Lost in Time: Temporal Monitoring Elicits Clinical Decrements in Sustained Attention Post-Stroke.

OBJECTIVES: Mental fatigue, 'brain fog', and difficulties maintaining engagement are commonly reported issues in a range of neurological and psychiatric conditions. Traditional sustained attention tasks commonly measure this capacity as the ability to detect target stimuli based on sensory features in the auditory or visual domains. However, with this approach, discrete target stimuli may exogenously capture attention to aid detection, thereby masking deficits in the ability to endogenously sustain attention over time. METHODS: To address this, we developed the Continuous Temporal Expectancy Task (CTET) where individuals continuously monitor a stream of patterned stimuli alternating at a fixed temporal interval (690 ms) and detect an infrequently occurring target stimulus defined by a prolonged temporal duration (1020 ms or longer). As such, sensory properties of target and non-target stimuli are perceptually identical and differ only in temporal duration. Using the CTET, we assessed stroke survivors with unilateral right hemisphere damage (N = 14), a cohort in which sustained attention deficits have been extensively reported. RESULTS: Stroke survivors had overall lower target detection accuracy compared with neurologically healthy age-matched older controls (N = 18). Critically, stroke survivors performance was characterised by significantly steeper within-block performance decrements, which occurred within short temporal windows (˜3 ½ min), and were restored by the break periods between blocks. CONCLUSIONS: These findings suggest that continuous temporal monitoring taxes sustained attention processes to capture clinical deficits in this capacity over time, and outline a precise measure of the endogenous processes hypothesised to underpin sustained attention deficits following right hemisphere stroke.

Differential regulation of osteopontin and CD44 correlates with infertility status in PCOS patients.

Endometrial receptivity is mediated by adhesion molecules at the endometrium-trophoblast interface where osteopontin (OPN) and CD44 form a protein complex that plays an important role in embryo recognition. Here, we undertook a prospective study investigating the expression and regulation of OPN and CD44 in 50 fertile and 31 infertile ovulatory polycystic ovarian syndrome (PCOS) patients in the proliferative and secretory phases of the natural menstrual cycle and in 12 infertile anovulatory PCOS patients. Endometrial biopsies and blood samples were evaluated for expression of OPN and CD44 using RT-PCR, immunohistochemistry and ELISA analysis to determine circulating levels of OPN, CD44, TNF-α, IFN-γ and OPN and CD44 levels in biopsy media. Our findings highlighted an increased level of circulating OPN and CD44 in serum from infertile patients that inversely correlated with expression levels in endometrial tissue and positively correlated with levels secreted into biopsy media. OPN and CD44 levels positively correlated to each other in serum and media from fertile and PCOS patients, as well as to circulating TNF-α and IFN-γ. In vitro analysis revealed that hormone treatment induced recruitment of ERα to the OPN and CD44 promoters with a concomitant increase in the expression of these genes. In infertile patients, inflammatory cytokines led to recruitment of NF-κB and STAT1 proteins to the OPN and CD44 promoters, resulting in their overexpression. These observations suggest that the endometrial epithelial OPN-CD44 adhesion complex is deficient in ovulatory PCOS patients and displays an altered stoichiometry in anovulatory patients, which in both cases may perturb apposition. This, together with elevated circulating and local secreted levels of these proteins, may hinder endometrium-trophoblast interactions by saturating OPN and CD44 receptors on the surface of the blastocyst, thereby contributing to the infertility associated with ovulating PCOS patients. KEY MESSAGES: • Endometrial epithelial OPN-CD44 adhesion complex levels are deficient in ovulatory PCOS patients contributing to the endometrial infertility associated with ovulating PCOS patients. • Circulating levels of OPN, CD44 and inflammatory cytokines TNF-α and IFN-γ are altered in infertile PCOS patients. • Increased levels of both OPN and CD44 in biopsy media and serum inversely correlate with endometrial expression of these markers in endometrial tissue. • In infertile PCOS patients, high levels of oestrogens and inflammatory cytokines stimulate the recruitment of transcription factors to the OPN and CD44 promoters to enhance gene transcription. • Our study identifies a novel crosstalk between the CD44-OPN adhesion complex, ERα, STAT1 and NF-κB pathways modulating endometrial receptivity.

Towards error categorisation in BCI: single-trial EEG classification between different errors.

