A carpet-based mechanism for direct antimicrobial peptide activity against vaccinia virus membranes.

Antimicrobial peptides have activity against a wide variety of biological membranes and are an important component of innate immunity in vertebrate as well as invertebrate systems. The mechanisms of action of these peptides are incompletely understood and a number of competing but not necessarily mutually exclusive models exist. In this study we examined the virucidal activity of four peptides, the human cathelicidin derived LL37, Xenopus alanine-substituted Magainin-2 amide, uperin-3.1, and a cecropin-LL37 hybrid against vaccinia virus. The peptides were shown to be differentially virucidal but all were shown to attack the viral envelope, with LL37 being the most effective and uperin-3.1 the least. Density gradient analysis of the treated virions indicated the virus outer membrane was efficiently removed by peptide action and suggests a mechanism of direct virus inactivation that is consistent with the carpet model for peptide-mediated membrane disruption. Interestingly, the least effective peptide uperin-3.1 was equally effective as the others at inducing susceptibility to neutralizing antibody. This suggests that in addition to direct killing by a carpet-based mechanism, the peptides may simultaneously operate a different mechanism that exposes sequestered antigen without membrane removal.

A prospective, randomised, single-blind pilot study to determine the effect of anaesthetic technique on troponin T release after off-pump coronary artery surgery.

Ischaemic damage to the myocardium inevitably occurs during coronary artery surgery. However, the extent of the damage may be influenced by the anaesthetic technique used. The most sensitive and reliable marker of myocardial damage is currently thought to be troponin T. We conducted a prospective, randomised, single-blind pilot study to determine the baseline values of troponin T release after off-pump coronary artery bypass surgery in 30 patients randomly allocated to receive either propofol, isoflurane or isoflurane and high thoracic epidural analgesia. All other treatment was standardised. Patients undergoing emergency surgery and those with unstable angina were excluded. Blood samples were taken at 0, 3, 6, 12, 24 and 48 h after surgery for troponin T analysis. Mean troponin T levels at 24 h were not significantly different between the groups (p = 0.41). These data allows appropriate power calculations for further, large-scale studies to determine the anaesthetic technique that provides optimal myocardial protection.

Predicting blood pressure reactivity and heart rate variability from mood state following coronary artery bypass surgery.

STUDY OBJECTIVES: Coronary Artery Bypass Graft (CABG) surgery is a common and successful procedure for revascularisation. However, the experience can induce emotional reactions prior to and following surgery. This study aimed to document changes in blood pressure (BP) reactivity and heart rate variability (HRV) following CABG surgery, and to determine the impact of mood state, particularly anxiety and depression upon cardiovascular functioning. METHOD: Twenty-two patients preparing to receive elective, first time CABG surgery were recruited from The Cardiothoracic Centre, Liverpool, UK and psychologically assessed using the Hospital Anxiety and Depression Scale (HAD), Global Mood Scale (GMS) and the Dispositional Resilience Scale (DRI). BP and heart rate responses were also measured during four conditions: baseline response; laboratory session; ambulatory monitoring; and self-initialised recordings during the ambulatory period. In addition, HRV was measured for 12 h in conjunction with the ambulatory monitoring period. All measures were assessed 1 week prior to surgery and 2 months following surgery. RESULTS: A significant decrease in negative mood and an increase in positive mood were reported following surgery. Forty percent of patients were clinically anxious and depressed prior to surgery although this was reduced to 27% after surgery. Depression was the strongest independent predictor of pre-operative BP and HRV whilst anxiety was most significantly related to follow-up BP reactivity. DBP was most strongly predicted by mood state. CONCLUSIONS: These results suggest that patients with higher levels of anxiety and depression are at risk of reduced HRV and increased BP reactivity in response to mental stressors. The study also strongly suggests that current patient services should be expanded to acknowledge the role of psychological factors within clinical prognosis after CABG surgery.

Radiographic and morphologic findings in a previously undescribed type of mesomelic dysplasia resembling atelosteogenesis type II.

The mesomelic chondrodysplasias are a heterogeneous group of dwarfing disorders characterized by shortness of the middle segments of limbs. We report on a 25-week fetus with disproportionate shortness of limbs with an apparently distinct form of mesomelic dysplasia. Radiographic findings at necropsy included ulnar deviation of hands, talipes equinovarus, distal tapering of the humeri, and hypoplastic fibulae, radii, and ulnae. Chondro-osseous morphology showed mild shortness of the physeal columns, overgrowth of perichondral bone, peripheral ingrowth of mesenchymal cells into the physis, and numerous areas of fibrillar degeneration with rings of collagen surrounding the chondrocytes. Ultrastructural findings included a degenerated territorial matrix, pericellular halos of collagen, and dilated loops of rough endoplasmic reticulum in chondrocytes. The radiographic appearance of the long bones is distinct from that of previously described mesomelic dysplasias. The chondro-osseous morphologic findings and the distal tapering of the humerus are somewhat reminiscent of atelosteogenesis type II, but the pattern of matrix degeneration and the presence of inclusion bodies in the chondrocytes distinguish it from disorders of sulfate transport.

