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T Scheinin

Publications and source records attributed to T Scheinin.

At least 19 recordsLinked to original sources
PubMed2006

Laparoscopic rectal prolapse surgery combined with short hospital stay is safe in elderly and debilitated patients.

BACKGROUND: We report the results of patients treated from January 2000 to June 2004 for full-thickness rectal prolapse with trans-abdominal surgery in Helsinki. METHODS: Sixty-five of 75 patients were treated laparoscopically, with a 6% conversion rate. Ten patients were operated on openly. Half of the patients were scored as American Society for Anesthesiologists III or IV. RESULTS: The operation time was similar in the laparoscopic and the open rectopexy procedures (p = 0.15), whereas laparoscopic resection rectopexy was more time-consuming compared to the open procedure (p = 0.007). Intraoperative bleeding during laparoscopic surgery was minimal in comparison to open surgery (p = 0.006). Patients treated laparoscopically had a shorter median hospital stay than those treated with an open procedure (rectopexy, 3 and 7 days, respectively; resection rectopexy, 4 and 7.5 days, respectively) (p < 0.00001). There was no mortality and minor morbidity. During follow-up, there were two prolapse recurrences. All surgical techniques improved fecal continence considerably. Eighty-four percent of rectopexy patients and 92% of resection rectopexy patients considered the surgical outcome to be excellent or good. CONCLUSIONS: Both rectopexy and resection rectopexy cure prolapse with good results and can be performed safely in older and debilitated patients. The laparoscopic approach enables a shortened hospital stay and is well tolerated in elderly patients.

Adult↗
PubMed2003

Validation of the interleukin-10 knockout mouse model of colitis: antitumour necrosis factor-antibodies suppress the progression of colitis.

Advances in understanding pathogenesis and developing new therapies are hastened by the use of effective animal models of disease. In inflammatory bowel disease, such as Crohn's disease, a variety of models have been used, including the IL-10 knockout mouse. However, in order to be truly valuable, the models need to respond to existing therapy in a way which resembles the human disease. In the light of recent developments, in which refractory Crohn's disease responds well to anti-TNF antibody therapy, we set out to validate the IL-10 knockout model of Crohn's disease by examining its response to anti-TNF therapy. We developed a new scoring system for IL-10 knockout mice, similar to the Crohn's Disease Activity Index in humans, analysed stool samples for cytokines and compared the findings with histology. We found that anti-TNF antibody therapy starting at 4 weeks markedly ameliorated the disease, as judged by the clinical score or by histological analysis of the gut. Furthermore, analysis of stool samples for cytokines revealed a marked diminution of inflammatory cytokines, adding a further accurate measure of the improvement. This model may thus be useful for evaluating other therapeutic modalities of relevance to Crohn's disease.

Animals↗
PubMed2003

Local delivery of adenoviral vectors encoding murine interleukin 10 induces colonic interleukin 10 production and is therapeutic for murine colitis.

INTRODUCTION: Interleukin 10 knockout (IL-10-/-) mice spontaneously develop a Th1 T cell mediated colitis with many similarities to Crohn's disease. Daily injections of IL-10 are unable to induce remission in mice with established disease. In contrast, we have shown previously that intravenous administration of adenoviral vectors encoding IL-10 (AdvmuIL-10) induces hepatic IL-10 release and leads to long term disease suppression with profound systemic immunoregulatory changes. AIMS: To determine whether rectal delivery of AdvmuIL-10 induces localised colonic IL-10 expression without systemic immune suppression, and assess its therapeutic efficacy in IL-10-/- mice with established colitis. RESULTS: A single rectal infusion of 5 x 10(8) PFU AdvmuIL-10 to 10 week IL-10-/- mice resulted in a median level of 27.3 pg/mg IL-10 in colonic homogenates harvested one week later. IL-10-/- mice with established colitis treated with an enema of 5 x 10(8) PFU AdvmuIL-10 entered clinical and histological remission whereas empty cassette adenovirus (Adv0) or phosphate buffered saline (PBS) treated mice developed progressive disease. After four weeks, the histological score of AdvmuIL-10 treated mice (4.4 (1.5)) was significantly lower than that of Adv0 (11.1 (1.1); p<0.001) and PBS (10.9 (1.0); p<0.01) treated controls. In addition, the stool concentration of IL-1 beta over the four week experiment was significantly higher in mice treated with saline or Adv0 than in those treated with AdvmuIL-10 (p<0.01). CONCLUSION: Local AdvmuIL-10 therapy reverses colitis in IL-10-/- mice without the systemic effects seen after intravenous administration. Gene therapy strategies using adenoviral vectors encoding immunoregulatory cytokines may prove to be a potent approach to the treatment of chronic inflammatory diseases such as Crohn's disease.

