In a population prevalence questionnaire study we demonstrated that constipation and fecal incontinence are common problems in the general Swedish population with a similar magnitude as in other Western countries. 95.6% of the population had between three bowel movements per day and three per week. Constipation was mostly defined by “hard stools” and “the need of using laxatives”. Irritable Bowel Syndrome (IBS) is characterized by abdominal pain/discomfort and abnormal bowel habits. The diagnostic criteria of IBS are based on clinical symptoms. Division of IBS patients into symptom subgroups appears important as their bowel symptoms are characterized by heterogeneity. International criteria to subgroup IBS (Rome II) are based on expert consensus and not on evidence. We investigated the variation of stool consistency and defecatory symptoms in 135 IBS patients by symptom diary cards. Most patients had alternating stool consistency. When subgroups were based on stool consistency, all kinds of defecatory symptoms (straining, urgency, and feeling of incomplete evacuations) were frequently present in all subgroups. Stool frequency was in the normal range in the majority of patients. We propose that IBS subgroups should be based on stool consistency. We suggest that Rome II supportive criteria must be reconsidered as the determination of presence or absence of specific symptoms does not work as an instrument for categorization of IBS patients into diarrhoea- and constipation-predominant. We also propose that abnormal stool frequency should be excluded to define subgroups of IBS. Alternating stool consistency and presence of different defecatory symptoms, regardless of stool consistency should be included as criteria for IBS. Stress is known to play an important role in the onset and modulation of IBS symptoms. From experimental studies there is evidence for a stress-dependent alteration of visceral sensitivity. The biological mechanisms responsible for the causal link between stress and IBS symptoms are not completely understood, but the hypothalamic-pituitary-adrenocortical axis and the autonomous nervous system seem to play a prominent role in the pathophysiology of IBS. We investigated visceral sensitivity and the effect of repeated maximal tolerable rectal distensions on salivary cortisol levels and skin conductance in patients with IBS, chronic constipation and healthy volunteers. We found that the expectancy of the experimental situation per se (provocation of bowel symptoms by rectal distensions) compared to non-experimental days at home measured as salivary cortisol had a high impact on the level of arousal in IBS. IBS patients had higher skin conductance values than controls in the beginning of distension series and lower rectal thresholds for first sensation, urge and discomfort than healthy controls and constipation patients. IBS patients demonstrated habituation to repeated subjective maximal tolerable rectal distensions according to sympathetic activity although patients continued to rate their discomfort as maximal. Constipation patients had lower sympathetic activity than IBS patients before and during repeated rectal distensions. None of the groups demonstrated a significant increase in cortisol after repetitive rectal distensions. We conclude that Rome II supportive criteria for IBS should be reconsidered according to our findings. IBS patients are more sensitive to pre-experimental stress than healthy controls and patients with constipation. This should be considered in the design of experimental IBS studies. IBS patients habituated to subjective maximal tolerable, repetitive rectal distensions with decreasing sympathetic activity. Since responses to repeated stimuli of close-to-pain intensities are resistant to habituation this finding could be caused by psychological influences on perception, that is, perceptual response bias.

