Diagnostic challenges related to myeloid/natural killer cells, a variant of myeloblasts

The authors report herein two diagnostically challenging cases centered on the myeloid/natural killer (myeloid/NK) cells, a variant of myeloblasts, to illustrate the importance of advanced flow cytometric immunophenotyping and an updated understanding of surface markers in hematopoietic malignancies. Myeloid/NK cell acute leukemia is a very rare subtype of leukemia. Although its NK-cell nature is debatable, it represents a variant of leukemia with distinct morphological and immunophenotypical features. The first case is a de novo myeloid/NK-cell acute leukemia with a striking clinical, morphologic and immunophenotypic resemblance to acute promyelocytic leukemia (APL), but which could be distinguished by its CD11a, CD18, CD117 and CD9 expression. This case illustrates the importance of utilizing the APL surrogate surface phenotype of HLA-DR(low), CD11a(low) and CD18(low) by flow cytometric study to rule in/out APL immunophenotypically. In the second case, we show that myeloid/NK-cell blasts can present as a variant of blasts in a preleukemic disease as refractory anemia with excess blasts-1 (RAEB-1), where the blasts were negative for CD34, CD117 and HLA-DR. The recognition of such blast variant is important in appropriately classifying such preleukemic diseases by blast percentage.     

Abdominal ultrasonography in HIV/AIDS patients in southwestern Nigeria

Background

Though the major target of the HIV-virus is the immune system, the frequency of abdominal disorders in HIV/AIDS patients has been reported to be second only to pulmonary disease. These abdominal manifestations may be on the increase as the use of antiretroviral therapy has increased life expectancy and improved quality of life. Ultrasonography is an easy to perform, non invasive, inexpensive and safe imaging technique that is invaluable in Africa where AIDS is most prevalent and where sophisticated diagnostic tools are not readily available. Purpose: To describe the findings and evaluate the clinical utility of abdominal ultrasonography in HIV/AIDS patients in Ibadan, Nigeria

Methods

A Prospective evaluation of the abdominal ultrasonography of 391 HIV-positive patients as well as 391 age and sex-matched HIV-negative patients were carried out at the University College Hospital, Ibadan.

Results

Of the 391 cases studied, 260 (66.5%) were females; the mean age was 38.02 years, (range 15–66 years). The disease was most prevalent in the 4th decade with an incidence of 40.4%. Compared with the HIV-negative individuals, the HIV+ group of patients had a significantly higher proportion of splenomegaly (13.5% vs. 7.7%; p < 0.01), lymphadenopathy (2.0% vs. 1.3%; p < 0.70), and renal abnormalities (8.4% vs. 3.8%; p < 0.02). There were no differences in hepatic and pancreatic abnormalities between the HIV+ and HIV- groups. There were significantly fewer gallstones in the HIV+ group (1.4% vs. 5.1%; p < 0.01).

Conclusion

AIDS is a multi-systemic disease and its demographic and clinical pattern remains the same globally. Ultrasonography is optimally suited for its clinical management especially in Africa. Its accuracy and sensitivity may be much improved with clinico-pathologic correlation which may not be readily available in developing countries; further studies may provide this much needed diagnostic algorithms.     

The expression of cytokeratin 5/6 in invasive lobular carcinoma of the breast: evidence of a basal-like subset?

Analysis of gene expression profiling data on breast cancers has revealed "molecular subclasses" that may have prognostic significance. The "basal-like" breast cancers, one of these molecular subclasses, have been associated with a significantly worse overall and disease-free survival as compared with most of the other subclasses. Previous studies on basal-like cancers have been performed predominantly on the ductal histotype. This study was designed to evaluate the significance of the expression of cytokeratin (CK) 5/6, a commonly used surrogate marker for the basal-like phenotype, in invasive lobular carcinomas (ILCs). The immunohistochemical expression of CK5/6, estrogen receptor (ER), progesterone receptor (PR), HER2/neu, and E-cadherin was determined in a group of 82 consecutive archived ILCs diagnosed in 82 women (age range, 29-73 years; mean, 51.9 years). All cases were E-cadherin negative. CK5/6 was positive in 14 (17%) of 82 cases and was entirely negative in the remaining 68 cases (83%). In 8 of the 14 CK5/6[+] cases, staining was diffuse and intense. In the remaining 6 cases, staining was patchy (>1 low-power field between positive areas) but still of high intensity. CK5/6[+] cases were significantly more likely than CK5/6[-] cases to be ER[-] (43% versus 0%, respectively, P < .0001). CK5/6[+] cases were also significantly more frequently of modified Scarff-Bloom-Richardson histologic grade 3, as 7 (50%) of the 14 CK5/6[+] cases were of histologic grade 3, as compared with only 6 (8.8%) of 68 of the CK5/6[-] cases (P = .0009). Notably, the average mitotic index in the CK5/6[+] group was 11/10 high-power fields, as compared with 7/10 high-power fields in the CK5/6[-] group (P = .07). Overall, there were no distinct morphological differences between the 2 groups, and both displayed the well-characterized architectural and cytologic features of ILCs. CK5/6[+] and CK5/6[-] cases did not significantly differ with respect to patient age, frequency of PR expression, tumor size, rate of axillary node involvement, or HER2/neu overexpression. In summary, the present study demonstrated that 17% of ILCs express CK5/6, and that CK5/6[+] cases are more likely to be ER[-] and have a high modified Scarff-Bloom-Richardson histologic grade. Because these findings are a characteristic of ductal basal-like breast cancers, our results suggest that there is a basal-like subset for ILCs with potentially distinct clinicopathologic characteristics. Future studies are required to define the prognostic significance of CK5/6 expression in ILCs.     