OBJECTIVE: Error-related potentials (ErrP) are generated in the brain when humans perceive errors. These ErrP signals can be used to classify actions as erroneous or non-erroneous, using single-trial electroencephalography (EEG). A small number of studies have demonstrated the feasibility of using ErrP detection as feedback for reinforcement-learning-based brain-computer interfaces (BCI), confirming the possibility of developing more autonomous BCI. These systems could be made more efficient with specific information about the type of error that occurred. A few studies differentiated the ErrP of different errors from each other, based on direction or severity. However, errors cannot always be categorised in these ways. We aimed to investigate the feasibility of differentiating very similar error conditions from each other, in the absence of previously explored metrics. APPROACH: In this study, we used two data sets with 25 and 14 participants to investigate the differences between errors. The two error conditions in each task were similar in terms of severity, direction and visual processing. The only notable differences between them were the varying cognitive processes involved in perceiving the errors, and differing contexts in which the errors occurred. We used a linear classifier with a small feature set to differentiate the errors on a single-trial basis. MAIN RESULTS: For both data sets, we observed neurophysiological distinctions between the ErrPs related to each error type. We found further distinctions between age groups. Furthermore, we achieved statistically significant single-trial classification rates for most participants included in the classification phase, with mean overall accuracy of 65.2% and 65.6% for the two tasks. SIGNIFICANCE: As a proof of concept our results showed that it is feasible, using single-trial EEG, to classify these similar error types against each other. This study paves the way for more detailed and efficient learning in BCI, and thus for a more autonomous human-machine interaction.

Learning while multitasking: short and long-term benefits of brain stimulation.

We employed a simulated production task that mimics the real-world skill acquisition required of operators working in control rooms of power plants to assess short and long-term effects of transcranial random noise stimulation (tRNS). tRNS has shown potential for enhancing learning and performance of cognitive skills. Forty subjects (24 female) learned how to execute the simulated production task during the training phase and were required to perform a secondary task during the skill acquisition phase while they received active (12 min) or sham tRNS on DLPFC. After 2 weeks they had to recall the task again without any stimulation. The results demonstrate that tRNS promoted better multitasking as reflected by better performance in a secondary task during and immediately after tRNS. However, 2 weeks later, beneficial effect of tRNS on retention was moderated by general mental ability. Particularly, tRNS benefited those with lower general mental ability. Practitioner summary: By using a simulated production task, we assessed the effects of tRNS on learning and skill retention. The study indicates that neurostimulation can enhance the learning of multiple complex tasks. Moreover, it shows that retention of those tasks can be supported by neurostimulation, especially for those with lower general mental ability.

Human gestation-associated tissues express functional cytosolic nucleic acid sensing pattern recognition receptors.

The role of viral infections in adverse pregnancy outcomes has gained interest in recent years. Innate immune pattern recognition receptors (PRRs) and their signalling pathways, that yield a cytokine output in response to pathogenic stimuli, have been postulated to link infection at the maternal-fetal interface and adverse pregnancy outcomes. The objective of this study was to investigate the expression and functional response of nucleic acid ligand responsive Toll-like receptors (TLR-3, -7, -8 and -9), and retinoic acid-inducible gene 1 (RIG-I)-like receptors [RIG-I, melanoma differentiation-associated protein 5 (MDA5) and Laboratory of Genetics and Physiology 2(LGP2)] in human term gestation-associated tissues (placenta, choriodecidua and amnion) using an explant model. Immunohistochemistry revealed that these PRRs were expressed by the term placenta, choriodecidua and amnion. A statistically significant increase in interleukin (IL)-6 and/or IL-8 production in response to specific agonists for TLR-3 (Poly(I:C); low and high molecular weight), TLR-7 (imiquimod), TLR-8 (ssRNA40) and RIG-I/MDA5 (Poly(I:C)LyoVec) was observed; there was no response to a TLR-9 (ODN21798) agonist. A hierarchical clustering approach was used to compare the response of each tissue type to the ligands studied and revealed that the placenta and choriodecidua generate a more similar IL-8 response, while the choriodecidua and amnion generate a more similar IL-6 response to nucleic acid ligands. These findings demonstrate that responsiveness via TLR-3, TLR-7, TLR-8 and RIG-1/MDA5 is a broad feature of human term gestation-associated tissues with differential responses by tissue that might underpin adverse obstetric outcomes.

