Methylprednisolone enhances contraction of porcine femoral head epiphyseal arteries

The pathomechanism of steroid-induced femoral head necrosis is thought to be disturbed femoral head blood flow. We hypothesize that methylprednisolone increases vasocontraction of femoral head epiphyseal arteries, thereby reducing femoral head blood flow. Nine immature female domestic pigs were randomly selected from a group of 18 to receive 24-hour methylprednisolone treatment, whereas the nine remaining pigs received the placebo control in a blinded fashion. After sacrifice, lateral epiphyseal artery segments from the femoral heads were mounted as ring preparations on a small vessel myograph. Isometric active tension was measured in relation to cumulating doses of the vasoconstrictors noradrenaline and endothelin-1, and the vasodilator bradykinin. Vasocontraction to noradrenaline was not altered by methylprednisolone. Bradykinin elicited a concentration-dependent vasodilation which was lower in the corticosteroid-treated vessels. Vasoconstriction to endothelin-1 was stronger in the corticosteroid-treated vessels. Our data indicate that methylprednisolone enhances contraction of femoral head lateral epiphyseal arteries and may decrease femoral head blood flow. To our knowledge, this pathomechanic factor in femoral head necrosis has not been described before.     

Recurrent hemolysis-associated pseudoerysipelas of the lower legs in a patient with congenital spherocytosis

A 29-year-old patient presented with recurrent erythematous eruptions on both lower legs of 15 years' duration. Family history, along with clinical and laboratory examinations, revealed congenital hereditary spherocytosis and excluded other reasons for the erythematous eruptions of the lower legs. During two subsequent episodes, we detected increased hemolysis that disappeared concomittantly on spontanous resolution of the lesions. To our knowledge, this case is the first report showing a recurrent erythematous eruption on the lower legs in a patient with congenital hereditary spherocytosis. These eruptions might be caused by intermittent hemolysis-induced inflammation as a result of the increased osmotic fragility of the erythrocytes and may evolve to chronic leg ulcers later in life.     

Cytotoxicity of occupationally and environmentally relevant mycotoxins

Mycotoxins can cause various toxic effects in humans. Acute and chronic respiratory diseases were reported after inhalation of organic dust containing toxigenic moulds and mycotoxins, respectively. To gain first insights into health effects from airborne exposure to these compounds, five toxigenic airborne moulds of the genera Aspergillus and Penicillium collected at composting plants and eight reference mycotoxins were tested for cytotoxicity in four established cell lines as a surrogate of tissues known or suspected to be targets of toxic effects of mycotoxins. The known mycotoxins sterigmatocystin, fumagillin, verruculogen, penitrem A, and roquefortine C were detected in extracts of the moulds. All five extracts caused serious toxic effects in the cell lines. Sterigmatocystin caused a 80-fold higher toxicity in the A-549 lung cell line compared to Hep-G2 liver cells indicating a specific susceptibility of A-549 to this agent. Since only a minor part of the toxic effects of the extracts in A-549 cells and--to a lesser extent--in the other cell lines could be explained by contents of the identified mycotoxins, the presence of additional mycotoxins or other toxic principles is assumed in the mould extracts. However, the detected mycotoxins in the mould extracts and their distinctive cytotoxicity support the hypothesis that mycotoxins may be involved in the aetiology of lung diseases due to the inhalation of organic dust.     

Efficacy and tolerability of an ulcer compression stocking for therapy of chronic venous ulcer compared with a below-knee compression bandage: results from a prospective, randomized, multicentre trial

