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Biomedical subjects

A Ramsay

Publications and source records attributed to A Ramsay.

At least 19 recordsLinked to original sources
PubMed2007

Investing time in microscopy: an opportunity to optimise smear-based case detection of tuberculosis.

SETTING: St. Elizabeth Hospital, rural North-west Cameroon, an area with high tuberculosis (TB) and human immunodeficiency virus (HIV) incidence. OBJECTIVE: To measure the time spent during routine sputum smear microscopy and assess whether reexamining slides for 10 min translates into higher case detection of smear-positive cases. DESIGN: A prospective observational study over a 6-month period with three components: 1) timing of routine sputum smear examination; 2) blinded reexamination of all slides for 10 min and results compared with initial readings; and 3) blinded re-examination, by the original microscopists, of a portion of false-negative slides mixed with true negatives for 10 min. RESULTS: A total of 204 patients submitted 612 sputum specimens for screening. The median routine examination time was 2 min 6 seconds (interquartile range 1:30-2:30). A 10 min examination significantly increased the number of positive smears from 82 to 116 (P = 0.0083), and overall case detection from 28 to 48 patients (P = 0.011). On review by the original readers, more than half of the false-negative slides were reported as positive after 10 min. CONCLUSION: Sputum smear microscopy has low sensitivity if performed too quickly, and 10 min re-examination significantly increases case detection. Ensuring that smears are examined for the recommended duration may be a simple and low-cost way to improve case detection.

Cameroon↗
PubMed2006

Systemic vasculitis: a cause of indeterminate intestinal inflammation.

OBJECTIVES: Indeterminate intestinal inflammation may result from a variety of inflammatory conditions in addition to ulcerative colitis and Crohn disease. The primary systemic vasculitides may present with intestinal inflammation and an indeterminate colitis. We set out to describe a series of children with primary systemic vasculitis who initially presented with clinical features suggestive of inflammatory bowel disease (IBD) to establish criteria that might help discriminate between IBD and primary systemic vasculitis. METHODS: Ten children (6 boys, median age at presentation 8.9 years, range 0.9-14.5 years) satisfied inclusion criteria. RESULTS: All had abdominal pain, weight loss, diarrhea (6 of 10 bloody) and laboratory evidence of a severe acute phase response. Extraintestinal clinical features included vasculitic rash, renal impairment, myalgia, testicular pain and polyarthritis. Endoscopy showed vascular changes or other macroscopic findings suggestive of vasculitis in 5 of 10 patients. Gut histology revealed indeterminate chronic inflammatory mucosal changes and one patient with small artery fibrinoid necrosis in the submucosal vessels. Extraintestinal biopsy was performed in 6 patients and had a higher yield for the demonstration of vasculitis than intestinal biopsy. The results of selective visceral angiography was suggestive of vasculitis in all patients, but was normal in 7 cases of treatment-unresponsive classic IBD. Treatment comprised corticosteroid and azathioprine in all patients. Cyclophosphamide was given to 7 of 10 patients. CONCLUSIONS: Extraintestinal manifestations and inflammatory responses that may be disproportionate to the degree of intestinal inflammation provide clues to the presence of an underlying primary systemic vasculitis, and these data suggest that selective visceral angiography plays a key role in the diagnosis of vasculitis in this context. It is important to identify and treat any vasculitic component because failure to do so may result in consequential morbidity or mortality.

Abdominal Pain↗
PubMed2006

Sure Start graduates: predictors of attainment on starting school.

BACKGROUND: We report the analysis of the services used and the outcomes for children who used four Sure Start programmes prior to starting school in 2003. METHODS: A cohort study compared the intervention group both to classmates who lived in the areas covered by Sure Start but did not access it, and to a random sample of children in the same Local Education Authority who did not have access because they lived outside these areas. The impact of service use variables on various outcomes for users was explored using multiple linear regression analysis. RESULTS: No differences were found in school attainment between users and non-users on average. However, in one of the four areas, users' outcomes were consistently worse. By contrast, in one area, they appeared to be marginally superior on non-academic developmental scores. When we controlled for between-area differences, we also found an association between high use of Sure Start and personal and social development scores. IMPLICATIONS: Much of the variation in outcomes remains to be explained. Tentative findings suggest stronger associations between Sure Start use and better non-academic developmental outcomes. These findings add to our understanding of the impact of focused, high-quality pre-school provision. Methodological issues raised include rater bias, recruitment bias and a need to measure both frequency and type of service use.

