A Reminder of Methylene Blue's Effectiveness in Treating Vasoplegic Syndrome after On-Pump Cardiac Surgery

The inflammatory response induced by cardiopulmonary bypass decreases vascular tone, which in turn can lead to vasoplegic syndrome. Indeed the hypotension consequent to on-pump cardiac surgery often necessitates vasopressor and intravenous fluid support. Methylene blue counteracts vasoplegic syndrome by inhibiting the formation of nitric oxide.We report the use of methylene blue in a 75-year-old man who developed vasoplegic syndrome after cardiac surgery. After the administration of methylene blue, his hypotension improved to the extent that he could be weaned from vasopressors. The use of methylene blue should be considered in patients who develop hypotension refractory to standard treatment after cardiac surgery.     

Differences in the abilities of human tau isoforms to promote microtubule assembly.

Three isoforms of human tau protein were compared for their abilities to induce microtubule assembly. The three isoforms, tau 3 (tau containing three microtubule-binding domains), tau 4 (tau containing four microtubule-binding domains) and tau 4L (tau containing four microtubule binding domains plus a 58-amino-acid insert near the N-terminus) were expressed in E. coli and purified using ammonium sulfate precipitation, ion exchange, and size exclusion chromatography. All three isoforms induced microtubule assembly at micromolar concentrations and showed similar critical concentrations for assembly of 0.4-0.45 microM. However, tau 4 induced microtubule formation at a rate five- to tenfold faster than either tau 3 or tau 4L. The rate of microtubule elongation seen with tau 4 was twofold greater than with tau 3 or tau 4L, suggesting that the faster rate of microtubule assembly seen with tau 4 was due, at least in part, to faster elongation. Tau 4 induced a greater number of microtubules to form at steady state than did tau 3 or tau 4L. The microtubules generated with each tau isoform had similar steady-state length distributions and were equally susceptible to cold-induced disassembly. These results indicate that the additional microtubule-binding domain in tau 4 enhances microtubule assembly, while the 58-amino-acid insert negates the stimulatory effect of the fourth microtubule-binding domain.     

Calcium mobilization and entry by thapsigargin in neuronal tumor cell line, SK-N-SH.

Using fura-2 loaded neural tumour cells, SK-N-SH, we demonstrate that receptor-mediated activation of phosphoinositide hydrolysis not only causes the release of Ca2+ from intracellular stores but also causes a concomitant influx of extracellular Ca2+. Thapsigargin (TG), a sesquiterpene lactone, causes a sustained elevation of intracellular Ca2+ and depletion of the inositol 1, 4, 5-trisphosphate-sensitive intracellular Ca2+ stores. In the absence of extracellular Ca2+, the increase in intracellular Ca2+ concentration ([Ca2+]i) was transient, suggesting that thapsigargin activates both intracellular mobilization and the influx of Ca2+ from extracellular space. These results are consistent with the proposal that the depletion of the inositol 1, 4, 5-trisphosphate-sensitive intracellular Ca2+ pool serves as a signal for Ca2+ influx.     

Health beliefs and parenting attitudes influence breastfeeding patterns among low-income African-American women.

OBJECTIVE: To describe breastfeeding initiation among 210 urban African-American mothers with inadequate prenatal care. METHODS: This study is a case-control study of postpartum mothers recruited from four large urban hospitals. RESULTS: Mothers who chose to breastfeed were more educated, employed before birth, married, and using contraception postnatally. Regression model analysis controlling for demographic differences revealed that breastfeeding was significantly associated with a higher perception of severity of illness and higher confidence in the ability of health care to prevent illness. Breastfeeding mothers were less likely to reverse parent-child roles and had a lower perception of hassle from their infant's behavior. When comparing mothers who breastfed longer than 8 weeks to those who did not breastfeed, breastfeeding mothers had high scores related to empathy toward infants on the Adult-Adolescent Parenting Inventory as well as a low perception of hassle on the Parenting Daily Hassle. The perception of existing formal or informal social support did not influence breastfeeding behavior. CONCLUSION: Personal attributes of low-income urban mothers such as health beliefs and parental attitudes may play a role in the initiation and duration of breastfeeding. Low-income African-American mothers may be influenced in their choice to breastfeed by supportive messages from physicians and nurses delivering care to mothers and their newborns. Emphasis should be placed on the role breastfeeding can play in preventing childhood illnesses.     

Work stress and hypertension: A call from research into intervention

Annals of Behavioral Medicine -     

Application of intermaxillary fixation screws in maxillofacial trauma.

