A prospective cohort study assessing the appearance of retrieved aesthetic orthodontic archwires.

OBJECTIVES: To investigate the appearance of three esthetic nickel titanium (NiTi) wires after 6 weeks of intra-oral cycling and to determine the association between objective and subjective measures of esthetics. SETTING AND SAMPLE POPULATION: A prospective cohort study was undertaken involving participants undergoing upper fixed orthodontic appliance treatment with ceramic brackets. MATERIALS AND METHODS: Fifty participants were assigned to one of three groups of NiTi esthetic wires (American Orthodontics Ever White™, Forestadent Biocosmetic™ and GAC High Aesthetic™), with wires retrieved after 6 weeks in situ. Participants completed a bespoke questionnaire exploring perceptions of wire esthetics. Objective measurement of coating loss was undertaken using a custom arch wire jig. RESULTS: American Orthodontics Ever White™ had the greatest mean coating loss (50.7%) followed by Forestadent Biocosmetic™ (6%), with GAC High Aesthetic TM undergoing minimal loss (0.07%) (P < .001). The majority of coating loss with the American Orthodontics Ever White™ wires arose in the anterior region while Forestadent Biocosmetic™ wires and GAC High Aesthetic™ wires exhibited coating loss posteriorly (P < .001). These findings were reflected in the subjective assessment with a negative correlation found between coating loss and final Visual Analogue Scale scores (P < .001). CONCLUSIONS: Considerable esthetic variation between arch wires following 6 weeks of intraoral cycling was identified in this prospective cohort study. Intraoral cycling has a negative impact on participant perception of arch wire esthetics, and objective and subjective assessment of wire esthetics appears to be consistent.

Apical MUC1 expression revealed on the foveolar epithelium in H. pylori gastritis.

BACKGROUND: The membrane mucin MUC1 is altered in its pattern of expression in cancer, and also in other pathological situations, including Helicobacter pylori gastritis. Here we investigate the basis for the loss of apical staining of the gastric foveolar epithelium in H. pylori gastritis. METHODS: MUC1 was examined in the gastric antrum from cases of H. pylori gastritis and normal controls. We used tissue sections that were either treated or not treated with periodate to effect deglycosylation, and the monoclonal antibodies LICRLonM8, MUSE-11, CT2 and BC2. RESULTS: We show that the epitopes on the TR domain of MUC1 are partially cryptic due to glycosylation and that MUC1 is present on the apical surface of the gastric foveolar epithelium of gastritis patients. CONCLUSION: This observation suggests that there is no substantial loss of the mucin domain of MUC1 from the apical surface in gastritis, as suggested by others, but rather the H. pylori influences the glycosylation of MUC1. This paper highlights the issue of epitope specificity of monoclonal antibodies directed against disease-associated markers, specifically when they are glycoproteins, as is the case for many cancer markers.

Human monoclonal antibodies targeting carbonic anhydrase IX for the molecular imaging of hypoxic regions in solid tumours.

BACKGROUND: Hypoxia, which is commonly observed in areas of primary tumours and of metastases, influences response to treatment. However, its characterisation has so far mainly been restricted to the ex vivo analysis of tumour sections using monoclonal antibodies specific to carbonic anhydrase IX (CA IX) or by pimonidazole staining, after the intravenous administration of this 2-nitroimidazole compound in experimental animal models. METHODS: In this study, we describe the generation of high-affinity human monoclonal antibodies (A3 and CC7) specific to human CA IX, using phage technology. RESULTS: These antibodies were able to stain CA IX ex vivo and to target the cognate antigen in vivo. In one of the two animal models of colorectal cancer studied (LS174T), CA IX imaging closely matched pimonidazole staining, with a preferential staining of tumour areas characterised by little vascularity and low perfusion. In contrast, in a second animal model (SW1222), distinct staining patterns were observed for pimonidazole and CA IX targeting. We observed a complementary pattern of tumour regions targeted in vivo by the clinical-stage vascular-targeting antibody L19 and the anti-CA IX antibody A3, indicating that a homogenous pattern of in vivo tumour targeting could be achieved by a combination of the two antibodies. CONCLUSION: The new human anti-CA IX antibodies are expected to be non-immunogenic in patients with cancer and may serve as broadly applicable reagents for the non-invasive imaging of hypoxia and for pharmacodelivery applications.

