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Biomedical subjects

C Watson

Publications and source records attributed to C Watson.

At least 73 records · Page 4Linked to original sources
PubMed1998

Measuring the impact of conjugate vaccines on invasive Haemophilus influenzae type b infection in Western Australia.

Haemophilus influenzae type b (Hib) causes serious infections in 26-59 per 100,000 non-Aboriginal Australian children under five years of age. Aboriginal children suffer much higher rates of infection (> or = 150 per 100,000), and at an earlier age, and have a greater risk of death and disability due to Hib infection. In 1992 and 1993, four conjugate Hib vaccines were introduced in Australia, and a nationally funded program of infant vaccination was begun in July 1993. This study aimed at evaluating the effectiveness of Hib vaccination in Aboriginal and non-Aboriginal children in Western Australia using a population-based active surveillance system for non-Aboriginal children and a case control study for Aboriginal children. The incidence of invasive Hib disease in non-Aboriginal children fell from 30.9 per 100,000 before vaccination was available to 6.3 per 100,000 in the second year after its introduction. The vaccine efficacy was estimated to be 80 per cent for Aboriginal children (odds ratio 0.20, 95 per cent CI 0.01-2.76) and, after adjustment for confounders, 75 per cent (odds ratio 0.25, CI 0.02-3.66). Based on the adjusted value (75 per cent), and using a Bayesian approach, we estimate that the posterior probability was 0.55 that the true vaccine efficacy is greater than 70 per cent, and 0.69 that the efficacy is greater than 50 per cent. We conclude that Hib vaccination is effective in preventing invasive Hib disease in Aboriginal and non-Aboriginal children in Australia.

Bacteremia↗
PubMed1998

Recombinant human CXC-chemokine receptor-4 in melanophores are linked to Gi protein: seven transmembrane coreceptors for human immunodeficiency virus entry into cells.

This article describes the transient expression of the CXC chemokine receptor-4 in Xenopus laevis melanophores and the resulting functional assay for the endogenous ligand for this receptor stromal cell-derived factor (SDF)-1alpha. Specifically, it will be shown that SDF-1alpha produces increased light transmittance in transfected cells that is consistent with the activation of Gi protein. This stimulus pathway is further implicated by the abolition of this response after pretreatment of the cells with pertussis toxin, a known method for the inactivation of Gi protein. The fact that SDF-1alpha does not produce responses in nontransfected cells and that treatment of the cells with 12G5, an antibody specific for the CXC chemokine receptor-4, eliminates this response indicates that this ligand produces responses by activation of this receptor in these cells. The possible relevance to human immunodeficiency virus (HIV) entry into cells was explored by observing the effects of SDF-1alpha on HIV-mediated cell fusion. It was found that SDF-1alpha blocked cell-to-cell fusion (as has been previously reported) at concentrations 1200-fold greater than those required to produce Gi protein mediated responses. The implications of the functional assay to screening for new drugs to block HIV-mediated fusion is discussed.

Amino Acid Sequence↗
PubMed1998

Intraperitoneal rhabdomyosarcoma in children: incidence and imaging characteristics on CT.

OBJECTIVE: The purpose of this study was to determine the incidence and CT imaging features of intraperitoneal rhabdomyosarcoma in children. CONCLUSION: Approximately 10% of children with rhabdomyosarcoma may have intraperitoneal neoplastic involvement either at the time of diagnosis or subsequently. On CT, intraperitoneal rhabdomyosarcomas are associated with ascites, enhancing nodules, masses, a pseudomyxoma peritonei-like appearance, and omental caking.

Adolescent↗
PubMed1998

Glove usage and reporting of needlestick injuries by junior hospital medical staff.

The use of gloves when conducting invasive procedures and the reporting of needlestick injuries have been strongly encouraged. Despite this, neither practice appears to be universal. In order to determine the rates of glove usage and needlestick injury reporting, we conducted a survey of junior doctors in three hospitals in the UK. Of the 190 respondents, the majority rarely wore gloves for venesection, insertion of intravenous cannulas or arterial blood gas sampling. For more major procedures (insertion of central venous lines, insertion of thoracostomy tubes, suturing) gloves were invariably worn. Only 17.5% of needlestick injuries were reported. The rates of glove usage and needlestick injury reporting were lower than previous studies have demonstrated in North America. Surgeons suffered the most needlestick injuries and were the least likely to report them. The low reporting rate may have serious implications, particularly in view of the new Government guidelines on needlestick injuries which involve HIV-infected blood. By failing to use gloves and report needlestick injuries, junior doctors, in particular surgeons, are placing themselves and patients at increased risk of blood-borne transmissible diseases.

