Effects of an acute exposure to toluene on the DNA repair activity of the human 8-oxoguanine DNA glycosylase 1 (hOGG1) in healthy subjects.

The structure and previous studies on the biotransformation of toluene lead to the suspicion that metabolites may be formed which preferentially react with strongly nucleophilic partners such as sulfhydryl groups of cysteines in proteins. Human 8-oxoguanine DNA glycosylase 1 removes the major oxidative DNA damage and possesses eight cysteines. Its potential inactivation may lead to accumulation of DNA damage by reactive oxygen species formed by exogenous agents or by ubiquitous endogenous processes. The goal of the present investigation was to study the in vivo effect in humans of an acute toluene exposure on hOGG1 activity. Twenty healthy, non-smoking males were exposed to 50 ppm toluene and to filtered air in an exposure chamber for 270 min, using a cross-over design. Before and 30 min after the end of exposure, blood samples were taken and toluene concentrations and the hOGG1 activity were measured. hOGG1 activity was determined in peripheral mononuclear blood cells. Thirty minutes after exposure to toluene, we found a median blood concentration of 0.25 mg toluene/l. Compared with the activity before exposure, upon exposure to toluene a statistically insignificant median increase of hOGG1 activity by +0.4% and upon exposure to air by +2.3% was determined. Thus, no reduction of the hOGG1 repair activity after acute exposure to 50 ppm toluene was observed.

Tacrolimus monotherapy without steroids after liver transplantation--a prospective randomized double-blinded placebo-controlled trial.

Early steroid withdrawal after liver transplantation (LT) is desirable in order to reduce steroid side effects. Between February 2000 and August 2004, 110 patients after LT were included in this prospective, randomized, double-blind, placebo-controlled trial. Randomization was performed before LT. In all patients, tacrolimus was used without induction therapy. All patients received methylprednisolon for 14 days, thereafter a double-blinded medication containing either placebo (n = 56) or methylprednisolon (n = 54) for 6 months, which was completely stopped thereafter. End points were patient and graft survival, acute and chronic rejection, and incidence of steroid side effects during the first year after LT. One-year patient survival was 85.7% (placebo) and 88.8% (steroid) (p = 0.572). Twenty-seven (48.2%) and 19 (35.2%) patients experienced acute rejection (placebo versus steroid, respectively; p = 0.116). Two patients in the placebo group but none in the steroid group experienced chronic rejection (p = 0.257). The rates of side effects were (placebo versus steroid, respectively): CMV infection 25% versus 33% (p = 0.336), post-transplant diabetes 30% versus 53% (p = 0.024), hypertension 39% versus 52% (p = 0.248), hypercholesterolemia 10% versus 41% (p = 0.002) and hypertriglyceridemia 32% versus 54% (p = 0.046). In conclusion, early steroid withdrawal after LT is feasible under tacrolimus monotherapy without increased rejection rates and with a lower rate of side effects.

Would they follow what has been laid down? Cancer patients' and healthy controls' views on adherence to advance directives compared to medical staff.

UNLABELLED: Advance directives are propagated as instruments to maintain patients' autonomy in case they can no longer decide for themselves. It has been never been examined whether patients' and healthy persons themselves are inclined to adhere to these documents. Patients' and healthy persons' views on whether instructions laid down in advance directives should be followed because that is (or is not) "the right thing to do", not because one is legally obliged to do so, were studied and compared with that of medical staff. METHOD: Vignette study presenting five cases. Cancer patients, healthy persons, nursing staff and physicians (n = 100 in each group) were interviewed. An adherence score was calculated (maximum value 5). The adherence score is found to be low in all groups, yet lowest in patients (1.55; standard deviation 1.13) and healthy controls (1.60; 1.37). The scores are significantly different between nursing staff on the one hand and patients and healthy controls on the other (p < 0.005 and p < 0.05, respectively), and between doctors and patients (p < 0.05). Interviewees who want these documents to be followed tend to live alone and to have already written an advance directive. CONCLUSIONS: Cancer patients and healthy persons widely disregard instructions laid down in advance directives and consider them less binding than physicians and nursing staff do. Only a minority tends to adhere more to advance directives. To improve decision-making at the end of life when patients are no longer able to decide for themselves alternative concepts, such as advanced care planning, should be considered.

