Colorectal hemangioma: radiologic findings

The authors correlated radiographs with the clinical and histologic data of 12 patients with colorectal hemangioma. All patients presented with rectal bleeding, which was chronic in seven. Phleboliths were also visible in seven cases, which correlated with chronic bleeding in five. On barium studies, three masses were soft and three produced rigid narrowing. The atypical features of rigid luminal narrowing, which might mimic a carcinoma, and hypovascularity correlated with chronic bleeding or visible phleboliths, which suggest the correct diagnosis of colorectal hemangioma.     

Early human thymocyte proliferation is regulated by an externally controlled autocrine transforming growth factor-beta 1 mechanism

Early thymocytes undergo extensive proliferation after their entry into the thymus, but cellular interactions and cytokines regulating this intrathymic step remain to be determined. We analyzed the effects of various T-cell growth factors and cellular interactions on in vitro proliferation of early CD2+CD3/TCR-CD4-CD8- (triple negative [TN]) human thymocytes. Freshly isolated TN cells were then assayed for their growth capacity after incubation with CD2I+III-monoclonal antibody (MoAb), recombinant human interleukin-2 (IL-2), IL-7, and/or IL-4. These cells displayed significant proliferative responses with IL-4, IL- 7, or CD2-MoAb+IL-2. The addition of recombinant transforming growth factor beta (TGF beta) or autologous irradiated CD3+CD8+CD4- cells to TN cell cultures dramatically decreased their growth responses to IL-2 and IL-7, whereas IL-4-induced proliferation was less sensitive to growth inhibition. We thus asked whether the CD8+ cell-derived inhibitory effect was due to TGF beta. The addition of neutralizing anti-TGF beta MoAb completely abolished CD8+ cell-derived inhibition of TN cell growth. Analysis of CD8+ cell-derived supernatants indicated that these cells had low TGF beta 1 production capacity, whereas TN cells secrete significantly high levels of TGF beta 1. Cell fixation studies showed that TN cells were the source of the TGF beta. TGF beta 1 released from TN cells was in the latent form that became the active inhibitory form through interaction of TN cells with CD8+ cells. Together, these data suggest a role for TGF beta 1 as an externally controlled, autocrine inhibitory factor for human early thymocytes, with a regulatory role in thymic T-cell output.     

Analysis of local recurrence after breast conservative treatment for invasive breast cancer: a single institution cohort

In a group of 900 patients treated for carcinoma of the breast, we evaluated patient-, tumour- and treatment-related parameters, predicting the success or failure of conservative treatment for invasive breast cancer. Thirty-one patients developed local recurrences which were detected within 0.1-12.1 years after treatment of the primary tumour (with a median of 6.2 years), providing a risk of 2% at 5 years and 9% at 10 years. The locally recurrent tumours and their original primary tumours of 28 patients could be retrieved from the pathology laboratory archives. These 28 tumours of the recurrence group (RG) were matched with tumours without local recurrence, the non-recurrence group, for age at time of diagnosis, duration of follow-up and T- and N-stage. The tumours were studied for type and grade of invasive tumour including the in situ component and involvement of surgical margins. In addition, the expression of cell-cycle proteins, p53, Ki-67 (MIB-1) and BCL-1, as well as HER-2/ neu oncoprotein, estrogen and progesterone receptor were investigated. We found a mean age at diagnosis for the RG of 50 years, and the mean age at time of diagnosis for the whole group of 900 patients was 56 years (p=0.003). Thirty-nine percent of the RG had a positive surgical margin, which was the case for only 18% in the control group (p=0.09). The presence of the in situ component was also correlated with increased local recurrence (p=0.022). Furthermore, local recurrence was also associated with a significantly increased occurrence of distant metastases (p=0.001). We conclude that breast conservative treatment is safe with a low local recurrence rate.     

Relevance of methodological design for the interpretation of efficacy of drug treatment of premature ejaculation: a systematic review and meta-analysis

The aim of this systematic review and meta-analysis is to evaluate whether the design and methodology of drug-treatment studies of premature ejaculation affect the efficacy outcome differently. Therefore, methodological, design and efficacy data from 79 studies (3034 males), published between 1943 and 2003, are reviewed. A meta-analysis is performed on 43 selective serotonin reuptake inhibitors (SSRIs) and clomipramine studies (1514 males), published between 1973 and 2003; these studies were pooled to provide a summary variance-weighted effect size. The antidepressant-induced percentage increase of the intravaginal ejaculation latency time (IELT) was calculated and examined against various methodological items. A significant difference in efficacy between SSRIs was observed. Using daily treatment, paroxetine appeared more effective than the other SSRIs. Retrospective use of a questionnaire, subjective reports, single-blind and open study designs generate far greater variability of ejaculation time both at baseline and during active drug treatment than real time assessment by stopwatch. In conclusion, at daily treatment, the overall efficacy of paroxetine, clomipramine, sertraline and fluoxetine is comparable, but paroxetine exerts the strongest ejaculation delay. Only eight (18.5%) studies on antidepressant treatment fulfilled all criteria used in evidence-based medicine, for example, randomised, double-blind studies with prospective real time (stopwatch) assessment of the IELT at each intercourse. Single-blind studies, open designs, retrospective reporting, or the use of a questionnaire to assess ejaculation time should be avoided.     

