Clinical and neurohormonal characteristics in African Americans with neurogenic orthostatic hypotension.

PURPOSE: Neurogenic orthostatic hypotension (nOH) is the hallmark of neurodegenerative forms of autonomic failure, including pure autonomic failure, multiple system atrophy, and Parkinson's disease. Studies have shown autonomic physiological differences in Africans Americans (AA) such as lower heart rate variability, enhanced blood pressure reactivity, and blunted sympathetic neural response compared to non-Hispanic whites. However, the clinical characteristics and neurohormonal profile of autonomic failure in AA is unknown. METHODS: A total of 65 patients with nOH participated in this study (9 AA and 56 non-Hispanic whites). Both groups were of similar age and comorbidity status, and they underwent standardized autonomic testing and assessment of neurohormonal levels and renin activity and aldosterone in supine and upright positions. RESULTS: There were no significant differences in baseline autonomic clinical characteristics between non-Hispanic whites and AA with nOH. Non-Hispanic whites demonstrated a significant increase in upright renin activity compared to AA (295 ± 88% vs. 13 ± 13%, respectively). AA showed a blunted increase in aldosterone compared to non-Hispanic whites (188 ± 27% vs. 59 ± 38%, respectively). These results indicated persistent suppression of the renin-angiotensin system in AA, particularly during upright posture. CONCLUSION: Our findings demonstrate that AA with nOH have similar clinical characteristics and hemodynamic autonomic profiles, but lower upright renin activity and aldosterone levels, compared to non-Hispanic whites. Renin suppression persists in AA with severe autonomic failure and can potentially contribute to postural changes and supine hypertension.

Race and sex differences in cardiovascular autonomic regulation.

Racial and ethnic differences in cardiovascular morbidity and mortality persist despite advances in risk factor identification and implementation of evidence-based treatment strategies. African American men and women are disproportionately affected by cardiovascular risk factors, particularly hypertension. In this context, previous studies have identified sex and racial differences in autonomic cardiovascular regulation which may contribute to the development of hypertension and its high morbidity burden among African Americans. In this review, we provide a comprehensive evaluation of the potential pathophysiological mechanisms of blood pressure control and their differences based on sex and race. These mechanisms include obesity-induced sympathetic activation, sympatho-vascular transduction, baroreflex sensitivity and adrenoreceptor vascular sensitivity, which have been the subjects of prior investigation in this field. Understanding the racial differences in the pathophysiology of hypertension and its co-morbid conditions would allow us to implement better treatment strategies tailored to African Americans, with the ultimate goal of reducing cardiovascular mortality in this population.

Bilateral anterior and posterior scleritis in a patient with acute myelogenous leukemia.

Purpose: To report a novel case of bilateral anterior and posterior scleritis in a patient with acute myelogenous leukemia (AML). Observations: A 69-year-old African American man was admitted to the hospital for relapse of AML. After admission, but prior to induction of chemotherapy, the patient developed ocular redness and proptosis. The diagnosis of bilateral anterior and posterior scleritis was made following an ophthalmic examination, infectious and autoimmune lab work-up, and neuroimaging. The patient was administered immunosuppressive therapy, clinically monitored, and initiated on chemotherapy for AML relapse. About one week later, the patient showed clinical improvement and resolution of the scleritis and proptosis. Conclusion: Scleritis may present during AML relapse, and it may be due to a paraneoplastic syndrome or a reactive anti-leukemic inflammatory response. Clinicians should monitor patients with AML relapse for symptoms such as ocular redness, proptosis, pain, photophobia, and decreased vision, which may indicate development of scleritis.

Wernicke's encephalopathy mimicking multiple sclerosis in a young female patient post-bariatric gastric sleeve surgery.

We describe a case of Wernicke's encephalopathy secondary to thiamine (B1) deficiency in a patient status post-bariatric sleeve gastrectomy. The presenting symptoms of new-onset weakness, diplopia, and confusion in a young female patient raised suspicion for multiple sclerosis (MS), but given a history of bariatric surgery, thiamine levels were checked, revealing significant Vitamin B1 (thiamine) deficiency. This case highlights the importance of thorough history taking, as a misdiagnosis of MS in this case could have resulted in irreversible neurological deterioration and hematological and infectious consequences associated with the inappropriate administration of disease-modifying therapies. It is also important to note that severe vitamin deficiency occurred despite medication compliance.

Morbidity and mortality in orthostatic hypotension.

This review summarizes the current literature on the epidemiology of orthostatic hypotension (OH) in the elderly and in patients with autonomic impairment also known as neurogenic OH (nOH); these two conditions have distinct pathophysiologies and affect different patient populations. The prevalence of OH in the elderly varies depending on the study population. In community dwellers, OH prevalence is estimated at 16%, whereas in institutionalized patients, it may be as high as 60%. The prevalence of OH increases exponentially with age, particularly in those 75 years and older. Multiple epidemiological studies have identified OH as a risk factor for all-cause mortality and cardiovascular disease including heart failure and stroke. Real-world data from administrative databases found polypharmacy, multiple co-morbid conditions, and high health-care utilization as common characteristics in OH patients. A comprehensive evaluation of medications associated with OH is discussed with particular emphasis on the use of anti-hypertensive therapy from two large clinical trials on high-intensive versus standard blood pressure management. Finally, we also review the epidemiology of nOH based on the underlying neurodegenerative disorder (either Parkinson's disease or multiple system atrophy), and the presence of co-morbid conditions such as hypertension and cognitive impairment.

Sex- and Gamete-Specific Patterns of X Chromosome Segregation in a Trioecious Nematode.

Three key steps in meiosis allow diploid organisms to produce haploid gametes: (1) homologous chromosomes (homologs) pair and undergo crossovers; (2) homologs segregate to opposite poles; and (3) sister chromatids segregate to opposite poles. The XX/XO sex determination system found in many nematodes [1] facilitates the study of meiosis because variation is easily recognized [2-4]. Here we show that meiotic segregation of X chromosomes in the trioecious nematode Auanema rhodensis [5] varies according to sex (hermaphrodite, female, or male) and type of gametogenesis (oogenesis or spermatogenesis). In this species, XO males exclusively produce X-bearing sperm [6, 7]. The unpaired X precociously separates into sister chromatids, which co-segregate with the autosome set to generate a functional haplo-X sperm. The other set of autosomes is discarded into a residual body. Here we explore the X chromosome behavior in female and hermaphrodite meioses. Whereas X chromosomes segregate following the canonical pattern during XX female oogenesis to yield haplo-X oocytes, during XX hermaphrodite oogenesis they segregate to the first polar body to yield nullo-X oocytes. Thus, crosses between XX hermaphrodites and males yield exclusively male progeny. During hermaphrodite spermatogenesis, the sister chromatids of the X chromosomes separate during meiosis I, and homologous X chromatids segregate to the functional sperm to create diplo-X sperm. Given these intra-species, intra-individual, and intra-gametogenesis variations in the meiotic program, A. rhodensis is an ideal model for studying the plasticity of meiosis and how it can be modulated.