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Biomedical subjects

A M Thomas

Publications and source records attributed to A M Thomas.

At least 19 recordsLinked to original sources
PubMed2006

In vitro-clinical correlations for amphotericin B susceptibility in AIDS-associated cryptococcal meningitis.

Reliable measures of antifungal drug susceptibility are needed. We tested the susceptibility of Cryptococcus neoformans from patients treated with amphotericin B. In vitro susceptibility employed a modified broth macrodilution method. We demonstrate a strong correlation between the quantitative measures of in vitro amphotericin B susceptibility and the quantitative response observed in patients.

AIDS-Related Opportunistic Infections↗
PubMed2005

Sprouting of mossy fibers and presynaptic inhibition by group II metabotropic glutamate receptors in pilocarpine-treated rat hippocampal slice cultures.

Mossy fibre sprouting (MFS) is a phenomenon observed in the epileptic hippocampus. We have studied MFS, in 7, 14 and 21 day in vitro (DIV) organotypic slice cultures, or in slice cultures treated with pilocarpine (0.5 mM) or pilocarpine and atropine (0.1 mM or 0.5 mM) for 48-72 h at 5 DIV and tested at 21 DIV. Acute application of pilocarpine directly activated hilar neurons and elicited epileptic-like discharges in CA3 pyramids and mossy cells of 5-8 DIV cultures, without causing substantial cell death, as assessed by lactate dehydrogenase measurements. Timm staining revealed increases in MFS in chronic pilocarpine-treated cultures, which was prevented by prior application of atropine. Extracellular synaptic responses were recorded in the granule cell layer and elicited by antidromic mossy fibre stimulation. The GABA(A) antagonist 6-imino-3-(4-methoxyphenyl)-1(6H)-pyridazinebutanoic acid (1 microM) induced a greater increase in the coastline bursting index in pilocarpine-treated cultures than in 21 DIV controls. However, there was no significant increase in the frequency of spontaneous or miniature synaptic events recorded in granule cells from pilocarpine-treated cultures. Granule cells were filled with biocytin and morphometric analysis revealed that the length of axon collaterals in the granule and molecular layer was longer in pilocarpine-treated cultures than in 21 DIV controls. Dual recordings between granule cells and between granule and hilar neurons showed that pilocarpine-treated cultures had a larger proportion of monosynaptic and polysynaptic connections. The group II metabotropic glutamate receptor (mGluR) agonist LY354740 (0.5 microM) suppressed excitatory but not inhibitory monosynaptic currents. LY354740 also inhibited antidromically evoked action currents in granule cells from pilocarpine- and to a lesser extent in pilocarpine and atropine-treated cultures, suggesting that group II mGluRs can reside along the axon and suppress action potential invasion. We provide direct evidence for the development of functional MFS and suggest a novel, axonal mechanism by which presynaptic group II mGluRs can inhibit selected synapses.

Animals↗
PubMed2001

Both light-dependent protochlorophyllide oxidoreductase A and protochlorophyllide oxidoreductase B are down-regulated in the slender mutant of barley.

The gibberellin-insensitive overgrowth mutant of barley, slender, exhibits altered expression of a number of nuclear genes in comparison with the wild type. There is a particularly marked reduction in slender seedlings of transcript encoding protochlorophyllide oxidoreductase (POR), the enzyme which catalyses the penultimate and only light-requiring step in chlorophyll biosynthesis. The expression of the two barley genes encoding light-dependent POR, PORA and PORB was investigated. Expression of both genes was found to be reduced in slender seedlings relative to the wild type, in both etiolated and light-grown leaf tissue; this was most marked in the zone of rapid cell extension. Western blot analysis showed that POR protein was also less abundant in etiolated and in light-grown slender than in the equivalent wild-type leaf tissue, although the effect was less pronounced than at the transcript level. Protochlorophyllide content in etiolated slender seedlings was reduced in comparison with wild-type seedlings, though chlorophyll content in light-grown leaf blades was unaffected. The reduction in POR expression in slender barley may reflect a novel response to the constitutive activation of gibberellin signalling in this mutant. Despite the consequences of the mutation for POR gene expression, slender seedlings develop apparently normal chloroplasts in the light, and etioplasts with well-defined prolamellar bodies when grown in continuous darkness. This suggests that the POR content of wild-type barley seedlings is well in excess of the minimum required for normal plastid development.

Blotting, Northern↗
PubMed2000

In vivo measurements of glutamine + glutamate (Glx) and N-acetyl aspartate (NAA) levels in human partial epilepsy.

