Three-dimensional gravity modelling of a Quaternary overdeepening fill in the Bern area of Switzerland discloses two stages of glacial carving.

The geometry of glacial overdeepenings on the Swiss Plateau close to Bern was inferred through a combination of gravity data with a 3D gravity modelling software. The target overdeepenings have depths between 155 and > 270 m and widths between 860 and 2400 m. The models show incisions characterized by U-shaped cross-sectional geometries and steep to over-steepened lateral flanks. Existing stratigraphic data reveals that the overdeepenings were formed and then filled during at least two glacial stages, which occurred during the Last Glacial Maximum (LGM) within the Marine Isotope Stage (MIS) 2, and possibly MIS 6 or before. The U-shaped cross-sectional geometries point towards glacial erosion as the main driver for the shaping of the overdeepenings. The combination of the geometries with stratigraphic data suggests that the MIS 6 (or older) glaciers deeply carved the bedrock, whereas the LGM ice sheet only widened the existing valleys but did not further deepen them. We relate this pattern to the different ice thicknesses, where a thicker MIS 6 ice was likely more powerful for wearing down the bedrock than a thinner LGM glacier. Gravity data in combination with forward modelling thus offers robust information on the development of a landscape formed through glaciers.

Bedrock sculpting under an active alpine glacier revealed from cosmic-ray muon radiography.

Mountain glaciers form landscapes with U-shaped valleys, roche moutonées and overdeepenings through bedrock erosion. However, little evidence for active glacial carving has been provided particularly for areas above the Equilibrium Line Altitude (ELA) where glaciers originate. This is mainly due to our lack of information about the shape of the bedrock underneath active glaciers in highly elevated areas. In the past years, the bedrock morphology underneath active glaciers has been studied by geophysical methods in order to infer the subglacial mechanisms of bedrock erosion. However, these comprise surveys on the glaciers' surface, from where it has been difficult to investigate the lateral boundary between the ice and the bedrock with sufficient resolution. Here we perform a muon-radiographic inspection of the Eiger glacier (Switzerland, European Alps) with the aid of cosmic-ray muon attenuation. We find a reach (600 × 300 m) within the accumulation area where strong lateral glacial erosion has cut nearly vertically into the underlying bedrock. This suggests that the Eiger glacier has profoundly sculpted its bedrock in its accumulation area. This also reveals that the cosmic-ray muon radiography is an ideal technology to reconstruct the shape of the bedrock underneath an active glacier.

A comparison of three methods for detecting KRAS mutations in formalin-fixed colorectal cancer specimens.

BACKGROUND: KRAS mutation testing is required to select patients with metastatic colorectal cancer (CRC) to receive anti-epidermal growth factor receptor antibodies, but the optimal KRAS mutation test method is uncertain. METHODS: We conducted a two-site comparison of two commercial KRAS mutation kits - the cobas KRAS Mutation Test and the Qiagen therascreen KRAS Kit - and Sanger sequencing. A panel of 120 CRC specimens was tested with all three methods. The agreement between the cobas test and each of the other methods was assessed. Specimens with discordant results were subjected to quantitative massively parallel pyrosequencing (MPP). DNA blends were tested to determine detection rates at 5% mutant alleles. RESULTS: Reproducibility of the cobas test between sites was 98%. Six mutations were detected by cobas that were not detected by Sanger, and five were confirmed by MPP. The cobas test detected eight mutations which were not detected by the therascreen test, and seven were confirmed by MPP. Detection rates with 5% mutant DNA blends were 100% for the cobas and therascreen tests and 19% for Sanger. CONCLUSION: The cobas test was reproducible between sites, and detected several mutations that were not detected by the therascreen test or Sanger. Sanger sequencing had poor sensitivity for low levels of mutation.

Selective FLT3 inhibition of FLT3-ITD+ acute myeloid leukaemia resulting in secondary D835Y mutation: a model for emerging clinical resistance patterns.

