Qualitative assessment and morphometry in the study of the ileal reservoir after restorative proctocolectomy

Little is known about the long-term effects on the reservoir mucosa in patients with ulcerative colitis and familial polyposis coli who undergo proctocolectomy with subsequent construction of ileal reservoir/pouch and ileoanal anastomosis. In these patients, questions regarding adaptation towards a more colon-like mucosa and/or development of (pre)malignant changes are of particular importance. With the aim of designing a method for reliable evaluation of the mucosa in the ileal pouch, biopsies from 10 patients were studied by semiquantitative assessment and morphometry. The findings were compared with those obtained from normal jejunum, ileum, and colon. The following parameters were found to be important: Villous surface density, quantity of goblet cells, number of mitoses, and the presence/absence of predominantly sulphated mucin+ goblet cells. The number of Paneth cells did not show significant changes. The villous surface density was determined by a cycloid test system applied to vertical sections. Semiquantitative assessment was a sufficiently precise method for the evaluation of the quantity of goblet cells. The counting of sulphated mucin+ goblet cells was not reproducible, instead a simple statement about the presence or absence of these cells was judged to be adequate. The number of mitoses and of Paneth cells were counted directly. During the first year of function the ileal pouch showed signs of adaptation towards a colon-like mucosa: Reduction of villous surface density, increased mitotic activity, and appearance of sulphated mucin+ goblet cells. The number of Paneth cells did not show significant changes. The amount of goblet cells was generally not increased, rather reduced in some patients.     

Restorative proctocolectomy with ileal reservoir: pathological and histochemical study of mucosal biopsy specimens.

Mucosal biopsy specimens from the ileal reservoirs of 92 patients who had undergone restorative proctocolectomy (12 with familial adenomatous polyposis, 78 with ulcerative colitis, and two with functional bowel disease) were studied. Chronic inflammation was found in almost all, as was villous atrophy of varying severity. Other changes included pyloric metaplasia and mucosal prolapse. Acute inflammatory changes and ulceration were less common but, when present, corresponded to the clinical condition of "pouchitis". A grading system was devised to score acute and chronic inflammatory changes. There was a significant increase in acute inflammatory scores in ulcerative colitis compared with those in familial adenomatous polyposis, and pouchitis was present only in patients who had had ulcerative colitis; the morphological features of pouchitis are similar to those seen in the colorectal mucosa in ulcerative colitis. Histochemical studies of mucin in the reservoirs of mucosa showed that there may have been a change from small intestinal mucin to colonic mucin.     

医学院校大学生心理症状两年随访研究

目的:了解医学院校大学生2年新出现心理症状的检出率及影响因素。方法:选取某医科院校大一全体新生2910人,用大学生人格问卷(UPI)对其中心理症状阴性的大学生(n=2376)进行大三后测,采用自编人口学问卷、抑郁自评量表(SDS)、自杀行为问卷(SBQ-R)、家庭功能量表(APGAR)、心理复原力量表(ERS)、痛苦表露指数(DDI)评估心理症状的相关因素。结果:大三心理症状阳性率为15.3%。Logistic回归结果显示,女性(OR=1.60,95%CI:1.22～2.10)、精神疾病家族史(OR=1.83,95%CI:1.11～3.02)、熟人自杀史(OR=1.52,95%CI:1.01～2.28)心理咨询史(OR=2.63,95%CI:1.50～4.62)及SBQ-R得分越高(OR=1.15,95%CI:1.05～1.25)是医学院校大学生心理症状阴性转阳性的危险因素,而DDI得分越高是其保护因素(OR=0.98,95%CI:0.96～0.99)。结论:医学院校大学生入学2年后超过15%的人新出现心理症状,对有精神疾病家族史、熟人自杀史、心理咨询史、高自杀风险及低自我表露程度的学...     