The value of Ems Mineral Salts in the treatment of rhinosinusitis in children. Prospective study on the efficacy of mineral salts versus xylometazoline in the topical nasal treatment of children.

UNLABELLED: The treatment of rhinosinusitis seen in the light of uncertain pathogenesis and variable symptoms is under discussion and ranges from the administration of antibiotics, decongestants and anti-allergic agents to no treatment. In this randomized, prospective, double-blind and controlled study the effect of a 14-day treatment (1-2 sprays into each nostril t.d.) with either isotonic Ems Mineral Salts (EMS) solution (Siemens & Co., Bad Ems, Germany) or xylometazoline solution (0.05%) was tested in children (n=66) aged 2-6 years. MAIN OUTCOMES: the degree of mucosal inflammation, nasal patency, general state of health, condition of the middle ear, auditory function as well as an assessment of complaints by the parents. With the exception of the hearing defects, all parameters showed a clear improvement in both treatment groups at the end of the observation period (p>0.001). The hearing defects showed only a trend towards improvement. At the end of the study no differences between the treatment groups could be determined. However, at the intermediate examination after the first 7 days of treatment more favourable results were seen in the group treated with EMS. No undesired medicinal effects were observed, although in 7 out of 34 cases the nasal spray was improperly used in the group treated with xylometazoline. The results of the study show that there is no difference in efficacy between an exclusive treatment by EMS solution in children aged 2-6 years and a treatment with xylometazoline, but with the distinction that with EMS the length of use was not restricted, there were not the potential side effects of nasal decongestants, and there was no contraindication in the newborn and infants.

Attitudes towards and barriers to writing advance directives amongst cancer patients, healthy controls, and medical staff.

OBJECTIVES: After years of public discussion too little is still known about willingness to accept the idea of writing an advance directive among various groups of people in EU countries. We investigated knowledge about and willingness to accept such a directive in cancer patients, healthy controls, physicians, and nursing staff in Germany. METHODS: Cancer patients, healthy controls, nursing staff, and physicians (n = 100 in each group) were surveyed by means of a structured questionnaire. RESULTS: Only 18% and 19% of the patients and healthy controls respectively, and 10% of the medical staff had written an advance directive. However, 50-81% of those surveyed indicated that they wished to write one. This intention was associated with deteriorating health (p < 0.001). Only 29% of the healthy controls and 43% of the patients knew about the possibility of appointing a health care proxy. A majority in all groups believed that advance directives may influence the course of treatment (79-85%), yet half of those surveyed in all groups fear that patients could be pressurised into writing an advance directive, and 38-65% thought that relatives could abuse such documents. CONCLUSIONS: Only a minority of the participants had written an advance directive and knew about the possibility of authorizing a health care proxy. Deteriorating health was associated with increasing willingness to make a directive. Despite a majority belief that advance directives may influence treatment at the end of life, other factors limit their employment, such as fear of abuse.

What are cancer patients' preferences about treatment at the end of life, and who should start talking about it? A comparison with healthy people and medical staff.

GOALS OF THE WORK: In order to strengthen cancer patients' autonomy and to improve quality of palliative care, it is necessary to know what are the patients' preferences for treatment at the end of life, whether they accept the idea of advance directives, and who should initiate the process of fulfilling such a document. PATIENTS AND METHODS: We compared cancer patients' preferences with respect to particular treatment options at the end of life, acceptance of the idea of advance directives, and preferences for whom should initiate writing such a document with that of healthy controls, nursing staff, and physicians (n=100 each group) using a structured questionnaire. RESULTS: Cancer patients wanted treatment with antibiotics and infringing treatments such as chemotherapy and dialysis significantly more often than healthy controls, nursing staff, and physicians (p<0.01 and p<0.001, respectively). Determinants associated with the wish to opt for these treatments were reduced health condition and older age. The groups did not differ with respect to their acceptance of advance directives; 58-75% of all those surveyed wanted their physicians to initiate a discussion about writing such a document if they thought it appropriate. CONCLUSIONS: Cancer patients' preferences for treatment at the end of life significantly differ compared to other groups. Oncologists should initiate a discussion about an advance directive when/if the course of the illness seems to make this appropriate, which corresponds to the wish of the majority of cancer patients, healthy controls, and medical staff.

[The choice between transperitoneal and retroperitoneal adrenalectomy. A prospective study]. / Transperitoneale oder retroperitoneale Adrenalektomie. Ergebnisse einer prospektiven Verlaufsbeobachtung.

