Adapting sanitary inspections for the monitoring of small drinking water supplies in Iceland.

Sanitary inspections (SIs) are checklists of questions used to identify actual and potential sources and pathways of drinking water contamination. Though the importance of SI adaptation to local contexts is widely acknowledged, there is currently limited guidance on how this should be undertaken in practice. During this research, World Health Organization (WHO) draft template SI forms for spring and borehole supplies were adapted for use in Iceland based on a series of desk reviews and field tests, an approach which may guide other future SI adaptation processes. SI results were collected from 25 spring supplies and nine borehole supplies in three regions of Iceland using adapted SI forms. These results were combined with 10-year historical water quality data from the same supplies to explore potential relationships between both data sets. Binary logistic regression test results indicated a statistically significant association (P = 0.025; odds ratio (OR) 1.864, 95% CI 1.080-3.220) between SI Question 3 (Does ponding from surface water occur around the spring/borehole?) receiving a 'High' risk level assignment and at least one historical incidence of water quality noncompliance for the parameters heterotrophic plate count 22 °C, total coliforms, Escherichia coli, and turbidity at the same supply. The significant modifications applied to the starting template during the testing and development of the Icelandic SI form emphasises the importance of a robust adaptation process to ensure SI forms are appropriate for the local context. Results from the analysis of SI and water quality test results demonstrated the potential for these data sets to identify the primary risks at a supply. This information may then be used to direct remedial actions, especially when the amount of relevant data increases over time.

Clinical cell-based versus cell-free regenerative endodontics: clarification of concept and term.

There is no consensus on the true meaning of clinical regenerative endodontics, and there is confusion over the concept and the term. Commonly used terms include revitalization and revascularization. The clinical methods for endodontic revitalization procedures and the tissue engineering concept differ depending on whether there is exogenous delivery of cells - called cell therapy, or not. Here, in this review, the difference is clarified by emphasizing the correct terminology: cell-free versus cell-based regenerative endodontic therapy (CF-RET versus CB-RET). The revitalization procedures practised clinically do not fit into the modern tissue engineering concepts of pulp regeneration but can be categorized as CF-RET. The modern tissue engineering concept in pulp regeneration is a CB-RET, which so far is at the clinical trial stage. However, histological examination of teeth following regenerative endodontic treatments reveals healing with repair derived from stem cells that originate from the periodontal, bone and other tissues. The aim of regenerative endodontics is regeneration of the pulp-dentine complex. This review discusses why CF-RET is unlikely to regenerate a pulp-dentine complex with current protocols. The American Association of Endodontists and the European Society of Endodontology have not yet recommended autologous stem cell transplantation (CB-RERT) which aspires for regeneration. Therefore, an understanding of the concept, term, difficulties and differences in current protocols is important for the clinician. However, rather than being discouraged that ideal regeneration has not been achieved to date, repair can be an acceptable outcome in clinical regenerative endodontics as it has also been accepted in medicine. Repair should also be considered in the context that resolution of the clinical signs/symptoms of pulp necrosis/apical periodontitis is generally reliably obtained in clinical regenerative endodontics.

Regenerative endodontics: a comprehensive review.

The European Society of Endodontology and the American Association for Endodontists have released position statements and clinical considerations for regenerative endodontics. There is increasing literature on this field since the initial reports of Iwaya et al. (Dental Traumatology, 17, 2001, 185) and Banchs & Trope (Journal of Endodontics, 30, 2004, 196). Endogenous stem cells from an induced periapical bleeding and scaffolds using blood clot, platelet rich plasma or platelet-rich fibrin have been utilized in regenerative endodontics. This approach has been described as a 'paradigm shift' and considered the first treatment option for immature teeth with pulp necrosis. There are three treatment outcomes of regenerative endodontics; (i) resolution of clinical signs and symptoms; (ii) further root maturation; and (iii) return of neurogenesis. It is known that results are variable for these objectives, and true regeneration of the pulp/dentine complex is not achieved. Repair derived primarily from the periodontal and osseous tissues has been shown histologically. It is hoped that with the concept of tissue engineering, namely stem cells, scaffolds and signalling molecules, that true pulp regeneration is an achievable goal. This review discusses current knowledge as well as future directions for regenerative endodontics. Patient-centred outcomes such as tooth discolouration and possibly more appointments with the potential for adverse effects needs to be discussed with patients and parents. Based on the classification of Cvek (Endodontics and Dental Traumatology, 8, 1992, 45), it is proposed that regenerative endodontics should be considered for teeth with incomplete root formation although teeth with near or complete root formation may be more suited for conventional endodontic therapy or MTA barrier techniques. However, much is still not known about clinical and biological aspects of regenerative endodontics.

