Functional mucous layer and healing of proximal colonic anastomoses in an experimental model.

BACKGROUND: Anastomotic leakage (AL) is the most dreaded complication after colorectal surgery, causing high morbidity and mortality. Mucus is a first line of defence against external factors in the gastrointestinal tract. In this study, the structural mucus protein Muc2 was depleted in genetically engineered mice and the effect on healing of colonic anastomoses studied in an experimental model. METHODS: Mice of different Muc2 genotypes were used in a proximal colonic AL model. Tissues were scored histologically for inflammation, bacterial translocation was determined by quantitative PCR of bacterial 16S ribosomal DNA, and epithelial cell damage was determined by assessing serum levels of intestinal fatty acid-binding protein. RESULTS: Of 22 Muc2-deficient (Muc2-/- ) mice, 20 developed AL, compared with seven of 22 control animals (P < 0·001). Control mice showed normal healing, whereas Muc2-/- mice had more inflammation with less collagen deposition and neoangiogenesis. A tendency towards higher bacterial translocation was seen in mesenteric lymph nodes and spleen in Muc2-/- mice. Intestinal fatty acid-binding protein levels were significantly higher in Muc2-/- mice compared with controls (P = 0·011). CONCLUSION: A functional mucous layer facilitates the healing of colonic anastomoses. Clinical relevance Colorectal anastomotic leakage remains the most dreaded complication after colorectal surgery. It is known that the aetiology of anastomotic leakage is multifactorial, and a role is suggested for the interaction between intraluminal content and mucosa. In this murine model of proximal colonic anastomotic leakage, the authors investigated the mucous layer at the intestinal mucosa, as the first line of defence, and found that a normal, functioning mucous layer is essential in the healing process of colonic anastomoses. Further research on anastomotic healing should focus on positively influencing the mucous layer to promote better postoperative recovery.

ICIQ symptom and quality of life instruments measure clinically relevant improvements in women with stress urinary incontinence.

AIMS: To determine whether changes in questionnaire scores on symptoms and condition-specific quality of life reflect clinically relevant improvements in women with stress urinary incontinence (SUI). METHODS: We retrospectively analyzed questionnaires collected during a randomized controlled trial in women with SUI, that received pelvic floor muscle training (PFMT) in two different formats. We included 218 women that answered validated self-assessment questionnaires at baseline and at a 4-month follow-up. We registered changes on two questionnaires, the International Consultation on Incontinence Modular Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF) and the Lower Urinary Tract Symptoms Quality of Life (ICIQ-LUTSqol). We compared these score changes to responses from the Patient Global Impression of Improvement (PGI-I) questionnaire. Differences were analyzed with the Spearman rho and one-way-ANOVA. The minimum important difference (MID) was the mean change in score for women that experienced a small improvement. RESULTS: The PGI-I correlated significantly to both the ICIQ-UI SF (r = 0.547, P < 0.0001) and ICIQ-LUTSqol (r = 0.520, P < 0.0001). Thus, larger reductions in symptoms or quality of life scores were associated with greater impressions of improvement. The changes in ICIQ-UI SF and ICIQ-LUTSqol scores were significant across all PGI-I groups from "no change" to "very much improved" (P < 0.05). The MIDs were 2.52 (SD 2.56) for ICIQ-UI SF and 3.71 (SD 4.95) for ICIQ-LUTSqol. CONCLUSIONS: The change in ICIQ-UI SF and ICIQ-LUTSqol scores after PFMT reflected clinically relevant improvements in women with SUI. The MIDs established for this population may facilitate future research, treatment evaluations, and comparisons between studies.

Bovine recto-anal junction squamous epithelial (RSE) cell adhesion assay for studying Escherichia coli O157 adherence.

