: There is an elevation of Hcy during AMI that may be related to an increase in the acute-phase reactant proteins. Thus, Hcy measurement should be deferred for 6 weeks in order to determine the true baseline level.

Acute-Phase Proteins↗
PubMed2000

Analytic solutions to compartmental models of the HIV/AIDS epidemic.

For many years compartmental models have provided useful insights into the spread of epidemics. Such models are usually fairly easy to set up, but even the simpler models have the disadvantage that they are intractable to analytic solution. In this paper we examine models of the HIV/AIDS epidemic, and show that the equations may be linearized in a piecewise manner over time, thus allowing analytic solutions to be obtained. Indications of the usefulness of this approach are provided. In particular, an analytic solution gives insight into the mechanism of the epidemic, together with a clearer picture of the sensitivity of results to changes in parameter values. Further, the processes of parameter estimation and the methodology of back-calculation also benefit from the provision of functional forms for the state variables.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Interleukin-1 beta production in dysthymia before and after pharmacotherapy.

BACKGROUND: Like major depression, dysthymia has been associated with elevated production of interleukin-1 (IL-1 beta) in mitogen-stimulated lymphocytes. In the present investigation, we assessed whether the elevated IL-1 beta production in dysthymic patients would normalize following treatment with sertraline. METHODS: The production of IL-1 beta was determined in dysthymic patients and in nondepressed control subjects. Patients then received 12 weeks of doses of either sertraline or placebo in a double-blind trial, after which cytokine production was again determined. RESULTS: Basal IL-1 beta was elevated in dysthymic patients relative to control subjects. Cytokine production was modestly correlated with the severity of symptoms and with the age of illness onset. Relative to placebo treatment, sertraline attenuated the symptoms of depression; however, this was not accompanied by normalization of IL-1 beta production. CONCLUSIONS: While dysthymia is associated with elevated IL-1 beta production, the failure for the cytokine to normalize following symptom alleviation suggests that either the IL-1 beta may be a trait marker of the illness, or that more sustained treatment is necessary to reduce cytokine production. Given the neuroendocrine and central neurochemical consequences of exogenously administered IL-1 beta, the possibility ought to be explored that increased IL-1 beta production may play a role in the pathophysiology of dysthymia.

Adult↗
PubMed1999

Feasibility of direct discharge from the coronary/intermediate care unit after acute myocardial infarction.

OBJECTIVES: This investigation was designed to determine the feasibility and cost-effectiveness of direct discharge from the coronary/intermediate care unit (CICU) in 497 consecutive patients with an acute myocardial infarction (AMI). BACKGROUND: Although patients with an AMI are traditionally treated in the CICU followed by a period on the medical ward, the latter phase can likely be incorporated within the CICU. METHODS: All patients were considered for direct discharge from the CICU with appropriate patient education. The 6-week postdischarge course was evaluated using a structured questionnaire by a telephone interview. RESULTS: There were 497 patients (men = 353; women = 144; age 63.5 +/- 0.6 years) in the study, with 29 in-hospital deaths and a further 11 deaths occurring within 6 weeks of discharge. The mode length of CICU stay was 4.0 days (mean 5.1 +/- 0.2 days): 1 to 2 (12%), 3 (19%), 4 (21%), 5 (14%), 6 to 7 (19%) and > or = 7 (15%) days, respectively with 87.2% discharged home directly. Of the 425 patients surveyed, 119 (28.0%) indicated that they had made unscheduled return visits (URV) to a hospital or physician's office: 10.6% to an emergency room, 9.4% to a physician's office and 8.0% readmitted to a hospital. Of these URV, only 14.3% occurred within 48 h of discharge. Compared to historical controls, the present management strategy resulted in a cost savings of Cdn. $4,044.01 per patient. CONCLUSIONS: Direct discharge from CICU is a feasible and safe strategy for the majority of patients that results in considerable savings.

Adult↗
PubMed1999

Influence of acute tryptophan depletion on mood and immune measures in healthy males.