Gloves, Surgical↗
PubMed1997

Specificity of volumetric magnetic resonance imaging in detecting hippocampal sclerosis.

BACKGROUND: Magnetic resonance imaging (MRI)-based volumetric measurements of the hippocampal formation are useful in detecting unilateral hippocampal sclerosis (HS) in patients with temporal lobe epilepsy. In this pathologic entity, volumetric MRI analysis shows the epileptogenic structure to be atrophic when compared with the normal, nonepileptogenic side. Some authors have suggested that the radiological features of atrophy of medial temporal lobe structures are common in patients with complex partial seizures, but also are seen frequently in other seizure types and can occur even in patients without epilepsy. OBJECTIVE: To determine if seizures originating in extrahippocampal sites cause gliosis, cell loss, and atrophy of medial temporal lobe structures (i.e., HS). METHODS: We studied 110 patients with chronic epilepsy using volumetric MRI measurements of the hippocampal formation. Seventeen patients had pathologically proven HS, 27 patients had seizures due to extratemporal structural lesions, 15 patients had seizures caused by extrahippocampal temporal lobe lesions, 29 patients had primary generalized epilepsy, and 22 patients had secondary generalized epilepsy. RESULTS: All 17 patients with HS showed significantly reduced absolute hippocampal formation volumes of greater than 2 SDs below the mean of the control groups. The preoperative hippocampal formation volume measurements correlated well with the severity of HS on pathological examination. Hippocampal volumes were within the normal range in all patients with primary generalized epilepsy, secondary generalized epilepsy, extratemporal structural lesions, and extrahippocampal temporal lobe lesions. CONCLUSIONS: Seizures originating at extrahippocampal sites do not cause gliosis, cell loss, or atrophy of medial temporal structures. Significant reduction in hippocampal volumes is a specific marker for HS.

Adolescent↗
PubMed1997

Volumetric magnetic resonance imaging. Clinical applications and contributions to the understanding of temporal lobe epilepsy.

In recent years, magnetic resonance imaging-based volumetric measurements of the amygdala and hippocampus have proved useful in the diagnosis and treatment of patients with temporal lobe epilepsy. This imaging modality allows amygdaloid and hippocampal volumes to be correlated with neurophysiological, neuropathological, and neuropsychological findings, surgical outcome, and clinical findings. We evaluated the technical and anatomical aspects underlying the successful use of the modality that were reported in previous studies. We also evaluated issues such as the sensitivity and specificity of volumetric magnetic resonance imaging, its use in bilateral temporal lobe epilepsy, and the debate concerning the sensitivity of qualitative visual analysis vs quantitative volumetric analysis of magnetic resonance images. Volumetric magnetic resonance imaging, when used in conjunction with video electroencephalographic monitoring, neuropsychological studies, and other neuroimaging studies, will enable patients with temporal lobe epilepsy to be treated in an appropriate, efficient, and cost-effective manner.

Amygdala↗
PubMed1997

Periventricular nodular heterotopia and intractable temporal lobe epilepsy: poor outcome after temporal lobe resection.

We describe 5 women and 5 men with periventricular nodular heterotopia and electroclinical features suggestive of temporal lobe epilepsy, who were surgically treated for control of medically refractory seizures. Magnetic resonance imaging revealed bilateral periventricular nodular heterotopia in 7 of the 10 patients. Because of the lack of clear localization, 6 patients were studied with intracranial depth electrode recordings. Seizures were of hippocampal onset (3 patients), regional temporal lobe onset (2 patients), or occipital-temporal onset (1 patient). Anterior temporal lobectomy was performed in 6 patients; selective amygdalohippocampectomy, in 1; and anterior temporal lobectomy plus resection of the heterotopic tissue, in 3. None of the 9 patients followed for more than 12 months postoperatively were seizure free. Two patients were initially seizure free for approximately 18 months, but then seizures recurred. One patient had a major reduction in seizure frequency at a 39-month follow-up after most of the unilateral heterotopic tissue was included in the temporal resection. Temporal resection did not lead to a long-term favorable outcome in this group of patients with periventricular nodular heterotopia and epileptogenic discharges involving the temporal lobe. This suggests a more widespread disorder with epileptogenic activity possibly originating in or near the heterotopic tissue. The clinical and electrographic features of periventricular nodular heterotopia pointing to temporal lobe origin are misleading and temporal resection does not result in long-term cessation of seizures.