Mucin expression in the ileoanal reservoir reflects incomplete mucosal adaptation

Restorative proctocolectomy is regarded as a standard surgical procedure for patients who require a proctocolectomy for ulcerative colitis and familial adenomatous polyposis. The ileal mucosa undergoes colonic phenotypic change with time, but the extent and relevance of these changes to the long-term safety of the ileoanal pouch are unclear. The aim of this study was to study the mucin biology of this adaptive process in order to assess its extent and possible impact on pouch safety. Ileoanal pouch biopsies from a cohort of patients and normal ileal and colonic controls were subjected to histological, biochemical, histochemical, and immunohistochemical mucin analysis. Mucin sulphation and sialic acid O-acetylation were studied as parameters of colonic phenotypic change. Fifty-one patients, 16 ileal, and 22 colonic controls were studied. Seventy per cent of biopsies retained villous mucosal architecture, with no cases of dysplasia detected. Ileoanal pouch mucosal sulphation and sialic acid O-acetylation did not reach colonic levels, thus indicating limited evidence for a more colonic phenotype. The data from this study suggest that colonic phenotypic change within the ileoanal reservoir is incomplete, with no cases of dysplasia detected. The degree of phenotypic change is less than in previous studies, which may support, but not prove, our hypothesis that there may be a process of reversion to an ileal type mucosa in the ileoanal reservoir with time.     

Hypertrophy of ileal smooth muscle after construction of ileal reservoir in the rat

Summary An experimental model of the continent ileostomy reservoir used in clinical practise has been adapted for rats in order to evaluate changes in the smooth muscle layers of the ileal wall. The reservoir was constructed in the distal part of ileum, with intestinal continuity in order to avoid emptying problems. The rats were sacrificed 3–7 months after construction of the reservoir. There was a significant dilatation of the reservoir with a 26-fold increase in the mean reservoir volume. Morphometric studies of the smooth muscle in the intestinal wall revealed an increased thickness of the circular and longitudinal layers after construction of the reservoir (p<0.001). The number of muscle cell nuclei per section in samples of the ileal reservoir was reduced (p/s<0.01), whereas the mean size of the individual nuclei was greater (p/s<0.001). These results indicate that the enormous dilatationof this ileal reservoir is related to a clear hypertrophy of the smooth muscle layer. Whether there is a concomitant hyperplasia remains to be studied.     

Personality traits that can affect adaptation after colectomy. A study of 10 patients treated for ulcerative colitis either with proctocolectomy and ileostomy or with colectomy, proctomucosectomy, ileal pouch and ileoanal anastomosis

The purpose of the present study was to examine how specific personality traits and/or conflicts could serve to predict nonadaptability after surgical treatment for ulcerative colitis. In order to define the scope of the study and to establish more specific hypotheses, retrospective studies were conducted by in depth interviews with 10 patients. Five of the patients had undergone colectomy with proctomucosectomy and ileal pouch ad modum Parks, and 5 had had a proctocolectomy with ileostomy ad modum Brooke. The interviews were recorded on tape and analyzed by the interviewer as well as by an independent evaluator. In addition, the operating surgeon provided an independent evaluation of the patients' post-operative adaptation. There was good consensus between both sets of assessments based on interviews as well as between the interview diagnoses and the surgeon's evaluation. There was no observed correlation between prevailing psychiatric diagnostic categories and postoperative adaptation. Psychological factors, such as a discrepancy between body image and body ideal, alexithymic characteristics, abnormal aggression patterns, extensive physical exercise and muscular training, showed varying degrees of negative correlation with postoperative adaptation.     

Reconfirming the role of life events for the timing of depressive episodes. A two-year prospective follow-up study