Depressive illness has been associated with variations of several aspects of immune functioning, as well as alterations of cytokine production in stimulated lymphocytes. In the present investigation we sought to determine whether pharmacologically-induced reductions of mood in healthy, male subjects would be associated with alterations in the levels of circulating IL-1 beta or IL-6 or to in vitro lymphocyte proliferation in response to T cell mitogens, PHA and Con A. Lowering tryptophan levels by means of a tryptophan-deficient amino acid mixture, which reduced plasma tryptophan and serotonin (5-HT) levels, produced a lowering of mood in a subset of male subjects (that had no personal or family history of depression) relative to subjects that received a balanced amino acid mixture. Correlational analyses revealed that the change of mood (particularly depression and anger) in subjects that received the tryptophan-free mixture was related to the extent of the tryptophan or 5-HT reductions. However, while fenfluramine administration resulted in recovery of tryptophan and 5-HT levels, this was not accompanied by recovery of mood. Furthermore, it was observed that the lowering of tryptophan levels and the reduced mood were not accompanied by variations of the cytokine levels or cell proliferation. Evidently, transient and modest alterations of 5-HT or mood induced by a tryptophan-free amino acid mixture were insufficient to promote variations of immune activity or circulating IL-1 beta or IL-6 levels. Even if depression were related to immune disturbances, the mood and 5-HT alterations associated with this type of manipulation may be too brief to promote immune changes comparable with those ordinarily associated with severe or chronic depressive illness.

Adolescent↗
PubMed1999

An in vitro study of the use of photodynamic therapy for the treatment of natural oral plaque biofilms formed in vivo.

Seven-day oral plaque biofilms have been formed on natural enamel surfaces in vivo using a previously reported in situ device. The devices are then incubated with a cationic Zn(II) phthalocyanine photosensitizer and irradiated with white light. Confocal scanning laser microscopy (CSLM) of the biofilms shows that the photosensitizer is taken up into the biomass of the biofilm and that significant cell death is caused by photodynamic therapy (PDT). In addition, the treated biofilms are much thinner than the control samples and demonstrate a different structure from the control samples, with little evidence of channels and a less dense biomass. Transmission electron microscopy (TEM) of the in vivo-formed plaque biofilms reveals considerable damage to bacteria in the biofilm, vacuolation of the cytoplasm and membrane damage being clearly visible after PDT. These results clearly demonstrate the potential value of PDT in the management of oral biofilms.

Biofilms↗
PubMed1999

31P magnetic resonance spectroscopy as a predictor of efficacy in photodynamic therapy using differently charged zinc phthalocyanines.

Photodynamic therapy (PDT) is a developing approach to the treatment of solid tumours which requires the combined action of light and a photosensitizing drug in the presence of adequate levels of molecular oxygen. We have developed a novel series of photosensitizers based on zinc phthalocyanine which are water-soluble and contain neutral (TDEPC), positive (PPC) and negative (TCPC) side-chains. The PDT effects of these sensitizers have been studied in a mouse model bearing the RIF-1 murine fibrosarcoma line studying tumour regrowth delay, phosphate metabolism by magnetic resonance spectroscopy (MRS) and blood flow, using D2O uptake and MRS. The two main aims of the study were to determine if MRS measurements made at the time of PDT treatment could potentially be predictive of ultimate PDT efficacy and to assess the effects of sensitizer charge on PDT in this model. It was clearly demonstrated that there is a relationship between MRS measurements during and immediately following PDT and the ultimate effect on the tumour. For all three drugs, tumour regrowth delay was greater with a 1-h time interval between drug and light administration than with a 24-h interval. In both cases, the order of tumour regrowth delay was PPC > TDEPC = TCPC (though the data at 24 h were not statistically significant). Correspondingly, there were greater effects on phosphate metabolism (measured at the time of PDT or soon after) for the 1-h than for the 24-h time interval. Again effects were greatest with the cationic PPC, with the sequence being PPC > TDEPC > TCPC. A parallel sequence was observed for the blood flow effects, demonstrating that reduction in blood flow is an important factor in PDT with these sensitizers.

Animals↗
PubMed1999

Endocrine and cytokine correlates of major depression and dysthymia with typical or atypical features.