Myocardial ischaemia after coronary artery bypass grafting: early vs late extubation.

The technique of early extubation after coronary artery bypass grafting is increasing in popularity, but its safety and effect on myocardial ischaemia remain to be established. In a randomized, prospective study, patients undergoing routine elective coronary artery bypass grafting were managed with either early or late tracheal extubation. The incidence and severity of electrocardiographic myocardial ischaemia were compared. Data were analysed from 85 patients (43 early extubation; 42 late extubation). Median time to extubation was 110 min in the early extubation patients and 757 min in the late extubation patients. After correction for randomization bias, there were no significant differences between groups in ischaemic burden, maximal ST-segment deviation, incidence of ischaemia and area under the ST deviation-time curve (integral of ST deviation and time). Similarly, there were no differences between groups in postoperative creatine kinase MB-isoenzyme concentrations and duration of stay in the ICU or hospital. Therefore, this study provides evidence for the safety of early extubation after routine coronary artery bypass grafting.

Attitudes toward genetic carrier screening for cystic fibrosis among pregnant women: the role of health beliefs and avoidant coping style.

In this study we examined the relations among psychosocial factors associated with pregnant women's attitudes toward genetic carrier testing for cystic fibrosis (CF). A sample of 511 pregnant women attending various health clinics for general prenatal care were educated about CF. Women's health beliefs, coping styles, and attitudes toward CF carrier screening were assessed. Results from structural equation modeling analyses indicated that women who perceived themselves as more likely to be carriers of the CF gene and who perceived greater benefits of screening were positively inclined toward genetic screening. Perceived barriers to screening were negatively associated with women's attitudes toward CF genetic testing. In addition, the findings suggest that some types of avoidant coping styles may indirectly influence one's decision to undergo genetic screening through perceptions of risk, benefits, and barriers. Given the advent of genetic screening options for many diseases, in this study we address some issue in women's attitudes toward prenatal screening that are relevant to a variety of genetic screening programs.

PCR-based screening for cystic fibrosis carrier mutations in an ethnically diverse pregnant population.

As the most common lethal autosomal recessive disorder in North America, cystic fibrosis (CF) is an obvious candidate for general population carrier screening. Although the identification of the causative gene has made detection of asymptomatic carriers possible, the extreme heterogeneity of its mutations has limited the sensitivity of the available DNA screening tests and has called into question their utility when they are applied to patients with no family history of the disease. The purpose of this study was to determine the technical feasibility, patient acceptance and understanding, and psychosocial impact of large-scale CF carrier screening in an ethnically diverse pregnant population. A total of 4,739 pregnant women attending prenatal clinics located in both an academic medical center and a large HMO were invited in person to participate. Of this group, 3,543 received CF instruction and assessments of knowledge and mood, and 3,192 underwent DNA testing for the six most common CF mutations, by means of a noninvasive PCR-based reverse-dot-blot method. Overall participation rates (ranging from 53% at the HMO to 77% at the academic center) and consent rates for DNA testing after CF instruction (>98%) exceeded those of most other American studies. The PCR-based screening method worked efficiently on large numbers of samples, and 55 carriers and one at-risk couple were identified. Understanding of residual risk, anxiety levels, and overall satisfaction with the program were acceptable across all ethnic groups. Our strategy of approaching a motivated pregnant population in person with a rapid and noninvasive testing method may provide a practical model for developing a larger CF screening program targeting appropriate high-risk groups at the national level, and may also serve as a paradigm for population-based screening of other genetically heterogeneous disorders in the future.

Gastroesophageal reflux and tracheobronchial contamination after cardiac surgery: should a nasogastric tube be routine?

