Cryosurgical treatment of basal cell carcinoma of the eyelids

Fifty-nine basal cell carcinomas of the eyelids were treated by cryosurgery and followed up for at least three years. Only one recurrence was seen after three years. All lesions except one healed with good cosmetic results.     

Hyposensitisation to wasp venom in six hours

Eleven patients with a history of anaphylaxis, positive reactions to skin tests, and specific IgE antibody to wasp venom underwent hyposensitisation in a six hour procedure. No general reactions occurred. Complement activation and proteinuria could not be shown. The patterns of specific IgE, IgG1, and IgG4 were as described in other procedures--namely, IgE increased sharply and then decreased; IgG1 and IgG4 increased steadily and then decreased--but increase and decrease came earlier. Challenge by a stinging insect at least four weeks after treatment proved complete protection. The skin reactivity two years later showed an unpredictable pattern.     

Patient–expert partnerships in research: how to stimulate inclusion of patient perspectives

Objective To gain more insight into exclusion mechanisms and inclusion strategies in patient–expert partnerships. Background Patient participation in health research, on the level of ‘partnerships with experts’ is a growing phenomenon. However, little research is conducted whether exclusion mechanisms take place and to what extent patients’ perspectives are included in the final outcomes of these partnerships. Case study A dialogue meeting attended by experts, patients and patient representatives to develop a joint research agenda. Different inclusion strategies were applied during the dialogue meeting to avoid possible exclusion. Method Data were collected by the means of audio and video recordings, observations, document analysis and evaluative interviews. The data are clustered using a framework that divides exclusion mechanisms in three categories: circumstances, behaviour and verbal communication. The data are analysed focusing on the experiences of participants, observation of occurrence of exclusion and difference between input and outcome of the dialogue meeting. Results The circumstances of the dialogue and the behaviour of the participants were experienced as mainly inclusive. Some exclusion was observed particularly with respect to verbal communication. The input of the patients was less visible in the outcome of the dialogue meeting compared to the input of the experts. Conclusion This case study reveals that exclusion of patients’ perspective occurred during a dialogue meeting with experts, despite the fact that inclusion strategies were used and patients experienced the dialogue meeting as inclusive. To realize a more effective patient–expert partnership, more attention should be paid to the application of some additional inclusion strategies.     

E1A-mediated suppression of EGFR expression and induction of apoptosis in head and neck squamous carcinoma cell lines

Previous studies have shown early region 1A (E1A) gene to inhibit the proliferation of tumour cells with wild-type, but not mutant, p53. E1A has also been shown to downregulate c-erb-B-2/neu expression, resulting in inhibition of growth in c-erb-B-2/neu overexpressing tumour cells. In this study, we have investigated the effect of E1A expression on four head and neck squamous cell carcinoma (HNSCC) cell lines that do not overexpress c-erb-B-2/neu. Cell cycle and Western blot analysis show E1A-mediated induction of apoptosis in all cell lines examined. This induction of apoptosis was independent of the p53 status as it occurred in the cell lines with wild-type, mutated or deleted p53. However, there was no evidence of E1A-induced apoptosis in a p53(+ve) normal human fibroblast cell line, 1BR3. Analysis of apoptosis in the SCC cell lines demonstrated E1A-mediated downregulation of EGFR, which was overexpressed in each of these cell lines. Overexpression of an exogenously introduced EGFR, under the control of an E1A-insensitive heterologous promoter, blocked E1A induction of apoptosis in these cells. Therefore, E1A-mediated downregulation of EGFR expression appears to be the cause, rather than a consequence of E1A-induced apoptosis in these SCC cell lines. Previous studies have shown downregulation of EGFR expression by PML. Interestingly, E1A expression in the HNSCC cells altered the pattern of PML distribution and induced the level of PML protein, thus suggesting that E1A-mediated downregulation of EGFR may occur via direct or indirect interactions with PML. These findings demonstrate a novel pathway by which E1A can induce apoptosis and identify EGFR as a potential target for the development of therapeutic strategies against epithelial malignancies, the majority of which have abnormal EGFR expression.     

Luteinizing hormone induction of the cholesterol side-chain cleavage enzyme in cultured immature rat Leydig cells: no role of insulin-like growth factor-I?

