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Biomedical subjects

S Stenman

Publications and source records attributed to S Stenman.

At least 19 recordsLinked to original sources

High frequency of silent inflammatory bowel disease in spondylarthropathy.

OBJECTIVE: To search for an association between gut infection, gut inflammation, and spondylarthropathies. METHODS: Ileocolonoscopy was performed in 118 patients with various inflammatory and noninflammatory joint diseases and in 24 patients with uncomplicated acute bacterial gastroenteritis. RESULTS: Endoscopic lesions were more frequent in patients with spondylarthropathy (44%) compared with those with other inflammatory arthritides (6%; P = 0.001). Ileal changes were observed only in patients with spondylarthropathy (20% versus 0%; P = 0.01). Inflammatory bowel disease was the endoscopic diagnosis in 19% of the arthritis patients. Possible or definite Crohn's disease was diagnosed in 26% of patients with chronic spondylarthropathy, and ulcerative colitis in 1 patient with rheumatoid arthritis and in 1 with chronic uroarthritis. Histologic evidence of inflammation differed less distinctly than endoscopy findings between patients groups. There was no association of gut lesions with the use of nonsteroidal antiinflammatory drugs or with the presence of HLA-B27. CONCLUSION: Gut inflammation is frequent in patients with spondylarthropathy, and one-fourth of the patients who have chronic disease have early features of Crohn's disease.

Adolescent

Relationship between carbohydrate metabolism and serum insulin-like growth factor system in postmenopausal women: comparison of endometrial cancer patients with healthy controls.

Insulin is a major regulator of circulating insulin-like growth factor (IGF)-binding protein-1 (IGFBP-1), suppressing the hepatic production of IGFBP-1. Postmenopausal age, obesity, hypertension, and impaired glucose tolerance, which are known risk factors for endometrial cancer, are all associated with hyperinsulinemia and insulin resistance. In this study, we investigated the relationship among serum insulin, glucose, insulin-like growth factors (IGF-I and IGF-II), and IGFBP-, -2, and -3 in 32 nondiabetic postmenopausal women with endometrial cancer and in 18 healthy controls. The mean fasting levels of glucose and insulin were higher, whereas the mean basal IGF-I, IGF-II, and IGFBP-3 levels were lower in the endometrial cancer patients than in the healthy control subjects. The mean fasting IGFBP-1 and IGFBP-2 levels did not differ between the groups, and no correlation was found between fasting insulin and IGFBP-1 concentrations or between insulin and IGFBP-2 concentrations in either of the study groups. During an oral glucose tolerance test, the mean glucose levels at 1 and 3 h as well as the mean insulin level at 3 h were significantly higher in the endometrial cancer patients than in the controls, and the area under the glucose curve was larger in the first group. An oral glucose load resulted in a similar fall in serum IGFBP-1 levels in endometrial cancer patients and controls (51% and 55% at 3 h). When the cancer patients were divided into two subgroups according to the body mass index (kilograms per m2), the obese group had higher glucose and insulin indices than the nonobese group. No difference was found by the same measures in healthy controls. The fasting serum IGFBP-1 levels tended to be lower in the obese than in the normal weight subjects, but the difference did not reach statistical significance. In summary, these results provide preliminary evidence that the inverse relation between fasting insulin and IGFBP-1, well established in children and young adults, disappears in elderly women, although short term suppression by insulin still occurs. Further, our data indicate that in addition to carbohydrate metabolism, postmenopausal women with endometrial cancer have alterations in their circulating IGF system compared to controls.

Aged

Diagnostic significance of angiographically observed visceral aneurysms with regard to polyarteritis nodosa.