Adenoviridae↗
PubMed2003

Local delivery of adenoviral vectors encoding murine interleukin 10 induces colonic interleukin 10 production and is therapeutic for murine colitis.

INTRODUCTION: Interleukin 10 knockout (IL-10-/-) mice spontaneously develop a Th1 T cell mediated colitis with many similarities to Crohn's disease. Daily injections of IL-10 are unable to induce remission in mice with established disease. In contrast, we have shown previously that intravenous administration of adenoviral vectors encoding IL-10 (AdvmuIL-10) induces hepatic IL-10 release and leads to long term disease suppression with profound systemic immunoregulatory changes. AIMS: To determine whether rectal delivery of AdvmuIL-10 induces localised colonic IL-10 expression without systemic immune suppression, and assess its therapeutic efficacy in IL-10-/- mice with established colitis. RESULTS: A single rectal infusion of 5 x 10(8) PFU AdvmuIL-10 to 10 week IL- 10-/- mice resulted in a median level of 27.3 pg/mg IL-10 in colonic homogenates harvested one week later. IL-10-/- mice with established colitis treated with an enema of 5 x 10(8) PFU AdvmuIL-10 entered clinical and histological remission whereas empty cassette adenovirus (Adv0) or phosphate buffered saline (PBS) treated mice developed progressive disease. After four weeks, the histological score of AdvmuIL-10 treated mice (4.4 (1.5)) was significantly lower than that of Adv0 (11.1 (1.1); p<0.001) and PBS (10.9 (1.0); p<0.01) treated controls. In addition, the stool concentration of IL-1beta over the four week experiment was significantly higher in mice treated with saline or Adv0 than in those treated with AdvmuIL-10 (p<0.01). CONCLUSION: Local AdvmuIL-10 therapy reverses colitis in IL-10-/- mice without the systemic effects seen after intravenous administration. Gene therapy strategies using adenoviral vectors encoding immunoregulatory cytokines may prove to be a potent approach to the treatment of chronic inflammatory diseases such as Crohn's disease.

Adenoviridae↗
PubMed2001

The prevention and treatment of murine colitis using gene therapy with adenoviral vectors encoding IL-10.

IL-10-deficient (IL-10(-/-)) mice develop colitis with many similarities to Crohn's disease. Daily IL-10 injections have a short systemic half-life and are unable to induce complete remission in IL-10(-/-) mice with established disease. In this paper, we investigate the duration, potency, and immunogenicity of gene therapy using an adenoviral vector encoding murine IL-10 (AdvmuIL-10). A single systemic injection of AdvmuIL-10 was sufficient not only to prevent the onset of colitis for at least 10 wk but also to induce clinical and histological remission in mice with established disease. In addition, AdvmuIL-10 diminished the systemic manifestations of disease, including elevated acute-phase proteins, as well as the local consequences of inflammation such as raised stool IL-1beta concentrations. Both IL-10 protein and the effects of secreted IL-10 were detectable for 10 wk after AdvmuIL-10 injection. Furthermore, the immunoregulatory effect of a single AdvmuIL-10 injection was manifest both by a reduction in TNF-alpha, IFN-gamma, and RANTES release from stimulated splenocyte cultures, and also by a change in the proportion of CD45RB(high/low) lymphocytes in the spleen compared with control mice. The delivery of AdvmuIL-10 resulted in a significantly diminished host antiadenoviral response compared with control adenoviral vectors. Thus, gene therapy strategies using adenoviral vectors encoding immunoregulatory and antiinflammatory cytokines may prove to be a potent approach for the treatment of chronic inflammatory disease. Antiinflammatory cytokine expression protects against immune responses directed at gene vectors.

Adenoviridae↗
PubMed2000

Laparoscopic repair of rectal prolapse: a prospective study evaluating surgical outcome and changes in symptoms and bowel function.

