CD4+ immune response as a potential biomarker of patient reported inflammatory bowel disease (IBD) activity.

BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBDs) which are characterized by dysfunctional regulation of the immune system. A number of immune modifying drugs are used to treat CD and UC. Therapy is adjusted largely on the bases of subjective reports of disease activity and non-specific laboratory tests. Identification of a single or combination of immune markers of disease activity could be useful to select and monitor therapeutic responses. However, to date no reliable quantitative associations between IBD activity and laboratory measures of immune function have been identified. This study was designed to evaluate the usefulness of a commercially available laboratory measure of CD4(+) immune function, the Cylex® ImmuKnow®, as a surrogate marker of IBD activity. METHODS: Adult IBD patients with either CD (N=55, 27 males, mean, SD age=38.5, 11.5 years) or UC (N=45, 24 males, mean, SD age=41.7, 15.4 years) were enrolled. Patients both in clinical remission and with active disease provided responses to structured, validated questionnaires (CDAI and HBI for CD patients and SCCAI for UC patients) used to monitor IBD activity. Whole blood and plasma samples were collected to quantify various markers of disease status including routine cell counts and differentials (CBCs), CRP, and albumin (Alb), as well as CD4(+) immune response (Cylex® ImmuKnow®, N=98). Results were compared between all IBD patients as well as between CD and UC subgroups. RESULTS: There was a good correlation between the results of CDAI and HBI scores (r=0.811, p<0.01, Spearman-Rho) but HBI scores correlated slightly better (r=0.575, p<0.001) than the CDAI's (r=0.449, p=0.001) with CD patients' reported perception of their general condition. CDAI and HBI scores categorized 12/55 versus 36/55 of CD patients respectively as having active disease. SCCAI scores indicated that 25/45 of UC patients had active disease. Cylex® results (in ng/mL of ATP) were increased in 74/98 IBD subjects (≥525 ng/mL) but were influenced by the use of systemic corticosteroids (SCS) and infliximab. There were weak but statistically significant Spearman-Rho correlations between Alb concentrations and both CDAI (r=0.413, p=0.002) and HBI (r=0.325, p=0.017) scores as well as between CRP values and HBI scores (r=0.331, p=0.016). Correlations between CRP and both CDAI and SCCAI scores and between Alb and SCCAI scores were not significant and there were no significant positive associations between any of the three clinical scores and Cylex® results. CONCLUSIONS: CD4(+) immune responses were significantly elevated in IBD patients whether or not they were in clinical remission but were influenced by treatment. There were some significant correlations between the clinical scores and CRP or Alb but not with the CD4(+) results. Both other clinical scoring systems, other measures of immune function, and CD4(+) immune response changes over time should be examined to see if this or other laboratory measures of immune response are predictive of actual disease activity or symptoms in CD or UC patients.

Persistent effects of cognitive-behavioral stress management on cortisol responses to acute stress in healthy subjects--a randomized controlled trial.

Psychosocial stress leads to a release of cortisol. While this psychoneuroendocrine response helps to maintain physiological as well as psychological equilibrium under stress, exaggerated secretion of cortisol has been shown to have negative effects on somatic health and cognitive functioning. The study set out to examine the long-term effects of cognitive-behavioral stress management training on cortisol stress responses in healthy men and women. Eighty-three healthy subjects were randomly assigned to cognitive-behavioral stress management (CBSM) training or a control condition. Four months after the CBSM, 76 subjects underwent a standardized psychosocial stress test. Salivary cortisol responses were assessed repeatedly before and after the stress test. Subjects in the CBSM group showed significantly reduced cortisol stress responses. With regard to gender, this effect was observed in both men and women. However, the magnitude of the CBSM effect on cortisol responses was smaller in women than in men. Use of oral contraceptives in women influenced the cortisol response, but did not have an impact on the CBSM effect on cortisol. The results show that the previously reported attenuation of cortisol stress responses through CBSM persists and are observable in both men and women. Since stress-induced alterations of hypothalamus pituitary adrenal axis functioning are discussed to be involved in the onset and maintenance of both somatic and psychiatric conditions, similar interventions could be used for prevention and therapy of these detrimental stress effects.

Granulocyte function in patients with L-ferritin iron-responsive element (IRE) 39C-->T-positive hereditary hyperferritinaemia-cataract syndrome.

