Rapamycin Improves Vascular Remodelling in a Controlled Rat Model of Monocrotaline-Induced Pulmonary Hypertension

ABSTRACT Background: Pulmonary arterial hypertension (PAH) is a serious disease characterized by the progressive elevation of the pulmonary arterial resistance, leading to the right ventricular failure and death. Objective: To evaluate the effect of rapamycin (RAPA), a potent cell-cycle inhibitor, on exercise capacity, right ventricular hypertrophy and pulmonary vascular remodelling on rats. Methods: A total of 39 nine-week-old male Wistar rats (160-240 g) were divided into three groups: the control (n = 10), PAH control (n = 15) and PAH-RAPA (n = 14) groups. On the 1st day, 60 mg/kg monocrotaline was injected intraperitoneally to induce PAH in the PAH control group and PAH-RAPA groups. On the 21st day, 3 mg/kg/day RAPA was started orally, and the animals were followed for 35 days. On the 35th day, the exercise capacity of the rats was analysed through a modified forced swimming test. After measuring their right ventricular systolic pressure using an open-chest method, their hearts and lungs were excised and analysed histopathologically for right ventricular hypertrophy and pulmonary vascular remodelling. Results: Rapamycin treatment provided limited and insignificant improvements in exercise capacity, right ventricular systolic pressure and right ventricular hypertrophy of the rats. However, there was significant recovery in the rats' pulmonary artery muscular layer thickness with the RAPA treatment (p < 0.049). On the 35th day, the mortality rate was 0% in the control group, 53.1% in the PAH control group and 42.9% in the PAH-RAPA group. No statistically significant decrease was observed in their mortality rates with the RAPA treatment (p > 0.16); however, a significant recovery was noted in terms of the rats' median life span (p < 0.006). Conclusion: Pulmonary artificial hypertension is a progressive disease that is not curable with current therapies. Rapamycin may have the potential to reverse vascular remodelling and prolong life expectancy in cases of pulmonary hypertension.

Short-term effects of intravitreal ranibizumab and bevacizumab administration on 24-h ambulatory blood pressure monitoring recordings in normotensive patients with age-related macular degeneration.

PurposeTo evaluate effects of intravitreal ranibizumab and bevacizumab administration on ambulatory blood pressure monitoring (ABPM) recordings in normotensive patients with age-related macular degeneration (AMD).Patients and methodsA total of 72 patients (mean age: 61.8(6.2) years, 52.8% were females) diagnosed with AMD were included in this study as divided into ranibizumab (n=34) and bevacizumab (n=38) treatment groups. Twenty-four hour, nighttime, and daytime ABMP values for systolic and diastolic BP were recorded in study groups before and after the third intravitreal injection of ranibizumab or bevacizumab.ResultsRanibizumab injection had no impact on ABPM recordings and dipping status. In the bevacizumab group, increased daytime (129.0(6.6) vs 127.7(6.6) mm Hg, P=0.002) and nighttime systolic (116.9(7.5) vs 112.6(7.1) mmHg, p<0.001) BP and decreased daytime diastolic (80.1(6.5) vs 82.4(6.1)mm Hg, P=0.001) BP were noted in the post-injection period. Also, percentage of non-dippers was significantly increased from 5.3% at pre-injection to 28.9% (P=0.004) at the post-injection period.ConclusionIn conclusion, given that it has no significant impact on ABPM recordings and dipping status, in our study, intravitreal ranibizumab injection may be the better choice in the management of AMD.

Post-transplantation Malignancy After Kidney Transplantation in Turkey.

