Salivary response to esophageal acid in normal subjects and patients with reflux esophagitis

We studied the effect of esophageal acid perfusion on salivation in patients with reflux esophagitis and in normal subjects. Serial 10-min saliva collections were obtained by expectoration during perfusion of the esophagus with water, and then 0.1 N HCl (pH 1.2) for 50 min or 0.01 N HCl (pH 2.1) for 120 min. Within 1-5 min of beginning 0.1 N HCl perfusion, all 8 patients with esophagitis developed heartburn accompanied by an increase in saliva flow. By the time the severity of heartburn required discontinuation of HCl perfusion (10-40 min), saliva flow had increased nearly fourfold. With 0.1 N HCl perfusion, 8 of 10 volunteers developed mild heartburn after 22 +/- 3 min (mean +/- SE), whereas 0.01 N HCl induced heartburn in 6 of 10 volunteers after 57 +/- 12 min of perfusion. Saliva flow increased concurrently with the onset of heartburn and doubled in those volunteers who developed heartburn. Saliva flow did not change in those volunteers who were without heartburn. We conclude that esophageal acid perfusion unaccompanied by heartburn does not affect salivation. However, saliva flow increases concurrently with the onset of heartburn, a phenomenon called "water brash" when clinically evident. The increased saliva flow that accompanies heartburn may act as an endogenous antacid that serves as a protective response to symptomatic gastroesophageal reflux.     

Unhealthy geopolitics: can the response to COVID-19 reform climate change policy?

The geopolitics of pandemics and climate change intersect. Both are complex and urgent problems that demand collective action in the light of their global and trans-boundary scope. In this article we use a geopolitical framework to examine some of the tensions and contradictions in global governance and cooperation that are revealed by the pandemic of coronavirus disease 2019 (COVID-19). We argue that the pandemic provides an early warning of the dangers inherent in weakened international cooperation. The world’s states, with their distinct national territories, are reacting individually rather than collectively to the COVID-19 pandemic. Many countries have introduced extraordinary measures that have closed, rather than opened up, international partnership and cooperation. Border closures, restrictions on social mixing, domestic purchase of public health supplies and subsidies for local industry and commerce may offer solutions at the national level but they do not address the global strategic issues. For the poorest countries of the world, pandemics join a list of other challenges that are exacerbated by pressures of scarce resources, population density and climate disruption. COVID-19’s disproportionate impact on those living with environmental stresses, such as poor air quality, should guide more holistic approaches to the geopolitical intersection of public health and climate change. By discussing unhealthy geopolitics, we highlight the urgent need for a coordinated global response to addressing challenges that cannot be approached unilaterally.     

Criteria for the diagnosis of endocarditis and the role of echocardiography

When infective endocarditis is a diagnostic possibility, echocardiography permits noninvasive imaging of cardiac structures. As involvement of the endocardium is a sine qua non of endocarditis, echocardiography may assist in its diagnosis by demonstrating such involvement. The ability of echocardiography to detect the intracardiac manifestations of infective endocarditis has continued to improve, especially with the introduction of transesophageal imaging. This article will discuss some of the echocardiographic findings in endocarditis and elucidate the incorporation of these findings in the new Duke criteria for the diagnosis of endocarditis.     

The mechanism for the inhibition of acetylcholinesterases by irinotecan (CPT-11)

Irinotecan (CPT-11) is an anticancer drug that occasionally produces acute cholinergic side effects. Preliminary findings suggest that these are mediated through the inhibition of acetylcholinesterase (AChE). In this study, the inhibition of various AChEs by CPT-11 was studied. The lactone form of CPT-11 resulted in apparent noncompetitive inhibition of electric eel and both human recombinant and erythrocyte AChE with K(i) values of 0.065, 0.19, and 0.29 microM, respectively. The carboxylate form of CPT-11 was approximately 10 times less potent. Apparent noncompetitive inhibition of AChE may arise through several mechanisms, and those relevant to CPT-11 were identified from key experimental findings. First, the inhibition by CPT-11 was found to be instantly reversible in dilution studies. Second, incubation of the enzyme with CPT-11 before the introduction of neostigmine protected the enzyme from inactivation. Third, regeneration of the active enzyme after preincubation with neostigmine was totally suppressed by the addition of 2 microM CPT-11, indicating that CPT-11 is a potent inhibitor of decarbamoylation and, by inference, deacylation. Additional experiments with tacrine revealed functional differences between these two inhibitors. Also, preliminary molecular modeling of the interaction between AChE and CPT-11 indicated that the latter does not bind at the same site as tacrine. Displacement studies with the peripheral site-specific ligand, propidium, confirmed that CPT-11 binds at this site. The rapid reversibility of the inhibition of AChE by CPT-11 and the lower activity of the carboxylate form are likely reasons for the transient nature of the cholinergic toxicity observed clinically.     