BACKGROUND: There have been few large series that have focused on the feasibility of the laparoscopic approach for rectal prolapse. This single-institution study prospectively examines the surgical outcome and changes in symptoms and bowel function following the laparoscopic repair of rectal prolapse. METHODS: In a selected group of 34 patients (total prolapse, 28; intussusception, six), 17 patients underwent laparoscopic-assisted resection rectopexy and 17 patients received a laparoscopic sutured rectopexy. Preoperative and postoperative evaluation at 3, 6, and 12 months included assessment of the severity of anal incontinence, constipation, changes in constipation-related symptoms, and colonic transit time. RESULTS: Median operation time was 255 min (range, 180-360) in the resection rectopexy group and 150 min (range, 90-295) in the rectopexy alone group. Median postoperative hospital stay was 5 days (range, 3-15) and median time off work was 14 days (range, 12-21) in both groups. There were no deaths. Postoperative morbidity was 24%. Incontinence improved significantly regardless of which method was used. The main determinant of constipation was excessive straining at defecation. Constipation was cured in 70% of the patients in the rectopexy group and 64% in the resection rectopexy group. Symptoms of difficult evacuation improved, but the changes were significant only after resection rectopexy. Two patients (7%) developed recurrent total prolapse during a median follow-up of 2 years (range 12-60 months). CONCLUSIONS: Laparoscopic-sutured rectopexy and laparoscopic-assisted resection rectopexy are feasible and carry an acceptable morbidity rate. They eliminate prolapse and cure incontinence in the great majority of patients. Constipation and symptoms of difficult evacuation are alleviated.

Adult↗
PubMed1999

Decreased expression of protectin (CD59) in gut epithelium in ulcerative colitis and Crohn's disease.

Without adequate protection, the cells of the human body would be susceptible to destruction by the complement system. The main defense against complement lysis is a molecule called protectin (CD59) that is widely distributed in human tissues. Because the complement system has been suggested to be involved in the pathogenesis of inflammatory bowel diseases, we examined the expression of protectin in the colonic epithelium of patients with ulcerative colitis or Crohn's disease and controls. Colorectal specimens from 6 patients with ulcerative colitis, 8 patients with Crohn's disease, and 4 controls were obtained from surgical resections. Frozen sections of the specimens were immunostained for protectin using the Bric 229 monoclonal antibody. The expression of protectin was found to be decreased in the epithelium of patients with ulcerative colitis. In patients with Crohn's disease, the epithelial expression of protectin was decreased in diseased areas of gut while the expression did not significantly differ from that in controls in macroscopically normal areas. There was no difference in the expression of protectin on vascular endothelium, mononuclear cells, or smooth muscle. The reduction in epithelial expression of protectin in patients with ulcerative colitis or Crohn's disease may render epithelial cells vulnerable to complement lysis and lead to the destruction of gut epithelium as seen typically in these diseases.

Adult↗
PubMed1998

Effect of temperature of insufflated CO2 during and after prolonged laparoscopic surgery.

BACKGROUND: Pneumoperitoneum with room temperature carbon dioxide (CO2) has been shown to decrease core temperature and urine output. METHODS: The effect of 37 degrees C (warm) and room temperature (cool) CO2 pneumoperitoneum on core temperature, urine output, and central hemodynamics was compared in 26 randomized patients undergoing prolonged laparoscopic surgery (>90 min). RESULTS: The core temperature (p < 0.05) and cardiac index (p < 0.05) were significantly higher after warm than after cool pneumoperitoneum. Urine output was significantly higher during warm (2.3 +/- 1.6 ml/kg/h) than during cool (0.9 +/- 0.7 ml/kg/h) insufflation (p < 0. 05). Two of 13 patients with warm and 11 of 13 patients with cool pneumoperitoneum needed mannitol to maintain adequate diuresis (p < 0.05). CONCLUSIONS: Warm insufflation probably causes a local vasodilation in the kidneys and may be beneficial to patients with borderline renal function.

Body Temperature↗
PubMed1996

Islet cell and glutamic acid decarboxylase antibodies and heat-shock protein 65 responses in children with newly diagnosed insulin-dependent diabetes mellitus.

Islet cell antibodies (ICA) were detected in 66% and glutamic acid decarboxylase (GAD) antibodies in 64% of children (n = 47) with newly diagnosed insulin-dependent diabetes mellitus (IDDM). Fifteen percent of the patients had neither GAD nor ICA antibodies. Responses to mycobacterial heat-shock protein 65 (Hsp65) were detected in all patients. There was a significant correlation between anti-GAD antibodies and proliferation of peripheral blood mononuclear cells to Hsp65, and between ICA and antibodies to Hsp65.

Adolescent↗
PubMed1996

Number of activated T-helper cells and NK cells in peripheral blood is decreased in severe Crohn's disease.

