Disease burden of osteoporosis and other non-communicable diseases in Lebanon.

Osteoporosis is more common than most feared non-communicable diseases in the Middle East. This justifies the need to place osteoporosis as a health priority in the region. INTRODUCTION: Osteoporosis is a common disease associated with severe debilitating consequences. The objective of this study is To evaluate and compare disease burden from osteoporosis and other non-communicable diseases (NCDs) in Lebanon. METHODS: We assessed the prevalence of osteoporosis and other NCDs, such as obesity, diabetes, hypertension, dyslipidemia, and cardiovascular diseases, based on a published population-based study of Lebanese ≥ 65 years. We compared incidence rates of hip fractures and major osteoporotic fractures (MOF) (spine, hip, humerus, and forearm) to the five commonest cancers in women ≥ 50 years. Rates were based on the national hip fracture and cancer registry data, provided by the Lebanese Ministry of Public Health. MOF incidence rates were derived from national hip fracture incidence rates and MOF/hip fractures incidence rate ratios from the literature. RESULTS: Over 70% of elderly Lebanese had osteoporosis defined by densitometric criteria or prevalent morphometric vertebral fractures. This by far exceeded the prevalence of other NCDs, such as hypertension (53%), diabetes (21%), dyslipidemia (31%), and cardiovascular diseases (30%). Morphometric vertebral fractures (grades 2 and 3) were present in 19% of women and 12% of men. The incidence rates for MOF were 1.6 times greater than those for breast cancer, and 7.4-9.9 folds higher than those for the next commonest cancers of the lungs, colon, and ovaries. Hip fracture incidence rates were lower than those of breast cancer but were 2.1-2.8 folds higher than those of the above-mentioned cancers. CONCLUSION: This first of its kind study in the Middle East demonstrates that osteoporosis is a common disease, more common than most feared NCDs. Our findings are comparable to those in western populations and justify placing osteoporosis on the top of NCDs' priority list in our country and possibly the region.

Investigation of the vitamin D receptor gene (VDR) and its interaction with protein tyrosine phosphatase, non-receptor type 2 gene (PTPN2) on risk of islet autoimmunity and type 1 diabetes: the Diabetes Autoimmunity Study in the Young (DAISY).

The present study investigated the association between variants in the vitamin D receptor gene (VDR) and protein tyrosine phosphatase, non-receptor type 2 gene (PTPN2), as well as an interaction between VDR and PTPN2 and the risk of islet autoimmunity (IA) and progression to type 1 diabetes (T1D). The Diabetes Autoimmunity Study in the Young (DAISY) has followed children at increased risk of T1D since 1993. Of the 1692 DAISY children genotyped for VDR rs1544410, VDR rs2228570, VDR rs11568820, PTPN2 rs1893217, and PTPN2 rs478582, 111 developed IA, defined as positivity for GAD, insulin or IA-2 autoantibodies on 2 or more consecutive visits, and 38 IA positive children progressed to T1D. Proportional hazards regression analyses were conducted. There was no association between IA development and any of the gene variants, nor was there evidence of a VDR*PTPN2 interaction. Progression to T1D in IA positive children was associated with the VDR rs2228570 GG genotype (HR: 0.49, 95% CI: 0.26-0.92) and there was an interaction between VDR rs1544410 and PTPN2 rs1893217 (p(interaction)=0.02). In children with the PTPN2 rs1893217 AA genotype, the VDR rs1544410 AA/AG genotype was associated with a decreased risk of T1D (HR: 0.24, 95% CI: 0.11-0.53, p=0.0004), while in children with the PTPN2 rs1893217 GG/GA genotype, the VDR rs1544410 AA/AG genotype was not associated with T1D (HR: 1.32, 95% CI: 0.43-4.06, p=0.62). These findings should be replicated in larger cohorts for confirmation. The interaction between VDR and PTPN2 polymorphisms in the risk of progression to T1D offers insight concerning the role of vitamin D in the etiology of T1D.

