Activity and components of the granulocyte colony-stimulating factor pathway in hidradenitis suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory disease, characterized by painful, purulent and destructive skin alterations in intertriginous areas. OBJECTIVES: We investigated the expression and role in HS of granulocyte colony-stimulating factor (G-CSF), the regulator of neutrophil biology, as clinical signs of a neutrophilic granulocyte-driven inflammation are distinctive in the disease. METHODS: Skin and blood samples obtained from different cohorts of patients with HS and control individuals were assessed by RNA sequencing, quantitative polymerase chain reaction on reverse transcribed mRNA, and/or enzyme-linked immunosorbent assay. Mechanistic studies using keratinocytes, dermal fibroblasts, immune cell populations and skin biopsies were performed. RESULTS: G-CSF was abundant in HS skin, particularly in inflamed nodules and abscesses. Its levels even exceeded those found in other inflammatory skin diseases. Interleukin (IL)-1 and IL-17, respectively, induced G-CSF production by fibroblasts and keratinocytes. These effects were enhanced by tumour necrosis factor (TNF)-α and IL-36. Accordingly, fibroblasts separated from HS lesions expressed G-CSF, and IL-1 receptor antagonist reduced G-CSF levels in explanted HS skin. G-CSF blood levels positively correlated with severity of HS. Elevated lesional G-CSF receptor levels were linked to upregulation of molecules that contribute to prolonged activation of neutrophils by components of bacteria and damaged host cells [formyl peptide receptor 1 (FPR1), FPR2 and free fatty acid receptor 2 (FFAR2)], neutrophil survival [TNF receptor superfamily member 10C (TNFRSF10C/TRAIL-R3) and TNF receptor superfamily member 6B], kinases (tyrosine-protein kinase HCK and hexokinase 3), and skin destruction [MMP25 (matrix metalloproteinase 25) and ADAM8 (disintegrin and metalloproteinase domain-containing protein 8)]. G-CSF elevated the expression of FPR1, FFAR2, and TNFRSF10C/TRAIL-R3 in neutrophils and synergized with bacterial components to induce skin-destructive enzymes. CONCLUSIONS: The G-CSF pathway engages both tissue and immune cells, is strongly activated in HS lesions, and offers the opportunity to target the neutrophil-driven inflammation.

Computed tomography of the abdomen in Saanen goats: I. reticulum, rumen and omasum.

Computed tomography (CT) of the reticulum, rumen and omasum was carried out in 30 healthy goats and the images were compared to corresponding body sections obtained at postmortem. A multidetector CT was used to examine goats in sternal recumbency. A setting of 120 KV and 270 mA was used to produce 1.5-mm transverse slices from the fifth thoracic vertebra to the sacrum. Soft tissue structures were assessed in a soft tissue with a window width (W) of 400 Hounsfield Units (HU), and a window level (L) of 40 HU. The layering of the ruminal contents was assessed in an ingesta window with a W of 1500 HU and an L of 30 HU. After subjective evaluation, the size of the rumen and omasum, the thickness of the walls of the reticulum, rumen and omasum and the height of the gas cap and fibre and liquid phases of the rumen were measured. Fifteen goats were euthanised after CT examination, placed in sternal recumbency and frozen at -18 ºC for three to 10 days. Thirteen goats were then cut into 1.0- to 1.5-cm-thick transverse slices. One goat was cut in dorsal-plane slices and another in sagittal slices. The structures in the CT images were identified by using the corresponding anatomical slices.

Computed tomography of the abdomen in Saanen goats: II. liver, spleen, abomasum, and intestine.

This study describes the results of computed tomography (CT) of the liver, spleen, abomasum, small intestine and large intestine in 30 healthy Saanen goats. CT examination and anatomical slice preparation postmortem were performed as described in the first communication. After subjective evaluation of the CT images, various variables including the length/size, volume and density of the liver, spleen and gallbladder, the wall thickness of the abomasum, small intestine and large intestine and the diameter of the intestine were measured. The liver, spleen, abomasum, small intestine and large intestine could be accurately visualised using CT.

Computed tomography of the abdomen in Saanen goats: III. kidneys, ureters and urinary bladder.