During a 10-year period, intraparenchymal aneurysms were found in 38 of 748 patients at selective abdominal angiography with magnification technique. According to strict criteria, 17 patients were classified as suffering from necrotizing vasculitis of the polyarteritis nodosa group (PAN), 7 from severe arterial hypertension, and 3 from rheumatoid arthritis. The diagnoses of 5 patients remained to be confirmed, and each of the remaining 6 patients suffered from various other diseases. PAN was diagnosed histopathologically in 2 patients without angiographic aneurysms. Based on the 156 patients in whom the indication for angiography was suspicion of arteritis, the angiographic diagnosis of PAN had a sensitivity of 89 percent and a specificity of 90 percent, a positive predictive value of 55 percent and a negative predictive value of 98 percent. The mean number of both renal and hepatic aneurysms was higher in patients with PAN than in the other patients (p less than 0.01 and p less than 0.05, respectively). Five PAN patients had numerous and large aneurysms, whereas the aneurysms of the other 12 PAN patients did not differ from those of patients with other diseases. Patients with PAN had renal infarcts more often than the other patients (p less than 0.05). Our findings suggest that visceral angiography is useful in establishing the diagnosis of PAN, but the angiographic finding of aneurysms is not pathognomonic.

Adult

Urinary excretion of kappa light chains in patients with diabetes mellitus.

The urinary excretion of kappa light chains, beta 2-microglobulin and albumin was examined in patients with newly diagnosed and long-standing insulin-dependent (IDDM) and non-insulin-dependent (NIDDM) diabetes mellitus, and compared to age-matched control subjects. Patients with IDDM diagnosed within two months, presented with normal albumin excretion, whereas the concentrations of beta 2-microglobulin and kappa light chain in urine were higher than in control subjects. The initiation of insulin therapy reduced, but did not completely normalize, the elevated rate of kappa light chain excretion. Patients with IDDM of long duration showed increased urine excretion of kappa light chains and albumin. In keeping with the findings in IDDM, patients with newly diagnosed NIDDM (within one year) showed increased urinary excretion of kappa light chains compared with control subjects. There was, however, no further increase in light chain excretion with longer duration of NIDDM. To study the effect of short-term hyperglycemia on urinary protein excretion, 12 normal subjects participated in a three-step hyperglycemic clamp study, during which their plasma glucose concentration was raised by +50, +125 and +300 mg/dl. The urine excretion of albumin and beta 2-microglobulin rose progressively with each hyperglycemic clamp step, whereas that of kappa light chain excretion was unaffected by hyperglycemia. We conclude that increased urinary excretion of kappa light chain is a consistent finding in all types of diabetes mellitus, and can be observed even when the albumin excretion is normal. Since the serum concentration of kappa light chain is normal in diabetes, the increased urinary excretion of kappa light chains must be of renal origin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Combined insulin-sulfonylurea therapy in treatment of NIDDM.

For the past few years, interest has focused on the combination of insulin and sulfonylurea in the search for effective treatments for non-insulin-dependent diabetes mellitus (NIDDM) patients who fail on oral hypoglycemic agents. Although several studies have demonstrated beneficial effects of such therapy in NIDDM patients, the average effect is small and is observed in only about half of the patients. However, there are several problems with most previous studies, including small sample size, selection of patients, and simultaneous use of several end points. First, residual beta-cell function has been considered to be a prerequisite for a beneficial effect of combination therapy. Therefore, most studies have failed to demonstrate improved glycemic control after adding sulfonylurea to insulin therapy in patients with insulin-dependent diabetes mellitus. Inclusion of patients with impaired beta-cell function will therefore attenuate the effect of combination therapy. Second, most studies have used glycemic control as an end point. Nevertheless, the insulin dose has been reduced by 20-30% to avoid hypoglycemia after adding sulfonylurea to insulin. Thus, the comparison has been made between treatments with a smaller insulin dose with sulfonylurea and a larger insulin dose without sulfonylurea. The patient most likely to benefit from combination therapy is slightly obese, has had NIDDM for a relatively short period, and has preserved beta-cell function. In such a patient, combined insulin-sulfonylurea therapy predominantly stimulates basal insulin secretion, resulting in more effective suppression of hepatic glucose production and lower fasting plasma glucose. The side effects are few, most notably more frequent but mild hypoglycemic reactions.