Autoimmune hepatitis (AIH) was identified as an entity by the Swedish professor Jan Waldenström in the 1950s. It was then denoted lupoid hepatitis, characterized by liver inflammation and most often affecting young women. During the years the diagnosis has become more defined (as the non A non B hepatitis has been identified as Hepatitis C) and now can be safely separated from other diseases with liver inflammation. Studies of epidemiological data and long term prognosis have been scarce in the literature. Within a collaboration between the university hospitals in Sweden, we collected what we believe is the largest cohort in the world of patients with AIH. Data from the medical records of 473 individuals was, after AIH-score calculations where the diagnosis was confirmed, collected in a data base, in which most of the analysis was done. Data from the Swedish national registers of cancer, death cause, and birth register was searched for these patients as well as controls. The aim of the thesis was to explore epidemiological and clinical outcome of AIH.The onset of AIH may be at any age, but the incidence seems to increase after 50 years of age; 75% are females, the overall incidence (0.85/ 100,000 inhabitants and year) and prevalence (11/100,000 inhabitants) are figures that are within the range of another but smaller Scandinavian study. Approximately 30 % had cirrhosis already at diagnosis and 87% displayed at some time positive auto-antibodies indicating AIH (Smooth muscle ab and or antinuclear ab).  Indications of future risk for liver transplantation or death is an advanced AIH at diagnosis with liver cirrhosis, decompensated liver disease, elevated PK INR as well as age. Acute hepatitis-like onset seems to carry a lower risk for later liver transplantation or death. Current Swedish national therapy traditions with immune suppression seem to be well tolerated. Five and ten years overall life expectancy does not differ from controls. Thirty-five women gave birth to 63 children, for 3 after liver transplantation of the mother. Thirteen of the women had liver cirrhosis. Current pharmacological treatment seems to be safe both for the patient and the foetus. Thirty percent of the patients experienced flair after delivery. It has been supposed that there is an overrisk for hepatocellular cancer (HCC) associated with AIH. Our figures are the first in the world to be presented that confirms a twenty-three fold overrisk (95% Confidence Interval 7.5-54.3) for hepatobiliar cancer. We found as well an overrisk of non-Hodgkin lymphomas of 13.09 (95% CI 4.2-30.6).Conclusion:  Our epidemiological results confirm that AIH is a fairly uncommon disease, and that many already at time of diagnosis have an advanced disease with liver cirrhosis. There is a clear overrisk for HCC and lymphoma. For those women with AIH who become pregnant the prognosis for the child as well as for the mother is good, even for those women who already have compensated cirrhosis. There is a risk for relapse after delivery. The overall survival for AIH patients with current therapy is good.

En la presente tesis se ha analizado la actividad hepática de una enzima (prolilhidroxilasa) que interviene en la síntesis del colágeno y la concentración sérica de un péptido (péptido aminoterminal del procolágeno tipo III) que se origina durante el proceso de síntesis del mismo en un grupo de pacientes con una hepatopatía alcohólica de diversa severidad diagnosticados por biopsia hepática y se ha observado una relación entre los niveles de actividad hepática de la prolil-hidroxilasa y la concentración sérica del péptido aminoterminal del procolágeno tipo III con la intensidad de la fibrosis hepática. También se ha hallado una relación lineal directa entre ambos parámetros lo que sugiere que ambos marcadores son índices de fibrosis y fibrogénesis hepatica en la hepatopatía alcohólica y podrían ser de utilidad en el control evolutivo de estos pacientes.

No description available.

INTRODUCTION: Celiac disease is a chronic immune disorder for which the only treatment is strict life-long adherence to a gluten-free diet (GFD). Collaborative management through regular follow-up with a care team that includes physicians and dietitians may improve long-term outcomes. However, many individuals with celiac disease are lost to follow-up. OBJECTIVE: This primary objective of this study was to identify factors associated with pediatric celiac disease patients being lost to follow-up. Secondary aims included identifying adherence to recommended care practices by both patients and providers. METHODS: A chart review of 250 randomly selected children with biopsy-confirmed celiac disease diagnosed between 2010 and 2014 at Boston Children’s Hospital (BCH) was conducted. Follow-up records were reviewed from diagnosis to 2017. Eligible children were diagnosed prior to age 18 and did not attend BCH solely for a second opinion. Demographics, medical history, visit information, and lab results were collected using an online database. RESULTS: Of the 241 eligible subjects (64% female, 1-17 years, median 9.7 years) the median time until lost to follow-up was 2.8 years from diagnosis (IQR, 1.0-4.7 years) with 22 subjects (9%) not attending any follow-up visits with their pediatric gastroenterologist (GI) after diagnosis and an additional 37 subjects (14%) lost within the first year. A majority of subjects (83%) attended a GFD education visit with a registered dietitian, although this was not associated with follow-up adherence (P>0.5). Excluding those who had aged out of the clinical practice, children who were adherent to follow-up had a younger mean age of diagnosis (95% CI 0.5-3.1, P<0.01). Children who were insured under Medicaid/CHIP (N=20) were more likely to be lost within one year compared to those with private health insurance (P<0.01). Celiac serologies taken at time of last clinical visit were abnormal in 25% of the subjects with available results (N=141) and the median time since diagnosis in this positive serology subgroup was 20 months (IQR, 12-29 months). DISCUSSION: The present study illustrates that children with celiac disease are not being followed-up adequately and that identifiable disparities exist in the pediatric celiac disease population. Within three years of diagnosis, 50% of the cohort was lost to follow-up with the majority of subjects lost within the first year of diagnosis. Children diagnosed at a younger age were more adherent to follow-up compared to those diagnosed during adolescence. Factors associated with decreased adherence included reliance on public medical insurance and older age at diagnosis. Improvement in long-term management of celiac disease may be achieved by increased outreach and education.

