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Biomedical subjects

C Dow

Publications and source records attributed to C Dow.

At least 19 recordsLinked to original sources

Cerebellar atrophy in temporal lobe epilepsy affects procedural memory.

The authors examined a cognitive function mediated by the cerebellum, classical eyeblink conditioning, and its relationship to cerebellar volume in healthy controls (n = 59) and temporal lobe epilepsy subjects (n = 77). Controls demonstrated better conditioning, larger cerebellar volumes, and an association between conditioning and cerebellar volume that was not observed in epilepsy patients. These findings provide support for the hypothesis that cerebellar atrophy in epilepsy affects procedural memory.

Acoustic Stimulation↗

The nature and course of neuropsychological morbidity in chronic temporal lobe epilepsy.

OBJECTIVE: To characterize the nature and degree of cognitive morbidity in patients with chronic temporal lobe epilepsy compared with healthy control subjects, determine the association between the duration of epilepsy and cognitive morbidity, and ascertain whether there are factors that moderate the association between duration of disorder and cognitive impairment. METHODS: Temporal lobe epilepsy (n = 96) and healthy control (n = 82) subjects were assessed with a comprehensive neuropsychological battery. Test performances were adjusted for age, gender, and education and transformed to a common metric (z scores). Analyses included group comparisons and correlations of duration of epilepsy with cognitive morbidity. RESULTS: Patients with temporal lobe epilepsy exhibited not only worse memory function (p < 0.05) but worse performance across measures of intelligence, language, executive function, and motor speed (p < 0.05). Chronicity of epilepsy was related to worsening mental status (r = 0.42, p < 0.001). This relationship was particularly evident among those individuals with less (r = 0.58, p < 0.001) compared with more (r = 0.25, NS) cerebral reserve, operationally defined by years of formal education. CONCLUSIONS: Neuropsychological morbidity in chronic temporal lobe epilepsy is widespread in nature despite a focal epileptic process. Cross-sectional analyses demonstrate that increasing duration of epilepsy is associated with worsening mental status. Individuals with less educational attainment (low cerebral reserve) exhibit especially poor cognitive function in association with chronicity of epilepsy.

Adolescent↗

Biliary epithelial trefoil peptide expression is increased in biliary diseases.

AIMS: Maintenance of the cellular integrity of the biliary epithelium may involve the production of mucins and mucin-associated peptides. In the luminal gastrointestinal tract, mucins and the mucin-associated trefoil peptides (TFF) are integral to cytoprotection and cellular repair of the mucosa. METHODS AND RESULTS: Samples of normal and diseased human liver tissue were examined using histological and immunohistochemical techniques, for the expression of TFF and mucins. Bile ducts were classified as small, medium or large depending upon the number of biliary epithelial cells. TFF expression was demonstrated in biliary epithelial cells of both normal and diseased liver tissue. TFF expression was greatest in the large bile ducts. In normal liver tissue, expression of at least one TFF was demonstrated in 2-7% of small bile ducts, 5-31% of medium bile ducts and 31-85% of large bile ducts. Seventy-seven percent of large bile ducts secreted mucins and all three TFF concurrently, compared with 3% of medium bile ducts and no small bile ducts. Biliary disease resulted in an increased expression of TFF1 and TFF3 in the medium bile ducts. CONCLUSIONS: The biliary epithelial cells in normal and diseased human liver tissue express TFF, particularly in the larger bile ducts. TFF expression may be up-regulated or induced in biliary diseases as a response to injury, as is seen in epithelial damage elsewhere in the gastrointestinal tract.

Adult↗

Id2 is a target of the beta-catenin/T cell factor pathway in colon carcinoma.

Activation of beta-catenin/T cell factor (TCF) transcription as a result of mutations in the adenomatous polyposis coli (APC) and/or beta-catenin genes occurs in the majority of colon tumors. An increasing number of genes, including c-myc and cyclin D1, have been implicated as targets of this pathway. We now report that the dominant negative helix-loop-helix regulator Id2 is also a target of the beta-catenin/TCF transcription pathway in colon adenocarcinoma. Investigation of the mechanism for the overexpression of Id2 in colon carcinoma cells demonstrated that the Id2 promoter is activated, and the Id2 protein is up-regulated by beta-catenin. Conversely, reducing free beta-catenin blocked this induction of promoter activity. We have also used an electrophoretic mobility shift assay and supershift to identify a motif in the Id2 promoter that binds to TCF4 protein. Site-directed mutagenesis of this motif abolished promoter reporter activity. Both transfection of Id2 into SW480 cells and induction of Id2 in HT29 colon cells was found to increase anchorage-independent survival of these cells. Growing evidence associates disruption to Id2 expression with tumorigenesis, and our findings suggest that this dysregulation of Id2 expression is due to the activation of the beta-catenin/TCF pathway.

