Effect of melatonin on the regulation of proenkephalin and prodynorphin mRNA levels induced by kainic acid in the rat hippocampus

The in vivo short-term effect of melatonin on kainic acid (KA)-induced proenkephalin (proENK) or prodynorphin (proDYN) mRNA, and on AP-1 protein levels in the rat hippocampus, were studied. Melatonin (5 mg/kg) or saline was administered intraperitoneally (i.p.) to rats 30 min prior to and immediately after i.p. injection of KA (10 mg/kg). Rats were sacrificed 1 and 3 h after KA injection. The proENK and proDYN mRNA levels were significantly increased 3 h after KA administration. The elevations of both proENK and proDYN mRNA levels induced by KA were significantly inhibited by the preadministration with melatonin. The increases of proENK and proDYN mRNA levels induced by KA were well-correlated with the increases of c-Fos, Fra-2, FosB, c-Jun, and JunB protein levels, which were significantly increased 3 h after KA administration and effectively inhibited by administration with melatonin. In an electrophoretic mobility shift assay, both AP-1 and ENKCRE-2 DNA binding activities were increased by KA, which were also attenuated by the administration of melatonin. In addition, cross-competition studies revealed that AP-1 or ENKCRE-2 DNA binding activity was effectively reduced by the 50x unlabeled cross-competitor. Therefore, these data suggest that melatonin has an inhibitory role in KA-induced gene expression, such as proENK and proDYN mRNA expression, and this may be due to a reduction of KA-induced AP-1 or ENKCRE-2 DNA binding activity.     

Interfractional variation in position of the uterus during radical radiotherapy for cervical cancer.

BACKGROUND AND PURPOSE: This study was conducted to investigate the positional change of the uterus during radiotherapy which can degrade the accuracy of three-dimensional conformal radiotherapy (3DCRT) and intensity modulated radiotherapy (IMRT). PATIENTS AND METHODS: Sixty-six patients received radical radiotherapy for cervical cancer in Samsung Medical Center. For each patient, two MRI scans were taken; one was before beginning radiotherapy and the other was in the third or fourth week of radiotherapy. In T2-weighted MRI images, the positional change of the uterus was quantified by measuring six parameters; the distance from the external uterine opening to the isthmus of the uterus (Dcx), the distance from the isthmus of the uterus to the uterine fundus (Dco), the perpendicular distance of the uterine body to the uterine corpus (Dco-per), the angle between the vertical line and the cervical canal in sagittal images (Acx), the uterine corpus angle from the vertical line in sagittal plan (Aco), the angle between the uterine corpus from an arbitrary bony landmark and a vertical mid line in axial images (Aco-axi) RESULTS: Mean value of change in Dcx+Dco of tumor size during treatment was 8.0 mm in small tumors and 17.9 mm in large tumors. Among 44 anteflexed uterus patients, 5 changed into a retroflexed position. 12 patients (18%) had a greater than 30 degrees variation in any angle. For patients under 60 years, the difference in Acx was statistically significant. CONCLUSIONS: Positional changes of the uterus during radiotherapy should be considered in the treatment planning of 3DCRT or IMRT, particularly in patients under 60 years or those with tumor size greater than 4 cm in diameter.     

Radiation Therapy Results for Patients Undergoing Inappropriate Surgery in the Presence of Invasive Cervical Carcinoma

Total vaginal or abdominal hysterectomy was considered an inadequate treatment method for invasive uterine cervix cancer. Usually the procedure was inadvertently performed on patients who were thought preoperatively to have benign or premalignant conditions. Between 1985 and 1993, 64 patients undergoing hysterectomy in the presence of invasive cervical cancer were treated with external radiation therapy and/or intracavitary radiotherapy. Preoperative diagnoses were carcinomain situ(36), severe dysplasia (2), and early invasive cancer (14), and others were benign disease. Overall 5-year survival and relapse-free survival rates were 75.8 and 77.5%, respectively. For patients in retrospective stage IA, IB, and IIB (gross residual after surgery), overall 5-year survival rates were 90.9, 88.8, and 27.9%, respectively. Thirteen patients developed treatment failure; most of them (10/13) were patients with gross residual disease. Patients with early invasive cervical cancer (stage IA) had no treatment-related failure. Prognostic factors affecting survival by univariate analysis were retrospective stage (P= 0.0000) and preoperative diagnosis (P= 0.0021). Tumor histology was marginally significant factor (P= 0.0938). By multivariate analysis, only retrospective stage was significant prognostic factor (P= 0.0001). Adjuvant radiotherapy appears to be an effective treatment method for patients with presumed stage IA and IB after inadvertent hysterectomy. Survival for patients with gross disease remaining after inappropriate hysterectomy is poor. So, early cancer detection and proper management with precise pretreatment staging is necessary to avoid inadherent hysterectomy, especially in cases of gross residual disease.     