PURPOSE: The use of intermaxillary fixation (IMF) in the treatment of maxillofacial trauma represents the cornerstone of fracture reduction and immobilization. Many modalities of IMF have been described; recently IMF screws have been introduced into clinical practice, however, hardware failure can occur. We performed a retrospective study evaluating hardware-associated complications for self-drilling/tapping IMF screws. MATERIALS AND METHODS: A retrospective study on 49 patients requiring IMF was performed. The diagnosis, duration of IMF, screw site, use of elastic or wire fixation, and associated complications were recorded. IMF screws were used to adjunct open reduction techniques, for definitive closed reduction, or fracture prevention following dentoalveolar surgery. Follow-up examinations were performed until fracture healing was complete (6 to 8 weeks). RESULTS: A single adverse event occurred in 19 patients (39%) while 4 patients (8%) had more than 1 complication. The most common event was screw loosening; 29% of patients had at least 1 screw dislodged in the treatment period. Of the total number of screws placed (229), 15 (6.5%) became loose, and were equally distributed among the mandible and maxilla. The remaining complications noted were root fracture, 4% (2 of 49); loosened wires, 6% (3 of 49); screw shear, 2% (1 of 49); malocclusion, 2% (1 of 49); and ingested hardware, 2% (1 of 49). CONCLUSIONS: Overall the IMF self-drilling/tapping screws have been shown to be a useful modality to establish maxillomandibular fixation. It is a safe, and time-sparing technique; however, it is not without limitations or potential consequences which the surgeon must be aware of in order to provide safe and effective treatment.     

Electrophysiologic mechanisms of ventricular arrhythmias

In this work the electrophysiologic mechanisms of ventricular arrhythmias have been briefly summarized. Ventricular arrhytmias can be caused either by pacemaker activity or by reentrant excitation. Enhancement of normal automaticy can generate a parasystolic rhythm in normal fibers. Abnormal automaticity may arise fom fibers in which maximum diastolic potential has been reduced by a variety of interventions. Triggered activity is caused by either an early (EAD) or delayed (DAD) afterdepolarization and requires a prior normal action potential for initiation. While there is growing evidence that EAD-induced triggered activity plays a significant role in the Long QTU syndrome and Torsade de Pointes, no clinical arrhythmias has definitely been ascribed to DADs, although DADs have been recorded in man after acute digoxin intoxication.Ventricular arrhytmias can be also caused by reentrant excitation, which can be subdivided into reflection or circus movement reentry (CMR). In the reflection model impulses in both directions are transmitted over the same pathway. In the CMR three models can be differentiated: the ring model, which requires a fixed anatomical obstacle; the figure-eight model and the leading circle model, where functional rather than fixed anatomical obstacles are involved.Abbreviations AV atrio-ventricular - CMR circus movement reentry - DAD delayed afterdepolarization - EAD early afterdepolarization - ECG electrocardiogram - LV left ventricle - MAP monophasic action potential - MF muscle fiber - PF Purkinje fiber - RV right ventricle - TdP Torsade de Pointes     

Concomitant administration of cyclosporine and ketoconazole in idiopathic nephrotic syndrome.

BACKGROUND: The deliberate use of ketoconazole to reduce the need for cyclosporine (CsA) is not new, but it is particularly relevant because of the high cost of CsA. Many studies have documented this benefit in renal and cardiac transplants, but this co-administration has not been reported in patients with nephrotic syndrome. METHODS: This retrospective study included 207 nephrotic patients who were steroid resistant, dependent or frequent relapsers and received CsA therapy. Among these patients 153 received daily ketoconazole therapy in a dose of 50 mg with concomitant decrease of one-third of the CsA dose while 54 patients received CsA alone. The majority of our cases were children (179 were below 18 years) and male to female ratio was 1.7:1. RESULTS: The great majority of the study population received the drugs for 1-2 years. Patients who received CsA and ketoconazole were comparable with those who received CsA alone regarding age, sex, duration of renal disease, renal pathology, severity of nephrotic syndrome, renal function, hepatic function and steroid response. Co-administration of ketoconazole significantly reduced mean doses of CsA by 37% after 1 month and 47% at 1 year with overall net cost savings of 37%. Hepatic functions remained within the normal range in both groups. Additionally, co-administration of ketoconazole significantly improved the response to CsA therapy, successful steroid withdrawal and decreased the frequency of renal impairment. CONCLUSIONS: Co-administration of keto with CsA in idiopathic nephrotic patients significantly reduces CsA costs and may improve its response.     

Autoantibodies and drug-or metabolite-dependent antibodies in patients with diclofenac-induced immune haemolysis

Two patients with acute immune haemolytic anaemia caused by diclofenac are described. Both patients had developed IgG drug-independent autoantibodies and drug-dependent antibodies. The drug-dependent antibodies in one patient reacted with red blood cells (RBC) only in the presence of urine from patients receiving diclofenac (ex vivo antigen) but not in the presence of the drug itself or its known metabolites. This antibody appeared to recognize a trace metabolite which has not yet been identified. The drug-dependent antibodies in the second patient reacted with RBC in the presence of urine as ex vivo antigen as well as in the presence of the drug itself and its main metabolites. Incorrect diagnosis of such cases often is due to the occurrence of autoantibodies and/or unusual drug metabolism and excretion.