Adenocarcinoma↗

Evaluation of a new rapid urine screening analyser: CellFacts.

The aim of this study was to evaluate a new urine screening analyser in a Hospital Bacteriology Laboratory: the Cellfacts Urine Screening Analyser (Microbial Systems Limited (MSL), Coventry, England). A cohort of 1036 urine specimens were analysed by both the CellFacts and routine traditional methods. Using the CDC urinary tract infection decision levels, and compared to reference methods, the sensitivity and specificity were respectively 88.9% and 76.2%, and the predictive negative value and predictive positive value respectively 93.3% and 64.8%. Compared to the microscopy, the correlations of white blood cell count and red blood cell count were good, respectively (r = 0.8, p < 0.0001) and (r = 0.6, p < 0.0001). These results indicate that, although several positive samples were not reported, CellFacts facilitates efficient, rapid screening of infected urine specimens. This leads to perform a cytobacteriological analysis only on those results screened as positive by the automatic analysis system.

Adolescent↗

Methylation of exon 2 of p16 is associated with late stage oesophageal cancer.

Methylation of the p16 gene was studied in 16 oesophageal tumours. Five (31%) of the tumours were found to be methylated in exon 1 and eight (50%) were methylated in exon 2. The loss of p16 protein correlated with methylation of exon 1 (P = 0.005). However, methylation of exon 2, but not exon 1, was found to be associated with late stage tumours (P = 0.01). We conclude that the methylation of exon 2 of p16 may have effects on the progression of oesophageal tumours that are independent of the expression of the p16 protein.

Adenocarcinoma↗

Utility of history, examination and laboratory tests in screening those returning to Europe from the tropics for parasitic infection.

OBJECTIVES: To examine the utility of the different elements of screening expatriates and travellers returned from the tropics for parasitic disease (exposure history, symptoms, examination and laboratory tests). METHODS: In phase 1 (conducted prospectively 1990-91), 1029 asymptomatic returnees had a detailed questionnaire and interview on risk-behaviour, physical examination and laboratory tests. In phase 2 (1997-98), 510 consecutive patients referred for routine screening (276 symptomatic and 234 asymptomatic) were screened with laboratory tests. RESULTS: Exposure history did not correlate reliably with parasite burden. In phase 1 physical examination revealed 387 abnormalities, only three of which indicated parasitic disease. Schistosomal serology was positive in 11% (CI 9-13) of these asymptomatic cases including patients with light or no reported freshwater exposure. Stool microscopy was positive in 19% (CI 16-22) of cases not correlated with reported eating habits, and eosinophilia was present in 8% (CI 6-10). In phase 2 reported symptoms did not correlate with parasitic disease. Schistosomiasis was present in 15% (CI 13-24) of asymptomatic and 18% (CI 13-22) of symptomatic individuals (OR 1.2 P = 0.46); stool microscopy was positive in 14% of both symptomatic and asymptomatic patients, and eosinophilia in 9% of symptomatic and 6% of asymptomatic individuals. CONCLUSION: Potentially serious asymptomatic infection is common in travellers. Detailed exposure history, symptom history and physical examination added little to detecting cases. Stool microscopy, schistosomal serology and eosinophil count all had good yield. Filarial serology had low yield in patients without eosinophilia.

Adolescent↗

Necrotizing pulmonary granulomata in a marijuana smoker.

We describe the case of a heavy marijuana and tobacco smoker who presented with progressive exertional dyspnea of 2 months' duration, and bilateral nodular lung infiltrates. Examination of the lung fields was normal, and lung function tests showed mild airflow obstruction with moderately reduced gas transfer. BAL returned green-black fluid consisting predominantly of macrophages laden with carbon pigment. Thoracoscopic lung biopsy showed miliary necrotizing granulomata with an alveolar exudate of carbon-laden macrophages within macroscopically blackened lung. The differential diagnosis of pulmonary granulomata in this patient is discussed.

Adult↗

Murine allergic respiratory responses to the major house dust mite allergen Der p 1.