Acquired resistance to selective FLT3 inhibitors is an emerging clinical problem in the treatment of FLT3-ITD(+) acute myeloid leukaemia (AML). The paucity of valid pre-clinical models has restricted investigations to determine the mechanism of acquired therapeutic resistance, thereby limiting the development of effective treatments. We generated selective FLT3 inhibitor-resistant cells by treating the FLT3-ITD(+) human AML cell line MOLM-13 in vitro with the FLT3-selective inhibitor MLN518, and validated the resistant phenotype in vivo and in vitro. The resistant cells, MOLM-13-RES, harboured a new D835Y tyrosine kinase domain (TKD) mutation on the FLT3-ITD(+) allele. Acquired TKD mutations, including D835Y, have recently been identified in FLT3-ITD(+) patients relapsing after treatment with the novel FLT3 inhibitor, AC220. Consistent with this clinical pattern of resistance, MOLM-13-RES cells displayed high relative resistance to AC220 and Sorafenib. Furthermore, treatment of MOLM-13-RES cells with AC220 lead to loss of the FLT3 wild-type allele and the duplication of the FLT3-ITD-D835Y allele. Our FLT3-Aurora kinase inhibitor, CCT137690, successfully inhibited growth of FLT3-ITD-D835Y cells in vitro and in vivo, suggesting that dual FLT3-Aurora inhibition may overcome selective FLT3 inhibitor resistance, in part due to inhibition of Aurora kinase, and may benefit patients with FLT3-mutated AML.

Minimal incision in parotidectomy.

Conservative parotidectomy has been for years an effective and well-established technique. Recently, aesthetic considerations have been reviewed. A minimal pre- and retroauricular incision is proposed that does not extend to the hair-bearing skin. This reduces the length of the scar and the extent of the dissection improving aesthetic results. This is a retrospective study of 32 parotidectomies performed through this incision because of benign parotid diseases and diagnosed by fine needle aspiration cytology. The minimal incision is mainly indicated in small and medium-sized tumours located in the superficial lobe of the parotid gland. Neither operating time nor the morbidity associated with parotidectomy is increased with this safe and effective technique for the treatment of benign parotid masses.

Autotransfusión sanguínea en cirugía ortognática: no necesario / Autologous blood transfusion in orthognathic surgery: not necessary

La cirugía de las deformidades maxilofaciales ha evolucionado de manera importante en las últimas décadas y el número de pacientes que reciben este tipo de tratamiento ha aumentado de forma considerable.Uno de los temas más debatidos en la literatura reciente se refiere a la necesidad de autodonación sanguinea preoperatoria. hacemos una revisiónde las publicaciones relevantes en años recientes, que demuestran puntos de vista opuestos

Surgery for maxillofacial deformities has seen important developments over the last decades and the number of patients undergoing these types of treatment has increased considerably. One of the most debated issues in the recent literature concerns the need for preoperative autologous blood donation. A revision of therelevant publications of recent years reveals opposite views

Blood donor and component management strategies to prevent transfusion-related acute lung injury (TRALI).

OBJECTIVE: Discuss the pros and cons of using donor and blood product-management strategies to prevent transfusion-related acute lung injury (TRALI). DATA SOURCE: A review of the literature was performed. RESULTS: Despite therapeutic advances in pulmonary and critical care medicine, TRALI is now considered to be one of the leading causes of transfusion-associated mortality, and thus determining how to prevent TRALI is extremely important. Donor and product-management strategies to prevent this life-threatening condition have been suggested, but because of gaps in our understanding of TRALI, blood-bankers do not know how beneficial these interventions will be, nor the amount of potential harm-such as decreasing the availability of blood-that could arise if they were implemented. This article discusses the advantages and disadvantages of the various preventive measures that have been described in the literature. CONCLUSIONS: Preventing TRALI poses a difficult challenge for blood-banking experts, because it is unknown which measures will be effective in decreasing the incidence of TRALI and which could have significant drawbacks. Only additional research into TRALI prevention will provide the answers on how to best protect patients from this potentially fatal reaction.

Hemolysis during percutaneous mechanical thrombectomy can mimic a hemolytic transfusion reaction.

