Simple faecal preparation and efficacy of frozen inoculum in faecal microbiota transplantation for recurrent Clostridium difficile infection--an observational cohort study.

BACKGROUND: Faecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile infection (rCDI). The finding of suitable donor, donor screening and preparation of faecal transplants are challenging in clinical work. AIM: To develop a practical protocol for preparing frozen transplants and to compare the efficacy of previously frozen and fresh faeces in treating rCDI. METHODS: Two healthy volunteers acted as universal donors for the frozen faecal preparations, which were prepared by suspending faeces into physiological saline, adding glycerol to a final concentration of 10% and storing at -80 °C. We compared the outcomes of patients with rCDI who had undergone FMT at colonoscopy and received infusion of previously prepared, freeze-stored faeces (n = 23) or fresh faeces from individual (n = 15) or universal donors (n = 11) (total n = 49). Clinical failure was defined as persistent or recurrent symptoms with a positive C. difficile toxin stool test, and a need for new therapy. RESULTS: At 12 weeks post-FMT, symptoms were resolved in 22 of 23 patients receiving previously frozen faeces, and in all 11 or 14 of 15 patients receiving fresh faeces from the universal or individual donors respectively (totally 25 of 26; P = ns, success rate 96%). Mild transient fever appeared for two patients receiving frozen faeces, but no other significant side effects were observed. 42 patients were followed up for a year post-FMT and the success rate was 88% in both fresh and frozen faeces groups. CONCLUSIONS: Preparation of frozen transplants simplifies the practical aspects of faecal microbiota transplantation without loss of efficacy or safety.

Colonic involvement in a patient with chronic lymphocytic leukaemia.

Various gastrointestinal infiltrations have been described in patients with chronic lymphocytic leukaemia (CLL). Here, we report a 69-year-old man with CLL and anaemia in whom the macroscopic finding of colonoscopy was normal, but the histological specimens revealed lymphocytic leukemia in ileum and in colon. If a CLL patient has any symptoms suggesting a possible GI manifestation of the haematologic disease or anaemia not explained by bone marrow infiltration or hemolysis, the diagnostic evaluation should include endoscopies with adequate biopsies.

Prevalence and distribution of gastric intestinal metaplasia and its subtypes.

BACKGROUND AND STUDY AIMS: Intestinal metaplasia, especially type III intestinal metaplasia is considered to be a precursor of gastric cancer and because of this it is suggested that these patients should be followed up by gastroscopy. Our aim was to find out the prevalence of intestinal metaplasia and its subtypes, the appearance of intestinal metaplasia in different parts of the stomach, and the correlation of intestinal metaplasia with other histological and endoscopic findings. PATIENTS AND METHODS: A total of 505 consecutive patients, with a mean age+/-S.D. of 54+/-16 years, had two biopsies taken from the antrum, two from the corpus, and, in 272 cases, two from the angulus of the stomach during routine upper gastrointestinal endoscopy. Histological specimens were examined according to the updated Sydney system and the ones with incomplete intestinal metaplasia were further stained for sulphomucin visualisation to divide these into types II and III. RESULTS: The overall prevalence of intestinal metaplasia was 19%. The prevalence of type III intestinal metaplasia was 2.8%, type II intestinal metaplasia was 4.4%, and complete intestinal metaplasia was 11%. Intestinal metaplasia was found most frequently in the antrum and also in the angulus. There was no type III intestinal metaplasia in the corpus. Intestinal metaplasia was found more frequently in patients with atrophic gastritis than in other patients (p < 0.01). The patients with type III intestinal metaplasia were older than the patients without intestinal metaplasia (mean age of 73 versus 51 years). None of the patients with a totally normal appearing stomach in upper gastrointestinal endoscopy had type II or type III intestinal metaplasia. CONCLUSION: The relatively high overall prevalence of intestinal metaplasia was found in patients referred for gastroscopy in a region of low prevalence of Helicobacter pylori infection and low incidence of gastric cancer. Intestinal metaplasia was most often found in the antrum and angulus. Type III intestinal metaplasia was more prevalent in older patients and intestinal metaplasia was more frequently found in patients with atrophic gastritis. Normal appearing endoscopic finding seems to exclude type II and III intestinal metaplasia.

