Three dimensional reconstruction to visualize atrial fibrillation activation patterns on curved atrial geometry.

BACKGROUND: The rotational activation created by spiral waves may be a mechanism for atrial fibrillation (AF), yet it is unclear how activation patterns obtained from endocardial baskets are influenced by the 3D geometric curvature of the atrium or 'unfolding' into 2D maps. We develop algorithms that can visualize spiral waves and their tip locations on curved atrial geometries. We use these algorithms to quantify differences in AF maps and spiral tip locations between 3D basket reconstructions, projection onto 3D anatomical shells and unfolded 2D surfaces. METHODS: We tested our algorithms in N = 20 patients in whom AF was recorded from 64-pole baskets (Abbott, CA). Phase maps were generated by non-proprietary software to identify the tips of spiral waves, indicated by phase singularities. The number and density of spiral tips were compared in patient-specific 3D shells constructed from the basket, as well as 3D maps from clinical electroanatomic mapping systems and 2D maps. RESULTS: Patients (59.4±12.7 yrs, 60% M) showed 1.7±0.8 phase singularities/patient, in whom ablation terminated AF in 11/20 patients (55%). There was no difference in the location of phase singularities, between 3D curved surfaces and 2D unfolded surfaces, with a median correlation coefficient between phase singularity density maps of 0.985 (0.978-0.990). No significant impact was noted by phase singularities location in more curved regions or relative to the basket location (p>0.1). CONCLUSIONS: AF maps and phase singularities mapped by endocardial baskets are qualitatively and quantitatively similar whether calculated by 3D phase maps on patient-specific curved atrial geometries or in 2D. Phase maps on patient-specific geometries may be easier to interpret relative to critical structures for ablation planning.

Electrical Substrate Ablation for Refractory Ventricular Fibrillation: Results of the AVATAR Study.

[Figure: see text].

Dietary analysis and nutritional counselling for caries prevention in dental practise: a pilot study.

BACKGROUND: Dental practitioners agree that dietary counselling is essential for caries prevention; however, they provide advice infrequently due to a lack of confidence and competence. This study aimed to improve practises through an online training module exploring the use of a brief counselling method, and a diet assessment of caries risk form. METHODS: Dental practitioners (N = 41) completed a survey on current practises and confidence in providing dietary advice, followed by an online training module. Ten practitioners were involved in recruiting patients, eliciting a diet assessment of caries risk, and using brief counselling techniques with these patients. Patients were followed up at 6 months for a risk assessment review. Dental practitioners also completed a 6-month follow-up survey exploring changes in confidence and perceived barriers. RESULTS: Dental hygienists' confidence improved significantly following the intervention (P < 0.025). Patients showed a significant reduction in high-risk behaviour pertaining to quantity and timing of sugar intake, and significant trends in improvement of behaviours relating to frequency, exposure time and drinking style (P < 0.05). CONCLUSIONS: It appears that a simple online learning module can improve hygienists' confidence in dietary advice provision, and have a positive impact on patient behaviour change, within a relatively short time-frame.

Improvement in hepatic insulin sensitivity after Roux-en-Y gastric bypass in a rat model of obesity is partially mediated via hypothalamic insulin action.

AIMS/HYPOTHESIS: Roux-en-Y gastric bypass (RYGB) surgery, an effective treatment for morbid obesity, commonly leads to near complete resolution of type 2 diabetes. The underlying mechanisms, however, remain unclear and factors other than weight loss alone may be involved. METHODS: To determine whether increased hypothalamic insulin sensitivity after RYGB drives the rapid improvement in glucose metabolism, high-fat-fed rats received either an insulin receptor (IR) antisense vector or a control lentiviral vector that was microinjected into the ventromedial hypothalamus (VMH). Six weeks later, rats underwent RYGB or control gastrointestinal surgery. RESULTS: Four weeks after surgery, weight loss was comparable in RYGB and surgical controls. Nevertheless, only RYGB rats that received the control vector demonstrated both improved hepatic and peripheral insulin sensitivity. Insulin suppressed hepatic glucose production (HGP) by 50% (p < 0.05) with RYGB, whereas the effect of insulin on HGP was completely absent in VMH IR knockdown (IRkd) rats. By contrast, both RYGB groups displayed an identical twofold increase in insulin-stimulated peripheral glucose uptake. The animals that underwent control gastrointestinal surgery failed to show any improvement in either hepatic or peripheral insulin sensitivity; VMH IRkd did not influence the magnitude of insulin resistance. CONCLUSIONS/INTERPRETATION: Our findings demonstrate that RYGB surgery in high-fat-fed obese rats enhances hepatic and peripheral insulin sensitivity independently of weight loss. The improved hepatic, but not the peripheral, response to insulin is mediated centrally at the level of the VMH. These data provide direct evidence that the metabolic benefits of RYGB surgery are not simply a consequence of weight loss but likely in part involve the central nervous system.