OBJECTIVE: Kidney transplantation is the best treatment option for end-stage renal disease patients. Increased incidence of post-transplantation malignancy can be caused by immunosuppressive drugs and some oncogenic infections. The aim of this study is to show the incidence of post-transplantation malignancy in patients who had surgery and were followed up in the Organ Transplant Center, Medical Park Antalya, Antalya, Turkey. METHOD: The study was based on 2100 kidney transplantation patients who had surgery between May 2008 and December 2012 and also on 1900 patients who had surgery by members of our team in other centers and who were followed up routinely. In all of our patients, the type of malignancy, the time that malignancy developed, immunosuppressive regimens, and viral status (Epstein-Barr virus and cytomegalovirus) were investigated. RESULTS: Malignancy was developed in 30 patients (60% of them were male, median age was 52.1 years). Post-transplantation malignancy development time was a median of 5.1 years. The types of malignancies were as follows: non-melanoma skin cancer in 12 patients (40%), urogenital cancer in 7 patients (24%), breast cancer in 4 patients (14%), lymphoproliferative disease in 3 patients (10%), thyroid cancer in 2 patients (6%), and lung cancer in 2 patients (6%). DISCUSSION: In this study, we did not find any increased post-transplantation malignancy risk in our patients. This finding could be due to the low-dosage immunosuppressive protocols that we used.

Comparison of the protoscolocidal effectiveness of hypertonic saline, povidone-iodine and albendazole solutions in an experimental lung hydatid cyst model.

Secondary hydatidosis is an important problem encountered during the surgical treatment of hydatid cysts. This study describes an experimental model of secondary hydatidosis by cyst inoculation, used to explore whether simultaneous inoculation of protoscolocidal agents could prevent secondary hydatidosis. Fertile cyst fluid was injected into the pleural space of rabbits alone (group 1, n = 8), and in combination with 2% albendazole solution (group 2, n = 8), 20% hypertonic saline (group 3, n = 8) or 10% povidone-iodine (group 4, n = 8). Computed tomography imaging of the thorax, indirect haemagglutination (IHA) titres and eosinophil counts were used to determine cyst development. After 16 months, three control rabbits had pneumothorax, seven had cysts and four had parenchymal nodules. Histopathological investigation of nodules revealed 87.5% cyst formation. Pleural thickening was observed in rabbits from all groups. Cyst formation rates, IHA titres and eosinophilia counts were higher in group 1 than in groups 2-4. This study demonstrated the experimental formation of secondary hydatidosis and found that topical protoscolocidal agents were beneficial in preventing cyst recurrence.

Tissue leptin levels in patients with breast cancer.

PURPOSE: High leptin serum levels, overexpression of leptin and its two main receptor isoforms, OBR-L and OBR-S, have been documented in breast cancer patients. In the present study, the relationship between tissue leptin levels and breast cancer was evaluated. METHODS: Thirty-three normal breast tissue samples and 33 breast cancer tissue samples from 33 patients with breast cancer were evaluated. The association of tissue leptin levels and important prognostic factors related to breast cancer was analyzed. RESULTS: Mean tissue leptin levels in breast cancer tissue samples (5.02 + or - 1.06 pg/ml) were significantly higher than those found in normal breast tissue (2.02 + or - 0.83 pg/ml; p=0.01). No correlation was found in tissue leptin levels and menopausal status, hormone receptor and HER-2/neu status, lymph node involvement, and histopathologic features. CONCLUSION: High leptin levels were significantly higher in breast cancer tissue compared with normal tissue. No special correlation was found between tissue leptin levels and different clinicopathological characteristics.

Relapse patterns and related prognostic factors in patients with mobile tongue cancer treated with postoperative radiotherapy.