BACKGROUND: Since the 1960s the association of stressful life events and depression seemed to be firmly established. However, a few recent studies did not confirm those earlier findings. One of the reasons discussed for the inconsistencies was the sampling of milder depressed neurotic out-patients in the earlier studies vs. more severely ill endogenous type in-patients in recent studies. METHODS: This investigation was carried out with 50 consecutively admitted in-patients with endogenous depression according to ICD 9 and unipolar major depression according to DSM-III-R as ascertained by SCID. The control sample consisted of 26 healthy volunteers. Life events and chronic distressing life conditions were recorded with the Munich Interview for the Assessment of Life Events and Conditions (MEL) every 3 months over a period of 2 years along with psychopathological symptoms and recurrencies. Hence the design was prospective in the sense that life events were recorded for one 3-month cross-section, the depressive reaction for the subsequent one. BDI scores taken at the respective cross section were used to control for depressive bias of the subjective part of the patient's life event evaluation. RESULTS: Three months prior to the index hospitalization patients were more often affected by life events and conditions than controls. The number of stressful conditions prior to the index hospitalization indicated the time to relapse after discharge. Controls showed more desirable positive conditions than patients. Relapse patients suffered more often stressful life events and conditions than non-relapsers 3 months prior to their relapse. Multivariate analysis indicates that the cumulative number of life events within the 2-year course is the best predictor of the BDI score at the end of the follow-up period. Limitations: Since the subjective component of life event assessment by MEL displayed a higher impact on the course of depression than the objective part of the assessment, confounding of subjective ratings, attributional styles, and depressive symptoms may be a problem although controlled for in this study. CONCLUSION: The results support the importance of stressful life events and chronic distressing conditions for the 2-year course and outcome of major depression in an in-patient sample. Since the overall consistency of significant results was more pronounced in the subjective than in the objective part of the MEL the results fit best a circular pathogenetic model of interactions between life events, their individual evaluation by the patient, and depressive symptoms.     

Isolated ileal erosions in patients with mildly altered bowel habits. A follow-up study of 28 patients

This study evaluated 28 patients to characterize the morphologic features associated with typical Crohn disease (CD). All patients had similar complaints, an endoscopically normal colon, and small isolated, aphthoid erosions in the terminal ileum. The mean length of follow-up was 5.8 years. Of 28 patients, 25 (89%) were female (mean age, 32.3 years). Four patients were ingesting nonsteroidal anti-inflammatory drugs. All 28 lesions were morphologically similar, with focal lamina propria edema, mild active inflammation, and crypt disarray. Most had a lymphoid aggregate within the region of edema. Erosion was identified histologically in 21 cases. Following colonoscopy, symptoms resolved in all 28 patients. Typical, full-blown CD developed in 8 patients (29%) after a mean interval of 3.6 years. CD lesions were morphologically identical to non-CD lesions. Most focal ileal erosions in patients with mildly altered bowel habits are idiopathic and clinically insignificant. They represent early CD in approximately 30% of patients. The interval between initial examination and typical CD can be long. Pathologists should remain diagnostically vigilant when examining ileal biopsy specimens obtained from patients with previous abnormal ileal biopsy findings, regardless of the interval. Persistent, mild morphologic abnormalities have a high likelihood of being CD.     

Antinucleosome antibodies in SLE: a two-year follow-up study of 101 patients

We prospectively analyzed the diagnostic sensitivity and specificity as well as the clinical relevance of antinucleosome antibodies in SLE. One hundred and one consecutive SLE patients were followed for 3 years. Three serial serum samples from each patient were tested for antinucleosome antibodies by ELISA (optimum cut-off value 10 U/ml), and for anti-dsDNA antibody (by ELISA and IIF on Crithidia luciliae), and anti-dsDNA avidity (by Scatchard plot analysis). Sera from 100 healthy individuals (HI), 35 patients with systemic sclerosis (SSc), 30 with primary Sj?gren's syndrome (SS), 20 with rheumatoid arthritis (RA) and 48 with infectious diseases (ID), were assayed as controls. SLE activity and damage were evaluated using the ECLAM score and the SLICC/ACR index. At baseline, antinucleosome antibodies were found in 87 patients with SLE (86.1%), in 8 patients with SSc (22.8%), in 2 HI (2%), and in 1 ID (2.1%). The sensitivity and specificity of antinucleosome testing for SLE were 86.1% and 95.3%, respectively. The prevalence of antinucleosome antibodies in SLE was significantly higher than that of anti-dsDNA antibodies, with a correlation between them. No relevant relationship was found between antinucleosome antibodies and disease features, including renal involvement, disease activity, and disease damage. During follow-up, no significant variation was observed in antinucleosome level, nor in anti-dsDNA antibody level or avidity. We conclude that antinucleosome antibodies are commonly found in SLE. Low antibody levels can be detected in SSc, whereas medium/high levels are highly specific for SLE. Their clinical relevance during the disease course and utility for monitoring the individual patient seem to be poor.     

Intestinal ganglioneuromatosis: mucosal and transmural types. A clinicopathologic and immunohistochemical study of six cases.

