p21WAF1/CIP1 expression in gestational trophoblastic disease: correlation with clinicopathological parameters, and Ki67 and p53 gene expression.

BACKGROUND: The p21WAF1/CIP1 gene mediates growth arrest by inhibiting G1 cyclin dependent kinases and has been considered as a downstream effector of the tumour suppressor gene p53. AIM: To analyse the role of p21WAF1/CIP1 in gestational trophoblastic disease. METHODS: The immunohistochemical expression of p21WAF1/CIP1 gene was measured in 33 placentas, 28 partial hydatidiform moles, 54 complete hydatidiform moles, and 13 choriocarcinomas in paraffin wax embedded tissue. The results were correlated with p53 (DO7) and Ki67 (MIB1) immunoreactivity as well as clinical progress. RESULTS: p21WAF1/CIP1 immunoreactivity was found predominantly in the nuclei of the syncytiotrophoblasts. p21WAF1/CIP1 protein expression correlated with gestational age in normal placentas (p = 0.0001) but not in hydatidiform moles (p = 0.89). Complete hydatidiform moles and choriocarcinomas had a significantly higher p21WAF1/CIP1 expression compared with normal placentas and partial hydatidiform moles (p < 0.001); there was no difference between placentas and partial hydatidiform moles. No correlation between p21WAF1/CIP1 expression and either the proliferation (Ki67) index (p = 0.34) or p53 protein accumulation (p = 0.68) was demonstrated. There was no significant difference (p > 0.05) in p21WAF1/CIP1 expression between the 17 patients who developed persistent gestational trophoblastic disease and those who did not. CONCLUSIONS: This study suggests that p21WAF1/CIP1 expression in trophoblastic disease may be induced by a p53 independent pathway. The proliferative activity of gestational trophoblastic diseases might not be determined solely by the control of the cell cycle operated by p21WAF1/CIP1. p21WAF1/CIP1 expression is not an accurate prognostic indicator of gestational trophoblastic disease.     

Adenoviruses from human immunodeficiency virus-infected individuals, including two strains that represent new candidate serotypes Ad50 and Ad51 of species B1 and D, respectively

Adenovirus (Ad) isolates from a large number of human immunodeficiency virus (HIV)-infected individuals were compared serologically and genetically with Ad isolates from immunocompetent patients. Between 1982 and 1994, stool and urine samples from 137 subjects with AIDS hospitalized in The Netherlands yielded 143 Ad strains. Forty additional Ad strains were obtained from 35 HIV-positive patients in Manchester, United Kingdom, in 1992 and 1993. Of these 183 HIV-associated Ad strains, 84% belonged to species D and 3% belonged to species C. These strains were compared with 2,301 Ad strains collected during general diagnostic examinations in The Netherlands from 1973 to 1992. Of the latter strains, 5% belonged to species D and 49% belonged to species C. Two of the Ads isolated from fecal specimens of AIDS patients represent new serotypes: candidate Ad serotype 50 (prototype strain, Wan) of subspecies B1 and candidate Ad serotype 51 (prototype strain, Bom) of species D. The DNA restriction enzyme patterns of strains Wan and Bom differed from the patterns of all established prototypes.     

Comparison of MRI with CT for the radiotherapy planning of prostate cancer: a feasibility study

This feasibility study was performed to evaluate the suitability of MRI in defining appropriate pelvic radiotherapy treatment volumes, and to compare MRI sequences with CT for prostate cancer radiotherapy. Five patients with localized prostate cancer, imaged with four MRI sequences (spin echo (SE) T1, turbo SE (TSE) T2, high resolution TSE (HR) T2, and FLASH 3D (F3D)), compared with their corresponding CT planning scans. Segmentation ability of the following pelvic structures: prostatic apex (PA), prostate, rectum, bladder and seminal vesicles (SV), were evaluated by three independent observers. They used a five point grading scale based on the anatomical definition of the organ boundary, tissue contrast and multiplanar display. Results were averaged for the group and for each sequence. There was no significant interobserver variation in the assessed scores (p > 0.1). The average scores (+/- 1 SD) for all pelvic structures assessed by each imaging sequence were CT 1.3 +/- 0.6; SE T1 2.4 +/- 0.9; TSE T2 2.4 +/- 0.7; HR T2 2.2 +/- 0.7 and F3D 3.4 +/- 0.6. Compared with CT, the average MR score for each assessed pelvic structure was higher with a trend for all transaxial MR sequences to provide improved segmentation of the PA and rectum. The F3D sequence scored highest as it provided multiplanar views and avoided the problem of partial volume averaging. MRI, compared with CT, appears to provide improved definition of pelvic treatment volumes but further work is required to confirm this and to address the issues of MRI associated distortion and dosimetry before MRI can be used routinely for pelvic radiotherapy planning.     