AIM: To develop a new adherence assay, using cattle recto-anal junction squamous epithelial (RSE) cells, for evaluating bacterial adherence to cells of bovine origin. METHODS AND RESULTS: Proof of concept was demonstrated using the human gastrointestinal pathogen Escherichia coli O157:H7, for which cattle are reservoirs. Adherence assays were conducted using both RSE and HEp-2 cells, in the presence and absence of D+Mannose. E. coli O157 specifically adhered in a type I fimbriae-independent manner to RSE cells in significantly higher numbers and also bound significantly higher numbers of RSE cells than diverse laboratory strains of nonpathogenic E. coli. CONCLUSION: The RSE cell adhesion assay output highly reproducible and interpretable results that compared very well with those obtained using the more extensively used HEp-2 cell adherence assay. SIGNIFICANCE AND IMPACT OF THE STUDY: The RSE cell adhesion assay provides a convenient means of directly defining and evaluating pathogen factors operating at the bovine recto-anal junction. The RSE cell adhesion assay further has the potential for extrapolation to diverse bacteria, including food-borne pathogens that colonize cattle via adherence to this particular anatomical site.

Thyroid volume in Swedish school children: a national, stratified, population-based survey.

BACKGROUND/OBJECTIVES: Sweden has had a salt iodination program since 1936. This first national surveillance study on iodine nutrition infers an adequate level of urinary iodine concentration (UIC 125 µg/l) and the aim is now to evaluate thyroid volume (Tvol) in the same national sample. SUBJECTS/METHODS: A stratified probability proportionate to size cluster sampling was used to obtain a representative national sample of Swedish children aged 6-12 years. Median Tvol obtained ultrasonographically and the prevalence of enlarged thyroid glands were compared with an international reference standard. Regional differences were evaluated through comparisons of Tvol between coastal and inland areas, urban and rural regions, and former goitre and non-goitre regions. RESULTS: Tvol was correlated with age, body surface area (BSA), weight, height and body mass index for both sexes (P<0.0001) but not with UIC. The most important predictors for Tvol were age (girls: P<0.0001, boys: P=0.001) and BSA (girls: P<0.0001, boys: P<0.01). Median Tvol was higher in Sweden than in the reference study (P<0.0001). The prevalence of goitre was higher in Sweden (correlated to age 22.3%, BSA 15.7%, weight 17.6%, height 12.9%) than in the international reference (correlated to age 2.5%, BSA 2.5%, weight 2.5%, height 2.5%) (P<0.0001). Thyroids were larger in boys from urban and former non-goitre areas. CONCLUSIONS: Tvols were higher in Swedish school children than in the international reference study although iodine intake is considered optimal in Sweden. These findings underline the importance of regular monitoring of iodine intake, especially with regard to the decreased intake of table salt that is likely to follow initiation of health campaigns.

Adequate iodine nutrition in Sweden: a cross-sectional national study of urinary iodine concentration in school-age children.

BACKGROUND/OBJECTIVES: Sweden has a long-standing salt iodization program; however, its effects on iodine intake have never been monitored on a national level. The objective of this study was to evaluate iodine nutrition in the Swedish population by measuring the urinary iodine concentration (UIC) in a national sample of Swedish school-age (6-12 years of age) children. SUBJECTS/METHODS: A stratified probability proportionate to size cluster sampling method was used to obtain a representative national sample of school-age children from 30 clusters. Spot urine samples were collected for UIC analysis using a modified Sandell-Kolthoff method. RESULTS: The median UIC of the children (n=857) was 125 microg/l (range 11-757 microg/l). The proportion of children with a UIC <100 microg/l was 30.0% and the proportion of children with a UIC <50 and >300 microg/l was 5.5 and 3.0%, respectively. CONCLUSIONS: The iodine nutritional status of the Swedish population is adequate. Iodized table salt remains the main dietary source of iodine in Swedish diet. Recommendations to reduce total salt intake in the population urge increased use of iodized salt in the production of processed foods. Pregnant and lactating women with high iodine requirements may still be at risk for low iodine intake. This study will serve as the basis for future monitoring of iodine nutritional status in Sweden.

A 9-14 year follow-up of onlay bone grafting in the atrophic maxilla.