Detection of Lassa Virus-Reactive IgG Antibodies in Wild Rodents: Validation of a Capture Enzyme-Linked Immunological Assay

The aim of this study was to evaluate the use of a capture enzyme-linked immunosorbent assay (ELISA) for the detection of LASV-reactive IgG antibodies in Mastomys rodents. The assay was used for laboratory-bred Mastomys rodents, as well as for animals caught in the wild in various regions of West Africa. The ELISA reached an accuracy of 97.1% in samples of known exposure, and a comparison to an immunofluorescence assay (IFA) revealed a very strong agreement between the ELISA and IFA results (Cohen’s kappa of 0.81). The agreement is valid in Nigeria, and in Guinea and Sierra Leone where the lineages II and IV are circulating, respectively. Altogether, these results indicate that this capture ELISA is suitable for LASV IgG serostatus determination in Mastomys rodents as an alternative to IFA. This assay will be a strong, accurate, and semi-quantitative alternative for rodent seroprevalence studies that does not depend on biosafety level 4 infrastructures, providing great benefits for ecology and epidemiology studies of Lassa fever, a disease listed on the Research and Development Blueprint of the WHO.     

Burden of disability in type 2 diabetes mellitus and the moderating effects of physical activity

The growing diabetic epidemic has created a substantial burden, not only on the people with diabetes but also on society at large. This mini-review discussed the limitations and patterns of disability in type 2 diabetes mellitus and put forward a case for the moderating effects of physical activity (PA) in the management of diabetes. The limitations and impairments associated with diabetes include vascular, neurological, cardiac, and renal impairments. Moreover, individuals participate less in their daily lives and in their instrumental activities of daily living, which negatively impacts the quality of life of individuals with diabetes. This often leads to a loss of quality of life due to disabilities, resulting in an increased rate of disability-adjusted life years among people with type 2 diabetes mellitus. Moreover, there are psychosocial sequelae of diabetes mellitus. This necessitates looking for moderating factors that may reduce the burden of the disease. PA has been shown to be one of the factors that can mitigate these burdens. PA does this in several ways, including through the benefits it confers, such as a reduction of hemoglobin A1c, a reduction of excess fat in the liver and pancreas, and the reduction of cardiovascular risk factors, all of which favorably affect glycemic parameters. Specifically, PA regulates or moderates diabetes disability through two mechanisms: The regulation of glucolipid metabolism disorders and the optimization of body mass index and systemic conditions. Therefore, efforts should be directed at PA uptake through identified strategies. This will not only prevent diabetes or diabetes complications but will reduce its burden.     

Neurotoxic and behavioral deficit in Drosophila melanogaster co-exposed to rotenone and iron

Exposure to environmental toxicants has been linked with the onset of different neurodegenerative diseases in animals and humans. Here, we evaluated the toxic effects of co-exposure to iron and rotenone at low concentrations in Drosophila melanogaster. Adult wild-type flies were orally exposed to rotenone (50.0 µM) and ferrous sulfate (FeSO₄; 1.0 and 10.0 µM) through the diet for 10 days. Thereafter, we evaluated markers of oxidative damage (Hydrogen Peroxide (H₂O₂), Nitric Oxide (NO), Protein Carbonyl, and malondialdehyde (MDA)), antioxidant status (catalase, Glutathione S-Transferase (GST), Total Thiol (T-SH) and Non-protein Thiol (NPSH), neurotransmission (monoamine oxidase; MAO and acetylcholinesterase, AChE) and mitochondrial respiration. The results indicated that flies fed rotenone and FeSO₄ had impaired locomotion, reduced survival rate, and AChE activity with a corresponding increase in MAO activity when compared with the control (p?<?0.05). Furthermore, rotenone and FeSO₄ significantly decreased the antioxidant status with a concurrent accumulation of NO, MDA, and H₂O₂. Additionally, the activity of complex 1 and mitochondria bioenergetic capacity was compromised in the flies. These findings suggest that the combination of rotenone and FeSO₄ elicited a possible synergistic toxic response in the flies and therefore provided further insights on the use of D. melanogaster in toxicological studies.