Update on the management of neuromuscular block: focus on sugammadex

Steroidal neuromuscular blocking agents (NMBAs), such as rocuronium, are widely used in clinical anesthesia and emergency medicine to facilitate endotracheal intubation and artificial ventilation and to allow surgical access to body cavities. Reversal of neuromuscular blockade is important for the acceleration of patient recovery and prevention of postoperative residual neuromuscular blockade and reduces the incidence of severe morbidity and mortality associated with anesthesia management. Sugammadex is the first selective relaxant binding agent (SRBA) and has been designed to reverse the steroidal neuromuscular blocking drug rocuronium. Encapsulation of the rocuronium molecule by sugammadex results in a rapid decrease in free rocuronium in the plasma and subsequently at the nicotinic receptor at the motor endplate. After encapsulation, rocuronium is not available to bind to the nicotinic receptor in the neuromuscular junction. This promotes the liberation of acetylcholine receptors, and muscle activity reappears. This new concept of reversal of neuromuscular block induced by rocuronium (or vecuronium) led to impressive results in animal and phase 1 and 2 studies. Sugammadex is currently in phase 3 clinical studies and may be commercially available by 2008.     

Incompatibility of contrast agents with intravascular medications. Work in progress

In vitro and in vivo precipitation of iodinated contrast agents when ioxaglate and papaverine are given together has been reported. To verify these reports and to investigate other medications not previously tested, the authors analyzed mixtures of contrast agents and medications in vitro with a light spectrophotometer and observed them for visible precipitates for up to 120 minutes. Previously reported incompatibilities between ionic or low-osmolality contrast media and medications were verified, and several new incompatibilities were discovered. No incompatibilities were found when the drugs tested were mixed with the new nonionic contrast media.     

Two-week stimulation or blockade of the sympathetic nervous system in man: influence on body weight, body composition, and twenty four-hour energy expenditure

Seven lean healthy young men were studied for 6 weeks during exposure to pharmacologic inhibition or stimulation of the sympathetic nervous system. For a period of 2 weeks their beta-adrenergic receptors were either blocked with propranolol hydrochloride (160 mg/d) or stimulated with terbutaline sulphate (15 mg/d). After a further 2 weeks of placebo administration (500 mg lactose/d), the subjects crossed over to the drug they had not been taking at the beginning of the experiment for another 14 days. During the last five days of each 2-week period, the subjects consumed a weight-maintaining diet, composed of 12% protein, 48% carbohydrate, and 40% fat. They consumed exactly the same menus on the same days during the subsequent study periods. Body weight and physical activity were measured every day for 6 weeks. Daily heart rate and nitrogen excretion were measured continuously for days at the end of each 2-week period, the last two days of which were spent in a respiration chamber where energy expenditure and a variety of metabolic parameters were measured. In the respiration chamber on the propranolol, placebo, and terbutaline treatments, respectively, significant differences were observed in mean daily heart rate (65 +/- 3, 75 +/- 4, and 84 +/- 4 beats/min), mean sleeping heart rate (51 +/- 2, 56 +/- 3, and 62 +/- 3 beats/min), nitrogen excretion (13.6 +/- 0.7, 12.6 +/- 0.6, and 11.9 +/- 0.6 g/d), fat oxidation (+1,045 +/- 95, +1,243 +/- 148, and +1,278 +/- 84 kcal/d) and thyroid hormones (12.0 +/- 0.7, 15.7 +/- 0.9, and 17.2 +/- 1.0 T3/T4 ratio).(ABSTRACT TRUNCATED AT 250 WORDS)     

Low-grade angiosarcoma of the skin of the breast: a complication of lumpectomy and radiation therapy for breast carcinoma.

A case of low-grade angiosarcoma arising in the skin of a breast previously irradiated for breast carcinoma is reported. Initially, an asymptomatic breast mass was detected. Excisional biopsy and axillary lymph node dissection revealed a 1.5-cm infiltrating ductal carcinoma with 21 negative lymph nodes. The neoplasm was staged as T1, N0, M0. The patient was entered in a research protocol and was treated with high-dose external beam (4,860 rad) and iridium implant (1,860 rad) irradiation. Seven years later the patient developed low-grade angiosarcoma of the breast skin. The lesion recurred following excision and eventually was treated by simple mastectomy. The patient never had evidence of lymphedema. Cutaneous angiosarcomas occurring as a complication of lumpectomy and radiation therapy for breast carcinoma are rare. In some reported cases the patients have had lymphedema, a known factor predisposing to angiosarcoma. Furthermore, almost all cases previously reported have been high grade. This case suggests that radiation therapy for breast carcinoma may also be complicated by low-grade angiosarcoma.     