INTRODUCTION: The aim of this prospective study was to evaluate the optimal surgical approach to endoscopic adrenalectomy. PATIENTS AND METHODS: Between March 1997 and February 2003, we performed 221 endoscopic adrenalectomies in 202 patients (right side 83, left side 100, bilateral 19), with an conversion rate of 2,5%. In 197 patients endoscopic adrenalectomy was carried out via retropertioneal approach 128 times and via transperitoneal approach 88 times. RESULTS: Endoscopic adrenalectomy was performed in 98% of the total number patients. No statistically significant influence ( P=0.05) was found for the parameters intraoperative blood loss, rate of postoperative complications, or duration of hospitalization in regard to the procedure. The operative time and learning curve were significantly longer with the retroperitoneal approach. Multivariate analysis identified surgical approach, tumor size (5 cm), and body mass index (25) as independent factors for operative time. CONCLUSION: The lateral transperitoneal approach is the optimal procedure for endoscopic adrenalectomy.

Different patterns of beta-catenin expression in gastric carcinomas: relationship with clinicopathological parameters and prognostic outcome.

AIMS: The cadherin-catenin complex is known to play a critical role in maintenance of cell adhesion. Additionally beta-catenin (beta-ct) can also take part in signal transduction and nuclear beta-ct expression could be correlated with poor prognosis in several malignancies. Since, in gastric cancer, this role of beta-ct is still uncertain, we investigated the expression pattern of beta-ct as well as the possible prognostic role. METHODS AND RESULTS: beta-catenin expression was immunohistochemically investigated in a retrospective series of 401 R0-resected gastric carcinomas. Out of these cases, 54 tumours (13.5%) revealed a preserved membranous beta-ct expression similar to that in normal gastric mucosa. In 80 tumours beta-ct expression was moderately reduced and in 117 tumours highly reduced. In 150 tumours (37.4%), no or only a weak membranous beta-ct expression was found. Additionally, in 53 tumours, a strong beta-ct expression could be observed in the cytoplasm with a simultaneous nuclear beta-ct immunoreactivity in 17 of these 53 tumours, while nine tumours only showed nuclear immunoreactivity without cytoplasmic staining. There were no significant correlations between the degree of membranous beta-ct expression or the different staining pattern (membranous vs. cytoplasmic/nuclear) and the grade of tumour differentiation, the histological tumour type according to Lauren, as well as with the prognostic parameters pT, pN category and vascular invasion. No associations could be found with tumour cell proliferation and the expression of E-cadherin, irrespectively of the different beta-ct staining pattern. Univariate analysis revealed no influence on survival, either for membranous or for cytoplasmic/nuclear beta-ct expression. CONCLUSION: Our data on 401 tumours suggest that activation of the Wnt/beta-catenin signalling does also occur in a subset of gastric carcinomas. However, in gastric cancer, neither the presence of cytoplasmic/nuclear beta-ct expression nor the reduction or loss of membranous beta-ct expression is correlated with a specific histological tumour type, tumour progression or prognosis.

The presence of HPV DNA in cervical cancer: correlation with clinico-pathologic parameters and prognostic significance: 10 years experience at the Department of Obstetrics and Gynecology of the Mainz University.

The objective of this study was to assess whether the presence of human papillomavirus (HPV) DNA and/or several genotypes of HPV DNA in cervical cancer are correlated with several clinicopathologic parameters of well-defined prognostic significance and whether virologic parameters are predictors of long-term survival in cancer patients. Two hundred twenty three cases of cervical cancer patients included in this retrospective study underwent follow-up evaluation. Survival and cause of death were examined for 204 (91.4%) patients, with a mean follow-up time of 4.4 years. HPV DNA was detected using the highly sensitive polymerase chain reaction (PCR) method followed by HPV DNA sequencing for HPV genotyping. These results were correlated with well-defined clinicopathologic parameters and survival data. HPV DNA was detected by PCR in 150 of 193 (73.4%) tissue specimens of cervical cancer patients. DNA sequence analysis revealed the presence of HPV 16 (n = 68, 45.3%), HPV 18 (n = 49, 32.6%) and rare HPV types (n = 33, 22.1%). HPV genotypes correlated significantly with histologic tumor types, node status, tumor oxygenation, blood vessel invasion, and lymph space involvement. The presence of HPV DNA in cervical cancer as well as the genotype of HPV 16 could also be confirmed as significant prognostic factors in the univariate Cox regression analysis (RR 2.856, P < 0.003 resp. RR 3.444, P < 0.0001). In the multivariate analysis, however, HPV DNA status failed to be of prognostic relevance. Exclusively HPV 16 appears to have an independent impact on the overall survival in cervical patients (RR 3.653, P < 0.002). We conclude that the detection of HPV 16 genotype may play an important adjunct role in assessing prognosis of cervical cancer patients. The clinical impact of the presence of HPV DNA in primary tumors of uterine cervix remains to be investigated in further studies, and the exact mechanisms by which HPV influences the prognosis of cervical cancer patients have to be defined.