The effect of the 'Gait keeper' mutation in the DMRT3 gene on gaiting ability in Icelandic horses.

A nonsense mutation in DMRT3 ('Gait keeper' mutation) has a predominant effect on gaiting ability in horses, being permissive for the ability to perform lateral gaits and having a favourable effect on speed capacity in trot. The DMRT3 mutant allele (A) has been found in high frequency in gaited breeds and breeds bred for harness racing, while other horse breeds were homozygous for the wild-type allele (C). The aim of this study was to evaluate further the effect of the DMRT3 nonsense mutation on the gait quality and speed capacity in the multigaited Icelandic horse and demonstrate how the frequencies of the A- and C- alleles have changed in the Icelandic horse population in recent decades. It was confirmed that homozygosity for the DMRT3 nonsense mutation relates to the ability to pace. It further had a favourable effect on scores in breeding field tests for the lateral gait tölt, demonstrated by better beat quality, speed capacity and suppleness. Horses with the CA genotype had on the other hand significantly higher scores for walk, trot, canter and gallop, and they performed better beat and suspension in trot and gallop. These results indicate that the AA genotype reinforces the coordination of ipsilateral legs, with the subsequent negative effect on the synchronized movement of diagonal legs compared with the CA genotype. The frequency of the A-allele has increased in recent decades with a corresponding decrease in the frequency of the C-allele. The estimated frequency of the A-allele in the Icelandic horse population in 2012 was 0.94. Selective breeding for lateral gaits in the Icelandic horse population has apparently altered the frequency of DMRT3 genotypes with a predicted loss of the C-allele in relatively few years. The results have practical implications for breeding and training of Icelandic horses and other gaited horse breeds.

[International Association of Dental Traumatology guidelines for the management of traumatic dental injuries: 1. Fractures and luxations of permanent teeth. Hebrew edition].

Traumatic dental injuries (TDIs) of permanent teeth occur frequently in children and young adults. Crown fractures and luxations are the most commonly occurring of all dental injuries. Proper diagnosis, treatment planning and follow up are important for improving a favorable outcome. Guidelines should assist dentists and patients in decision making and for providing the best care effectively and efficiently. The International Association of Dental Traumatology (IADT) has developed a consensus statement after a review of the dental literature and group discussions. Experienced researchers and clinicians from various specialties were included in the group. In cases where the data did not appear conclusive, recommendations were based on the consensus opinion of the IADT board members. The guidelines represent the best current evidence based on literature search and professional opinion. The primary goal of these guidelines is to delineate an approach for the immediate or urgent care of TDIs. In this first article, the IADT Guidelines for management of fractures and luxations of permanent teeth will be presented. The Hebrew Edition is part of the IADT global effort to provide accessibility to these guidelines worldwide.

[International Association of Dental Traumatology guidelines for the management of traumatic dental injuries: 2. Avulsion of permanent teeth. Hebrew edition].

Avulsion of permanent teeth is one of the most serious dental injuries, and a prompt and correct emergency management is very important for the prognosis. The International Association of Dental Traumatology (IADT) has developed a consensus statement after a review of the dental literature and group discussions. Experienced researchers and clinicians from various specialties were included in the task group. The guidelines represent the current best evidence and practice based on literature research and professionals' opinion. In cases where the data did not appear conclusive, recommendations were based on the consensus opinion or majority decision of the task group. Finally, the IADT board members were giving their opinion and approval. The primary goal of these guidelines is to delineate an approach for the immediate or urgent care of avulsed permanent teeth. The Hebrew Edition is part of the IADT global effort to provide a worldwide accessibility to these guidelines. This scond part of the guidelines will focus on avulsion of permanent teeth.