PURPOSE: To retrospectively assess prognostic factors and patterns of relapse in patients with oral tongue cancer treated by adjuvant radiotherapy (RT). PATIENTS AND METHODS: Between 1995 and 2005, 65 patients with stage II-IV oral tongue cancer were treated with postoperative adjuvant RT at our institution. The influence of multiple patient- and treatment-related factors on local and regional control, and overall survival (OS), locoregional failure- free survival (LRFFS) and cause-specific survival (CSS) were evaluated. Median patient follow-up was 74 months. RESULTS: Five-year disease-free survival (DFS), LRFFS and CSS rates were 56, 60 and 58%, respectively. During the study period 27 (41.5%) patients had locoregional failures. Seventeen of the recurrences were in the primary tumor region, 4 in the neck, 6 in both regions. Most of the local failures occurred in the first year (median 13 months, range 5-15). Gender, T stage, stage (AJCC TN stage), surgical margin, localization of tumor, and hemoglobin level had predictive value for improved local-regional control in univariate analysis. In total, 35 deaths occurred: 28 patients died of progressive disease, one patient died due to another primary tumor (esophageal cancer) and 6 patients died of other causes. CONCLUSION: Local failure was the most important problem concerning the final outcome. High local recurrence rates and poor survival rates are important issues in the management of oral tongue cancer. Further strategies should be directed to enhancing cure rates.

Incidence and management of acute endophthalmitis after intravitreal bevacizumab (Avastin) injection.

INTRODUCTION: The aim of this study was to report the incidence and management of acute endophthalmitis after intravitreal injection of Avastin (bevacizumab), and visual acuity outcomes of three eyes of three patients who developed acute endophthalmitis following intravitreal injection of Avastin. METHODS: This clinical retrospective, non-comparative study included 3022 intravitreal injections of 1.25 mg bevacizumab consecutively performed for 1822 eyes with exudative age-related macular degeneration and other retinal diseases. Of 3022 injections, 1200 were reinjections. After clinical appearance of post-injection endophthalmitis, immediate intervention was performed, including injection of intravitreal antibiotics and early pars plana vitrectomy. RESULTS: Three eyes of three patients with acute postoperative endophthalmitis were identified in the first week following intravitreal injections of 1.25 mg bevacizumab. Among of these patients, two cases were culture-positive and one case was culture-negative. Compared with presenting visual acuities, all of three patients improved at the end of follow-up time. The overall incidence rate of post-injection culture-proven endophthalmitis was 0.066%. DISCUSSION: Acute culture-proven endophthalmitis is still a potential complication of intravitreal bevacizumab injection (approximately 0.066%) despite using maximal sterile techniques. Acute post-injection endophthalmitis following intravitreal bevacizumab occurs rapidly and can result in severe loss of vision. Prompt recognition and treatment are key in maximizing outcomes in patients who developed endophthalmitis after intravitreal injection of bevacizumab.

The effect of intravitreal bevacizumab (avastin) administration on systemic hypertension.

AIMS: To determine the short-term effect of intravitreal bevacizumab administration on systemic blood pressure levels of patients and to evaluate the safety of the drug in these patients. METHODS: Study population was divided into two groups: group A comprised patients who had hypertension and were under medication with antihypertensive drugs; group B comprised patients with normal blood pressure and were not under medication with antihypertensive drugs. All patients were graded according to their blood pressure levels before single dose of bevacizumab (0.05 ml; 1.25 mg) injection, and at day 1 and weeks 1, 3, and 6 thereafter. The blood pressure levels were analysed using repeated measures of analysis of variance (ANOVA). A P-value of <0.05 was considered significant. RESULTS: The study population included 82 patients with a mean age of 67.2+/-5.2 years. In group A, the systolic blood pressure levels showed significant increases at weeks 1, 3, and 6 (P=0.001, P<0.001, and P=0.003, respectively) compared with baseline. Similarly, diastolic blood pressure levels were significantly higher at weeks 3 (P<0.001) and 6 (P=0.016). In group B, the mean systolic and diastolic blood pressure levels showed significant elevations only at week 3 (P=0.004 and P<0.001, respectively). The percentages of both group A and B patients with normal blood pressure decreased at week 3 compared with baseline (P<0.001 and P=0.012 for groups A and B, respectively). CONCLUSIONS: The findings of this study show that there is a risk of disregulation of blood pressure levels or persistence of hypertension in hypertensive patients after intravitreal bevacizumab injections.