Treatment of the atrophic edentulous maxilla is challenging especially when bone graft procedures are necessary. In this study an onlay bone graft, a saddle or veneer, with or without maxillary sinus floor inlay graft, harvested from the anterior iliac crest, in combination with implants was used in the reconstruction of patients with extreme atrophy in their maxillae. The aim was to investigate treatment outcome, and the impact of gender and smoking, in 44 patients in a prospective, long-term, follow-up study concerning implant survival rate and marginal bone loss adjacent to the surfaces of the implant. Mean follow-up time was 11 years. Of 334 inserted Brånemark implants, with machined surface, 27 failed. Estimated implant survival rate was 90%. Marginal bone loss was 1.8 mm 1 year after implant surgery; 2.3 mm after 5 years; and 2.4 mm after 10 years. There was a significant difference between genders in implant survival. Marginal bone loss differed significantly between smokers and non-smokers up to the 5-year examination and between genders after the 4-year examination. The onlay bone graft, with or without a maxillary inlay graft, results in high implant survival rate, good oral function and stabilised marginal bone. All patients are still wearing their original fixed bridges.

Reconstruction of the atrophic maxilla with interpositional bone grafting/Le Fort I osteotomy and endosteal implants: a 11-16 year follow-up.

A Le Fort I osteotomy and interpositional bone graft in combination with implants was used in the reconstruction of patients with extreme atrophy in their maxillae. Surgery was performed in a two-stage procedure. The patients in this study had conditions with reversed intermaxillary relationships with or without increased vertical intermaxillary distance. The aim of the study was to investigate treatment outcome for patients in a prospective, long-term, follow-up with a mean of 13 years (range 11-16 years), concerning implant survival rate and marginal bone loss adjacent to the surfaces of the implant. The impact of gender and smoking was also investigated. Twenty-six patients were included in the study. Of 167 implants, 24 failed. The implant estimated survival rate was 85% at the end of the follow-up. There was no significant difference between smokers and non-smokers or genders concerning implant survival. Marginal bone loss was 2.5, 2.9, 3.0 and 3.1mm from the implant-abutment junction, after 1, 2, 5 and 10 years, respectively. The bone level stabilised after 2 years. This technique results in good facial morphology, good oral function and aesthetics. All patients are still wearing their original fixed bridges.

Dexamethasone depletes gammadelta T cells and alters the activation state and responsiveness of bovine peripheral blood lymphocyte subpopulations.

Administration of dexamethasone (DEX) to cattle is commonly used in models of stress-induced effects on host defense, including models investigating interactions of microorganisms with their host. Much less is known about the effects of DEX on the adaptive immune response in cattle compared with other species. The objective of the present study was to characterize subsets of circulating lymphocytes in calves before and 48 h after the onset of parenteral DEX treatment. Treatment significantly reduced the overall percentage of circulating lymphocytes and disproportionately depleted the population of gammadeltaTCR(+)/CD8alpha(-) cells. Analysis within the CD8alpha(+) population of T cells revealed that DEX treatment also reduced the CD8alpha(low) subset of gammadeltaT cells coexpressing the activation marker ACT-2(+). By contrast, DEX treatment did not affect the percentage of CD8alpha(low)/CD25(+) cells, indicating that cells with a special activation state were affected. Dexamethasone treatment reduced the number of gammadeltaT cells but increased the percentages of CD14(+) monocytes and activated CD25(+) cells (both CD4(-) and CD4(+)) in peripheral blood mononuclear cell (PBMC) preparations. Although DEX treatment reduced the overall proliferative capacity of PBMC, it enhanced the relative number of proliferating CD4(+) lymphocytes. Lower levels of mRNA for several Th-prototype cytokines (IL-2, IFN-beta, IL-4, transforming growth factor-beta) were detected in short-term PBMC cultures established from DEX-treated calves compared with PBMC cultures from control calves; the amount of il-10 transcripts, however, was unaffected. Results of the study reported here clearly show that DEX treatment does not uniformly suppress the bovine immune system but has differential effects on lymphocyte sub-populations and functions. This information must be considered when using DEX treatment as a bovine stress model.

Determination of intrathyroidal iodine by X-ray fluorescence analysis in 60- to 65-year olds living in an iodine-sufficient area.

