Radiofrequency catheter ablation of persistent atrial fibrillation by pulmonary vein isolation with or without left atrial posterior wall isolation: long-term outcomes of the CAPLA trial.

BACKGROUND AND AIMS: Posterior wall isolation (PWI) is commonly incorporated into catheter ablation (CA) strategies for persistent atrial fibrillation (AF) in an attempt to improve outcomes. In the CAPLA randomized study, adjunctive PWI did not improve freedom from atrial arrhythmia at 12 months compared with pulmonary vein isolation (PVI) alone. Whether additional PWI reduces arrhythmia recurrence over the longer term remains unknown. METHODS: In this multicenter, international, randomized study patients with persistent AF undergoing index CA using radiofrequency (RF) were randomized to PVI+PWI versus PVI alone. Patients underwent regular follow-up including rhythm monitoring for a minimum of 3 years post CA. AF burden at 3 years post-ablation was evaluated with either 28-day continuous ambulatory ECG monitoring, twice daily single-lead ECG or from cardiac implanted device. Evaluated endpoints included freedom from any documented atrial arrhythmia recurrence after a single procedure, AF burden, need for redo catheter ablation, rhythm at last clinical follow-up, healthcare utilisation metrics and AF-related quality of life. RESULTS: 333 of 338 (98.5%) patients (mean age 64.3±9.4 years, 23% female) completed 3-year follow-up, with 169 patients randomized to PVI+PWI and 164 patients to PVI alone. At a median of 3.62 years post-index ablation, freedom from recurrent atrial arrhythmia occurred in 59 patients (35.5%) randomized to PVI+PWI vs 68 patients (42.1%) randomized to PVI alone (HR 1.15, 95% CI 0.88-1.51, p=0.55). Median time to recurrent atrial arrhythmia was 0.53 years (IQR 0.34-1.01 years). Redo ablation was performed in 54 patients (32.0%) in the PVI+PWI group vs 49 patients (29.9%, p=0.68) in the PVI alone group. Pulmonary vein reconnection was present in 54.5% (mean number of reconnected PVs 2.2±0.9) and posterior wall reconnection in 75%. Median AF burden at 3 years was 0% in both groups (IQR 0-0.85% PVI+PWI vs 0-1.43% PVI alone, p=0.49). Sinus rhythm at final clinical follow-up was present in 85.1% with PVI+PWI vs 87.1% with PVI alone (p=0.60). Mean AF Effect On Quality-Of-Life (AFEQT) score at 3 years post-ablation was 88.0±14.8 with PVI+PWI vs 88.9±15.4 with PVI alone (p=0.63). CONCLUSIONS: In patients with persistent AF, the addition of PWI to PVI alone at index RF catheter ablation did not significantly improve freedom from atrial arrhythmia recurrence at long-term follow-up. Median AF burden remains low and AF quality of life high at 3 years with either ablation strategy.

Anti-biofouling efficacy of three home and personal care product preservatives: Pseudomonas aeruginosa biofilm inhibition and prevention.

Due to increasing water scarcity, it is essential to determine cost-effective and efficient methods of producing potable water, especially ones that utilize non-traditional sources. Although reverse osmosis (RO) shows promise as a key-player in mitigating water scarcity, it is limited by biofouling. It is therefore integral to identify effective antifoulants that also do not damage the membrane, cause resistance, or negatively impact human health and the environment. Potential antifoulants include preservatives used in home and personal care products. It is hypothesized that safer preservatives can be applied to RO systems to remove or prevent biofouling. Three preservatives including methylisothiazolinone (MIT), phenoxyethanol (PE), and sodium benzoate (SB) were tested via antimicrobial susceptibility tests against P. aeruginosa biofilms grown in 96-well plates to investigate both biofilm prevention and biofilm removal. Data were collected in the form of minimum biofilm inhibitory concentration (MBIC) and minimum biofilm eradication concentration (MBEC), respectively. MIT was the most effective of the three preservatives but also poses the highest hazard to human health and the environment. Due to efficacy and safety concerns, MIT, PE, and SB are not the final solution; however, a process was demonstrated for determining the efficacy of novel, safer antifoulants. Ultimately, further investigations into safer antifoulants, paired with a greater understanding of biofilm removal and prevention doses will help make RO a better solution for water scarcity.