Adult↗
PubMed1997

Isolation and characterization of phenoloxidase from egg masses of the gastropod mollusc, Biomphalaria glabrata.

Previous studies have shown that phenoloxidase activity is present in the albumen gland and egg masses of Biomphalaria glabrata, and its potential role in egg formation in this snail has been proposed. In the present study, a phenoloxidase enzyme has been isolated from the supernatant of egg mass homogenates using a combination of hydrophobic interaction chromatography and gel filtration high-performance liquid chromatography (GF-HPLC). The isolated phenoloxidase eluted as a single peak of activity upon GF-HPLC (representing a 132-fold purification) and subsequently was detected as a single band with an estimated molecular mass of 35 kDa by SDS-PAGE analysis. Phenylthiourea-inhibitable mono- and diphenoloxidase activities were demonstrated for the isolated enzyme suggesting that both enzyme activities are associated with a single, tyrosinase-type molecule.

Ammonium Sulfate↗
PubMed1997

Expression cloning and receptor pharmacology of human calcitonin receptors from MCF-7 cells and their relationship to amylin receptors.

Human breast cell carcinoma MCF-7 cells were found to bind 125I-labeled rat amylin (rAmylin) and the peptide amylin antagonist radioligand 125I-AC512 with high affinity. This high affinity binding possessed characteristics unique to the already defined high affinity binding site for amylin in the rat nucleus accumbens [Mol. Pharmacol. 44:493-497 (1993); J. Pharmacol. Exp. Ther. 270:779-787 (1994); Eur. J. Pharmacol. 262:133-141 (1994)]. To further define this receptor, we report results of expression cloning studies from an MCF-7 cell library. We isolated two variants of a seven-transmembrane receptor that were identical to two previously described human calcitonin receptors (hCTR1 and hCTR2). These receptors were characterized by expression in different surrogate host cell systems. Transient expression of hCTR1 in COS cells yielded membranes that bound 125I-AC512 and 125I-salmon calcitonin with high affinity, but no high affinity binding was observed with 125I-human calcitonin (hCAL) or 125I-rAmylin. Stable expression of hCTR1 in HEK 293 cells produced similar data. In contrast, expression of hCTR2 in COS cells yielded membranes that bound 125I-AC512, 125I-hCAL, and 125I-rAmylin with high affinity. The agonists 125I-hCAL and 125I-rAmylin bound 65% and 1.5%, respectively, of the sites bound by the antagonist radioligand 125I-AC512 in this expression system. This pattern of binding was repeated in HEK 293 cells stably transfected with hCTR2 (125I-hCAL = 24.8% Bmax, 125I-rAmylin = 8% Bmax). In both expression systems, the agonists hCAL and rAmylin were much more potent in displacing their radioligand counterparts than was the antagonist radioligand 125I-AC512. For example, the pKi value for displacement of 125I-AC512 by rAmylin was 7.2 in HEK 293 cells but rose to 9.1 when displacing 125I-rAmylin. Finally, hCTR2 was expressed in baculovirus-infected Ti ni cells. In this system, only specific binding to the antagonist 125I-AC512 and agonist 125I-hCAL was observed; no binding to 125I-rAmylin could be detected. These data are discussed in terms of two working hypotheses. The first is that amylin is a weak agonist for hCTR2 and that this receptor is unrelated to the amylin receptor found in this cell line. The second is that hCTR2 couples to different G proteins for calcitonin and amylin function in different cells. At present, these data cannot be used to disprove conclusively either hypothesis.

Amino Acid Sequence↗
PubMed1997

Evaluation of a project to enhance knowledge of hereditary diseases and management.

During 1992 and 1993, in a designated suburban area of Perth, Western Australia, information on hereditary disease was provided for health professionals and the general community. This information was in the form of posters, pamphlets, postal flyers and return letter cards, a static display, newspaper articles, advertisements and radio broadcasts, and professional seminars. The aim of this project was to evaluate the effectiveness of combined strategies to convey practical information about hereditary disease to the community and health professionals. Multiple measures of response evaluation were used, which included structured questionnaire surveys of health professionals and members of the community before and after the project. In the community surveys, respondents who were female, married, middle aged, and parents, and had a higher level of education or were born in Australia, New Zealand, or the United Kingdom were generally better informed about hereditary diseases. This intervention resulted in only meagre changes in community knowledge about hereditary disease, even though promotional materials were shown to be appropriate. General Practitioners (GPs) and Child Health Nurses (CHNs) were supportive of clinical genetic services and recognised a need for continuation of education in this field. There is a rapidly increasing need for community and health professional comprehension of the applications of the new genetic technology. This project indicates that routine educational and health promotion strategies will not be enough to achieve desired levels of knowledge and attitude change.