Diabetes Mellitus, Type 2

The effect of exercise on urinary excretion of different size proteins in patients with insulin-dependent diabetes mellitus.

To examine whether exercise-induced proteinuria in diabetes is dependent upon the size of the excreted protein, we measured urinary excretion of beta 2-microglobulin, kappa light chains, albumin and IgG before and after 20 min of moderate ergometer exercise in 34 patients with insulin dependent diabetes mellitus (IDDM) and in eight healthy control subjects. Seventeen patients with newly diagnosed IDDM and 17 patients (seven of which had elevated albumin excretion rate) with longstanding IDDM were studied. Exercise did not significantly influence protein excretion in control and newly diagnosed IDDM subjects. In contrast, exercise enhanced excretion of beta 2-microglobulin (p less than 0.05-0.01), kappa light chains (p less than 0.001), albumin (p less than 0.005-0.001) and IgG (p less than 0.01-0.001) in patients with long-standing IDDM independently of whether the patient had proteinuria in the resting state or not. In conclusion, proteinuria induced by moderate exercise is not observed in the early stages of IDDM, and is independent of the size of the excreted protein. Therefore, moderate exercise does not appear to influence the size selectivity of the glomerular capillary wall in patients with longstanding IDDM.

Adult

The expression of extracellular matrix and cytoskeleton in fused cells.

In the present paper results from our studies on the expression and regulation of the differentiated normal and transformed epithelial and fibroblastic phenotypes are reviewed. The expression of the extracellular matrix- and basement membrane-associated proteins, fibronectin and laminin, and different intermediate filament proteins were studied in different fused cells. Heterokaryons and cytoplasmic hybrids (cybrids) were formed by fusing normal or malignant epithelial cells with normal fibroblasts or malignant glial cells. No differences were observed in the expression of these phenotypic markers between unfused parental cells and the corresponding homokaryons. Thus, the fusion process itself does not cause changes in the expression of these phenotypic markers. In heterokaryons formed after fusion of normal or malignant epithelial cells with normal fibroblasts or malignant glial cells, two or even three different types of intermediate filaments could be co-expressed. Thus, no suppression of the expression of the various intermediate filaments is caused by the non-homologous parental cell. Expression of the extracellular matrix proteins, fibronectin and laminin, on the other hand, could be extinguished by cells and cytoplasts not expressing fibronectin matrix, such as transformed fibroblasts and HeLa cells. These results support the role of transacting regulatory factors controlling the expression of the different extracellular matrix proteins. Alternatively, the results can be explained by changes in the distribution and concentration of the extracellular matrix receptor proteins in the fused cells.

Animals

Effects of the combination of insulin and glibenclamide in type 2 (non-insulin-dependent) diabetic patients with secondary failure to oral hypoglycaemic agents.

The effects of combined insulin and sulfonylurea therapy on glycaemic control and B-cell function was studied in 15 Type 2 (non-insulin-dependent) diabetic patients who had failed on treatment with oral hypoglycaemic agents. The patients were first treated with insulin alone for four months. Five patients were given two daily insulin doses and ten patients one dose. During insulin treatment the fasting plasma glucose fell from 14.5 +/- 0.8 to 8.8 +/- 0.4 mmol/l and the HbA1 concentration from 12.6 +/- 0.4 to 9.2 +/- 0.2%. This improvement of glycaemic control was associated with a suppression of basal (from 0.31 +/- 0.04 to 0.10 +/- 0.02 nmol/l) and glucagon-stimulated (from 0.50 +/- 0.08 to 0.19 +/- 0.04 nmol/l) C-peptide concentrations. Four months after starting insulin therapy the patients were randomised to a four-month double-blind cross-over treatment with insulin combined with either 15 mg glibenclamide per day or with placebo. Addition of glibenclamide to insulin resulted in a further reduction of the fasting plasma glucose (7.9 +/- 0.5 mmol/l) and HbA1 (8.3 +/- 0.2%) concentration whereas the basal (0.21 +/- 0.03 nmol/l) and glucagon-stimulated C-peptide concentrations (0.34 +/- 0.06 nmol/l) increased again. Addition of placebo to insulin had no effect. The daily insulin dose could be reduced by 25% after addition of glibenclamide to insulin, while it remained unchanged when insulin was combined with placebo. The fasting free insulin concentration did not differ between the glibenclamide and placebo periods (28 +/- 6 vs 30 +/- 5 mmol/l).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral

Enhancement of radiation effects by alpha interferon in the treatment of small cell carcinoma of the lung.

The effects on lung tissue and tumor of natural human alpha interferon (IFN) and radiotherapy were investigated in a multimodality treatment program for selected patients with small cell carcinoma of the lung (SCLC). Interferon was given first as a single agent, then concomitantly with radiotherapy to 12 previously untreated patients with limited disease. At disease progression outside the chest, interferon was discontinued and combination chemotherapy was initiated. In the first series, 7 patients received a high interferon induction dose (800 X 10(6) IU i.v. over 5 days) followed by low-dose maintenance therapy (6 X 10(6) IU i.m. TIW), median total dose 1380 X 10(6) IU (range 794-2074). At local progression, split-course radiotherapy, 55 Gy/20 F/7 wk, was added to interferon therapy. In the second series, 5 patients received low-dose interferon from the start (6 X 10(6) IU i.m. daily) combined with twice-a-day fractionated radiotherapy 44 Gy/40 F/4 wk. Median total dose of interferon in this series was 698 X 10(6) IU (range 354-828). Tumor response and normal tissue reactions were evaluated by monthly chest X rays, 3-monthly CT scans, restaging bronchoscopies and by serial respiratory function tests. Autopsy specimens from both lungs within and outside the radiation field were systematically evaluated when available. After the completion of radiotherapy, there were 4/7 CR in the high-dose IFN group compared to 3/5 CR in the low-dose IFN group. Rapid shrinkage of huge tumor masses was observed. At 2 months post radiotherapy radiological grade III fibrosis occurred in 4/7 patients in the high-dose and 1/5 patients in the low-dose group. Lung function studies showed a significant decrease in diffusing capacity and in lung volumes. Seven patients died within 12 months from start of interferon treatment, one of them from treatment complication. At autopsy the tumor area was in most cases replaced by severe fibrosis. Outside the radiation field lung fibrosis was mild. Our results suggest enhancement of radiation effect by interferon with a possible dose and/or schedule dependence of interferon and radiotherapy and call for more clinical studies of IFN and radiotherapy in combination.

Carcinoma, Small Cell

Radiation pneumonitis and fibrosis following split-course radiation therapy for lung cancer. A radiologic and physiologic study.

Radiographic signs of radiation pneumonitis and fibrosis were assessed and pulmonary function monitored in lung cancer patients after two different split-course radiation therapy schedules, one with a rest interval of 3 weeks and the other with a rest interval of 5 weeks, the total radiation dose being the same in both treatments (55 Gy/20 fractions/7 or 9 weeks). Post-mortem findings were analysed when available. Spirometric measurement of vital capacity, determination of diffusing capacity for carbon monoxide (DL) and alveolar volume with the single breath technique, and determination of regional distribution of lung perfusion by two different techniques, radiospirometry and gamma camera digital display following intravenous injection of 133Xe, were carried out before and at various times after the completion of irradiation. Of the physiologic parameters, only DL showed a significant decrease 6 as well as 9 months post-treatment (p less than 0.05). No difference between the two treatment schedules could be shown with regard to grade or time pattern of radiologic changes or decrease in DL. The findings suggest that measurement of DL may be of value in monitoring patients included in research protocols for radiation therapy of lung cancer as well as in selection of patients for this treatment.

