Exogenous surfactant application in a rat lung ischemia reperfusion injury model: effects on edema formation and alveolar type II cells

BACKGROUND: Prophylactic exogenous surfactant therapy is a promising way to attenuate the ischemia and reperfusion (I/R) injury associated with lung transplantation and thereby to decrease the clinical occurrence of acute lung injury and acute respiratory distress syndrome. However, there is little information on the mode by which exogenous surfactant attenuates I/R injury of the lung. We hypothesized that exogenous surfactant may act by limiting pulmonary edema formation and by enhancing alveolar type II cell and lamellar body preservation. Therefore, we investigated the effect of exogenous surfactant therapy on the formation of pulmonary edema in different lung compartments and on the ultrastructure of the surfactant producing alveolar epithelial type II cells. METHODS: Rats were randomly assigned to a control, Celsior (CE) or Celsior + surfactant (CE+S) group (n = 5 each). In both Celsior groups, the lungs were flush-perfused with Celsior and subsequently exposed to 4 h of extracorporeal ischemia at 4 degrees C and 50 min of reperfusion at 37 degrees C. The CE+S group received an intratracheal bolus of a modified natural bovine surfactant at a dosage of 50 mg/kg body weight before flush perfusion. After reperfusion (Celsior groups) or immediately after sacrifice (Control), the lungs were fixed by vascular perfusion and processed for light and electron microscopy. Stereology was used to quantify edematous changes as well as alterations of the alveolar epithelial type II cells. RESULTS: Surfactant treatment decreased the intraalveolar edema formation (mean (coefficient of variation): CE: 160 mm3 (0.61) vs. CE+S: 4 mm3 (0.75); p < 0.05) and the development of atelectases (CE: 342 mm3 (0.90) vs. CE+S: 0 mm3; p < 0.05) but led to a higher degree of peribronchovascular edema (CE: 89 mm3 (0.39) vs. CE+S: 268 mm3 (0.43); p < 0.05). Alveolar type II cells were similarly swollen in CE (423 microm3(0.10)) and CE+S (481 microm3(0.10)) compared with controls (323 microm3(0.07); p < 0.05 vs. CE and CE+S). The number of lamellar bodies was increased and the mean lamellar body volume was decreased in both CE groups compared with the control group (p < 0.05). CONCLUSION: Intratracheal surfactant application before I/R significantly reduces the intraalveolar edema formation and development of atelectases but leads to an increased development of peribronchovascular edema. Morphological changes of alveolar type II cells due to I/R are not affected by surfactant treatment. The beneficial effects of exogenous surfactant therapy are related to the intraalveolar activity of the exogenous surfactant.

Prevention of delayed cerebral vasospasm by continuous intrathecal infusion of glyceroltrinitrate and nimodipine in the rabbit model in vivo

OBJECTIVE: Intrathecal bolus administration of nitric oxide donors and calcium channel antagonists has been proposed to reduce cerebral vasospasm (CVS) in animal subarachnoid hemorrhage (SAH) models. Intrathecal continuous administration of these substances for CVS prevention has not been extensively evaluated. This study compared the efficacy of continuous intrathecal infusions of the NO donor glyceroltrinitrate and nimodipine in preventing delayed CVS associated with SAH in an animal model in vivo. METHODS: New Zealand White rabbits were randomly assigned to six groups: no SAH/NaCl, no SAH/NO, no SAH/nimodipine, SAH/NaCl, SAH/NO, or SAH/nimodipine. Glyceroltrinitrate (GTN) at 0.5 microg/microl (0.5 microl/h) or nimodipine at 0.2 microg/microl (10 microl/h) or NaCl was continuously infused into the cisterna magna via an Alzet osmotic pump from day 0 to day 5 after injection of 1.0 ml autologous blood. The magnitude of spasm in the basilar artery was determined by comparison of pre- and posttreatment angiography and was calculated as proportional change in intraluminal diameter based on automatic measurements. RESULTS: A total of 55 experiments and 110 angiograms were performed. SAH was associated with vasoconstriction of the basilar artery (SAH/NaCl group 19.85+/-2.94%). Continuous intrathecal injection of GTN and nimodipine prevented SAH-induced CVS. There was significant prevention of CVS in animals treated with GTN (SAH/NO group 5.93+/-5.2%, n=11) and nimodipine (SAH/nimodipine group: 0.55+/-2.66%, n=9). There was no significant difference between the treatment groups and controls in prevention of CVS. CONCLUSIONS: This study demonstrates that prophylactic continuous intrathecal administration of either GTN or nimodipine equally prevents SAH-associated CVS in an animal model.