The Influence of Prebiotics on Neurobiology and Behavior.

Manipulating the intestinal microbiota for the benefit of the brain is a concept that has become widely acknowledged. Prebiotics are nondigestible nutrients (i.e., fibers, carbohydrates, or various saccharides) that proliferate intrinsic, beneficial gut bacteria, and so provide an alternative strategy for effectively altering the enteric ecosystem, and thence brain function. Rodent studies demonstrating neurobiological changes following prebiotic intake are slowly emerging, and have thus far revealed significant benefits in disease models, including antiinflammatory and neuroprotective actions. There are also compelling data showing the robust and favorable effects of prebiotics on several behavioral paradigms including, anxiety, learning, and memory. At present, studies in humans are limited, though there is strong evidence for prebiotics modulating emotional processes and the neuroendocrine stress response that may underlie the pathophysiology of anxiety. While the mechanistic details linking the enteric microbiota to the central nervous system remain to be elucidated, there are a number of considerations that can guide future studies. These include the modulation of intestinal endocrine systems and inflammatory cascades, as well as direct interaction with the enteric nervous system and gut mucosa. Our knowledge of gut microbiome-brain communication is steadily progressing, and thorough investigations validating the use of prebiotics in the treatment of neuropsychiatric disorders would be highly valued and are encouraged.

Reflux composition influences the level of NF-κB activation and upstream kinase preference in oesophageal adenocarcinoma cells.

Oesophageal adenocarcinoma (OA) incidence is rising and prognosis is poor. Understanding the molecular basis of this malignancy is key to finding new prevention and treatment strategies. Gastroesophageal reflux disease is the primary cause of OA, usually managed with acid suppression therapy. However, this often does little to control carcinogenic bile acid reflux. The transcription factor nuclear factor kappa B (NF-κB) plays a key role in the pathogenesis of OA and its activity is associated with a poor response to chemotherapy, making it an attractive therapeutic target. We sought to decipher the role of different bile acids in NF-κB activation in oesophageal cell lines using short, physiologically relevant exposure times. The effect of an acidic or neutral extracellular pH was investigated concurrently, to mimic in vivo conditions associated with or without acid suppression. We found that some bile acids activated NF-κB to a greater extent when combined with acid, whereas others did so in its absence, at neutral pH. The precise composition of an individual's reflux, coupled with whether they are taking acid suppressants may therefore dictate the extent of NF-κB activation in the oesophagus, and hence the likelihood of histological progression and chemotherapy success. Regardless of pH, the kinase inhibitor of κB kinase was pivotal in mediating reflux induced NF-κB activation. Its importance was confirmed further as its increased activation was associated with histological progression in patient samples. We identified further kinases important in acid or bile induced NF-κB signalling in oesophageal cells, which may provide suitable targets for therapeutic intervention.

Inducible nitric oxide synthase (iNOS) and nitric oxide (NO) are important mediators of reflux-induced cell signalling in esophageal cells.

Nitric oxide (NO) produced by inducible nitric oxide synthase (iNOS) has been implicated in both DNA damage induction and aberrant cell signalling in various tissue and cell backgrounds. We investigated here the role of iNOS and NO in DNA damage induction and nuclear factor-kappa B (NF-κB) signalling in esophageal cells in vitro. As esophageal adenocarcinoma develops in a background of Barrett's esophagus secondary to reflux disease, it is possible that inflammatory mediators like NO may be important in esophageal cancer development. We show that reflux components like stomach acid and bile acids [deoxycholic acid (DCA)] can induce iNOS gene and protein expression and produce NO generation in esophageal cells, using real-time PCR, western blotting and NO sensitive fluorescent probes, respectively. This up-regulation of iNOS expression was not dependent on NF-κB activity. DCA-induced DNA damage was independent of NF-κB and only partially dependent on iNOS and NO, as measured by the micronucleus assay. These same reflux constituents also activated the oncogenic transcription factor NF-κB, as measured by transcription factor enzyme-linked immunosorbent assay and gene expression studies with NF-κB linked genes (e.g. interleukin-8). Importantly, we show here for the first time that basal levels of NF-κB activity (and possibly acid and DCA-induced NF-κB) are dependent on iNOS/NO and this may lead to a positive feedback loop whereby induced iNOS is upstream of NF-κB, hence prolonging and potentially amplifying this signalling, presumably through NO activation of NF-κB. Furthermore, we confirm increased protein levels of iNOS in esophageal adenocarcinoma and, therefore, in neoplastic development in the esophagus.