BACKGROUND: Hereditary hyperferritinaemia-cataract syndrome (HHCS) is an autosomal dominant trait associated with mutations in the iron responsive element (IRE) of the ferritin light-chain (L-ferritin) gene. Patients typically show elevated serum ferritin concentrations without iron overload and a bilateral cataract. Hyperferritinaemia can be associated with granulocyte dysfunction in patients with thalassemia beta and in haemodialysis patients. The effect of increased L-ferritin levels on granulocyte function in patients with HHCS is unknown. MATERIAL AND METHODS: We examined glucose uptake, oxidative burst, chemotaxis, phagocytosis, apoptosis and intracellular calcium concentrations in polymorphonuclear leucocytes (PMNLs) of five affected members of a family with HHCS and in five healthy individuals matched for age and gender. RESULTS: Mutation testing revealed a 39C-->T transition in IRE in all five patients with HHCS. Serum ferritin levels of patients ranged between 907 and 2030 microg L(-1), respectively. In comparison with healthy individuals, PMNLs of patients with HHCS showed a significant increase in PMA-mediated stimulation of the oxidative burst, as well as a significantly higher stimulation of glucose uptake but no difference with respect to chemotaxis, phagocytosis, apoptosis and intracellular calcium concentrations. CONCLUSION: In summary, our study suggests that hyperferritinaemia in patients with IRE 39C-->T-positive HHCS is associated with activation of PMNLs but not with disturbance of fundamental PMNL function.

[Quality control after hernia operation]. / Qualitätskontrolle nach Hernienoperationen.

QUESTION: An important feature in surgery is the absence of wound infection after elective sterile operation. That's why the VQG (Verein zur Qualitätssicherung im Gesundheitswesen) from Berne recommends as a standard control the surveillance of wound healing, where hernia repair is suited for a tracer operation [1]. METHOD: In our hospital retrospectively all 106 patients of the year 1999 were asked by a questionnaire, 3 month after operation, if their wound healed primarily or if they noticed any signs of infection or even had to be re-operated again. RESULTS: Most hernias were indirect (71) or direct (11), followed by umbilical hernias (11), epigastric or incisional hernias (4), femoral hernias (2). The majority of procedures were a Shouldice repair (43), followed by mesh implantation according to Lichtenstein (33) or Bassini repair (15). 14 times an umbilical or epigastric hernia was operated by Mayo's method. One Stoppa operation was performed. 7 Hernias were incarcerated at the time of operation. 51 hernias were on the right, 41 on the left side, 5 on both sides. Mean age of patients was 52.9 years; mean duration of hospital stay was 4.42 days. After Shouldice repair hospital stay was 3.9 days with an average patients age of 48.3 years, after Bassini 5.41 days (mean age 46.4 years), after Lichtenstein repair 5.23 days (mean age 66.0 years). 82 (77.4%) from 106 patients returned the questionnaire. 67 (81.7%) were completely satisfied, 11 (13.6%) mentioned minor problems. So 95.1% had a normal primary wound healing without infection. There was no correlation between wound healing, type of hernia, age, hospital stay, surgeon or method of operation. In the same study other complications occurred (e.g. 5% recurrences of hernias, nerve lesions), that could not be integrated into the evaluation because they were excluded by definition. CONCLUSION: Studying the tracer "wound healing after groin hernia repair" allows an approximate follow-up for quality control with little expense. Because of the narrow point of view and the neglect of other complications in the same investigation we estimate the power of the result as limited.

Glucagon-producing neuroendocrine tumour associated with hypoaminoacidaemia and skin lesions.

A nine-year-old neutered female crossbred Bernese mountain dog was diagnosed with superficial necrolytic dermatitis and a glucagon-producing islet cell tumour. Laboratory findings included hyperglucagonaemia and hypoaminoacidaemia. The dog was euthanased because of progression of the disease, and necropsy revealed liver metastases of a neuroendocrine carcinoma with immunohistochemical expression of glucagon and somatostatin. This report represents a case of canine glucagonoma syndrome; the previously reported cases in dogs are also briefly described.

The phytoestrogens Genistein and Daidzein, and 17 beta-estradiol inhibit development of neointima in aortas from male and female rabbits in vitro after injury.

