HE4 as a predictor of adjuvant chemotherapy resistance and survival in patients with epithelial ovarian cancer

The aim of this study was to investigate the value of serum human epididymis protein 4 (HE4) and HE4 tissue protein expression to predict tumor resistance to adjuvant chemotherapy, progression‐free survival (PFS), and overall survival in patients with epithelial ovarian cancer (EOC). Consecutive inclusion of 198 patients diagnosed with EOC was conducted. Blood samples were collected prior to surgery and tissue samples during surgery. Patient data were registered prospectively in the Danish Gynecologic Cancer Database. The association between serum HE4 and HE4 tissue protein expression, resistance to adjuvant chemotherapy, PFS, and overall survival were analyzed in univariate analyses and in multivariate analyses adjusted for age, performance score, surgical outcome, stage, grade, and histological subtype. Serum HE4 levels predicted chemotherapy resistance, PFS, and overall survival correlated significantly (p < 0.001) in the univariate analyses; but after adjustment in a multivariate model, serum HE4 was insignificant, except in a subgroup analysis of postmenopausal women, where serum HE4 significantly predicted resistance to chemotherapy and progression‐free survival. HE4 tissue protein expression predicted PFS (p = 0.022) and overall survival (p = 0.047) in the univariate analysis, while HE4 tissue protein expression failed to predict these outcomes in the adjusted multivariate analyses. Serum HE4 or HE4 tissue protein expression are not independent factors of chemotherapy resistance or survival in patients with EOC, but serum HE4 might predict chemotherapy resistance and PFS in postmenopausal women.     

A rare presentation of cardiac amyloid deposits isolated to intramural vessels

The present case illustrates the diagnostic challenges in symptomatic patients with heart failure of unknown etiology. The patients were previously diagnosed with κ‐light chain amyloidosis without cardiac involvement. Echocardiography showed heart failure with mildly reduced ejection fraction but no signs of amyloidosis. Coronary angiogram showed normal arteries and 11C‐PIB positron emission tomography was negative for amyloid deposits. Exercise testing revealed severe heart failure and reduced coronary flow velocity reserve. Endomyocardial biopsies showed amyloid in the intramural coronary arteries without interstitial amyloid deposits. Hence, the patient was diagnosed with microvascular dysfunction‐induced heart failure due to vessel wall amyloidosis.     

Narrative Therapy for Adoption Issues in Families,Couples, and Individuals: Rationale and Approach

This article explores the application of narrative therapy to clinical work with clients’ adoption-related issues. The importance of therapist competency in addressing adoption-related issues is the primary focus for exploring the application of narrative therapy with individual, couple, and family clients experiencing adoption issues. The narrative method can be effective in exploring and understanding the diversity of experience and meanings adoption triad members report in regard to their adoption experiences (Baden & Wiley, 2007; Daniluk & Hurtig-Mitchell, 2003). Multiple realities and meanings emerge as a theme in the adoption literature and as core concepts in the narrative framework.     

Critical elements and outcomes of a residential family-based intervention for aphasia caregivers

Background: Families living with aphasia often have unmet needs despite intervention provided in hospital and rehabilitation environments (Denman, 1998; Michallet, Le Dorze, & Tétreault, 2001). Michallet and colleagues found that families living with aphasia need information and support throughout the care continuum. If needs are unmet during the early stages of rehabilitation they persist, and as families deal with the long term sequelae of aphasia, new needs emerge in relation to communication and role changes. Few recent interventions have addressed the complex needs experienced by caregivers of people with aphasia (e.g., Hinckley & Packard, 2001; Hinckley, Packard, & Bardach, 1995; Pound, Parr, & Duchan, 2001). Aims: This research aimed to identify the critical elements and outcomes of a residential intervention for families living with aphasia. Methods & Procedures: Narrative data were collected from 19 spouses, siblings, and adult children of persons with aphasia who attended a residential intervention over 3 years. Data collected from participants during and following the intervention were triangulated with field notes recorded by 34 students trained in field observation techniques. All narrative data were transcribed, coded, and analysed using procedures described by Luborsky (1994). Outcomes & Results: Data analysis revealed four critical intervention elements: (a) an emotionally and physically safe environment; (b) respite from the demands of caregiving; (c) peer learning; and (d) participation of families with different amounts of time post aphasia onset. Outcomes from the perspective of the participants included: (a) a renewed sense of hope; (b) improved ability to access their social support resources; (c) improved ability of caregivers to monitor their well-being; (d) greater acceptance of the family's altered state; and (e) emergence of a new social support network. Analysis of thematic relationships showed a web of interconnections between all critical elements and outcomes of the intervention. A central intervention element was learning from peers with different levels of caregiving experience. Conclusions: Some aspects of caregiver learning appear to depend on interventions that are structured to maximise reflective learning from peers. Professionals may underestimate the value of such learning in intervention for caregivers of persons with aphasia.     