The clinical value of taking routine biopsies from the incisura angularis during gastroscopy.

BACKGROUND AND STUDY AIMS: The incisura angularis is considered to be a typical site for Helicobacter pylori colonization, glandular atrophy, intestinal metaplasia, gastric ulcer, and gastric carcinoma. Our aim was to clarify whether it is necessary to biopsy the incisura angularis routinely during gastroscopy, in addition to obtaining biopsies of the corpus and antrum. PATIENTS AND METHODS: A total of 272 consecutive patients, with a mean age +/- SD of 53.8 +/- 15.5 years, had two biopsies taken from the angulus, two from the antrum, and two from the corpus of the stomach during routine upper gastrointestinal endoscopy. Histological specimens were examined according to the updated Sydney System for the classification and grading of gastritis. RESULTS: Of the 272 patients, 11 (4.0 %) showed chronic inflammation in the angulus biopsy only. Similarly, the angulus was the only biopsy site which showed neutrophil polymorph infiltration (or "activity") in two patients (0.7 %), intestinal metaplasia in 13 patients (4.7 %), atrophy in three patients (1.1 %), and H. pylori colonization in one patient (0.4 %). Dysplasia (intraepithelial neoplasia) was not found in any of the biopsied sites in any of the 272 patients. H. pylori was found in 39 of the 272 patients (14 %). Of the 272 patients, 120 patients showed abnormalities at the incisura angularis, 101 having gastropathy or erosions, and only 19 showing more specific macroscopic changes, the main ones being ulcer, ulcer scarring, and atrophy. Of the 152 patients with a normal-looking mucosa at the angulus, only six (3.9 %) showed the histological changes of chronic inflammation in the angulus alone. Similarly, the angulus was the only biopsy site which showed neutrophil polymorph infiltration in one patient (1/152, 0.7 %), and intestinal metaplasia in five patients (5/152, 3.3 %). Atrophy and H. pylori colonization were not seen exclusively at the angulus in any of the patients with a macroscopically normal-looking angulus. CONCLUSION: Based on our data, routine biopsy of the incisura angularis would provide little additional clinical information to that obtainable from antrum and corpus biopsies.

Biochemical markers of types I and III collagen and limited joint mobility in type 1 diabetic patients.

Limited joint mobility (LJM), a long-term complication of diabetes, has been shown to be associated with microvascular complications of diabetes. Connective tissue alterations may contribute to the development of LJM and other diabetic complications. We tested whether biochemical markers of types I and III collagen metabolism are associated with LJM in type 1 diabetes. We studied 28 male patients of mean age 43.4 years (SD=9.5) and with a duration of diabetes of 25.2 years (SD=9.7) years. LJM assessment included goniometric measurements of the joints and classification by Rosenbloom's method. We measured serum concentrations of aminoterminal propeptide of type III procollagen (PIIINP), carboxyterminal propeptide of type I procollagen (PICP) and carboxyterminal crosslinked telopeptide of type I collagen (ICTP); urinary excretion of crosslinked N-telopeptides of type I collagen (NTX) and deoxypyridinoline crosslinks (DPyr) was also measured. Although average serum PIIINP tended to be higher in subjects with moderate-severe LJM (3.1 +/- 1.3 microg/l) than in subjects with mild LJM (2.5 +/- 0.7 microg/l) or without LJM (2.6 +/- 0.4 microg/l), no significant association was found (p<0.27). Concentrations of the other collagen markers were not different in subjects with or without LJM. We conclude that synthesis and degradation of types I and III collagen in diabetic subjects with LJM did not differ from those without LJM to reflect changes in the biochemical markers of these proteins.

Biochemical markers of type III and I collagen: association with retinopathy and neuropathy in type 1 diabetic subjects.

