Angiogenesis and Ewing sarcoma--relationship to pulmonary metastasis and survival

Background/Purpose

Intratumoral angiogenesis quantified by microvessel density (MVD) has been shown to be a strong prognostic indicator in a number of malignant tumors. Its association with prognosis in Ewing sarcoma has not been previously studied. The aim of our study was to investigate the relationship between angiogenesis and clinical outcome in Ewing sarcoma.

Methods

Twenty-seven patients with Ewing sarcoma were included in a retrospective immunohistochemical study. Sections from diagnostic biopsies were immunostained using anti-von Willebrand factor antibody and microvessels were counted at 400× magnification on three microscopic fields per patient. Microvessel density was correlated with overall and disease-free survival as a continuous variable using univariate regression analysis and as a dichotomous variable by Kaplan-Meier and log-rank analysis. Correlation between clinicopathologic variables and the degree of angiogenesis was tested using χ² test.

Results

Increasing MVD was not confirmed to be a poor prognostic factor in univariate analysis. Also, statistically significant difference was not found in overall survival or disease-free survival between patients with high (>31.6 vessels per field) and low (≤31.6 vessels per field) microvessel counts. Finally, there was no difference regarding the metastatic rate between patients with high and low microvessel counts.

Conclusions

Our results did not confirm increasing angiogenesis quantified by MVD to be predictive of prognosis or pulmonary metastasis in Ewing sarcoma. The diffuse pattern of distribution of microvessels found in Ewing sarcoma may be responsible for the observed lack of prognostic significance of angiogenesis. Future work is required to assess the prognostic importance of MVD in this disease.     

Ultralong peripheral nerve block by lidocaine:prilocaine 1:1 mixture in a lipid depot formulation: comparison of in vitro, in vivo, and effect kinetics

BACKGROUND: The aim of this study was to develop stable and easily injectable lipid depot preparations of local anesthetics in which the drug concentration can be varied according to desired duration of action. METHODS: The formulations contained a 2.0, 5.0, 10, 20, 40, 60, 80, or 100% eutectic mixture of lidocaine and prilocaine base in medium-chain triglyceride. Duration of sciatic nerve block and local neurotoxicity was investigated in rats with 2.0% lidocaine:prilocaine HCl solution and 99.5% ethanol as controls. The rate of release of local anesthetic from the site of administration and the possibility to predict in vivo depot characteristics from in vitro release data were investigated for the 20 and 60% formulations. RESULTS: The duration of sensory sciatic block was prolonged 3 times with the 20% formulation and approximately 180 times with the 60% formulation, in comparison with the 2% aqueous solution. With the 80 and 100% formulations, all animals still showed nerve block after 2 weeks. The in vivo release of local anesthetic could be approximately predicted from in vitro data for the 20% but not for the 60% formulation. The formulations of 60% or greater and ethanol showed neurotoxic effects. CONCLUSIONS: The pharmaceutical properties of these formulations compare favorably with those of other depot preparations. The high-percentage ones showed the longest duration of action yet reported for sciatic nerve block in rats. The possibility of using a high-concentration local anesthetic depot formulation as an alternative to ethanol or phenol for long-term nerve blocks in chronic pain merits further investigation.     

Impact of organ preservation using HTK for graft flush and subsequent storage in UW in rat kidney transplantation

BACKGROUND: In kidney transplantation, preservation has a significant influence on organ function. Since previous reports have indicated a benefit of combining histidine-tryptophan-ketoglutarate (HTK) and University of Wisconsin (UW) solution, we evaluated the effects of initial flush with low viscosity HTK, followed by storage in UW. MATERIAL AND METHODS: Kidneys from inbred Lewis rats were procured using HTK or UW for initially perfusion and re-flushed after 30 min with either solution. In a third group, after perfusion with HTK, organs were re-flushed with UW. Organs were stored for 16-24 h (4 degrees C). Study parameters were high-energy phosphates, histology, apoptosis, recipient survival and urine excretion of 15-F2t -isoprostanes (oxidative stress marker). RESULTS: Prior to transplantation, tissue ATP/ADP concentrations were: HTK/UW > UW-only > HTK-only. In transplanted kidneys, histological damage was highest after preservation in HTK-only. Twenty-four hours after transplantation (24 h cold ischemia time - CIT), cleaved-PARP was most abundant using UW-only. 16 h of CIT resulted in higher urine concentrations of isoprostanes in the order HTK-only (368 +/- 308) > UW-only (157 +/- 105) > HTK/UW (67 +/- 26), and was lower in HTK/UW after 24 h of CIT (146 +/- 38) vs. UW-only (507 +/- 33 pg/mg creatinine). Survival (24 h CIT) was significantly reduced, and percentage of initial non-functioning (INF) kidneys highest in HTK-only (2.6 +/- 0.3 days, 100%), compared to UW-only (13 +/- 4.4 days, 75%) and HTK/UW (18.5 +/- 4.6 days, 33%). CONCLUSIONS: In long-term preservation, UW is superior over HTK. However, our results indicate that perfusion with HTK prior to storage in UW may improve the results of UW alone which is reflected by better survival, lower rate of INF, higher cellular energy conservation and a decrease of free radicals.     

