Endoscopic treatment of superficial colorectal neoplasms. Retrospective analysis of a single center technique and results.

Endoscopic Submucosal Dissection (ESD) is a technique developed in Japan for "en bloc" resection of larger superficial neoplasms of the gastrointestinal tract as an alternative to the traditional Endoscopic Mucosal Resection (EMR), with removal of the lesion in multiple fragments ("piecemeal"). ESD offers a lower recurrence rate and allows a more accurate histopathological examination. This procedure is however considered technically difficult and therefore requires an adequate learning curve, it is time consuming with more discomfort for the patient, it has a higher complication rate, it is more expensive. To overcome these disadvantages, in the Western countries a hybrid technique called Circumferential Submucosal Incision - Endoscopic Mucosal Resection (CSI-EMR) has been developed and is especially employed for colonic lesions. This article analyzes retrospectively the results obtained in a single centre by a single operator in the treatment of 23 patients (12 men and 11 women, average age 65,6 years), all suffering from superficial, larger than ≥ 20 mm colorectal neoplasms: 9 were treated with ESD for rectal lesions and 14 were treated with CSI-EMR for colonic lesions. Findings show a technical success rate of 66,6% for ESD and 78,5% for CSI-EM, and a 0% recurrence rate during follow-up, 4,3% bleeding and 13% perforation complications. The histology of the removed lesions showed 13 (56,5%) low grade dysplasia adenomas, 8 (34,7%) high grade dysplasia adenomas, one grade 1 sigmoid colon adenocarcinoma infiltrating the submucosal layer without lymphovascular invasion, with free margins (R0), treated conservatively, and one grade 1 cecum adenocarcinoma, infiltrating the submucosal layer, with lymphovascular invasion and involved excision margin, treated surgically with no residual neoplastic disease in the surgical specimen. These data are in line with the most significant ones in literature, except for the higher complication rate, which the authors ascribe to the "learning curve" and the smaller number of treated patients.

The experience of caregiving for children with rare musculoskeletal conditions: a qualitative study in arthrogryposis multiplex congenita.

BACKGROUND: Arthrogryposis multiplex congenita (AMC) is a group of rare musculoskeletal conditions that is associated with complex healthcare needs and long-term follow up. The literature reports significant direct, indirect, and psychosocial costs for caregivers of children with neuromuscular conditions. Due to mobility limitations and frequent hospital visits, caring for a child with AMC is complex. Other challenges experienced by caregivers include financial strain, job changes, changes in interpersonal relationships and abandonment. This study was aimed at exploring the lived experience of caregivers of children with AMC. METHODS: The present study is part of a larger global mixed methods study. In the initial quantitative aspect of the study, caregivers (n = 158) of children and youths with AMC (aged 0-21 years) responded to a cost of care survey on an electronic platform. Of the 158 participants, 13 caregivers then further consented to participate in the qualitative aspect of the study in which a 60-min semi-structured, individual interview was conducted remotely. Open-ended questions were developed to gain a deeper understanding of the direct and indirect costs of care, their impact on the caregivers' lives and the quality of the care-giving experience. Interviews were transcribed, and a coding scheme was developed drawing from both the existing literature and the content of the interviews. A deductive and inductive thematic analysis was used to analyze the qualitative data using the NVivo® qualitative data analysis software. RESULTS AND CONCLUSION: Five themes describing the experiences of caregivers of children with AMC emerged from the analysis of the qualitative data: 1. Impact of the caregiving experience; 2. Cost of childcare; 3. Support system for care; 4. Managing and navigating care; 5. Supporting the child's growth and development. In addition to the results of the thematic analysis, specific recommendations shared by the caregivers included the need for support groups and provision of support to youths to prepare them for adolescence. These findings will inform resource allocation, policymaking, and support services for children with rare conditions, their caregivers and families.

Mice deficient in Six5 develop cataracts: implications for myotonic dystrophy.