BACKGROUND: Interventional radiologists have developed percutaneous mechanical thrombectomy (PMT) devices to remove intravascular thrombi. Hemolysis, secondary to thrombus destruction from these devices, has been described in radiology journals, but similar reports appear to be lacking in the transfusion medicine literature. Two cases of hemolysis after PMT are described that involved the transfusion service, one of which was reported as a hemolytic transfusion reaction. CASE REPORTS: The first patient received 4 units of red cells (RBCs) during a thrombectomy and subsequent placement of a transjugular intrahepatic portosystemic shunt. The patient developed hemoglobinuria, and it was reported to the blood bank as a possible hemolytic transfusion reaction. After RBC mismatch and bacterial contamination were excluded, the hemolysis was attributed to thrombectomy-related mechanical hemolysis. In the second case, a hemolyzed sample was sent to the blood bank for a type and cross-match. Upon requesting that the sample be redrawn, it was learned that the sample was obtained after PMT. CONCLUSION: Patients who have undergone PMT can have clinical and laboratory findings suggestive of hemolytic transfusion reactions. Although interventional radiologists are familiar with these side effects, the blood bank profession needs to be aware that these procedures cause nonimmune hemolysis and must consider this possibility when evaluating transfusion reactions in these patients.

The Fontan procedure for tricuspid atresia: early and late results of a 25-year experience with 216 patients.

OBJECTIVES: We assessed the operative and late mortality and the present clinical status of 216 patients with tricuspid atresia who had a nonfenestrated Fontan procedure performed at the Mayo Clinic in the 25-year period 1973 to 1998. BACKGROUND: The Fontan operation eliminates the systemic hypoxemia and ventricular volume overload characteristic of prior forms of palliation. However, it originally did so at the cost of systemic venous and right atrial hypertension, and the long-term effects of this "price" were unknown when the procedure was initially proposed. METHODS: We reviewed the clinical records of the 216 patients retrospectively. These were arbitrarily grouped into early (1973 through 1980), middle (1981 through 1987) and late (1988 through 1997) surgical eras. Patient outcome was also analyzed according to age at surgery. Operative and late mortality rates were determined and present clinical status was ascertained in 167 of 171 surviving patients. RESULTS: Overall survival was 79%. Operative mortality steadily declined and was 2% (one of 58 patients) during the most recent decade. Late survival also continues to improve. Age at operation had no effect on operative mortality, and late mortality was significantly increased only in patients who were operated on at age 18 years or older. Eighty-nine percent of surviving patients are currently in New York Heart Association class I or II. CONCLUSIONS: The initial 25-year experience with the nonfenestrated Fontan procedure for tricuspid atresia has been gratifying, with most survivors now leading lives of good quality into adulthood. These results justify continued application of this procedure for children born with tricuspid atresia.

Late results of the Rastelli operation for transposition of the great arteries.

The Rastelli operation, first performed in 1968, was developed for repair of transposition of the great arteries with associated ventricular septal defect and severe pulmonary stenosis. This operation includes placement of an intracardiac baffle to direct left ventricular blood to the aorta and an extracardiac valved conduit to establish continuity between the right ventricle and the pulmonary arteries. Over the last 3 decades, the Rastelli operation has been performed with a progressive decline in early mortality, and it remains the preferred repair for transposition, ventricular septal defect, and severe fixed valvular or subvalvular pulmonary stenosis. This chapter examines the late results of our 33-year experience with the Rastelli operation and describes our operative technique.

Effects of sparfloxacin, grepafloxacin, moxifloxacin, and ciprofloxacin on cardiac action potential duration.

