Pleural fluid residue as a diagnostic tool for cytology-negative malignant pleural effusion: A proof-of-concept study.

Background: Pleural fluid residue, or macroscopic tissue, circulating freely in the pleural fluid obtained through direct filtration, may carry diagnostic histopathological information. We aimed to determine the histopathological concordance of pleural fluid residue in diagnosing TPE and MPE, compared with conventional pleural biopsy. This was a prospective cohort study of consecutive inpatients with cytology-negative exudative effusion who underwent pleuroscopy and had their initial suctioned pleural fluid filtered for residue samples. Pleural fluid residue demonstrated malignant cells in four out of seven cases of pleural biopsy-confirmed malignancy. Pleural fluid residue has comparable cytomorphology but reduced cellularity compared with pleural biopsy. No tuberculous histological features were present in the pleural fluid residue samples. In this preliminary study pleural fluid residue provided histopathological information for malignant pleural effusion, but no incremental diagnostic information for tuberculous effusion. However larger and more definitive studies are required to clarify these findings, and to explore the utility and suitability of pleural fluid residue for mutational analysis. What the study adds: This study demonstrates the potential of pleural fluid residue as a non-invasive diagnostic method for confirming malignancy in cytology-negative exudative effusion. What are the implications of the findings: In resource-limited settings or patients contraindicated for pleural biopsy, pleural fluid residue may provide a viable diagnostic alternative; however, this observation needs further validation.

Vitamin D Binding Protein and Vitamin D Levels in Multi-Ethnic Population.

INTRODUCTION: Low levels of 25-hydroxyvitamin D (25(OH)D) has been associated with many negative health outcomes including falls and fractures. 25(OH)D is largely bound to vitamin D binding protein (VDBP). There is increasing evidence that free or bioavailable 25(OH)D may be a better measure of vitamin D deficiency. OBJECTIVE: To determine the prevalence of 25(OH)D deficiency and VDBP levels in multi-ethnic population, and its impact on muscle strength. DESIGN AND METHODS: Cross-sectional study of older adults in Western region of Singapore. 295 participants from three ethnic groups were selected from the Healthy Older People Everyday (HOPE) cohort for measurements of total 25(OH)D and VDBP levels. Total 25(OH)D, VDBP, frailty status, Timed-Up-and-Go (TUG) and grip strength (GS) were assessed. Albumin, free and bioavailable 25(OH)D were only available for 256 participants. RESULTS: 53% of Malay and 55% of Indians were deficient in 25(OH)D compared with 18.2% of ethnic Chinese participants. Chinese also had higher total 25(OH)D concentrations with a mean of 29.1 ug/l, (p = <0.001). Chinese had the lowest level of VDBP (169.6ug/ml) followed by Malay (188.8 ug/ml) and Indian having the highest (220.1 ug/ml). Calculated bioavailable and free 25(OH)D levels were significantly higher in Chinese, followed by Malays and Indians, which also correlated with better grip strength measures amongst the Chinese. CONCLUSION: The Malays and Indians had overall lower free, bioavailable and total 25(OH)D compared with ethnic Chinese. Chinese ethnic group also had the lowest VDBP and better overall grip strength.

The role of tests of frontal executive function in the detection of mild dementia.

OBJECTIVE: To compare the performance of patients with mild dementia (Mini Mental State Examination (MMSE) >23), depression (Montgomery-Asberg depression rating scale (MADRS) >12) and controls on tests of frontal executive function (FEF), to see if simple tools could be an adjunct to early recognition of dementia in primary care. DESIGN: Subjects were required to score above 23 on the MMSE, and to be non-depressed unless in the depression group. Tests of FEF used were a letter based verbal fluency test, a cognitive estimates test, trail marking parts A and B, and a Stroop colour word test. Subjects were followed up at one year to assess long-term outcomes. SETTING: The Thornhill Unit, an old age psychiatry unit, Moorgreen Hospital, Southampton, UK. PATIENTS: Sixteen patients with a clinical diagnosis of dementia but with normal or borderline MMSE scores, 16 subjects with depression and 19 healthy control subjects. RESULTS: Subjects with mild dementia scored significantly worse than control subjects on all FEF tests used other than verbal fluency. Subjects with mild dementia were only found to score worse than depressed subjects on the cognitive estimates test and Stroop test, with the Stroop test providing better discrimination between these groups. At follow-up, MMSE scores of both dementia and depression groups were worse. CONCLUSIONS: Many simple tests of FEF can distinguish subjects with mild dementia from controls, although caution must be taken in the presence of depression. Of these tests, the cognitive estimates test may provide a simple test which can be used in conjunction with screening tests for dementia, such as the MMSE. The Stroop colour test was the most successful at distinguishing subjects with mild dementia from those with depression, but was more difficult to use. The depression group remained cognitively impaired at follow-up, despite improvements in depressive symptoms.

The role and histological classification of needle core biopsy in comparison with fine needle aspiration cytology in the preoperative assessment of impalpable breast lesions.