Monoclonal antibodies and flow cytometry were used to analyse the proportions of T-cell subsets and NK cells in blood of patients (n = 45) with Crohn's disease. In patients with severe activity disease decreased numbers of activated (CD25+CD4+) T-helper cells and NK (CD16+CD56+) cells were found, while in patients with low activity disease the numbers of activated T-helper cells were increased and the numbers of NK cells were similar to those in normal controls. Thus, 8% of T cells were CD25+CD4+ and 16% of mononuclear cells were CD16+CD56+ in patients with severe disease. In patients with quiescent disease, 11% of T cells were CD25+CD4+ and 26% of mononuclear cells were CD16+CD56+. The results suggest that disease activity may be reflected in the proportions of blood circulating mononuclear cells, perhaps because of accumulation of CD25+CD4+ T-helper cells and NK cells in the affected tissue during exacerbation of the disease.

Adolescent↗
PubMed1992

Anti-endothelial cell antibodies in insulin-dependent diabetes mellitus.

The prevalence of IgG class antibodies to endothelial cells (AECA) was studied in 136 young patients with insulin-dependent diabetes mellitus by an enzyme immunoassay using human umbilical cord vein endothelial cells. The patients were divided into four groups according to the time between diagnosis and study and their results were compared with those in control children and blood donors. AECA became progressively more frequent with the duration of diabetes, being 4% in diabetics tested within 2 weeks of diagnosis and reaching 34% after an average disease duration of 11.2 years. They were not more common in patients with neuropathy, retinopathy or nephropathy than in patients without these complications, but were associated with co-existing thyroid disease and IgA deficiency. The results suggest that in insulin-dependent diabetes mellitus AECA are associated with co-existing autoimmune disorders but not with diabetic microvascular disease.

Adolescent↗
PubMed1991

Frequencies of HLA-DR3, -DR4, -B8 and -Bw62 in diabetic children diagnosed between 1960 and 1990.

An analysis of the HLA-types of 351 children in whom a diagnosis of insulin dependent diabetes mellitus (IDDM) had been made between 1960 and 1990 revealed that although the frequencies of HLA-DR3, -DR4, -DR3/4, -B8 and -Bw62 were increased there was, depending on the year of diagnosis, a marked fluctuation in the frequencies of these HLA-antigens and in the frequency with which -B8 was associated with -DR3 and -Bw62 with -DR4 suggesting heterogeneity/variation in agents initiating/triggering IDDM.

Chickenpox↗
PubMed1990

Immune responses to insulin and lymphocyte subclasses at diagnosis of insulin-dependent diabetes and one year later.

Insulin induced proliferation of blood mononuclear cells, numbers of blood B and T cells, of blood lymphocytes bearing interleukin 2 receptors or HLA class II molecules were assayed at diagnosis and one year later in children with insulin-dependent diabetes mellitus (IDDM) and in healthy children. Insulin and islet cell antibodies were also studied. The numbers of lymphocytes expressing HLA class II molecules and NK cells were increased at diagnosis. T cells of the helper/inducer (CD4+) phenotype and interleukin 2 receptor positive lymphocytes were increased both at diagnosis and one year later. At diagnosis, insulin induced proliferation of blood mononuclear cells in 65% and one year later in 50% of the patients. Insulin antibodies were detected in 10% and islet cell antibodies in 90% of patients at diagnosis, and in 67% and 78%, respectively, one year later.

Adolescent↗
PubMed1989

Immune responses to insulin in patients with insulin-dependent diabetes mellitus.

To examine the effect of the major histocompatibility locus (HLA) and the duration of insulin-dependent diabetes (IDDM) on immune responses to insulin we assayed insulin induced proliferation of blood mononuclear cells and measured insulin antibodies in 66 patients with newly diagnosed and in 56 patients with longstanding IDDM matched for the age at onset (less than or equal to 15 years). In up to two thirds of the patients blood mononuclear cells responded to insulins by proliferation, and insulin antibodies were found in two thirds of patients with IDDM of long duration. Insulin proliferation or antibodies were not associated to any particular HLA antigen. The frequency of HLA-DR3 in patients with newly diagnosed IDDM was not increased unlike in patients with IDDM of long duration. In addition, HLA-B8 was associated to HLA-DR3 nearly twice as often in patients with newly diagnosed IDDM as in patients with longstanding IDDM. Thus, patients with IDDM of recent onset and diagnosed within the last three years more frequently responded to insulin by proliferation and less often had HLA-DR3 than patients with IDDM of long duration and diagnosed about 20-25 years earlier.

Adult↗