[International Association of Dental Traumatology guidelines for the management of traumatic dental injuries: 3. Injuries in the primary dentition. Hebrew edition].

Traumatic injuries to the primary dentition present special problems and the management is often different as compared with the permanent dentition. The International Association of Dental Traumatology (IADT) has developed a consensus statement after a review of the dental literature and group discussions. Experienced researchers and clinicians from various specialities were included in the task group. In cases where the data did not appear conclusive, recommendations were based on the consensus opinion or majority decision of the task group. Finally, the IADT board members were giving their opinion and approval. The primary goal of these guidelines is to delineate an approach for the immediate or urgent care for management of primary teeth injuries. The IADT cannot and does not guarantee favorable outcomes from strict adherence to the guidelines, but believe that their application can maximize the chances of a positive outcome. The Hebrew Edition is part of the IADT global effort to provide a worldwide accessibility to these guidelines. This third part will discuss injuries in the primary dentition.

Comparative micro-computed tomographic evaluation of two carrier-based obturation systems.

OBJECTIVES: The aim of the study was to measure the percentage of volume of voids and gaps in the apical third of root canals obturated with two techniques using micro-computed tomography. MATERIALS AND METHODS: Fifty-four single-rooted teeth were collected and root canal-prepared. The roots were randomly allocated into two groups; each group was obturated by using thermoplasticized technique with a different material (gutta-percha and Topseal for Thermafil, Resilon and RealSeal for RealSeal 1). Roots were then scanned, and volume measurements for voids and gaps in the obturated roots were carried out using specialized CT software. Percentage of gaps and voids was calculated. RESULTS: The present study showed that none of the root canal-filled teeth was gap free. Student t test was conducted. No significant difference was found between Thermafil and RealSeal 1 concerning percentage of voids in the apical third (P > 0.05). Both materials showed statistically significant difference between the levels where 1 mm showed the highest volume of voids (P < 0.05). CONCLUSIONS: Both carrier-based techniques allowed a good sealing ability in root canals but none of the materials was gap free. Statistically significant difference between the levels was found and 1 mm showed the highest volume of voids. CLINICAL RELEVANCE: This study shows the efficiency of carrier-based obturation systems in filling root canals hermetically. It compares new adhesive endodontic materials with the traditional gold standard gutta-percha. Results show the good sealing ability of both techniques making them appropriate to use in daily endodontic obturations.

Estimation of genetic parameters and response to selection for a continuous trait subject to culling before testing.

The consequences of assuming a zero environmental covariance between a binary trait 'test-status' and a continuous trait on the estimates of genetic parameters by restricted maximum likelihood and Gibbs sampling and on response from genetic selection when the true environmental covariance deviates from zero were studied. Data were simulated for two traits (one that culling was based on and a continuous trait) using the following true parameters, on the underlying scale: h² = 0.4; r(A) = 0.5; r(E) = 0.5, 0.0 or -0.5. The selection on the continuous trait was applied to five subsequent generations where 25 sires and 500 dams produced 1500 offspring per generation. Mass selection was applied in the analysis of the effect on estimation of genetic parameters. Estimated breeding values were used in the study of the effect of genetic selection on response and accuracy. The culling frequency was either 0.5 or 0.8 within each generation. Each of 10 replicates included 7500 records on 'test-status' and 9600 animals in the pedigree file. Results from bivariate analysis showed unbiased estimates of variance components and genetic parameters when true r(E) = 0.0. For r(E) = 0.5, variance components (13-19% bias) and especially (50-80%) were underestimated for the continuous trait, while heritability estimates were unbiased. For r(E) = -0.5, heritability estimates of test-status were unbiased, while genetic variance and heritability of the continuous trait together with were overestimated (25-50%). The bias was larger for the higher culling frequency. Culling always reduced genetic progress from selection, but the genetic progress was found to be robust to the use of wrong parameter values of the true environmental correlation between test-status and the continuous trait. Use of a bivariate linear-linear model reduced bias in genetic evaluations, when data were subject to culling.