Fluoroquinolone antibiotics have been associated with QT prolongation following administration to humans. This study compares the effects of four fluoroquinolones, sparfloxacin, grepafloxacin, moxifloxacin and ciprofloxacin on action potential duration recorded from canine isolated cardiac Purkinje fibres. Left and right ventricular Purkinje fibres were isolated from canine hearts and continuously superfused with physiological salt solution. Action potential duration at 90% repolarization was recorded via intracellular microelectrodes. Sparfloxacin, grepafloxacin, moxifloxacin and ciprofloxacin prolonged action potential duration in a concentration dependent manner. Mean concentrations causing a 15% prolongation of action potential duration recorded at a stimulation frequency of 1 Hz were: sparfloxacin 4.2+/-0.7 microg/ml; grepafloxacin 9.3+/-0.9 microg/ml; moxifloxacin 9.9+/-1.6 microg/ml and ciprofloxacin 72.8+/-26.4 microg/ml. Prolongation was inverse frequency dependent with larger increases in action potential duration occurring when the stimulation frequency was reduced to 0.5 Hz. These results indicate that effects on action potential duration vary within this class of compound. Rank order of potency was sparfloxacin > grepafloxacin = moxifloxacin > ciprofloxacin.

Influence of ventricular morphology on outcome after the Fontan procedure.

The modified Fontan procedure has gained wide acceptance in the treatment of various congenital heart defects. Determination of risk factors for mortality remains an important issue for optimizing patient selection for the Fontan procedure. Conflicting results have been reported about whether ventricular morphology is a risk factor in these patients. Survival free of Fontan takedown or cardiac transplantation was assessed in the first 500 patients undergoing the Fontan procedure at our institution. This survival was correlated with ventricular morphology as evaluated by angiography. Both multivariate and univariate analyses indicated ventricular morphology was predictive of early survival free of Fontan takedown or cardiac transplantation following the procedure. However, there was no statistical evidence for ventricular morphology being a risk factor for mortality in patients alive 6 months after the procedure. Ventricular morphology is a risk factor for early survival in patients undergoing a Fontan procedure, with left ventricular morphology associated with a better early survival than right ventricular morphology.

Metabolic aspects of myocardial disease and a role for L-carnitine in the treatment of childhood cardiomyopathy.

OBJECTIVES: A multicenter retrospective study was conducted to investigate the possible metabolic causes of pediatric cardiomyopathy and evaluate the outcome of patients treated with L-carnitine. METHODS: Seventy-six patients diagnosed with cardiomyopathy were treated with L-carnitine in addition to conventional cardiac treatment, and 145 patients were treated with conventional treatment only. There were 101 males and 120 females between 1 day and 18 years old. Cardiomyopathy diagnoses included dilated (148 patients), hypertrophic (42 patients), restrictive (16 patients), mixed diagnosis (11 patients), and 4 with an unknown type. Of 76 L-carnitine-treated patients, 29 (38%) had evidence to suggest a disorder of metabolism, and of 145 control patients, 15 (10%) were suspected to have a disorder of metabolism. These metabolic disorders were thought to be the cause for the cardiomyopathy of the patients. The duration of L-carnitine treatment ranged from 2 weeks to >1 year. Information was collected on length of survival (time-to-event), clinical outcome, echocardiogram parameters, and clinical assessments. Data were collected at intervals from baseline to study endpoint, death, transplant, or last known follow-up visit. RESULTS: L-Carnitine-treated patients were younger than control patients and had poorer clinical functioning at baseline, yet they demonstrated lower mortality and a level of clinical functioning and clinical severity comparable to control patients on conventional therapy by the end of the study. An analysis of the interaction between clinical outcome and concomitant medications unexpectedly revealed that the population of patients treated with angiotensin-converting enzyme (ACE) inhibitors (40% of patients) had significantly poorer survival (although their greater likelihood for poor survival may possibly have made them more likely to receive ACE inhibitors). CONCLUSION: Results suggest that L-carnitine provides clinical benefit in treating pediatric cardiomyopathy. There is a need for further exploration of potential explanatory factors for the higher mortality observed in the population of patients treated with ACE inhibitors.

Opioid-induced emesis among hospitalized nonsurgical patients: effect on pain and quality of life.