A cooperative interaction between LPHN3 and 11q doubles the risk for ADHD.

In previous studies of a genetic isolate, we identified significant linkage of attention deficit hyperactivity disorder (ADHD) to 4q, 5q, 8q, 11q and 17p. The existence of unique large size families linked to multiple regions, and the fact that these families came from an isolated population, we hypothesized that two-locus interaction contributions to ADHD were plausible. Several analytical models converged to show significant interaction between 4q and 11q (P<1 × 10(-8)) and 11q and 17p (P<1 × 10(-6)). As we have identified that common variants of the LPHN3 gene were responsible for the 4q linkage signal, we focused on 4q-11q interaction to determine that single-nucleotide polymorphisms (SNPs) harbored in the LPHN3 gene interact with SNPs spanning the 11q region that contains DRD2 and NCAM1 genes, to double the risk of developing ADHD. This interaction not only explains genetic effects much better than taking each of these loci effects by separated but also differences in brain metabolism as depicted by proton magnetic resonance spectroscopy data and pharmacogenetic response to stimulant medication. These findings not only add information about how high order genetic interactions might be implicated in conferring susceptibility to develop ADHD but also show that future studies of the effects of genetic interactions on ADHD clinical information will help to shape predictive models of individual outcome.

Nanospace engineering of KOH activated carbon.

This paper demonstrates that nanospace engineering of KOH activated carbon is possible by controlling the degree of carbon consumption and metallic potassium intercalation into the carbon lattice during the activation process. High specific surface areas, porosities, sub-nanometer (<1 nm) and supra-nanometer (1-5 nm) pore volumes are quantitatively controlled by a combination of KOH concentration and activation temperature. The process typically leads to a bimodal pore size distribution, with a large, approximately constant number of sub-nanometer pores and a variable number of supra-nanometer pores. We show how to control the number of supra-nanometer pores in a manner not achieved previously by chemical activation. The chemical mechanism underlying this control is studied by following the evolution of elemental composition, specific surface area, porosity, and pore size distribution during KOH activation and preceding H(3)PO(4) activation. The oxygen, nitrogen, and hydrogen contents decrease during successive activation steps, creating a nanoporous carbon network with a porosity and surface area controllable for various applications, including gas storage. The formation of tunable sub-nanometer and supra-nanometer pores is validated by sub-critical nitrogen adsorption. Surface functional groups of KOH activated carbon are studied by microscopic infrared spectroscopy.

Genome-wide copy number variation analysis in attention-deficit/hyperactivity disorder: association with neuropeptide Y gene dosage in an extended pedigree.

Attention-deficit/hyperactivity disorder (ADHD) is a common, highly heritable neurodevelopmental syndrome characterized by hyperactivity, inattention and increased impulsivity. To detect micro-deletions and micro-duplications that may have a role in the pathogenesis of ADHD, we carried out a genome-wide screen for copy number variations (CNVs) in a cohort of 99 children and adolescents with severe ADHD. Using high-resolution array comparative genomic hybridization (aCGH), a total of 17 potentially syndrome-associated CNVs were identified. The aberrations comprise 4 deletions and 13 duplications with approximate sizes ranging from 110 kb to 3 Mb. Two CNVs occurred de novo and nine were inherited from a parent with ADHD, whereas five are transmitted by an unaffected parent. Candidates include genes expressing acetylcholine-metabolizing butyrylcholinesterase (BCHE), contained in a de novo chromosome 3q26.1 deletion, and a brain-specific pleckstrin homology domain-containing protein (PLEKHB1), with an established function in primary sensory neurons, in two siblings carrying a 11q13.4 duplication inherited from their affected mother. Other genes potentially influencing ADHD-related psychopathology and involved in aberrations inherited from affected parents are the genes for the mitochondrial NADH dehydrogenase 1 α subcomplex assembly factor 2 (NDUFAF2), the brain-specific phosphodiesterase 4D isoform 6 (PDE4D6) and the neuronal glucose transporter 3 (SLC2A3). The gene encoding neuropeptide Y (NPY) was included in a ∼3 Mb duplication on chromosome 7p15.2-15.3, and investigation of additional family members showed a nominally significant association of this 7p15 duplication with increased NPY plasma concentrations (empirical family-based association test, P=0.023). Lower activation of the left ventral striatum and left posterior insula during anticipation of large rewards or losses elicited by functional magnetic resonance imaging links gene dose-dependent increases in NPY to reward and emotion processing in duplication carriers. These findings implicate CNVs of behaviour-related genes in the pathogenesis of ADHD and are consistent with the notion that both frequent and rare variants influence the development of this common multifactorial syndrome.