AIMS: Connective tissue alterations may contribute to the development of diabetic long-term complications in eyes, kidneys and peripheral nerves. Collagen deposition may be increased in micro- and macrovascular disease in diabetic subjects. We tested whether biochemical markers of type III and I collagen metabolism are associated with retinopathy and neuropathy in Type 1 diabetes. METHODS: A total of 28 patients, mean age 43.4 +/- 9.5 (sd) and duration of diabetes 25.2 +/- 9.7 years, were studied. Stereoscopic colour fundus photographs were taken for assessment of retinopathy which was classified as no, background or proliferative. Concentrations of aminoterminal propeptide of type III procollagen (PIIINP), carboxyterminal propeptide of type I procollagen (PICP) and carboxyterminal cross-linked telopeptide of type I collagen (ICTP) in serum and urinary excretion of cross-linked N-telopeptides of type I collagen (NTX) and deoxypyridinoline crosslinks (DPyr) into urine were measured. RESULTS: Average serum PIIINP was higher in subjects with proliferative (3.2 +/- 1.1 microg/l) than without proliferative retinopathy (2.5 +/- 0.6 microg/l) (P = 0.03). Average serum PICP was higher in subjects without retinopathy (181.7 +/- 19.5 microg/l) than in subjects with background retinopathy (132.1 +/- 42.7 microg/l) (P = 0.02). Concentrations of other collagen markers were not different in subjects with or without retinopathy. No association between collagen markers and neuropathy was found. CONCLUSIONS: The increased synthesis of type III collagen, reflecting deposition of matrix and basement membrane connective tissue, may be involved in the pathogenesis of proliferative retinopathy in Type 1 diabetic subjects. On the other hand, we observed decreased synthesis of Type I collagen, which can result in weakened vascular integrity in subjects with retinopathy.

Intestinal type of thromboangiitis obliterans (Buerger disease) preceding symptoms of severe peripheral arterial disease.

The case of a 50-year-old man with intestinal type thromboangiitis obliterans (Buerger disease) is reported. Intestinal manifestations included stricture and perforation of the colon, and these preceded any symptoms of peripheral vascular disease. Only the histological examination was able to show that our patient had the intestinal type of thromboangiitis obliterans.

Diabetic complications are associated with liver enzyme activities in people with type 1 diabetes.

This study was performed to clarify if diabetic complications are associated with liver enzyme activities in type 1 diabetic outpatients. Elevated activities of serum aminotransferases are a common sign of liver disease and are observed more frequently among people with diabetes than in the general population. Many studies have shown an association between specific diabetic complications and disturbances in various tissues, such as diabetic nephropathy and cardiovascular diseases, but only limited data are available on the possible association between diabetic complications and liver function. We studied 28 patients with type 1 diabetes. Mean age was 43.4+/-9.5 (S.D.), and duration of diabetes 25.2+/-9.7. Limited joint mobility (LJM) was assessed by the Rosenbloom's method. Background and proliferative retinopathy, and peripheral symmetrical polyneuropathy were also assessed. Activities of alanine amino transferase (ALT), gamma-glutamyl transferase (GGT) and alkaline phosphatase (ALP) in serum were determined. The metabolic control of the diabetes was evaluated by the glycosylated haemoglobin A(1c) (HbA(1c)) level and lipid values were also measured. ALT activity was associated with LJM (P<0.01) and with neuropathy (P<0.01). Association between GGT activity and LJM (P<0.01) and neuropathy (P<0.01) were also found. GGT activity was also associated with the severity of retinopathy (P<0.01). None of these associations was explained by confounding effects of diabetes duration, age, body mass index (BMI), HbA(1c) or alcohol consumption. In conclusion, diabetic complications such as LJM, retinopathy and neuropathy are associated with liver enzyme activities independent of alcohol consumption, BMI and metabolic control of diabetes.

Dupuytren's disease in type I diabetic subjects: investigation of biochemical markers of type III and I collagen.