Age Factors↗
PubMed2006

A one-day method for the diagnosis of pulmonary tuberculosis in rural Ethiopia.

Smear diagnosis of pulmonary tuberculosis (PTB) requires three sputum examinations over 2 days. We evaluated the performance of two sputum specimens obtained on a single day (the second specimen submitted 1 h after the first) against the standard 2-day method in rural Ethiopia. A total of 243 suspects were enrolled; 52 had confirmed PTB: 49 (94%) were detected by the same-day method and 51 (98%) by the standard method (P > 0.5). The same-day approach would reduce the number of visits required for diagnosis, save resources for the health system and the patient, and ultimately improve case detection in poorer countries.

Ethiopia↗
PubMed2006

The bleach microscopy method and case detection for tuberculosis control.

The World Health Organization (WHO) and the International Union Against Tuberculosis and Lung Disease (The Union) recommend direct sputum smear microscopy for tuberculosis (TB) case finding in resource-poor settings. This method is associated with poor sensitivity. Digestion of sputum with bleach prior to smear preparation has been reported to increase sensitivity. Some workers, having reviewed the relevant literature, have called for the WHO and The Union to advocate for a shift to this methodology for TB case finding. This article highlights deficiencies in the scope and detail of available evidence, and cautions against the premature, and possibly counter-productive, adoption of so-called 'bleach microscopy'. Further well-guided research is required to answer policy-relevant gaps in our knowledge about this promising technology.

Humans↗
PubMed2005

Microbiological validation of smear microscopy after sputum digestion with bleach; a step closer to a one-stop diagnosis of pulmonary tuberculosis.

BACKGROUND: Smear microscopy is relatively insensitive for the diagnosis of TB. The digestion of sputum with household bleach prior to smear preparation has been reported to improve its sensitivity. This method has not been validated. METHODS: Seven hundred and fifty six patients with symptoms suggestive of pulmonary TB (PTB) were asked to submit 3 sputum specimens for direct microscopy. One specimen was selected at random for culture and another specimen was digested to prepare a further smear. The WHO case definition (>or=2 positive smears or one positive smear and positive culture) was used to compare the sensitivity and specificity of the smears. FINDINGS: Four hundred and fifty five (60%) patients were culture-positive. Of these, 235 (31%) had "definite" PTB and 223 (29%) "very likely" PTB (smear-negative, culture-positive). The WHO case definition identified 51% (235/458) of the patients with "definite" or "very likely" PTB. One digested smear detected 219 (93%) of the 235 patients with "definite" PTB and 10 patients with "very likely" PTB (sensitivity (95%CI) 50% (45-55%); specificity 99% (97-100%)). The positive and negative predictive values for one digested smear were 98% (95-99%) and 56% (52-60%) respectively, which were not different (p>0.5) to the WHO case definition (100% and 57%, respectively). INTERPRETATION: One bleach-digested smear is as sensitive and specific as the WHO case definition for the diagnosis of PTB.

Bacteriological Techniques↗
PubMed2005

Comparison of scanty AFB smears against culture in an area with high HIV prevalence.

To verify among tuberculosis (TB) suspects attending hospitals in Abuja, Nigeria, if sputum smears graded as scanty are false-positive, sputum smears from 1068 patients were graded with the International Union Against Tuberculosis and Lung Disease classification. One specimen was cultured. Eight hundred and twenty-four (26%) smears were positive, 137 (4%) scanty and 2243 negative. Of 1068 cultures, 680 (64%) were positive. One hundred and thirty (95%) scanty and 809 (98%) positive smears were culture-positive. Twelve of 18 patients with a single scanty smear and 51 of 52 with > or = 2 scanty smears were culture-positive. Fewer than < 5% scanty results, < 1% of the patients treated for TB, are false-positive.

Colony Count, Microbial↗
PubMed2004

A mixed thyroglossal cyst.

