Autoimmune hepatitis associated with the use of black cohosh: a case study

Herbal remedies generate more than 1.8 billion dollars in annual sales in the United States. Herbal products have been associated with a wide spectrum of hepatic toxicities. With the recent Women's Health Initiative Study demonstrating increased risk of breast cancer and cardiovascular events associated with hormone therapy, many women may resort to herbal remedies for persistent menopause symptoms. We report a case of autoimmune hepatitis likely triggered by the use of black cohosh (Actaea racemosa), an agent marketed to treat menopause symptoms. Given this case report, we recommend close monitoring of women using this herbal preparation.     

Monitoring, past, present, future

Summary A little over 40 years ago, anesthesiology in the United States became recognized as a specialty. At that time, its practice was largely that of an art, the science of which was yet to come. A finger on the pulse, observation of color, skin turgor, perspiration, and perhaps a blood pressure cuff in adults, and an estimation of the reflex signs of anesthesia were the standards for the assessment of the patient status and the depth of anesthesia. How far have we come in the intervening years? The journey, as reflected in the experience of one physician, will be held up to the looking-glass; easily as astounding as that through which Alice passed.Caught as we are in the socio-economic climate of the present, how shall we react? Has the gadgetry and electronics of this day given us a meaningful cost-effective handle on a decreased morbidity and mortality? What impact is there on decision-making and outcome? What indeed is the contribution of the machine versus the newer agents, techniques, and the advanced educational milieu.The first attempts at monitoring were clearly directed toward the cardiovascular system. The devices developed were simple and non-invasive. The Riva-rocci method of measuring blood pressure was first applied in anesthesia by Harvey Cushing at the turn of the century. But it was 40 years before the electrocardiogram was introduced as an instrument of potential importance. It took another 25 years for it to have general acceptance, and even later for the anesthesiologist to become comfortable with it as a diagnostic tool. In the early 40s, Peterson, at Pennsylvania, began the applications of invasive blood pressure monitoring for clinical purposes. Subsequently, the use of the central venous catheter, and finally the Swan-Ganz catheter, became acceptable. The application for the technology of cardiac output was a long time in gaining clinical credence. However, this last link surely depended on the computer to make it a clinically useful instrument. The measurement of the cardiovascular system was first, because the means were there.The assessment of respiratory function was more cumbersome, and while the pneumotachygraph was available 40 years ago, its vagaries made it a research tool. Meters for respiration also were available, but too cumbersome for clinical use. The integration of respiratory measurements and blood gas analysis have gone hand-in-hand, the latter far outstripping the former in clinical utility. Shall it be invasive or non-invasive, what is the price? Lastly, our technology has introduced the means for what is a meaningful clinical measurement of neurological and neuromuscular activity. Nerve-muscle stimulators, electromyography, processed electroencephalogram, and the evoked potential as devices for assessment are only the beginning. In all this technological advance there is the black box and the electronic marvels that are part of this age. While invasive techniques surely have a place, the utilization of non-invasive techniques like the measurement of oxygen, carbon dioxide, and all the agents that we employ have changed forever the nature of our practice. Finally, the need to document the anesthesia course objectively will, and has already begun, to impact on our practice. How did we get where we are and where are we going will be explored in this personal journey.     

Working conditions and health behavior as causes of educational inequalities in self-rated health: an inverse odds weighting approach