OBJECTIVE: To clarify whether biochemical markers of collagen type III and I metabolism show alterations in type I diabetic subjects with Dupuytren's disease (DD) compared to those without DD. METHODS: DD was assessed in a total of 28 type I diabetic subjects, mean age 43.4 +/- 9.5 (SD) and duration of diabetes 25.2 +/- 9.7 years. Concentrations of aminoterminal propeptide of type III procollagen (PIIINP), carboxyterminal propeptide of type I procollagen (PICP) and carboxyterminal cross-linked telopeptide of type I collagen (ICTP) in serum and excretion of cross-linked N-telopeptides of type I collagen (NTX) and deoxypyridinoline crosslinks (DPyr) into urine were measured. RESULTS: The prevalence of DD was 32% (9 of 28 diabetic subjects). Average serum ICTP was 2.7 +/- 0.8 micrograms/l in subjects without DD and 3.6 +/- 1.2 micrograms/l with DD (p = 0.0276). No significant association between other collagen markers and DD was found. The reference intervals of PIIINP and ICTP were exceeded only in 1 and 2 subjects, respectively, and they both had DD. CONCLUSION: The degradation of type I collagen might be increased in diabetic subjects with DD. The overall implication was that synthesis or degradation of type III and I collagen in diabetic subjects with DD did not differ enough from those without DD to reflect changes in the biochemical markers of type III and I collagen.

Limited joint mobility in non-insulin-dependent diabetic (NIDDM) patients: correlation to control of diabetes, atherosclerotic vascular disease, and other diabetic complications.

This study examined the association between limited joint mobility (LJM) and diabetic control, atherosclerotic vascular disease and other diabetic complications in non-insulin-dependent diabetic (NIDDM) patients. LJM was studied in 139 [age (mean +/- SD) 61.3 +/- 12.3 years] NIDDM patients. Limitation of several joints was examined with a goniometer and LJM was classified by the Rosenbloom method. The NIDDM patients were examined for the following diseases: history of myocardial infarction, coronary heart, cerebrovascular and peripheral vascular diseases. The diabetic complications, background and proliferative retinopathy, nephropathy, and neuropathy, were also assessed. The metabolic control of the diabetes was evaluated by the average glycosylated hemoglobin Alc (GHbA kappa) concentration and lipid values were also measured. Mean levels of GHbAlc were 8.9 vs. 8.2% (p < 0.05) in NIDDM patients with and without LJM. NIDDM patients with LJM had a 3.1- (95% confidence interval, 1.2-7.7) and a 4.0-fold risk (95% confidence interval, 1.2-13.0) for coronary heart and cerebrovascular disease respectively, when the confounding effects of age, duration of diabetes and control of diabetes were controlled using stepwise logistic regression analysis. Patients with LJM had a 9.3- (95% confidence interval, 1.1-79.0) and a 3.3-fold risk (95% confidence interval, 1.0-10.5) of proliferative retinopathy and nephropathy respectively, when the confounding effects of age and duration of diabetes were controlled, but the correlation disappeared when control of diabetes was included in the model. In conclusion, the presence of LJM is associated with the control of diabetes and with the presence of coronary heart and cerebrovascular diseases in NIDDM patients.

Dupuytren's disease: association with chronic diabetic complications.

OBJECTIVE: To evaluate the prevalence of Dupuytren's disease and its association with the clinical characteristics in subjects with type I (insulin dependent) and II (non-insulin dependent) diabetes. To examine the association between Dupuytren's disease and chronic diabetic complications. METHODS: We studied 297 patients with type I [age (mean +/- SD) 33.2 +/- 10.0 yrs] and 139 with type II diabetes [age 61.3 +/- 12.3 yrs]. We investigated the presence of Dupuytren's disease, limited joint mobility, and the following complications: retinopathy, micro- and macroalbuminuria, and somatic peripheral symmetrical polyneuropathy (neuropathy). RESULTS: The prevalence of Dupuytren's disease was 14% in type II patients; prevalence was the same in both sexes. Dupuytren's was associated with age and duration of diabetes in type I patients (p < 0.001). Its presence was significantly related to retinopathy, neuropathy, limited joint mobility, and shoulder capsulitis in type I and to macroalbuminuria in type II patients, by chi-squared test. However, all these associations, except to macroalbuminuria in type II subjects, disappeared when the confounding effect of age and duration of diabetes was controlled by logistic regression analysis. CONCLUSION: The prevalence of Dupuytren's was the same in type I and II subjects although type I subjects were younger. No sex difference of the prevalence of Dupuytren's was seen in patients with diabetes. The disease was associated with macroalbuminuria in type II subjects independent of time related variables. Other associations between Dupuytren's disease and diabetic complications were explained by time related variables in type I and in type II subjects.