BACKGROUND: 17 beta-Estradiol and phytoestrogens are known to have beneficial effects on the cardiovascular systems of women. The exact mechanisms for how estrogens and phytoestrogens influence the cardiovascular system are not yet understood in detail. OBJECTIVE: The objective of this study was to investigate whether 17 beta-estradiol and the phytoestrogens Genistein and Daidzein have an effect on post-injury processes in vessel walls. METHODS: In this in-vitro experiment, the sex-specific effects of 50 micrograms/ml 17 beta-estradiol (equivalent to 180 mumol/l), and of the isoflavones Genistein (5 and 50 micrograms/ml, equivalent to 18.5 and 185 mumol/l), and Daidzein (5 and 50 micrograms/ml, equivalent to 19.7 and 197 mumol/l) on endothelium-denuded aortas from female and male rabbits after vascular injury were studied. Morphometry and immunohistochemistry were performed for quantitative and qualitative analysis. RESULTS: Neointimal cells were in part positive for alpha-actin staining of smooth muscle cells. Staining with 5'-bromo-2'deoxyuridine plus 2'-deoxycytidine showed that proliferative activity in the neointima had significantly decreased after 28 days for groups that had been treated with 50 micrograms/ml Genistein. Immunofluorescence staining for the expression of nuclear estrogen receptor protein in the arterial wall for aortic rings from female and male rabbits was positive. 17 beta-Estradiol, Genistein, and its analog Daidzein (with no protein tyrosine kinase activity) inhibited formation of neointima sex-independently at equivalent concentrations of 50 micrograms/ml. However, a concentration of 5 micrograms/ml Genistein decreased formation of neointima significantly for aortic rings from male rabbits only, whereas 5 micrograms/ml Genistein increased formation of neointima in rings from female rabbits, which corresponded to the increase in proliferative activity detected after 28 days. CONCLUSION: Genistein and Daidzein both inhibited proliferation at certain concentrations, so this effect is supposed to be independent from Genistein's protein tyrosine kinase activity. The antiproliferative properties of all three estrogens were observed in the absence of endothelium and therefore are independent from endothelium-mediated effects.

Effect of omeprazole treatment on plasma concentrations of the gastric peptides, xenin, gastrin and somatostatin, and of pepsinogen.

The peptide xenin 25 is a gastric mucosal constituent like gastrin, somatostatin and pepsinogen. Gastrin and pepsinogen plasma concentrations increase when the secretion of gastric acid is reduced by proton pump inhibitors. In the present investigation, treatment with omeprazole led to an increase in fasting and postprandial plasma concentrations of xenin, gastrin and pepsinogens A and C (P < 0.05, in each instance), whereas somatostatin plasma levels remained unchanged. Because subcutaneous injection of pentagastrin did not raise xenin plasma concentrations, a direct effect of gastrin on xenin production seems unlikely. This study indicates that xenin plasma concentrations are regulated by intragastric pH, as are those of gastrin and pepsinogen.

Gastroenteropancreatic effects of xenin in the dog.

Xenin is a 25 amino acid peptide detected in the gastric mucosa of various mammals. It has since been found in low concentrations in other tissues. Xenin plasma concentrations increase after meals. The present study reports some gastroenteropancreatic effects of this peptide in the dog. Intravenous infusion of 64 pmol/kg min synthetic xenin significantly inhibited pentagastrin-stimulated gastric acid secretion and stimulated exocrine pancreatic secretion of volume and protein. Further, intravenous infusion of xenin in a dose of 1.0 pmol/kg min stimulated jejunal motility in the anaesthetized dog. An intravenous infusion of 32 pmol/kg min xenin raised plasma concentrations of pancreatic polypeptide, vasoactive intestinal polypeptide, insulin and glucagon. The present experiments therefore indicate manifold bioactive properties of intravenously infused xenin in the dog, with jejunal motility the most sensitive target. Conclusions as to the physiological role of xenin cannot be drawn from the present experiments. The release of other hormonal peptides indicates a complex action of xenin.

[Abnormal increase in pancreatic polypeptide in the secretin-provocation test: hypoglycemia-induced?]. / Abnormer Anstieg des pankreatischen Polypeptids im Sekretin-Provokationstest: hypoglykämiebedingt?