Tolerance of human placental tissue to severe hypoxia and its relevance for dual ex vivo perfusion

In the dual ex vivo perfusion of an isolated human placental cotyledon it takes on average 20-30 min to set up stable perfusion circuits for the maternal and fetal vascular compartments. In vivo placental tissue of all species maintains a highly active metabolism and it continues to puzzle investigators how this tissue can survive 30 min of ischemia with more or less complete anoxia following expulsion of the organ from the uterus and do so without severe damage. There seem to be parallels between "depressed metabolism" seen in the fetus and the immature neonate in the peripartum period and survival strategies described in mammals with increased tolerance of severe hypoxia like hibernators in the state of torpor or deep sea diving turtles. Increased tolerance of hypoxia in both is explained by "partial metabolic arrest" in the sense of a temporary suspension of Kleiber's rule. Furthermore the fetus can react to major changes in surrounding oxygen tension by decreasing or increasing the rate of specific basal metabolism, providing protection against severe hypoxia as well as oxidative stress. There is some evidence that adaptive mechanisms allowing increased tolerance of severe hypoxia in the fetus or immature neonate can also be found in placental tissue, of which at least the villous portion is of fetal origin. A better understanding of the molecular details of reprogramming of fetal and placental tissues in late pregnancy may be of clinical relevance for an improved risk assessment of the individual fetus during the critical transition from intrauterine life to the outside and for the development of potential prophylactic measures against severe ante- or intrapartum hypoxia. Responses of the tissue to reperfusion deserve intensive study, since they may provide a rational basis for preventive measures against reperfusion injury and related oxidative stress. Modification of the handling of placental tissue during postpartum ischemia, and adaptation of the artificial reperfusion, may lead to an improvement of the ex vivo perfusion technique.

The timing of surgical antimicrobial prophylaxis

OBJECTIVE: To obtain precise information on the optimal time window for surgical antimicrobial prophylaxis. SUMMARY BACKGROUND DATA: Although perioperative antimicrobial prophylaxis is a well-established strategy for reducing the risk of surgical site infections (SSI), the optimal timing for this procedure has yet to be precisely determined. Under today's recommendations, antibiotics may be administered within the final 2 hours before skin incision, ideally as close to incision time as possible. METHODS: In this prospective observational cohort study at Basel University Hospital we analyzed the incidence of SSI by the timing of antimicrobial prophylaxis in a consecutive series of 3836 surgical procedures. Surgical wounds and resulting infections were assessed to Centers for Disease Control and Prevention standards. Antimicrobial prophylaxis consisted in single-shot administration of 1.5 g of cefuroxime (plus 500 mg of metronidazole in colorectal surgery). RESULTS: The overall SSI rate was 4.7% (180 of 3836). In 49% of all procedures antimicrobial prophylaxis was administered within the final half hour. Multivariable logistic regression analyses showed a significant increase in the odds of SSI when antimicrobial prophylaxis was administered less than 30 minutes (crude odds ratio = 2.01; adjusted odds ratio = 1.95; 95% confidence interval, 1.4-2.8; P < 0.001) and 120 to 60 minutes (crude odds ratio = 1.75; adjusted odds ratio = 1.74; 95% confidence interval, 1.0-2.9; P = 0.035) as compared with the reference interval of 59 to 30 minutes before incision. CONCLUSIONS: When cefuroxime is used as a prophylactic antibiotic, administration 59 to 30 minutes before incision is more effective than administration during the last half hour.

Surgical management of gynecomastia--a 10-year analysis

BACKGROUND: Gynecomastia is defined as the benign enlargement of the male breast. Most studies on surgical treatment of gynecomastia show only small series and lack histopathology results. The aim of this study was to analyze the surgical approach in the treatment of gynecomastia and the related outcome over a 10-year period. PATIENTS AND METHODS: All patients undergoing surgical gynecomastia corrections in our department between 1996 and 2006 were included for retrospective evaluation. The data were analyzed for etiology, stage of gynecomastia, surgical technique, complications, risk factors, and histological results. RESULTS: A total of 100 patients with 160 operations were included. Techniques included subcutaneous mastectomy alone or with additional hand-assisted liposuction, isolated liposuction, and formal breast reduction. Atypical histological findings were found in 3% of the patients (spindle-cell hemangioendothelioma, papilloma). The surgical revision rate among all patients was 7%. Body mass index and a weight of the resected specimen higher than 40 g were identified as significant risk factors for complications (p < 0.05). CONCLUSIONS: The treatment of gynecomastia requires an individualized approach. Caution must be taken in performing large resections, which are associated with increased complication rates. Histological tissue analysis should be routinely performed in all true gynecomastia corrections, because histological results may reveal atypical cellular pathology.