OBJECTIVES: X-ray fluorescence (XRF) is a non-invasive method for determining the iodine content of the thyroid gland in vivo. In spite of the obvious clinical value of such a method in situations of iodine deficiency or iodine overload, the method has not so far been widely used. The objective was to investigate the applicability of the XRF method in a larger number of subjects. DESIGN AND SUBJECTS: The study comprised 37 individuals, aged 60-65 years, who had spent their entire life with iodine supplementation through iodinated table salt. Individuals with (previous) thyroid disease were excluded. The individual thyroid function had previously been evaluated by measurements of thyroid-related hormones, thyroid volume and 131-Iodine (131I) uptake which indicated a sufficient iodine intake of the population in the area. Iodine in the right thyroid lobe in each subject was examined using XRF. RESULTS: The mean thyroid iodine concentration was 0.4 mg mL(-1), corresponding to a mean total iodine content of 5.2 mg (range 0.9-20.2). There was a pronounced difference between individuals. No correlation was found between iodine concentration and 131I uptake or thyroid volume. Neither was iodine content and 131I uptake correlated. CONCLUSIONS: In a population living under iodine-sufficient conditions, a large variation of iodine stored in the thyroid is compatible with euthyroidism. Determination of the iodine pool by XRF investigation is feasible in a clinical setting and the method offers a unique possibility to study the intrathyroidal iodine pool in subjects with thyroid disease. The low radiation dose enables the use of the method in pregnant women and also in young individuals.

Amiodarone inhibits thyroidal iodide transport in vitro by a cyclic adenosine 5'-monophosphate- and iodine-independent mechanism.

Thyroid side effects are common in patients treated for cardiac arrhythmias with amiodarone (AM). A major disturbance is inhibited thyroidal radioiodine uptake in AM-induced thyrotoxicosis, which makes 131I therapy ineffective. On the other hand, failure to escape from the Wolff-Chaikoff effect by down-regulation of the sodium/iodide symporter (NIS) is proposed to explain AM-induced hypothyroidism. However, previously no experimental studies on the possible mechanisms have been conducted. We therefore investigated the early effects of AM on thyroidal iodide transport using bicameral chamber cultures of primary pig thyrocytes that reproduce the three tissue compartments (epithelium, lumen, and extrafollicular space) of the gland. AM dose-dependently (1-50 microm) inhibited the TSH-stimulated transepithelial (basal to apical) transport of 125I- by up to 90%. The inhibitory effect was noticed already after 8 h and was further pronounced after 1-4 d, depending on the AM concentration. The intracellularly accumulated 125I- was reduced by perchlorate but not AM, and quantitative real-time RT-PCR revealed no change in the NIS expression in AM-treated cells. Blocking of cAMP degradation with 3-isobutyl-1-methylxanthine or withdrawal of AM reversed AM-induced changes in electrolyte transport but were unable to recover the suppressed 125I- transport. The iodine-free AM analog dronedarone also inhibited 125I- transport to the same extent as AM. The findings indicate that AM blocks thyroidal iodide uptake by reducing the iodide permeability of the apical plasma membrane of the thyroid epithelial cells. The effect is iodine independent and long-lasting and does not involve impaired function of NIS or the TSH receptor/cAMP signaling pathway.

Effect of lifelong iodine supplementation on thyroid 131-I uptake: a decrease in uptake in euthyroid but not hyperthyroid individuals compared to observations 50 years ago.

BACKGROUND: In Sweden, iodine has been added to table salt (10 mg/kg) since 1936; this amount was increased in 1966 to 50 mg/kg. OBJECTIVE: To investigate a euthyroid Swedish population (n = 44, 60-65 years) with its entire lifespan with iodine supplementation as for 24-h 131-I uptake (24 h IU) and thyroid nodularity (thyroid scintigraphy). To compare the euthyroid 24 h IU with uptake of thyrotoxic individuals, and with observations from 1955. METHODS: The 24 h IU was used in euthyroid individuals after oral administration of 0.1 MBq/2.7 microCi radioiodine and imaging of the thyroid gland was carried out using 99mTc-pertechnetate. RESULTS: In 1999-2000, the mean 24 h IU in the euthyroid individuals was 21% (range 11-33%) and the normal (central 95%) reference interval was 14-30%. Scintigraphy suggested multinodular goitre in three euthyroid individuals. In Graves' patients (n = 53, 50-65 years), the mean 24 h IU was 61% (range 29-89%). In 1955, the 24 h IU in euthyroid individuals was higher (38%, range 10-70%), while hyperthyroid patients had uptake values similar to those recorded in the present investigation (mean 62%, range 40-90%). CONCLUSIONS: The population sample studied had to be small for ethical reasons. We conclude that the reference interval for 24 h IU is 14-30% in this population that had spent its entire lifespan with iodine supplementation. This is lower than that recorded in a Swedish euthyroid population half a century ago having had low-grade table-salt iodine supplementation for 20 years. Values for hyperthyroid patients, however, do not appear to have been affected likewise.