The case is described of a boy who presented at age six months with symptoms and signs of a thyroglossal cyst, which seemed to be confirmed by ultrasound findings. The cyst slowly increased in size, and eventually the patient underwent Sistrunk's procedure at age four years. Histology showed that the cyst was in fact a mixed thyroglossal and dermoid cyst. This casts doubt on the doctrine that thyroglossal cysts and dermoid cysts are anatomically and histologically separate entities, and strengthens the view that these cysts should be more appropriately named 'thyroglossal abnormalities'.

Child, Preschool↗
PubMed2003

Altered placental development in interleukin-10 null mutant mice.

Placental morphogenesis and nutrient transfer function are regulated by growth factors at the foeto-maternal interface. Interleukin (IL)-10, expressed in the decidua and placenta, is implicated in regulating extravillous cytotrophoblast invasion through inhibiting matrix metalloproteinase expression and influencing the quality of the maternal immune response. Our laboratory has previously found that IL-10 deficiency in both the mother and foetus increases foetal weight at day 18 without altering placental weight suggesting that the placenta has a greater functional capacity when IL-10 is absent. The present study has used IL-10 null mutant (IL-10-/-) mice to investigate the role of IL-10 in placental development. Placental structure was assessed in adult virgin IL-10-/- or wild-type (IL-10+/+) mice mated with males of the same genotype and sacrificed at day 18 of gestation. Mid-sagittal cross sections of placental tissue were stained with Masson's trichrome or immuno-labelled with MTS-12 and pan-cytokeratin reactive antibodies to identify foetal endothelial cells and trophoblasts, respectively, and examined with video image analysis. IL-10 deficiency increased the total cross sectional area of the placenta by 28 per cent (IL-10-/- n=22 placentae from 8 dams, IL-10+/+n =21 placentae from 9 dams, P=0.026), principally through increasing the cross sectional area of placental labyrinth by 37 per cent (P=0.025). The proportion of maternal blood space in the labyrinth was increased by 26 per cent (P=0.001) and that of trophoblast was decreased by 16 per cent (P=0.001) in IL-10-/- placentae. The surface area of trophoblast per gram of labyrinth was increased by 41 per cent (P=0.0005) in IL-10-/- placentae. In the absence of IL-10, structural correlates of placental function are enhanced consistent with concomitant increases in foetal growth. These data indicate that IL-10 is a regulator of placental morphogenesis, acting to retard expansion of the placental labyrinth and to modify the architecture of the maternal blood sinuses. Since previous studies have paradoxically shown that postnatal growth is impaired in IL-10 null mutants, these observations are consistent with a role for IL-10 in regulating placental development and foetal programming.

Animals↗
PubMed2002

Tyrosine phosphorylation in human lymphomas.

In a previous study, we showed that the high level of protein tyrosine phosphorylation present in lymphomas containing an anaplastic lymphoma kinase (ALK) can be demonstrated in routinely processed paraffin tissue sections using immunolabelling techniques. In the present study we investigated whether oncogenic tyrosine kinase activation also occurs in other categories of lymphoma by staining 145 cases of lymphoma covering those tumours with a range of different subtypes including those with morphological similarity to ALK-positive anaplastic large cell lymphoma (ALCL). Twelve cases of the borderline malignant disorder lymphomatoid papulosis were also studied. Twenty seven of the 28 cases of ALK-positive ALCL showed the extensive cytoplasmic labelling for phosphotyrosine in the neoplastic cells. The remaining case containing moesin-ALK exhibited membrane-associated phosphotyrosine expression. There was no nuclear phosphotyrosine labelling in any of the ALK-positive ALCL, even though ALK was present within the cell nuclei in 23 of the tumours. Variable degrees of phosphotyrosine labelling, usually membrane-restricted, were observed in 7/40 cases of ALK-negative ALCL, 9/29 cases of diffuse large B-cell lymphoma, 3/6 cases of mediastinal B-cell lymphoma, 2/7 cases of Hodgkin's lymphoma, 3/6 cases of peripheral T-cell lymphomas unspecified, 4/6 cases of B-cell chronic lymphocytic leukaemia, 2/6 cases of follicular lymphomas and 2/12 cases of lymphomatoid papulosis studied. However none of these phosphotyrosine-positive cases showed the strong cytoplasmic labelling comparable to that seen in ALK-positive lymphoma. We conclude that activation of a tyrosine kinase is probably not a major oncogenic event in lymphomas other than ALK-positive ALCL.