Outcome analysis of breast reconstruction with free transverse rectus abdominis musculocutaneous (TRAM) flaps

QUESTIONS UNDER STUDY: With the reduction in breast cancer mortality in recent years the aesthetic outcome after treatment has gained increasing attention. The aim of this study was to assess the outcome quality of our single institution concept of free TRAM flap breast reconstruction with the aim of providing data to assist the patient's decision-making when breast reconstruction is an option. PRINCIPLES/METHODS: Thirty-two consecutive patients receiving immediate (n = 14) or delayed (n = 18) breast reconstruction with free transverse rectus abdominis musculocutaneous (TRAM) flaps were included. The selection of patients was based on their own wish and the availability of abdominal tissue, without excluding patients at risk for wound healing complications. Patient data were assessed prospectively and the aesthetic outcome was rated after the final result had been achieved. RESULTS: Ten patients sustained wound healing complications (4 of 9 smokers, 8 of 16 patients with a BMI over 25 kg/m2), 8 of them requiring revisional surgery. An average of 1.06 corrective procedures were performed per patient. The aesthetic outcome was judged to be good by 20 patients, fair by 5 and poor by 1 patient who sustained severe tissue loss. CONCLUSIONS: Our results revealed that a large measure of satisfaction is achievable from breast reconstruction with free TRAM flaps, in spite of the invasive nature of the procedure and the inclusion of patients at risk for wound healing complications. These data may be used in the decision-making process by patients eligible for breast reconstruction after mastectomy.

Comparison of oral antiviral therapy with valacyclovir or acyclovir after penetrating keratoplasty for herpetic keratitis

AIMS: To compare the outcome of prophylactic oral valacyclovir (VAL) or oral acyclovir treatment (ACV) in patients having undergone penetrating keratoplasty for herpetic keratitis (HK). METHODS: All patients having received a penetrating keratoplasty for HK and being treated postoperatively with either oral VAL or oral ACV (inclusion period from 12/97 to 3/06 and 5/92 to 9/96, respectively) were retrospectively evaluated. Records were analysed for postoperative reactivation of recurrent HK, graft rejection, endothelial cell loss, central corneal thickness and visual acuity after a follow-up of up to 5 years. RESULTS: Twenty patients received VAL and were compared with 19 patients being treated with ACV. Two patients developed clinical signs of recurrent herpetic disease in the VAL group compared with three patients in the ACV group. Two patients from both groups each developed an irreversible graft failure. Best corrected visual acuity improved in both treatment groups from baseline (logMAR) -1.97 (VAL), -1.47 (ACV) to -0.85, -0.72, respectively, at the 1-year follow-up and slightly deteriorated after 5 years in the ACV group (-0.71 VAL vs -1.14 ACV). CONCLUSION: Prophylactic oral VAL treatment is at least as effective as ACV in preventing recurrence in patients who underwent corneal transplantation for HK. The tolerability of the two drugs is similar, but the dosing for VAL might be more comfortable for patients.

Persistent symptoms after elective sigmoid resection for diverticulitis

PURPOSE: Despite technically successful surgery for diverticular disease, a significant group of patients who experience persistent or recurrent symptoms remains. This study was designed to determine the incidence and pattern of persistent symptoms and their association with peroperative parameters. METHODS: Follow-up (33 (range, 4-72) months) through structured interviews with patients who had surgery for diverticulitis in our department from December 1999 to November 2004 was conducted. Of 162 patients, 124 (76.5 percent) were available for follow-up. Nonparametric tests were used for comparison of patients who had undergone elective (n = 68) or emergency (n = 56) procedures. RESULTS: Of patients who had elective surgery, 25 percent suffered persistent symptoms, including painful constipation, painful abdominal distension, abdominal cramps, and frequent painful diarrhea. Neither the stage of disease (complicated or uncomplicated) nor the surgical technique (laparotomy or laparoscopy) were significantly related to the occurrence of symptoms. Recurrent diverticulitis was not observed. Similar results were obtained from comparisons with emergency patients. CONCLUSIONS: The prevalence of persistent symptoms after successful surgery for diverticular disease may be an additional reason to carefully discuss the indication for prophylactic surgery. In any case, preoperative counseling and informed consent regarding the possibility of persistent symptoms after prophylactic elective surgery is essential.