This study describes the findings of computed tomography (CT) of the kidneys, ureters, urinary bladder and adrenal glands in 28 healthy female Saanen goats. CT examination and anatomical slice preparation postmortem was performed as described in the first communication. After subjective evaluation of the CT images, various variables including the size, volume and density of the kidneys, the diameter of the ureters and the size of the adrenal glands were measured. The targeted organs could be accurately visualised using CT and there was very good topographical agreement between the CT images and the anatomical preparations. The kidneys, renal vessels, ureters, urinary bladder and adrenal glands were seen in all goats.

[Ultrasonographic findings in a cow with extraskeletal chondroblastic osteosarcoma of the neck region]. / Ultraschallbefunde bei einer Kuh mit extraskelettalem chondroblastischem Osteosarkom am Hals.

This case report describes the clinical, ultrasonographic and pathological findings in a five-year-old Swiss Braunvieh cow with extraskeletal chondroblastic osteosarcoma of the neck region. The cow was referred because of a firm, non-painful swelling, approximately 25 cm in diameter, which was situated mainly on the lower left side of the neck but extended to the right. Ultrasonographic examination of the mass revealed a chambered structure containing echoic material that was separated by hyperechoic septa. Chondroblastic osteosarcoma was diagnosed based on histological evaluation of a biopsy sample, and the diagnosis was confirmed by postmortem examination.

Ultrasonographic findings in 63 cows with haemorrhagic bowel syndrome.

Cows with haemorrhagic bowel syndrome were examined by ultrasonography. A 5.0 MHz linear transducer was used to scan the right side of 63 standing, non-sedated cows. The small intestine was found to be dilated and had a diameter of 4.3 to 12.0 cm (mean [sd] 6.76 [1.78] cm), and there was markedly reduced or absent small intestinal motility in all the cows. In 22 (34.9 per cent) cows, empty poststenotic segments of small intestine were seen in addition to empty prestenotic intestine. In 12 (19 per cent) cows, the intestinal lumen contained localised hyperechoic material consistent with blood clots. Fluid with or without fibrin was seen between intestinal loops in 39 (61.9 per cent) cows. Accumulation of ingesta in the abomasum and sometimes in the omasum and rumen was seen in 14 (22.2 per cent) cows. Ultrasonography was considered to be a useful tool for the diagnosis of ileus. However, this imaging modality could be used to make a definitive diagnosis of haemorrhagic bowel syndrome only when a blood clot was seen in the intestinal lumen.

[Ultrasonographic findings in a goat with ascites due to a mesothelioma]. / Ultraschallbefunde bei einer Ziege mit Aszites infolge Mesotheliom.

The aim of this case report was to describe the clinical, ultrasonographic and postmortem findings in a goat with a mesothelioma. The most striking clinical sign was marked bilateral distension of the abdomen caused by ascites. Other signs included abnormal general condition, weight loss, hypothermia and increased heart rate. Ultrasonographic examination revealed accumulation of a massive amount of hypoechoic fluid in the abdominal cavity and nodular lesions on the peritoneum, omentum and wall of the omasum. Based on the clinical and ultrasonographic findings, a tentative diagnosis of ascites attributable to neoplasia was made, and the goat was euthanized. Postmortem examination confirmed the diagnosis, and based on the results of histological examination, a mesothelioma was diagnosed.

[Ultrasonographic and computed tomographic findings in a goat with mediastinal lymphocytic thymoma]. / Ultraschall- und CT-Befunde bei einer Ziege mit Thymom im Mediastinum.

This case report describes the clinical, sonographic, computed tomographic and pathological findings in a 9-year-old goat with mediastinal lymphocytic thymoma. The goat was referred to the Department of Farm Animals because of weight loss and dyspnoea. The lead clinical findings were increased heart rate, increased respiratory rate and heart sounds heard only on the right side. Ultrasonographic examination revealed a massive amount of fluid and an echogenic corrugated mass ventral to the lungs in the thoracic cavity on the left side. Computed tomography showed that the mass was very large and diffusely mineralised. A tentative diagnosis of mediastinal neoplasia was made, and the goat was euthanized. Postmortem examination revealed a cauliflower-like, pedunculated tumour, which occupied the entire left thoracic cavity and displaced the left lung. Based on histological evaluation, the tumour was diagnosed as a lymphocytic thymoma.