A common variant of the latrophilin 3 gene, LPHN3, confers susceptibility to ADHD and predicts effectiveness of stimulant medication.

Attention-Deficit/Hyperactivity Disorder (ADHD) has a very high heritability (0.8), suggesting that about 80% of phenotypic variance is due to genetic factors. We used the integration of statistical and functional approaches to discover a novel gene that contributes to ADHD. For our statistical approach, we started with a linkage study based on large multigenerational families in a population isolate, followed by fine mapping of targeted regions using a family-based design. Family- and population-based association studies in five samples from disparate regions of the world were used for replication. Brain imaging studies were performed to evaluate gene function. The linkage study discovered a genome region harbored in the Latrophilin 3 gene (LPHN3). In the world-wide samples (total n=6360, with 2627 ADHD cases and 2531 controls) statistical association of LPHN3 and ADHD was confirmed. Functional studies revealed that LPHN3 variants are expressed in key brain regions related to attention and activity, affect metabolism in neural circuits implicated in ADHD, and are associated with response to stimulant medication. Linkage and replicated association of ADHD with a novel non-candidate gene (LPHN3) provide new insights into the genetics, neurobiology, and treatment of ADHD.

Coeliac disease-associated risk variants in TNFAIP3 and REL implicate altered NF-kappaB signalling.

OBJECTIVE: Our previous coeliac disease genome-wide association study (GWAS) implicated risk variants in the human leucocyte antigen (HLA) region and eight novel risk regions. To identify more coeliac disease loci, we selected 458 single nucleotide polymorphisms (SNPs) that showed more modest association in the GWAS for genotyping and analysis in four independent cohorts. DESIGN: 458 SNPs were assayed in 1682 cases and 3258 controls from three populations (UK, Irish and Dutch). We combined the results with the original GWAS cohort (767 UK cases and 1422 controls); six SNPs showed association with p<1 x 10(-04) and were then genotyped in an independent Italian coeliac cohort (538 cases and 593 controls). RESULTS: We identified two novel coeliac disease risk regions: 6q23.3 (OLIG3-TNFAIP3) and 2p16.1 (REL), both of which reached genome-wide significance in the combined analysis of all 2987 cases and 5273 controls (rs2327832 p = 1.3 x 10(-08), and rs842647 p = 5.2 x 10(-07)). We investigated the expression of these genes in the RNA isolated from biopsies and from whole blood RNA. We did not observe any changes in gene expression, nor in the correlation of genotype with gene expression. CONCLUSIONS: Both TNFAIP3 (A20, at the protein level) and REL are key mediators in the nuclear factor kappa B (NF-kappaB) inflammatory signalling pathway. For the first time, a role for primary heritable variation in this important biological pathway predisposing to coeliac disease has been identified. Currently, the HLA risk factors and the 10 established non-HLA risk factors explain approximately 40% of the heritability of coeliac disease.

Six new coeliac disease loci replicated in an Italian population confirm association with coeliac disease.