There is very little information in the medical literature regarding opioid-induced emesis and its relationship to patient outcomes. Two-hundred and six nonsurgical patients in a 400-bed teaching hospital with minimal known risks of disease-associated emesis were interviewed to examine emesis and associated outcomes following the administration of opioids for acute pain management. The mean age, weight, and height of the study group were 54.4 (+/- 19.6) years, 175.8 (+/- 45.7) pounds, and 67.1 (+/- 4.4) inches, respectively. Seventy-three (35.4%) patients experienced nausea; 28 (13.6%) patients vomited; and 15 (7.3%) patients retched following the opioid therapy. These symptoms were mild and discomforting for relatively short periods of time. The patients' ability to concentrate and eat was affected by the incidence of nausea/vomiting. The intensity, duration, and severity of nausea were positively associated with the magnitude of the functional limitations. The symptoms also influenced patients' ratings of various hospital satisfaction measures. In conclusion, emesis due to opioids represents a notable burden on nonsurgical patients. Successful therapies that prevent opioid-induced emesis are likely to positively influence patient outcomes by reducing adverse effects, improving functional outcomes, and enhancing quality of life.

The Fontan procedure for pulmonary atresia with intact ventricular septum: operative and late results.

OBJECTIVES: The goals of the study were to evaluate the operative and late mortality associated with the Fontan procedure in patients with pulmonary atresia and an intact ventricular septum and to obtain follow-up information on the current clinical status of surviving patients. BACKGROUND: Between 1979 and October 1, 1995, 40 patients with the anomaly had a nonfenestrated Fontan procedure performed at the Mayo Clinic. Because there are no previously published reports involving a series of this size in which the Fontan approach was used for this condition, a review of patient outcomes was thought to be of value. METHODS: The medical records of the 40 patients were reviewed retrospectively, and 34 were determined to be alive. The status of the survivors as of late 1995 was then ascertained by direct examination, questionnaire or telephone follow-up. RESULTS: There were three operative deaths and three late deaths. The current ages of the 34 survivors ranged from 4 to 30 years (median 13). Thirty-three of the 34 survivors were thought to be in New York Heart Association functional class I or II, and all but three of these patients, of school age or older, were either full-time students or working full time. The three adults who were not employed thought they were capable of working but were not doing so because of socioeconomic reasons. More than half of the patients were not receiving cardiovascular medications. CONCLUSIONS: These overall gratifying early and late results encourage continued application of this operation for appropriately selected patients with this complex congenital cardiovascular anomaly.

Rapid identification of bacterially contaminated platelets using reagent strips: glucose and pH analysis as markers of bacterial metabolism.

BACKGROUND: One in every 1000 units of platelets is bacterially contaminated, which puts patients at risk for transfusion-associated sepsis and death. However, there is currently no screening test in place to detect contaminated units. The use of commercially available multiple-reagent urine dipsticks for this purpose was evaluated. STUDY DESIGN AND METHODS: Platelet concentrates were inoculated with either sterile saline or suspensions of Staphylococcus aureus, Staphylococcus epidermidis, Bacillus cereus, Klebsiella pneumoniae, or Serratia marcescens to a final concentration of 50 colony-forming units (CFU) per mL. The platelets were analyzed daily by the use of multiple-reagent strips, quantitative culture, and glucometry. RESULTS: B cereus grew rapidly, reaching 10(7) CFU per mL 1 day after inoculation, while S. epidermidis grew slowly, achieving similar concentration 4 to 6 days after inoculation. Two of 10 dipstick reagents, glucose and pH, proved useful in detecting bacteria. Both were lower in bacterially contaminated units than in controls. Glucose data obtained from automated analyzers validated the dipstick data. All organisms were detected at concentrations > or = 10(7) CFU per mL, and S. aureus and K. pneumoniae were detected in the range of 10(3) to 10(5) CFU per mL. CONCLUSION: The multiple-reagent test used had a sensitivity and specificity of 95 percent (> or = 10(7) CFU/mL) and 98 to 100 percent, respectively. These data indicate that urine dipsticks can be used to rapidly and inexpensively detect bacterial contamination in platelet concentrates, which potentially will reduce morbidity and mortality at minimal cost.

Apheresis. New opportunities.