Expansion of a CTG trinucleotide repeat in the 3' UTR of the gene DMPK at the DM1 locus on chromosome 19 causes myotonic dystrophy, a dominantly inherited disease characterized by skeletal muscle dystrophy and myotonia, cataracts and cardiac conduction defects. Targeted deletion of Dm15, the mouse orthologue of human DMPK, produced mice with a mild myopathy and cardiac conduction abnormalities, but without other features of myotonic dystrophy, such as myotonia and cataracts. We, and others, have demonstrated that repeat expansion decreases expression of the adjacent gene SIX5 (refs 7,8), which encodes a homeodomain transcription factor. To determine whether SIX5 deficiency contributes to the myotonic dystrophy phenotype, we disrupted mouse Six5 by replacing the first exon with a beta-galactosidase reporter. Six5-mutant mice showed reporter expression in multiple tissues, including the developing lens. Homozygous mutant mice had no apparent abnormalities of skeletal muscle function, but developed lenticular opacities at a higher rate than controls. Our results suggest that SIX5 deficiency contributes to the cataract phenotype in myotonic dystrophy, and that myotonic dystrophy represents a multigenic disorder.

Conversion of Xenopus ectoderm into neurons by NeuroD, a basic helix-loop-helix protein.

Basic helix-loop-helix (bHLH) proteins are instrumental in determining cell type during development. A bHLH protein, termed NeuroD, for neurogenic differentiation, has now been identified as a differentiation factor for neurogenesis because (i) it is expressed transiently in a subset of neurons in the central and peripheral nervous systems at the time of their terminal differentiation into mature neurons and (ii) ectopic expression of neuroD in Xenopus embryos causes premature differentiation of neuronal precursors. Furthermore, neuroD can convert presumptive epidermal cells into neurons and also act as a neuronal determination gene. However, unlike another previously identified proneural gene (XASH-3), neuroD seems competent to bypass the normal inhibitory influences that usually prevent neurogenesis in ventral and lateral ectoderm and is capable of converting most of the embryonic ectoderm into neurons. The data suggest that neuroD may participate in the terminal differentiation step during vertebrate neuronal development.

Diagnostic value of endoscopic markers for celiac disease in adults: a multicentre prospective Italian study.

AIM: Some endoscopic features of duodenal mucosa are marker of mucosal injury, the most common cause being celiac disease (CD). The aim of this study was to prospectively assess the diagnostic value of the endoscopic markers for the diagnosis of CD in the adult population undergoing routine upper endoscopy. METHODS: This was a prospective multicenter study conducted at 37 Italian endoscopic centers. A total of 509 consecutive patients submitted to routine upper endoscopy who presented one or more of following endoscopic markers were included: 1) mucosal mosaic pattern in the bulb and/or descending duodenum (DD); 2) nodularity in the bulb and/or DD; 3) scalloping of Kerkring's folds; 4) reduction in the number or absence of folds in the DD. 4 biopsies samples were taken from descending duodenum. In patients with histological findings consistent with CD, according to Oberhuber classification, sierologic test (EMA, tTGA) were performed for confirm the diagnosis. RESULTS: At endoscopy, 249 patients showed an isolated marker; 260 subjects showed a coexistence of more than one marker; 369 patients (72.5%) presented mucosal lesions at histological examination and in 347 of these patients the diagnosis of CD was confirmed by serologic markers (94.0%). For 10 patients the diagnosis remained uncertain because of negative sierology and exclusion of other other cause of mucosal lesions. The diagnosis of CD was made in 61.3% patients who showed the mosaic pattern, in 65.7% of patients with nodular mucosa, in 64.4% of patients with scalloping of folds, in 40.2% of patients with reduction of folds, and in 61.5% of patients with loss of folds and in 83.6% of patients who showed the coexistence of more than one marker. The endoscopic markers overall had a PPV of 68% for the diagnosis of CD; the markers that singularly have demonstrated a higher correlation with CD are: mosaic mucosa of DD (PPV 65.0%), nodular mucosa of the bulb and DD (PPV 75.5%), and scalloping of folds (PPV 64.4%). CONCLUSION: The study confirms the important role of endoscopy in the diagnostic process of CD not only for the bioptic sampling in patients with clinical suspicion of CD, but especially for the opportunity to evaluate alterations of the duodenal mucosa suggestive of CD in the general population and, consequently, to identify those patients who should undergo a duodenal biopsy.