Association between vitamin D receptor gene polymorphisms, falls, balance and muscle power: results from two independent studies (APOSS and OPUS).

SUMMARY: Fall prevention is a key strategy for reducing osteoporotic fractures. We investigated the association between vitamin D receptor (VDR) polymorphisms and reported falls in postmenopausal women. Bsm1 polymorphisms were associated with falls, balance and muscle power measurements. These results may explain some of the excess fracture risk associated with VDR in some studies. INTRODUCTION: Fall prevention is a key strategy for reducing osteoporotic fractures. It has been suggested that vitamin D supplementation may reduce the incidence of falls by reducing body sway and increasing muscle power. The vitamin D receptor gene is a well-studied candidate gene for osteoporosis. We investigated the association between VDR polymorphisms and reported falls in postmenopausal women. METHODS: Falls data were collected in two separate population cohorts. Five polymorphisms of the VDR gene were analysed (Cdx-2, Fok-1, BsmI, Taq1 and Apa1) in the Aberdeen Prospective Osteoporosis Screening Study (APOSS) cohort. Results found in APOSS were then validated in an independent cohort--the Osteoporosis and Ultrasound (OPUS) study (Bsm1 and Fok1 only), where muscle power and balance were also measured. RESULTS: Carriers of the 'B' allele (Bsm1) showed an increased risk for falls. In APOSS, this was statistically significant for visit 3 multiple falls (p = 0.047) and for recurrent falls (p = 0.043). Similar results were found in OPUS for visit 1 falls (p = 0.025) and visit 1 multiple falls (p = 0.015). Bsm1 polymorphisms were also associated with balance and muscle power measurements. CONCLUSIONS: In conclusion, these results demonstrate an association between the Bsm1 polymorphism and risk of falling that may explain some of the excess fracture risk associated with VDR in some studies.

Counting the cost of complementary and alternative therapies in an Irish neurological clinic.

BACKGROUND AND PURPOSE: Complementary and alternative therapy (CAT) use is frequent in patients with the common neurological disorders despite little scientific evidence of its efficacy. Little is known about the cost of regular CAT use. The purposes of this study were to determine the frequency and cost of CAT use in patients attending a neurology out-patient clinic and to determine whether neurological diagnosis affects CAT use. METHODS: All patients attending the neurology out-patient clinic were asked to complete a structured questionnaire which included demographic information, details on the underlying neurological diagnosis, use and cost of CAT. RESULTS: Six hundred and seventy-one patients completed the questionnaire. Over 60% of the patients had used CAT, and 25% used CAT on a regular basis. Only 25% of patients using CAT had informed their doctor. Rates of CAT use varied with neurological diagnosis. Of those using CAM on a regular basis, the mean annual cost was Euro 1351. CONCLUSION: Patients attending our neurology out-patient department use CAT frequently and often do not inform their doctor. Patients spend a significant amount of personal income on CAT. Given the implications, including potential interactions with prescribed medication, these findings should prompt doctors to ask every patient about CAT use.

Brief communication: the Thule migration: rejecting population histories using computer simulation.

Locked within our genetic code are the histories of our genes and the genes of our ancestors. Deciphering a population's history from genetic data often involves lengthy investigations of many loci for many individuals. We test hypothetical population histories of the Thule expansion using a new coalescent simulation method that uses little more than mitochondrial haplogroup data. This new methodology rejects a severe bottleneck at expansion and reveals the range of probable population histories on which to focus future research.

Barium enema: use of increased copper filtration to optimize dose and image quality.