Objective:Using a novel mediation method that presents unbiased results even in the presence of exposure–mediator interactions, this study estimated the extent to which working conditions and health behaviors contribute to educational inequalities in self-rated health in the workforce.Methods:Respondents of the longitudinal Survey of Health, Ageing, and Retirement in Europe (SHARE) in 16 countries were selected, aged 50–64 years, in paid employment at baseline and with information on education and self-rated health (N=15 028). Education, health behaviors [including body mass index (BMI)] and working conditions were measured at baseline and self-rated health at baseline and two-year follow-up. Causal mediation analysis with inverse odds weighting was used to estimate the total effect of education on self-rated health, decomposed into a natural direct effect (NDE) and natural indirect effect (NIE).Results:Lower educated workers were more likely to perceive their health as poor than higher educated workers [relative risk (RR) 1.48, 95% confidence interval (CI) 1.37–1.60]. They were also more likely to have unfavorable working conditions and unhealthy behaviors, except for alcohol consumption. When all working conditions were included, the remaining NDE was RR 1.30 (95% CI 1.15–1.44). When BMI and health behaviors were included, the remaining NDE was RR 1.40 (95% CI 1.27–1.54). Working conditions explained 38% and health behaviors and BMI explained 16% of educational inequalities in health. Including all mediators explained 64% of educational inequalities in self-rated health.Conclusions:Working conditions and health behaviors explain over half of the educational inequalities in self-rated health. To reduce health inequalities, improving working conditions seems to be more important than introducing health promotion programs in the workforce.     

Stapedectomy in Patients With Small Air-Bone Gaps

Controversy exists concerning stapedectomy for patients with small air-bone gaps. The purpose of this study was to examine the results for patients who had a stapedectomy to correct a small (10 dB or less) air-bone gap. One hundred fifty-four patients with suspected otosclerosis were explored and a stapedectomy was performed in 136 (88.3%) of these cases. The mean pure-tone average (PTA) improved 16.7 dB and overclosed the preoperative bone conduction PTA by 8.1 dB. The majority of the stapedectomy patients (89.7%) had a PTA closure greater than or equal to 0 dB. These results showed that stapedectomy can be an effective procedure for eliminating and overclosing even small air-bone gaps due to otosclerosis.     

Study on the Mechanism Responsible for the Incompatibility of Enalapril Maleate with Sodium Starch Glycolate

Enalapril maleate (EM) is known to suffer from incompatibilities in the solid state. This study investigates the destabilizing effect of sodium starch glycolate (SSG) on EM. This was done by varying the mixing ratio and moisture content of binary mixtures. Differential scanning calorimetry and microscopy show a loss of crystallinity of EM at the contact surface with SSG. It is shown that this is followed by decomposition of E to diketopiperazine (DKP). These phenomena are modulated by moisture. The environmental pH turned out to be crucial; when the zwitterion is formed at the appropriate pH, ring closure into DKP is promoted.     

Malan syndrome: Sotos-like overgrowth with de novo NFIX sequence variants and deletions in six new patients and a review of the literature

De novo monoallelic variants in NFIX cause two distinct syndromes. Whole gene deletions, nonsense variants and missense variants affecting the DNA-binding domain have been seen in association with a Sotos-like phenotype that we propose is referred to as Malan syndrome. Frameshift and splice-site variants thought to avoid nonsense-mediated RNA decay have been seen in Marshall–Smith syndrome. We report six additional patients with Malan syndrome and de novo NFIX deletions or sequence variants and review the 20 patients now reported. The phenotype is characterised by moderate postnatal overgrowth and macrocephaly. Median height and head circumference in childhood are 2.0 and 2.3 standard deviations (SD) above the mean, respectively. There is overlap of the facial phenotype with NSD1-positive Sotos syndrome in some cases including a prominent forehead, high anterior hairline, downslanting palpebral fissures and prominent chin. Neonatal feeding difficulties and/or hypotonia have been reported in 30% of patients. Developmental delay/learning disability have been reported in all cases and are typically moderate. Ocular phenotypes are common, including strabismus (65%), nystagmus (25% ) and optic disc pallor/hypoplasia (25%). Other recurrent features include pectus excavatum (40%) and scoliosis (25%). Eight reported patients have a deletion also encompassing CACNA1A, haploinsufficiency of which causes episodic ataxia type 2 or familial hemiplegic migraine. One previous case had episodic ataxia and one case we report has had cyclical vomiting responsive to pizotifen. In individuals with this contiguous gene deletion syndrome, awareness of possible later neurological manifestations is important, although their penetrance is not yet clear.