Nasogastric (NG) tubes are routinely used in patients undergoing cardiac surgery. This randomized study was designed to assess gastroesophageal reflux (GER) without a NG tube (control) compared with a NG tube managed either by gravity drainage (gravity) or continuous low-grade suction (suction). Antimony pH probes were placed in the lower esophagus and trachea after induction of anesthesia in 51 patients, and pH was recorded every 5 s until the time of tracheal extubation. GER was defined as reversible decrease in esophageal pH to less than 4.0. No significant difference was found between groups in age, weight, gender, duration of postoperative ventilation, morphine use, or antiemetic use. All indicators of GER were seen more frequently in the gravity group compared with the two other groups (P < 0.001). One episode of sudden decrease in tracheal pH was observed in a patient in the gravity group, indicating tracheal aspiration, which was associated with delayed extubation and postoperative pneumonia. The absence of a NG tube is not associated with reflux, probably since the gastroesophageal sphincter remains competent. NG tubes are not routinely necessary for cardiac surgery in patients without risk factors for GER, and increase reflux risk if managed without low-grade suction.

Renal function and proteinuria after cardiopulmonary bypass: the effects of temperature and mannitol.

We studied three groups of patients without previous renal impairment, undergoing elective coronary artery bypass surgery. Group H (n = 7) underwent open heart surgery using moderate hypothermia (28 degrees C); Groups N and M (n = 8, each) were managed at normothermia. The extracorporeal circuit was primed with Hartmann's solution 2.5 L with the addition of mannitol 0.5 g/kg in Group M. Serum concentrations of sodium and creatinine, and the urinary concentrations of microalbumin and N-acetyl-beta-D-glucosaminidase (NAG) were measured in each patient at six different time intervals: T0, 6 h prior to surgery; T1, between sternotomy and 45 min into cardiopulmonary bypass (CPB); T2, in the interval from 45 min into, to prior to weaning off CPB; T3, from coming off CPB to skin closure; T4, in the first 6 h in the intensive care unit; and T5, at 6 days postoperatively. Creatinine clearance (CCR) and fractional sodium excretion (FENA) were calculated at each time point. Urine output during CPB at Interval T2 was significantly higher in Group H compared to Group N (P = 0.03) but not Group M. We found no significant differences in CCR, FENA, microalbuminuria, and urinary NAG among the three groups at any time. However, there were overall significant changes in measured variables over time compared to baseline. We conclude that CPB is associated with a significant alteration in renal function as shown by increased FENA, microalbuminuria, and urinary NAG. The use of hypothermic or normothermic CPB and the use of prophylactic mannitol did not produce any significant modification of these changes.

Transmitral Doppler assessment of left ventricular diastolic function during coronary artery bypass surgery.

OBJECTIVE: To evaluate which Doppler transmitral velocity indices of left ventricular diastolic function change with alteration of left ventricular filling pressure. METHODS: Twenty-two patients undergoing coronary artery bypass surgery. The effect of fluid loading on indices derived from the transmitral Doppler waveform, recorded by a trans-oesophageal echocardiography, was evaluated using a generalised linear statistical model. RESULTS: E-wave maximum velocity, E-wave acceleration time and slope, E-wave deceleration slope, A-wave maximum velocity and E/A wave maximum velocity ratio showed significant changes after alterations in left ventricular filling pressure. E-wave deceleration time and E-wave maximum velocity/time velocity integral showed no significant change after fluid loading. CONCLUSION: Several commonly used Doppler derived indices of left ventricular diastolic function are significantly affected by changes in filling pressure of the left ventricle. This may limit the usefulness of the Doppler method for serial assessment of diastolic function when the left ventricular filling pressure has changed between assessments. Only the E-wave deceleration time did not show significant changes and might be a useful Doppler index for the serial measurement of left ventricular compliance but this needs to be confirmed with haemodynamic measurements.

Education and testing strategy for large-scale cystic fibrosis carrier screening.

Population-based screening for cystic fibrosis carrier mutations presents a number of challenges for genetic counselors, owing primarily to the inability of current DNA testing technology to identify all possible mutations and the difficulty involved in conveying the concept of residual risk to those patients who test negative. To address these issues, we are conducting a pilot study, as part of a consortium established by the National Center for Human Genome Research, to explore the efficacy, acceptance, and psychosocial impact of various approaches to carrier screening in an ethnically diverse Southern California population. This article reports the patient instructional and screening strategies we developed in the initial phase of the project in order to optimize our chances of answering these questions and delivering this service on a large scale.

The Australian Incident Monitoring Study. Problems before induction of anaesthesia: an analysis of 2000 incident reports.