BACKGROUND AND AIMS: The first genome wide association study on coeliac disease (CD) and its follow-up have identified eight new loci that contribute significantly towards CD risk. Seven of these loci contain genes controlling adaptive immune responses, including IL2/IL21 (4q27), RGS1 (1q31), IL18RAP (2q11-2q12), CCR3 (3p21), IL12A (3q25-3q26), TAGAP (6q25) and SH2B3 (12q24). METHODS: We selected the nine most associated single nucleotide polymorphisms to tag the eight new loci in an Italian cohort comprising 538 CD patients and 593 healthy controls. RESULTS: Common variation in IL2/IL21, RGS1, IL12A/SCHIP and SH2B3 was associated with susceptibility to CD in our Italian cohort. The LPP and TAGAP regions also showed moderate association, whereas there was no association with CCR3 and IL18RAP. CONCLUSION: This is the first replication study of six of the eight new CD loci; it is also the first CD association study in a southern European cohort. Our results may imply there is a genuine population difference across Europe regarding the loci contributing to CD.

Genome-wide linkage analysis of ADHD using high-density SNP arrays: novel loci at 5q13.1 and 14q12.

Previous genome-wide linkage studies applied the affected sib-pair design; one investigated extended pedigrees of a genetic isolate. Here, results of a genome-wide high-density linkage scan of attention-deficit/hyperactivity disorder (ADHD) using an array-based genotyping of approximately 50 K single nucleotide polymorphism (SNPs) markers are presented. We investigated eight extended pedigrees of German origin that were non-related, not part of a genetic isolate and ascertained on the basis of clinical referral. Two parametric analyses maximizing LOD scores (MOD) and a non-parametric analysis for both a broad and a narrow phenotype approach were conducted. Novel linkage loci across all families were detected at 2q35, 5q13.1, 6q22-23 and 14q12, within individual families at 18q11.2-12.3. Further linkage regions at 7q21.11, 9q22 and 16q24.1 in all families, and at 1q25.1, 1q25.3, 9q31.1-33.1, 9q33, 12p13.33, 15q11.2-13.3 and 16p12.3-12.2 in individual families replicate previous findings. High-resolution linkage mapping points to several novel candidate genes characterized by dense expression in the brain and potential impact on disorder-relevant synaptic transmission. Our study provides further evidence for common gene effects throughout different populations despite the complex multifactorial etiology of ADHD.

Intraperitoneal chemotherapy with taxanes for ovarian cancer with peritoneal dissemination.

Paclitaxel and docetaxel are currently the two clinically available taxanes. The combination of a taxane and a platinum compound has become the systemic chemotherapy of choice for primary ovarian cancer. Despite the high activity of these drugs in systemic chemotherapy, the majority of patients with advanced ovarian cancer will develop recurrent disease and ultimately decease of this disease. Therefore, more effective systemic chemotherapy regimens or alternative treatment modalities are warranted. Intraperitoneal chemotherapy is such an alternative treatment option. Pharmacokinetic studies on intraperitoneal administration of paclitaxel and docetaxel demonstrated very high locoregional drug concentrations and exposure. Their activity and response seem to be dose-dependent and hence higher efficacy with limited systemic toxicity is to be expected. Intraperitoneal chemotherapy may be combined intraoperatively with hyperthermia, which enhances tissue penetration and cytotoxic activity of many drugs. The data concerning thermal enhancement of taxanes are inconsistent, but at the high locoregional concentrations provided by intraperitoneal drug administration such a thermal enhancement seems to exist. Clinical studies have clearly demonstrated the feasibility and efficacy of intraperitoneal instillation chemotherapy with taxanes in patients with ovarian cancer. Preliminary results of a phase III study demonstrated improved outcome with the addition of intraperitoneal instillation chemotherapy to systemic chemotherapy after optimal primary cytoreductive surgery. Intraoperative hyperthermic intraperitoneal chemotherapy with docetaxel has been performed in a single study, in which promising results were observed. Further clinical investigations with an adequate follow-up period are needed to confirm the promising initial results and to determine the exact efficacy of intraperitoneal chemotherapy with these drugs.

Correspondence regarding Ballana et al., "Mitochondrial 12S rRNA gene mutations affect RNA secondary structure and lead to variable penetrance in hearing impairment".