Com o objetivo de estudar os possíveis efeitos da administração sistêmica de glutamina ou da associação de hidrocortisona, dimetilsulfóxido, ácido ascórbico e pentoxifilina nas lesões de isquemia e reperfusão no cólon maior, foram utilizados dezoito equinos. Sob anestesia geral e controle da oximetria de pulso e pressão arterial, os equinos foram submetidos a laparotomia e em um segmento do cólon maior foi induzida isquemia venosa total. Após uma hora de isquemia, seis equinos do Grupo G receberam glutamina (25mg/Kg IV), seis equinos do Grupo A receberam uma associação de hidrocortisona (4mg/Kg IV), dimetilsulfóxido (20mg/Kg IV), ácido ascórbico (50mg/Kg IV), e pentoxifilina (10mg/Kg IV) e os seis equinos do Grupo C receberam apenas solução de Ringer com lactato e constituíram o Grupo controle. Após duas horas de isquemia o fluxo sanguíneo local foi restabelecido. Decorridas duas horas de reperfusão foi realizada a laparorrafia e permitiu-se a recuperação anestésica. Seis horas após o início da reperfusão os equinos do Grupo G receberam novamente 25mg/Kg de glutamina, enquanto os equinos dos Grupos A e C receberam apenas solução de Ringer com lactato. Doze horas após o início da reperfusão os equinos foram eutanasiados. Foram colhidas amostras de cólon antes da indução da isquemia, após duas horas de isquemia e após duas e doze horas de reperfusão, que foram submetidas a avaliação histomorfológica, ultra-estrutural e determinação da atividade de mieloperoxidase. Os resultados para todas as variáveis estudadas foram semelhantes entre os grupos, permitindo concluir que os tratamentos, nas condições em que foram empregados neste estudo, não foram eficazes em atenuar as alterações decorrentes de isquemia e reperfusão no cólon maior de equinos. / This study was designed to evaluate the effects of intravenous administration of glutamine or the association of hydrocortisone, dimethyl sulphoxide, ascorbic acid and pentoxifylline on ischemia reperfusion lesions of the large colon. A segment of the large colon was isolated in 18 horses under inhalant general anesthesia and total venous ischemia was induced. One hour after the onset of ischemia, glutamine (25mg/Kg IV) was administered to six horses (G group), an association of hydrocortisone (4mg/Kg IV), dimethyl sulphoxide (20mg/Kg IV), ascorbic acid (50mg/Kg IV) and pentoxifylline (10mg/Kg IV) was administered to six horses, and the others received only isotonic fluids and remained as the control group (C). After 2 hours of ischemia and 2 hours of reperfusion the abdomen was closed and the horses were allowed to recover from anesthesia. After 6 hours of reperfusion, horses of group G received another dose of glutamine (25mg/Kg IV) whereas groups A and C received only isotonic fluids. Horses were euthanatized 12 hours after reperfusion. Biopsies were taken from the large colon before and after 2 hours of ischemia and after 2 and 12 hours of reperfusion. Alterations were evaluated under light and scanning electronic microscopy and scored. Additionally, mieloperoxidase (MPO) activity was measured. Results showed that scores for mucosal lesion, edema, hemorrhage, neutrophil infiltration and MPO activity during IR were similar between groups G, A and C. It was concluded that treatments were not effective in attenuating effects of ischemia and reperfusion in the equine large colon.

