Karl Thomas

Down regulation of the angiotensin II receptor subtype AT2 in human myometrium during pregnancy

Samples of human myometrium have been collected during pregnancy and from non-pregnant women. Binding studies revealed the presence of a 50-fold higher density of angiotensin II AT2 receptor in the non-pregnant state than during gestation. Low levels of the AT1 receptor subtype (approx. 20 fmol/mg protein) were detected in both pregnant and non-pregnant myometrium. Outside pregnancy, the AT2 receptor accounted for greater than 95% of all angiotensin receptors, whereas during pregnancy the value dropped to about 40%. The down regulation of the human myometrial AT2 receptor during pregnancy may be related to the high hormonal content of the environment induced by gestation. The mechanism by which the AT2 receptor is regulated appears to be different to that of the AT1 receptor.

Incidence of pathological factors not revealed by hysterosalpingography but disclosed by laparoscopy in 500 infertile women

Hysterosalpingography and laparoscopy were performed in 500 infertile women. Results obtained by both techniques were compared. Taking into consideration only the tubal patency, the present study shows an agreement in 90% of cases. In total of 980 fallopian tubes examined, fimbrial conglutination was suspected in 79 tubes (8%) and diagnosed by laparoscopy in 154 tubes (15.7%). Peritubal adhesions with tubal patency are a frequent pathology (23.8%) and hysterosalpingography alone permits the diagnosis in only 68.8% of the cases confirmed by laparoscopy. Other additional findings by laparoscopy are frequent: endometriosis was found in 124 women. Isolated periovarian adhesions were disclosed in 48 women. The high incidence of unsuspected pathology is an additional support in favor of laparoscopy in each case of infertility.

Presumed antepartum amniotic fluid embolism.

BACKGROUND Amniotic fluid embolism is seldom recognized in nonperipartum patients. The pathophysiology is uncertain and diagnosis imprecise, making management after stabilization difficult. CASE A 37-year-old woman at 28 weeks gestation presented with signs and symptoms consistent with amniotic fluid embolism including disseminated intravascular coagulopathy. A ventilation-perfusion scan demonstrated unmatched perfusion defects, but other radiographic studies were negative; the patient was treated with heparin. Four days after presentation she had spontaneous rupture of membranes followed by hypoxemia, necessitating cesarean delivery. A pulmonary arteriogram after the operation showed multiple filling defects; the patient was discharged on warfarin. CONCLUSION Amniotic fluid embolism is a difficult diagnosis to make, at best. Anticoagulation may be a therapeutic option.

Use of mechanical and noninvasive ventilation in black and white chronic obstructive pulmonary disease patients within the Veterans Administration health care system.

Background:Black patients are more likely than white patients to prefer and receive more life-sustaining interventions in advanced stages of disease. However, little is known about potential racial differences in use of mechanical ventilation (MV), and the newer modality of noninvasive ventilation (NIV), in treatment of chronic obstructive pulmonary disease (COPD). Objective:To determine if rates of MV and NIV use differ among black and white patients admitted to Veterans Administration (VA) hospitals for COPD exacerbation. Research Design:Retrospective cohort analysis of VA database FY2003 to FY2005 including 153 hospitals nationwide. Subjects:All black (n = 5479) and white (n = 31,537) patients admitted with COPD exacerbation. Measures:Ventilation use during hospitalization as identified by ICD-9-CM codes for MV and NIV. Hierarchical logistic regression compared rates of MV or NIV use among black and white patients, adjusting for patient characteristics and accounting for hospital-level variation. Results:Unadjusted rates of MV were higher in black patients than in white patients (4.1% vs. 3.0%; P < 0.001), but similar for NIV (6.0% vs. 6.1%; P = 0.65). The adjusted odds of MV for black patients relative to white patients remained higher (OR = 1.27, 95% CI: 1.01–1.54; P < 0.01) while the adjusted odds of NIV remained similar (OR = 0.94, 95% CI: 0.82–1.08; P = 0.38). Conclusions:Black patients with COPD exacerbation in VA hospitals are more likely than white patients to receive MV, and this difference is not explained by available clinical or demographic variables. By contrast, black and white patients are equally likely to receive NIV. These findings suggest that unmeasured factors, such as patient preferences or disease severity, may be affecting the use of MV in this setting and therefore warrant further investigation.