Disease outcome for children who present with oral manifestations of Crohn's disease.

AIM: To describe the outcome for children with oral Crohn's disease (OCD) at diagnosis, and to determine if there was a difference in the Paediatric Crohn's Disease Activity Index (PCDAI) scores between those with and those without oral lesions at follow-up. METHODS: Thirty-one patients with OCD who had enrolled in two previous studies were invited to participate. Clinical and laboratory data were collected to calculate the PCDAI. Details of the management of Crohn's disease were also recorded. RESULTS: Twenty-four of 31 patients participated (77%), of whom 17 were boys (M:F = 2.4:1). Mean age at follow-up was 15.7 years (SD 1.98, range 11.9-19.7 years). Mean duration of follow-up was 55 months (SD 22, range 20-97 months). Oral manifestations were present at follow-up in 7 (29%) of 24 patients. There were no differences between patients with and without OCD at follow-up with regard to medical treatments received or intestinal disease location. There was no difference in median PCDAI scores between those who had and those who had not oral lesions at follow-up. CONCLUSIONS: OCD resolved in the majority of children treated for intestinal Crohn's disease. The occurrence of mouth lesions during follow-up of children who had oral manifestations at initial diagnosis was not a marker for Crohn's disease activity elsewhere in the intestinal tract.

Sensory-motor polyneuropathy occurring in variant maple syrup urine disease.

Maple syrup urine disease (MSUD; OMIM 248600) results from an inherited deficiency of the branched-chain ketoacid dehydrogenase (BCKD) complex. Approximately 20% of patients with BCKD deficiency are non-classic variants of MSUD with differing clinical severity. Outcomes for this cohort are generally favourable; episodes of metabolic decompensation do not appear to correlate with adverse events if acute management is promptly provided. A case of predominantly axonal sensory-motor neuropathy following metabolic decompensation which persisted for a number of months is presented in an adolescent girl with variant (intermediate type) MSUD. EMG and nerve conduction studies suggested a pre-existent asymptomatic chronic neuropathy, exacerbated by the acute decompensation. Peak leucine concentration at decompensation was 1083 µmol/L. The patient had laboratory signs of secondary mitochondrial respiratory chain dysfunction at presentation. She had been on a moderate dose of thiamine prior to decompensation; thiamine and pyridoxine blood concentrations were normal. This, to our knowledge, is the first report of a neuropathy presenting in a patient with a decompensation of variant MSUD. We propose that this presentation resembles the intermittent neuropathy observed in pyruvate dehydrogenase deficiency and may reflect secondary inhibition of pyruvate dehydrogenase activity by MSUD metabolites.

Wheeze, eczema and rhinitis in 6-7 year old Irish schoolchildren.

The aim of this study was to determine the prevalence of wheeze, eczema and rhinitis in 6-7 year old schoolchildren in Louth and Meath and assess their risk factors. The ISAAC (International Study for Asthma and Allergies in Childhood) questionnaire was used. The response rate was 64.1% (n = 1899). The prevalence rates for wheeze, eczema and rhinitis were 17.4%, 11.2% and 20.2% respectively, with 2.4% of children reported to be suffering from all 3 conditions. The main risk factors for wheeze were male sex and smoking in the home. Ninety-five (28.7%) children with wheeze had no diagnosis of asthma. Of these children 36 (37.9%) had wheeze with exercise, 55 (59.9%) had a dry cough not associated with a cold or flu and 13 (13.7%) reported more than 4 attacks of wheeze in the last year. This study suggests underdiagnosis and undertreatment of atopic illness in this age group. It also suggests decreasing exposure to passive smoking and early recognition and treatment will improve quality of life for many children.

Focally enhanced gastritis in children with Crohn's disease and ulcerative colitis.

