Oxygen tension-dependent variability in the cancer cell kinome impacts signaling pathways and response to targeted therapies.

Most cells in solid tumors are exposed to oxygen levels between 0.5% and 5%. We developed an approach that allows collection, processing, and evaluation of cancer and non-cancer cells under physioxia, while preventing exposure to ambient air. This aided comparison of baseline and drug-induced changes in signaling pathways under physioxia and ambient oxygen. Using tumor cells from transgenic models of breast cancer and cells from breast tissues of clinically breast cancer-free women, we demonstrate oxygen-dependent differences in cell preference for epidermal growth factor receptor (EGFR) or platelet-derived growth factor receptor beta (PDGFRß) signaling. Physioxia caused PDGFRß-mediated activation of AKT and extracellular regulated kinase (ERK) that reduced sensitivity to EGFR and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) inhibition and maintained PDGFRß+ epithelial-mesenchymal hybrid cells with potential cancer stem cell (CSC) properties. Cells in ambient air displayed differential EGFR activation and were more sensitive to targeted therapies. Our data emphasize the importance of oxygen considerations in preclinical cancer research to identify effective drug targets and develop combination therapy regimens.

Mutant RAS-driven Secretome Causes Skeletal Muscle Defects in Breast Cancer.

Cancer-induced skeletal muscle defects differ in severity between individuals with the same cancer type. Cancer subtype-specific genomic aberrations are suggested to mediate these differences, but experimental validation studies are very limited. We utilized three different breast cancer patient-derived xenograft (PDX) models to correlate cancer subtype with skeletal muscle defects. PDXs were derived from brain metastasis of triple-negative breast cancer (TNBC), estrogen receptor-positive/progesterone receptor-positive (ER+/PR+) primary breast cancer from a BRCA2-mutation carrier, and pleural effusion from an ER+/PR- breast cancer. While impaired skeletal muscle function as measured through rotarod performance and reduced levels of circulating and/or skeletal muscle miR-486 were common across all three PDXs, only TNBC-derived PDX activated phospho-p38 in skeletal muscle. To further extend these results, we generated transformed variants of human primary breast epithelial cells from healthy donors using HRASG12V or PIK3CAH1047R mutant oncogenes. Mutations in RAS oncogene or its modulators are found in approximately 37% of metastatic breast cancers, which is often associated with skeletal muscle defects. Although cells transformed with both oncogenes generated adenocarcinomas in NSG mice, only HRASG12V-derived tumors caused skeletal muscle defects affecting rotarod performance, skeletal muscle contraction force, and miR-486, Pax7, pAKT, and p53 levels in skeletal muscle. Circulating levels of the chemokine CXCL1 were elevated only in animals with tumors containing HRASG12V mutation. Because RAS pathway aberrations are found in 19% of cancers, evaluating skeletal muscle defects in the context of genomic aberrations in cancers, particularly RAS pathway mutations, may accelerate development of therapeutic modalities to overcome cancer-induced systemic effects. SIGNIFICANCE: Mutant RAS- and PIK3CA-driven breast cancers distinctly affect the function of skeletal muscle. Therefore, research and therapeutic targeting of cancer-induced systemic effects need to take aberrant cancer genome into consideration.

Epidemiology of influenza in Nigeria: A secondary analysis of the sentinel surveillance data in Nigeria from 2010 - 2020.

BACKGROUND: Influenza is a leading cause of morbidity and mortality globally. Little is known of the true burden and epidemiology of influenza in Africa. Nigeria has a sentinel surveillance system for influenza virus (IFV). This study seeks to describe the epidemiological characteristics of influenza cases in Nigeria through secondary data analysis of the sentinel surveillance data from 2010 to 2020. METHODOLOGY: A retrospective secondary data analysis of data collected from patients with influenza-like illness (ILI) and severe acute respiratory infection (SARI) in the four Nigeria Influenza Sentinel Surveillance sites from January 2010 to December 2020. Data was cleaned and analyzed using Microsoft Excel and Epi info 7.2 for frequencies and proportions. The results of the analysis were summarized in tables and charts. RESULTS: A total of 13,828 suspected cases of influenza were recorded at the sentinel sites during the study period. About 10.3% (1421/13,828) of these tested positive for IFV of which 1243 (87.5%) were ILI patients, 175 (12.3%) SARI patients, and 3 (0.2%) novel H1N1 patients. Males accounted for 54.2% (770/1421) of the confirmed cases. The median age of confirmed cases was 3 years (range: <1month-97 years). Children 0-4 years accounted for 69.3% (985/1421) of all cases. The predominant subtypes were B lineage not determined (32.3%), A/H1N1 pdm09 (28.8%) and A/H3 (23.0%). There were periods of sustained transmission in most years with 2011 having the highest number of cases. Overall, there were more cases around January to March and August to November. Heart disease and chronic shortness of breath were the most common co-morbidities identified among confirmed cases. CONCLUSION: Influenza remains a significant cause of respiratory illness, especially among children aged less than 4 years. Influenza cases occur all year round with irregular seasonality in Nigeria. Children less than 4 years and those with co-morbidities should be prioritized for vaccination. Vaccine composition in the country should take cognizance of the prevailing strains which are type B (lineage not determined), A/H1N1 pdm09 and A/H3.