Randomised clinical trial: mesalazine versus placebo in the prevention of diverticulitis recurrence.

BACKGROUND: Previous studies have reached conflicting conclusions regarding the efficacy of mesalazine in the prevention of recurrent diverticulitis. AIM: To investigate the efficacy and safety of mesalazine granules in the prevention of recurrence of diverticulitis after acute uncomplicated diverticulitis. METHODS: Two phase 3, randomised, placebo-controlled, double-blind multicentre trials (SAG-37 and SAG-51) investigated mesalazine granules in patients with prior episodes (<6 months) of uncomplicated left-sided diverticulitis. Patients were randomised to receive either 3 g mesalazine once daily or placebo (SAG-37, n=345) or to receive either 1.5 g mesalazine once daily, 3 g once daily or placebo for 96 weeks (SAG-51, n=330). The primary endpoint was the proportion of recurrence-free patients during 48 weeks (SAG-37 and SAG-51) or 96 weeks (SAG-51) of treatment. RESULTS: Mesalazine did not increase the proportion of recurrence-free patients over 48 or 96 weeks compared to placebo. In SAG-37, the proportion of recurrence-free patients during 48 weeks was 67.9% with mesalazine and 74.4% with placebo (P=.226). In SAG-51, the proportion of recurrence-free patients over 48 weeks was 46.0% with 1.5 g mesalazine, 52.0% with 3 g mesalazine and 58.0% with placebo (P=.860 for 3 g mesalazine vs placebo) and over 96 weeks 6.9%, 9.8% and 23.1% respectively (P=.980 for 3 g mesalazine vs placebo). Patients with only one diverticulitis episode in the year prior to study entry had a lower recurrence risk compared to >1 episode. Safety data revealed no new adverse events. CONCLUSION: Mesalazine was not superior to placebo in preventing recurrence of diverticulitis.

Doctors' recognition and management of melanoma patients' risk: An Australian population-based study.

BACKGROUND: Guidelines recommend that health professionals identify and manage individuals at high risk of developing melanoma, but there is limited population-based evidence demonstrating real-world practices. OBJECTIVE: A population-based, observational study was conducted in the state of New South Wales, Australia to determine doctors' knowledge of melanoma patients' risk and to identify factors associated with better identification and clinical management. METHODS: Data were analysed for 1889 patients with invasive, localised melanoma in the Melanoma Patterns of Care study. This study collected data on all melanoma diagnoses notified to the state's cancer registry during a 12-month period from 2006 to 2007, as well as questionnaire data from the doctors involved in their care. RESULTS: Three-quarters (74%) of patients had doctors who were aware of their risk factor status with respect to personal and family history of melanoma and the presence of many moles. Doctors working in general practice, skin cancer clinics and dermatology settings had better knowledge of patients' risk factors than plastic surgeons. Doctors were 15% more likely to know the family history of younger melanoma patients (<40years) than of those ≥80 years (95% confidence interval 4-26%). Early detection-related follow-up advice was more likely to be given to younger patients, by doctors aware of their patients' risk status, by doctors practising in plastic surgery, dermatology and skin cancer clinic settings, and by female doctors. CONCLUSION: Both patient-related and doctor-related factors were associated with doctors' recognition and management of melanoma patients' risk and could be the focus of strategies for improving care.

Early perceptual anomaly of negative facial expression in depression: An event-related potential study.

