Circumscribed choroidal hemangiomas: long-term visual prognosis

Twenty-one patients with a circumscribed choroidal hemangioma in one eye were followed for various intervals ranging from three years to over nine years after diagnosis. Eighteen of the 21 were treated with xenon arc and/or argon laser photocoagulation to the hemangioma in an attempt to reduce or eliminate a secondary retinal detachment at some point during the follow-up period. Only four of the 21 had visual acuity of 6/12 or better in the involved eye at the time of the most recent follow-up, and 15 of the 21 had visual acuity of 6/60 or worse. Persistent nonrhegmatogenous retinal detachment involving the fovea and degenerative changes in the macular retina secondary to prior retinal detachment accounted for most of the visual impairment in these 21 eyes.     

Nonoperative techniques for tissue diagnosis in the management of thyroid nodules and goiters

As only 10% of thyroid nodules are malignant, the surgical oncologist is faced with the challenge of selecting for thyroidectomy only those patients likely to benefit therapeutically from surgery. Demonstration of nonfunction on scintigraphic thyroid scan increases the yield of cancer only by 15% to 20%. Aspiration cytology and needle biopsy are potent aids in selecting patients for thyroidectomy. In 1,504 patients for whom a benign or malignant cytological diagnosis was made prior to thyroidectomy, the sensitivity of this technique was 92.0%, specificity was 97.3%, and overall diagnostic accuracy 95.7%. Morbidity is minimal. The reliability of these techniques is dependent on proficient specimen procurement and the cytopathologist's expertise and experience. Differentiation of benign from malignant follicular and lymphocytic lesions is not possible with conventional cytology preparations; 28% of such "indeterminant" lesions prove to be cancer at thyroidectomy. Aspiration cytology is a simple, reliable technique for selection of patients with thyroid nodules for surgery.     

Clinical presentation of a group of NF2 patients to a tertiary referral skull base unit

The objective of the investigation was to document the clinical presentations of a group of patients with neurofibromatosis type two syndrome (NF2), and took the form of a retrospective case note review. The investigation took place in the tertiary referral skull base unit. The dominant presentation of patients with NF2 is with auditory/vestibular symptoms (56%), with a smaller proportion of presentations being due to non-acoustic intracranial and spinal tumours (44%). At the time of presentation the majority of clinically significant tumours could be demonstrated in each patient with MRI of the head and spine, with few new tumours arising during the subsequent follow-up period. The range of presentation of patients with NF2 results in their management being fragmented into a variety of clinical setting, diluting the experience amassed in any one centre.     

Enhancement of in vivo antitumor activity of classical anticancer agents by combination with the new, glutathione-interacting DNA minor groove-binder, brostallicin.

PURPOSE: Brostallicin (PNU-166196) is a alpha-bromoacrylic DNA minor groove binder, currently in clinical evaluation. This drug has the peculiarity of showing enhanced antitumor activity in cells with high glutathione S-transferase (GST)/glutathione content. The purpose of the study was to study multiple combinations of brostallicin with classical anticancer agents. EXPERIMENTAL DESIGN: The cis-dichloro-diammine-platinum (cDDP)/brostallicin combination was tested in the human colon carcinoma (HCT-116) model transplanted in nude mice. Two treatment schedules were tested: cDDP followed by brostallicin 48 h after or brostallicin followed by cDDP. These two schemes were selected from the observation that tumor cells in vitro show an increased activity of GST 48 h after cDDP treatment. The HCT-116 model was used also to test the irinotecan (cPT-11)/brostallicin combination. The effect of brostallicin in combination with doxorubicin (DX) was studied in the i.v. injected murine L1210 leukemia. Three administration schedules were tested. The antitumor activity of brostallicin and Taxotere was tested on the A549 lung cancer xenografts. RESULTS: In line with the increased GST activity observed after treatment with cDDP, the cDDP/brostallicin interaction was sequence-dependent, leading to a more than additive antitumor effect, without additional toxicity, only when cDDP was given before brostallicin. The antitumor effect of CPT-11 was enhanced significantly by brostallicin cotreatment. A more than additive antitumor effect, without additional toxicity, was observed when DX/brostallicin were sequentially administered in L1210-bearing mice. Finally, additivity was observed when brostallicin/Taxotere simultaneous combination was tested. CONCLUSIONS: Although the precise molecular mechanism of interaction between brostallicin and the other tested cytotoxics has not yet been identified, a clear therapeutic gain is observed in preclinical models when brostallicin is combined with anticancer agents such as cDDP, DX, CPT-11, and Taxotere. These results indicate the potential therapeutic value of brostallicin in cancer combination treatment therapy.     