Leptin, soluble interleukin-6 receptor, C-reactive protein and soluble vascular cell adhesion molecule-1 levels in human coronary atherosclerotic plaque.

The aim of the present study was to explore the relationship between tissue levels of leptin, soluble interleukin-6 receptor (sIL-6R), high-sensitive-C-reactive protein (hs-CRP) and soluble vascular cell adhesion molecule-1 (sVCAM-1) in atherosclerotic plaques, and traditional risk factors. Coronary artery specimens were obtained from 35 consecutive patients (26 men and nine women) who underwent coronary artery bypass grafting procedure. The mean tissue levels of leptin, hs-CRP and sIL-6R were significantly higher in patients with diabetes mellitus than without diabetes mellitus. When patients were classified according to the smoking status, the mean tissue levels of leptin, hs-CRP and sIL-6R were significantly higher in current smokers than both former smokers and non-smokers. In addition, the mean tissue levels of leptin and sIL-6R were significantly higher in former smokers than non-smokers. There was a positive association between leptin and hs-CRP, sIL-6R and plasma glucose in all patients. Plasma HDL levels were associated negatively with atherosclerotic tissue levels of leptin. Tissue levels of sIL-6R were associated significantly in a positive manner with leptin, hs-CRP and plasma glucose, while tissue levels of hs-CRP were associated with both leptin and sIL-6R. In conclusion, it is attractive to speculate that hs-CRP, sIL-6R and leptin could act synergistically in course of local inflammatory activity and those molecules may not be just markers of inflammation and cardiovascular risk but are also likely to play a pathogenic role in atheromatous plaque. In addition, atherosclerotic tissue levels of CRP, sIL-6R and leptin were significantly higher in current smokers and patients with diabetes.

Thyroid cancer in hyperthyroidism: incidence rates and value of ultrasound-guided fine-needle aspiration biopsy in this patient group.

Three hundred and thirty-three hyperthyroidism cases were retrospectively investigated to provide information about the association between hyperthyroidism and thyroid cancer. There were 112 cases of toxic multinodular goiter (TMNG), 77 cases of toxic nodular goiter (TNG) and 144 cases of Graves' disease (GD). All nodules detected in GD patients, all nodules greater than 1 cm diameter in nodular goiter patients, nodules 5-10 mm size diameter if they had calcification were fine-needle biopsied (FNAB) under ultrasound guidance (US-guided), and a total of 612 such biopsies were performed. The biopsy samples were cytologically assessed as benign (no.=552; 90.2%), suspicious (no.=6; 1.1%), malignant (no.=13; 2.1%), or inadequate for diagnosis (no.=41; 6.7%). All patients with a biopsy diagnosis of malignant or suspicious nodules underwent surgery. Histological examination confirmed the diagnosis of thyroid cancer in all 13 (2.1%) patients with malignant FNAB findings. Papillary thyroid carcinoma (PTC) was identified in 2 patients with TMNG (%1.8), 5 with TNG (%6.5) and 5 with GD (%3.5). Metastatic follicular thyroid carcinoma (FTC) was identified in a patient with TNG. Thyroid malignancy (micro- or macrocarcinoma) was diagnosed pre-operatively in all 13 cases by US-guided FNAB. Thyroid cancer was diagnosed in 6 (5.5%) of the 109 nodules detected in the TNG group, 2 (0.44%) of the 452 nodules detected in the TMNG group, and 5 (9.8%) of the 51 nodules detected in the GD group. Two (2.6%) of the 77 functioning nodules in the TNG patients were malignant, but none of the 402 functioning nodules in the TMNG patients was malignant. In patients with hyperthyroidism, US-guided FNAB is useful for detecting thyroid cancer in nodules greater than 5 mm diameter before radioiodine therapy or surgery.

Chimerical anti-TNF-alpha, infliximab, inhibits neutrophil chemotaxis and production of reactive oxygen species by blocking the priming effect of mononuclear cells on neutrophils.