Depressed patients have a demonstrated cognitive bias in emotional information processing. However, it is unknown how early perceptual processing is modulated by emotional stimuli in depression. To examine this question, we studied 22 depressed patients and 22 healthy controls performing a cued target-response task with emotional facial expression as the cue. The early perceptual processes were examined using event-related potential (ERP) components, i.e., P1 and N170. Results showed that depressed patients had larger P1 amplitudes than healthy controls, implying that early perceptual abnormality for face processing in depression may occur as early as the P1 stage. There was no significant interaction between emotion types and groups on P1 amplitudes, which suggested that cognitive biases in depression might not yet have arisen. Following the P1 stage, N170 amplitudes for sad faces were larger than for other emotion types in depressed patients, whereas N170 amplitudes for happy faces were larger than for other emotion types in healthy controls. These results implied that depressed patients might have a perceptual bias associated with sad emotions, which may be detectable from the N170 time window. In summary, this study provides new insights for understanding the negative cognitive bias in depression using the electroneurophysiological biomarker N170.

Can total thyroidectomy be performed as safely by general surgeons in provincial centers as by surgeons in specialized endocrine surgical units? Making the case for surgical training.

OBJECTIVE: To determine whether surgeons who had received appropriate training in the technique of total thyroidectomy could continue to perform the procedure with minimal morbidity after moving to a provincial surgical practice. DESIGN: Comparison of the complication rates from total thyroidectomy between a specialized endocrine surgical unit and provincial centers. SETTING AND PATIENTS: Six hundred fifty patients undergoing total thyroidectomy by two surgeons over a 5-year period in the endocrine surgical unit at Royal North Shore Hospital, St Leonards, Australia, were compared with 120 patients undergoing total thyroidectomy by seven provincial surgeons who were former trainees in the unit. MAIN OUTCOME MEASURES: Indications for surgery and specific complications of thyroidectomy including recurrent laryngeal nerve palsy, permanent hypoparathyroidism, and postoperative bleeding. RESULTS: Each of the seven surgeons in provincial practice performed only between two and 16 thyroidectomies annually. The percentage of total thyroidectomies for benign and malignant disease was identical for both the endocrine surgical unit and provincial center groups (44%). There was no difference in the incidence of recurrent laryngeal nerve palsy, permanent hypoparathyroidism, or postoperative bleeding between the two groups. CONCLUSION: Total thyroidectomy is an operation that always engenders controversy relating to the morbidity of recurrent laryngeal nerve and parathyroid injury. Surgeons who have completed a well-designed training program and who have become proficient at total thyroidectomy as trainees will remain proficient at the procedure despite practicing in a provincial center. Achieving a low morbidity rate demands meticulous attention to operative technique and anatomical detail.

Magnetic resonance imaging of pituitary and parasellar abnormalities.

The ease, safety, accuracy, reliability, specificity, and sensitivity of the diagnosis of disorders of the sellar region all have been enhanced by MRI. This article demonstrates the normal anatomy and the wide array of pathology that can be visualized by MRI. Magnetic resonance has become the imaging modality of choice for most of the disorders within and about the sella.

Peptidolytic, esterolytic and amino acid catabolic activities of selected bacterial strains from the surface of smear cheese.

Enzymes produced by bacteria present on the surface of smear cheeses play essential roles in flavour development during cheese ripening. In this study, strains including brevibacteria, corynebacteria, staphylococci and brachybacteria, from the surface of two smear cheese (Tilsit and Gubeen) were screened for a range of enzyme activities including aminopeptidase (substrates: Leu-pNA and His-pNA), dipeptidase (Met-Ala, Ala-Met, Pro-Ala, His-Leu and Pro-Leu), tripeptidase (Phe-Gly-Gly, Gly-Gly-Gly and Leu-Ala- Pro), esterase (beta-naphthyl butyrate, beta-naphthyl caprate and beta-naphthyl palmitate). L-methionine aminotransferase and cystathionine lyase activities. There were marked differences in the activities observed between different bacteria studied. Brachybacteria showed low activity on all substrates assayed. There was no consistency in activities within groups of related bacteria. For example, Staphylococcus equorum 14 showed higher activity than S. equorum 6 on all the substrates tested. Among the corynebacteria, Coryebacterium ammoniagenes CA8 had greatest aminopeptidase, esterase and cystathionine lyase activity while C. casei B showed more di- and tri-peptidase activity. It was noted that individual bacteria displayed similar activities on all three esterase substrates, i.e., the chain length of the fatty acid did not appear to affect activity. L-Methionine aminotransferase activity was observed in only one strain (S. equorm 14) whereas all strains had cystathionine lyase activity.