Progression of steroid-associated osteoporosis after heart transplantation

BACKGROUND: Osteoporosis has been recognized as an important side effect of long-term and of pulsed steroid application after heart transplantation. METHODS: In June 1989 a prospective clinical trial was started to study bone demineralization by quantitative computed tomographic scan. All patients received vitamin D and calcium. In group I (n = 30) synthetic calcitonin (40 Medical Research Council Standard Units subcutaneously per day was administered in 14-day cycles, whereas group II patients (n = 31) received a placebo preparation. Repeat trabecular and cortical quantitative computed tomographic scans of the thoracic (T12) and lumbar spine (L1, L2, L3) were obtained within 48 weeks after heart transplantation. RESULTS: Expressed as the means of T12, L1, L2, and L3, trabecular bone density decreased significantly from 100+/-24 to 79+/-29 mg/mL within 3 weeks after heart transplantation, followed by a further reduction to 67+/-29 mg/mL after 3 months in the calcitonin group. The values for cortical bone density decreased significantly from 229+/-37 to 202+/-40 mg/mL (calcitonin) 3 weeks after heart transplantation. Comparable results were obtained in the placebo group. In both groups bone density remained stable thereafter. Intergroup differences were not of statistical significance. CONCLUSIONS: In heart transplant recipients progressive trabecular bone demineralization is limited to the first 3 postoperative months. Thereafter, bone density remained stable. A positive effect of synthetic calcitonin in addition to prophylactic calcium and vitamin D application could not be proved by repeat quantitative computed tomography.

Differences in endplate deformation of the adjacent and augmented vertebra following cement augmentation

Vertebral cement augmentation can restore the stiffness and strength of a fractured vertebra and relieve chronic pain. Previous finite element analysis, biomechanical tests and clinical studies have indirectly associated new adjacent vertebral fractures following augmentation to altered loading. The aim of this repeated measures in situ biomechanical study was to determine the changes in the adjacent and augmented endplate deformation following cement augmentation of human cadaveric functional spine units (FSU) using micro-computed tomography (micro-CT). The surrounding soft tissue and posterior elements of 22 cadaveric human FSU were removed. FSU were assigned to two groups, control (n = 8) (loaded on day 1 and day 2) and augmented (n = 14) (loaded on day 1, augmented 20% cement fill, and loaded on day 2). The augmented group was further subdivided into a prophylactic augmentation group (n = 9), and vertebrae which spontaneously fractured during loading on day 1 (n = 5). The FSU were axially loaded (200, 1,000, 1,500-2,000 N) within a custom made radiolucent, saline filled loading device. At each loading step, FSUs were scanned using the micro-CT. Endplate heights were determined using custom software. No significant increase in endplate deformation following cement augmentation was noted for the adjacent endplate (P > 0.05). The deformation of the augmented endplate was significantly reduced following cement augmentation for both the prophylactic and fracture group (P < 0.05, P < 0.01, respectively). Endplate deformation of the controls showed no statistically significant differences between loading on day 1 and day 2. A linear relationship was noted between the applied compressive load and endplate deflection (R (2) = 0.58). Evidence of significant endplate deformation differences between unaugmented and augmented FSU, while evident for the augmented endplate, was not present for the adjacent endplate. This non-invasive micro-CT method may also be useful to investigate endplate failure, and parameters that predict vertebral failure.

Rivastigmine for the prevention of postoperative delirium in elderly patients undergoing elective cardiac surgery--a randomized controlled trial