Access to hospital care for California and Michigan Medicaid recipients

This article is a comparison of the characteristics of hospitals serving the general population and Medicaid recipients in California and Michigan, using data from Medicaid uniform claims files and the American Hospital Association Annual Survey for 1984. A greater concentration of discharges in a small number of "high Medicaid volume" urban and rural hospitals in each State was observed for Medicaid recipients compared with the general population. In addition, discharge data suggest that Supplemental Security Income crossovers (individuals covered by both Medicaid and Medicare) and other recipients (mostly children not enrolled in the Aid to Families with Dependent Children program) receive inpatient care in different hospitals from the general population as well as from other Medicaid eligibility groups. Medicaid cost-containment policies and differential access to hospital care are discussed.     

Afferent innervation of outer and inner hair cells is normal in neonatally de-efferented cats

It has been hypothesized that normal pruning of exuberant branching of afferent neurons in the developing cochlea is caused by the arrival of the olivocochlear efferent neurons and the resulting competition for synaptic sites on hair cells. This hypothesis was supported by a report that afferent innervation density on mature outer hair cells (OHCs) is elevated in animals deefferented at birth, before the olivocochlear system reaches the outer hair cell area (Pujol and Carlier [1982] Dev. Brain Res. 3:151-154). In the current study, this claim was evaluated quantitatively at the electron microscopic level in four cats that were de-efferented at birth and allowed to survive for 6-11 months. A semiserial section analysis of 156 OHCs from de-efferented and normal ears showed that, although de-efferentation essentially was complete in all four cases, the number and distribution of afferent terminals on OHCs was indistinguishable from normal, and the morphology of afferent synapses was normal in both the inner hair cell area and the OHC area. Thus, the postnatal presence of an efferent system is not required for the normal development of cochlear afferent innervation, and the synaptic competition hypothesis is not supported.     

The Association Between Influenza Vaccine in Pregnancy and Adverse Neonatal Outcomes

ObjectiveTo determine whether neonatal outcomes differ between women vaccinated during pregnancy and those not vaccinated.MethodsSelf-reported history of receipt of influenza vaccination during pregnancy was collected from women at the time of admission for obstetrical delivery at the IWK Health Centre in Halifax, Nova Scotia, beginning in April 2006. The cohort for this study included women who delivered a singleton infant prior to November 2009, reflecting the pre-pandemic H1N1 vaccination period. Neonatal outcomes were compared using logistic regression between vaccinated and non-vaccinated women.ResultsOverall, 1957 of 9781 women (20%) included in the cohort received influenza vaccine during their pregnancy. The adjusted odds ratio and 95% confidence interval for a small for gestational age infant (lowest 10th percentile birth weight for gestational age and sex) was 0.80 (95% CI 0.65 to 0.95) for vaccinated women relative to non-vaccinated women. The adjusted odds ratio for a low birth weight infant was 0.74 (95% CI 0.58 to 0.95). Rates of preterm birth and a composite indicator of adverse neonatal outcomes were lower among vaccinated women, but were not statistically significant. The effects of maternal vaccination on neonatal outcomes did not differ between high- and low-risk women.ConclusionAs evidence continues to mount in support of improved neonatal outcomes associated with receiving influenza vaccination during pregnancy, enhanced public health measures are necessary to encourage pregnant women to receive the influenza vaccine.