Polymorphism in an androgen-regulated mouse gene is the result of the insertion of a B1 repetitive element into the transcription unit.

The single-copy RP2 gene in mice produces three major mRNAs, the abundances of which are significantly increased in the kidneys by the administration of testosterone. S1 nuclease analysis of the kidney mRNAs indicated that they differ in the lengths of their 3' untranslated regions as a result of the use of different polyadenylation sites. When the mRNAs from different inbred mouse strains were examined by Northern blot analysis, it was observed that the largest mRNA varies in size, whereas the sizes of the other mRNAs remain the same. In DBA/LiHa and DBA/2J mice, the largest mRNA is approximately 2,150 nucleotides long, whereas the corresponding mRNA in C57BL/6J and BALB/cJ mice is only 1,950 nucleotides in length. All of these strains also have RP2 mRNAs that are 1,450 and 1,350 nucleotides long. By S1 nuclease mapping and comparison of the sequence of cDNA clones representing these mRNAs in DBA/LiHa and C57BL/6J mice, we determined that this size difference or polymorphism observed in the largest mRNA is the result of the insertion of a member of the B1 family of repeats into the 3' untranslated region of the RP2 gene in DBA mice. This particular B1 repeat is transcribed by RNA polymerase III in vitro, and its transcriptional orientation is opposite to that of the RP2 transcript. The polymorphism described here is evidence for the mobility of B1 repetitive elements within the genome.

NeuroD2 and neuroD3: distinct expression patterns and transcriptional activation potentials within the neuroD gene family.

We have identified two new genes, neuroD2 and neuroD3, on the basis of their similarity to the neurogenic basic-helix-loop-helix (bHLH) gene neuroD. The predicted amino acid sequence of neuroD2 shows a high degree of homology to neuroD and MATH-2/NEX-1 in the bHLH region, whereas neuroD3 is a more distantly related family member. neuroD3 is expressed transiently during embryonic development, with the highest levels of expression between days 10 and 12. neuroD2 is initially expressed at embryonic day 11, with persistent expression in the adult nervous system. In situ and Northern (RNA) analyses demonstrate that different regions of the adult nervous system have different relative amounts of neuroD and neuroD2 RNA. Similar to neuroD, expression of neuroD2 in developing Xenopus laevis embryos results in ectopic neurogenesis, indicating that neuroD2 mediates neuronal differentiation. Transfection of vectors expressing neuroD and neuroD2 into P19 cells shows that both can activate expression through simple E-box-driven reporter constructs and can activate a reporter driven by the neuroD2 promoter region, but the GAP-43 promoter is preferentially activated by neuroD2. The noncongruent expression pattern and target gene specificity of these highly related neurogenic bHLH proteins make them candidates for conferring specific aspects of the neuronal phenotype.

Inhibition of Tcf3 binding by I-mfa domain proteins.

We have determined that I-mfa, an inhibitor of several basic helix-loop-helix (bHLH) proteins, and XIC, a Xenopus ortholog of human I-mf domain-containing protein that shares a highly conserved cysteine-rich C-terminal domain with I-mfa, inhibit the activity and DNA binding of the HMG box transcription factor XTcf3. Ectopic expression of I-mfa or XIC in early Xenopus embryos inhibited dorsal axis specification, the expression of the Tcf3/beta-catenin-regulated genes siamois and Xnr3, and the ability of beta-catenin to activate reporter constructs driven by Lef/Tcf binding sites. I-mfa domain proteins can regulate both the Wnt signaling pathway and a subset of bHLH proteins, possibly coordinating the activities of these two critical developmental pathways.

Characterization of oligosaccharide chains on mouse mammary tumor virus envelope proteins and the implications for the mechanism of their glucocorticoid regulated processing.