Sonographic findings in an alpaca with Mycobacterium kansasii infection.

This case report describes the clinical, ultrasonographic and postmortem findings in an alpaca with Mycobacterium kansasii infection. The alpaca was referred because of chronic weight loss and weakness. The results of clinical examination, haematology and serum biochemistry were not diagnostic. Ultrasonography of the liver revealed multiple, hyperechogenic lesions with a diameter of 1 to 3 cm. Histological evaluation of a liver biopsy sample showed acute, multifocal, suppurative, necrotising hepatitis. Despite treatment with antibiotics, the alpaca died. Postmortem examination revealed nodular to coalescing lesions in the liver, lungs, mediastinum, pleura and greater omentum, which could not be differentiated macroscopically or histologically from lesions caused by tuberculosis. Ziehl-Neelsen staining showed massive numbers of rods within epithelioid macrophages, which were identified as Mycobacterium kansasii by polymerase chain reaction analysis.

An unusual cause of traumatic reticulitis/reticuloperitonitis in a herd of Swiss dairy cows nearby an airport.

This report describes the findings in five cows from one dairy herd, in which all 31 cows were slaughtered or euthanised because of traumatic reticuloperitonitis. All the cows had numerous thin sharp pieces of metal attached to a magnet in the reticulum, giving the magnet a hedgehog-like appearance. Investigation revealed that the cattle had eaten forage harvested from a field immediately adjacent to an airport. The snow was cleared from the airport runways with a machine that had a wire-bristle brush attachment. Mechanical wear resulted in numerous wire bristles breaking and these were blown with the snow onto the field in question. The wire then became accidentally incorporated into the hay and grass silage at harvest the next summer and was ingested by the cattle in the fall and winter. To prevent further cases, approximately 200 tonnes of hay and grass silage contaminated with wire were discarded and 30 hectares of the 50-hectare field were cultivated and re-sown. The wire-bristles of the snow plow were replaced with plastic bristles. The cost of this and the livestock loss was several hundred thousand Swiss Francs.

Influence of patient position in myocardial SPECT on the diagnosis of CHD.

AIM: Of the study was to show that changing patient position from supine to prone results in improved specificity of myocardial SPECT (MS). METHODS: We examined the influence of patient position in MS on the diagnosis of coronary heart disease (CHD) in 151 patients. By using a Tc-99m-labeled compound (Tetrofosmin, Myoview, Nycomed, Amersham) examinations could be performed in supine and prone position within 35 minutes. Examinations were performed as a two-day stress-rest protocol with one gamma camera head and 180 degrees rotation without absorption correction. RESULTS: Semi-quantitative patient and heart phantom data show similar values for anterior and inferior wall in prone position in contrast to a lower count ratio of inferior to anterior wall in supine position. This demonstrates the importance of patient position with respect to artifacts specificity. Changing patient position from supine to prone mainly improves diagnostic specificity for CHD in the inferior wall in men (from 58% to 90%) and in the anterior wall in women (from 80% to 93%). Sensitivity is the same for both techniques. CONCLUSION: Changing patient position from supine to prone significantly improves diagnostic specificity while sensitivity remains unchanged.

Effectiveness of digitoxin versus trichlormethiazide/amiloride in congestive heart failure NYHA class II/III and sinus rhythm.