Human papillomavirus (HPV) DNA in primary cervical cancer and in cancer free pelvic lymph nodes--correlation with clinico-pathological parameters and prognostic significance.

OBJECTIVE: To assess whether the presence of human papilloma virus (HPV) DNA and/or several genotypes of HPV DNA in primary cervical cancer and cancer free pelvic lymph nodes are correlated with several clinicopathological parameters of well-defined prognostic significance and whether virological parameters are predictors of long-term survival in cancer patients. PATIENTS AND METHODS: 223 cases of cervical cancer patients included in this retrospective study underwent follow-up evaluation. Survival and cause of death were examined for 204 (91.4%) patients, with a mean follow-up time of 4.4 years. HPV DNA was detected using the high sensitive polymerase chain reaction (PCR) method followed by HPV DNA sequencing for HPV genotyping. These results were correlated with well-defined clinicopathological parameters and survival data. RESULTS: HPV DNA was detected by PCR in 150 of 203 (73.4%) tissue specimens of cervical cancer patients. DNA sequence analysis revealed the presence of HPV 16 (n = 68, 45.3%), HPV 18 (n = 49, 32.6%) and rare HPV types (n = 33, 22.1%). HPV genotypes correlated significantly with histological tumor types, node status, blood vessel invasion and lymph space involvement. The presence of HPV DNA in cervical cancer as well as the genotype of HPV 16 could also be confirmed as significant prognostic factors in the univariate Cox Regression Analysis (RR 2.856, p < 0.003 resp. RR 3.444, p < 0.0001). The presence of HPV DNA in cancer free pelvic lymph nodes was significantly correlated to the concomitant manifestation of pelvic lymph node metastases (RR 3.1, p < 0.0001). In the multivariate analysis, however, HPV DNA in primary tumor and in negative pelvic lymph nodes failed to be of prognostic relevance. Exclusively, HPV 16 appears to impact independently on the overall survival in cervical cancer patients (RR 3.653, p < 0.002). CONCLUSION: The detection of HPV 16 genotype may play an important adjunct role in assessing prognosis of cervical cancer patients. The clinical impact of the presence of HPV DNA in primary tumors and cancer free pelvic lymph nodes remains to be investigated in further studies. The exact mechanisms by which HPV influence the prognosis of cervical cancer patients have to be defined.

Effects of intraocular cefotaxime on the human corneal endothelium.

PURPOSE: To ascertain whether 0.4 mL of cefotaxime 0.25% applied intracamerally causes toxic alteration of the human corneal endothelium. METHODS: In this prospective randomized masked study, 66 patients had cataract extraction using phacoemulsification, a frown incision, and implantation of a poly(methyl methacrylate) intraocular lens. This was followed by intraocular injection of 0.4 mL of cefotaxime 0.25% or balanced salt solution (BSS(R)). Contact specular microscopy and photography were performed preoperatively and 1 to 4 days and 3 months postoperatively. RESULTS: In the cefotaxime group, the mean endothelial cell count was 2729 cells/mm(2) +/- 474 (SD) preoperatively, 2520 +/- 462 cells/mm(2) 1 to 4 days postoperatively, and 2560 +/- 495 cells/mm(2) 3 months postoperatively. The mean endothelial cell count in the BSS (control) group was 2657 +/- 413 cells/mm(2), 2475 +/- 384 cells/mm(2), and 2486 +/- 427 cells/mm(2), respectively. There was no significant difference in cell count or morphology between groups (P <.05). CONCLUSIONS: Intraocular application of cefotaxime produced no significant changes in endothelial cell count or morphology when compared with application of a control substance. With its broad spectrum of antibiotic activity, cefotaxime might be an appropriate alternative to other intraocularly administered antibiotics in anterior segment surgery for prophylaxis and management of infection.