Effects of integrated genetic evaluations for Icelandic horses on predictive ability, accuracy and selection bias.

The genetic evaluation of Icelandic horses is currently based on results from breeding field tests of riding ability and conformation. The effect of integrating competition traits and/or test status into the genetic evaluation was studied concerning estimation bias, predictive ability, accuracy, correlations between breeding values and ranking of sires. Breeding field test data included 19 954 records from horses assessed in 11 countries during 1994-2008. Competition data included 44 160 records from 7687 horses competing in Iceland and Sweden in 1998-2008. Test status was defined as attendance of horses born in Iceland at breeding field tests and/or in competition. Overall, there were trivial differences between different genetic evaluation models regarding estimation bias and predictive ability. Very strong correlations were estimated between breeding values for combined indexes of conformation, riding ability and total score from different models. Higher accuracy was achieved for most of the traits when competition traits and/or test status were added to the model. Sires ranked differently when the new traits were added to the genetic evaluation model. It was concluded that competition traits should be integrated into the genetic evaluation. Further analyses on genetic parameters for test status and its relationship with the other traits are needed for future inclusion of test status in the genetic evaluation.

Genetic analysis of 'breeding field test status' in Icelandic horses.

Genetic evaluation of Icelandic horses is currently based on results from breeding field tests where riding ability and conformation of the horses are evaluated over the course of 1-2 days. Only a small part of registered horses attend these field tests, and it can be assumed that these are not a random sample of the population. In this study, the trait test status was introduced, describing whether a horse was assessed in a breeding field test. This trait was analysed to find out whether it has a genetic variation and how it correlates genetically to other traits in the breeding goal. Breeding field test data included 39,443 mares born in Iceland in 1990-2001, of which 7431 were assessed in the period 1994-2007. The trait was defined in relation to age, gender and stud of horses. Variance and covariance components were estimated using the Markov Chain Monte Carlo method by applying the Gibbs sampler procedure in the DMU program. Three multivariate analyses were performed where the test status trait was analysed with breeding field test traits. Animal models and sire models were applied. Based on estimated heritabilities (0.51-0.67) and genetic correlations (0.00-0.87), the test status trait showed significant genetic variation and was strongly correlated to some traits. The test status trait reflects preselection in the breeding field test traits and should be included in the genetic evaluation to enhance the procedure, reduce selection bias and increase accuracy of the estimation.

Band erosion after laparoscopic gastric banding: a retrospective analysis of 865 patients over 5 years.

