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.     

The long‐term influence of repetitive cellular cardiac rejections on left ventricular longitudinal myocardial deformation in heart transplant recipients

The aim of the study was to evaluate the long‐term influence of repeated acute cellular rejections on left ventricular longitudinal deformation in heart transplantation (HTX) patients. One hundred and seventy‐eight HTX patients were included in the study. Rejections were classified according to the International Society of Heart and Lung Transplantation (ISHLT) classification (0R–3R). Patients were divided into three groups according to rejection scores (RSs). Group 1: <50% of biopsies with 1R rejection and no ≥2R rejections; Group 2: ≥50% of biopsies with 1R rejection or one biopsy with ≥2R rejection; Group 3: ≥Two biopsies with ≥2R rejections. All patients had a comprehensive echocardiographic examination and coronary angiography. We found significantly decreasing global longitudinal strain (GLS) comparing to rejection groups (GLS group 1: ?16.8 ± 2.4 (%); GLS group 2: ?15.9 ± 3.3 (%); GLS group 3: ?14.5 ± 2.9 (%), P = 0.0003). After excluding patients with LVEF < 50% or vasculopathy, GLS was still significantly reduced according to RS groups (P = 0.0096). Total number of 1R and 2R rejections correlated significant to GLS in a linear regression model. In contrast, we found fractional shortening and LVEF to be unaffected by repeated rejections. In conclusion, repeated cardiac rejections lead to impaired graft function as detected by decreasing magnitude of GLS. In contrast, traditional systolic graft function surveillance by LVEF did not correlate to rejection burden.     

Tachykinins in the porcine pancreas: potent exocrine and endocrine effects via NK-1 receptors

The localization, release, and effects of substance P and neurokinin A were studied in the porcine pancreas and the localization of substance P immunoreactive nerve fibers was examined by immunohistochemistry. The effects of electrical vagus stimulation and capsaicin infusion on tachykinin release and the effects of substance P and neurokinin A infusion on insulin, glucagon, somatostatin, and exocrine secretion were studied using the isolated perfused porcine pancreas with intact vagal innervation. NK-1 and NK-2 receptor antagonists were used to investigate receptor involvement. Substance P immunoreactive nerve fibers were localized to islets of Langerhans, acini, ducts, and blood vessels. Vagus stimulation had no effect on substance P and neurokinin A release, whereas capsaicin infusion stimulated release of both. Substance P and neurokinin A infusion increased release of insulin, glucagon, and exocrine secretion, whereas somatostatin secretion was unaffected. The effect of substance P on insulin, glucagon, and exocrine secretion was blocked by the NK-1 receptor antagonist. The effect of electrical stimulation of vagus nerves on insulin and exocrine secretion was not influenced by tachykinin receptor antagonists. We conclude that tachykinins stimulate both endocrine and exocrine pancreatic functions through NK-1 receptors. Tachykinins are not involved in vagal regulation of pancreatic secretion in pigs but could constitute part of an alternative stimulatory system.     

Evaluation of erythropoiesis in long-term hamster bone marrow suspension cultures: absence of a requirement for adherent monolayer cells

In long-term hamster bone marrow cultures, proliferation and differentiation of hemopoietic stem cells occurs for several months without need for hydrocortisone or adherent stromal elements, which are requirements for bone marrow growth in all other species studied. Only the most primitive erythroid progenitors (BFU-E) are produced in the cultures. Following treatment of the cells with erythropoietin, these progenitor cells undergo differentiation into mature hemoglobinized red blood cells. Concomitant addition of erythropoietin (Epo) and prostaglandin-E1 (PGE1) results in the production of large numbers of maturing red blood cells. In cultures stimulated with Epo and PGE1, as many as 70% of the cells are benzidine-positive, while Epo alone stimulated as many as 45% of the cells to become erythroid. Epo and PGE1 do not have any apparent deleterious effect on the continuous hemopoiesis occurring in these cultures. Under identical conditions, syngeneic adherent cell cultures do not produce any erythroid elements. The development of mature red blood cells from primitive erythroid precursors occurs in the presence of Epo alone and without any apparent need for adherent stromal elements. These cultures provide a useful in vitro model for dissecting the positive and negative signals that regulate erythropoiesis.     

Fc gamma receptor II (CD32) on malignant B cells influences modulation induced by anti-CD19 monoclonal antibody

Antigenic modulation is one of many factors determining the effectiveness of monoclonal antibody (MoAb)-mediated therapy. To select the isotype of a CD19 MoAb most suitable for radioimmunotherapy of patients with B-cell malignancies, we studied the influence of MoAb isotype on modulation, after binding of the MoAb to different cell-line cells. The CD19-IgG1 MoAb was found to induce modulation of CD19 antigens on Daudi cell line cells more rapidly than did its IgG2a switch variant. We provide evidence that this difference in modulation rate is caused by the expression of Fc gamma receptor II (Fc gamma RII) on these cells. Experiments aimed at elucidating the mechanism of Fc gamma RII involvement in modulation induction by CD19-IgG1 showed that Fc gamma RII did not comodulate with CD19 MoAbs. However, cocrosslinking of CD19 and Fc gamma RII with CD19-IgG1 MoAb resulted in enhanced calcium mobilization in Daudi cells. This increased signal induction accompanies the enhanced capping and subsequent modulation of CD19 antigens. Because Fc gamma RII is expressed in varying densities on malignant B cells in all differentiation stages, our results have implications for the MoAb isotype most suitable for use in MoAb-based therapy of patients with B-cell malignancies.