Ballana et al. [E. Ballana, E. Morales, R. Rabionet, B. Montserrat, M. Ventayol, O. Bravo, P. Gasparini, X. Estivill, Mitochondrial 12S rRNA gene mutations affect RNA secondary structure and lead to variable penetrance in hearing impairment, Biochem. Biophys. Res. Commun. 341 (2006) 950-957] detected a T1291C mutation segregating in a Cuban pedigree with hearing impairment. They interpreted it as probably pathogenic, based on family history, RNA conformation prediction and its absence in a control group of 95 Spanish subjects. We screened a sample of 203 deaf subjects and 300 hearing controls (110 "European-Brazilians" and 190 "African-Brazilians") for the mitochondrial mutations A1555G and T1291C. Five deaf subjects had the T1291C substitution, three isolated cases and two familial cases. In the latter, deafness was paternally inherited or segregated with the A1555G mutation. This doesn't support the hypothesis of T1291C mutation being pathogenic. Two "African-Brazilian" controls also had the T1291C substitution. Six of the seven T1291C-carriers (five deaf and two controls) had mitochondrial DNA of African origin, belonging to macrohaplogroup L1/L2. Therefore, these data point to T1291C substitution as most probably an African non-pathogenic polymorphism.

Treatment of advanced malignant eccrine poroma with locoregional chemotherapy.

Malignant eccrine poroma is a rare disease with approximately 200 cases reported in the literature. Regional cutaneous and systemic metastases are rarely observed and their management has been generally unsuccessful. We report on a case in which topical 5-fluorouracil application and intra-arterial chemotherapy with docetaxel resulted in a histologically confirmed complete response of multiple regional skin metastases for more than 2 years. Despite intravenous administration of docetaxel, slow progression of systemic disease was observed.

Primary psoas abscess. Report of three cases.

BACKGROUND: Primary psoas abscesses are a rare clinical entity with subtle and non specific symptoms, most commonly seen in patients predisposed to infections. Early diagnosis and appropriate management are therefore challenging aspects for physicians. PATIENTS AND METHODS: We present three patients with primary pyogenic psoas abscess, treated at the Heraklion University Hospital, during a 5-year period. The two male and one female patient, aged 36-51 years were admitted with fever, abdominal pain and a palpable tender mass. RESULTS: The classical sign of limping was absent in all cases. Positive psoas symptoms were detected in only two patients. CT scan accurately confirmed the diagnosis in all cases. The patients were successfully treated with antibiotics and prolonged surgical drainage. Staphylococcus aureus was the causative microorganism in the first two and Bacteroides fragilis in the third patient. This is the first reported case resulting from this specific bacteria. None of our patients had any predisposing risk factor. CONCLUSIONS: A high index of suspicion is mandatory to enable early recognition of this rare clinical disease. CT scan is the standard diagnostic tool to confirm diagnosis. Prolonged drainage and appropriate antibiotics are essential for the successful treatment of primary psoas abscesses.

A dose-finding study of irinotecan (CPT-11) plus a four-day continuous 5-fluorouracil infusion in advanced colorectal cancer.