The effects of digitoxin and/or diuretic agents were investigated in patients with congestive heart failure (CHF) in sinus rhythm with respect to changes in hemodynamic parameters, cardiac dimensions, and bicycle ergometric exercise capacity. In a randomized, double-blind study 16 male patients with CHF NYHA class II and III received a placebo for 1 week (baseline) and then were randomly allocated, double blind, to take either digitoxin (digitalis group, DI: N = 8) or trichlormethiazide/amiloride (diuretic group, DG: N = 8) for 3 weeks (VP I). The patients who were first treated with digitoxin received the diuretic agent for a further 3 weeks and vice versa (VP II). At baseline and after VP I and II, a physical examination, two-dimensional echocardiography, and bicycle ergometry were performed. Heart rate (HR), systolic (BPs), and diastolic (BPd) blood pressure at rest, and BPs and 50 watts, were not significantly changed during the observation period. HR at 50 watts was decreased in DI (11.5 +/- 10.1 beats/min.) after VP I and II, but not in DG. BPd was significantly reduced after VP II in DI (8.2 +/- 4.6 mmHg) and in DG (9.3 +/- 8.9 mmHg). DI presents at baseline significantly higher end-diastolic (LVEDV) and end-systolic (LVESV) left ventricular dimensions, whereas left atrial diameter (LA) and stroke volume (SV) and ejection fraction (LVEF) were not significantly different. After VP I, a significantly decreased LA was found in DI, but not in DG. After VP II, all cardiac dimensions were significantly reduced compared with the baseline in DI, whereas in DG only a decrease in LVESV was found. SV was significantly increased in DI, but not in DG after VP I, SV and LVEF were significantly improved in DI and in DG after VP II. Exercise capacity did not change significantly in DI and DG. Digitoxin in combination with trichlormethiazide/amiloride is effective in reducing primarily enlarged left atrial and left ventricular dimensions, and is sufficient to improve the impaired systolic left ventricular function in CHF of NYHA class II and III in sinus rhythm. However, a significant increase in exercise capacity was not found. Treatment with digitoxin seems to be more relevant as a monotherapy with trichlormethiazide/amiloride.

[Sports in the heart rehabilitation group--experiences with ambulatory rehabilitation at home]. / Sport in der Herzgruppe--Erfahrungen zur ambulanten kardialen Rehabilitation am Wohnort.

Regular physical exercise has shown to be beneficial for patients with cardiovascular disease. Therefore cardiac rehabilitation in Germany is continued for years after hospital discharge in outpatient cardiac exercise groups which meet twice a week under the guidance of a physician and a sports instructor. Before participation cardiac patients have to be examined including exercise tests and echocardiography for assessment of contraindications for exercise therapy as well as individual exercise capacity. Patients are assigned to two groups with different levels of exercise intensity according to their symptom-free work-capacity (cutoff level 1 W/kg). During exercise sessions sports-specific forms of exercise such as stretching, aerobic exercise or ball games are accompanied by psychosocial elements such as stress management. This global approach is intended to improve cardiovascular risk factors, cardiac function, and work capacity as well as to stabilize the patient psychologically in order to accelerate social integration. Recently these groups have opened towards patients after cardiac transplantation or with severe heart failure. Therefore, cardiac exercise groups play a central role in cardiac rehabilitation long after the acute cardiac event.

Highland mountain hiking and coronary artery disease: exercise tolerance and effects on left ventricular function.

Physical exercise has become a well-established concept in the secondary prevention of coronary artery disease. We investigated the exercise requirements of extensive highland mountain hiking (8.7 km, 470 m to 1220 m over sea level, average incline 8.5%, mean walking velocity < 3 km x h-1) in 11 regularly exercising male patients with history of MI and stable coronary artery disease (CAD; mean age +/- SD:61.0 +/- 3.9 yr) and 9 age-matched male healthy controls (CO; mean age +/- SD:61.2 +/- 5.0 yr). All subjects underwent continuous ECG monitoring; arterial blood pressure and blood lactate concentrations were measured several times during mountain hiking. Before and after exercise, cardiac dimensions and functions were assessed by two-dimensional echocardiography and Doppler echocardiography. The mean exercise levels for heart rate and blood lactate were compared with the corresponding data of a multistage upright cycle ergometry. Clinical manifestations of coronary insufficiency, left ventricular myocardial dysfunction, or cardiac arrhythmias > Lown IIIb were not observed in any case. No significant differences in left atrial and left ventricular dimensions and no changes in systolic left ventricular function compared with the preexercise values were found after the mountain hike tour. Doppler echocardiography demonstrated significant changes in diastolic left ventricular function in CAD, but not in CO. The peak exercise intensity during mountain hiking was equivalent to a workload of 100-125 W (1.25-1.5 W x kg-1 body weight) in a multistage upright cycle ergometry. Extensive highland mountain hiking may be a low risk alternative within the outpatient rehabilitation program for secondary prevention of CAD for MI patients with a cycle ergometric exercise tolerance > 1.5 W x kg-1 body weight.