The overall aim of this thesis was to study epidemiological and clinical changes in the natural history of Crohn’s disease, its phenotype, the need for surgery and pharmacological therapy over time, as well as the role of faecal calprotectin as a biomarker of pathophysiology and disease course. An increased incidence and prevalence of Crohn’s disease was seen in the period 1963-2010. The proportion of patients with non-stricturing, non-penetrating disease behaviour at diagnosis increased, suggesting that either patients with Crohn’s disease are diagnosed earlier in their disease course today or that the Crohn’s disease phenotype is changing. A decrease in complicated disease behaviour, an increased use of immunomodulators, and a reduced frequency of surgical procedures five years after Crohn’s diagnosis was observed. The decrease in surgery at five years seemed to be explained mainly by a decrease in early surgery within three months from diagnosis, likely reflecting an increased proportion of patients with non-stricturing, non-penetrating disease. This suggests that the introduction of new treatment alternatives alone does not explain the reduction in surgery rates, and an increasing proportion of patients with uncomplicated disease at diagnosis may also play an important role. Subclinical mucosal inflammation, mirrored by increased NFkB activity and increased neutrophil activity (i.e. FC and MPO expression), was observed in healthy twin siblings in both discordant monozygotic and discordant dizygotic twin pairs with IBD. These findings strongly support the hypothesis of an ongoing subclinical mucosal inflammation at the molecular level in healthy first-degree relatives of IBD patients. Baseline FC as well as consecutive FC measurements predict relapse in IBD. The doubling of FC value increased the risk of relapse by 101% in the following three months. This increased risk attenuates with time by 20% for every three month period since the sample was obtained.

The efficacy of multidisciplinary inpatient and outpatient treatment for transitioning children with severe pediatric feeding disorders from gastrostomy tube dependency to oral nutrition was investigated utilizing caloric and fluid intakes as an outcome measure. The study involved 29 children ages 12 months to 5 years of age with gastrostomy tube dependency. Treatments were provided by speech therapists, occupational therapist, dietician and psychologist for a 30 day period. Four treatment groups were evaluated and average intakes compared at 4 observation periods including pretreatment, initiation of treatment, completion of treatment at 30 days and 4 month follow-up. Children receiving inpatient treatment for feeding disorders evidenced significant differences in oral caloric intake from pretreatment to discharge than outpatient treatment (p < .01) and wait list control group (p = .04). Oral caloric intake from discharge to 4 month follow up yielded no significant differences indicating treatment gains were maintained. Change in environment and caretaker showed a significant effect for the inpatient group (d = 1.89). Effects of treatment by age and weight at 4 month follow up were also analyzed.

Artificial urinary sphincters have been used for decades for treatment of urinary incontinence. A commonly used device, the AMS 800 consists of a urethral cuff, pump and an abdominal reservoir. Notable complications of this system include scrotal or labial hematomas, infection or erosion of the cuff and rarely migration of its components. Although there are few reported cases related to effects from pump migration, those documenting reservoir related complications are even rarer. We present a case of reservoir migration adjacent to the ascending colon causing ischemic changes mimicking colonic neoplasm. Our patient, a 66-year old male with medical history of adenocarcinoma of prostate status post radical prostatectomy, had been having abdominal pain for a month. A CT scan showed cecal and proximal ascending colonic irregular nodular thickening suggestive of colonic mass. It also revealed a low-density structure next to the ascending colon abutting into area of the mass. A follow up colonoscopy showed a fungating, ulcerated mass extending from cecum to ascending colon concerning for a malignancy of which biopsy was also done. The patient then underwent right open hemicolectomy. During surgery, a balloon reservoir was seen in the abdominal cavity with its adherence to the right colon but not eroding into it. The surgeon dissected the balloon, repositioned and re-peritonealized it before closing the abdomen. The colonoscopic and surgical pathology instead demonstrated findings of ischemic colitis with mucosal ulceration in cecum and ascending colon limited to the mucosa but no evidence of cancer. Retrospective chart review revealed history of artificial urinary sphincter implantation for urinary incontinence related to radical prostatectomy for adenocarcinoma eight years prior. With manufacturer suggested implant location of the reservoir in prevesical space, the possibility of migration needs to be accounted for. Although there are not many reports of artificial sphincter reservoir related complications, there are cases documenting inflatable penile prosthesis reservoir erosion into abdominal and pelvic structures. As the CT scan demonstrated reservoir indentation into the ascending colon, it likely led to chronic irritation of the adjacent colonic wall due to mass effect. It is hypothesized that constant pressure on colonic wall likely led to localized ischemia. This resulted in localized inflammation including submucosal edema, which can create a mass-like appearance when severe. This case emphasizes that, while preliminary radiographic imaging and even gross colonoscopy findings may be suggestive of a malignancy, it is imperative to await biopsy results to confirm the diagnosis of a malignant neoplasm. Our case report emphasizes the consideration of diagnoses other than colon cancer when faced with a colonic mass especially in the setting of implanted intra-abdominal foreign body to avoid unnecessary surgery and related complications.