Effects of oral prednisolone on biomarkers in synovial tissue and clinical improvement in rheumatoid arthritis

OBJECTIVE: To create greater understanding of the changes in synovial tissue parameters that occur in conjunction with clinical response by using an effective therapy, in order to facilitate the planning of future studies with therapeutic agents for rheumatoid arthritis (RA). METHODS: Twenty-one patients with active RA were randomized to receive either oral prednisolone (n = 10) or placebo (n = 11) for 2 weeks. In all patients, synovial tissue biopsy specimens were obtained by arthroscopy directly before treatment and after 14 days of treatment. Immunohistochemical analysis was performed to characterize the cell infiltrate and vascularity. Stained tissue sections were analyzed by digital imaging. Statistical analysis was performed using an analysis of covariance model. RESULTS: After treatment, the mean Disease Activity Score in 28 joints (DAS28) was 2.0 units lower (95% confidence interval [95% CI] 1.0-3.0) in patients who received prednisolone than in those who received placebo. In the prednisolone group, the mean (+/-SD) DAS28 decreased from 6.27 +/- 0.95 to 4.11 +/- 1.43 after therapy; minimal change was observed in the placebo group. For macrophages, the estimated effect of prednisolone was large. Patients receiving active treatment had fewer (mean 628 cells/mm(2) [95% CI 328-927]) macrophages after therapy compared with those receiving placebo. A reduction in the total number of CD68+ macrophages, from 1,038 +/- 283 cells/mm(2) before treatment to 533 +/- 248 cells/mm(2) after treatment, was observed in the prednisolone group. There were clear trends toward decreased infiltration by T cells, plasma cells, and fibroblast-like synoviocytes after active treatment. We observed a trend toward a reduction in alphavbeta3+ newly formed blood vessels and expression of vascular growth factors after prednisolone therapy. CONCLUSION: Prednisolone therapy in RA is associated with a marked reduction in macrophage infiltration in synovial tissue, suggesting that synovial macrophage numbers could be used as a biomarker for clinical efficacy.     

Recurrent cervical cancer: detection and prognosis

BACKGROUND: Only a small proportion of cervical cancer recurrences is detected during routine follow-up. We investigated which percentage of recurrences is detected during follow-up, which diagnostic tools are helpful to detect recurrent disease and which factors are of prognostic significance once recurrent disease has been established in patients treated for cervical cancer stage IB-IVA. METHODS: Characteristics of the primary tumor, characteristics of recurrent disease and follow-up were collected retrospectively from clinical records of 277 patients who achieved a complete remission of at least 3 months after primary treatment for cervical cancer in 1992, 1993 and 1994 in three university hospitals in the Netherlands. RESULTS: Of 277 patients, 47 (17%) developed recurrent disease; this was most often detected after self-referral (45%), and in 32% during routine follow-up. Survival did not differ significantly between these two groups. The presence of symptoms (87%) was the most important first abnormal test result leading to diagnosis of recurrence. In univariate analysis, disease-free interval (DFI) and treatment modality were significant prognostic factors for crude survival of recurrence. However, treatment modality varied considerably and the subgroups were small. Therefore, multivariate analysis was not feasible and clinically valid conclusions could not be drawn. CONCLUSIONS: In only 32% of all cases, recurrence was detected during a scheduled follow-up visit. In the majority of patients, recurrent cervical cancer was detected by symptoms (87%). In recurrent disease, DFI was a prognostic factor for survival.     