BACKGROUND: Gastric band erosion is a well-reported complication after laparoscopic adjustable gastric banding (LAGB). The published literature is limited and inconclusive with regard to its management. The authors therefore reviewed all band erosions detected during a 5-year period in a high-volume bariatric practice. Because a significant proportion of the band insertions (65%) were undertaken by an operator beyond his learning curve, the authors hoped to gain a mature, comprehensive understanding of this significant complication. METHODS: The authors retrospectively reviewed the operative log of the operating theaters in their obesity surgery unit to find all the operations performed on LAGB patients for erosion from January 2003 to December 2007. The clinical notes and electronic records for each patient were reviewed. These data were cross-referenced against the authors' obesity surgery database, and denominator data such as the total number operations performed and demographics were found. Finally, postoperative outcomes were collated from the outpatient follow-up data and telephonic interviews, and the results were analyzed. RESULTS: From January 2003 to December 2007, a single surgeon performed 865 LAGBs in the authors' unit. The authors identified 18 operations performed for LAGB erosions. The 18 patients (one referred from elsewhere, 14 women) formed the final study cohort (median preoperative body mass index [BMI], 46 kg/m(2)). Of the 17 erosions, 15 occurred relatively early in the series. The patients with the 213 Swedish adjustable gastric bands experienced 12 erosions (incidence, 5.6%) compared with 6 erosions with the 652 LAP-BANDs (incidence, 0.9%). The median time to presentation was 7 months (range, 1-60 months). However, 55% of the erosions (n = 10) occurred within the first year, and only 10% occurred after the second year. The most common presenting symptom was pain followed by weight regain. None of the patients experienced peritonitis. After surgical management of the erosion, three patients had a second LAGB and at this writing are well. Of the remaining patients, 11 are well, but 6 of these patients have returned to their previous weight (4 patients were lost to follow-up evaluation). CONCLUSIONS: The overall incidence of LAGB erosions in our series was 1.96%. This incidence fell with increasing experience to 0.5% after the initial 300 bands were excluded from the analysis (3 band erosions in the last 565 band insertions). However, further increases in incidence are likely with a longer follow-up period. The most common presentation was abdominal pain followed by weight regain and port-site sepsis. In the authors' hands, laparoscopic omental plugging and band removal through a separate anterior gastrotomy appear to be effective methods for dealing with band erosions. Band erosion is a significant source of morbidity, with at least one-third of the erosion patients in our series not achieving their final goal of weight loss despite appropriate treatment. This study highlights the need for a future prospective randomized study to clarify the apparent strong influence of band design and construction on the etiopathogenesis of band erosion.

Influence of psychological factors on risk of temporomandibular disorders.

Psychological characteristics potentially may be a cause or consequence of temporomandibular disorder (TMD). We hypothesized that psychological characteristics associated with pain sensitivity would influence risk of first-onset TMD, but the effect could be attributed to variation in the gene encoding catechol-O-methyltransferase (COMT). We undertook a prospective cohort study of healthy female volunteers aged 18-34 yrs. At baseline, participants were genotyped, they completed psychological questionnaires, and underwent quantitative sensory testing to determine pain sensitivity. We followed 171 participants for up to three years, and 8.8% of them were diagnosed with first-onset TMD. Depression, perceived stress, and mood were associated with pain sensitivity and were predictive of 2- to 3-fold increases in risk of TMD (P < 0.05). However, the magnitude of increased TMD risk due to psychological factors remained unchanged after adjustment for the COMT haplotype. Psychological factors linked to pain sensitivity influenced TMD risk independently of the effects of the COMT haplotype on TMD risk.

Gastric bezoar complicating laparoscopic adjustable gastric banding with band slippage.

Gastric bezoars may develop in the proximal pouch after gastric restriction, eg. by laparoscopic adjustable gastric banding (LAGB). To date, only two centers have reported this rare complication. We report an additional case with band slippage, to emphasize that bezoars should be considered in the differential diagnosis in patients presenting with new onset nausea and vomiting after LAGB.

Laparoscopic repair of large paraesophageal hiatus hernia: quality of life and durability.

BACKGROUND: Laparoscopic repair of large paraesophageal hiatus hernias (LPOHH) is shown to be a safe and effective operation in the short term. However, its long-term durability and its effect on quality of life are less well established. This study aimed to assess the midterm outcome for laparoscopic repair of LPOHH with validated quality-of-life symptom scores and barium studies. METHODS: Between January 2000 and July 2004, 49 patients (27 women) with LPOHH underwent laparoscopic repair. The median age of these patients was 68 years (range, 38-90 years). The laparoscopic repair included resection of the hernia sac, reduction of its contents, esophageal mobilization up to the aortic arch, crural repair with sutures (mesh reinforcement in 17 cases), Nissen fundoplication, and fixation of the wrap to the crura. Follow-up assessment was prospective with quality-of-life questionnaires, the Gastrointestinal Symptom Rating Scale (GSRS), the Gastroesophageal Reflux Disease-Health-Related Quality of Life (GERD-HRQOL) scale, and barium studies. RESULTS: The presenting symptoms were pain for 21 patients, reflux for 27 patients, bleeding or anemia for 14 patients, and dysphagia for 17 patients. Five emergency operations were performed. Short esophagus was present in 24 patients. There were two conversions to open surgery. The major morbidity (atrial fibrillation, pulmonary embolism, and splenectomy) rate was 10.2%, and the minor morbidity (chest infection, jaundice, dysphagia, small pneumothorax) rate was 20.4%. Six patients were deceased of unrelated causes at the time of follow-up evaluation. Responses to the questionnaires were obtained in 31 cases (75%). Using the Wilcoxon signed rank test, the results from the questionnaires showed a statistically significant improvement (p < 0.001) in abdominal pain, reflux, and indigestion scores (GSRS) and GERD-HRQOL scores. Follow-up barium studies for 27 patients (66%) showed recurrence in 4 patients (14.8%), 2 of which were symptomatic. CONCLUSION: Laparoscopic repair of LPOHH is associated with good quality of life as well as an acceptable midterm recurrence rate.