Clinical experience with anti-tumor necrosis factor alpha (anti-TNF-alpha) agents implies that these agents can cause a rapid onset amelioration of the symptoms and laboratory parameters in some inflammatory diseases. Precise explanation of this fast antiinflammatory action is not known. The aim of our study is to investigate the direct and indirect effects of anti-TNF agents on the chemotaxis and reactive oxygen species (ROS) production of neutrophils. For this purpose, isolated neutrophil cultures (INCs) and mixed leukocyte cultures were prepared from the venous blood of healthy subjects. Those cultures were separated to different groups according to the presence of anti-TNF or the stimulation of phytohemagglutinin (PHA). In this study, anti-TNF treatment did not change the migration ability of neutrophils in INCs. However, we established that chimerical anti-TNF-alpha, infliximab, inhibits neutrophil chemotaxis and production of ROS by blocking the priming effect of PHA-stimulated circulating mononuclear cells. These results may explain, at least partly, the rapid onset antiinflammatory actions of these agents observed in clinical practice.

Gonadotropin treatment restores in vitro interleukin-1beta and tumour necrosis factor-alpha production by stimulated peripheral blood mononuclear cells from patients with idiopathic hypogonadotropic hypogonadism.

In the present study, we aimed to investigate the effects of testosterone deficiency and gonadotropin therapy on the in vitro production of tumour necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) by peripheral blood mononuclear cells (PBMCs) from patients with idiopathic hypogonadotropic hypogonadism (IHH) in order to elucidate the modulatory role of androgen in cytokine production. Fifteen male patients with untreated IHH and 15 age-matched healthy male subjects were enrolled in the study. Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), free testosterone (FT), sex hormone binding globulin (SHBG), prolactin, and IL-2 and IL-4 levels were also measured. In unstimulated cultures, IL-1beta and TNF-alpha secretion were not significantly different between patient and control groups. However, after stimulation with lipopolysaccharide (LPS), secretion of IL-1beta and TNF-alpha was significantly higher in cultures from untreated patients with IHH than in control subjects. Mean FSH, LH and FT levels were significantly lower, whereas SHBG, IL-2 and IL-4 levels were significantly higher in patients with IHH compared than in controls. In patients with IHH, FT negatively affected the serum levels of IL-4 and in vitro secretion of IL-1beta and TNF-alpha. In addition, IL-2 and IL-4 affected the in vitro secretion of IL-1beta in a positive manner. Gonadotropin therapy decreased both TNF-alpha and IL-1beta in PBMCs from patients with IHH. The levels of serum IL-2 and IL-4 were also decreased by therapy. In conclusion, in the present study, gonadotropin treatment restored the in vitro production of IL-1beta and TNF-alpha by PBMCs from patients with IHH, suggesting that androgen modulates proinflammatory cytokine production, at least directly through its effects on PBMCs. It seems probable that this effect plays an important role in the immunosuppressive action of androgens.

Changes in immunological recovery in patients who received post-transplant G-CSF or GM-CSF after autologous peripheral blood stem cell transplantation (PBSCT).

In this prospective study, the effects of granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) on immunological reconstitution after autologous peripheral blood stem cell transplantation (PBSCT) were investigated for 6 months. Thirty-five patients received G-CSF 5 microg/kg per day and 26 patients received GM-CSF SC 5 microg/kg per day from day 1 to leukocyte engraftment (>1000 per mm3). Peripheral blood samples were obtained on 14, 28, 100, and 180 days after transplantation for immunological evaluation. CD3+, CD4+, CD8+, CD19+, and CD56+ cells were analysed by flow cytometry. Immunoglobulin levels (IgG, IgA, and IgM) and complement levels (C3c and C4) were measured by nephelometry. Both G-CSF and GM-CSF groups were comparable with respect to age, sex, the period from diagnosis to transplantation, total nucleated cells infused, the number of CD34+ cells, conditioning regimens (TBI and non-TBI), and post-transplant infection. CD3+ and CD8+ cells on day 14 following autologous PBSCT + G-CSF were significantly higher than following autologous PBSCT + GM-CSF (p = 0.008 and p = 0.021, respectively). The number of CD4 cells and the CD4/CD8 ratio were not different at several time points between the two groups. CD19+, CD56+ cells and immunoglobulin levels showed a faster recovery pattern in the autologous PBSCT + G-CSF group. The effect of G-CSF on immune reconstitution after autologous PBSCT is more prominent than that of GM-CSF. The possible role of haematopoietic growth factor on immune recovery and its clinical importance should be investigated in further studies.