Granulocyte colony-stimulating factor administration to healthy volunteers: analysis of the immediate activating effects on circulating neutrophils

In four healthy volunteers, we analyzed in detail the immediate in vivo effects on circulating neutrophils of subcutaneous administration of 300 micrograms of granulocyte colony-stimulating factor (G-CSF). Neutrophil activation was assessed by measurement of degranulation. Mobilization of secretory vesicles was shown by a decrease in leukocyte alkaline phosphatase content of the circulating neutrophils. Furthermore, shortly postinjection, Fc gamma RIII was found to be upregulated from an intracellular pool that we identified by immunoelectron microscopy as secretory vesicles. Intravascular release of specific granules was shown by increased plasma levels of lactoferrin and by upregulation of the expression of CD66b and CD11b on circulating neutrophils. Moreover, measurement of fourfold elevated plasma levels of elastase, bound to its physiologic inhibitor alpha 1- antitrypsin, indicated mobilization of azurophil granules. However, no expression of CD63, a marker of azurophil granules, was observed on circulating neutrophils. G-CSF--induced mobilization of secretory vesicles and specific granules could be mimicked in whole blood cultures in vitro, in contrast to release of azurophil granules. Therefore, we postulate that the most activated neutrophils leave the circulation, as observed shortly postinjection, and undergo subsequent stimulation in the endothelial microenvironment, resulting in mobilization of azurophil granules. Our data demonstrate that G-CSF should be regarded as a potent immediate activator of neutrophils in vivo.     

Review: Head and neck squamous cell carcinoma in sub-Saharan Africa

Aim

Review the literature from 1990 to 2013 to determine known anatomic sites, risk factors, treatments, and outcomes of head and neck squamous cell carcinoma (HNSCC) in sub-Saharan Africa.

Methods

Using a systematic search strategy, literature pertaining to HNSCC in sub-Saharan Africa was reviewed and patient demographics, anatomic sites, histology, stage, treatment, and outcomes were abstracted. The contributions of human immunodeficiency virus (HIV), human papillomavirus (HPV) and behavioural risk factors to HNSCC in the region were assessed.

Results

Of the 342 papers identified, 46 were utilized for review, including 8611 patients. In sub-Saharan Africa, the oropharyngeal/oral cavity was found to be the most common site, with 7750 cases (90% of all cases). Few papers distinguished oropharyngeal from oral cavity, making identification of possible HPV-associated oropharyngeal squamous cell carcinoma (SCC) difficult. SCC of the nasopharynx, nasal cavity, or paranasal sinuses was identified in 410 patients (4.8% of all cases). Laryngeal SCC was found in 385 patients (4.5% of all cases), and only 66 patients (0.8% of all cases) with hypopharyngeal SCC were identified. In 862 patients with data available, 43% used tobacco and 42% used alcohol, and reported use varied widely and was more common in laryngeal SCC than that of the oropharyngeal/oral cavity. Toombak and kola nut use was reported to be higher in patients with HNSCC. Several papers reported HIV-positive patients with HNSCC, but it was not possible to determine HNSCC prevalence in HIV-positive compared to negative patients. Reports of treatment and outcomes were rare.

Conclusions

The oropharyngeal/oral cavity was by far the most commonly reported site of HNSCC reported in sub-Saharan Africa. The roles of risk factors in HNSCC incidence in sub-Saharan Africa were difficult to delineate from the available studies, but a majority of patients did not use tobacco and alcohol.     