High incidence of loss of heterozygosity in breast tumors from carriers of the BRCA2 999del5 mutation.

Germ-line mutation in the BRCA2 gene confers an increased risk of breast cancer. An elevation of additional genetic defects in tumors of patients with germ-line mutation in the BRCA2 gene compared with sporadic breast tumors has been reported. To evaluate the nature of the difference, we did detailed mapping of chromosomes 1p, 3p, 6q, 11, 13q, 16q, 17, and 20q, using microsatellite markers. We found that the frequency of loss of heterozygosity was similar at some chromosomal regions in the BRCA2 999del5 and sporadic tumors but significantly different at others. These others include chromosomal arms 3p, 6q, 11p, 11q, 13q, and 17p. Loss of heterozygosity mapping suggests that the same chromosome regions are involved in both tumor groups but at elevated frequencies in BRCA2 999del5 tumors. This higher frequency of genetic aberrations could pinpoint genes that selectively promote tumor progression in individuals predisposed to breast cancer due to the BRCA2 999del5 germ-line mutation. Accumulation of somatic genetic changes during tumor progression may follow a specific and more aggressive pathway of chromosome damage in these individuals.

Sensitivity of patients with painful temporomandibular disorders to experimentally evoked pain: evidence for altered temporal summation of pain.

Temporomandibular disorders (TMD) represent a group of chronic painful conditions involving the muscles of mastication and the temporomandibular joint. Several studies have reported that TMD is associated with enhanced sensitivity to experimental pain. Twenty-three TMD subjects and 24 pain-free matched control subjects participated in a set of studies which were designed to evaluate whether the temporal integrative aspects of thermal pain perception are altered in TMD patients compared with control subjects. Specifically, we have examined in both TMD patients and in age- and gender-matched control subjects: (1) the time-course and magnitude of perceived pain evoked by the application of sustained 7-s noxious thermal stimuli (45-48 degrees C) to the face and forearm, (2) the central summation of C-fiber-mediated pain produced by applying brief trains of noxious heat pulses to the skin overlying the ventral aspect of the right palm and (3) the ability to discriminate small increments in noxious heat applied to facial and volar forearm skin. Data collected from these studies indicate that TMD patients show enhanced temporal integration of thermal pain compared with control subjects. TMD patients show greater thermal C-fiber-mediated temporal summation than pain-free subjects and they report a greater magnitude of sustained noxious heat pulses applied to either the face or the forearm than control subjects. In contrast to these findings, TMD and pain-free subjects are equally able to discriminate and detect small increments of heat applied to noxious adapting temperatures. These findings suggest that the augmented temporal integration of noxious stimuli may result from alterations in central nervous system processes which contribute to the enhanced pain sensitivity observed in TMD patients.

Loss of heterozygosity at chromosome 6q correlates with tumor progression and patient survival.