Pancreatic polypeptide (PP) can be used as a marker for endocrine active tumors originating from the pancreas. After intravenous administration of secretin, individually divergent increases in plasma PP concentration can be observed hampering interpretation of the stimulation test. Under certain circumstances elevated basal PP concentrations can be observed. Besides age, renal insufficiency and diabetes, hypoglycemia can cause high PP levels. We therefore inquired whether in patients with atypically high increase of PP after secretin this increase could be caused by hypoglycemia during the secretin stimulation test. In order to test this hypothesis we prospectively determined the plasma glucose and insulin concentrations in addition to the routinely measured gastro-intestinal hormones in 19 patients referred for secretin provocation test. In the 16 patients in whom the increase of PP was not due to an endocrine active tumor or renal insufficiency, PP rose to 170 +/- 57 pmol/l (+/- SEM) 2 minutes after secretin administration. In parallel, plasma insulin concentration increased to 365 +/- 51 pmol/l 2 minutes after secretin. The maximal insulin concentrations correlated significantly with the PP concentrations observed at the same time (R = 0.73, p < 0.01). The mean glucose concentration, however, remained constantly between 4.8 +/- 0.3 and 5.2 +/- 0.3 mmol/l and there was no correlation between the peak plasma PP concentrations after secretin and the plasma glucose concentrations (R = 0.07). The minimal glucose concentrations observed were 3.3 mmol/l in three patients (30 minutes after secretin in 2 patients and 45 minutes after secretin in one). The mean plasma glucagon concentration rose to 22.5 +/- 4.1 pmol/l 10 minutes after secretin.(ABSTRACT TRUNCATED AT 250 WORDS)

[Gastrointestinal hormone profile in medullary thyroid carcinoma]. / Gastrointestinales Hormonprofil beim medullären Schilddrüsenkarzinom.

Medullary thyroid carcinoma (MTC) can be important for gastroenterologists because 20-30% of patients with MTC suffer from chronic diarrhea and the tumor is capable of producing--besides other bioactive substances--a multitude of gastroenteropancreatic hormones. Gastrointestinal hormone profiles of 5 patients with MTC were determined both basally and after intravenous stimulation with secretin and calcium respectively. Diagnosis of MTC was confirmed histologically or cytologically and by demonstration of elevated serum concentration of calcitonin both basally and after calcium stimulation. 4/5 patients had chronic diarrhea. Normal values or only borderline increases were found for the following hormones: vasoactive intestinal polypeptide (VIP), neurotensin, substance P, growth hormone releasing hormone (GRH), glucagon, neurokinin A, peptide YY, and pancreatic polypeptide. Somatostatin was elevated after calcium stimulation in 1/5 patients only. The main findings were increased basal concentrations for GAWK in 5/5 patients and elevated concentrations for gastrin-releasing peptide (GRP, human bombesin) after calcium stimulation in 4/5. Probably as a consequence of the GRP increase, an increase in gastrin occurred in parallel, indicating bioactivity of the GRP released from the tumor. Besides calcitonin as the main tumor marker for MTC, determination of GAWK and GRP seems to provide helpful additional markers in laboratory diagnosis of MTC. GRP determination after i.v. calcium infusion allowed identification of patients with normal basal plasma GRP concentration.

[Long-term follow-up of surgically treated intra-articular calcaneus fractures]. / Langzeitnachkontrolle operierter intraartikulärer Kalkaneusfrakturen.

Between 1980 and 1991 we treated 150 joint fractures of the os calcis with open reduction and internal fixation with a special AO-plate. In this report we show the results of 36 fractures in 33 patients after an average follow-up of 89 months (43-132). Patients got back their working ability between 4.6 and 5.6 months. At the time of the clinical control two third of the patients had a working ability of 100%. 4 patients changed their profession due to the poor result of the fracture. 12% of the cases ended in spontaneous or secondary arthrodesis of the lower ankle joint. One third of the patients need orthopedic supports or special shoes. 73% of the patients are satisfied with the result.

Risk factors and consequences of bacteriuria in non-catheterized nursing home residents.