Shiga-toxigenic Escherichia coli-inoculated neonatal piglets develop kidney lesions that are comparable to those in humans with hemolytic-uremic syndrome.

Kidney lesions similar to those in humans with hemolytic-uremic syndrome were observed histologically in 82 of 122 piglets inoculated intragastrically with Shiga-toxigenic Escherichia coli but not in 29 controls. The locations of lesions matched locations where Stx-2 binding and Gb3 (globotriasylceramide receptors for Stx) were identified immunohistochemically.

10-year follow-up of onlay bone grafts and implants in severely resorbed maxillae.

Thirty patients with extremely resorbed maxillae had reconstructive bone grafts from the ala iliaca and endosseous implants in a one-stage procedure. The first ten patients constituted a development group and the following 20 patients a routine group. The marginal bone level and implants success rate was evaluated in a prospective long-term follow-up for a minimum of 10 years (10-13 years). Clinical and radiographic examinations were performed at 6 months and then annually up to 5 years. The final examinations were performed at the 10-year follow-up. The bridges were removed at every clinical examination. Marginal bone loss was seen up to the 3-year examination, where it averaged 4.6 mm in the routine group. Between the 3- and 10-year follow-up no significant change was registered. The initial bone loss was probably due to the design of the 3.6 mm conical unthreaded marginal part of the implant. The implant success rate was 83.1% in the routine group. Failures mostly occurred during the first 2 years (14 out of 20). A substantial amount of bone can be gained in patients with extremely resorbed maxillae, when treated with bone graft according to the procedure described in this study.

Urinary iodine and thyroid volume in a Swedish population.

OBJECTIVE: To evaluate the present efficacy of an iodine supplementation programme working in Sweden since 1936 by studying the iodine excretion in urine and determining the thyroid volume in a population in a semi-rural community. DESIGN: A cross-sectional population screening comprising three age groups with randomly selected individuals: group 1 (children): 7-9 years, n = 61 (invited 70); group 2 (teenagers): 15-17 years, n = 61 (invited 63), and group 3 (adults): 60-65 years; n = 57 (invited 73). MAIN MEASUREMENTS: Urinary iodine was measured spectrophotometrically; thyroid volume by ultrasonography. RESULTS: The median values for urinary iodine concentration in the three age groups were 194 microg L(-1), 246 microg L(-1) and 190 microg L(-1), respectively, indicating an adequate iodine intake. In the 7-9 year olds, the median value of the thyroid volume was 4.7 mL, which coincides with the recently established upper limit of normal children of that age, 4.0-4.8 mL (ICCIDD, International Council for control iodine deficiency disorders). One eight-year-old boy had a pronounced goiter. Four teenagers and one adult were found to have an enlarged thyroid gland according to earlier established reference volumes (15 years >16 mL; adults > 25 mL). CONCLUSION: We conclude that the iodine intake in our region is sufficient in age groups ranging from young children to pre-retirement adults.

Bone graft remodelling and implant success rate in the treatment of the severely resorbed maxilla: a 5-year longitudinal study.

A total of 30 patients, 10 in a developmental group and 20 in a routine group, with extremely resorbed maxillae were treated with bone grafting from the hip and implant placement in a one-stage procedure. All patients were followed for a minimum of 5 years and were examined regarding the long-term success rate of the implants and marginal bone level. The implant success rate was 74.6% for the whole patient group and 85.8% for the routine group, after 5 years. The marginal bone along the implant surface decreased continuously, up to 3 years and thereafter the bone level stabilized. In the routine group, changes in bone graft dimensions over time were also evaluated by computerized tomography. The mean height of the bone graft postoperatively at all implant sites was 8.3 mm. The total mean bone height, including bone graft and residual alveolar crest, was 12.4 mm. After 5 years the total bone height had decreased to a mean of 10 mm. The mean width of the bone graft was 12 mm postoperatively and 8.7 mm at the 5-year examination. A substantial amount of bone can be gained in patients with extremely resorbed maxillae, when treated with bone graft according to the procedure described in this study.