Leaf extract of Anacardium occidentale ameliorates biomarkers of neuroinflammation, memory loss, and neurobehavioral deficit in N(ω)-nitro-L-arginine methyl ester (L-NAME) treated rats.

PURPOSE: Anacardium occidentale commonly known as Cashew is a plant that is widely used in African traditional medicine. It is endowed with phytochemical constituents that are responsible for its medicinal properties. METHODS: Twenty-five male Wistar rats were grouped as follows: Control (Group A), Group B (L-NAME 40 mg/kg), Group C (100 mg/kg Anacardium occidentale extract plus 40 mg/kg L-NAME), Group D (200 mg/kg extract plus 40 mg/kg L-NAME) and Group E (10 mg/kg of Lisinopril plus 40 mg/kg L-NAME). The animals were treated with oral administration of either the extracts or Lisnopril daily for 4 weeks. Neuro-behavioural tests such as the Morris Water Maze and Hanging Wire Grip tests were carried out to evaluate memory/spatial learning and muscular strength, respectively. Makers of oxidative stress, antioxidant enzymes and immunohistochemical staining of Glial Fibrillary Acidic Protein and Ionised Calcium Binding Adaptor molecule 1 were assessed. RESULTS: L-NAME administration caused significant increases in biomarkers of oxidative stress, decreased antioxidant status, acetylcholinesterase activity, altered neuro-behavioural changes, astrocytosis, and microgliosis. However, Anacardium occidentale reversed exaggerated oxidative stress biomarkers and improved neuro-behavioural changes. CONCLUSIONS: Combining all, Anacardium occidentale enhanced brain antioxidant defence status, improved memory and muscular strength, thus, suggesting the neuroprotective properties of Anacardium occidentale.

Modeling Preclinical Cancer Studies under Physioxia to Enhance Clinical Translation.

Oxygen (O2) plays a key role in cellular homeostasis. O2 levels are tightly regulated in vivo such that each tissue receives an optimal amount to maintain physiologic status. Physiologic O2 levels in various organs range between 2% and 9% in vivo, with the highest levels of 9% in the kidneys and the lowest of 0.5% in parts of the brain. This physiologic range of O2 tensions is disrupted in pathologic conditions such as cancer, where it can reach as low as 0.5%. Regardless of the state, O2 tension in vivo is maintained at significantly lower levels than ambient O2, which is approximately 21%. Yet, routine in vitro cellular manipulations are carried out in ambient air, regardless of whether or not they are eventually transferred to hypoxic conditions for subsequent studies. Even brief exposure of hematopoietic stem cells to ambient air can cause detrimental effects through a mechanism termed extraphysiologic oxygen shock/stress (EPHOSS), leading to reduced engraftment capabilities. Here, we provide an overview of the effects of ambient air exposure on stem and non-stem cell subtypes, with a focus on recent findings that reveal the impact of EPHOSS on cancer cells.

Tumor collection/processing under physioxia uncovers highly relevant signaling networks and drug sensitivity.

Preclinical studies of primary cancer cells are typically done after tumors are removed from patients or animals at ambient atmospheric oxygen (O2, ~21%). However, O2 concentrations in organs are in the ~3 to 10% range, with most tumors in a hypoxic or 1 to 2% O2 environment in vivo. Although effects of O2 tension on tumor cell characteristics in vitro have been studied, these studies are done only after tumors are first collected and processed in ambient air. Similarly, sensitivity of primary cancer cells to anticancer agents is routinely examined at ambient O2. Here, we demonstrate that tumors collected, processed, and propagated at physiologic O2 compared to ambient air display distinct differences in key signaling networks including LGR5/WNT, YAP, and NRF2/KEAP1, nuclear reactive oxygen species, alternative splicing, and sensitivity to targeted therapies. Therefore, evaluating cancer cells under physioxia could more closely recapitulate their physiopathologic status in the in vivo microenvironment.