Recent advances in apheresis have emerged in a variety of clinical settings. Improvements in granulocyte and peripheral blood stem cell collection and mobilization, the changing role of intravenous gamma globulin, the importance of patient assessment and selection of replacement fluids, and the progress in both affinity apheresis and photopheresis are presented. These current trends, their limitation, and their promise in treating a diversity of diseases inspire the future of this technology.

False-positive hepatitis B surface antigen screening test results in patients receiving granulocyte-colony-stimulating factor.

BACKGROUND: Granulocyte-colony-stimulating factor (G-CSF) is used for the mobilization of progenitor cells and granulocytes. False-positive hepatitis B surface antigen (HBsAg) enzyme-linked immunosorbent assays (ELISAs) (NML) from one manufacturer in individuals receiving G-CSF have been observed. STUDY DESIGN AND METHODS: Sixty-six autologous peripheral blood progenitor cell donors from 1994 were retrospectively reviewed. Donors typically received 5 to 10 micrograms of G-CSF per kg subcutaneously for 5 days before collection. Additional ELISA dilutional studies (1-in-10, 1-in-100, 1-in-1000) with known HBsAg-negative serum were made with G-CSF. Testing was performed by the University of North Carolina, the American Red Cross in Charlotte, NC, or the National American Red Cross, Washington, DC. RESULTS: Of the 66 patients, none reacted for antibody to hepatitis B core antigen, and 30 (45%) had a positive reaction in the ELISA. Surface antigen positivity was "confirmed" on 6 of the 30 patients by neutralizing ELISA reactivity with an antibody to HBsAg test from the same manufacturer. In all cases, the clinical presentation was not suggestive of hepatitis, and these individuals were not at high risk for hepatitis B. Twenty-seven of the 30 cases were tested with a monoclonal HBsAg ELISA (AUSZYME) from another manufacturer in the peridonation period and did not react. In 1994, 256 autologous whole-blood donors not receiving G-CSF were similarly tested and only 1 (0.4%) had a positive reaction with the second manufacturer's HBsAg ELISA (p < 0.001). Of this group, 41 patients with histories of malignancy were identified, which is comparable to the history of the peripheral blood progenitor cell donors in this study, and none of these blood donors tested positive for HBsAg (p < 0.001). Dilutional studies with G-CSF produced no reactions. CONCLUSION: The NML HBsAg ELISA studied has an unacceptably high false-positive rate in patients or donors receiving G-CSF. The false reactivity of this assay appears to be an indirect consequence of G-CSF administration, which can also lead to spurious confirmation by the HBsAg neutralization assay from the same manufacturer.

Pregnancy outcomes after the Fontan repair.

OBJECTIVES: This study sought to determine risks and outcome of pregnancy and delivery after the modified Fontan operation. BACKGROUND: Increasingly, female Fontan patients reaching child-bearing years are interested in having children. To date, the number of reported pregnancies is small, and pregnancy has therefore been discouraged. METHODS: One hundred ten of 126 female patients from the Fontan registries of the Mayo Clinic and University of California Los Angeles Medical Center responded to a mailed questionnaire. An additional six patients with a reported pregnancy from other centers were identified and reviewed to assess pregnancy outcomes. RESULTS: Among the participating centers, a total of 33 pregnancies after Fontan operation for various types of univentricular heart disease were reported. There were 15 (45%) live births from 14 mothers, with 13 spontaneous abortions and 5 elective terminations. In the 14 women with live births, the median number of years between operation and pregnancy was 4 (range 2 to 14). Reported prepregnancy problems in these gravidas included atrial flutter in one patient and ventricular dysfunction, aortic regurgitation and atrioventricular valve regurgitation in another. One patient developed supraventricular tachycardia during pregnancy and had conversion to sinus rhythm. No maternal cardiac complications were reported during labor, delivery or the immediate puerperium. There were six female and nine male infants (mean gestational age 36.5 weeks; median weight 2,344 g). One infant had an atrial septal defect. At follow-up, mothers and infants were alive and well. CONCLUSIONS: Pregnancy after the Fontan operation appears to have been well tolerated in 13 to 14 gravidas. There does appear to be an increased risk of miscarriage. The tendency to routinely discourage pregnancy may need to be reconsidered.