Glucocorticoid hormone is required for complete posttranslational processing of the glycosylated mouse mammary tumor virus envelope precursor, Pr74env in the murine T-lymphosarcoma cell line, W7MG1. Metabolic labeling studies with [35S]methionine, [3H]galactose, and [3H]mannose, combined with enzymatic digestion analyses with a variety of endoglycosidases, demonstrated that both proteolytic processing and N-linked oligosaccharide maturation depended, either directly or indirectly, on glucocorticoid action. Pr74 is found in both control and hormone-treated cells. In both cases Pr74 molecules carry high mannose and/or hybrid, but not complex, oligosaccharide chains with very little or no sialic acid. When cells are grown with glucocorticoid, Pr74 is converted to gp52 and gp33 with greatly increased efficiency, and these mature glycoproteins carry complex oligosaccharides containing sialic acid. No O-linked carbohydrate was detected on any of these species. According to this evidence, the glucocorticoid-regulated step in this pathway must occur at or before the final mannose trimming step in the Golgi that is required for formation of complex carbohydrate chains.

The PANDAS subgroup: recognition and treatment.

A subgroup of patients with childhood-onset obsessive-compulsive disorder (OCD) has been identified who share a common clinical course characterized by dramatic symptom exacerbations following Group A beta-hemolytic streptococcal (GABHS) infections. The term PANDAS has been applied to the subgroup, to indicate the postulated etiology of their symptoms: Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections. Five clinical characteristics define the PANDAS subgroup: presence of OCD and/or tic disorder, prepubertal symptom onset, sudden onset or abrupt exacerbations (sawtooth course), association with neurological abnormalities (presence of adventitious movements or motoric hyperactivity during exacerbations), and temporal association between symptom exacerbations and GABHS infections. Post-streptococcal symptom exacerbations are typically quite dramatic, with patients reporting that their symptoms "...came on overnight" or "...appeared all of a sudden a few days after I had a sore throat." The post-streptococcal inflammatory nature of the neuropsychiatric symptoms provides novel opportunities for treatment and prevention, including immunomodulatory therapies such as therapeutic plasma exchange (TPE) and intravenous immunoglobulin (IVIG). A recently completed placebo-controlled trial revealed that both IVIG and TPE were effective in reducing neuropsychiatric symptom severity (40% to 55% reductions, respectively) for a group of severely ill children with OCD and/or tic disorders. Further research is required to determine why the treatments are helpful, as well as to ascertain whether or not antibiotic prophylaxis can help prevent post-streptococcal symptom exacerbations.

A comparison of the effectiveness of sensory integrative therapy and perceptual-motor training in treating children with learning disabilities.

This study compared the effect of sensory integration therapy (SI), perceptual-motor training (PM) and no treatment (NT) on the performance of 103 children with learning disabilities and sensory integrative dysfunction, aged 58 to 107 months, who were randomly assigned to one of the two treatment groups or to no treatment. After receiving a total of 72 1-hour sessions of therapy for 3 hours per week, PM-treated subjects showed significant gains over the other two groups, primarily in gross motor performance. SI-treated subjects showed an advantage in motor planning. There were no accompanying group differences in visual perception, handwriting readiness, copying ability, cognitive, academic, language and attentional skills or in self-concept. These findings demonstrate motor gains resulting from motor treatments without carry-over to functional skills and abilities more directly associated with school performance.

The Kentucky Homeplace Project: family health care advisers in underserved rural communities.

The Kentucky Homeplace Project (KHP) is a state-legislated program designed to address well-documented deficits in the health status of and health resources available to many of Kentucky's rural residents. Since its inception in 1994, the KHP has served approximately 80,000 clients, primarily through home visits by trained, locally residing paraprofessionals known as family health care advisers. These family health care advisers employ culturally appropriate strategies to meet immediate needs as well as to foster long-term client empowerment and the adoption of health prevention strategies. This descriptive examination of KHP provides information regarding (a) the advantages of the program, with specific attention to its orientation toward provision of culturally appropriate health services; (b) the disadvantages of KHP, including competing budgetary priorities and its vulnerability to local economic and political trends; and (c) the potential application of similar programs for other rural, difficult-to-reach populations.

Experience with silastic gel sheeting in pediatric scarring.

Silicone gel sheeting was applied to five hypertrophic scars on five pediatric outpatients at an acute care pediatric hospital. After silicone gel application, three of the five scars showed initial positive results including reduction in the scar size, reduction in the scar thickness, softening of the scar, a decrease in vascularity of the scar, and more uniform pigmentation. Many negative results including rash, skin breakdown, cessation of scar responsiveness, problems with the gel sheet application, and poor durability were documented. Preliminary results indicate that topical silicone gel application is not a viable treatment option for the control of hypertrophic scarring with a pediatric population.