Right test, right time, right patient.

190 www.ccmjournal.org January 2014 • Volume 42 • Number 1 The expense and harms from excessive and inappropriate clinical testing have been discussed for years, but there have been no sustained multisystem improvements that reduce unnecessary testing. In addition to resource limitations and financial pressure, two recent developments are keeping this discussion on center stage. First, patient and consumer advocacy groups have developed an increased awareness of inappropriate testing and now encourage patients themselves to avoid unnecessary testing (1). Second, broad-based professional organizations have sponsored programs such as the Choosing Wisely Campaign with the main goal of reducing unnecessary tests, treatments, and procedures (2). The concept that an ideal set of laboratory, imaging, and physiologic tests can be determined for a patient who presents with a specific problem is more challenging than it initially appears. Ordering and completion of clinical tests is influenced by a highly complex set of variables related to the patient, provider, subspecialty profession, hospital, and the test itself (Table 1). Seen in this very broad context, the intensivist’s task to determine the right test at the right time for the right patient cannot be reduced to rules that assign highest priority to value, efficiency, cost, and harm without regard to other important clinical factors. Few would disagree that appropriate tests could be defined as having a direct link to the clinical condition and should drive management decisions. However, other priorities such as diagnostic hypothesis testing, screening, costs, patient preferences, and harms prevent the emergence of a single definition for the most appropriate testing. Conversely, inappropriate tests can be more easily described. Tests that are not directly related to the patient’s condition and are not useful in clinical decision making have been used in research to describe inappropriate testing (3) (Table 2). Although the complexity of this issue could halt progress for improving testing practice, one way forward has been to examine variation in test utilization within hospitals and between physicians. One underlying assumption of this approach is that variation between providers and groups indicates unnecessary testing, and detailed study of variations can provide solutions to improve rates of appropriate testing. In this issue of Critical Care Medicine, Spence et al (4) have described the variation in test orders in nine ICUs in Winnipeg, Canada. They measured the cumulative number of common basic laboratory, radiograph, and electrocardiogram tests per patient. Using a population-based, clinical ICU database, the investigators evaluated 10,262 patients and compared testing utilization by ICU and teaching status. Adjustments were made for length of stay, demographics, severity of illness, and specific medical interventions. The main findings of Spence et al (4) are that total testing is influenced strongly by length of stay and teaching versus nonteaching status of the ICU. Other notable findings include a lower rate of testing for older patients and a worrisome and significant increase in the rate of testing over the 4 years of observation. Although other investigators have described variation in testing between teaching and nonteaching hospitals (5), this study is particularly notable because of the size of the patient population as well as the multivariate logistic regression used to control for multiple clinical factors including severity of illness. The patients treated in teaching and nonteaching ICUs had comparable 30-day mortality and all had the same singlepayer government health insurance. There were differences in age and Acute Physiology and Chronic Health Evaluation II score as well as the organizational features of the nonteaching ICUs, which were smaller, and mixed medical-surgical units compared with the teaching ICUs that included exclusive medical, surgical, and coronary care units. The finding of higher test utilization in teaching ICUs suggests that inexperienced and in-training providers have different 11. Fuursted K, Hjort A, Knudsen L: Evaluation of bactericidal activity and lag of regrowth (postantibiotic effect) of five antiseptics on nine bacterial pathogens. J Antimicrob Chemother 1997; 40:221–226 12. Seguin P, Laviolle B, Dahyot-Fizelier C, et al; for the Study of Povidone Iodine to Reduce pulmonary Infection in head Trauma and cerebral hemorrhage patients (SPIRIT) ICU Study and AtlanRéa Groups: Effect of Oropharyngeal Povidone-Iodine Preventive Oral Care on Ventilator-Associated Pneumonia in Severely Brain-Injured or Cerebral Hemorrhage Patients: A Multicenter, Randomized Controlled Trial. Crit Care Med 2014; 42:1–8 13. Seguin P, Tanguy M, Laviolle B, et al: Effect of oropharyngeal decontamination by povidone-iodine on ventilator-associated pneumonia in patients with head trauma. Crit Care Med 2006; 34:1514–1519 14. Howe DJ: Aspiration pneumonia from povidone-iodine (Betadine): Report of case. J Oral Surg 1981; 39:224–225 15. Numazawa R, Morimoto Y, Yokota S, et al: [Pneumonia due to aspiration of povidone-iodine during anesthesia—A case report]. Masui 1992; 41:846–849 16. Cheong SH, Yang YI, Choi MY, et al: Lung injury induced by the pulmonary instillation of povidone-iodine in rats. J Anesth 2012; 26:70–79