Depression has been associated with both suppression and enhancement of various aspects of immune functioning. It was of interest to determine whether cytokine alterations associated with depression, including interleukin-1 (IL-1beta) and interleukin-2 (IL-2), were related to the neurovegetative symptom profile or to the chronicity of the illness. Circulating ACTH, cortisol, norepinephrine (NE) and epinephrine levels, and production of IL-1beta and IL-2 from mitogen-stimulated lymphocytes were assessed in classical major depression, atypical depression (ie, with reversed neurovegetative features), and dysthymia (chronic depression without comorbid major depression) with either typical or atypical profiles, as well as nondepressed control subjects. Among atypical depressives, plasma ACTH levels were elevated while cortisol was reduced relative to controls. Irrespective of neurovegetative profile, IL-1beta production was increased in dysthymic patients, and was highly correlated with age-of-onset and duration of illness. In contrast, IL-2 production was reduced in each of the groups, although less so among atypical major depressives. Moreover, IL-2 production in the depressive groups was directly related to plasma NE levels. While neither depressed mood per se nor neurovegetative features accounted for this effect, it seemed likely that chronicity of illness or age-of-onset were associated with cytokine alterations. Given that circulating cytokines influence neuroendocrine functioning, and may affect neurovegetative features, a role for interleukins may exist with respect to the pathophysiology of certain subtypes of depression.

Adrenocorticotropic Hormone↗
PubMed1999

The wider implications of an audit of care plan documentation.

This article describes how the results of an audit of district nursing care plan documentation have been used to inform practice development in a community trust. The principle aim of the audit was to discover whether the evaluation of patient care was being adequately recorded in nursing care plans. To establish this, four commonly occurring areas of district nursing work were selected and an ideal assessment of care developed from the available evidence. The areas were: the management of leg ulceration, bath care, pressure area care and catheter care. Data capture forms were developed to record whether the features of an ideal assessment of these four areas of care were reflected in the written evaluation of that care. The results of the audit demonstrated that the evaluation of care was often inadequately recorded, which reflected poor written documentation of the initial nursing assessment. The implications of the findings of the audit for practice development in the four areas of care are discussed.

Documentation↗
PubMed1999

Treatment of primary dysthymia with group cognitive therapy and pharmacotherapy: clinical symptoms and functional impairments.

OBJECTIVE: This study assessed the efficacy of antidepressant treatment (sertraline) and group cognitive behavior therapy, alone or in combination, in primary dysthymia. The clinical features of dysthymia, as well as the functional impairments associated with the illness (e.g., quality of life, stress perception, coping styles), were evaluated. METHOD: Patients (N = 97) diagnosed with primary dysthymia, but no other current comorbid disorder, received either sertraline or placebo in a double-blind design over 12 weeks. In addition, a subgroup of the patients (N = 49) received a structured, weekly group cognitive behavior therapy intervention. RESULTS: Treatment with sertraline, with or without group cognitive behavior therapy, reduced the functional impairment of depression. The reductions were similar in the drug-cognitive therapy group and in subjects who received the drug alone. Furthermore, while group cognitive behavior therapy alone reduced the depression scores, this effect was not significantly greater than the effect of the placebo. The drug treatment also induced pronounced improvement in the functional measures, and in some respects these effects were augmented by group cognitive behavior therapy. Among patients who responded favorably to cognitive behavior therapy, the improvements in the functional measures were similar to those who responded to drug treatment, whereas such functional changes were not seen among patients who responded to placebo. CONCLUSIONS: Sertraline treatment effectively reduces the clinical symptoms and functional impairments associated with dysthymia. Although the group cognitive behavior therapy intervention was less effective in alleviating clinical symptoms, it augmented the effects of sertraline with respect to some functional changes, and in a subgroup of patients it attenuated the functional impairments characteristic of dysthymia.

Adult↗
PubMed1999

A comparative study of the cellular uptake and photodynamic efficacy of three novel zinc phthalocyanines of differing charge.