Periodontal maintenance therapy.

The rationale for therapy is to establish an environment conducive to maintenance by the patient and the dental team. Hence, maintenance therapy becomes the "steady state" for the patient, with all treatment endeavors channeled into achieving a healthy periodontal status that can be effectively maintained. In this light, maintenance therapy becomes the most critical aspect of dental treatment. Recognition of of its place in the therapeutic spectrum is long overdue, and adequate time should be included for this phase of treatment in the dental school curriculum.

Therapists' consistency in following their treatment plans for sensory integrative and perceptual-motor therapy.

OBJECTIVES: Treatment integrity is concerned with whether treatment conditions as provided are consistent with specifications for the treatment. Therapists' consistency in following their treatment plans that called for the use of sensory integrative and perceptual-motor techniques was evaluated. METHOD: Three occupational therapists were rated on their consistency in 46 sessions each of sensory integrative and perceptual-motor therapy. Ratings were made both earlier (1 month) and later (4 months) in treatment. Consistency was rated with a five-point scale for 10 categories of the treatment plans. RESULTS: Overall consistency did not differ significantly (86% for sensory integrative techniques and 79% for perceptual-motor techniques). Perceptual-motor activities showed less consistency early in treatment but approached the level for sensory integrative techniques by later treatment sessions. Consistency differed significantly among therapists for sensory integrative activities that addressed tactile defensiveness and perceptual-motor activities associated with fine coordination and dexterity. CONCLUSION: Despite the less structured, more child-centered nature of sensory integrative techniques, consistency in using these techniques was as high as that found for more scripted, program-centered, perceptual-motor techniques. Therapists reported that gaining the interest and attention of some children with the more structured perceptual-motor activities was more difficult early in treatment but could be achieved with time. Differences in consistency among therapists require verification with a larger sample.

Evidence of nonverbal learning disability among learning disabled boys with sensory integrative dysfunction.

The presumed sensorimotor basis of the nonverbal learning disability syndrome was investigated among 90 learning disabled boys (M age = 6 yr., 8 mo., SD = 12.2 mo.) with sensory integrative dysfunction. The majority of the boys were Caucasian, lower to middle socioeconomic status, and from urban, English-speaking families. 14% (n = 13) of the boys satisfied core discrepancy criteria for nonverbal learning disability, including both a significantly higher Wechsler Verbal than Performance IQ and a higher standard score in Reading than Arithmetic on the Wide Range Achievement Test. Compared with a control group of 19 boys from the same sample who had no significant discrepancies, boys with nonverbal learning disability had significantly greater weaknesses in space visualization and visuomotor coordination. As predicted, rote verbal memory and syntactical strengths were also exhibited by boys with nonverbal learning disability, but the two groups did not differ significantly.

Actual vs. best practices for young children with cerebral palsy: a survey of paediatric occupational therapists and physical therapists in Quebec, Canada.

RATIONALE: Cerebral palsy (CP) constitutes a substantial portion of paediatric rehabilitation, yet little is known regarding actual occupational therapy (OT) and physical therapy (PT) practices. This study describes OT and PT practices for young children with CP in Quebec, Canada. METHODS: This was a cross-sectional survey. All eligible, consenting paediatric occupational therapists (OTs) and physical therapists (PTs) were interviewed using a structured telephone interview based on vignettes of two typical children with CP at two age points--18 months and 4 years. Reported practices were grouped according to the International Classification of Functioning, Disability and Health (ICF). RESULTS: 91.9% of PTs (n=62; 83.8% participation rate) and 67.1% of OTs (n=85; 91.4% participation rate) reported using at least one standardized paediatric assessment. OT and PT interventions focused primarily on impairments and primary function (such as gait function and activities of daily living). Both professions gave little attention to interventions related to play and recreation/leisure. Clinicians reported the need for more training and education specific to CP and to the use of research findings in clinical practice. CONCLUSION: Wide variations and gaps were identified in clinicians' responses suggesting the need for a basic standard of OT and PT management as well as strategies to encourage knowledge dissemination regarding current best practice.