Six cases of intestinal ganglioneuromatosis (GN) included in this study reveal the occurrence of two morphologic patterns. Transmural GN was characterized by neural hyperplasia in all layers of the bowel wall with predominant involvement of the myenteric plexus. It was found in three patients affected by multiple endocrine neoplasia IIb. Mucosal GN, having predominant involvement of the mucosa without concomitant hyperplasia of the myenteric plexus, was associated with von Recklinghausen's disease, adenocarcinoma of the colon, and multiple adenomas with megacolon in one case each. Clinicopathologic correlations and review of the literature suggest that mucosal GN might represent a distinct entity with a lower morbidity rate than the transmural variant. Immunohistochemical stains reveal considerable heterogeneity. S-100 protein, neuron-specific enolase, and synapto-physin immunostaining followed the distribution of the nervous hyperplasia in the different intestinal layers as identified morphologically and allowed precise determination of the proliferating cells. Increased reactivity for vasoactive intestinal polypeptide, opioid peptides leu-enkephalin and met-enkephalin, and substance P was present in all cases with transmural involvement; mucosal GN showed normal reactivity for opioid peptides and focal increased staining for substance P (one case) and vasoactive intestinal polypeptide (two cases) in the lamina propria. Mild increased immunoreactivity for tyrosine hydroxylase was present in the myenteric plexus of four out of four cases. Histochemical determination of acetylcholinesterase, performed in one case of transmural type, demonstrated hyperplasia of parasympathetic fibers and neurons. Electron microscopic study of another case suggested the presence of several neurotransmitters. These results indicate that the physiopathology of GN is related to a complex hyperplasia of several peptidergic, cholinergic, and probably adrenergic nerve fibers instead of a selective overgrowth of one type of nerve fiber.     

A two-year prospective study of treatment compliance in patients with schizophrenia.

The study is a prospective investigation of the factors associated with treatment compliance in 61 patients discharged from hospital with a ward diagnosis of schizophrenia. All cases were classified using reliable diagnostic criteria and all were followed up for two years. Compliance was assessed by inspection of records and by analysis of urine. Sociodemographic factors and illness variables were unrelated to compliance. Some aspects of a patient's insight and attitude, namely, a belief that medication had helped during the admission, a stated willingness to take treatment after discharge and a generally optimistic outlook, were associated with improved compliance. Other variables which showed such an association were the absence of the drug side-effect akinesia, good previous compliance and voluntary, as opposed to compulsory, admission to hospital.     

Rabbit model for mucosal immunity in the bowel: I. Establishment of virus-infected ileal loops

An animal model was designed for use in studies of initial cellular immune responses to virus infection of the intestinal mucosa. The animal chosen was the New Zealand White rabbit and the mucosal site the subterminal ileum, isolated in a Thirty-Vella loop. The antigen used was parainfluenzavirus type 3, which would normally be destroyed by bile salts if ingested. Loops approximately 20 cm in length, each containing at least one Peyer's patch, were exteriorised through left paramedian stomata. Atrophic changes began to appear in the loops by 7 days, but no observable diminution in their associated lymphoid tissues was evident. The genesis of parainfluenzavirus type 3 infection in the loops was monitored by assay of sequential loop washings for infectious virus and in fluorescent antibody studies of cells from infected loop epithelia. Infectious virus was recovered for up to 13 days after inoculation and specific intracytoplasmic immunofluorescence was detected in loop epithelial cells. There was little serological evidence of systemic spread of the virus. A localised cellular immune response against parainfluenzavirus type 3 was mounted in the lymphoid tissues associated with the infected loops by day 14, but was not detected in systemic lymphoid tissues. No reactivity was detected in rabbits given inactivated virus via their loops or in those receiving infectious virus intravenously. This model appears to be capable of generating mucosal cellular responses to infection and may therefore be suitable for further studies in this field.     