OBJECTIVE: To investigate the possibility of improving healing rates in ulcus cruris venosum by using an ulcer compression stocking (U-Stocking) (Venotrain ulcertec) as compared to compression bandages. RESEARCH DESIGN AND SETTING: Prospective, multicentre, open-labelled, randomized, active-controlled study with blinded assessment of the primary endpoint. Sixteen phlebology outpatient clinics in Germany or the Netherlands or German medical practices specialized in phlebology. PATIENTS AND METHODS: 134 patients with venous leg ulcers entered the study. Among others, patients with infected ulcer or obesity were excluded. 121 patients were eligible for primary efficacy analyses. U-Stocking or bandages applied for at least eight hours per day and for up to 12 weeks. The primary endpoint was the healing rate after 12 weeks as assessed by planimetric measures. The secondary outcome variables were time to healing, changes in ulcer size (planimetry), experience of use and patient compliance. MAIN OUTCOME MEASURES: Therapy with the U-Stocking produced a significantly higher rate of complete healing of 47.5% (29/61) versus 31.7% (19/60) with bandages, 1-sided p = 0.0129 [CI: 95% for differences: 4.3% to 28.5%]. Mean time to healing was 46 days in both groups. Time required for application of the U-Stocking was a mean of 5.4 min (SD 5.4) versus 8.5 min (SD 6.5) for bandages, p = 0.0001. Around three patients in each treatment group were affected by serious adverse events. All treatment-related adverse events are known for compression therapy. CONCLUSIONS: The U-Stocking was superior to bandages in compression therapy for venous ulcer. This is of significance to new treatment standards as well as to future studies of longer term therapy (> 12 weeks) for unhealed ulcers or prevention of recurrence.     

Chemoembolization of rat liver metastasis with microspheres and gemcitabine followed by evaluation of tumor cell load by chemiluminescence

An orthotopic, isogenic rat model was used to determine the potential of chemoembolization (CHE) for reducing the tumor cell load of a diffusely metastatic liver. Seven days after injecting CC531-lac-Z cells intraportally to male WAG/Rij rats, tumor positive animals were treated by injection into the hepatic artery with solvent (n=17), degradable starch microspheres (DSM, 30 mg/kg; n=16), DSM plus 5-fluorouracil (5-FU, dosages: 90, 60, and 40 mg/kg) or DSM plus gemcitabine (Gem, dosages: 100, 80, 50, and 10 mg/kg). After 3 more weeks the experiment was terminated, the livers were weighted and the number of CC531-lac-Z cells per liver was determined. Injection of DSM reduced the tumor cell load by 21% (T/C%=79), the combination with 5-FU caused a stimulation of growth at 40 mg/kg (T/C%=291; n=10), but effected dose-dependent reductions in tumor cell number at 60 mg/kg (T/C%=86; n=16), and 90 mg/kg (T/C=19; n=17). None of these effects was significantly different from controls. The combination of DSM plus Gem was toxic at the highest dose (100 mg/kg), but well tolerated and highly effective at 80 mg/kg (T/C%= 16; n=12), 50 mg/kg (T/C%=9; n=12), and 10 mg/kg (T/C%=26; n=14). These results were significantly different from controls (p<0.05), respectively. In summary, the comparison of CHE with 5-FU or Gem shows that the efficacy of Gem in reducing the hepatic tumor cell load was significantly higher and its therapeutic ratio was greater than that of 5-FU.     

Evolution of myelofibrosis in chronic idiopathic myelofibrosis as evidenced in sequential bone marrow biopsy specimens

Although the new World Health Organization (WHO) classification acknowledges "prefibrotic" phases, progression of myelofibrosis in chronic idiopathic myelofibrosis (cIMF) is controversial because there are only a few studies about sequential biopsy specimens, and they yield conflicting results. The conflicting results might be due to a mixture of different degrees of myelofibrosis and therapy regimens within the respective groups studied. To prove this hypothesis, we studied sequential bone marrow biopsy specimens from patients with cIMF and compared 3 groups with different degrees of myelofibrosis at initial diagnosis with a group of patients with primarily unfibrosed disease who met the WHO criteria for prefibrotic cIMF. Patients receiving chemotherapy were considered separately from patients without treatment. Our results favor a steady progression of myelofibrosis unrelated to therapy modalities, whereas confusing literature data can be explained: fibrosis may remain static or lessen, especially in more advanced stages of cIMF.     