OBJECTIVE: To investigate whether cerebral levels of N-acetyl aspartate (NAA), and glutamine + glutamate (Glx), are interictally altered in the epileptogenic regions of patients with partial seizures. MATERIAL AND METHODS: NAA, Glx, creatine (Cr), choline (Cho) and myo-inositol (mI) was measured in 28 patients with partial epilepsy and 10 healthy controls using localized 1H magnetic resonance spectroscopy. According to the multimethodological consensus, the epileptogenic region was mesial temporal in 18 and neocortical in 10 patients. RESULTS: The Glx/NAA and Glx/Cr ratios in epileptogenic regions were higher, and the NAA/Cr ratios lower than in the homologous regions (P=0.013, P=0.002 and P<0.0001). Applying the 95% confidence interval of controls, 17 of the 20 mesial temporal epileptogenic regions were correctly identified by an increased Glx/NAA and 15 of 20 by a decreased NAA/Cr ratio. Among patients with neocortical epilepsy the Glx/NAA ratio was increased in 8 of the 10 epileptogenic regions, whereas the NAA/Cr ratio was decreased in three. CONCLUSION: Both Glx and NAA are useful to identify the epileptogenic zone. The Glx/NAA ratios may be particularly useful to indentify neocortical epileptogenic regions.

Adolescent↗
PubMed2000

Disturbances of endometrial bleeding with hormone replacement therapy.

Breakthrough bleeding is a common problem in postmenopausal women taking hormone replacement therapy (HRT) and is often the single most important factor deterring women from continuing to use HRT, or from starting it in the first place. The mechanisms which underlie this unscheduled bleeding are poorly understood. The benefits of HRT in terms of longevity and quality of life are becoming increasingly apparent, and a greater understanding of why this bleeding occurs and how we can prevent or treat it, will undoubtedly enable more women to reap the potential considerable benefits of long-term oestrogen and progestogen replacement. What sets postmenopausal women apart from their counterparts in the mid-reproductive years is the increased likelihood of endometrial adenocarcinoma in which unscheduled bleeding is the presenting symptom. Therefore, spontaneous postmenopausal bleeding must always be appropriately evaluated. Hence, the occurrence of unscheduled bleeding with HRT may provide a dilemma with diagnosis as well as a challenge to acceptability. Combined HRT regimens tend to be predominantly progestogenic, and there is increasing evidence to suggest that some of the vascular changes seen in women taking long-term, low-dose progestogen-only contraceptives may also occur in women taking HRT.

Adenocarcinoma↗
PubMed2000

Fear of intimacy among dating couples.

Fear of intimacy among heterosexual dating couples was examined with the Fear-of-Intimacy Scale (FIS) and the Personal Assessment of Intimacy in Relationships (PAIR). Following a 6-month interval, couples were again contacted to determine whether they continued to date. Males reported higher FIS scores than females, and FIS scores were positively correlated within couples. Also, FIS scores of males and females were significantly correlated with indices of actual and desired intimacy; however, for females, correlations of FIS scores with desired intimacy were significantly lower than correlations with actual intimacy. Females who were no longer in the dating relationship at the 6-month follow-up had higher FIS scores than those who were continuing in their dating relationship. These findings increase our understanding of fear of intimacy, especially gender differences in dating couples.

Adult↗
PubMed1999

Evidence that high-density lipoprotein cholesterol is an independent predictor of acute platelet-dependent thrombus formation.

Plasma total and low-density lipoprotein (LDL) cholesterol are established risk factors for atherosclerotic vascular disease and may also contribute to a prothrombotic risk via enhanced platelet reactivity. This study examines whether high-density lipoprotein (HDL) cholesterol, which is inversely correlated with coronary artery disease, is associated with a reduced thrombogenic potential. Platelet thrombus formation was evaluated by exposing porcine aortic media placed in Badimon perfusion chambers to flowing nonanticoagulated venous blood for 5 minutes at a shear rate of 1,000 s(-1). Forty-five subjects, 23 normal (LDL 104 +/- 31, HDL 50 +/- 15 mg/dl) and 22 hypercholesterolemic (LDL 181 +/- 45, HDL 41 +/- 10 mg/dl) patients without coronary artery disease were studied. Platelet aggregation and CD62 antigen expression, and assay for circulating prothrombotic factors were also performed. In univariate analysis platelet thrombus formation correlated with weight (r = 0.33, p = 0.03), diastolic blood pressure (r = 0.39, p = 0.01), HDL cholesterol (r = -0.45, p = 0.003), total/HDL cholesterol (r = 0.43, p = 0.004) and LDL/HDL (r = 0.38, p = 0.01) ratios, and platelet CD62 expression (r = 0.41, p = 0.02). In multiple regression analysis only HDL cholesterol showed significant correlation with platelet thrombus formation (p = 0.03). Platelet aggregation and circulating prothrombotic factors did not correlate with platelet thrombus formation. A comparison between normal and hypercholesterolemic subjects revealed enhanced thrombus area (0.026 +/- 0.20 vs 0.045 +/- 0.039 mm2/mm; p = 0.04), resting CD62 expression (6 +/- 7% vs 15 +/- 10% positive platelets, p = 0.02), and platelet aggregation (16.7 +/- 5.2 vs 21.7 +/- 6.7 ohms, p = 0.04) in hypercholesterolemic subjects. Our results demonstrate that HDL cholesterol is a significant independent predictor of ex vivo platelet thrombus formation.

Adult↗
PubMed1999

Comorbidity of headache and depressive disorders.