Placental passage of metformin in women with polycystic ovary syndrome

Metformin passes the placenta. Fetal serum levels are comparable with maternal values.     

The Hohl instrument for optimizing total laparoscopic hysterectomy procedures

STUDY OBJECTIVE: To evaluate the feasibility of total laparoscopic hysterectomy (TLH) using the Hohl instrument in an initial cohort of patients. DESIGN: Retrospective cohort analysis (Canadian Task Force classification II-3). SETTING: Department of Obstetrics and Gynecology, Erlangen University Hospital, Erlangen, Germany. PATIENTS: Forty-four women underwent the new TLH procedure using the Hohl instrument from May 2004 through January 2005. The laparoscopic approach was used when the patient had undergone more than one previous pelvic abdominal operation and/or had a reduced vaginal capacity. The indications for hysterectomy were symptomatic leiomyoma in 25 patients and hypermenorrhea in 19 patients. INTERVENTION: Total laparoscopic hysterectomy using the Hohl instrument. MEASUREMENTS AND MAIN RESULTS: No ureteral or bladder injury occurred in any of the patients. The complication rate during surgery and in the postoperative period was zero. The mean loss of hemoglobin was 1.68+/-0.96 g/dL, the mean operating time was 108+/-21 minutes, and the mean uterine weight was 302+/-121 g. CONCLUSION: Total laparoscopic hysterectomy using the Hohl instrument simplifies the surgical procedure. The reported technique is an option comparable with laparoscopic-assisted vaginal hysterectomy and may be effective in preventing minor and major complications during TLH.     

Effects of Intercostal Nerve Blocks (Etidocaine 0.5%) on Chest Wall Mechanics in Cholecystectomized Patients

In 20 patients who had undergone cholecystectomy through a right oblique incision, an intercostal nerve block with etidocaine 0.5% was performed on the day after operation — in 10 patients on the right side only and in the other 10 bilaterally. The block was applied to the 5th-11th intercostal nerves, inclusive.
Tidal volumes, respiratory variations in the perimetry of the chest and abdomen, and intraoesophageal and intragastric pressures were recorded before and after the blockades. From analyses of the relations between the relative contributions of costal and abdominal respiration, on the one hand, and intragastric pressure variations, on the other, it was found that before the blockade the intercostal muscles contributed to respiratory movements at rest, but that this contribution decreased after the blockade - to a greater extent after bilateral than after unilateral blockade. It is assumed that this return to a more normal type of breathing at rest implies relief for the patients. The nerve block led to no significant change of the fraction of abdominal breathing. Pulmonary elastance decreased after bilateral blockade, but remained unchanged after unilateral. Changes in the functional residual capacity (FRC) were evaluated by transthoracic electrical impedance pneumography. Signs of a reduction were noted after unilateral blockade, but there appeared to be no change after bilateral blockade.
Bilateral intercostal block thus seems more satisfactory than unilateral in certain respects. The differences cannot be ascribed such importance, however, that bilateral blocks should be considered obligatory in cholecystectomized patients. Probably the most important effect - the pain relief- is achieved in these patients by a right-sided block only.     