MUC4 and MUC5AC are highly specific tumour-associated mucins in biliary tract cancer.

Alterations in epithelial mucin expression are associated with carcinogenesis, but there are few data in biliary tract cancer (BTC). In pancreatic malignancy, MUC4 is a diagnostic and prognostic tumour marker, whereas MUC5AC has been proposed as a sensitive serological marker for BTC. We assessed MUC4 and MUC5AC expression in (i) prospectively collected bile and serum specimens from 72 patients with biliary obstruction (39 BTC) by real-time reverse transcriptase-PCR (qPCR) and western blot analysis, and (ii) 79 archived biliary tissues (69 BTC) by immunohistochemistry. In bile, MUC4 protein was detected in 27% of BTC and 29% of primary sclerosing cholangitis (PSC) cases, but not in other benign and malignant biliary diseases (P<0.01 and P=0.06). qPCR revealed a 1.9-fold increased MUC4 mRNA expression in BTC patients' bile compared with benign disease. In archived tissues, MUC4 protein was detected in 37% of BTC but in none of the benign samples (P=0.03). In serum, MUC5AC was found exclusively in BTC and PSC sera (44% and 13%, respectively; P<0.001 for BTC vs non-BTC) and correlated negatively with BTC survival. Biliary MUC4 and serum MUC5AC are highly specific tumour-associated mucins that may be useful in the diagnosis and formulation of therapeutic strategies in BTC.

Relationship between human tumour angiogenic profile and combretastatin-induced vascular shutdown: an exploratory study.

Combretastatin-A4-phosphate (CA4P) acts most effectively against immature tumour vasculature. We investigated whether histological angiogenic profile can explain the differential sensitivity of human tumours to CA4P, by correlating the kinetic changes demonstrated by dynamic MRI (DCE-MRI) in response to CA4P, with tumour immunohistochemical angiogenic markers. Tissue was received from 24 patients (mean age 59, range 32-73, 18 women, 6 men). An angiogenic profile was performed using standard immunohistochemical techniques. Dynamic MRI data were obtained for the same patients before and 4 h after CA4P. Three patients showed a statistically significant fall in K(trans) following CA4P, and one a statistically significant fall in IAUGC(60). No statistically significant correlations were seen between the continuous or categorical variables and the DCE-MRI kinetic parameters other than between ang-2 and K(trans) (P=0.044). In conclusion, we found no strong relationships between changes in DCE-MRI kinetic variables following CA4P and the immunohistochemical angiogenic profile.

Cranial Ultrasonography in Infantile Encephalitic Beriberi: A Useful First-Line Imaging Tool for Screening and Diagnosis in Suspected Cases.

BACKGROUND AND PURPOSE: Brain imaging is central to the diagnosis of infantile encephalitic beriberi. Because cranial sonography findings have not been described in infantile encephalitic beriberi, our aim was to investigate its role in the diagnosis of this condition. MATERIALS AND METHODS: We performed a retrospective review of head sonography of infants (admitted between November 1, 2014, and March 31, 2015) who presented with encephalopathy. Cranial ultrasonography scans were studied for the alteration of echogenicity of the basal ganglia. RESULTS: Of the 145 consecutive infants who presented with encephalopathy, 58 had thiamine-responsive encephalopathy (infantile encephalitic beriberi) and 87 had encephalopathy due to other causes. Forty-eight of 145 infants with encephalopathy showed hyperechoic basal ganglia. A hyperechoic appearance of the basal ganglia on cranial ultrasonography was found to have a sensitivity of 71% (41/58) and a specificity of 92% (80/87) in diagnosing infantile encephalitic beriberi. The sensitivity of cranial sonography increased with age. It was a maximum of 93% (14/15) in the 5 months and older age group. Specificity was a maximum of 100% (18/18) in infants older than 5 months of age. Sensitivity was maximum in Wernicke encephalopathy at 90% (18/20) and least in the acidotic form at 43% (10/23). Follow-up showed gradual normalization of the hyperechoic appearance of the basal ganglia during 8 weeks in 26/41 (63%), with mild atrophy of the basal ganglia in 6/41 (15%) CONCLUSIONS: Hyperechogenicity of the basal ganglia on cranial ultrasonography is a sensitive finding for the diagnosis of infantile encephalitic beriberi in infants who present with Wernicke encephalopathy.