Metabolic and clinical effects of progestogens.

Synthetic progestogens differ not only in their hormonal potency, but also in their spectrum of hormonal activities. Beside their progestogenic and anti-oestrogenic effects, they may exert oestrogenic, androgenic, antiandrogenic, glucocorticoid and/or anti-mineralocorticoid activities. Consequently, progestogens may influence various metabolic parameters and modulate oestrogen-induced alterations in lipid metabolism, haemostasis, and various other factors. Progestogens with androgenic properties may counteract ethinyloestradiol (EE)-induced changes in lipoprotein metabolism, but do not cause atherosclerosis in the presence of EE. Oral contraceptives (OCs) containing androgenic progestogens which attenuate the EE-dependent changes in haemostasis, may be associated with a lower risk of venous thromboembolic disease than OCs whose progestogens have a less androgenic profile. Progestogens with androgenic activity may also antagonize oestrogen-induced alterations in various other hepatic proteins and modulate the effect of EE on growth factors. Progestogens with antiandrogenic activity may enhance the beneficial effect of EE in women with hyperandrogenic manifestations. Progestogens with glucocorticoid effects may increase procoagulatory activity in the vessel wall, while progestogens with anti-mineralocorticoid activity may reduce the aldosterone-induced water-retention in some women. For most women the differences in the hormonal pattern of progestogens used in OCs are without clinical relevance, but may be useful for women predisposed for the development of certain disorders.     

Subtle CD20 positivity in the bone marrow of a patient who has a mucosa‐associated lymphoid tissue lymphoma should not be regarded as evidence of involvement in the bone marrow

Aims: Bone marrow (BM) biopsies of some mucosa‐associated lymphoid tissue (MALT) lymphoma patients show scattered or small clusters of CD20+ cells without definite lesions (subtle CD20 positivity). The aim of this study was to evaluate the clinical significance of BM involvement and subtle CD20 positivity in 122 patients diagnosed with MALT lymphoma. Methods and results: Patients were divided into three categories: BM involvement [BM(+)], subtle CD20 positivity, and no BM involvement [BM(?)]. Eleven (9%) showed BM involvement, and 17 (14%) showed subtle CD20 positivity. BM(+) patients had significantly worse progression‐free survival (PFS) than BM(?) patients [hazard ratio (HR) 6.25, P = 0.01], but there was no significant difference between subtle CD20 positivity and BM(?) patients. Patients with >30 CD3+ cells among 100 nucleated cells in the areas with increased numbers of CD3+ cells had significantly worse PFS than those with <15 CD3+ cells (HR 5.49, P = 0.02). BM(+) patients with >30 CD3+ cells had worse PFS than those with ≤30 CD3+ cells (P = 0.029), with an extent of BM(+) involvement of >10% positively correlating with >30 CD3+ cells (P = 0.015). Conclusions: Patients with BM(+) MALT lymphoma showed significantly worse PFS than those with subtle CD20 positivity and BM(?) MALT lymphoma, but the PFS of patients with subtle CD20 positivity MALT lymphoma was not significantly different from that of those with BM(?) MALT lymphoma. Increased numbers of BM T cells in MALT lymphoma patients might be suggestive of a worse prognosis.     

Barotrauma-Induced Pneumocephalus Experienced by a High Risk Patient after Commercial Air Travel

A 49-year-old female with a history of several neurosurgical and otolaryngologic procedures for occipital meningioma and cerebrospinal fluid leaks was diagnosed with pneumocephalus after a one hour flight on a domestic jet airliner. Despite multiple operations, the air appeared to enter the cranium through a weak portion of the skull base due to the low atmospheric pressure in the cabin. The intracranial air was absorbed with conservative management. The patient was recommended not to fly before a definite diagnostic work up and a sealing procedure for the cerebrospinal fluid leak site had been performed. Recent advances in aviation technology have enabled many people to travel by air, including individuals with medical conditions. Low cabin pressure is not dangerous to healthy individuals; however, practicing consultant neurosurgeons should understand the cabin environment and prepare high risk patients for safe air travel.