Commonly recommended daily intake of vitamin D is not sufficient if sunlight exposure is limited

OBJECTIVES: Sunlight exposure of the skin is known to be the most important source of vitamin D. The aims of this study were: (i) to estimate vitamin D status amongst sunlight-deprived individuals (veiled Arab women, veiled ethnic Danish Moslem women and Danish controls); and (ii) through food intake analysis to estimate the oral intake of vitamin D necessary to keep a normal vitamin D status in sunlight-deprived individuals. DESIGN: Cross-sectional study amongst randomly selected Moslem women of Arab origin living in Denmark. Age-matched Danish women were included as controls. To control for racial differences, a group of veiled ethnic Danish Moslem women (all Caucasians) was included. SETTING: Primary Health Care Centre, City Vest and Department of Endocrinology and Metabolism C, University Hospital of Aarhus, Aarhus Amtssygehus, Aarhus, Denmark. SUBJECTS: Sixty-nine Arab women (60 veiled, nine non-veiled) and 44 age-matched Danish controls were randomly selected amongst patients contacting the primary health care centre for reasons other than vitamin D deficiency. Ten ethnic Danish Moslem women were included through a direct contact with their community. MAIN OUTCOME MEASURES: Serum levels of 25-hydroxyvitamin D were used as estimates of vitamin D status. Intact parathyroid hormone (PTH) was used to control for secondary hyperparathyroidism. Alkaline phosphatase and bone-specific alkaline phosphatase were used as markers for osteomalacic bone involvement. Oral intake of vitamin D and calcium were estimated through a historical food intake interview performed by a trained clinical dietician. RESULTS: Veiled Arab women displayed extremely low values of 25-hydroxyvitamin D: 7.1 +/- 1.1 nmol L-1, compared with 17.5 +/- 2. 3 (P < 0.002) in ethnic Danish Moslems and 47.1 +/- 4.6 (P < 10-17) in Danish controls. PTH was increased amongst veiled Arab women: 15. 6 +/- 1.8 pmol L-1, compared with 5.7 +/- 1.4 in ethnic Danish Moslems and 2.7 +/- 0.3 (P < 10-6) in Danish controls. The vitamin D intake (including food supplementation) was very low amongst Arab women: 1.04 microg day-1, compared with 13.53 amongst ethnic Danish Moslems and 7.49 amongst Danish controls (P < 0.0005). CONCLUSIONS: Severe vitamin D deficiency is prevalent amongst sunlight-deprived individuals living in Denmark. In veiled Arab women, vitamin D deficiency is the result of a combination of limitations in sunlight exposure and a low oral intake of vitamin D. The oral intake of vitamin D amongst veiled ethnic Danish Moslems was, however, very high, at 13.53 microgram (approximately 600 IU), but they were still vitamin D-deficient. Our results suggest that the daily oral intake of vitamin D in sunlight-deprived individuals should exceed 600 IU; most probably it should be 1000 IU day-1 to secure a normal level of 25-hydroxyvitamin D. This finding is in contrast with the commonly used RDA (recommended daily allowance) for adults in Europe: 200 IU day-1.     

Simultaneous analysis of 29 synthetic cannabinoids and metabolites,amphetamines, and cannabinoids in human whole blood by liquid chromatography–tandem mass spectrometry – A New Zealand perspective of use in 2018

We describe the validation of a method for the simultaneous analysis of 29 synthetic cannabinoids (SCs) and metabolites, 4 amphetamines, and 2 cannabinoids in human whole blood. This method enables one analysis to cover what previously required multiple analyses for these classic and novel drugs‐of‐abuse with diverse physicochemical properties. The scope of targeted analytes was based on the most prevalent drugs‐of‐abuse and SCs encountered at the New Zealand border in 2017 and included parent compounds and metabolites belonging to the indole and indazole carboxamide, quinolinyl indole carboxylate, and naphthoylindole classifications. Samples were prepared by supported‐liquid‐extraction (SLE) followed by liquid chromatography?tandem mass spectrometry (LC?MS/MS) analysis with positive electrospray ionization (ESI). The method was validated with respect to selectivity, matrix effects, process efficiency, sensitivity, repeatability, extract stability, and carryover for qualitative confirmation. Linearity as well as accuracy and precision data at target decision concentrations were also evaluated. The limits of detection and confirmation ranged from 0.1 to 6.0 ng/mL and 1.0 to 6.0 ng/mL, respectively. The described method was successfully applied to the analysis of 564 ante‐ and post‐mortem blood samples in 2018. There were 132 cases (23%) with positive findings of at least one SC, with the five most commonly detected SCs being AMB‐FUBINACA and/or acid (61%), 5F‐ADB and/or acid (40%), ADB‐FUBINACA (11%), 5F‐MDMB‐PICA acid (6%), and MDMB‐FUBINACA acid (6%). The results also demonstrate the predominant presence of metabolites at higher levels than the unchanged parent SCs in blood, highlighting the need to maintain forensic screening methods capable of the simultaneous detection of both parent compounds and metabolites.