The purpose of this study was to determine and validate the optimum copper filtration for adult double contrast barium enema examinations. Entrance surface dose rates to polymethyl methacrylate slabs and corresponding image intensifier input kermas, were measured for various added copper filters. Image contrast was assessed using a Leeds TO.10 test object. Copper filter thickness of 0.3 mm was chosen, as this reduced entrance surface dose rate by 56%, without substantially degrading image contrast due to kV and mA saturation. 20 sets of clinical films taken with each of 0.3 mm copper, 0.1 mm copper and no copper were reviewed following randomization, by a specialist gastrointestinal radiologist. Each set of digital spot and conventional films was allocated a score for each of three regions of the bowel, on a scale of 0-3 for perceived barium coating. The Kruskal-Wallis test showed no significant difference in perceived coating between the three groups (Digital spot: sigmoid colon p=0.207, splenic flexure p=0.103, hepatic flexure p=0.894. Screen-film: left colon p=0.803, right colon p=0.487, transverse colon p=0.905). All examinations but one were classified as diagnostic. The remaining one was classified indeterminate, due to poor distension of the colon. On adding 0.3 mm copper filtration, the mean dose-area product per examination was reduced by 57%, from 17.7 Gy cm(2) to 7.6 Gy cm(2). The estimated reduction in effective dose was 11%, from 3.0 mSv to 2.7 mSv. X-ray tube loading increased by 30%, but this caused no overheating with our local examination protocol and schedule. Additional filtration of 0.3 mm copper for adult double contrast barium enemas has now been implemented in routine clinical use at our hospital.

Green tea extracts decrease carcinogen-induced mammary tumor burden in rats and rate of breast cancer cell proliferation in culture.

Epidemiological evidence suggests tea (Camellia sinensis L.) has chemopreventive effects against various tumors. Green tea contains many polyphenols, including epigallocatechin-3 gallate (EGCG), which possess anti-oxidant qualities. Reduction of chemically induced mammary gland carcinogenesis by green tea in a carcinogen-induced rat model has been suggested previously, but the results reported were not statistically significant. Here we have tested the effects of green tea on mammary tumorigenesis using the 7,12-dimethylbenz(a)anthracene (DMBA) Sprague-Dawley (S-D) rat model. We report that green tea significantly increased mean latency to first tumor, and reduced tumor burden and number of invasive tumors per tumor-bearing animal; although, it did not affect tumor number in the female rats. Furthermore, we show that proliferation and/or viability of cultured Hs578T and MDA-MB-231 estrogen receptor-negative breast cancer cell lines was reduced by EGCG treatment. Similar negative effects on proliferation were observed with the DMBA-transformed D3-1 cell line. Growth inhibition of Hs578T cells correlated with induction of p27(Kip1) cyclin-dependent kinase inhibitor (CKI) expression. Hs578T cells expressing elevated levels of p27(Kip1) protein due to stable ectopic expression displayed increased G1 arrest. Thus, green tea had significant chemopreventive effects on carcinogen-induced mammary tumorigenesis in female S-D rats. In culture, inhibition of human breast cancer cell proliferation by EGCG was mediated in part via induction of the p27(Kip1) CKI.

Transpupillary thermotherapy of subfoveal occult choroidal neovascularization.

Choroidal neovascularization secondary to age-related macular degeneration is a leading cause of vision loss in adults. Although most patients present with occult CNV, treatment has focused on the small percentage of eyes with well-delineated, classic CNV. Transpupillary thermotherapy is a recent advancement in the management of occult CNV. Transpupillary thermotherapy acts in a subthreshold manner by slightly raising the choroidal temperature. A recent pilot study demonstrated that 56% of treated eyes remained stable one year after treatment with only 25% losing two lines of visual acuity. The TTT4CNV study will further evaluate the effectiveness of transpupillary thermotherapy in a randomized, double-blind trial.

Abnormal response to negative feedback in depression.

BACKGROUND: Recent studies have suggested that subjects with depression suffer a diagnosis-specific motivational deficit, characterized by an abnormal response to negative feedback that endures beyond clinical recovery. Furthermore, it has been suggested that negative feedback may motivate non-depressed controls, but not depressed patients, to improve their performance in neuropsychological tests. METHODS: We describe two studies. The first compared performance on the simultaneous and delayed match to sample (SDMS) task from the CANTAB neuropsychological test battery, in 20 patients with severe depression with 20 with acute schizophrenia, 40 with chronic schizophrenia and 40 healthy controls. The second examined the performance of depressed patients with diurnal variation in symptoms and cognitive function. RESULTS: All patients groups showed impairments on the simultaneous and delayed match to sample task compared to controls. Depressed patients did not show an abnormal response to negative feedback. Controls did not show a motivational effect of negative feedback. Depressed patients with diurnal variation showed no variation in their response to perceived failure. There was no evidence of abnormal response to negative feedback in any patient group using the 'runs test' or of a motivational effect in controls. Conditional probability analysis was not independent of the total number of errors made in the SDMS task. CONCLUSIONS: Further studies are suggested to examine whether an abnormal response to negative feedback characterizes particular subgroups of patients suffering from depression.