Effect of physical exercise and vitamin C on absorption of ferric sodium citrate.

The effect of physical exercise and vitamin C on iron absorption after oral iron administration was investigated. Eight healthy male subjects without iron deficiency were studied after administration of 100 mg ferric sodium citrate complex, 100 mg ferric sodium citrate complex with 200 mg ascorbic acid, and without iron intake, both under resting conditions and after a 1-h bicycle ergometer test at moderate exercise. Serum concentrations for iron, transferrin, and ferritin were measured before and 30 min, and 1, 2, and 4 h after each administration. Under resting conditions administration of 100 mg ferric sodium citrate led to a significant increase in serum iron concentrations. When ferric sodium citrate was administered with vitamin C, iron values increased significantly further. Ingestion of iron together with physical exercise resulted in a higher serum iron concentration than under resting conditions. The maximum increase, reached after 4 h, was 48.2% with exercise and 8.3% without. In combination with exercise, the addition of 200 mg vitamin C did not further increase serum iron concentration. In conclusion, 1 h of moderate exercise enhanced the rate of iron absorption. Under resting conditions the combination of ferric sodium citrate with vitamin C led to significantly increased postabsorption serum iron concentrations compared with iron administration without vitamin C.

The relationship between heart rate and QT interval during atrial stimulation.

The relationship between heart rate and QT interval was investigated during atrial stimulation (intrinsic effect of heart rate) in ten healthy male volunteers prior to and after administration of sotalol. The QT interval in the ECG (paper speed 200 mm/s) was determined at rates of 70, 85, 100, 115, 130, 145, and 160 beats/min and at pacing periods of 180 s each at 30, 60, 120, and 180 s. After a 15-minute period, 2.0 mg sotalol/kg body weight were administered iv and the stimulation protocol was repeated. The analysis of QT interval behavior reveals contradictions to the mathematical implications of Bazett's equation QT = QTc square root of 60/HR, so that the relationship between heart rate and QT interval is not adequately described under the given conditions. After examination of approaches reported in the literature and our own approaches, the expression QT = a e-b (HR-60) is used as a possibility differentially to describe the data by nonlinear regression. The parameters a and b may be interpreted as QT reference value and shortening parameter. The QT reference value a, a parameter in reference to heart rate of 60 beats/min, has a comparable significance to the expression QTc in the Bazett equation. A reduction in the shortening parameter b indicates whether substances influencing the QT interval additionally produce overproportional shortening of the QT interval with increasing heart rate. After administration of sotalol, an increase can be observed in both the QT reference value and also in the shortening parameter. The suggested approach is an attempt to provide a more precise assessment of the QT interval under different conditions.

Activation of sodium transport in human erythrocytes by beta-adrenoceptor stimulation in vivo.

Beta-adrenoceptor stimulation in vivo shifts potassium into the cells. To examine whether human erythrocytes participate in this process, we measured, along with serum or plasma potassium, the concentrations of potassium and sodium in erythrocytes. Beta-adrenoceptor stimulation was obtained by infusion of either fenoterol or hexoprenaline into 6 volunteers at rest or by endogenous amines provoked in 14 volunteers during ergometric exercise. Metabolic effects were followed at rest on serum insulin, C-peptide, and growth hormone levels, and during exercise on pH on lactate concentration in blood. The potassium concentration (mean +/- S.E.M.) dropped (p less than 0.01) in serum from 4.64 +/- 0.37 to 3.19 +/- 0.43 mmol x l-1 in the first hour at rest and in plasma from 5.70 +/- 0.93 to 4.63 +/- 0.45 in 90 sec directly after exercise. The concentration of erythrocyte sodium dropped (p less than 0.001) from 9.68 +/- 0.73 to 8.81 +/- 0.62 mmol x l-1 in cells and from 9.62 +/- 1.16 to 8.55 +/- 1.24 during exercise for 90 s, respectively. Changes in the concentration ratio of cellular sodium to potassium confirmed this sodium shift. An increased sodium transport in erythrocytes due to beta-adrenoceptor stimulation in vivo appears to complement a shift of serum potassium into the cells and may be mediated by the membrane-bound sodium, potassium ATPase.