Adult↗
PubMed1997

Surgical treatment of patients with single and dual pathology: relevance of lesion and of hippocampal atrophy to seizure outcome.

Modern neuroimaging can disclose epileptogenic lesions in many patients with partial epilepsy and, at times, display the coexistence of hippocampal atrophy in addition to an extrahippocampal lesion (dual pathology). We studied the postoperative seizure outcome of 64 patients with lesional epilepsy (median follow-up, 30 months) and considered separately the surgical results in the 51 patients with a single lesion and in the 13 who had dual pathology. In patients with a single lesion, 85% were seizure free or significantly improved (Engel's class I-II) when the lesion was totally removed compared with only 40% when there was incomplete resection (p < 0.007). All three patients with dual pathology who had both the lesion and the atrophic hippocampus removed became seizure free. In contrast, only 2 of the 10 patients with dual pathology undergoing surgery aimed at the lesion or at the hippocampus alone became seizure free (p < 0.05), although 4 of them showed significant improvement (Engel's class II). We conclude that the outcome in patients with single epileptogenic lesions is usually dependent upon the completeness of lesion resection. In patients with dual pathology, surgery should, if possible, include resection of both the lesion and the atrophic hippocampus.

Adolescent↗
PubMed1997

Gender, race and poverty: bringing the sociopolitical into psychotherapy.

OBJECTIVE: To explore the modification of traditional psychotherapy to provide a more relevant service for non-dominant groups including women, Maori and the poor. METHOD: The philosophy and practice of a psychotherapy service that made overt sociopolitical issues for women, Maori and the poor was analysed and linked with literature on psychotherapy for non-dominant groups. RESULTS: Traditional psychotherapy, with its focus on the intrapsychic, has not addressed the condition of marginalised groups such as the poor, ethnic minorities including Maori, and some women, whose mental health difficulties have major contributions from external sources. The service analysed, and much of the literature, used social analysis as a therapeutic tool to break the cycle of self-blame and doubt and to contextualise intrapsychic experience. As non-dominant groups lack power, power differences in the therapy relationship should be lessened to avoid retraumatising the patient. CONCLUSION: It is possible for psychotherapy to broaden its traditional base to include a sociopolitical viewpoint. This would make it more available and meaningful to a wider range of people, especially those with the double disadvantage of adverse intrapsychic and sociopolitical factors.

Adult↗
PubMed1997

Regulation of aromatase activity within the breast.

Local oestrogen biosynthesis within the breast can be highly variable, in vitro aromatase activity both in breast cancers and mammary adipose tissue displaying over a 40-fold range between the highest and lowest levels. Evidence is presented to show that: (i) transcriptional activity may influence oestrogen biosynthesis within breast cancers in that both aromatase mRNA and STAT nuclear binding are correlated positively to in vitro aromatase activity; (ii) the local presence of cancer may enhance aromatase activity in particulate fractions and primary fibroblast cultures from mammary adipose tissue; (iii) tumour extracts and breast cyst fluids may induce aromatase in cultured fibroblasts, the active principles responsible for these effects being incompletely defined (although the combination of interleukin (IL)-6 and its soluble receptor dramatically enhances aromatase activity, it is unclear whether this particular cytokine system can account for the stimulatory effects of breast extracts and fluids); (iv) the aromatase activities in both breast cancer and adipose tissues are susceptible to classical aromatase inhibitors such as aminoglutethimide and 4-hydroxyandrostenedione (and to newer inhibitors such as CGS16949 and CGS20267 at low nanomolar concentrations) but reduced sensitivity to 4-hydroxyandrostenedione may be observed in certain breast cancers. These findings may have important implications for the development and progression of hormone-dependent cancers within the breast.

Adipose Tissue↗
PubMed1996

Differential patterns of neutrophil adhesion molecules during cardiopulmonary bypass in humans.