Implant versus tooth-implant supported prostheses in the posterior maxilla: a 2-year report.

When implants are used for restoration of a jaw with a residual dentition, the possibility of combining implants with natural abutments may be considered. In a longitudinal comparative study, 26 patients (15 women & 11 men, age 49-84 years) with residual anterior dentitions were treated with two different designs of fixed partial dentures bilaterally in the posterior maxilla. On one side the reconstruction was supported by implants only, while on the contralateral side an implant and a tooth in combination were used. The patients were followed at intervals of 3, 6, 12 and 24 months after loading of the implants. 95 implants were placed, of which 11 non-loaded. A total of 10 implants failed, 7 prior to loading and three within the first three months of service (88.0+/-SE 6.7% cumulative survival for tested implants after two years' follow-up). There was no difference in failure rate for the implants in the two different prosthesis designs. The total mean loss of marginal bone height close to the implants was within acceptable standards, but was more pronounced at the implants not combined with teeth. The results indicate a correlation between the prosthesis design and the loss of marginal bone.

Screening for thyroid disease of 15-17-year-old schoolchildren in an area with normal iodine intake.

OBJECTIVE: The prevalence of thyroid disease in Swedish schoolchildren is today insufficiently known. The aim of the study was therefore to determine the prevalence of abnormal thyroid function and thyroid autoimmunity in teen-age schoolchildren and to compare the findings with a healthy control group of 60-65-year-old inhabitants from the same community. SETTING: A semirural community of approximately 15,000 inhabitants. DESIGN: Cross-sectional study. MAIN OUTCOME MEASURES: Thyroid volume and serum concentrations of serum thyrotropin (TSH), total and free thyroxine (T4), total and free 3,5,3'-triiodothyronine (T3), and antithyroperoxidase antibodies (TPOAb). RESULTS: Four schoolchildren (7%, 59 screened) had elevated TPOAb concentration, three of the subjects being girls (8%). One girl with a goitre was overtly hypothyroid and one girl showed borderline-high serum TSH concentration suggesting subclinical autoimmune thyroid disease. One euthyroid boy had a goitre and high concentration of TPOAb. The serum free T3 concentration was significantly higher in 15-17-year-old than 60-65-year-old (7.4 vs. 6.4 pmol L(-1), P < 0.001). The concentrations of other thyroid hormones and of TSH in 15-17-year-old did not differ from those of the 60-65-year-old. CONCLUSIONS: We found three cases of thyroid disease in need of immediate attention or later follow-up. The prevalence of autoimmune thyroid disease was high as indicated from TPOAb measurements. Thyroid tests including TPOAb measurement should be performed on wide indications when teenagers seek medical advice. The reference intervals for teen-age children for commonly used first line tests (TSH and free T4) do not differ from those for adults.

Combined spinal and epidural anesthesia for labor and cesarean delivery in a patient with Guillain-Barre syndrome.

BACKGROUND AND OBJECTIVES: The anesthetic management of labor, delivery, and cesarean delivery in patients with active or resolving Guillain-Barre syndrome is not well defined. Using a combined spinal and epidural (CSE) technique in such a rare clinical situation has not been previously reported. CASE REPORT: A 32-year-old woman gravida 2, para 0 was diagnosed with Guillain-Barre syndrome at 21 weeks of pregnancy. Paralysis spread up to the T4 level. Three months later, she was admitted for labor at term. She presented in severe labor pain and it was decided to proceed with CSE analgesia. No unusual hemodynamic instability, signs of autonomic dysfunction, or increased sensitivity to local anesthetics was noted. After several hours, delivery by cesarean section was required and epidural anesthesia was then used. The patient had an uncomplicated postpartum course. CONCLUSION: Careful evaluation and documentation of the patient's baseline neurological status, a thorough discussion with the patient regarding the risks and benefits of the technique for labor analgesia, and an appreciation of the limited experience with this kind of clinical situation are important.