Three novel substituted zinc (II) phthalocyanines (one anionic, one cationic and one neutral) were compared to two clinically used photosensitizers, 5,10,15,20-tetra(m-hydroxyphenyl)chlorin (m-THPC) and polyhematoporphyrin (PHP), as potential agents for photodynamic therapy (PDT). Using the RIF-1 cell line, photodynamic efficacy was shown to be related to cellular uptake. The cationic phthalocyanine (PPC, pyridinium zinc [II] phthalocyanine) had improved activity over the other two phthalocyanines and slightly improved activity over PHP and m-THPC. The initial subcellular localization of each photosensitizer was dependent upon the hydrophobicity and plasma protein binding. The phthalocyanines had a punctate distribution indicative of lysosomes, whereas m-THPC and PHP had a more diffuse cytoplasmic localization. A relocalization of phthalocyanine fluorescence was observed in some cases following low-level light exposure, and this was charge dependent. The anionic phthalocyanine (TGly, tetraglycine zinc [II] phthalocyanine) relocalized to the nuclear area, the localization of the hydrophobic phthalocyanine (TDOPc, tetradioctylamine zinc [II] phthalocyanine) was unchanged, whereas the distribution of the cationic phthalocyanine (PPC) became more cytoplasmic. This suggests that relocalization following low-level irradiation is a critical factor governing efficacy, and a diffuse cytoplasmic distribution may be a determinant of good photodynamic activity.

Animals↗
PubMed1998

Vibrio viscosus in farmed Atlantic salmon Salmo salar in Scotland: field and experimental observations.

Winter mortality occurred in market-sized (2 to 3 kg) Atlantic salmon Salmo salar reared in sea cages in Scottish waters. Many of the fish had skin ulcers. Internally prominent dark-brown petechiae or ecchymotic haemorrhage was observed. Splenomegaly was associated with congestion and widespread necrosis. A Vibrio sp. was isolated from internal organs. Biochemically isolates of the bacterium were similar to a previously described bacterium, Vibrio viscosus, recorded in a phenotypic study from farmed salmon in Norway. This work examines the occurrence of V. viscosus in marine-reared Atlantic salmon for the first time in Scottish waters. An experimental study reproduced the field observations and Koch's postulates were fulfilled. The histopathology associated with natural infection was compared with that in laboratory-infected fish.

Animals↗
PubMed1998

Primary care groups. Growing pains.

The management costs of primary care groups are likely to be higher than envisaged. Duplication of all functions in all PCGs is likely to be more expensive than current health authority commissioning arrangements. In the long term, the most effective deployment of management costs will depend on deciding which PCG commissions what.

Budgets↗
PubMed1998

The characterisation of three substituted zinc phthalocyanines of differing charge for use in photodynamic therapy. A comparative study of their aggregation and photosensitising ability in relation to mTHPC and polyhaematoporphyrin.

Three substituted zinc (II) phthalocyanines (one anionic, one cationic and one hydrophobic) have been compared to two clinically used photosensitisers, 5,10,15,20-tetra (m-hydroxyphenyl) chlorin (mTHPC) and polyhaematoporphyrin (PHP), as potential agents for photodynamic therapy (PDT). Oxygen-consumption experiments, performed to follow the photo-oxidation of tryptophan, histidine and bovine serum albumin (BSA), suggest that the anionic phthalocyanine is the most efficient photosensitiser. The efficacy of BSA oxidation is much greater than that of tryptophan or histidine, which is partly due to monomerisation of the sensitisers upon binding to BSA. Spectra recorded in aqueous solution reveal that all five compounds are highly aggregated, but monomerisation is induced upon the addition of BSA or methanol. Using a range of methanol-buffer solutions, the aggregation state has been directly related to the efficacy of tryptophan photo-oxidation with maximal rates of oxidation achieved when the sensitiser is monomeric. Using erythrocytes as a simple membrane model, the efficacy of each sensitiser exhibits a different trend from that predicted by oxygen-consumption experiments. The anionic phthalocyanine is the least effective at photohaemolysis, whereas the cationic and hydrophobic phthalocyanines have improved activity over PHP and mTHPC.

Animals↗
PubMed1998

Pathology attributed to Mycobacterium chelonae infection among farmed and laboratory-infected Atlantic salmon Salmo salar.

This study was promoted following concern over increasing mortality on 2 farms rearing Atlantic salmon Salmo salar in the Shetland Isles, Scotland. A Mycobacterium sp. was isolated from moribund, market-sized Atlantic salmon. Biochemical tests, lipid analysis and PCR (polymerase chain reaction) techniques confirmed the bacterium to be Mycobacterium chelonae. Multiple greyish-white miliary granuloma-like nodules were observed in several tissues. Dense hard-packed nodules contained abundant acid-fast bacteria. Atlantic salmon injected with M. chelonae remained sub-clinically infected, demonstrating the chronic nature of this disease. The source of the pathogen was not identified.

Animals↗