[Surgical therapy of primary hyperparathyroidism. Quality of life after 10 years prospective observation]. / Operative Therapie des primären Hyperparathyreoidismus. Lebensqualität nach 10jähriger prospektiver Beobachtung.

AIM OF THE STUDY: The quality of life after surgery for primary hyperparathyroidism was evaluated in a prospective long-term follow-up study. PATIENTS AND METHODS: Altogether 383 patients, 374 with the first manifestation, 6 with recurrent and 3 with persistent disease, who underwent operation from August 1, 1987 to February 15, 1999 were prospectively investigated and included in a long-term follow-up study. All patients underwent reexaminations at regular surveillance intervals. The postoperative course is known in 93.7% of all patients. We carried out 1,504 follow-up examinations (per patient: 1-12, median 4). The follow-up period ranged from 1 month to 10 years with a median of 24 months (mean 34.5 +/- 29.8 months). RESULTS: The true frequency of asymptomatic primary hyperparathyroidism could be confirmed only postoperatively, because a part of the patients were unaware of mild symptoms of hypercalcaemic syndrome prior to surgery. Therefore the prevalence of asymptomatic primary hyperparathyroidism was 5.6% in our patients. Surgical cure was obtained in 97.6% of patients after initial neck exploration. Successful parathyroidectomy provided long-term relief of symptoms in our patients. In 58% of the patients with hypercalcaemic syndrome recovery occurred within the first month after surgery. Bone and joint pain persisted for a longer period of time and was present in 24% of patients two years after the operation. During the follow-up period the mortality of our study population was significantly higher (p = 0.00024) than the expected mortality risk for the German population as a whole. CONCLUSIONS: The present prospective follow-up study yielded conclusive outcome research data after operative therapy for primary hyperparathyroidism. The high biochemical cure rate with long-term relief of symptoms, as well as the increased mortality after successful parathyroidectomy emphasize the importance of early diagnosis and early surgical treatment for primary hyperparathyroidism, even in the absence of manifest symptoms.

Prognostic value of the cyclin-dependent kinase inhibitor p27Kip1 in gastric cancer.

In the present study, the expression and prognostic role of p27 were immunohistochemically investigated in 413 curatively resected gastric carcinomas. Strong p27 expression in more than 50% of the tumour cells could be detected in 57.4% (n = 237) whereas 42.6% of the tumours (n = 176) only showed p27 expression in less than 50% of the tumour cells. No significant correlation could be observed between p27 expression and the prognostic parameters pT category, pN category, blood and lymphatic vessel invasion as well as with tumour histology. Concerning other cell cycle associated proteins, p27 expression was inversely correlated with p21 expression, however, there was no correlation either with cyclin D1 and cyclin E or with expression of p53, bcl-2 and tumour cell proliferation. Univariate survival analysis revealed a poorer prognostic outcome for patients with tumours expressing p27 in more than 50% of the tumour cells (p < 0.049). However, by multivariate analysis, this prognostic influence of p27 could not be verified as independent from the known prognostic parameters of the pTNM-system (p < 0.325). The present data on 413 curatively resected gastric carcinomas suggest, that expression of p27, analyzed alone or in combination with multiple cell cycle regulatory proteins, has no prognostic value in gastric cancer.

Association between blood rheology, thrombosis and cancer survival in patients with gynecologic malignancy.