BACKGROUND: Although many studies have examined chronic asthma, limited data exist on acute immunopathogenic events induced by allergens. The aim of the study was to investigate the acute cellular, serologic and histopathologic events in airway inflammation produced by intranasal challenge of mice sensitised to the major house dust mite allergen Der p 1. METHODS: C57BL/6 mice were immunised subcutaneously with Der p 1 in alum. Mice were bled and challenged intranasally with Der p 1 on day 14 and killed on day 17. Lungs were fixed in situ, processed and stained with haematoxylin and eosin. The degree of inflammation and eosinophil infiltration was quantified by image analysis. Specific IgE was determined by passive cutaneous anaphylaxis. Cells from spleen and draining lymph nodes were cultured for 24 h with Der p 1, and IL-3/GM-CSF released into supernatants was measured by bioassay. RESULTS: Intranasal challenge of sensitised mice induced eosinophilic influx into the large and small airways and the alveolar regions of the lung, mucus plugging and in severe cases numerous Charcot-Leyden crystals. The quantitation of the inflammation induced by different sensitisation and challenge doses showed that optimal inflammation could be produced using only 1 microg of allergen for both sensitisation and challenge. The degree of inflammation was not related to the titre of IgE antibody and was indeed produced in its absence. T cell reactivity of spleen cells to the allergen was decreased suggesting cell migration or inactivation. CONCLUSIONS: Mice sensitised and challenged intranasally with as little as 1 microg of Der p 1 produced an extensive pulmonary eosinophilic inflammation which shared many of the features of the inflammation found in asthma. The small amount of allergens required and the use of intranasal challenge should provide a useful model.

Allergens↗

Measurement of acute phase proteins for assessing severity of Plasmodium falciparum malaria.

Seventeen adult patients with acute Plasmodium falciparum malaria, admitted to the Hospital for Tropical Diseases, were studied. Serial measurements of the serum concentration of C-reactive protein, serum amyloid A protein, and percentage parasitaemia were determined, together with initial measurement of serum electrolytes, liver function, haemoglobin, white cell and platelet counts. Initial C-reactive protein and serum amyloid A concentrations were increased (C-reactive protein mean 49.0 mg/l serum amyloid A 28 mg/l) falling towards the normal range by the seventh day of treatment. There was a significant correlation between the pretreatment parasite count and clinical and laboratory markers of inflammation. C-reactive protein and serum amyloid A concentrations correlated inversely with the serum sodium. These results indicate that measurement of acute phase reactants such as C-reactive protein and serum amyloid A may prove valuable in assessing the severity of P falciparum malaria, and in following the response to antimalarial treatment.

Acute Disease↗

Ivermectin in the treatment of onchocerciasis in Britain.

Thirty-one patients with onchocerciasis were treated with a single dose of 150-200 micrograms/kg ivermectin. They were observed for three days to detect acute reactions and were reassessed clinically and parasitologically three, six and twelve months after treatment. 22 patients were expatriates. All had early, light and often localised infections and were not reexposed to infection during the course of the study. 25 patients completed follow-up. Patients who relapsed were retreated with the same dose after an interval of not less than five months. Adverse reactions were less severe than those experienced by similar patients treated with diethylcarbamazine and only one patient was given corticosteroids. 17 patients (68%) relapsed within one year and two thirds of these had done so within 6 months. A similar pattern was seen after the second dose. A single dose of ivermectin, repeated every three to six months as necessary, is likely to be the treatment of choice for patients in non-endemic areas, lightly infected with Onchocerca volvulus, until a safe macrofilaricidal drug emerges. One third of such patients may be cured with each treatment.

Adolescent↗

The primary antibody response of malaria patients to Plasmodium falciparum sexual stage antigens which are potential transmission blocking vaccine candidates.

Thirty serum samples collected from adult patients attending the Hospital for Tropical Diseases, London, with P. falciparum malaria, were studied. Sera were screened by indirect immunofluorescence for anti-gametocyte antibodies. Twelve of the serum samples taken from 14 patients with primary infections were found to have both IgM and IgG antibodies to gametocyte antigens and total Ig titres comparable with those of patients who had had previous malaria attacks. Sera of individuals from hyperendemic areas have been found to immunoprecipitate the 230 and 48/45 kD gametocyte surface antigens which are known targets of transmission blocking antibodies. To investigate the epitope specificity of the serum samples from our adult patients, competitive ELISAs with 3 monoclonal antibodies (MAbs) that block transmission and recognize different epitopes on the 48/45 Kd antigen, were carried out. Specific antibodies for these epitopes were found in 60% of the sera while nearly a third were able to inhibit the binding of at least two MAbs.

Adult↗

Human gnathostomiasis.

Following a meal that included raw fish in Bangladesh, a woman aged 40 years had symptoms suggestive of gnathostomiasis. The presentation of her illness and the results of investigations are reported.

Adult↗