OBJECTIVE: Irinotecan (CPT-11) has shown considerable activity in colorectal cancer, and its combination with 5-fluorouracil (5-FU) represents an attractive approach. A phase I study was conducted to determine the maximum tolerated dose (MTD) and the dose-limiting toxicities (DLTs) of CPT-11 in combination with a continuous infusion of 5-FU for 4 days. METHODS: Forty-two patients with histologically confirmed metastatic colorectal cancer who had not received prior treatment for advanced disease were enrolled. The patients' median age was 64 years; 26 (62%) patients were men, and the performance status (WHO) was 0 in 26 (62%) patients, 1 in 15 (36%) and 2 in 1 (2%). Twenty-two (52%) patients had 2 or more metastatic sites. CPT-11 (starting dose 200 mg/m(2)) was administered as a 30-min intravenous infusion with increments of 50 mg/m(2) on day 4. 5-FU (starting dose 400 mg/m(2)) was administered as a 4-day continuous intravenous infusion with increments of 50 mg/m(2) on days 1-4. Treatment was repeated every 4 weeks. RESULTS: The MTD of the combination was found to be 600 mg/m(2) for 5-FU and 350 mg/m(2) for CPT-11. Neutropenia, febrile neutropenia and delayed diarrhea were the DLTs. Grade 3/4 neutropenia was observed in 22 (13%) out of 169 administered treatment cycles, febrile neutropenia in 7 (4%) and grade 3/4 diarrhea in 20 (12%). Other toxicities were mild. Among 36 patients evaluable for response, partial response was achieved in 8 (22%), stable disease in 12 (33%) and progressive disease in 16 (44%) patients. Responses were mostly seen at the higher dose levels. CONCLUSIONS: The combination of a 4-day continuous infusion of 5-FU followed by CPT-11 represents an active and well-tolerated regimen for patients with colorectal cancer. This regimen merits further evaluation in phase II studies.

Peritoneal expansion by artificially produced ascites during perfusion chemotherapy.

HYPOTHESIS: In cases of peritoneal carcinomatosis, continuous hyperthermic peritoneal perfusion chemotherapy (CHPPC) accomplishes homogeneous distribution of the drug and heat to the entire peritoneal cavity and exposure of the visceral and parietal surfaces to the perfusate. A new closed technique for expansion that produces artificial ascites is safer for medical personnel because of less heat and drug loss and more efficacious in its hemodynamic effect on the patient. DESIGN: Prospective study. SETTING: University hospital. PATIENTS: Twenty-one patients with peritoneal carcinomatosis. INTERVENTIONS: We performed 23 continuous hyperthermic peritoneal perfusion chemotherapy (CHPPC) procedures with peritoneal cavity expansion to an intra-abdominal pressure up to 26 mm Hg, using artificially produced ascites with 4 to 9 L normal saline solution. MAIN OUTCOME MEASURES: Intraoperative and postoperative complications and hemodynamic changes during CHPPC. RESULTS: No intraoperative complications were recorded. The artificially produced ascites did not cause significant hemodynamic changes. During the immediate postoperative period, 1 patient died of intra-abdominal hemorrhage and leakage of a colorectal anastomosis, resulting in a mortality rate of 4% in our series. Minor complications were seen in 14 patients. The complications were not attributable to the expansion technique. CONCLUSIONS: Our proposed modification of closed-circuit CHPPC appears to be well tolerated and safe in patients with a high tumor load, as well as for the theater personnel. It remains to be investigated whether the theoretical advantages of the proposed technique will also lead to better long-term results.

Repeated multi-centre prevalence surveys of hospital-acquired infection in Greek hospitals. CICNet. Cretan Infection Control Network.

Three prevalence studies for the estimation of hospital-acquired infections (HAIs) were carried out in eight Greek hospitals on an annual basis during the years 1994-1996. The overall prevalence of HAI was 6.8, 5.5 and 5.9% for the three years, respectively. Among these, urinary tract infections ranged from 22.4 to 38.2%, lower respiratory tract infections ranged from 21.1 to 32.6%, surgical site infections ranged from 14.6 to 22.7% and bloodstream infections ranged from 9.0 to 13.2%. The prevalence of antibiotic usage among the hospitalized patients was found to be 49.3% in 1994, 47.3% in 1995 and 52.7% in 1996. Unjustified prescription of prophylactic usage was found to be the major component of these high percentages. Appropriate use of antibiotics for prophylaxis is one of the priorities of the current infection control programmes. The development of a nationwide network for the surveillance of HAIs in Greece is planned using the experience gained.

Outcome of 200 restorative proctocolectomy operations: the John Radcliffe Hospital experience.