Elevated triglyceride-rich lipoproteins in diabetes. A study of apolipoprotein B-48.

The role of the intestine in cholesterol metabolism in human diabetes is unclear, although abnormalities have been demonstrated in cholesterol synthesis and absorption in diabetic animals. This study examines the relationship between fasting and post-prandial apolipoprotein B-48 in type 2 (non-insulin-dependent) diabetic and non-diabetic subjects. Eight type 2 diabetic patients and ten healthy non-diabetic control subjects were given a high-fat meal (1300 kcal), and the triglyceride-rich lipoprotein fraction was isolated by ultracentrifugation (d < 1.006 g/ml) from fasting and post-prandial plasma. Apolipoprotein B-48 and apo B-100 were separated on 4%-15% gradient gels and quantified by densitometric scanning with reference to a purified low-density lipoprotein (LDL) apo B-100 preparation. Diabetic patients had significantly higher concentrations of apo B-48 and apo B-100 in both the fasting (P < 0.05) and post-prandial (P < 0.001) triglyceride-rich lipoprotein samples compared with non-diabetic subjects. The diabetic patients also exhibited a significantly different post-prandial profile for apo B-48 and apo B-100, with a prolonged increase and a later post-prandial peak, than the non-diabetic subjects (P < 0.01). These results suggest that the raised fasting triglyceride-rich lipoproteins, often found in diabetes, are associated with apo B-48 and may be derived from increased intestinal chylomicron production. The post-prandial pattern suggests an abnormality in intestinal production as well as hepatic clearance of apo B-48 in type 2 diabetes.

Intestinally derived lipoprotein particles in non-insulin-dependent diabetic patients with and without hypertriglyceridaemia.

We have previously demonstrated alterations in apolipoprotein B-48 metabolism in the post-prandial state in patients with non-insulin-dependent diabetes mellitus. This study investigates the relationship between hypertriglyceridaemia and post-prandial lipoprotein metabolism. Four groups of patients were examined: non-insulin-dependent diabetic patients, with normal serum triglyceride levels (serum triglyceride < 2.1 mmol l-1; haemoglobin HbA1c 5.5% +/- 0.4%); poorly controlled, non-insulin-dependent diabetic patients with hypertriglyceridaemia (serum triglyceride > 2.1 mmol l-1; HbA1c 8.8% +/- 0.9%); non-diabetic subjects with serum triglycerides < 2.1 mmol l-1; and non-diabetic subjects with hypertriglyceridaemia (serum triglyceride > 2.1 mmol l-1). Subjects were studied fasting and following a high-fat meal (1300 kcal). The triglyceride-rich lipoprotein fraction was isolated by ultracentrifugation (d < 1.006 g ml-1). Apoprotein B-48, apoprotein B-100 and apoprotein E were separated on 4%-15% gradient gels and quantified as a percentage of the fasting concentration by densitometric scanning. Triglyceride-rich lipoprotein apolipoprotein B-48 and apolipoprotein B-100 post-prandial profiles demonstrated a maximum increase either at 2 h or rising still further to a peak at 6 h before falling in the diabetic groups and hypertriglyceridaemic non-diabetic subjects when compared with the normotriglyceridaemic control subjects whose levels decreased after 2 h (P < 0.05). A significantly different triglyceride-rich lipoprotein apolipoprotein E profile was also exhibited by the diabetic patients (P < 0.05). Levels of triglyceride-rich lipoprotein, cholesterol, triglyceride, total protein and apoprotein B were elevated in the hypertriglyceridaemic subjects, both diabetic and non-diabetic. These results indicate that hypertriglyceridaemia is associated with altered metabolism and composition of post-prandial triglyceride-rich lipoprotein particles in both poorly controlled diabetic and non-diabetic subjects.

Heterothermy, torpor, respiratory gas exchange, water balance and the effect of feeding in Gould's long-eared bat Nyctophilus gouldi.