Microangiopathy in young diabetic men

Summary Skin punch biopsy was performed on 38 diabetic men with varying durations of diabetes and 17 non-diabetic men, all between the ages of 17–45 years. — Light microscopical changes in venules, capillaries, and arterioles without an internal elastic lamina were arbitrarily graded twice by two of us independently with no access to clinical data. A grading system with 5 degrees was used for assessing the wall thickness. — The most characteristic lesion was thickening of the walls of the blood vessels. Significant thickening was noted in 14 diabetics and 1 control. No definite changes in the endothelial cells were demonstrated. The nuclei of the pericytes often seemed conspicuous, comparatively large and hyperchromatic. Positive significant correlation was shown between the wall thickness and this pericyte change in the diabetics, but not in the controls. — The wall thickness was significantly and positively correlated with the age of the diabetics, duration of diabetes and diastolic blood pressure. Multivariate correlation, however, revealed a significant correlation between the wall thickness and the duration of diabetes, and a tendency to correlation with age. This presumably means that the correlation with diastolic blood pressure, and probably part of the correlation with age, can be accounted for by the dependence of the wall thickness on the duration of diabetes. In the control group no correlation was shown between the wall thickness and age, systolic blood pressure or diastolic blood pressure. Positive significant correlation independent of the duration was demonstrated between wall thickness and retinopathy. — The investigation indicates that the wall thickness is increasing with the duration of diabetes, and that the pericytes may be involved in the development of dermal capillary and venule lesions in diabetes. It is suggested that skin biopsy may serve as an examination, supplementary to ophthalmoscopy, in the early diagnosis of diabetic microangiopathy.Presented in part at the Annual Meeting of the Swedish Medical Society, Stockholm 1965 (Säve-Söderbergh et al., 1966)     

Umsatz von Trichloräthylen im Organismus

Zusammenfassung Bei Versuchen mit Hunden und Ratten sind Trichloräthylen, Trichloräthylalkohol, Trichloräthylaldehyd (Chloral) und Trichloressigsäure durch subcutane Injektion zugeführt und die ausgeschiedene Menge von Trichloressigsäure im Urin untersucht worden. Von den 3 zuerst genannten Stoffen werden nur wenige Prozent mit dem Urin in Form von Trichloressigsäure ausgeschieden. Nach Zufuhr von Natriumtrichloracetat werden 1/3–1/2 als Trichloressigsäure ausgeschieden. Zufuhr von Disulfiram per os bei Ratten hemmt die Trichloressigsäureausscheidung im Urin sehr stark nach Zufuhr von Trichloräthylen und Trichloräthylalkohol. Eine deutliche, aber nicht ganz so ausgesprochene Herabsetzung wird nach der Zufuhr von Trichloräthylaldehyd (Chloral) festgestellt. Die Ausscheidung nach Zufuhr von Natriumtrichloracetat wird nicht durch Disulfiram beeinflußt. Die erhaltenen Resultate sind wahrscheinlich darauf zurückzuführen, daß Disulfiram die Oxydation des Trichloräthylaldehyds hemmt. Der Reaktionsverlauf für den Umsatz von Trichloräthylen im Organismus dürfte daher wahrscheinlich als eine Oxydation via Trichloräthylalkohol und Trichloräthylaldehyd zu Trichloressigsäure anzusehen sein.Herrn Professor Heinrich Zangger zum 80. Geburtstag gewidmet.     

MUCUS IN INTESTINAL CONTENTS OF GERMFREE RATS

The fecal excretion of total nitrogen and of total hexosamines has been determined in germfree and conventional rats. Germfree rats excreted more hexosamines than the conventional rats, while no difference in the nitrogen excretion was found. Infection of the germfree rats with a normal flora resulted in a temporarily increased excretion of hexosamines and nitrogen over a period of 2 to 3 days after which they reached the level of the conventional animals. The contents of the germfree cecum contained 65 to 137 mg of hexosamines and 57 to 127 mg of nitrogen as compared to 1.2 to 5.3 and 7.4 to 23 mg in conventional animals. The high figures for hexosamines were due to an increase in the total amount of contents in the cecum and to a fivefold increase in the concentration of hexosamine-containing material. Studies on the distribution of hexosamine-containing cecal contents between sediment and supernatant after centrifugation at 20,000 g for 2 hours demonstrated that 5 to 10 per cent of the hexosamines occurred in the sediment in the germfree rats, while 75 to 85 per cent was found in this fraction in the conventional rats. The soluble part of the cecal contents in germfree as well as in the conventional rats contained 70 per cent of hexosamines in molecules with a molecular weight above approximatively 100,000 as found by gel filtration experiments on sephadex gels. The higher weight of the germfree cecal wall was reflected in a high total amount of nitrogen and hexosamines. Isolated strains of bacteria capable of reducing the cecal size in vivo did not show any capacity to degrade the mucus in vitro in a test system, where a full intestinal flora was highly active.