Several chromosome regions exhibit loss of heterozygosity (LOH) in human breast carcinoma and are thought to carry tumor suppressor genes. We have analysed human breast tumors with 9 polymorphic microsatellite markers that are specific to chromosome 6q. The mapping of smallest region of overlap (SRO) indicated location of candidate suppressor genes at 6q23 and 6q27. Variations in estrogen receptor (ER) expression were independent of the number of copies of the corresponding gene. Tumors with and without LOH on chromosome 6q were tested for association with clinicopathological factors. A significant association was found between LOH at 6q and the following: high S-phase, aneuploidy, deletions at chromosomes 3p and 9p and lower survival rate. In a multivariate model LOH at 6q is an independent prognostic variable and patients having tumors with LOH have approximately twofold increase in relative risk of death. It can be concluded that the 6q deletions give additional prognostic information that might be useful in breast cancer treatment.

Loss of heterozygosity at chromosome 1p in human breast cancer.

232 human primary invasive breast tumors were analyzed with 13 polymorphic microsatellite markers specific to chromosome 1p. Loss of heterozygosity (LOH) was observed in 126 cases or 54% of the tumors. One marker, D1S496, at the 1p35 region showed the highest LOH, 28%. High frequencies of LOH were also detected by the markers, D1S488, D1S167 and D1S435, at the 1p31 region, 25%, 24% and 26% LOH, respectively. This suggests the presence of tumor suppressor genes at these two regions. Tumors with and without LOH at 1p were tested for association with clinico-pathological features of the tumors such as estrogen- and progesterone-receptor content (ER and PgR), age at diagnosis, tumor size, node status, histological type, S-phase fraction, ploidy, survival and LOH at chromosomes 3p, 6q, 9p, 11p, 11q, 13q, 16q, 17p and 17q. A significant association was found between LOH at chromosome 1p and high S-phase fraction and lower survival rate. Association was also found between LOH at 1p and chromosome regions 3p, 6q, 9p and 17q. A multivariate model including prognostic variables, showed that LOH at 1p is an independent prognostic variable and patients who have breast tumors with LOH at 1p have approximately a two-fold increase in relative risk of death. We conclude that screening for 1p deletions gives additional prognostic information that might be useful in breast cancer treatment.

Early neurohormonal effects of trandolapril in patients with left ventricular dysfunction and a recent acute myocardial infarction: a double-blind, randomized, placebo-controlled multicentre study.

Angiotensin-converting enzyme inhibitors improve long-term survival in patients with left ventricular dysfunction after a myocardial infarction, but their mechanism of action is not entirely clear. The neurohormonal effects may be important in this respect, as well as an early hemodynamic unloading induced by these drugs. The primary objective was to assess the effect of trandolapril on plasma levels of atrial natriuretic peptide. A secondary objective was to assess the effects of trandolapril on selected neurohormones, vasoactive peptides and enzymes, which may be important in the development of left ventricular remodeling and heart failure following an acute myocardial infarction. A total of 119 patients with an acute myocardial infarction and a wall motion index < or =1.2 (16-segment echocardiographic model) were randomized to double blind treatment with trandolapril or placebo within 3-7 days after the onset of infarction. Blind treatment was discontinued 21 days after the index infarction. Venous blood samples were collected at rest, before randomization and on the day after treatment was discontinued. At the end of the study, there were no differences in plasma levels of atrial natriuretic peptide between the two treatment groups. Angiotensin-converting enzyme activity was suppressed and plasma renin activity was higher in the trandolapril group. No differences in plasma levels of N-terminal pro-atrial natriuretic peptide, brain natriuretic peptide, aldosterone, noradrenaline, adrenaline, vasopressin, big endothelin-1 and neuropeptide Y were found between the two treatment groups. There were positive correlations between several markers of neurohormonal activation at baseline and variables expressing left ventricular dysfunction and clinical heart failure. Neurohormonal activation is related to left ventricular dysfunction. The effects of 2-3 weeks of angiotensin-converting enzyme inhibition on neurohormonal activation does not predict the already established beneficial long-term effects after myocardial infarction. Thus, early modulation of circulatory neurohormone levels may not be a major mechanism for the efficacy of angiotensin-converting enzyme inhibitors in these patients. Selected plasma hormone markers may still be used to identify patients who might get the greatest benefit from treatment.