Serial changes in response of hibernating myocardium to inotropic stimulation after revascularization: a dobutamine echocardiographic study.

OBJECTIVES: We sought to evaluate the serial changes in the response of the hibernating myocardium to dobutamine stimulation after revascularization. BACKGROUND: An improvement in myocardial contraction during dobutamine stress echocardiography (DSE), particularly a biphasic response, predicts recovery of rest function. However, little is known about the changes in the response of the myocardium to dobutamine after revascularization. METHODS: Thirty-four patients with stable coronary artery disease and regional left ventricular dysfunction underwent DSE before, early (within 1 week) and late (>6 weeks) after coronary angioplasty. Dobutamine was given in incremental doses from 2.5 to 40 microg/kg body weight per min. RESULTS: Of 180 revascularized segments with severe rest dysfunction, recovery of rest function was seen in 56 segments (31%) late after angioplasty, 80% of which had early recovery. Ventricular function during DSE was similar early and late after revascularization. Patients who showed a biphasic response to DSE before revascularization (n = 12) had the most improvement in function at rest (mean [+/-SD] wall motion score index [WMSI] 1.98 +/- 0.75 vs. 1.35 +/- 0.54, p < 0.05) and during DSE (2.11 +/- 0.67 vs. 1.21 +/- 0.41, p < 0.05) late after revascularization. Patients with sustained improvement during DSE before revascularization had no significant change in wall motion during DSE after angioplasty. However, patients without improvement in function at low dose DSE, who demonstrated worsening of function at a high dose, had significant augmentation in wall motion during DSE after revascularization (WMSI 2.16 +/- 0.50 vs. 1.60 +/- 0.57, p < 0.05). Patients who had no recovery of rest function had significant improvement in wall motion response to DSE, particularly when ischemia was inducible before revascularization. CONCLUSIONS: In myocardial hibernation, the majority of recovery of rest function occurs early after revascularization. Although patients who recover rest function show the most marked improvement in wall motion during DSE, those without recovery of rest function also have improved function during DSE, particularly when there is evidence of ischemia before revascularization.

End-diastolic wall thickness as a predictor of recovery of function in myocardial hibernation: relation to rest-redistribution T1-201 tomography and dobutamine stress echocardiography.

OBJECTIVES: The study assessed whether end-diastolic wall thickness (EDWT), measured with echocardiography, is an important marker of myocardial viability in patients with suspected myocardial hibernation, and it compared this index to currently established diagnostic modalities of dobutamine stress echocardiography (DSE) and rest-redistribution thallium-201 (T1-201) scintigraphy. BACKGROUND: Because myocardial necrosis is associated with myocardial thinning, preserved EDWT may provide a simple index of myocardial viability that is readily available from the resting echocardiogram. METHODS: Accordingly, 45 patients with stable coronary artery disease and ventricular dysfunction underwent rest 2D echocardiograms, DSE and rest-redistribution T1-201 tomography before revascularization and a repeat resting echocardiogram > or =2 months later. RESULTS: Global wall motion score index decreased from 2.38 +/- 0.73 to 1.94 +/- 0.82 after revascularization (p < 0.001). Thirty-eight percent of severely dysfunctional segments recovered resting function. Compared to segments without recovery of resting function, those with recovery had greater EDWT (0.94 +/- 0.18 cm vs. 0.67 +/- 0.22 cm, p < or = 0.0001) and a higher T1-201 uptake (78 +/- 13% vs. 59 +/- 21%; p < 0.0001). An EDWT >0.6 cm had a sensitivity of 94% and specificity of 48% for recovery of function. Similarly, a T1-201 maximal uptake of > or =60% had a sensitivity of 91% and specificity of 50%. Receiver operating characteristic curves for prediction of recovery of regional and global function were similar for EDWT and maximum T1-201 uptake. Combination of EDWT and any contractile reserve during DSE for recovery of regional function improved the specificity to 77% without a significant loss in sensitivity (88%). CONCLUSIONS: End-diastolic wall thickness is an important marker of myocardial viability in patients with suspected hibernation, and it can predict recovery of function similar to T1-201 scintigraphy. Importantly, a simple measurement of EDWT < or =0.6 cm virtually excludes the potential for recovery of function and is a valuable adjunct to DSE in the assessment of myocardial viability.