Patient Capacity in Mental Health Care: Legal Overview

The discriminatory effects of categorizing psychiatric patients into competent and incompetent, have urged lawyers, philosophers and health care professionals to seek a functional approach to capacity assessment. Dutch and English law have produced some guidelines concerning this issue. So far, most legal systems under investigation have concentrated on alternatives for informed consent by the patient in case of mental incapacity, notably substitute decision-making, intervention of a judge and advance directives. It is hard to judge the way in which the law may further adapt to a more functional assessment of capacity, because the nature of law shows that legal reforms usually take place only when new methods have been accepted by the field. This is not yet the case today.     

Cyclopeptide RA-V inhibits angiogenesis by down-regulating ERK1/2 phosphorylation in HUVEC and HMEC-1 endothelial cells

BACKGROUND AND PURPOSE

Anti-angiogenic agents have recently become one of the major adjuvants for cancer therapy. A cyclopeptide, RA-V, has been shown to have anti-tumour activities. Its in vitro anti-angiogenic activities were evaluated in the present study, and the underlying mechanisms were also assessed.

EXPERIMENTAL APPROACH

Two endothelial cell lines, human umbilical vein endothelial cells (HUVEC) and human microvascular endothelial cells (HMEC-1), were used. The effects of RA-V on the proliferation, cell cycle phase distribution, migration, tube formation and adhesion were assessed. Western blots and real-time PCR were employed to examine the protein and mRNA expression of relevant molecules.

KEY RESULTS

RA-V inhibited HUVEC and HMEC-1 proliferation dose-dependently with IC₅₀ values of 1.42 and 4.0 nM respectively. RA-V inhibited migration and tube formation of endothelial cells as well as adhesion to extracellular matrix proteins. RA-V treatment down-regulated the protein and mRNA expression of matrix metalloproteinase-2. Regarding intracellular signal transduction, RA-V interfered with the activation of ERK1/2 in both cell lines. Furthermore, RA-V significantly decreased the phosphorylation of JNK in HUVEC whereas, in HMEC-1, p38 MAPK was decreased.

CONCLUSIONS AND IMPLICATIONS

RA-V exhibited anti-angiogenic activities in HUVEC and HMEC-1 cell lines with changes in function of these endothelial cells. The underlying mechanisms of action involved the ERK1/2 signalling pathway. However, RA-V may regulate different signalling pathways in different endothelial cells. These findings suggest that RA-V has the potential to be further developed as an anti-angiogenic agent.     

First-trimester combined screening for Down syndrome: prediction of low birth weight, small for gestational age and pre-term delivery in a cohort of non-selected women

OBJECTIVE: To establish the relationship between the first-trimester screening markers [pregnancy-associated plasma protein A (PAPP-A), free human chorionic gonadotrophin-beta (beta-hCG), nuchal translucency (NT)], the Down syndrome (DS) risk estimate, and the adverse outcomes such as low birth weight, small for gestational age (SGA) and pre-term delivery. METHODS: A retrospective cohort study including 1,734 non-selected singleton pregnancies consecutively enrolled into the programme of first-trimester combined screening for DS in a 12-month period at a single centre. Data from the Prenatal Patient Registry in ASTRAIA were combined with the Danish National Newborn Screening Registry and Danish Birth Registry. RESULTS: There was a significant relation between low PAPP-A MoM, low beta-hCG MoM, increased risk estimate for DS and low birth weight and SGA. Low PAPP-A MoM and increased NT showed a significant relation to pre-term and spontaneous pre-term delivery. Low PAPP-A MoM showed a significant relation to early pre-term delivery. CONCLUSION: First-trimester screening markers exhibited a significant relation to low birth weight, SGA and to some extent, to pre-term and early pre-term delivery. The screening performance of individual markers was poor.     

First-trimester maternal serum progesterone in aneuploid pregnancies

BACKGROUND: First-trimester maternal serum screening for Down syndrome (DS) can be improved by the use of additional serum markers. We examined whether progesterone (P), synthesized by placenta, might be a first-trimester maternal serum marker for fetal DS. MATERIALS AND METHODS: P was quantified in first-trimester maternal serum from 42 DS, six trisomy 18 and two trisomy 13 pregnancies and 115 controls. Log-regression of P versus gestational age in days was used to convert P concentrations into multiples of the median (MoM). RESULTS: The P concentrations in controls increased with gestational age (p = 9.5 x 10(-7)). The log10MoM P distribution in DS pregnancies was not significantly different from that in controls. However, from day 58-67, the log10MoM P was elevated in DS pregnancies (n = 10) with a mean (SD) of 0.1040 (0.0956), compared to a mean (SD) of - 0.0109 (0.1661) in controls (n = 24) (p = 0.05). Five out of six trisomy 18 and both trisomy 13 pregnancies had a P MoM < 1. CONCLUSION: P is not a useful marker for DS in first trimester, except perhaps in a narrow gestational age window from day 58 to 67. P is a trisomy 18/13 marker.