In cancer patients impaired blood rheology in the presence of coagulation activation may reduce blood flow in the vascular microcirculation that favors thrombosis but may also support tumor progression and metastasis. In 451 patients with gynecological cancer and 177 patients with corresponding benign tumor disease preoperatively, during adjuvant treatment, when venous thrombosis (VT) or cancer progression was diagnosed hematocrit (micro centrifuge), hemoglobin, leukocytes, platelets (Coulter Counter); red blood cell (RBC) aggregation (aggr.) during stasis and low shear conditions (MA 1, Myrenne), plasma viscosity (viscosimeter KSPV 1 Fresenius), and fibrinogen (Multifibren Behring Dade) were investigated. One hundred and twelve healthy women served as controls. Preoperatively, mean plasma viscosity (pv) was significantly higher in cancer patients as compared to patients with the corresponding benign tumor disease (breast cancer: n = 261; pv = 1.32 vs. 1.27 mPa s; p = 0.023; ovarian cancer: n = 68; pv = 1.39 vs. 1.31 mPa s; p < 0.001; endometrial cancer: n = 70; pv = 1.37 vs. 1.25 mPa s; p < 0.001; cervical cancer: n = 52; pv = 1.33 vs. 1.26 mPa s; p = 0.004). RBC aggr. was significantly lower in controls compared to the preoperative values in cancer patients but mean (median) values (RBC aggr. stasis < 21) were within the normal range in all. Preoperatively, plasma viscosity was a significant risk factor for the overall survival in ovarian cancer patients (p = 0.02) and for subsequent thrombosis in ovarian (p = 0.02) and cervical cancer patients (p = 0.007). In the multivariate analysis plasma viscosity was an independent prognostic marker for the overall survival of breast cancer patients (r = 99.45; 95% CI: 7.32-980.2; p < 0.0001). An optimized preoperative cut-off value above 1.40 mPa s (Log-Rank-test) was significantly associated with poor outcome in the Kaplan-Mayer survival estimates, even in node-negative breast cancer. In gynecologic cancer patients the combination of an increase in RBC aggregation and plasma viscosity impairs blood-flow-properties and may induce hypoxia in the microcirculation that favors thrombosis, settlement of tumor-cells and thus metastasis. Improvement of blood fluidity and thus oxygen transfer in the tumor-vascular-microcirculation may increase susceptibility of systemic anti-cancer therapy.

Outcome after surgery for primary hyperparathyroidism: ten-year prospective follow-up study.

Clinical outcome after surgery for primary hyperparathyroidism was evaluated in a prospective long-term, follow-up study. From August 1, 1987 to August 31, 1998 a total of 360 patients were prospectively investigated and included in a follow-up study. All patients underwent follow-up examinations at regular surveillance intervals. The postoperative course is known for 94.5% of all patients. Follow-up was 1 month to 10 years (median 24 months; mean 34.5 +/- 29.8 months). Asymptomatic primary hyperparathyroidism was rare (6%), and its true frequency could be confirmed only postoperatively because some of the patients were unaware of mild symptoms of hypercalcemic syndrome prior to surgery. Surgical cure was obtained in 97.7% of patients after initial cervical exploration; and successful parathyroidectomy provided long-term relief of symptoms. Within 2 years postoperatively, 84% of the patients recovered fully from hypercalcemic syndrome: in 58% of these patients recovery occurred within the first month after surgery. Skeletal symptoms persisted in 24% of patients 2 years postoperatively. To date no patient has developed recurrence of primary hyperparathyroidism. During follow-up in our study population mortality was significantly higher than the expected mortality risk for the German population as a whole (p = 0.00024). The present prospective follow-up study yielded conclusive outcome research data after operative therapy for primary hyperparathyroidism. The high cure rate and low morbidity, as well as the increased mortality, in our study population during follow-up after successful operative therapy for the disease emphasize the importance of early diagnosis and early surgical treatment for primary hyperparathyroidism, even in the absence of manifest symptoms.

Interleukin-7 or interleukin-15 enhances survival of Mycobacterium tuberculosis-infected mice.

Both antigen-presenting cells and immune effector cells are required to effectively eradicate or contain Mycobacterium tuberculosis-infected cells. A variety of cytokines are involved to ensure productive "cross talk" between macrophages and T lymphocytes. For instance, infection of macrophages with mycobacteria leads to effective interleukin-7 (IL-7) and IL-15 secretion, and both cytokines are able to maintain strong cellular immune responses of alpha/beta and gamma/delta T cells. Here we show that either cytokine is able to enhance survival of M. tuberculosis-infected BALB/c mice significantly compared to application of IL-2, IL-4, or phosphate-buffered saline (as a control). Enhanced survival could be achieved only when IL-7 or IL-15 was delivered as a treatment (i.e., 3 weeks postinfection), not when it was administered at the time of infection. Increased survival of M. tuberculosis-infected animals was observed following passive transfer of spleen cells harvested from M. tuberculosis-infected, IL-7- or IL-15-treated animals, but not after transfer of spleen cells obtained from mice which received either cytokine alone. Histological examination revealed that IL-7 and IL-15 failed to significantly impact on the number and composition of granulomas formed or the bacterial load. Our data indicated that administration of IL-7 or IL-15 to M. tuberculosis-treated animals resulted in a qualitatively different cellular immune response in spleen cells as reflected by increased tumor necrosis factor alpha and decreased gamma interferon secretion in response to M. tuberculosis-infected antigen-presenting cells.