OBJECTIVES: Focally enhanced gastritis (FEG) has been suggested as a specific diagnostic marker for patients with Crohn's disease. However, the utility of FEG for distinguishing Crohn's disease from ulcerative colitis is uncertain in adults, and the occurrence of this lesion in children has not been defined. The aim of this study was to evaluate the occurrence of FEG and other gastric histological abnormalities in children with inflammatory bowel disease (IBD) and to examine the utility of FEG in discriminating between ulcerative colitis and Crohn's disease. METHODS: This is a retrospective, case-controlled study of upper GI histopathological findings in children with IBD. Gastric histopathology was defined and graded according to the Updated Sydney System. RESULTS: FEG was present in 28 of 43 (65.1%) children with Crohn's disease and five of 24 (20.8%) children with ulcerative colitis, compared to three of 132 (2.3%) children without IBD or one of 39 (2.6%) children with Helicobacter pylori infection. There were no differences between those with and without FEG with regard to upper GI symptoms or previous anti-inflammatory drug ingestion (5-aminosalicylic acid compounds or steroids). All patients with H. pylori infection had chronic antral gastritis, but only one child with H. pylori had FEG. In addition, mild to moderate chronic gastritis was present in 15 of 43 (34.9%) children with Crohn's disease and in 12 of 24 (50%) patients with ulcerative colitis. CONCLUSIONS: The presence of FEG suggests underlying IBD. Although FEG is particularly common in children with Crohn's disease, it does not reliably differentiate between Crohn's disease and ulcerative colitis.

Experience with twenty-eight cases of systolic anterior motion after mitral valve reconstruction by the Carpentier technique.

Systolic anterior motion of the mitral valve with left ventricular outflow tract obstruction after Carpentier-type mitral reconstruction with ring annuloplasty has led some surgeons to abandon an otherwise successful repair or to avoid use of a rigid ring. To assess the long-term significance of such motion, we studied 439 patients undergoing Carpenter mitral reconstruction at our institution between March 1981 and June 1990. The hospital mortality rate was 4.8% (21/439) overall and 3.7% (9/243) for isolated mitral reconstruction. Systolic anterior motion was found in 6.4% (28/438) after the operation, and 2.3% (10/438) had a coexisting left ventricular outflow tract gradient (mean 53 mm Hg). Of the 28 patients with systolic anterior motion, 27 (96.4%) had leaflet prolapse, 17 (60.7%) had undergone more than a 3 cm resection of the posterior leaflet, and two (7.1%) had preexisting idiopathic hypertrophic subaortic stenosis. All patients were treated medically, 14 with negative inotropic agents. Follow-up echocardiograms at a mean of 32 months demonstrated the disappearance of systolic anterior motion in 13 of 28 patients (46.4%) and resolution of the outflow tract gradient in 10 of 10 (100%). At follow-up only one patient was in New York Heart Association class III or IV and required reoperation for rheumatic mitral insufficiency. These data demonstrate that systolic anterior motion after Carpentier mitral reconstruction with ring annuloplasty is not prevalent and should be managed medically in most cases. Associated left ventricular outflow tract obstruction resolves with medical treatment.

Clinical evaluation of high-frequency (ultrasonic) mechanical débridement in the surgical treatment of calcific aortic stenosis.

Repair of aortic valve stenosis due to calcific degeneration may lead to hemodynamic and clinical improvement without the problems inherent with prosthetic valves. We have evaluated the use of a device capable of débriding calcium, the Cavitron ultrasonic aspirator (CUSA), as an adjunct to mechanical débridement in the repair of calcific aortic stenosis. Ten patients (five women), ages 63 to 83 years, were studied by M-mode, two-dimensional, and Doppler echocardiography before and an average of 26 (range 3 to 124) days after this procedure. The degree of calcification of the valve cusps was clearly reduced. The maximal cusp excursion increased from 0.7 +/- 0.1 cm preoperatively to 1.5 +/- 0.4 cm postoperatively (p = 0.006). The peak aortic gradient fell from 80 +/- 36 mm Hg to 28 +/- 10 mm Hg (p = 0.0007). The mean aortic gradient fell from 53 +/- 20 mm Hg to 16 +/- 5 mm Hg (p less than 0.0001). Aortic valve area calculated by the continuity equation increased from 0.6 + 0.2 cm2 to 1.6 +/- 0.6 cm2 (p = 0.0009). No patient had more than mild aortic insufficiency preoperatively. Postoperatively, color Doppler flow mapping revealed severe aortic insufficiency in two patients. Seven patients had further echocardiographic evaluation 99 (range 33 to 196) days after the procedure. These studies revealed the development of severe aortic insufficiency in an additional four patients. Four patients with severe symptomatic aortic insufficiency eventually underwent aortic valve replacement. Pathology revealed scarring and retraction of the aortic cusps. Widening of the commissures was responsible for the severe aortic insufficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

A comparison of mitral valve reconstruction with mitral valve replacement: intermediate-term results.