Global burden of influenza-associated lower respiratory tract infections and hospitalizations among adults: A systematic review and meta-analysis.

BACKGROUND: Influenza illness burden is substantial, particularly among young children, older adults, and those with underlying conditions. Initiatives are underway to develop better global estimates for influenza-associated hospitalizations and deaths. Knowledge gaps remain regarding the role of influenza viruses in severe respiratory disease and hospitalizations among adults, particularly in lower-income settings. METHODS AND FINDINGS: We aggregated published data from a systematic review and unpublished data from surveillance platforms to generate global meta-analytic estimates for the proportion of acute respiratory hospitalizations associated with influenza viruses among adults. We searched 9 online databases (Medline, Embase, CINAHL, Cochrane Library, Scopus, Global Health, LILACS, WHOLIS, and CNKI; 1 January 1996-31 December 2016) to identify observational studies of influenza-associated hospitalizations in adults, and assessed eligible papers for bias using a simplified Newcastle-Ottawa scale for observational data. We applied meta-analytic proportions to global estimates of lower respiratory infections (LRIs) and hospitalizations from the Global Burden of Disease study in adults ≥20 years and by age groups (20-64 years and ≥65 years) to obtain the number of influenza-associated LRI episodes and hospitalizations for 2016. Data from 63 sources showed that influenza was associated with 14.1% (95% CI 12.1%-16.5%) of acute respiratory hospitalizations among all adults, with no significant differences by age group. The 63 data sources represent published observational studies (n = 28) and unpublished surveillance data (n = 35), from all World Health Organization regions (Africa, n = 8; Americas, n = 11; Eastern Mediterranean, n = 7; Europe, n = 8; Southeast Asia, n = 11; Western Pacific, n = 18). Data quality for published data sources was predominantly moderate or high (75%, n = 56/75). We estimate 32,126,000 (95% CI 20,484,000-46,129,000) influenza-associated LRI episodes and 5,678,000 (95% CI 3,205,000-9,432,000) LRI hospitalizations occur each year among adults. While adults <65 years contribute most influenza-associated LRI hospitalizations and episodes (3,464,000 [95% CI 1,885,000-5,978,000] LRI hospitalizations and 31,087,000 [95% CI 19,987,000-44,444,000] LRI episodes), hospitalization rates were highest in those ≥65 years (437/100,000 person-years [95% CI 265-612/100,000 person-years]). For this analysis, published articles were limited in their inclusion of stratified testing data by year and age group. Lack of information regarding influenza vaccination of the study population was also a limitation across both types of data sources. CONCLUSIONS: In this meta-analysis, we estimated that influenza viruses are associated with over 5 million hospitalizations worldwide per year. Inclusion of both published and unpublished findings allowed for increased power to generate stratified estimates, and improved representation from lower-income countries. Together, the available data demonstrate the importance of influenza viruses as a cause of severe disease and hospitalizations in younger and older adults worldwide.

Nexus between PI3K/AKT and Estrogen Receptor Signaling in Breast Cancer.

Signaling from estrogen receptor alpha (ERα) and its ligand estradiol (E2) is critical for growth of ≈70% of breast cancers. Therefore, several drugs that inhibit ERα functions have been in clinical use for decades and new classes of anti-estrogens are continuously being developed. Although a significant number of ERα+ breast cancers respond to anti-estrogen therapy, ≈30% of these breast cancers recur, sometimes even after 20 years of initial diagnosis. Mechanism of resistance to anti-estrogens is one of the intensely studied disciplines in breast cancer. Several mechanisms have been proposed including mutations in ESR1, crosstalk between growth factor and ERα signaling, and interplay between cell cycle machinery and ERα signaling. ESR1 mutations as well as crosstalk with other signaling networks lead to ligand independent activation of ERα thus rendering anti-estrogens ineffective, particularly when treatment involved anti-estrogens that do not degrade ERα. As a result of these studies, several therapies that combine anti-estrogens that degrade ERα with PI3K/AKT/mTOR inhibitors targeting growth factor signaling or CDK4/6 inhibitors targeting cell cycle machinery are used clinically to treat recurrent ERα+ breast cancers. In this review, we discuss the nexus between ERα-PI3K/AKT/mTOR pathways and how understanding of this nexus has helped to develop combination therapies.