The goal of the present study was to investigate the clinical profile of patients with primary headache syndromes who also suffer from mood disorders. Four-hundred-and-seventy headache outpatients (170M, 300F) and 150 age- and sex-matched healthy subjects were screened using a specific questionnaire that included the Hamilton rating scales for anxiety and depression. The average scores of the Hamilton rating scales for anxiety and depression were significantly higher in headache sufferers (17.4 and 14.2, respectively) than in healthy people (6.8 and 5.7, respectively). The frequency of headache attacks, the history of headaches, and gender (women more than men) were correlated with the score of the Hamilton rating scale for both anxiety and depression. Sixteen headache patients (3.4%) achieved the DSM-IV criteria for major depression or dysthymia versus one among headache-free subjects (0.6%; OR 5.2). Patients suffering from drug-overuse and migraine with aura showed the higher odds ratios (35 and 17, respectively). These results suggest that those headache patients with long history and high frequency of headaches, or patients suffering from migraine with aura and drug-overuse might benefit from psychiatric evaluation.

Adult↗
PubMed1999

The structure and composition of chronic wound eschar.

Wounds with a covering of eschar require debridement before optimal wound healing can proceed. There are several different methods available but these have been derived empirically with no direct evidence of the structure or composition of the tissue they are designed to remove, or of the potential autolytic mechanisms which are the targets for some of these treatments. The aim of this study therefore was to determine the composition of chronic wound eschar and hence identify potential targets for the induction of autolytic debridement. Chronic wound eschar was removed by surgical debridement and analysed using immunohistochemistry, polyacrylamide gel electrophoresis (PAGE) and gelatin zymography. Immunohistochemistry using antibodies specific for extracellular matrix (ECM) proteins revealed a definite tissue structure, consisting of many fibrous regions and fine fibrillar elements separated by areas of tissue which were of a more irregular and amorphous nature. An antibody specific for all leucocytes revealed the presence of leucocytes in the region of tissue closest to the wound bed. The presence of this leucocyte population correlated to elevated levels of gelatinase activity as identified by gelatin zymography. PAGE analysis identified various protein species in the range 3.5-60 kDa molecular weight. These data indicate that wound debridement is likely to require multiple enzyme specificities to degrade the eschar and that these enzymes may be supplied by inflammatory leucocytes infiltrating the eschar from the wound bed. The various protein species demonstrated by PAGE may represent ECM proteins, those with lower molecular weight possibly representing the degradation products of autolytic debridement.

Chronic Disease↗
PubMed1998

Amphotericin B colloidal dispersion combined with flucytosine with or without fluconazole for treatment of murine cryptococcal meningitis.

Studies with animals and in vitro studies have demonstrated that flucytosine plus amphotericin B or fluconazole has significantly improved mycologic activity against meningitis caused by Cryptococcus neoformans compared to the activity of amphotericin B or fluconazole used alone. However, few doses have been tested in combination. This study evaluated the antifungal efficacy of amphotericin B colloidal dispersion (ABCD) combined with flucytosine with and without fluconazole in a murine model of cryptococcal meningitis. The following dosages were tested: ABCD at 0 to 12.5 mg/kg of body weight given intravenously 3 days/week, flucytosine at 0 to 110 mg/kg/day, and fluconazole at 0 to 50 mg/kg/day. Meningitis was established in male BALB/c mice by intracerebral injection of C. neoformans. Treatment with flucytosine with or without fluconazole dissolved in the sole source of drinking water was started on day 2; animals were sacrificed at 16 days, and the numbers of fungal colonies in the brain were quantified. A survival rate of 100% was achieved with ABCD plus flucytosine without fluconazole; however, the addition of fluconazole was required to prevent weight loss (P < 0.00001) and to achieve the maximum antifungal effect (P < 0.00001). The only region of dose combinations for which the 99% confidence intervals were less than 100 CFU/g of brain was defined by ABCD at 5.0 to 7.5 mg/kg combined with flucytosine at 20 to 60 mg/kg/day and fluconazole at 30 to 40 mg/kg/day. The triple combination of ABCD plus flucytosine and fluconazole was necessary to achieve the greatest antifungal activity.

Amphotericin B↗
PubMed1998

The role of radiology in pulmonary infectious disease.

This review of recently published papers focuses on the recent tious disease. Despite advances in thoracic imaging, the chest roentgenogram combined with the clinical history remain the cornerstone in the diagnosis, staging, and follow-up of pulmonary infectious disease. Examination of all prior films to document preexistent anatomic pulmonary or cardiac disease and to establish the progression or regression of the pulmonary infiltrate is essential prior to proceeding with more costly imaging.

Diagnosis, Differential↗
PubMed1997

Trichotillomania: a comprehensive behavioral model.

As our knowledge of chronic hair pulling as neither rare nor benign has increased, so has the need for a comprehensive framework to guide our conceptualization of this disorder for both research and clinical work. Such a model is presented which incorporates (a) the varied antecedents that both cue the impulse to pull and facilitate pulling, (b) the wide array of behaviors involved in the actual pulling, and (c) the full range of consequences of pulling. The cyclical nature of pulling episodes is highlighted.

Adult↗