Indices of cardiac function during treatment with betamimetic drugs (fenoterol and hexoprenaline).

The limiting factor in the treatment of preterm labor by betamimetics is the effect of these drugs on heart rate and cardiac action. In this paper we compare these effects produced by hexoprenaline and fenoterol, which are both beta-sympathomimetic drugs now in clinical use. As indices of cardiac action we measured the pre-ejection period (PEP), the left ventricular ejection time (LVET) and their sum, namely total electromechanical systole (QS2) by thoracic impedance cardiography. In 20 individual tests, seven subjects were given both hexoprenaline and fenoterol on separate occasions in a dose relationship of 1 : 12.5. We found a relation between PEP/LVET on the one hand and the Heather-index (an impedance specific parameter of response to stress) on the other. Both parameters represent inotropic effects in cardiac action. With increasing betamimetic stimulation there was a decrease of PEP/LVET (-23% for hexoprenaline and -29% for fenoterol) and an increase in the Heather-index (+98% for hexoprenaline and +117% for fenoterol). These results are not statistically significantly different and so we cannot agree with Lipshitz [19 ]who reported less beta 1-stimulation with hexoprenaline.

[Treatment of severe congestive heart failure with the beta-agonist fenoterol (author's transl)]. / Behandlung der schweren Herzinsuffizienz mit dem Beta-Stimulator Fenoterol.

The acute hemodynamic effects of the semiselective beta 2-stimulating compound Fenoterol were studied in 7 patients with severe congestive heart failure (IV NYHA) as a result of a low-output-syndrome of varying aetiology (coronary heart disease/cardiomyopathy). The continuous infusion of Fenoterol (2.5 micrograms/min for 60 min) induced the following changes in parameters of pump function: a slight but not yet significant fall of PCPm which we considered as a reference value of LVEDP from 24 +/- 9 to 20 +/- 6 mm Hg (13%); a highly significant increase in CI from 1.96 +/- 04 to 2.71 +/- 0.53 l/min . m2 (39%; p less than 0.001) and in SVI from 18.7 +/- 4.9 to 24.8 +/- 8.1 ml/m2 (32%; p less than 0.01); a clear reduction of TPR from 1374 +/- 427 to 977 +/- 282 dyn . s . cm-5 (28%; p less than 0.001). PVR was reduced from 245 +/- 158 to 192 +/- 85 dyn . s . cm-5 (n.s.). There were no significant changes in right ventricular filling pressure (15 +/- 8 to 15 +/- 9 mm Hg), mean arterial pressure (76 +/- 17 to 75 +/- 16 mm Hg) and heart rate (107 +/- 13 to 117 +/- 23 beats/min). The study indicates that the "selective" beta 2-agonist Fenoterol in severe congestive heart failure produces a significant improvement in pump function. We assume the increase in SV to be due to a positive inotropic effect -- caused by beta 1-stimulation -- and a reduction of impedance to left ventricular ejection by decrease in TPR -- caused by beta 2-stimulation. Thus Fenoterol seems to be useful in treatment of severe congestive heart failure with elevated TPR.

[Tocolysis with a beta-receptor stimulating compound in patients with WPW-syndrome. A casuistic report (author's transl)]. / Tokolyse mit einem beta-Mimetikum bei WPW-Syndrom. Ein kasuistischer Beitrag.

During a previous pregnancy supraventricular tachycardia complicated delivery in time in a woman with WPW-syndrome (Typ A) known since seven years. In the 34th week of the second pregnancy onset of preterm labor with a pelvic score of 7 and a tocolysis index of 5 was indication for tocolytic therapy. For protection against paroxysmal supraventricular tachycardia tocolysis with the semiselective beta 2-stimulating compound Fenoterol was started in combination with the beta 1-selective blocking compound Metoprolol. Tocolysis lasted 6 days without cardiac complications. Also during labor no tachycardia set on. The duration of tocolysis with Fenoterol/Metoprolol in this case was comparable with the duration of tocolysis reported for monotherapy with Fenoterol in similar obstetric states. In patients with WPW-syndrome the combination of a semiselective beta 2-simulating compound with a beta 1-blocking agent seems to offer a new possibility for tocolytic therapy.