ABSTRACT: Hepatitis C virus (HCV) is associated with various glomerulopathies and nephrotic syndrome. However nephrotic syndrome following treatment is rare. Ledipasvir/sofosbuvir (L/S) has recently come into favor in treating HCV due to its relatively mild side effects compared to the more traditional interferon therapy. To the best of our knowledge, there are no reported cases of nephrotic syndrome following treatment with L/S. We present a case of nephrotic syndrome suspected secondary to L/S in a patient with chronic kidney disease. Increased vigilance when assessing therapeutic options in HCV patients with renal comorbidities can improve patient outcomes. A 63 year-old male patient presented to the hospital with shortness of breath, and a two-week history of bilateral lower extremity edema. Past medical history was significant for liver cirrhosis secondary to Hepatitis C genotype Ia, hepatocellular carcinoma status post liver transplantation 6 months prior to admission and Stage 3b chronic kidney disease with baseline creatinine (Cr) approximately 1.5 mg/dl. Medications included L/S for HCV and tacrolimus and prednisone for post-transplant treatment. Patient’s vitals were stable and physical exam was remarkable for facial swelling, mainly on the eyelids, decreased breath sounds bilaterally, distended abdomen with a fluid wave, and 2-3+ pitting edema up to the knees on lower extremities bilaterally. Laboratory work-up was remarkable for low albumin of 3.0 g/dl, and total protein of 5.6 g/ dl. Creatinine of 1.8 mg/dl was elevated from patient’s baseline. HCV viral load was undetectable and electrolytes, transaminases and the complete blood count were within normal limits. Subsequently, urine protein to creatinine ratio was measured because of generalized swelling and hypoproteinemia, which was found to be significantly high at 8.80, compared to 0.04 one year prior. 24-hour total urine protein was found to be 2065 mg/day. Renal ultrasonography showed no hydronephrosis and was otherwise unremarkable. Renal biopsy however, revealed changes suggestive of membranoproliferative glomerulonephritis (MPGN] most likely secondary to HCV. No immune complexes, lambda/kappa light chains, or cryogloblin were appreciated. Nephrotoxic agents such as diuretics and corticosteroids were held. Tacrolimus trough was appropriate to dose level and was continued along with L/S. As admission progressed the patient’s creatinine continued to get worse and rose up to 4.3 mg/dl with persistent proteinuria. With tacrolimus trough levels within normal limits and given L/S was the most recently initiated drug, L/S was thought to be the culprit and was thus held. The renal function began to improve gradually, and the patient was discharged in stable condition with close follow up. Follow up one month later found creatinine and renal function return to baseline and proteinuria resolved. Our case shows that Ledipasvir/sofosbuvir may possibly be related to nephrotic syndrome in HCV patients. Although further studies are needed to prove the causality our case seeks to raise clinical suspicion and increase vigilance when assessing therapeutic options in HCV patients with renal comorbidities such as chronic kidney disease.