BACKGROUND: Restorative proctocolectomy is now the operation of choice for the definitive management of ulcerative colitis and familial adenomatous polyposis (FAP). METHODS: A total of 200 patients (117 male, 83 female) underwent restorative proctocolectomy over a 12-year period. Information in a dedicated prospective database was supplemented by chart review. Some 177 had ulcerative colitis, 13 had indeterminate colitis and seven had FAP. Pouch designs were two-loop J (n = 142), four-loop W (n = 45) and three-loop S (n = 13). The majority (73.5 per cent) had a stapled ileoanal anastomosis and 139 patients had a defunctioning ileostomy. RESULTS: There were no deaths. Early morbidity (less than 30 days after operation) included 76 complications in 71 patients (35.5 per cent), of which 35 were related to the pouch itself. Long-term follow-up data were available for 196 patients at a median of 27 months. Sixteen pouches (8.0 per cent) have been excised. Mean daytime frequency was 4.5 (range 1-15). Of 175 patients with colitis, 42 (24.0 per cent) had one or more episodes of pouchitis. CONCLUSION: Continuous improvements in operative technique have simplified the procedure, and functional results, although variable, have generally been acceptable.

Restorative proctocolectomy in children and adolescents.

Children and adolescents with colitis present specific problems for surgeons. There has been a fashion, particularly in North America, for restoring continuity after colectomy by a direct ileo-anal anastomosis. The authors reviewed their experience with restorative proctocolectomy with ileal reservoir (RPC) in patients under 18 years of age to evaluate the outcome and to discuss the problems and challenges associated with the procedure in this age group. Fifteen patients (6 boys, 9 girls) were operated on between 1984 and 1995. The diagnoses included 12 patients with ulcerative colitis (UC), two with familial adenomatous polyposis (FAP), and one with total colonic neuronal dysplasia. The median age of the patients at the time of ileal pouch formation was 15 years, and follow-up data were available for all patients at a median of 43 months. Ten patients with UC underwent pouch surgery 4 to 14 months after initial total abdominal colectomy (7 for acute severe disease, 3 for chronic disease). Four patients (2 with chronic UC, 2 with FAP) underwent primary RPC. There were no deaths in this series. Three (20%) patients suffered serious early morbidity (pouch hemorrhage, pelvic sepsis, severe psychological crisis). Late morbidity included three patients who had small bowel obstruction, one who required laparotomy, two who required pouch revision, and five of 12 (42%) patients with UC who presented with a documented episode of pouchitis between 2 and 72 months after ileostomy closure. All patients had acceptable bowel frequency and quality of continence. This experience suggests that RPC provides an important surgical option for children and adolescents with UC or FAP.

Ambulatory manometric examination in patients with a colonic J pouch and in normal controls.

Anorectal function after anterior resection may be impaired as a result of reduced luminal capacity in the pelvis. The aim of this study was to evaluate the colonic J pouch neorectum by means of ambulatory manometry. Twelve patients with a colonic pouch following anterior resection and seven healthy controls were studied for a median of 6 (range 6-24) h using a probe with two pouch-rectal and two anal canal transducers. Records were interpreted by visual inspection. Pressure values and wave frequencies were determined by software analysis. Pouches had been functioning for a median of 32 (range 11-55) months. All patients with a pouch had an acceptable stool frequency. Seven of 12 patients complained of incomplete evacuation. Resting anal canal pressure (73 versus 100 cmH2O), pouch-rectal pressure (29 versus 15 cmH2O) and anal canal pouch-rectal pressure gradients (60 versus 85 cmH2O) were similar in patients and controls. The frequency of slow-wave activity in patients with a pouch was significantly lower than that in controls (7 versus 16 cycles per min, P = 0.001). Coordination between the colonic J pouch and the anal canal, in the form of sampling episodes, was observed in more than half of the patients with a functioning pouch. Large isolated contractions (pressure greater than 30 cmH2O and lasting longer than 20 s) and rhythmic contractions were the most frequent pattern of pouch motility.