Cell Nucleus↗
PubMed2002

Triple cycle audit of primary retinal detachment surgery.

PURPOSE: To determine the effect of increasing subspecialisation on the results of retinal detachment surgery in one city. METHODS: Three audit cycles over a 10-year period when major subspecialisation and organisational changes were occurring. Retrospective case note reviews of all primary surgery for rhegmatogenous retinal detachments in each of the audit periods. Statistical analyses used contingency table/chi-square methods for comparing all three audits and Fisher's exact test/mean odds ratio with 95% confidence intervals (CIs) for the Audit 1 vs Audit 3 comparison. RESULTS: A marked improvement in success rates occurred: primary reattachment rose from 67% in Audit 1 to 87% in Audit 3 (P = 0.0004), and final success from 84% to 97% (P = 0.0003). There was a dramatic change in operative techniques over the same period: the percentage of vitrectomies increased from 1.5% in Audit 1 to 48% in Audit 3, while that of 'open' conventional procedures decreased from 78% to 32%. However, the improvement in anatomical success was not mirrored by an increase in the percentage of patients with 6/12 or better visual acuity postoperatively (55% in Audit 1, 49% in Audit 3; P = 0.34, mean odds ratio = 0.78; 95% CI 0.48-1.2). The percentage of patients with 6/18-6/36 post op visual acuity did increase in Audit 3 (18% in Audit 1; 29% in Audit 3; P = 0.03, mean odds ratio = 1.9; CI 1.1-3.3), and the percentage with 6/60 or worse decreased (27% in Audit 1, 20% in Audit 3; P = 0.26, mean odds ratio = 0.71; CI 0.40-1.2). CONCLUSIONS: With increased subspecialisation there has been an increase in anatomical success, but the goal of 100% reattachment is still not being attained. There remains scope for further improvement in anatomical and functional outcomes.

England↗
PubMed2001

Melioidosis and Pandora's box in the Lao People's Democratic Republic.

Melioidosis has not been recognized previously in Laos, but within months of starting a prospective study of community acquired septicemia in Vientiane, 2 patients with melioidosis were identified. One was a previously healthy, 44-year-old female rice farmer who presented with supraclavicular lymphadenitis and the other was a 74-year-old man with diabetes and renal calculi who was receiving corticosteroids and had septicemia and septic arthritis.

Adult↗
PubMed2001

PAX3-FKHR induces morphological change and enhances cellular proliferation and invasion in rhabdomyosarcoma.

Alveolar rhabdomyosarcoma (ARMS) is consistently associated with the characteristic translocations t(2;13)(q35;q14) and t(1;13)(p36;q14), which encode for the PAX3-FKHR and PAX7-FKHR fusion oncoproteins respectively. We have investigated the relationship between PAX3-FKHR expression and ARMS histogenesis in primary tumors and cell culture systems. In a blinded histological review of discrepant primary tumors in which there was PAX3-FKHR expression but embryonal histology, we found small areas of alveolar histology in 6 of 11 cases. This suggests that histology alone may under-represent the association between PAX3-FKHR and ARMS, and we investigated this link by examining the effect of ectopic PAX3-FKHR expression on RMS cells. Two cell lines, RD and HX170C, were stably transfected with a PAX3-FKHR expression construct. In cloned transfectants derived from both lines, PAX3-FKHR expression resulted in increased proliferative rate in vitro and promoted cell growth in the absence of added growth factors. Tumors that formed as xenografts in immunodeficient mice were faster growing, more locally invasive, and had a denser, more pleomorphic architecture than untransfected or empty vector transfected tumors. The characteristic clefts and alveolar spaces of ARMS, however, were not seen. In contrast, tumors grown as xenografts from individual clones derived from ARMS cell lines showed all of the classical morphological features of ARMS suggesting divergence in vivo from precursor cells propagated in culture.

Animals↗