Superior mesenteric artery stenting for mesenteric ischaemia in Sneddon's syndrome

Mesenteric ischaemia is a rare but serious cause of abdominal pain. We present the case of a man with Sneddon's syndrome, who had symptomatic mesenteric ischaemia secondary to a superior mesenteric artery stenosis in conjunction with a hepatic artery stenosis. As far as the authors are aware, this has not previously been described in Sneddon's syndrome, which is a vascular systemic disease characterized by an association between cerebrovascular accidents and a livedo reticularis skin rash. He was treated with balloon angioplasty and stent insertion, with good symptomatic improvement. This has implications for other stenoses in this condition should they become symptomatic.     

EEG correlates of the response to ECT: a possible antidepressant role of brain-derived neurotrophic factor

Studies on the relationship of electroencephalographic (EEG) data to the therapeutic response to electroconvulsive therapy (ECT) have been carried out since the 1940s, but for many years they did not yield any consistent correlates. Recent studies, however, are providing a growing body of evidence of relationships between the antidepressant response to ECT and both the ictal (recorded during ECT seizures) and interictal (recorded during waking) EEG. These studies appear to be consistent in pointing to the importance of electrophysiologic changes in the prefrontal cortex as a potential mediator of the antidepressant response to ECT. The available findings are reviewed and discussed in light of recent neurophysiologic and neuropsychiatric research, including that related to neurotrophic factors.     

Dose-response relationship for oral idazoxan effects in healthy human subjects: comparison with oral yohimbine

The effects of oral administration of the ₂ adrenergic receptor antagonists idazoxan (20 mg, 40 mg, 80 mg) and yohimbine (20 mg) were compared using a placebo-controlled within-subjects design. Healthy subjects completed 5 test days during which medication effects on mood and anxiety states, physiologic indices, plasma cortisol levels, and plasma levels of the norepinephrine metabolite 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) were assessed. Idazoxan dose-dependently increased plasma MHPG, plasma cortisol, systolic and diastolic blood pressure, and Panic Attack Symptom Scale scores in healthy subjects. Overall, yohimbine and idazoxan produced a similar pattern of behavioral and neuroendocrine responses. Since idazoxan possesses relatively greater receptor specificity compared to yohimbine, it may be a more useful ₂ antagonist in humans.     

Invited commentary: complexities in evaluating neurobiological models for stress resistance

Professors Salmon and Stanford are to be commended for their efforts in drawing attention to noradrenergic contributions to stress resistance and the potential importance of within-subject patterns of stress response. In commenting on their paper, I would like to develop the following points: (1) self-control over stress exposure strongly influences the noradrenergic response to stress; (2) β-receptor regulation may reflect a lower sensitivity to stress under a carefully specified range of conditions; and (3) genetic and environmental factors may interact in a complex fashion that may not fit simple linear models based on β-receptor function.     

Breast implant materials: sense and safety.

Cosmetic breast augmentation, and post-mastectomy breast reconstruction surgery using synthetic implants, have become established in surgical practice over more than 20 years. The operative technique for implant placement have changed somewhat during this time, as many different implant presentations have become available, but the same basic materials have remained in use. We have reviewed the present state of knowledge about breast implant materials with particular reference to the possible connection between polydimethylsiloxane and polyurethane to the so-called "Human Adjuvant Disease", and to carcinogenesis. Problems related to capsular contracture and mammography are also discussed.     

Predictive value of serial carcinoembryonic antigen levels in long-term follow-up of ovarian cancer.

The predictive value of serial levels of carcinoembryonic antigen (CEA) in tumor monitoring was examined in 213 patients with ovarian cancer; each patient had been followed-up at monthly intervals for at least 12 months. CEA was not detectable throughout the period of observation in 35% of the patients. In general. patterns showing a disappearance of CEA or persistently low levels were associated with a good prognosis, whereas those showing a reappearance or highly elevated and rising levels were associated with a poor prognosis. A transient reappearance of CEA was observed in 10 patients; this did not appear to be associated with tumor recurrence or progression. "False positive" results were obtained in 6 patients in whom no tumor has been clinically detectable to date. "False negative" results were obtained in 4 patients with obvious tumor progression. In terms of a good or poor prognosis, the use of CEA levels was highly accurate in patients with minimal or no residual disease (97% and 89%, respectively); the rate fell to 62% in patients with extensive disease. As the clinical significance and limitations become better known, serial CEA levels should contribute substantially to the monitoring of patients with ovarian cancer.