Teledentistry for screening new patient orthodontic referrals. Part 2: GDP perception of the referral system.

OBJECTIVE: To evaluate GDP opinion about a teledentistry system to screen new patient orthodontic referrals. STUDY DESIGN: Cross-sectional questionnaire. SAMPLE: Two hundred general dental practitioners (GDPs) were approached from Stockport, Rochdale, Oldham, Bury and Bolton in Greater Manchester, and High Peak in Derbyshire. METHOD: A questionnaire about a teledentistry system for new orthodontic patients was developed, following interviews with eight GDPs participating in a teledentistry trial. The questionnaire was posted to another 200 GDPs who were asked questions on issues such as the efficiency of a teledentistry system; the usefulness of a teledentistry system from the patients' point of view; their view of a teledentistry system; and any concerns they had relating to security, confidentiality and consent. RESULTS: Seventy one per cent of GDPs thought teledentistry for orthodontic referrals would be a good idea. At least 90% of responders agreed or neither agreed nor disagreed that patients would benefit from such a system. Over half of GDPs agreed or strongly agreed that there would be implications on their surgery time, expense and equipment security. CONCLUSIONS: GDPs generally supported a teledentistry system for new patient orthodontic referrals. Although perceived patient advantages were agreed, GDPs tended to be less sure about the impact on them in terms of set-up expenses, time in the surgery and appropriate remuneration.

Clinical and angiographic significance of a normal thallium-201 tomographic study in patients with a strongly positive exercise electrocardiogram.

Among 23,059 patients who underwent exercise myocardial tomography between 1985 and 1994 at our institution, there were 817 (3.5%) with a strongly positive exercise electrocardiogram and normal myocardial tomograms. Among these, 52 patients had no conditions known to be associated with a false-positive exercise electrocardiogram and no previous coronary revascularization, and underwent coronary angiography. Of the 32 patients with significant coronary stenoses, 50% had 1-vessel disease and only 22% had 3-vessel disease (p < 0.05). Among 55 stenosed arteries, 56% were of moderate severity (50 to 74%), whereas only 9% had subtotal or total occlusion (95 to 100%) (p < 0.001). There was a significant gender difference in the prevalence of significant coronary stenoses (80% in male vs 24% in female patients, p < 0.0001). A strongly positive exercise electrocardiogram coupled with normal exercise myocardial tomograms is a rare clinical finding. In women, this finding is usually associated with normal coronary arteries, whereas in men it often denotes coronary artery disease, usually of mild to moderate degree.

Renal microvascular features of hypertension in Japan, Guatemala, and the United States.