OBJECTIVE: Cardiac surgery is frequently followed by postoperative delirium, which is associated with increased 1-year mortality, late cognitive deficits, and higher costs. Currently, there are no recommendations for pharmacologic prevention of postoperative delirium. Impaired cholinergic transmission is believed to play an important role in the development of delirium. We tested the hypothesis that prophylactic short-term administration of oral rivastigmine, a cholinesterase inhibitor, reduces the incidence of delirium in elderly patients during the first 6 days after elective cardiac surgery. DESIGN:: Double-blind, randomized, placebo-controlled trial. SETTING: One Swiss University Hospital. PATIENTS: One hundred twenty patients aged 65 or older undergoing elective cardiac surgery with cardiopulmonary bypass. INTERVENTION: Patients were randomly assigned to receive either placebo or 3 doses of 1.5 mg of oral rivastigmine per day starting the evening before surgery and continuing until the evening of the sixth postoperative day. MEASUREMENTS AND MAIN RESULTS: The primary predefined outcome was delirium diagnosed with the Confusion Assessment Method within 6 days postoperatively. Secondary outcome measures were the results of daily Mini-Mental State Examinations and clock drawing tests, and the use of a rescue treatment consisting of haloperidol and/or lorazepam in patients with delirium. Delirium developed in 17 of 57 (30%) and 18 of 56 (32%) patients in the placebo and rivastigmine groups, respectively (p = 0.8). There was no treatment effect on the time course of Mini-Mental State Examinations and clock drawing tests (p = 0.4 and p = 0.8, respectively). There was no significant difference in the number of patients receiving haloperidol (18 of 57 and 17 of 56, p = 0.9) or lorazepam (38 of 57 and 35 of 56, p = 0.6) in the placebo and rivastigmine groups, respectively. CONCLUSION: This negative or, because of methodologic issues, possibly failed trial does not support short-term prophylactic administration of oral rivastigmine to prevent postoperative delirium in elderly patients undergoing elective cardiac surgery with cardiopulmonary bypass.

Prospective surveillance of varicella-zoster virus infections in an out-patient setting in Switzerland

Limited data are available on the clinical impact of varicella in the ambulatory setting. Our goal was to determine real-life data on the clinical outcomes, medical management, and resource utilization in patients with varicella in Switzerland, a country without a universal immunization program against varicella. A total of 236 patients (222 = 94% primarily healthy individuals) with a clinical diagnosis of varicella were recruited by pediatricians and general practitioners. Age range of patients was 0-47 years with a median of 5 years. The great majority of patients (179 = 76%) were prophylactic immunization.

[Foot problems in chronic polyarthritis: shoe advice and foot care]

Inflammatory alterations of the feet due to rheumatoid arthritis very often reduce the patient's quality of life. We present the pathogenetic mechanisms and discuss practicable and efficient prophylactic and therapeutic methods. A method recently developed by our occupational therapist for placing foot pads correctly in shoes is described.

Diseases in neonatal foals. Part 2: potential risk factors for a higher incidence of infectious diseases during the first 30 days post partum

REASON FOR PERFORMING STUDY: The development of clinical illness in foals is usually predetermined by perinatal history, management or stressful environmental conditions. OBJECTIVES: To determine potential risk factors for an increased incidence of infectious diseases during the first 30 days post partum. METHODS: The population consisted of Thoroughbred foals born on stud farms in the Newmarket (UK) area in 2005 (n = 1031). They were followed for their first 30 days. Factors suspected to influence the incidence of infectious neonatal diseases were examined in a logistic regression approach for each of the 3 outcomes (total infectious diseases, systemic disease with diarrhoea and total infectious diseases excluding diarrhoea). All 28 factors were either foal or mare or stud farm related. RESULTS: Several significant risk factors for a higher disease incidence, such as birth complications, colostrum intake by stomach tube and leucocytosis 12-48 h post partum were identified. The factor 'boarding stud' seemed to be protective against disease. CONCLUSION: Some factors, such as the mare's time at stud before foaling, the mare's rotavirus vaccination schedule and fibrinogen-values that empirically had been linked to the outcome previously were not confirmed as relevant. This included the reported useful prophylactic treatment with antimicrobial drugs. POTENTIAL RELEVANCE: Factors to be considered when evaluating newborn foals include: stud management, the birth process, route of colostrum intake, white and red blood cells, and the date of birth. These may help to detect foals at risk to develop an infection so that targeted prophylactic measures can be initiated.

[Occurrence of Clostridium perfringens type A and type C in piglets of the Swiss swine population]

Necrotizing enteritis (NE) of newborn piglets still represents an economical problem in Swiss pig breeding and production. The aim of our study was to identify risk factors for NE and evaluate the prevalence of C. perfringens with the toxingenes cpb and cpb2 in Swiss pig breeding farms. The prevalence of theses C. perfringens was investigated using fecal swabs followed by bacteriological culturing and genotyping. Close proximity to other breeding farms and large herd sizes were shown to predispose to NE. C. perfringens type C, carrying the genes cpa, cpb and cpb2 were frequently identified in herds with acute outbreaks of NE. Farms not affected by NE or those using prophylactic vaccination against NE were predominantly positive for C. perfringens type A strains with cpb2 and showed much lower prevalence of C. perfringens type C, compared to acutely affected herds. Our results demonstrate that C. perfringens type A strains with cpb2 are not associated with NE. Besides typical necropsy finding, only the identification of cpb can be used for the diagnosis of NE in affected herds.