The effects of temperature and nutritional status on the metabolic rate of Nyctophilus gouldi were examined. Bats fed marked meals first defecated approximately 1.34 h after feeding and were calculated to have a mean retention time of 5.38 +/- 0.57 h but to be truly post-absorptive after 9 h. Over the temperature range 1-35 degrees C, the metabolic rate (Vo2) and body temperature (Tb) of fasted bats were extremely labile. Below 30 degrees C, the bats all entered torpor and between 10 and 15 degrees C showed a mean 84% reduction over the maximal Vo2. Body temperature was also minimal over this range (Tb = 12.5 degrees C, Ta = 10-15 degrees C). Both total and dry thermal conductance increased in a curvilinear manner with temperature, total conductance from 3.38 +/- 0.65 J g-1 h-1 degree C-1 at 1 degree C to 24.25 +/- 1.99 J g-1 h-1 degree C-1 at 35 degrees C (mean +/- S.E.M.), while the rate of evaporative water loss increased with Ta by a maximum of 10-fold from 0.21 mg g-1 h-1 at 5 degrees C to 2.69 mg g-1h-1 at 35 degrees C. Between 10 and 25 degrees C, intermittent respiration characterised by episodic bouts of breathing/gas exchange and periods of apnoea with no measurable Vo2 occurred. Although the duration of apnoea decreased when temperature was increased, the volume of oxygen taken up in each episode did not change. Mean respiratory exchange ratio (RER) was low (0.64-0.77) in post-absorptive bats, typical of fat utilisation, but during torpor ranged from near 0 to near 2, indicating discontinuous and disproportional gas exchange. Feeding produced a condition of relatively sustained homeothermy and high RER in the bats which persisted for 9 h, after which the N. gouldi became torpid. Immediately after feeding, the Vo2 of the bats increased fivefold above the post-absorptive level, while the Vco2 increased by more than eightfold. Similarly, body temperature also increased, declining to torpid values after 9. The RER in immediately post-feeding bats was near 1.0 but subsequently declined to near 0.7, indicating a switch from carbohydrate to fat utilisation. Therefore, the N. gouldi were heterothermic, exhibited a highly labile metabolic rate, and rates of heat and water loss, and Tb which were influenced both by ambient temperature and by nutritional status.

Childhood intussusception in a regional hospital.

This study reviews all childhood intussusceptions treated over a 6 year period in a regional centre with six visiting general surgeons and two paediatricians. Clinical presentation, management, complications and outcomes were noted and an attempt was made to follow up all cases. There were 20 patients, with a median age of 6 months (range 10 weeks to 17 months). Only one patient had all four classical features of intussusception (pain, vomiting, 'red currant jelly' stools and abdominal mass). Seven patients were managed successfully by barium enema reduction, but 14 required operation, four following failed radiological reduction. There was one intestinal perforation due to attempted barium enema reduction and one patient required a reoperation for ileal gangrene following operative reduction. There were no deaths and there have been no subsequent recurrent intussusceptions although three cases were lost to follow up. There was a delay in diagnosis in some cases (average duration from onset to diagnosis was 34 h). Although delay was incurred by parents in some cases and in peripheral hospitals in others, there is a need for greater awareness by surgeons of the significance of subtle features such as pallor and lethargy in a child with persistent vomiting. Delay in diagnosis is likely to lead to an increased need for primary surgical intervention. Adverse features (age > 3 months or < 2 years; symptoms > 24 h; small bowel obstruction; dehydration > 5%) were predictive of an increased likelihood of surgical resection, and may help avoid inappropriate attempts at radiological reduction.(ABSTRACT TRUNCATED AT 250 WORDS)

Alterations in apolipoprotein B-48 in the postprandial state in NIDDM.