Long-term inductive effects of luteinizing hormone (LH) on cholesterol side-chain cleavage (CSCC) enzyme activity were studied, using cultured Leydig cells isolated from 21-day-old rats. Particular reference was given to the role of insulin-like growth factor-I (IGF-I) as an autocrine or paracrine modulator or as an essential extracellular mediator of LH action. The CSCC enzyme activity was measured using an excess of 22(R)-hydroxycholesterol as substrate to saturate the enzyme, and inhibitors of pregnenolone metabolism to concentrate all the products of the enzyme reaction in pregnenolone. The rate of sterol conversion into pregnenolone (CSCC enzyme activity) reflected the amount of cytochrome P-450scc (P-450scc), as was shown by Western blotting. In cells cultured without LH, the CSCC enzyme activity decreased to 10% on day 7 of the culture period. In the presence of various doses of LH ranging from 0.01 to 100 ng/ml, the CSCC enzyme activity also diminished during the first 3 days of culture, but during the following days, the amount of CSCC enzyme was stimulated by LH. In contrast to the absence of any LH effect on the activity of the CSCC enzyme during the first days of the culture, the endogenous steroid production (no added 22(R)-hydroxycholesterol) could be stimulated at least 10-fold by high doses of LH. When LH (1 ng/ml) was added to cells which had been cultured for 7 days without hormones, CSCC enzyme activity was elevated 8-fold after 4 days of exposure of LH. These effects of LH could be mimicked by dbcAMP (0.5 mM). No evidence could be provided that IGF-I plays any role in the LH induction of the CSCC enzyme; neither the addition of exogenous IGF-I or analogs that do not bind to IGF-I binding proteins (IGFBPs) nor the inactivation of endogenous IGF-I action (through binding to IGFBP and antibodies to IGF-I or via masking of IGF-I receptor by antibodies) could influence the LH induced CSCC enzyme activity. The present data raise the question under which conditions IGF-I is capable of modulating Leydig cell steroidogenesis.     

Formal and informal care costs of hospitalized older people at risk of poor functioning: A prospective cohort study

Hospitalized older people are at risk of poor functioning after hospital discharge. We aimed to relate formal and informal care costs to level of risk for low functioning of hospitalized older people up to one year after admission. We studied 460 patients 65 years or older who were admitted to a 450-bed hospital in the Netherlands between June 2010 and October 2010. Participants were classified into five risk groups at hospital admission using the Identification Seniors At Risk-Hospitalized Patients (ISAR-HP). Patients were interviewed at hospital admission and at three and twelve months after admission using validated questionnaires to measure health care utilization. Informal caregivers were interviewed by mailed paper questionnaires at the same time as patients. We estimated costs per unit from hospital information systems and nationally representative research. Mean healthcare costs were €30k euro per person per year, with one third for initial hospital stay (€9,8k), one third for formal healthcare costs between hospital discharge and twelve month follow up (€10,3k), and one third for informal healthcare costs between hospital discharge and twelve month follow up (€9,5k). Informal and formal healthcare costs were almost double for people with the highest risk score compared to people not at risk (p < 0.001). Older patients with high risk scores at hospital admission have substantially higher formal and informal care costs in the year after initial hospital admission than people with low risk scores. This implies that substantial investments may be made in preventive interventions for at-risk hospitalized older people.     

Broadening the factor V Leiden paradox: pulmonary embolism and deep-vein thrombosis as 2 sides of the spectrum

Risk factors for deep-vein thrombosis have been shown not to be always the same as for pulmonary embolism. A well-known example is the factor V Leiden (FVL) paradox: the FVL mutation poses a clearly higher risk for deep-vein thrombosis (DVT) than for pulmonary embolism. We aimed to expand this paradox and therefore present risk estimates for several established risk factors for DVT and pulmonary embolism separately. When such separate risk estimates could not be retrieved from the literature, we calculated these risks in our own data, a large population-based case-control study on venous thrombosis (the MEGA study). Our results showed that the FVL paradox can be broadened (ie, the risk factors oral contraceptive use, pregnancy, puerperium, minor leg injuries, and obesity have an effect comparable with FVL). Furthermore, we found that pulmonary conditions, such as chronic obstructive pulmonary disease, pneumonia, and sickle cell disease, were risk factors with an opposite effect: a higher risk of pulmonary embolism, but little or no effect on DVT. These findings suggest that pulmonary embolism and DVT may not always have the same etiology, and encourage unraveling this phenomenon in further studies.