Systemic scleroderma patients have improved skin perfusion after the transdermal application of PGE1 ethyl ester

BACKGROUND: Patients with systemic scleroderma exhibit a noticeable slowing of blood cell velocities or even stasis in the capillaries of the skin. In this study the effects of transdermally applied prostaglandin PGE1 ethyl ester on nutritive cutaneous perfusion and on Raynaud's symptoms were investigated. PATIENTS AND METHODS: 24 patients with systemic scleroderma were treated transdermally over a period of 14 days with prostaglandin E1 ethyl ester patches. The response of blood cell velocity in the nailfold capillaries to cold exposure was tested in 20 patients, and all of the patients recorded the number of Raynaud's episodes in a journal over a period of two weeks. RESULTS: After the transdermal application of prostaglandin E1 ethyl ester there was an increase in blood cell velocity in the nutritive capillaries of systemic scleroderma patients (increase from 0.35 +/- 0.14 mm/s to 0.47 +/- 0.11 mm/s, (p < 0.05)). At the same time there was a decrease in the number of Raynaud's episodes (2.9 +/- 2.4 per day to 2.6 +/- 2.0 per day (p < 0.05)). CONCLUSION: The transdermal application of prostaglandin E1 ethyl ester was shown to have a favourable effect on nutritive blood flow in the capillaries of the skin in systemic scleroderma patients.     

Longitudinal study on quality of life after gastrectomy for gastric cancer and starting points for intensified care

This prospective longitudinal study on gastric carcinoma patients with gastrectomy was designed to answer the question about changes in several determinants of the quality of life (QL) at various times before and after surgery and to obtain evidence for specific approaches of therapeutic intervention. METHODS AND PATIENTS: 36 patients were given a questionnaire structured according to Eypasch et al. (self- assessment) before surgery, at discharge from the hospital, and after 3 and 6 months. The dual structure of the questions makes it possible to determine whether a single item is present at all (prevalence) and to what extent it impairs the quality of life (no impairment/some/moderate/strong impairment--corresponding to 0-3). The data were evaluated per domain of QL as well as item-related. RESULTS: Postoperatively, 14 patients had to be excluded from the study because of non-radical surgery, complications, recurrences, etc. After 6 months the items of all QL-determinants showed the lowest prevalence with the exception, however, of the somatic determinants, the items of which showed a prevalence of 27 % preoperatively, 64 % at discharge from the hospital, 58 % after 3 months, and 46 % after 6 months. The average degree of QL-impairment increased continuously from 1.17 preoperatively to 1.61 after 6 months. Preoperatively the psychic domain was predominantly impaired, postoperatively the somatic domain. CONCLUSION: Analysis of the subjective quality of life can reveal care deficits. Gastrectomy-associated symptoms seem to influence the quality of life considerably in the first 6 months after surgery. More attention has to be paid to the sequelae of surgery. The high pre- and postoperative frequency of psychic impairment makes it desirable to provide special psychooncological offers of care.     

Dynamic gadolinium-enhanced MRI evaluation of porcine femoral head ischemia and reperfusion

OBJECTIVE: To examine the potential of gadolinium (Gd)-enhanced dynamic MRI in the detection of early femoral head ischemia. Furthermore, to apply a three-compartment model to achieve a clinically applicable MR index for femoral head perfusion during the steady state and arterial hip joint tamponade. DESIGN AND MATERIALS: In a porcine model femoral head perfusion was measured by radioactive tracer microspheres and by using a dynamic Gd-enhanced MRI protocol. Femoral head perfusion measurements and MRI tests were performed unilaterally before, during and after the experimentally induced ischemia of one of the hip joints. Ischemia was induced by increasing intra-articular pressure to 250 mmHg. RESULTS: All pigs showed ischemia of the femoral head epiphysis under hip joint tamponade followed by reperfusion to the same level as before joint tamponade. In two cases perfusion after removal of tamponade continued to be low. In dynamic MRI measurements increases in signal intensity were seen after intravenous infusion of Gd-DTPA, followed by a slow decrease in signal intensity. The signal-intensity curve during femoral head ischemia had a minor increase. Also the coefficient determined was a helpful indicator of femoral head ischemia. CONCLUSIONS: Femoral head blood flow as measured by microspheres fell significantly under joint tamponade. Early detection of this disturbed regional blood flow was possible using a dynamic MRI procedure. A biomathematical model resulted from the evaluation of the intervals of signal intensity over time which allows detection of bone blood flow changes at a very early stage. Using this new method earlier detection of femoral head necrosis may be possible.