Shoulder capsulitis in type I and II diabetic patients: association with diabetic complications and related diseases.

OBJECTIVE: To examine the association between shoulder capsulitis and chronic diabetic complications and diseases closely related to diabetes. METHODS: A cross sectional study in 291 type I [mean (SD) age 33.2 (9.9) years] and 134 type II [61.1 (12.4) years] diabetic patients. The presence of shoulder capsulitis, Dupuytren disease, and limited joint mobility was sought. The patients were assessed for background and proliferative retinopathy, nephropathy, autonomic neuropathy, and peripheral symmetrical somatic polyneuropathy. Diseases closely related to diabetes (hypertension, history of myocardial infarction, coronary heart disease, and peripheral vascular disease) were also recorded. RESULTS: Prevalence of shoulder capsulitis was 10.3% in type I and 22.4% in type II diabetic subjects. Shoulder capsulitis was associated with the age in types I (P < 0.01) and II (P < 0.05) diabetic patients, and with the duration of diabetes in type I patients (P < 0.01). Odds ratios for autonomic neuropathy in type I and type II diabetic subjects with shoulder capsulitis were 4.1 (95% confidence interval, 1.6 to 10.9) and 2.7 (95% CI, 1.1 to 7.0), respectively, after controlling for age and duration of diabetes. Odds ratio for history of myocardial infarction in type I diabetic subjects with shoulder capsulitis was 13.7 (95% CI, 1.3 to 139.5) after controlling for age, duration of diabetes, hypertension, and smoking habits. Other associations between shoulder capsulitis and diabetic complications, related diseases, and other hand abnormalities were fully explained by age and the duration of diabetes. CONCLUSIONS: Shoulder capsulitis is common in type I and type II diabetic patients. It is associated with age in type I and II diabetic patients and with the duration of diabetes in type I patients. It is associated with autonomic neuropathy in type I and II diabetic patients and with history of myocardial infarction in type I diabetic patients, independently of time related variables.

Limited joint mobility is associated with the presence but does not predict the development of microvascular complications in type 1 diabetes.

Previous cross-sectional studies have shown that limited joint mobility (LJM) is associated with microvascular complications in diabetic patients. This study was performed to see whether LJM predicts the development of other diabetic complications and which factors predispose to the development of LJM. A total of 206 Type 1 diabetic patients (mean age 30.0 +/- 9.5 (SD) years) was studied at baseline. The follow-up study was performed 5 years later in 167 of 206 (81.1%) patients. At the baseline the presence of LJM was assessed by asking patients to approximate the palmar surfaces of fingers in a praying position with fingers fanned and the wrists maximally flexed. LJM was confirmed by passive extension. At the follow-up LJM was first reassessed by the same method and then further studied by goniometer and classified by the method of Rosenbloom. The diabetic patients were assessed in terms of the following complications: background and proliferative retinopathy, peripheral symmetrical polyneuropathy, and clinical nephropathy. The prevalence of LJM was 52.9% at baseline. The odds ratio for proliferative retinopathy was 3.3 (95% confidence interval 1.2-9.5) and for neuropathy 2.5 (95% confidence interval 1.2-5.3) in diabetic patients with LJM compared to patients without LJM, when the confounding effect of the duration of diabetes, age and the body mass index was excluded. LJM developed in 30 patients during the 5-year follow-up (7% per year) and its development was not predicted by any of the microvascular complications at baseline. Proliferative retinopathy developed in 4 of 51 (7.8%) patients with and 3 of 63 (4.8%) patients without LJM at baseline (p = 0.3). Nephropathy developed in 11 of 56 (19.6%) patients with and 11 of 66 (16.7%) patients without LJM at baseline (p = 0.7) and peripheral symmetrical neuropathy in 14 of 45 (31.1%) and 20 of 64 (31.3%) patients respectively (p = 1.0). LJM did not predict diabetic microvascular complications or vice versa. Since LJM is associated with microvascular complications in cross-sectional studies, the clinical value of the assessment of LJM is limited to an orienteering examination in the clinical evaluation of a diabetic patient.