BACKGROUND: There has been disagreement over the significance of bacteriuria in nursing home residents. METHODS: During an 18-month period, the risks and consequences of bacteriuria (BU) in 195 residents of a skilled nursing facility without indwelling catheters were examined. Clinical and epidemiologic data and urine for culture were collected every 2 weeks to identify risk factors, symptoms, and occurrences of BU. A mean of 23 cultures per resident was collected. RESULTS: Forty-three percent of the study population (35% of men; 47% of women) had "persistent BU" defined as > 10(5) cfu/ml of urine on > 25% of an individual's collected cultures. Women with persistent BU more frequently were incontinent of bowel and bladder (OR 5.3, 6.3, respectively), more likely to be functionally disabled (OR 3.2), to carry a diagnosis of dementia (OR 2.4), and less likely to have suffered a stroke (OR 0.40). Cancer (OR 6.5) was the only risk factor for persistent BU in men. The number of antibiotic courses prescribed, frequency of hospitalizations, and mortality rates were not significantly different between the two BU groups in either men or women. CONCLUSIONS: Persistent BU is common in nursing home residents. The association of bowel and bladder incontinence and functional disability with persistent bacteriuria suggests that treatment or prevention of these risk factors may prevent or decrease the incidence of bacteriuria. There was no evidence of significant adverse outcomes resulting directly from the bacteriuric state. Higher mortality in the bacteriuric group was the result of underlying functional debility and severity of illness rather than the presence or persistence of BU.

[The gamma nail--an ideal implant for treatment of unstable fractures in elderly patients]. / Der Gamma-Nagel--ein ideales Implantat zur Behandlung instabiler Frakturen bei alten Patienten.

Altogether we used the Gamma-Nail in 150 cases. We show here a series of 50 instable pertrochanteric femur fractures in very old patients which we treated with a Gamma-Nail. All cases started with full weight bearing at the 4th day after operation. A clinical and radiological control 12 weeks later shows good mobilisation of the hip in 70% of the cases. Shortening of the operated leg is rare in comparison of cases treated with a DHS. Two thirds of the patients returned after dismission of the hospital to the old social situation. The advantages in treating instable pertrochanteric femur fractures with the Gamma-Nail are immediate full weight bearing without risks of shortening of the operated leg and the closed reduction of the fracture.

[Stable interlocking intramedullary nailing of humeral fractures with the Seidel nail]. / Stabile Verriegelungsmarknagelung bei Humerusfrakturen mit dem Seidel-Nagel.

22 fractures of the humerus (15 traumatological, 7 pathological) were treated with the Seidel-Nail. The results after a follow-up between 4 and 20 months showed good mobility of the shoulder. As major complications two paresis of the radial nerve occurred. One disappeared spontaneously. The Seidel-Nail is a good implant for all kind of shaft fractures with an intact distal fragment of 5 cm and also for fractures of an intact humerus head.

[The gamma-nail as a resilient alternative to the dynamic hip screw in unstable proximal femoral fractures in the elderly]. / Der Gamma-Nagel als belastungsstabile Alternative zur DHS bei der instabilen proximalen Femurfraktur des alten Menschen.

In a prospective randomised trial between September 1989 and June 1990 one hundred patients with per- and subtrochanteric fractures were consecutively treated by gamma-nail or DHS. The average age of both groups was about 80 years. The operation time for gamma-nailing was longer than for DHS implantation and also the postoperative blood loss was higher in the gamma-nail group. We found no difference of intraoperative blood loss, of perioperative lethality and in duration of hospital care. 90% of gamma-nail patients and 80% of DHS patients were successfully able to walk four days after operation with full weight bearing on the operated limb. Three patients in the DHS group with unstable fractures got cranial perforation of the cephalic screw mobilisation. Five patients of the gamma-nail group were reoperated, one case because of missed distal locking, one because of cranial perforation of the cephalic screw after varus dislocation of the proximal fragment. One patient suffered intraoperatively a proximal femur shaft fracture which was corrected during operation. In one case a wound hematoma was evacuated, an other patient needed secondary wound closure. Despite technical imperfection of implant and instruments, we conclude that the gamma-nail allows a very high percentage early and full weight bearing immediately after operation. So we consider that in the treatment of unstable pertrochanteric fractures of geriatric patients, the gamma-nail has proven to be more efficient than the DHS.

[Hook plate (so-called Balser plate) or tension banding with the Bosworth screw in complete acromioclavicular dislocation and clavicular fracture]. / Hakenplatte (sog. Balserplatte) oder Zuggurtung mit Bosworth-Schraube bei vollständiger Acromio-clavicular-Luxation und lateraler Claviculafraktur.

With both treatments good results are achieved. In cases treated with the hook-plate mobilisation and load putting are earlier possible. These patients are sooner back to work. The costs for the hook-plate are higher. To take out the hook-plate a second hospitalisation is necessary.