BACKGROUND: Neutrophils are activated during cardiopulmonary bypass, and it is believed that they play an important role in the postoperative inflammatory response. The effects of neutrophils are mediated by the surface adhesion molecules L-selectin, beta 2-integrins, and platelet-endothelial cell adhesion molecule-1 (PECAM-1), and it has been reported that beta 2-integrins are upregulated and L-selectin downregulated by cardiopulmonary bypass. However, the time course of these changes and their relative importance are unclear. METHODS AND RESULTS: To investigate the temporal changes in the expression of the neutrophil surface adhesion molecules L-selectin, beta 2-integrins, and PECAM-1 induced by cardiopulmonary bypass, we used immunofluorescent flow cytometry in blood samples obtained at various times (before anesthesia, before bypass, and 0.25, 0.5, 1, 2, 4, 24, and 48 hours after initiation of bypass) from patients undergoing routine coronary artery bypass graft surgery. Anesthesia had no effect on the expression of any of the study molecules. The expression of all beta 2-integrins was not significantly affected during the entire study period. The mean fluorescence (expressed as a percentage of control) of CD18 did not change significantly during the first 2 hours after the initiation of cardiopulmonary bypass, but then it declined by 4 hours (P = NS) and attained its lowest values after 24 and 48 hours. The mean fluorescence of CD11b and CD11c decreased by 2 and 4 hours and remained reduced after 24 hours and 48 hours. The expression of PECAM-I decreased rapidly after the initiation of cardiopulmonary bypass to achieve 60 +/- 8% of the preanesthesia control values (P < .05) after only 1 hour; it fell to its lowest after 4 hours (44 +/- 8%; P < .05); and then it recovered partially by 24 hours (60 +/- 11%; P < .05), with a further recovery toward control after 48 hours (77 +/- 8%; P = NS). The profile for the mean fluorescence of PECAM-I was identical to that observed with its expression. In contrast, the expression and mean fluorescence of L-selectin were not changed during the 48-hour period. CONCLUSIONS: This study has demonstrated that cardiopulmonary bypass in humans induces (1) a rapid reduction in the expression of PECAM-I of circulating neutrophils, (2) a later reduction of beta 2-intergrin activity without significant changes in their expression, and (3) no alterations in the expression and activity of L-selectin. Thus, although the mechanism for the absence of neutrophil upregulation of beta 2-integrins and downregulation of L-selectin (no activation) remains to be elucidated, the downregulation of PECAM-1 indicates an early neutrophil activation, and its inhibition may represent a target for reducing the inflammatory response usually associated with cardiopulmonary bypass.

CD18 Antigens↗
PubMed1996

IL-6 acts on endothelial cells to preferentially increase their adherence for lymphocytes.

Using a quantitative monolayer adhesion assay, the current report shows that treatment of human umbilical vein endothelial cells (HUVEC) with IL-6 increases their adhesiveness for blood lymphocytes, particularly CD4+ cells, but not for polymorphonuclear cells and monocytes. This effect, which was most pronounced when using low concentrations of the cytokine (0.1-1.0 U/ml) and a short incubation period (4h), was also apparent with microvascular endothelial cells and a hybrid endothelial cell line. Skin lesions from patients with mycosis fungoides contain high levels of IL-6, and blood lymphocytes from patients with this disorder also exhibited an enhanced adhesion to IL-6-treated HUVEC. The cytokine enhanced intercellular adhesion molecule-1 (ICAM-1) expression and induced the expression of vascular cell adhesion molecule-1 (VCAM-1) and E-selectin on endothelial cells. Antibody blocking studies demonstrated that the vascular adhesion molecules ICAM-1, VCAM-1 and E-selectin and the leucocyte integrin LFA-1 all contributed to lymphocyte binding to endothelium activated by IL-6. It is proposed that IL-6 may be involved in the recruitment of lymphocytes into non-lymphoid tissue.

Adjuvants, Immunologic↗
PubMed1996

Medial temporal lobe heterotopia as a cause of increased hippocampal and amygdaloid MRI volumes.

Magnetic resonance imaging (MRI)-based volumetric measurements of the hippocampus and amygdala are useful in detecting hippocampal and amygdaloid sclerosis in patients with temporal lobe epilepsy. In these pathological entities, volumetric MRI analysis shows the epileptogenic structures to be atrophic when compared to the normal, nonepileptogenic side. Described are 2 patients with increased hippocampal and amygdaloid volumes on the side of seizure onset due to medial temporal lobe heteroto pias. Care must be taken in the interpretation of volumetric MRI data to make certain that asymmetries in hippocampal and amygdaloid measurements are due to atrophy and sclerosis of the abnormal side and not to increased tissue such as heterotopic gray matter.

Adult↗