Influenza surveillance capacity improvements in Africa during 2011-2017.

BACKGROUND: Influenza surveillance helps time prevention and control interventions especially where complex seasonal patterns exist. We assessed influenza surveillance sustainability in Africa where influenza activity varies and external funds for surveillance have decreased. METHODS: We surveyed African Network for Influenza Surveillance and Epidemiology (ANISE) countries about 2011-2017 surveillance system characteristics. Data were summarized with descriptive statistics and analyzed with univariate and multivariable analyses to quantify sustained or expanded influenza surveillance capacity in Africa. RESULTS: Eighteen (75%) of 24 ANISE members participated in the survey; their cumulative population of 710 751 471 represent 56% of Africa's total population. All 18 countries scored a mean 95% on WHO laboratory quality assurance panels. The number of samples collected from severe acute respiratory infection case-patients remained consistent between 2011 and 2017 (13 823 vs 13 674 respectively) but decreased by 12% for influenza-like illness case-patients (16 210 vs 14 477). Nine (50%) gained capacity to lineage-type influenza B. The number of countries reporting each week to WHO FluNet increased from 15 (83%) in 2011 to 17 (94%) in 2017. CONCLUSIONS: Despite declines in external surveillance funding, ANISE countries gained additional laboratory testing capacity and continued influenza testing and reporting to WHO. These gains represent important achievements toward sustainable surveillance and epidemic/pandemic preparedness.

Clofibrate, a PPAR-α agonist, abrogates sodium fluoride-induced neuroinflammation, oxidative stress, and motor incoordination via modulation of GFAP/Iba-1/anti-calbindin signaling pathways.

Fluoride is an environmental contaminant that is ubiquitously present in air, water, and soil. It is commonly added in minute quantity to drinking water, toothpaste, and mouth rinses to prevent tooth decay. Epidemiological findings have demonstrated that exposure to fluoride induced neurodevelopmental toxicity, developmental neurotoxicity, and motor disorders. The neuroprotective effect of clofibrate, a peroxisome proliferator-activated receptor alpha agonist, was investigated in the present study. Forty male Wistar rats were used for this study and randomly grouped into 10 rats per group as control, sodium fluoride (NaF) alone (300 ppm), NaF plus clofibrate (250 mg/kg), and NaF plus lisinopril (10 mg/kg), respectively, for 7 days. NaF was administered in drinking water while clofibrate and lisinopril were administered by oral gavage. Markers of neuronal inflammation and oxidative stress, acetylcholinesterase activity, and neurobehavioral (hanging wire and open field) tests were performed. Immunohistochemistry was performed on brain tissues, and they were probed with glial fibrillary acidic protein, ionized calcium-binding adaptor molecule 1, and cerebellar Ca2+ -binding protein calbindin-D28k. The results showed that NaF significantly increased of oxidative stress and neuroinflammation and inhibited AChE activity. Immunostaining showed reactive astrocytes, microgliosis, loss of dendritic spines, and arborization in Purkinje cells in rats administered only NaF. Neurobehavioral results showed that cotreatment of NaF with clofibrate improved muscular strength and locomotion, reduced anxiety, and significantly reduced astrocytic count. Overall, cotreatment of NaF with either clofibrate or lisinopril showed neuroprotective effects by mitigating neuronal inflammation and oxidative and motor incoordination. Hence, clofibrate could be seen as a novel drug candidate against neurodegeneration and motor disorders.

Multiyear persistence of 2 pandemic A/H1N1 influenza virus lineages in West Africa.

Our understanding of the global ecology of influenza viruses is impeded by historically low levels of viral surveillance in Africa. Increased genetic sequencing of African A/H1N1 pandemic influenza viruses during 2009-2013 revealed multiyear persistence of 2 viral lineages within West Africa, raising questions about the roles of reduced air traffic and the asynchrony of seasonal influenza epidemics among West African countries in the evolution of independent lineages. The potential for novel influenza virus lineages to evolve within Africa warrants intensified influenza surveillance in Africa and other understudied areas.