Dupuytren's disease in type 1 diabetic patients: a five-year prospective study.

OBJECTIVE: To clarify which are the underlying factors in the development of Dupuytren's disease (DD) in diabetic patients and to evaluate if the presence of DD can predict the development of diabetic complications. METHODS: A total of 207 type 1 diabetic patients [age (mean +/- SD): 29.9 +/- 9.5 years] was studied at baseline. A follow-up study was performed five years later in 166 patients. The presence of DD was examined and the patients were assessed in terms of the following diabetic complications: background and proliferative retinopathy, peripheral symmetrical polyneuropathy, and clinical nephropathy. RESULTS: The prevalence of DD was 4% at the baseline study. DD was significantly associated with the age of the patient and the duration of diabetes, but not with the age at the onset of diabetes, BMI or the control of diabetes. DD was associated with somatic peripheral symmetrical polyneuropathy (p < 0.01), a history of myocardial infarction (p < 0.01) and limited joint mobility (LJM) (p < 0.05), but all of these associations could be exclusively explained by the age of the diabetic patients and the duration of diabetes. DD developed in 17 new subjects (2% per year) during the five years of the study. The subjects' age and the duration of diabetes were associated with the development of DD. There was a predominance of the development of DD in women (p < 0.05), and in subjects with retinopathy (p < 0.05), nephropathy (p < 0.05), neuropathy (p < 0.05) or hypertension (p < 0.01), but these associations could also be exclusively explained by the time-related variables. The presence of DD at the baseline study did not predict the development of diabetic complications or hypertension when the confounding effects of age and the duration of diabetes were controlled by logistic regression analysis. CONCLUSION: This study shows that the patient's age and the duration of diabetes are the most important factors predicting the development of DD in diabetic patients. The associations between DD and diabetic complications were exclusively explained by the age and the duration of diabetes. The presence of DD did not predict the development of diabetic complications.

Limited joint mobility in type 1 diabetic patients: correlation to other diabetic complications.

OBJECTIVES: To examine the association between limited joint mobility (LJM) and complications of diabetes in adult patients with type 1 diabetes. DESIGN: Cross-sectional study in diabetic patients and healthy controls. SETTING: The study was performed at the department of medicine in Turku University Hospital (n = 103), a private diabetes outpatient clinic (n = 153) and the municipal health centre of Turku (n = 29), Finland. SUBJECTS: We studied 285 diabetic patients [age (mean +/- SD): 33.4 +/- 10.0 years] and 288 healthy nondiabetic controls [age (mean +/- SD): 32.3 +/- 9.2]. MAIN OUTCOME MEASURES: The limitations of several joints were examined with a goniometer. The diabetic patients were assessed in terms of the following complications: background and proliferative retinopathy, peripheral symmetrical polyneuropathy, autonomic neuropathy, impotence as well as clinical and incipient nephropathy; serum lipid values were also measured. RESULTS: The prevalences of LJM were 58% and 14% in diabetic patients and in healthy controls, respectively. The diabetic patients with LJM had a 2.8-fold risk of proliferative retinopathy [95% confidence interval (CI): 1.1-7.3] and a 3.6-fold risk of nephropathy (95% CI: 1.4-9.3) compared to patients without LJM, when the confounding effect of the duration of diabetes was excluded. LJM was not related to metabolic control of diabetes, microalbuminuria, autonomic neuropathy or impotence. The association between LJM and peripheral symmetrical polyneuropathy was exclusively explained by the duration of diabetes. The correlation between LJM and serum total and low-density lipoprotein cholesterol was dependent on the association between LJM and nephropathy. LJM did not relate to serum high-density lipoprotein cholesterol or triglyceride values. CONCLUSIONS: The diabetic patients with LJM had an increased risk of proliferative retinopathy and nephropathy compared to patients without LJM.