Recurrent cervical cancer: detection and prognosis

BACKGROUND: Only a small proportion of cervical cancer recurrences is detected during routine follow-up. We investigated which percentage of recurrences is detected during follow-up, which diagnostic tools are helpful to detect recurrent disease and which factors are of prognostic significance once recurrent disease has been established in patients treated for cervical cancer stage IB-IVA. METHODS: Characteristics of the primary tumor, characteristics of recurrent disease and follow-up were collected retrospectively from clinical records of 277 patients who achieved a complete remission of at least 3 months after primary treatment for cervical cancer in 1992, 1993 and 1994 in three university hospitals in the Netherlands. RESULTS: Of 277 patients, 47 (17%) developed recurrent disease; this was most often detected after self-referral (45%), and in 32% during routine follow-up. Survival did not differ significantly between these two groups. The presence of symptoms (87%) was the most important first abnormal test result leading to diagnosis of recurrence. In univariate analysis, disease-free interval (DFI) and treatment modality were significant prognostic factors for crude survival of recurrence. However, treatment modality varied considerably and the subgroups were small. Therefore, multivariate analysis was not feasible and clinically valid conclusions could not be drawn. CONCLUSIONS: In only 32% of all cases, recurrence was detected during a scheduled follow-up visit. In the majority of patients, recurrent cervical cancer was detected by symptoms (87%). In recurrent disease, DFI was a prognostic factor for survival.     

Lack of relationships between cumulative methylprednisolone dose and bone mineral density in healthy men and postmenopausal women with chronic low back pain

 The medical use of glucocorticoids (GCs) is related to low bone mineral density (BMD). In this study we tested the hypothesis that the cumulative dose of GC is not related to BMD outcome. The study was cross-sectional in design and included healthy individuals with chronic low back pain resistant to conventional treatments. In two steroid-naive subjects cortisol and methylprednisolone (MP) concentrations were serially assessed after a single MP depot injection (160 mg epidurally). Furthermore, in 14 men and 14 postmenopausal women, previously treated with multiple epidural MP depots, endocrine parameters were analysed in relation to BMD outcomes. The minimal cumulative MP dose received by all 28 subjects was 3 g. In the two steroid-naive subjects, cortisol concentrations were completely suppressed for at least 6 days and partly recovered over the course of 30 days. During this period, MP concentrations remained detectable in plasma. In the 28 subjects, the cumulative MP dose received was 7.76±4.23 g in the men and 8.50±3.13 g in the women (mean±1SD). None of the men had osteoporosis, but osteopenia was prevalent in 78.5% according to WHO criteria extrapolated to men. Half of the women had osteoporosis and half of them had osteopenia. The body mass index (BMI) and endogenous oestradiol levels of the men were not related to BMD outcomes. Univariate linear relationships in women were found between BMI and spinal (r 0.62; P=0.02) and total hip BMD (r 0.61; P=0.03), but not femoral neck BMD. In women, relationships were also found between the total and, for protein binding-corrected oestradiol levels, and spinal BMD (r 0.70; P=0.01 and r 0.72; P=0.01, respectively) and total hip BMD (r 0.53; P=0.08 and r 0.56; P=0.05, respectively). No significance was observed between endogenous oestradiol levels and the BMD of the femoral neck. The administration of a single MP depot injection (160 mg) resembled a systemic low peak dose GC exposure. The administration of multiple MP depots in men and women with chronic low back pain revealed no relationship between cumulative GC dose and BMD. These findings support the hypothesis of a non-existent relationship between cumulative GC dose and BMD outcomes in healthy men and women with a prior GC administration of at least 3 g. Received: 18 February 2002 / Accepted: 14 June 2002 Acknowledgements We are indebted to Dr Oscar L.H. van Hemel for advice during the performance of the study and to Ineke Bosman for excellent laboratory support.     

Antidepressants and ejaculation: a double-blind, randomized, fixed-dose study with mirtazapine and paroxetine

A double-blind, fixed-dose study in healthy men with lifelong early ejaculation was performed to evaluate potential differences in their effects on ejaculation latency, between clinically relevant doses of the selective serotonin reuptake inhibitor paroxetine and the noradrenergic and specific serotonergic antidepressant mirtazapine. Twenty-four men with an intravaginal ejaculation latency time (IELT) less than 1 minute were randomly assigned to paroxetine (20 mg/d) or mirtazapine (30 mg/d) for a period of 6 weeks; half the dosage was given in the first week. During the preceding 1-month baseline and 6-week treatment period, intravaginal ejaculation latency times were measured at home using a stopwatch procedure. The trial was completed by 18 men. Analysis of variance revealed a between-group difference in the development of the delay in intravaginal ejaculation latency time over time (P < 0.001); the intravaginal ejaculation latency time after paroxetine and mirtazapine gradually increased from 15 to 119 s and from 23 to 28 s, respectively, after 6 weeks. Paroxetine 20 mg/d exerted a strong delay (maximum 5.7-fold increase), whereas mirtazapine 30 mg/d did not delay ejaculation (0.9-fold increase). These results confirm earlier findings that paroxetine, but not mirtazapine, significantly delays orgasm and ejaculation in men with early ejaculation, whereas mirtazapine is devoid of any effect on it.