Characterisation of heart failure with normal ejection fraction in a tertiary hospital in Nigeria.

BACKGROUND: The study aimed to determine the frequency and characteristics of heart failure with normal EF in a native African population with heart failure. METHODS: It was a hospital cohort study. Subjects were 177 consecutive individuals with heart failure and ninety apparently normal control subjects. All the subjects underwent transthoracic echocardiography. The group with heart failure was further subdivided into heart failure with normal EF (EF > or = 50) (HFNEF) and heart failure with low EF(EF <50)(HFLEF). RESULTS: The subjects with heart failure have a mean age of 52.3 +/- 16.64 years vs 52.1 +/- 11.84 years in the control subjects; p = 0.914. Other baseline characteristics except blood pressure parameters and height were comparable between the group with heart failure and the control subjects. The frequency of HFNEF was 39.5%. Compared with the HFLEF group, the HFNEF group have a smaller left ventricular diameter (in diastole and systole): (5.2 +/- 1.22 cm vs 6.2 +/- 1.39 cm; p < 0.0001 and 3.6 +/- 1.24 cm vs 5.4 +/- 1.35 cm;p < 0.0001) respectively, a higher relative wall thickness and deceleration time of the early mitral inflow velocity: (0.4 +/- 0.12 vs 0.3 +/- 0.14 p < 0.0001 and 149.6 +/- 72.35 vs 110.9 +/- 63.40 p = 0.001) respectively. The two groups with heart failure differed significantly from the control subjects in virtually all echocardiographic measurements except aortic root diameter, LV posterior wall thickness(HFLEF), and late mitral inflow velocity(HFNEF). HFNEF accounted for 70(39.5%) of cases of heart failure in this study. Hypertension is the underlying cardiovascular disease in 134(75.7%) of the combined heart failure population, 58 (82.9%) of the subjects with HFNEF group and 76(71%) of the HFLEF group. Females accounted for 44 (62.9%) of the subjects with HFNEF against 42(39.3%) in the HFLEF group (p = 0.002). CONCLUSION: The frequency of heart failure with normal EF in this native African cohort with heart failure is comparable with the frequency in other populations. These groups of patients are more likely female, hypertensive with concentric pattern of left ventricular hypertrophy.

Blood pressure control and left ventricular hypertrophy in hypertensive Nigerians.

BACKGROUND: Hypertension is a disease characterized by end-organ complications, leading to high morbidity and mortality in many cases. People with untreated or uncontrolled hypertension often run the risk of developing complications directly associated with the disease. Left ventricular hypertrophy (LVH) has been shown to be a significant risk factor for adverse outcomes both in patients with hypertension and in the general population. We investigated the prevalence and pattern of LVH in a treated hypertensive population at the University College Hospital, Ibadan, Nigeria, using non-hypertensive subjects as control. Design and Setting : A prospective observational study performed at the University College Hospital, Ibadan, Nigeria. METHODS: Patients had 6 visits, when at least one blood pressure measurement was recorded for each hypertensive subject and average calculated for systolic blood pressure (SBP) and diastolic blood pressure (DBP) separately. The values obtained were used for stratification of the subjects into controlled and uncontrolled hypertension. Subjects also had echocardiograms to determine their left ventricular mass. RESULTS: LVH was found in 14 (18.2%) of the normotensive group, 40 (20.8%) of the uncontrolled hypertensive group and 14 (24.1%) of the controlled hypertensive group when left ventricular mass (LVM) was indexed to body surface area (BSA). When LVM was indexed to height, left ventricular hypertrophy was found in none of the subjects of the normotensive group, while it was found present in 43 (22.4%) and 14 (24.1%) subjects of the uncontrolled and controlled hypertensive groups, respectively. Significant difference in the prevalence of LVH was detected only when LVM was indexed to height alone. CONCLUSION: Clinic blood pressure is an ineffective way of assessing BP control. Thus in apparently controlled hypertensive subjects, based on office blood pressure, cardiac structural changes do remain despite antihypertensive therapy. This population is still at risk of cardiovascular events.

Left ventricular geometric patterns in normotensive type 2 diabetic patients in Nigeria: an echocardiographic study.