The effects of folic acid application on IL-1beta levels of human gingival fibroblasts stimulated by phenytoin and TNFalpha in vitro: a preliminary study.

Folic acid (FA), that is required for the integrity of gingival tissues, was found to decrease in patients using phenytoin (PHT). Interleukin-1 beta (IL-1beta) was reported to enhance the extracellular matrix synthesis in fibroblasts. The purpose of this study was to assess the role of FA supplementation on PHT-induced overgrowth by investigating its effect on IL-1beta production of human gingival fibroblasts induced by tumor necrosis factor alfa (TNFalpha) in cell culture. PHT (20 microg/ml), FA (20 or 40 ng/ml) + PHT, PHT + TNF (10 ng/ml), FA (20 or 40 ng/ml) + PHT + TNF, or only culture medium (control) was added to 24-well plates containing fibroblasts. After an incubation period of 72 h, culture medium and cells were harvested separately. Then, IL-1beta levels in cell lysate were measured using enzyme-linked immunosorbent assay. The cellular IL-1beta level in the PHT group was 1 pg/ml. In PHT + 20 or 40 ng/ml FA-added cultures, the results obtained respectively were 0.8 and 0.7 pg/ml, whereas the control group value was 0.7 pg/ml. IL-1beta level was 4 pg/ml in the cultures that PHT and TNFalpha were applied simultaneously (P < 0.05). When PHT and either 20 or 40 ng/ml FA were simultaneously added into TNFalpha-induced cultures, the IL-1beta levels were 1.8 and 1.3 pg/ml, respectively. IL-1beta level in gingival tissues might play a role in PHT-induced overgrowth by increasing in the gingival tissues, and FA application might play a role in decreasing gingival tissues. However, further studies are needed for a more complete understanding of PHT-induced gingival overgrowth at the cellular level.

The effect of testosterone replacement treatment on immunological features of patients with Klinefelter's syndrome.

Although the effects of androgen deficiency in the immune system have long been appreciated, little is known about the immunological features of patients with Klinefelter's syndrome (KS). On the other hand, interest in androgens as a possible treatment for some autoimmune diseases is growing. In the present study, some immunological parameters were evaluated in 26 patients with KS prior to androgen replacement treatment (ART) and the results were compared with those in 19 healthy control subjects. Patients were then treated with testosterone for 6 months and the pre- and post-treatment findings were compared. Serum levels of IgG, IgA, IgM, C3c and C4 were measured by nephelometry and lymphocyte subsets and CD4+/CD8+ ratios were examined by flow cytometry. IL-2 and IL-4 levels were measured by ELISA. Pretreatment levels of the serum IgA, IgG, IgM, IL-2 and IL-4 of the patients were higher than those of the controls and were all decreased significantly following ART. The pretreatment absolute numbers and percentages of CD3+, CD4+, CD19+ cells and CD4+/CD8+ ratios of patients with KS were higher than those of the controls and were all decreased with ART. Percentages of CD8+ cells were increased significantly, while C3 and C4 levels were both significantly decreased after ART. It is concluded that the lack of testosterone in patients with KS enhances cellular and humoral immunity and that ART may suppress this.

A successful and simplified filgrastim primed single apheresis method without large volume apheresis for peripheral blood stem cell collection.