Evaluation and audit in a paediatric disability service

Parental and professional responses to questionnaires evaluating a paediatric disability service are reported and the viability of auditing structural, process, and outcome aspects of clinical practice are discussed. Expectations of waiting time to first appointment (met for only 52% of consumers) illustrate structural issues. Process issues are reflected in consumer reactions to outreach work (for example, 94% of parents and 84% of professionals found this supportive). Outcome measures such as consumer satisfaction with the service (76% of consumers reported being 'very satisfied' and 20% 'fairly satisfied') suggest that service aims are being met. Good concurrence of service aims with consumer needs is indicated by parental reasons for referral (for example, 75% for diagnostic help, 73% for a better understanding of the disorder, 88% for practical help), referrers' reasons (for example, 55% for a second diagnostic opinion, 45% due to lack of local expertise), and reports from most other professionals involved with the case that a similar service was not provided locally.     

"Sunday start" multiphasic oral contraception: ovulation prevention and delayed follicular atresia in primates

Utilization of the "sunday start" method for oral contraceptive therapy can result in the initiation of oral contraceptive administration as late as day 6 of the ovarian/menstrual cycle. Potentially, "breakthrough" ovulations could occur due to rapid follicular progression, especially if the dominant follicle is overtly established prior to the onset of estrogen-progestin administration. Here, we examined the efficacy of two new oral contraceptive regimens on potential "breakthrough" ovulations in the first cycle of treatment begun on cycle days 1 or 6 in cynomolgus monkeys having normal menstrual cycles. Our endocrine findings show that follicular recruitment, and probably selection of the dominant follicle, had occurred by day 6 of the follicular phase. Both oral contraceptive treatments (Loestrin 5/7/9R, LoDose 5/7/9R, Parke-Davis) were effective in blocking preovulatory-like gonadotropin and estradiol surges as well as luteal phase progesterone elevations, whether treatment was begun on day 1 or day 6 of the menstrual cycle. Despite hormonal evidence of significant maturational progression, oral contraceptive administration successfully blocked the completion of follicular maturation, thereby sustaining contraceptive reliability, even in the initial cycle of treatment using a "sunday start" regimen. Under these conditions, dissolution of the failed dominant follicle within ovarian stroma may be characterized by delayed follicular atresia.     

Lipoteichoic acid induces secretion of interleukin-8 from human blood monocytes: a cellular and molecular analysis.

Invasion by gram-positive and gram-negative bacterial organisms is characterized immunopathologically by the activation of mononuclear phagocytic cells, leading to the elaboration of macrophage-derived regulatory and chemotactic factors, and the resultant influx of inflammatory leukocytes. Little is known regarding the mechanisms by which gram-positive organisms initiate macrophage activation and subsequent inflammation. In this investigation, we postulated that lipoteichoic acid (LTA) purified from two different gram-positive bacterial species was an important signal for the expression of chemotactic cytokines from human peripheral blood monocytes (PBM). In initial experiments, we demonstrated that cell-associated interleukin-8 (IL-8) was expressed by mononuclear phagocytes present in inflamed areas of endocardium in cases of acute Staphylococcus aureus endocarditis. We next demonstrated that LTA purified from either Staphylococcus aureus or Streptococcus pyogenes induced the time- and dose-dependent expression of IL-8 mRNA and protein from human PBM. The expression of IL-8 mRNA from LTA- but not lipopolysaccharide (LPS)-treated PBM was superinduced by concomitant treatment with cycloheximide, indicating that the expression of IL-8 mRNA from LTA-treated PBM was negatively controlled by repressor proteins. Furthermore, mRNA stability studies indicated that IL-8 mRNA was less stable in the presence of LTA than in the presence of LPS. Our findings indicate that LTA can induce the secretion of the polymorphonuclear leukocyte chemotactic factor IL-8 and that LTA may be an important cellular mediator of inflammatory cell recruitment that characterizes immune responses to gram-positive bacterial infections.     

Ultrastructural observations of development ofEimeria tenella in a novel established avian-derived cell line

Transmission electron microscopy was used to study the in vitro development ofEimeria tenella in a novel established avian-derived cell line (designated CEV-1/F7) used for antigen production in chicken immunization studies. Sporozoites ofE. tenella were inoculated onto cell monolayers and the cells were fixed at 24-h intervals. Large numbers of intracellular sporozoites were seen at 24 h postinoculation (p.i.), and trophozoites were identified at 24–48 h p.i. Immature schizonts, some with budding merozoites, were seen by 48 h p.i. At 72–96 h p.i., immature and mature schizonts and extracellular merozoites were observed. No merozoite invasion occurred, but immature second-generation schizogony was seen in parasitophorous vacuoles of first-generation schizonts. No further development occurred and degeneration of most schizonts was seen by 120–144 h p.i. The results confirmed synchronous development ofE. tenella until 48 h p.i., followed by asynchronous development and ultrastructural degeneration with increased incubation time.