Left ventricular hypertrophy has been linked with diabetes mellitus and abnormal glucose tolerance in several studies. Most previous studies have been carried out in the western world with dearth of data in native Africans. A total of 122 type 2 diabetic patients with a mean age of 55.0+/-8.5 years and another 90 normal patients with a mean age of 55.4+/-8.7 years were recruited for the study. Two-dimensional guided M-mode echocardiography was performed on each patient. In the diabetic patients, 49.2% had normal geometry, 23.0% had concentric hypertrophy, 13.0% had concentric remodeling, and 14.8% had eccentric hypertrophy. In the control group, 72.2% had normal geometry, 4.4% had concentric hypertrophy, 11.2% had concentric remodeling, and 12.2% had eccentric hypertrophy. In a multiple regression analysis, there was significant difference in the geometric pattern of the diabetics and controls (chi(2)=11.09, P<.001). Diabetes mellitus is independently associated with left ventricular structural changes in Nigerian diabetics.

Characterisation of left ventricular function by tissue Doppler imaging technique in newly diagnosed, untreated hypertensive subjects.

BACKGROUND: Hypertension results in structural and functional changes in the heart. Early detection of abnormalities of cardiac structure and function is important in the assessment and treatment of hypertensive subjects. The aim of this study was to evaluate the utility of the tissue Doppler echocardiographic technique in characterising diastolic and systolic functions in untreated native black African hypertensive subjects. MATERIALS AND METHODS: Forty consecutive, newly diagnosed, untreated hypertensives with adequate conventional echocardiographic (2-D, M-mode, transmitral and pulmonary Doppler flow velocities) and tissue Doppler echocardiographic images were recruited into the study. The control subjects were apparently normal individuals. Each arm of the study consisted of 21 male and 19 female subjects. RESULTS: The two groups were comparable by age (48.6 +/- 11.35 years in the hypertensives vs 48.1 +/- 11.33 years in the controls; p = 0.844) and gender distribution (M/F: 21/19 in both groups). Other baseline characteristics, except for blood pressure parameters, which were predictably higher in the hypertensive subjects, were comparable between the two groups. The hypertensive subjects had a lower systolic myocardial velocity (Sm) and early diastolic myocardial velocity (Em) in comparison with the controls (p = 0.033 and p = 0.018, respectively). The late diastolic myocardial velocity (Am) was comparable in the two groups (p = 0.430). CONCLUSIONS: Tissue Doppler echocardiography demonstrates diastolic dysfunction relatively early in native African hypertensives and may be useful for detecting subtle deterioration in systolic function.

Left ventricular diastolic function in normotensive type-2 diabetic subjects.

BACKGROUND: Most previous studies on diastolic function in diabetics are confounded by coexisting ischemic heart disease, obesity and hypertension. Therefore, there may be advantages in studying patients with diabetes mellitus in developing nations where confounding variables are less prevalent. The aim of this study was to assess the effect of type-2 diabetes mellitus on left ventricular diastolic function in normotensive subjects in Nigeria. METHODS: One-hundred-twenty-two patients with type-2 diabetes mellitus aged 35-74 years with a mean age of 55.30 +/- 8.53 years were studied. Patients with blood pressure > or =140/90 mmHg or on treatment for hypertension were excluded from the study. Ninety-one healthy volunteers aged 40-75 years with a mean age of 55.30 +/- 8.56 years were recruited as normal controls. Transthoracic echocardiography was performed in all subjects to assess their left ventricular diastolic filling pattern by analyzing mitral and pulmonary flow velocities. RESULTS: Seventy-one (58%) of the type-2 diabetic subjects had evidence of impaired relaxation, 9 (7%) had pseudonormal filling and 7 (6%) had a restrictive filling pattern. Only 29% of the diabetics had a normal filling profile compared to 58% of the normal controls (X2 = 19.4, p = 0.0002). CONCLUSIONS: The result of the study shows that Nigerian type-2 diabetics have impaired left ventricular filling compared with normal subjects independent of confounding factors such as obesity and blood pressure. Therefore, not only Caucasians, African Americans and Asians but also African diabetic subjects suffered from diastolic dysfunction.

Changes in left atrial dimension and function and left ventricular geometry in newly diagnosed untreated hypertensive subjects.