Challenges, duty hours, and metrics in the intensive care unit resident rotation.

necessitating physician-assisted death is contentious (7). Palliative care has continued to improve and is available for all patients, barring the most unlikely circumstances. Further, if physicians were allowed legal authority to palliate by benevolent execution, this authority would not necessarily be specialty specific. A critical care physician with years of training and experience in effectively treating a dying patient with multiple organ failure would assuredly be an expert in the how, why, and wherefore of euthanizing patients. However, many other practitioners with the same MD degree have no training or experience in this area, and euthanasia by their hand might take on a radically different complexion. There would be no kind of quality assurance for the procedure if undertaken by these physicians. Physicians have traditionally enjoyed trust in their position as healers or, in the absence of healing potential, at least palliators (10). This trust is predicated on the premise that physicians have 100% incentive to benefit patients and 0% incentive to harm them. Should physicians take on the mantle of benevolent executioner, this clear delineation would be blurred, affecting public trust, especially in the context of organ donorship. Debating the rationale for our moral judgments is intellectually intriguing and a worthwhile pursuit. Ultimately, however, we find no difficulty in accepting that aversion to SDP is ingrained in our genetic and cultural makeup for meaningful reasons. Perhaps the author fears that society has blindly justified its reasons to fit such intuitions, but the rigorous and ongoing societal debate does not support this contention.

Changes in Bioactive and Immunoreactive Inhibin Levels Around Human Labor

The changes in bioinhibin (B-inhibin) and immunoinhibin (I-inhibin) levels were studied in the serum of healthy term pregnant women by ovine pituitary cell culture and immunoenzymatic assay systems before and 24 h after delivery. In the maternal serum, a sharp decline in both B-inhibin and I-inhibin levels was observed within first 6 h after delivery. B-inhibin and I-inhibin in maternal serum were 3.45 +/- 0.25 and 3.77 +/- 0.43 U/mL, respectively, before labor and decreased by 35.82% and 38.89% 30 min after labor. One hour after delivery, B-inhibin and I-inhibin were reduced by 56.74% and 61.48%, respectively. After 6 h, B-inhibin and I-inhibin levels were lowered by 93.86% and 78.90%, respectively. Twenty-four hours later, both inhibins were nearly undetectable. In the retroplacental serum, B-inhibin and I-inhibin were 4.92 +/- 0.34 and 10.13 +/- 1.16 U/mL, respectively, i.e. 42.48% and 168.60% higher than the levels of B-inhibin (P less than 0.05) and I-inhibin (P less than 0.001) in maternal serum before delivery. In the umbilical cord serum, the B-inhibin concentration was 0.75 +/- 0.16 U/mL, whereas the I-inhibin concentration was 9.58 +/- 0.75 U/mL, which was much higher than that of B-inhibin (P less than 0.001). No difference was found in B-inhibin or I-inhibin levels in the serum samples collected separately from umbilical arteries and veins (P greater than 0.05). In addition, inhibin levels were measured in amniotic fluid and placental extract. In amniotic fluid, B-inhibin and I-inhibin concentrations were 2.37 +/- 0.35 and 8.01 +/- 0.55 U/mL, respectively. In the comparison, B-inhibin in amniotic fluid was 31.3% lower than that in maternal serum before delivery (P less than 0.05), but I-inhibin was 112.5% higher than that in the maternal serum (P less than 0.001). In the placental extract, the B-inhibin concentration was 12.80 +/- 0.35 U/g tissue, while the I-inhibin concentration was 33.86 +/- 2.93 U/g tissue, which was more than twice as high as the B-inhibin level (P less than 0.001). Our data provide further evidence that inhibin may be mainly produced in the placenta during pregnancy.