BACKGROUND: There is a tendency to use only one apheresis collection to reduce the morbidity and the cost of peripheral blood stem cell collection. We studied whether rapid and complete engraftment could be achieved by single apheresis by using only Filgrastim without large volume apheresis in previously treated patients. METHODS: Engraftment of single apheresis in 25 patients was compared with those of multiple apheresis in 26 patients; 52% of patients in the single apheresis group and 62% of patients in the multiple apheresis group were heavily pretreated. All patients received 10-15 microg/kg/day of Filgrastim starting on day 14 after 3-4 cycles of induction chemotherapy. Apheresis was performed using Cobe Spectra on day 4, 5 or 6 in the single apheresis group and every other day in the multiple apheresis group after day 3. RESULTS: The median collection volume was 250 ml (250-300 ml) in the single apheresis group and 750 ml (200-1500 ml) in the multiple apheresis group. The median CD34(+) cell number was not significantly different in the two groups (11.79 vs. 9.38x10(6)/kg). The median times to achieve leukocytes > or =1x10(9)/l and platelets > or =50x10(9)/l counts were 10 days (8-21 days) and 15 days (9-38 days) in the single apheresis group vs 11 days (8-23 days) and 20 days (10-32 days) in the multiple apheresis group, respectively (p<0.05). Antibiotic use was less in the single apheresis group than the multiple apheresis group (9 vs. 12 days, p<0.05). CONCLUSION: Adequate numbers of peripheral stem cells were harvested by G-CSF in a single apheresis without large volume apheresis even in heavily pretreated patients. Rapid and complete engraftment occurred in all patients and it was faster in single than multiple apheresis.

A comparative trial of two surface subunit recombinant hepatitis B vaccines vs a surface and PreS subunit vaccine for immunization of healthy adults.

Hepatitis B virus (HBV) infection is the leading cause of chronic hepatitis and cirrhosis in Turkey. The prevalence of hepatitis B surface antigen (HBsAg) positivity in Turkey is 5 to 10%. HBV is almost completely preventable with the use of hepatitis B vaccines. The most commonly used vaccine is that which contains the predominant viral surface (S) polypeptide. It elicits protective antibodies in greater than 90% of healthy subjects. A vaccine containing the PreS1 and PreS2 antigenic domains has recently been reported as being more efficient in achieving successful immunization in individuals who have not previously responded to the isolated S-antigen vaccine. In this study, the efficacy of a S and PreS-containing vaccine was compared with that of two different standard isolated S-antigen-containing vaccines in terms of the immunization protection produced against HBV in normal healthy adults who had not previously been immunized. Seventy-six young adults (aged 17-22) were randomly assigned to receive 1 ml (20 micrograms) of either one of two standard S-subunit recombinant hepatitis B vaccines (Engerix B. or Hepavax) or the combined S and PreS subunit vaccine (Gen Hevac B) intramuscularly in the deltoid muscle at 0, 1 and 2 months. Hepatitis B surface antigen antibody titres were measured at 1, 2 and 12 months. A titre > or = 10 IU ml-1 was considered to be protective. All subjects receiving the two standard isolated S-antigen-containing vaccines responded to the vaccination with reasonable antibody titres. One-half to two-thirds of those vaccinated developed high antibody titres (> 100 IU ml-1). In contrast, 9% of those receiving the combined PreS1 and PreS2 plus S antigens failed to respond, as demonstrated by antibody titres below the level considered to be protective. The mean titres at 12 months were 107 +/- 12 IU ml-1 (Engerix B), 102 +/- 12 IU ml-1 (Gen Hevac B) and 117 +/- 12 IU ml-1 (Hepavax Gene). Hence, no important difference in term of response to vaccination was found between the two different types of vaccines. As recombinant S-subunit vaccines are less expensive than those that combine S and PreS antigens, it is suggested that, when immunizing normal healthy adults, a standard isolated S-antigen-containing vaccine should be used.