AIMS: To investigate the role of needle core biopsy (NCB) in the preoperative assessment of impalpable breast lesions, mainly derived from the NHS Breast Screening Programme (NHSBSP) and to assess our own modifications to a suggested system for the classification of breast NCBs. METHODS: The NCB, fine needle aspiration cytology (FNAC), and radiology scores from 298 women with non-palpable breast lesions presenting between January 1997 and December 1998, together with the open biopsy results (where available) were collated and analysed. RESULTS: The mean follow up period was 15.8 months (range, 5-28). The 298 NCB specimens were categorised as follows: unsatisfactory/non-representative (B1; n = 61; 20.5%), benign but uncertain whether representative (B2r; n = 52; 17.4%), benign (B2; n = 103; 34.6%), lesions possibly associated with malignancy but essentially benign (B3a; n = 9; 3.0%), atypical epithelial proliferations (B3b; n = 10; 3.4%), suspicious of malignancy (B4; n = 7; 2.3%), and malignant (B5; n = 56; 18.7%). Excision biopsy was performed in 43 cases within the B1 (n = 19), B2r (n = 8), B2 (n = 8), and the B3a (n = 8; data unavailable in one case) categories, revealing malignancy in 18 (42.8%) cases and in 65 cases within the B3b, B4, and B5 categories, revealing malignancy in 64 cases (98.5%). The sensitivity of NCB for malignancy was 87.7%, with a specificity and positive predictive value of 99.3% and 98.5%, respectively. FNAC had an inadequacy rate of 58.7%, a complete sensitivity of 34.5% and a specificity of 47.6%. CONCLUSIONS: This study confirms the value of NCB in the preoperative assessment of impalpable breast lesions. Two new categories are suggested for the NCB classification; category B2r for benign breast tissue where representativeness is uncertain, and the subdivision of category B3 into B3a for benign lesions potentially associated with malignancy (for example, radial scars and intraduct papillomas) and B3b for more worrisome atypical epithelial proliferations. These will aid the accurate audit of NCB and identify more clearly the intellectual pathway leading to a particular assessment.

The House-Brackmann system and assessment of corneal risk in facial nerve palsy.

PURPOSE: The House-Brackmann (HB) facial nerve grading system is widely used by ENT/head and neck surgeons, but is perhaps of less value to the ophthalmologist. Our aim was to assess the value of the numeric portion of this system in identifying those patients with facial nerve palsy who are at risk of corneal complications. We also sought to identify other factors that might be predictive of such complications. METHODS: Forty-two patients (43 palsies) were studied prospectively. The HB grade was recorded together with measurements of levator function, upper lid closure, Bell's phenomenon, lagophthalmos, ectropion, lower lid retraction and corneal sensation. Conjunctival injection and corneal staining were also graded. ROC (receiver operating characteristic) curves were used to assess the value of each parameter as a screening test for corneal complications. RESULTS: There was no cut-off of HB grade, levator function, Bell's phenomenon, ectropion or lower lid retraction that was sufficiently sensitive and specific to screen for corneal complications. However, on assessing lagophthalmos and upper lid closure, cut-offs with more favourable sensitivities and specificities were identified. CONCLUSIONS: The numeric portion of the HB grading system is not a useful guide in identifying those patients with facial nerve palsy who are at risk of corneal complications. Measurements of lagophthalmos and upper lid closure, alone or in combination with other tests, may be of more value.

Smoking habits in a cohort of U.K. adolescents.

Active smoking is an increasing problem amongst U.K. teenagers. The smoking habits of a cohort of 14-16-year-olds were determined and the association between regular active smoking and domestic and social factors investigated. Current smoking habits of a cohort of 2289 14-16-year-olds were assessed using a simple postal questionnaire. Data concerning potential factors associated with active smoking were collected from questionnaire completed by parents. Nine hundred and sixty-nine (44.8%) children admitted to having smoked at some time, with 562 (30.0%) having smoked in the previous 12 months. Three hundred and six (14.1%) children were regular smokers and 158 (51.6% of regular smokers, 7.3% of total cohort) smoked daily. Age, number of other children in the household, parental smoking, smoking sibling(s) and living in a single parent household were all independently associated with regular smoking. Regular smoking was a significant problem amongst this cohort of teenagers. Living with other smokers, age, household size and living with one parent all predicted a regular smoking habit.

Histamine releasability after adenosine challenge in subjects with allergic and non-allergic rhinitis: possible implications for mast cell priming.