The intestine is a major site of cholesterol synthesis and produces apolipoprotein B-48, which is critical for intestinal cholesterol absorption and secretion. The purpose of this study was to examine postprandial changes in apolipoprotein B-48 in diabetes. Six non-insulin-dependent diabetic patients and six non-diabetic control subjects were given a high-fat meal (1300 kcal) and blood samples were taken pre- and postprandially, from which the triglyceride-rich lipoprotein fraction was isolated by ultracentrifugation (density < 1.006 g/ml). Apolipoprotein B-48 was separated on 4-15% gradient gels and quantified as a percentage of the fasting concentration by densitometric scanning. Total protein, triglyceride and cholesterol in the triglyceride-rich lipoprotein fraction, blood glucose, and serum insulin were also measured. Diabetic patients exhibited a postprandial triglyceride-rich apolipoprotein B-48 profile significantly different from that of control subjects (p < 0.05). The triglyceride and total protein concentration in the triglyceride-rich lipoprotein fraction mirrored the post-prandial profile and apolipoprotein B-48 in both groups. Significantly different patterns for triglyceride (p < 0.02) and total protein (p < 0.05) following the fat-rich meal were observed in the two groups. Fasting and postprandial triglyceride-rich lipoprotein cholesterol and total apolipoprotein B were significantly higher in diabetic patients than in control subjects (p < 0.05). Since apolipoprotein B-48 is the structural protein of intestinally-derived lipoprotein particles, these studies suggest an abnormality in intestinal lipoprotein metabolism in diabetes.

MR imaging artifacts of the axial internal anatomy of the cervical spinal cord.

Transverse scans of the spinal cord routinely demonstrate signal variations related to the internal anatomy of the cord that do not accurately conform to histologic cross sections. This study evaluates the MR appearance of the axial anatomy of the spinal cord and provides correlation to histologic sections as a means to understand this discordance so that disease can be recognized more readily. Short TR/TE spin-echo studies, cardiac-gated multiecho spin-echo studies, and gradient-refocused-echo studies of normal excised human spinal cords, a normal volunteer, and gelatin phantoms were obtained by using the same imaging parameters at 1.5 T. Imaging artifacts were further investigated by using both a 128 x 256 and 256 x 256 matrix with a varying phase-encoded axis. Histologic sections of the excised cords, which were stained for myelin, iron, and cell bodies (Nissl), were used for correlation to the images. We found that significant Fourier truncation and partial-volume imaging artifacts modulated the MR display of the cord. On short TR/TE images a ring of high signal at the periphery of the cord was due to a truncation artifact. The appearance of the central portions of the gray and white matter was affected variably by partial-volume averaging depending on the matrix size. White-matter tracts of the cord were always lower in signal than was the gray matter on all pulse sequences. This finding was not due to iron deposition or CSF motion artifacts. We suspect that this probably was related to dense, longitudinal organization of spinal tracts and resultant anisotropy of water molecule motion similar to that seen in the pyramidal tracts, tendons, and ligaments. We recommend the use of a 128 x 256 matrix with two averages (four excitations) when obtaining axial scans of the spinal cord in living subjects. Although truncation artifacts diminish image quality, the quality is superior to that of images obtained with a 256 x 256 matrix, in which longer scanning times result in motion artifacts and reduced signal to noise.

Magnetic resonance imaging in dementia of Parkinson's disease.

The possibility that dementia in Parkinson's disease is associated with specific cerebral abnormalities identifiable by magnetic resonance imaging (MRI) was examined. Sixty eight patients with Parkinson's disease and 28 age and education matched normal controls were evaluated using neuropsychological procedures that included assessment of language, memory, cognition, visuospatial skills and mood. Twenty three patients (34%) were found to have developed significant impairment in at least three of the five areas, thus meeting criteria for a dementia syndrome. Eleven patients (16%) had no intellectual impairment and thirty four patients (50%) had a mild to moderate intellectual disturbance. Patients with (n = 10) and without dementia (n = 20), matched for severity of Parkinson's disease, and normal controls (n = 10) matched for age with the two patients groups, were evaluated by MRI. MRI scans were analysed for evidence of generalised cerebral atrophy, ventricular enlargement, visualisation of the substantia nigra and severity of focal brain lesions. Results indicated that the presence of dementia in patients with Parkinson's disease was not associated with any specific pattern of MRI abnormalities.