Normal ovulatory cycles in one subject receiving daily hypophyseal stimulation by LH-RH at two dose levels

n The ovulatory cycle in the human female during daily hypophyseal stimulation with LH releasing hormone (LH-RH) was investigated. A healthy, 28-year-old woman with regular ovulatory cycles was given 50 mcg of synthetic LH-RH by rapid iv injection each day for an entire cycle. 1 year later the experiment was repeated using 200 mcg. Neither of these procedures disturbed the normal events of the menstrual cycle: the typical midcycle LH surge occurred on the expected day, the basal body temperature continued to be biphasic, and the length of the cycles were in the normal range for the patient. It was found that pituitary sensitivity to LH-RH was increased when approaching the spontaneous LH surge and was greatest on the days of the luteal phase. No significant difference was seen in the magnitude of pituitary response to the 2 different doses of LH-RH.n

Masseter peripheral tissue oxygenation in sepsis: chew before swallowing whole.

multicenter, randomized, controlled study. Crit Care Med 2012; 40:420–429 14. Gowardman JR, Robertson IK, Parkes S, et al: Influence of insertion site on central venous catheter related colonization and bloodstream infection rates. Intensive Care Med 2008; 34:1038–1045 15. Guggenbichler JP, Boswald M, Lugauer S, et al: A new technology of micro dispersed silver in polyurethane induces antimicrobial activity in central venous catheters. Infection 1999; 27(Suppl):S16–S23 16. Corral L, Nolla-Salas M, Ibanez-Nolla J, et al: A prospective, randomised study in critically ill patients using the Oligon Vantex catheter. J Hosp Infect 2003; 55:212–219 17. Moretti EW, Ofstead CL, Kristy RM, et al: Impact of central venous catheter type and methods on catheter related colonization and bacteraemia. J Hosp Infect 2005; 61: 139–145 18. Sahay S, Panja S, Ray S, et al: Diurnal variation in hand hygiene compliance in a tertiary level multidisciplinary intensive care unit. Am J Infect Control 2010; 38: 535–539

Evaluation of a synthetic serum substitute to replace fetal cord serum for human oocyte fertilization and embryo growth in vitro**Presented in part at the VI World Congress, In Vitro Fertilization and Alternate Assisted Reproduction, Jerusalem, Israel, April 2 to 7, 1989.

A comparison was made between a serum substitute. UltroSer G (Gibco, Ghent, Belgium) (2%) (medium B) and 10% human fetal cord serum (medium A), as regards their ability to support 1-cell and 2-cell mice embryo development in vitro. Sixty percent and 56% of the 1-cell embryos reached the expanded blastocyst stage when cultured in media A and B, respectively. Eighty-four percent and 88% of 2-cell embryos reached the expanded blastocyst stage when cultured in media A and B, respectively. A prospective randomized study was then performed to evaluate this synthetic serum substitute in human in vitro fertilization. Among 141 ovum pick-up (OPU), oocytes retrieved in 74 cases were processed in medium A and oocytes retrieved in 67 others in medium B. In media A and B, the fertilization rate was 67% and 44.3% respectively, and the pregnancy rate/OPU 23% and 9%, respectively. The pregnancy rate/transfer was 28.8% and 12.2% respectively, and the implantation rate/transferred embryo 9.5% and 4.2%. In the human sperm survival assay, the vitality and residual motility after 24 hours of incubation were significantly lower in medium B. In conclusion, UltroSer G successfully sustained the development in vitro of mouse embyros. However in human, it reduced sperm survival, oocyte fertilization, and embryo viability.