Nasal provocation with adenosine 5'-monophosphate elicits nasal symptoms in subjects with rhinitis. Histamine released from airway mast cells may play a role in adenosine-induced nasal responses. To investigate the possible role of histamine in mediating adenosine-induced nasal responses, we measured its release in the fluid obtained by nasal lavage after adenosine 5'-monophosphate, guanosine 5'-monophosphate, and placebo instillations. Nasal lavages were performed before and 3, 5, 10, 15, 30 and 45 min after challenge with adenosine 5'-monophosphate, guanosine 5'-monophosphate, and normal saline in 11 patients with rhinitis and 7 normal subjects in a double-blind randomized placebo-controlled cross-over study to evaluate symptoms and to monitor changes in histamine levels. No symptoms or significant increases in histamine were observed after guanosine 5'-monophosphate and placebo challenge. Symptom scores increased in response to adenosine 5'-monophosphate challenge in the rhinitic subjects but not in the normal controls. Nasal provocation with adenosine elicited a significant release of histamine in the nasal lavage fluids with an immediate peak response: its median (range) concentration increased from the baseline value of 1.33 (0.16-14.54) ng/mL to 2.68 (0.31-61.11) ng/mL at 3 min. However, increased histamine levels were not associated with nasal symptom scores. When compared to non-atopic subjects, significantly higher levels of histamine were seen in the nasal lavage fluids of the atopic subjects following adenosine challenge. In the atopic subjects, the median (range) histamine concentration increased from the baseline value of 1.54 (0.16-14.54) ng/mL to that of 4.21 (0.70-61.11) ng/mL at 3 min, whereas no increment was seen in the non-atopic subjects, their histamine concentration being 0.81 (0.29-5.56) ng/mL and 0.74 (0.31-14.25) ng/mL at baseline and 3 min after adenosine challenge respectively. These findings indicate that adenosine elicits nasal responses in patients with rhinitis but not in normal controls. Moreover, adenosine elicits an immediate rise in histamine levels in the nasal lavage fluid, with the highest rise in atopic compared to non-atopic volunteers, suggesting that the nasal responses to adenosine may be an index of mast cell priming.

Histamine release upon adenosine 5'-monophosphate (AMP) nasal provocation in allergic subjects.

BACKGROUND: Nasal provocation with adenosine 5'-monophosphate (AMP) elicits nasal symptoms in subjects with rhinitis. Histamine released from mast cells may play a part in AMP induced nasal responses. METHODS: Symptoms of rhinitis were recorded and histamine release in the fluid obtained by nasal lavage after AMP, guanosine 5'-monophosphate (GMP), and placebo instillations was measured in nine subjects with allergic rhinitis and nine non-allergic controls in a double blind, randomised, placebo controlled study. RESULTS: No symptoms or significant increases in histamine were observed after GMP and placebo challenge. Significantly higher levels of histamine were seen in the nasal lavage fluids of allergic subjects following AMP challenge than in nonallergic controls, the median (range) histamine concentration increasing from the baseline value of 1.62 (0.44-6.99) ng/ml to 6.45 (0.81-16.17) ng/ml at three minutes. No increase in histamine levels was seen in the non-allergic subjects in whom the median histamine concentration was 1.13 (0.29-4.25) ng/ml at baseline and 0.97 (0.31-5.89) ng/ml three minutes after AMP challenge. CONCLUSIONS: AMP elicits an immediate rise in histamine levels in the nasal lavage fluid of allergic subjects compared with non-allergic individuals. These findings indicate that the exaggerated nasal response to adenosine may reflect mast cell priming in vivo, thus supporting its application as a potential new marker of allergic inflammation.

RANTES, macrophage-inhibitory protein 1alpha, and the eosinophil product major basic protein are released into upper respiratory secretions during virus-induced asthma exacerbations in children.

The presence of cytokines and the toxic eosinophil granule product major basic protein (MBP) was investigated in nasal aspirates from children with naturally occurring virus-induced asthma exacerbations and compared with levels in nasal aspirates taken from the same children when asymptomatic. Increased levels of MBP accompanied by increased levels of the chemokines RANTES and macrophage-inhibitory protein 1alpha were observed in nasal aspirates from children during the virus-induced exacerbations. Granulocyte-macrophage colony-stimulating factor was mostly undetectable in samples obtained during both symptomatic and asymptomatic periods. Interleukin-5 levels were low, but tended to increase in samples from symptomatic children. These data confirm that the eosinophil product MBP and the eosinophil chemoattractant chemokines RANTES and macrophage-inhibitory protein 1alpha are increased in upper respiratory viral infections associated with asthma exacerbations and suggest an important role for these chemokines in regulating eosinophil influx and activation. These chemokines may represent targets for therapeutic intervention in virus-induced asthma exacerbations.

Randomized double-blind placebo-controlled trial of homoeopathic 'proving' for Belladonna C30.

Homoeopathic drug pictures are developed by recording the symptomatic effects of homoeopathic remedies given to healthy volunteers (a 'proving'). In a double-blind randomized controlled trial we tested the hypothesis that individuals using an infinitesimal dilution of Belladonna (thirtieth potency, C30) would record more true symptoms, on a questionnaire that contained both true and false Belladonna proving symptoms, than those receiving placebo. 60 volunteers entered the study and 47 completed data collection. We were unable to distinguish between Belladonna C30 and placebo using our primary outcome measure. For the secondary outcome measure we analysed the number of individuals who proved to the remedy according to our predefined criteria: 4 out of 19 proved in the Belladonna C30 group and 1 out of 27 in the placebo group (difference not statistically significant). This pilot study does not demonstrate a clear proving reaction for Belladonna C30 versus placebo, but indicates how the question might be further investigated.