Effect of low molecular weight heparin (Certoparin) versus unfractionated heparin on cancer survival following breast and pelvic cancer surgery: A prospective randomized double-blind trial.

Recent studies suggest that low molecular weight heparin (LMW heparin) therapy in malignancy may improve cancer survival following surgical resection. We studied prospectively whether cancer mortality during follow-up in women with previously untreated breast, and pelvic cancer is reduced in those who randomly received LMW heparin (Certoparin) compared to patients given unfractionated heparin (UF heparin) for thrombosis prophylaxis during primary surgery. In a prospective, randomized, double-blind clinical trial, 160 patients received Certoparin and 164 UF heparin until post-operatively day 7. Survival estimations are based on the outcome data from a subset of 140 LMW heparin - and 147 UF heparin recipients. Long-term survival in the Certoparin group compared to the UF heparin group was significantly improved after 650 days (P=0. 0066) but not thereafter when analysis was performed on all cancer cell types combined. In the probability estimates survival benefit within this time was restricted to patients with pelvic cancer but was not observed in breast cancer. However, in breast cancer patients who received LMW heparin the impact of classical tumor prognostic markers was statistically significant after 1,050 days but not after 650 days. Thus, breast cancer patients with unfavorable prognosis seem to benefit in terms of survival advantage from LMW heparin within the 650 days after surgery. These results suggest that improvement in cancer survival can be achieved after even a short course of treatment with LMWH (compared to UFH) given for DVT prophylaxis in the post-operative period. An effect of UFH on disease outcome is not excluded. Further definitive trials of LMWH vs. placebo for cancer outcome (rather then DVT) using doses and schedules that may be more optimal are indicated.

Low- versus high-dose radiotherapy for Graves' ophthalmopathy: a randomized, single blind trial.

Orbital radiotherapy (Rx) is a commonly used treatment for Graves' ophthalmopathy (GO), but controlled clinical trials evaluating different Rx doses and application forms have not been performed. In euthyroid patients with moderately severe GO, we randomly compared the efficacy and tolerability of three Rx protocols. Orbital Rx (telecobalt) was administered either in 20 divided fractions of 1 Gray (Gy) weekly over 20 weeks (group A) or in 10 fractions of 1 Gy (B) and 2 Gy (C) daily over 2 weeks. Before and 24 weeks after starting Rx, ophthalmic investigation and magnetic resonance imaging were performed. Response to therapy, defined as a significant amelioration of three objective parameters, was noted in 12 A (67%), 13 B (59%), and 12 C (55%) subjects (C vs. A, P = 0.007). Ophthalmic symptoms and signs regressed most in group A; changes in lid fissure width were -1.5, -0.5, and 0 mm in the A, B, and C groups, respectively (A vs. C, P = 0.005), whereas changes in intraocular pressure (upgaze) were -3, +1, and -1.5 mm Hg, respectively (A vs. B, P = 0.002). The median decreases in proptosis were -2 mm (A, P = 0.0001), -1.5 mm (B, P = 0.02), and -1 mm (C, P = 0.007; A vs. C, P = 0.0380. Visual acuity (+0.15; P = 0.02) and eye muscle motility (bulbar elevation, 30 degrees vs. 37 degrees, P = 0.03, A vs. C, P = 0.0020; abduction, 45 vs. 49 degrees, P = 0.02; A vs. C, P = 0.017) improved in group A only. A significant change in all rectus muscle areas was noted in 14 A (78%), 12 B (55%), and 9 C (41%) subjects (C vs. A, P = 0.002). A decrease in the NOSPECS classes was observed in 12 A (67%), 13 B (59%), and 13 C (59%) patients (A vs. B/C, P = 0.01). Rx-induced conjunctivitis was not observed in group A, but was seen in 4 B (18%) and 8 C (36%) subjects (C vs. A, P = 0.003). At 24 weeks, satisfaction rates were 67%, 59%, and 55% in the A, B, and C groups, respectively (C vs. A, P = 0.008). Thus, in patients with moderately severe GO, similar response rates were observed for low and high Rx doses, but the 1 Gy/week protocol was more effective and better tolerated than the short arm regimens.