Dietary fat, body weight, and cancer: contributions of studies in rodents to understanding these cancer risk factors in humans.

Understanding diet and energy balance as risk factors for breast, colon, and other cancers requires information on the contribution of each factor and of interactions among factors to cancer risk. Rodent models for breast cancer provide extensive data on effects of dietary fat and calories, energy balance, body weight gain, and physical activity on tumor development. Analyses of the combined data from many studies have shown clearly that quality and quantity of dietary fat and energy balance contribute independently to increased mammary gland tumorigenesis. These findings were seen in female rats fed diets high in fat (35-40% of calories) compared to rats fed control diets, with approximately 10% of calories as fat (Fay and Freedman, 1997, Breast Cancer Res. Treat. 46, 215-223). The methods used permit comparison of experimental and epidemiological data, and they may be useful in extrapolating between species and developing public health recommendations. In addition to the contributions of lifetime-diet composition, intake, energy balance, and physical activity to cancer risk, there are questions about the timing and duration of alterations in these factors and about the "dose-response" characteristics of cancer risk to the factors. Endocrine mechanisms may be significant in mammary gland tumor risk, but experimental and epidemiological data indicate that cancers at other sites, such as colon and liver, also are influenced by the factors listed. Other diet and lifestyle factors that influence energy, or specifically fat, metabolism may also affect risk for cancers that are promoted by increased intake of fat and calories. Studies of separate and interactive effects of dietary fat, black tea, weight gain, and mammary gland tumorigenesis (Rogers, et al, 1998, Carcinogenesis 19, 1269-1273) have been analyzed. Using adjustment of carcinogenesis endpoints for body weight, tumor burden, and latency, they were found to be related to weight gain within treatment groups in 2 of 3 experiments.

Black tea and mammary gland carcinogenesis by 7,12-dimethylbenz[a]anthracene in rats fed control or high fat diets.

Epidemiological studies suggest that tea may reduce cancer risk, and in laboratory rodents, chemopreventive effects of tea or purified extracts of tea have been demonstrated in lung, gastrointestinal tract and skin. There is some evidence of chemoprevention by tea in the mammary gland, but the data are not conclusive. In order to evaluate more fully the possible influence of black tea on 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary gland tumors in the female S-D (Sprague-Dawley) rat, three large studies were performed: experiment 1, tumorigenesis in rats fed AIN-76A diet and given 25 mg/kg DMBA and 1.25 or 2.5% whole tea extract or water to drink; experiment 2, tumorigenesis in rats given 15 mg/kg DMBA and the same diet and fluids as in experiment 1; experiment 3, tumorigenesis in rats fed control or HF (high fat, corn oil) diet and given 15 mg/kg DMBA and 2% tea or water to drink. Tea was given throughout the experiment; DMBA was given by gastric gavage at 8 weeks of age. There was no consistent effect of tea on tumorigenesis in rats fed AIN-76A diet; there was, however, evidence in experiment 3 of a reduction of tumorigenesis by tea in rats fed the HF diet. In experiment 3, rats fed the HF diet and given water showed the expected increase in tumor burden (number and weight) compared with rats fed control diet. However, rats fed the HF diet and given 2% tea showed no increase in tumor burden; their tumor burden was significantly lower than in rats fed the HF diet and given water (P < 0.01) and was not different from rats fed control diet and given water or tea. In addition, in experiment 3, the number of malignant tumors per tumor-bearing rat was increased by the HF diet in water-drinking rats (P < 0.01) but not in tea-drinking rats. Therefore, it appears that tea partially blocked the promotion of DMBA-induced mammary tumorigenesis by the HF diet.

Nimodipine neuroprotection in cardiac valve replacement: report of an early terminated trial.