The first 2000 incidents reported to the Australian Incident Monitoring study (AIMS) were examined to identify those incidents which occurred preoperatively (defined as occurring prior to the commencement of general or regional anaesthesia). The 35 incidents, representing 1.7% of the total, which occurred in this time period were analysed with a view to identifying areas in which current practice could be improved. Almost all incidents led to significant delays in operating lists, and 9 resulted in cancellation of surgery. A number of areas of concern specific to the preoperative period were identified. Inadequate coordination between surgical and anaesthetic staff in patient preparation was a frequent cause of preoperative incidents. Improvement in this area may reduce surgical delays and patient morbidity. Problems with premedication drugs resulted in 8 of the 35 incidents, and care must be taken in the prescription and administration of these drugs to minimise adverse effects on patients. Only 2 cases of incorrect patient identification were reported. However, in view of its disastrous consequences, vigilance in patient identification by all members of the operating team, including the anaesthetist, is essential.

Selective decontamination of the digestive tract in cardiac surgical patients.

OBJECTIVE: To test the hypothesis that selective decontamination of the digestive tract improves outcome in cardiac surgical patients. DESIGN: Prospective, consecutive, controlled trial over two 4-month periods. SETTING: Eight-bed, open-plan postcardiac surgery ICU. PATIENTS: All patients undergoing cardiac bypass surgery were eligible. Patients requiring endotracheal intubation for greater than 4 days were included in the analysis. In the initial 4 months, 12 (8.5%) of 141 patients required greater than 4 days of intubation. These 12 patients were not treated with selective decontamination of the digestive tract. We therefore used these patients as the control group. In the second 4-month period, 12 (6.6%) of 180 patients were treated with selective decontamination of the digestive tract and formed the study group. MAIN OUTCOME MEASURES: The primary measure was mortality. Secondary measures included oropharyngeal decontamination and the presence of lower airway infection. INTERVENTIONS: Cephradine prophylaxis. The study group received every 6 hrs 4 mL orally and 20 mL intragastrically a suspension of antimicrobial agents (tobramycin 80 mg, polymyxin E 100 mg, amphotericin B 500 mg), starting on postoperative day 1. The control group did not receive any oral antimicrobial agents. RESULTS: Mortality rate was significantly (p less than .05) reduced from eight (66%) of 12 patients in the control group to two (16.7%) of 12 patients in the selective decontamination of the digestive tract group. No differences in oropharyngeal decontamination or lower airway infection rates between the two groups were found. CONCLUSIONS: There is a reduced mortality rate in patients receiving selective decontamination of the digestive tract. However, the reader should recognize the small sample size studied. A simple suspension of the antimicrobial agents failed to rid the oropharynx of bacteria.

Management of complex perineal soft-tissue injuries.

Debridement, fecal diversion, and rectal washout have been proposed as the primary therapy for complex perineal lacerations, but, in most series, survivors have a pelvic sepsis rate of 40-80%. In a retrospective study, six of 18 patients sustaining severe perineal lacerations died within the first few hours of injury due to exsanguination from pelvic injuries. The remaining 12 patients underwent sigmoidoscopy, diversion of the fecal stream with irrigation of the distal rectal stump, and radical initial debridement of necrotic soft tissue. Enteral access was obtained in two patients. In the patients with mandatory daily debridement and pulsatile irrigation, no pelvic sepsis occurred. In three patients without daily debridement, pelvic sepsis complicated recovery. The ability of patients to resume oral nutrition was significantly delayed, necessitating total parenteral nutrition in three patients. We conclude that sigmoidoscopy, total diversion of the fecal stream with irrigation of the distal rectal stump, enteral access for feeding, radical initial debridement of necrotic soft tissue, and mandatory daily debridement with pulsatile irrigation optimize recovery from this devastating injury.

Hard-shell cardiotomy reservoir for reinfusion of shed mediastinal blood.

We conducted a prospective, randomized, controlled trial comparing homologous blood consumption between groups of patients receiving conventional mediastinal drainage (group 1) or reinfusion of shed mediastinal blood (group 2) using hard-shell cardiotomy reservoir. One hundred consecutive patients who had elective coronary artery or valvular operations were studied. The two groups were comparable with regard to age, sex, weight, preoperative and postoperative hemoglobin levels, and surgical procedure. Group 2 patients had their shed mediastinal blood reinfused for up to 18 hours postoperatively; otherwise, the two groups were treated identically. For groups 1 and 2, average mediastinal blood losses were 705 +/- 522 and 822 +/- 445 mL and homologous blood consumption was 3.83 +/- 2.58 and 3.15 +/- 2.05 U, respectively (neither measure was significantly different). However, if blood losses exceeded 500 mL, there was a statistically significant reduction in homologous blood requirements in group 2 as compared with matched controls in group 1. This difference was most significant in patients with the greatest mediastinal losses.