The continued good results after mitral valve reconstruction prompted this retrospective study to compare operative and late results from our institutional experience since 1976 with 975 porcine mitral valve replacements (MVRs) (1976 to December 1987), 169 mechanical MVRs (1976 to December 1987), and 280 Carpentier-type mitral valve reconstructions (CVRs) (1980 to mid-1988). The operative mortality was 2.0% for isolated CVR, 6.6% for isolated mechanical MVR, and 8.5% for isolated porcine MVR. The overall operative mortality was 5.0% for CVR, 16.6% for mechanical MVR, and 10.6% for porcine MVR. The overall 5-year survival including hospital deaths was 76% for CVR, 72% for mechanical MVR, and 69% for porcine MVR. By multivariate analysis, the predictors of increased operative risk and of decreased survival were age, New York Heart Association functional class IV status, previous cardiac operation, and performance of concomitant cardiac surgical procedures. The type of valvular procedure was not predictive of operative risk or overall survival. The 5-year freedom from reoperation was 94.4% for nonrheumatic patients having CVR, 77.4% for rheumatic patients having CVR, 96.4% for mechanical MVR, and 96.6% for porcine MVR (p less than 0.05, rheumatic patients with CVR versus both MVR groups). The 5-year freedom from all valve-related morbidity and mortality was significantly better for valve reconstruction compared with both types of valve replacement. Thus, the operative risk and late survival obtained after mitral valve reconstruction were at least equivalent to those obtained after MVR. In addition, patients receiving mitral valve reconstruction had less valve-related combined morbidity than patients receiving valve replacement, thus making mitral valve reconstruction preferable in some patients with mitral insufficiency.

Current concepts of mitral valve reconstruction for mitral insufficiency.

In recent years, there has been a renewed interest in surgical reconstruction of the insufficient mitral valve because of reconfirmation of the limitations of existing prosthetic and bioprosthetic valves. A follow-up study, including late functional data, of 148 patients who underwent mitral valve reconstruction at our institution was combined with a review of the literature to assess the current status of mitral reconstruction. The results indicate that mitral reconstruction by Carpentier techniques is widely applicable, durable, and relatively free of complication. Freedom from late thromboembolic and anticoagulant complications is particularly notable. These factors could prove to justify earlier operative intervention in patients with mitral insufficiency before permanent myocardial damage evolves. As mitral valve reconstruction techniques become more familiar and widely used, mitral reconstruction may become the operative procedure of choice for mitral insufficiency, especially insufficiency due to degenerative disease.

Long-term results of mitral valve reconstruction with Carpentier techniques in 148 patients with mitral insufficiency.

There have been few relatively complete follow-up studies of long-term mitral valve function after Carpentier-type surgical reconstruction. Between January 1980 and May 1986, 148 patients underwent Carpentier reconstruction for mitral valve disease (43% degenerative and 30% rheumatic). Operative mortality was 5.4% overall (1.2% for isolated mitral reconstruction), and follow-up (mean, 26 months) was completed for all survivors. Five-year survival from late cardiac death was 90.0%, as was 5-year freedom from postreconstruction mitral valve replacement. Postreconstruction mitral replacement was needed in eight patients, in only five for failure of repair. Follow-up echocardiographic studies on 83.2% (104 of 125) of eligible patients showed 92.3% were free of significant (3+ or 4+) mitral regurgitation. Freedom from mitral valve replacement or recurrent severe (4+) insufficiency was 84.4% at 5 years overall, but was lower for the rheumatic type of mitral disease than for the degenerative type (71.6% vs. 88.3%). At 5 years, 95.2% of patients were free from thromboembolism without the necessity for long-term warfarin (Coumadin) therapy. At follow-up, 95.3% of survivors had improved to New York Heart Association Class I or II. The functional durability of mitral reconstruction and consistently high level of freedom from late endocarditis and thromboembolic and anticoagulant complications support the value of the Carpentier method of mitral reconstruction for mitral insufficiency, especially insufficiency due to degenerative disease.