Medial closing-wedge distal femoral varus osteotomy: Symptoms and functional impact in cases of associated patellofemoral osteoarthritis. A two-year follow-up prospective pilot study

PurposeTo date, indications for distal femoral varus osteotomy (FVO) in cases of associated patellofemoral osteoarthritis (PFO) have yet to be clarified. The purpose of this prospective study is to assess the short-term symptoms, functional and radiological impact of a medial closing-wedge femoral varus osteotomy on the patellofemoral joint in patients with valgus deformities who are afflicted with lateral tibiofemoral osteoarthritis (LTFO) associated with PFO.MethodsFourteen patients (15 knees) received a medial closing-wedge femoral varus osteotomy. The functional impact of an FVO on the patellofemoral joint was assessed based on the KOOS-PF (Knee Injury and Osteoarthritis Outcome Score-Patellofemoral Subscale), the Kujala score and the patellofemoral symptoms. Realignment of the patella was measured by the Merchant's patellofemoral congruence angle. The pre- and post-operative symptoms and functional scores were compiled prospectively and compared two years after the surgery.ResultsThe Kujala patellofemoral functional scores and the KOOS-PF showed considerable improvement with a differential of + 37.5 points ± 20.4 and + 42.7 points ± 19.3 (p < .01) respectively. The average Merchant's congruence angle went from 8.8° laterally to 3.6° medially, resulting in medialization of the patella, with a significant difference (p < .01). Based on the specific clinical analysis of the patellar joint, preoperative J-sign was identified in 26.7% of patients (n = 4) and was not found during postoperative examination (p = .1). Preoperative apprehension test was identified in 33.3% of patients (n = 5) against 13.3% (n = 2) after surgery (p = .39). Preoperative pain extension test was identified in 40% of patients (n = 6) against 20% during postoperative clinical analysis (p = .43).DiscussionAlthough the threshold of significance for patellofemoral symptoms was not reached, the medial closing-wedge femoral varus osteotomy induces a significant medialization of the patella (Merchant's congruence angle) and improves short-term functional results even with co-existing patellofemoral osteoarthritis. Due to the lack of specificity of the patellofemoral scores, patellofemoral osteoarthritis improvement is difficult to determine on its own, but does not represent a contraindication to FVO.Level of evidenceIII. Prospective clinical study.     

Stability of day and night sleep--a two-year follow-up of EEG parameters in three-shift workers.

Twenty rotating three-shift workers participated. Night and day sleep in connection with work on afternoon and night shifts, respectively, were recorded using 24-hour polysomnographic recording techniques. The procedure was repeated 2 years later. Both day and night sleep showed high significant correlations between years for rapid eye movement (REM) sleep, slow wave sleep (SWS-stages 3 + 4), total sleep time, slow wave energy, in the delta band (obtained via spectral analysis) and subjective sleep quality. Stage 2, stage 1, percent waking, sleep latency, SWS latency and REM latency were not correlated across years. None of the variables showed a significant difference between years. It was concluded that core variables of sleep show considerable interindividual stability across time and that a 2-year exposure to rotating shift work does not affect sleep in experienced shift workers.     

A follow-up study of the characteristics of dean's letters.

PURPOSE: To assess the content and quality of dean's letters since the publication of guidelines recommended by the Association of American Medical Colleges (AAMC) in 1989. METHOD: In 1998, the dean's letter writers at all 124 U.S. medical schools were surveyed. The questionnaire incorporated items from two previous surveys (1981 and 1992). In addition, samples of dean's letters (n = 451) from all U.S. medical schools for the graduating class of 1998 were rated based on the AAMC's guidelines. RESULTS: The response rate of the 1998 survey (66%) was lower than those of the two previous surveys (87% for 1992 and 85% for 1981). Schools that prepared letters that followed the AAMC's guidelines were somewhat more likely to have responded. According to the letter writers in 1998, close to 300,000 letters (approximately 1,050,000 pages total) were sent to residency directors, at an estimated cost of $26,000 per school. A total of 65% of schools produced adequate dean's letters based on the 1989 AAMC's guidelines, compared with 55% in 1992. Many schools were organizing the dean's letter in more readable formats, and more schools provided information that allowed for a comparison of students within the same school. CONCLUSION: The improvements in dean's letters are encouraging, but ten years after the AAMC's guidelines, 35% of U.S. schools still produce unacceptable letters. With the addition of the electronic submission of information, it is time to review further improvements to the dean's letter.