Effects of gonadotropin and testosterone treatments on prostate volume and serum prostate specific antigen levels in male hypogonadism.

It is known that prostate specific antigen (PSA) is strongly androgen dependent, but little is known about the effects of gonadotropin and testosterone treatments on the prostate and serum PSA levels in male hypogonadism. We have therefore determined serum PSA levels before and 3 months after treatment in 13 patients with idiopathic hypogonadotropic hypogonadism (IHH) and 14 patients with Klinefelter's syndrome. Plasma FSH, LH, testosterone, PRL, testis and prostate volumes were also determined before and 3 months after treatments. Patients with IHH were treated with hCG/hMG and patients with Klinefelter's syndrome received testosterone treatment. PSA levels were determined by a kinetic enzyme immunoassay method. In patients with Klinefelter's syndrome FSH and LH levels were significantly decreased but total and free testosterone and PSA levels were significantly increased after 3 months of treatment. Right and left testicular volumes were not significantly changed whereas prostate volumes were significantly increased after treatment. In this group PSA levels were significantly and positively correlated with the prostate volume both before (r=0.54, P=0.048) and after treatment (r=0.61, P=0.012). In the IHH group total and free testosterone and PSA levels were significantly increased after gonadotropin treatment but FSH and LH levels did not change significantly. Right and left testicular volumes and the prostate volumes were also significantly increased after 3 months of gonadotropin treatment. In this group PSA levels were correlated with prostate volume before (r=0.74, P=0.004) treatment but not after therapy (r=0.35, P=NS). Our results show that serum PSA levels increase after gonadotropin and testosterone treatment in male hypogonadism, but this could not be used as an index for the evaluation of the androgen action in the treatment of male hypogonadism, since PSA levels following treatments were correlated with the prostate volume or T levels only in patients with Klinefelter's syndrome but not in the IHH group.

Soluble intercellular adhesion molecule-1 concentrations in patients with subacute thyroiditis and in patients with Graves' disease with or without ophthalmopathy.

Increased circulating soluble ICAM-1 (sICAM-1) levels has been previously reported in Graves' disease (GD) patients with or without ophthalmopathy (GO) and in patients with toxic nodular goiter but not in patients with subacute thyroiditis. Conflicting results have also been reported about the usefulness of sICAM-1 levels as a marker for the activity of hyperthyroidism. We have therefore determined sICAM-1 levels by a sandwich enzyme linked immunosorbent assay (ELISA) method in 10 patients with subacute thyroiditis (Group 1), who are at the initial or acute phase of thyroiditis, in 10 hypothyroidic patients with Hashimoto's thyroiditis (Group 2), in 10 patients with euthyroid nodular goiter (Group 3), in 10 patients with untreated GD patients with active ophthalmopathy (Group 4), in 10 hyperthyroid GD patients without clinical ophthalmopathy (Group 5), in 10 patients with GO who are euthyroid and treated with glucocorticoids for 3 months (Group 6) and in 20 normal subjects (Control Group). Groups 1,2,4,5 and 6 (P < 0.00001 for Groups 1,4,5,6 and P < 0.05 for Group 2) but not Group 3 showed increased sICAM-1 levels compared with the control group. However Groups 4 and 6 (patient with GO) showed significantly higher sICAM-1 levels (P = 0.0003 for Group 4 and P = 0.00013 for Group 6) than Group 5. Furthermore Group 4 showed slightly but not significantly higher sICAM-1 levels than Group 6. Mean sICAM levels were significantly decreased 3 months after glucocorticoid treatment (Group 6), but had not returned to normal levels. Three patients did not respond to steroid therapy and their sICAM-1 levels were not decreased. We concluded that patients with GO with or without hyperthyroidism and patients with subacute thyroiditis have elevated sICAM-1 levels. Moreover, sICAM-1 levels reflect the degree of inflammatory activity in the thyroid gland or orbital tissue independent of the thyroidal status, since we found elevated levels in both hyperthyroidism and hypothyroidism.