BACKGROUND: We conducted a double-blind, randomized clinical trial in patients undergoing cardiac valve replacement to determine whether nimodipine, a dihydropyridine calcium antagonist, reduced the risk of new neurological, neuro-ophthalmologic, or neuropsychological deficits-common complications associated with cardiac surgery-1 week after surgery. METHODS AND RESULTS: Enrollment for a total of 400 patients started in May 1992 and was stopped in September 1994, with 150 patients randomized to the study. Nimodipine was given to the patients during the perioperative period. Patients underwent examinations before surgery and at approximately 1 week, 1 month, and 6 months after surgery. Major adverse events, including deaths and strokes, were monitored monthly. The trial was terminated early because of both an unexpected disparity in death rates between groups and a lack of evidence of a beneficial effect of nimodipine. New deficits were observed in 72% of the placebo group versus 77% of the nimodipine group (p=.55). In the 6-month follow-up period, 8 deaths (10.7%) occurred in the nimodipine group (n=75) compared with 1 death (1.3) in the placebo group (n=74) (p=.02). Major bleeding occurred in 10 patients in the nimodipine group versus 3 in the placebo group (13.3% versus 4.1%; P=.04). Six (46.2%) of the 13 patients with major bleeding died compared with 3 deaths (2.2%) among the 136 patients without major bleeding. CONCLUSIONS: Our findings add to the growing evidence that calcium antagonists have a prohemorrhagic effect in some patients and suggest that nimodipine use should be restricted perioperatively in patients scheduled for cardiac valve replacement.

Treatment of systemic candidiasis in a neutropenic murine model using immunoglobulin G bearing liposomal amphotericin B.

Efficacy of immunoglobulin G (IgG) bearing liposomal amphotericin B (LAMB-IgG), liposomal amphotericin B without IgG (LAMB) or free amphotericin B (fAMB/Fungizone) was investigated in the treatment of systemic candidiasis in a neutropenic mouse model. Treatment with a single dose (0.6 or 0.9 mg amphotericin B per kg body weight) of LAMB-IgG resulted in a significant increase in the survival rate of neutropenic mice infected with 3 x 10(5) cfu of Candida albicans compared to untreated controls, mice injected with IgG, or liposome alone. Survival was also better in neutropenic mice treated with LAMB-IgG than in neutropenic mice treated with the same dose of LAMB or fAMB. Moreover, 65% of all mice survived the infection after treatment with a single dose of 0.6 mg AMB of the LAMB-IgG formulation. Quantitative culture counts of organs showed that both fAMB and LAMB-IgG formulations even at a dose of 0.3 mg AMB/kg, cleared C. albicans from the spleens, livers, and lungs but not from the kidneys. However, a decreased number of C. albicans cells was recovered from the kidneys of mice that survived the infection. Results of the study suggest that LAMB-IgG is more effective than LAMB or fAMB in the therapy of disseminated candidiasis in neutropenic mice.

Giant colonic diverticulum: an unusual manifestation of a common disease.

Giant colonic diverticula are an uncommon manifestation of colonic diverticular disease. This report documents another case of this rare entity. The clinical presentation is variable, but abdominal pain and the presence of an abdominal mass are common. Their etiology is uncertain, but they are thought to originate from pulsion diverticula. Abdominal plain films and barium enema are helpful in making the diagnosis. Computerized tomography is useful when the diagnosis is unclear. Surgical resection is recommended to alleviate symptoms and avoid complications.

Effect of attachment of anticandidal antibody to the surfaces of liposomes encapsulating amphotericin B in the treatment of murine candidiasis.

The effect produced by antibody specific to Candida albicans when attached to liposomes containing amphotericin B was studied in vivo. Liposomal amphotericin B bearing specific immunoglobulin (LAMB-Ab) was compared with the unencapsulated drug (fAMB) and other liposomal amphotericin B formulations in the short-term survival (21 days) of mice with disseminated candidiasis. Both the treatment and prophylaxis of the murine model of candidiasis were explored in these trials. LAMB-Ab increased survival rates in the model more than other liposomal preparations containing amphotericin B. Liposomal amphotericin B compounds as a group prolonged survival over fAMB. Liposomal preparations used for comparison included liposomes with attached nonspecific antibody (LAMB-Ab-), liposomes without antibody (LAMB), and liposomes with unattached specific antibody (LAMB+).