The finding of benign arteriolar nephrosclerosis at autopsy usually implies the prior existence of essential hypertension. It was found in this study that minor degrees of incipient nephrosclerosis in young people can be shown to correlate with seemingly trivial blood pressure elevations. In this study, autopsy tissues were used to assess the magnitude of early nephrosclerosis in five population groupings. A comparison of males in Tokyo, Japan, Guatemala, and New Orleans, La (blacks and whites); and females in Tokyo revealed significant differences among these populations. Blacks exceeded whites in New Orleans in the magnitude of incipient nephrosclerosis in all 10-year age groups from 15 through 24 years to 45 through 54 years. Guatemalan males were, on average, less affected than New Orleans whites in all age groups. The data for all males (age range, 15 through 54 years) in Tokyo revealed little difference in nephrosclerosis from those in New Orleans whites. Blood pressure data were obtained from reports of cross-sectional surveys in these five populations. Blood pressure in males varied across age x race subgroups in close parallel with nephrosclerosis (r = .90), implying that variation in blood pressure among groups of subjects is strongly nephrosclerosis linked, even at very young ages; findings for Tokyo females were aberrant in this correlation. The results suggest that the lifelong progression toward the hypertensive state begins in childhood, and that these beginnings are measurably in the population averages of both nephrosclerosis and blood pressure elevations. Moreover, population differences in these two commensurate measures of the early precursors of hypertension were found to be well established by the ages of 15 through 24 years and were sustained at least into the ages of 45 through 54 years. The years of adolescence are here brought under suspicion of special importance in setting the lifelong course toward the hypertensive state.

Combined lesions of hippocampus and subiculum Do not produce deficits in a nonspatial social olfactory memory task.

Rats transmit information to each other about which foods are safe to eat. If a rat smells a food odor on the breath of another rat, it is subsequently more likely to eat that food than an alternative. Work by Galef et al. (1988) has shown that the observer rat forms an association between two olfactory stimuli on the breath of the demonstrator rat that has eaten the food, the food odor and carbon disulphide, which is normally present in the rat breath. Bunsey and Eichenbaum (1995) claimed that the hippocampus/subicular region is required for the long-term retention of this nonspatial form of associative memory on the basis that combined lesions of the hippocampus and subiculum produced a deficit, but lesions of either structure alone did not. We report here a failure to repeat this finding. Rats with either combined lesions of the hippocampus and subiculum or with amygdala lesions were tested on their ability to remember this association either immediately (testing short-term memory) or after a 24 hr delay (testing long-term memory). Neither lesion group exhibited significant memory deficits on this nonspatial associative task at either test interval. In contrast, a deficit was observed on a spatial memory task (forced-choice alternation t-maze) for animals with combined lesions of the hippocampus and subiculum. These results contradict the findings of Bunsey and Eichenbaum (1995) and support the idea that the hippocampus/subicular region is not required for this nonspatial associative memory.

Dobutamine echocardiography and quantitative rest-redistribution 201Tl tomography in myocardial hibernation. Relation of contractile reserve to 201Tl uptake and comparative prediction of recovery of function.

BACKGROUND: The purposes of this study were to evaluate the comparative accuracy of dobutamine echocardiography and quantitative rest-redistribution 201Tl tomography in the prediction of recovery of function after revascularization and to assess the relation of contractile reserve to thallium uptake. METHODS AND RESULTS: Thirty-four patients with stable coronary disease and regional dysfunction underwent dobutamine echocardiography (2.5 up to 40 micrograms.kg-1.min-1) and rest-redistribution 201Tl tomography 1 day before revascularization. Resting echocardiography and scintigraphy were repeated at > or = 6 weeks. Before revascularization, resting 201Tl uptake was similar in segments demonstrating biphasic or sustained improvement and was higher than in those exhibiting no change or worsening function during dobutamine. After revascularization, 201Tl uptake increased only in segments that showed a biphasic response (from 66 +/- 12% to 78 +/- 13%; P < .05). Biphasic response had a sensitivity of 74% and specificity of 89% for prediction of recovery. The use of biphasic or sustained improvement responses increased the sensitivity to 86% with a decrease in specificity to 68%. Qualitative thallium assessment provided a high sensitivity (98%) but poor specificity (27%). Quantification of thallium uptake, however, improved its accuracy: a maximal uptake (at rest or redistribution) of > or = 60% yielded a 90% sensitivity and a 56% specificity. CONCLUSIONS: In patients with myocardial hibernation, biphasic response during dobutamine is less sensitive but more specific for recovery of function, whereas indexes of 201Tl scintigraphy are in general more sensitive and less specific, the least accurate being a qualitative assessment of thallium uptake. The sensitivity and specificity of both methods, however, can be altered depending on the quantitative criteria of thallium uptake or combination of responses of the myocardium to dobutamine.