Aged

Collagens, laminin, fibronectin, and cytoskeletal composition of cells in syngeneic aortal vein grafts in the rat.

The supradiaphragmatic vena cava of the rat was transplanted to the abdominal aorta in syngeneic recipients. The cells and the connective tissue matrix of these grafts were studied 3 days to 12 weeks after transplantation by immunofluorescence staining of the cytoskeletal proteins desmin, vimentin, and myosin. The matrix proteins, collagen Types I and III, laminin, fibronectin, and fibrin(ogen) were similarly demonstrated. Blood coagulation Factor VIII was used as a marker for endothelial cells. Inflammatory cells invaded the graft during Week 1, but later on the grafts were crowded with cells containing vimentin. Intimal thickenings developed already after 1 week. Smooth muscle cells containing desmin proliferated in these thickenings. After transplantation collagen Type I increased in the graft, but collagen Type III rather decreased. During the phase of intense proliferation of smooth muscle cells the media contained a rich matrix of diffusely distributed laminin. The laminin of older grafts was confined mostly to the subintimal zone and to the intimal plaques.

Animals

Relation between serum group II pepsinogen concentration and the degree of Brunner's gland hyperplasia in patients with chronic renal failure.

Serum concentrations of group I and II pepsinogens (PG I and PG II) were determined in 15 patients with chronic renal failure. Gastroduodenoscopy with biopsy and acid secretion tests were also performed. Five patients had histologically confirmed severe Brunner's gland hyperplasia manifesting as multiple polyps in the duodenal bulb. Five patients had a mild form of Brunner's gland hyperplasia which was evident only by histological analysis. Five had no signs of such alterations. The three groups of patients were comparable in age, sex, mean level of serum creatinine, mean duration of dialysis treatment, distribution of non-dialysed and dialysed patients, and gastric histology. In patients with severe Brunner's gland hyperplasia the mean serum PG II concentration was significantly higher than in the other patients. Both the serum PG I and the serum PG II concentrations decreased after receiving a well functioning renal transplant in the two patients who underwent transplantation.

Adult

Chronic gastritis and gastric acid secretion in uraemic and renal transplant patients.

Upper gastrointestinal endoscopy with biopsies from the antrum, body and duodenum, as well as tests for acid secretion were performed on 43 uraemic patients, 17 women and 26 men, (mean age 49.7 years) and on 46 patients with well-functioning renal transplant received 10 months earlier (12 women and 34 men, mean age 40.6 years) in order to study the background of peptic lesions in uraemic patients. Eighty-nine age- and sex-matched subjects selected from a random population sample consisting of 434 persons served as a control group. All groups of renal patients were similar with respect to the prevalence and severity of antral or body chronic gastritis. Compared with control subjects their antrum had significantly less advanced chronic gastritis, which was due to the lack of atrophic changes. Furthermore, the gastric body tended to show fewer alterations than that of the controls. The acid secretion capacity in the renal patients decreased with the increasing severity of atrophic changes in the body mucosa. However, definite hypoacidity was found in some of the renal patients with normal body mucosa. Thus, a true "state of hypoacidity" seems to occur in chronic uraemia.

Adult

Tuberculosis of the colon in a kidney transplant patient.

A 58-year-old woman experienced recurrent fever episodes after kidney transplantation. She was treated with antibiotics because of suspicion of staphylococcus infection. Abdominal pain combined with haemorrhagic diarrhoea occurred eight months after transplantation. A barium enema revealed a stenotic process in the middle part of the ascending colon mimicking carcinoma, and hemicolectomy was consequently performed. Histological examination revealed tuberculosis with little granuloma formation and abundant acid-fast tubercle bacilli in the mucosa and submucosa, and only slight perigranulomatous reactions. The patient was successfully treated with triple antituberculous chemotherapy without deterioration of allograft function. Tuberculosis should be suspected in immunosuppressed patients suffering from pyrexia of unknown origin, even when chest X-ray is normal.

Colonic Diseases