BACKGROUND: It is known that a spectrum of changes in structure, size and function of the different chambers of the heart occur in individuals with hypertension. The earliest changes and the sequence of these changes are still being studied. AIMS: The present study aimed to assess early changes in the left atrial size and function in hypertension, and its relationship with left ventricular geometry and other factors that may influence left atrial size. METHODS: One hundred consecutive subjects who were newly diagnosed with hypertension and 50 apparently normal individuals were recruited into the study. Standard M-mode, two-dimensional and Doppler echocardiography were performed. The endocardial border of the left atrium was traced to obtain the atrial area and left atrial volumes and emptying fractions were derived from measured areas. RESULTS: The hypertensive patients and the controls were comparable by age, sex and body mass index. Thirty-seven (37%) of the hypertensive subject had increased left ventricular mass versus eight subjects (16%) in the normal controls. The patients with hypertension had a higher linear left atrial dimension (3.5 +/- 0.48 cm versus 3.1 +/- 0.47 cm, P < 0.0001), longer pre-atrial contraction length (3.8 +/- 0.56 cm versus 3.6 +/- 0.45 cm; P = 0.02) and higher peak late mitral inflow velocity (0.64 +/- 0.19 m/s versus 0.56 +/- 0.15 m/s; P = 0.010). CONCLUSIONS: Changes in the geometry of the left ventricle occur early in hypertension and precede deterioration in left ventricular systolic function. The corresponding left atrial changes are marginal and are indicative of increased left atrial length and accentuated atrial systolic function.

Characterisation of left ventricular function by tissue Doppler imaging technique in newly diagnosed, untreated hypertensive subjects

BACKGROUND:Hypertension results in structural and functional changes in the heart. Early detection of abnormalities of cardiac structure and function is important in the assessment and treatment of hypertensive subjects. The aim of this study was to evaluate the utility of the tissue Doppler echocardiographic technique in characterising diastolic and systolic functions in untreated native black African hypertensive subjects.MATERIALS AND METHODS:Forty consecutive, newly diagnosed, untreated hypertensives with adequate conventional echocardiographic (2-D, M-mode, transmitral and pulmonary Doppler flow velocities) and tissue Doppler echocardiographic images were recruited into the study. The control subjects were apparently normal individuals. Each arm of the study consisted of 21 male and 19 female subjects.RESULTS:The two groups were comparable by age (48.6 +/- 11.35 years in the hypertensives vs 48.1 +/- 11.33 years in the controls; p = 0.844) and gender distribution (M/F: 21/19 in both groups). Other baseline characteristics, except for blood pressure parameters, which were predictably higher in the hypertensive subjects, were comparable between the two groups. The hypertensive subjects had a lower systolic myocardial velocity (Sm) and early diastolic myocardial velocity (Em) in comparison with the controls (p = 0.033 and p = 0.018, respectively). The late diastolic myocardial velocity (Am) was comparable in the two groups (p = 0.430). CONCLUSIONS:Tissue Doppler echocardiography demonstrates diastolic dysfunction relatively early in native African hypertensives and may be useful for detecting subtle deterioration in systolic function

Echocardiographic partition values and prevalence of left ventricular hypertrophy in hypertensive Nigerians.

BACKGROUND: Left ventricular hypertrophy (LVH) is a well known independent risk factor for cardiovascular events. It has been shown that combination of left ventricular mass (LVM) and relative wall thickness (RWT) can be used to identify different forms of left ventricular (LV) geometry. Prospective studies have shown that LV geometric patterns have prognostic implications, with the worst prognosis associated with concentric hypertrophy. The methods for the normalization or indexation of LVM have also recently been shown to confer some prognostic value especially in obese population. We sought to determine the prevalence of echocardiographic lLVH using eight different and published cut-off or threshold values in hypertensive subjects seen in a developing country's tertiary centre. METHODS: Echocardiography was performed in four hundred and eighty consecutive hypertensive subjects attending the cardiology clinic of the University college Hospital Ibadan, Nigeria over a two-year period. RESULTS: Complete data was obtained in 457 (95.2%) of the 480 subjects (48.6% women). The prevalence of LVH ranged between 30.9-56.0%. The highest prevalence was when LVM was indexed to the power of 2.7 with a partition value of 49.2 g/ht2.7 in men and 46.7 g/ht2.7 in women. The lowest prevalence was observed when LVM was indexed to body surface area (BSA) and a partition value of 125 g/m2 was used for both sexes. Abnormal LV geometry was present in 61.1%-74.0% of our subjects and commoner in women. CONCLUSION: The prevalence of LVH hypertensive patients is strongly dependent on the cut-off value used to define it. Large-scale prospective study will be needed to determine the prognostic implications of the different LV geometry in native Africans.