In vitro and in vivo targeting properties of iodine-123- or iodine-131-labeled monoclonal antibody 14C5 in a non-small cell lung cancer and colon carcinoma model.

PURPOSE: The monoclonal antibody (mAb) 14C5 is a murine IgG1 directed against a yet undefined molecule involved in cell substrate adhesion found on the surface of malignant breast cancer tissue. mAb 14C5 is able to inhibit cell substrate adhesion and invasion of breast cancer cells in vitro. In normal tissues as well as in the stroma surrounding in situ carcinomas of the breast, no expression of the antigen 14C5 occurs. The aim of this study was to investigate the in vitro and in vivo targeting properties of 123I- and 131I-labeled mAb 14C5 as a novel agent for radioimmunodetection and radioimmunotherapy. EXPERIMENTAL DESIGN: Internalization of mAb 14C5 was investigated with 125I-labeled mAb 14C5 and by confocal laser scanning microscopy. Biodistribution studies of 131I-labeled mAb 14C5 and planar gamma imaging were done in nude mice bearing an A549 (non-small cell lung carcinoma) or a LoVo (colon carcinoma) tumor. RESULTS: Internalization studies with both A549 and LoVo cells showed that 125I-labeled mAb 14C5 is slowly internalized with approximately 30% of the initially bound mAb 14C5 internalized after 2 hours at 37 degrees C. Internalization of mAb 14C5 could be visualized with confocal laser scanning microscopy. In vivo, radioisotope uptake peaked at 24 hours for both tumor models (n = 5) with no significant difference in percentage of injected dose/g tissue (A549 10.4 +/- 0.8 and LoVo 9.3 +/- 0.8). Via planar gamma camera imaging, A549 lung tumors as well as LoVo colon tumors could be clearly visualized. CONCLUSIONS: The in vitro and in vivo targeting properties of 123I- and 131I-labeled mAb 14C5 are promising and could provide a new antibody-based agent for radioimmunodetection and radioimmunotherapy of patients bearing antigen 14C5-expressing tumors.     

Cytochrome P450 epoxygenases as EDHF synthase(s)

The metabolism of arachidonic acid by cytochrome P450 (CYP) epoxygenases generates epoxyeicosatrienoic acids (EETs) which affect numerous cellular process including Ca(2+) signaling and the activity of Ca(2+)-dependent K(+) channels. The expression of the CYP epoxygenase(s) that generate EETs in endothelial cells is not constitutive but is determined by a number of physical (fluid shear stress and cyclic stretch) and pharmacological stimuli which also affect responses attributed to an endothelium-derived hyperpolarizing factor (EDHF). This review summarizes the role played by EETs, and the enzymes that generate and metabolize them, in EDHF-mediated responses.     

Food effects on tablet disintegration.

The aims of the present study was to investigate if food components, as represented by a multi-component nutritional drink for tube feeding, could affect tablet disintegration of standard tablets in vitro as well as in vivo and propose a mechanism for potential food effects on tablet disintegration. The tablet disintegration was delayed between 5 min and more than 1h in the simulated gastric fed medium compared to a simple buffer. This effect was dependent on the tablet composition. A similar delay in tablet disintegration was also found in vivo after administration of the nutritional drink to three Labradors as observed by removing the tablet from the stomach at different times through a gastric fistula. The delay in tablet disintegration appeared to be caused by precipitation of a film, mainly consisting of protein, on the tablet surface as indicated by disintegration studies with pure nutrients, identification by IR spectroscopy of contents of precipitates obtained in a model study were the nutrients were incubated with different tablet excipients and visual observations of tablets exposed to the simulated fed medium. The drug dissolution of a soluble compound, metoprolol tartrate, from a standard tablet was also strongly delayed in the simulated fed medium. In conclusion, food, could significantly delay tablet disintegration and drug dissolution in the stomach by formation of a film around the tablets. This effect could be monitored by a simple in vitro disintegration test using a test medium based on a nutritional drink. More studies are needed to investigate the significance of the slow tablet disintegrations on bioavailability and for which types of food the present effect occurs.     

Dental care utilization: a study of 50- to 75-year-olds in Southern Sweden

This study investigates dental care utilization in an adult population in Southern Sweden in relation to dental and social conditions, attitudes to costs, and perceived need to obtain dental services. The study was based on responses to a questionnaire sent in 1998 to a random sample, 1974 persons, aged 50-75 years. The response rate was 66%. A significantly higher probability of dental care utilization less than once a year was found for men, for those with few remaining teeth, and for those with removable dentures. A higher probability of dental care utilization less than once a year was found for those who stated perceived need to obtain dental care with no possibility because of the cost and for those who stated that the cost had influenced their attendance for dental care. The results showed that there were differences for sex and dental conditions in dental care utilization and that dental care utilization was related to attitudes towards costs of dental care.     

When people with dementia are perceived as witches. Consequences for patients and nurse education in South Africa

Aims and Objectives

To explore and describe the link between culture and dementia care with the focus on the influence of the belief in dementia as witchcraft and people with dementia as witches.

Background

In South Africa, especially in townships and rural areas, dementia is often perceived as connected to witchcraft rather than to disease. Persons labelled as witches—mostly older women—may be bullied, ostracised, beaten, stoned, burned, even killed.

Method

One strand of findings from a larger international study is presented with in‐depth qualitative interviews of one close family member and seven nurses caring for patients with severe dementia in nursing homes in Tshwane in South Africa. A hermeneutic analytic approach was used.

Results

Two main themes are found, namely “Belief in witchcraft causing fear of persons with dementia” and “Need of knowledge and education.” Fear of and violence towards people with dementia are based on the belief that they are witches. Some of the nurses had also held this belief until they started working with patients with dementia. There is a great need for education both among healthcare workers and the populace.

Discussion

The “witch” belief prevents seeking professional help. As nursing homes tend to be private and expensive, professional dementia care is virtually unattainable for the poor. Dementia needs a more prominent place in nursing curricula. Nurses as educators need to know the local culture and language to be accepted in the various communities. They need to visit families affected by dementia, give awareness talks in churches, schools and clinics and facilitate support groups for carers of people with dementia in the local language.

Conclusion

Improved nurses’ education in gerontology and geriatric care is needed. Trained specialist nurses may work as mediators and help eradicate the witchcraft beliefs connected to severe dementia.     

Novel Nickel Contact Dermatitis in a Patient Taking Isotretinoin

There are many reports about contact dermatitis to nickel and side effects of isotretinoin, but the development of contact dermatitis to a previously tolerated allergen while taking isotretinoin is not well described. We report the case of a 19‐year‐old man who developed a new nickel allergy during isotretinoin treatment. We theorize that thinning of the stratum corneum by this medication allows for greater antigen presentation and thus sensitization to contact allergens.