Lipoprotein(a): a genetically determined lipoprotein containing a glycoprotein of the plasminogen family

Lp(a) represents a genetically transmitted class of plasma LDL having apo B-100 linked by a disulfide bridge to a glycoprotein, apo(a). Lp(a) is heterogeneous in size and density. Apo(a) is also heterogeneous in size (molecular weight between approximately 300,000 and 700,000) due probably to the polymorphism of both polypeptide and carbohydrate chains. Recent studies have shown that apo(a) has a striking amino acid sequence homology with plasminogen, a serine protease zymogen that following activation to plasmin enters the fibrinolytic system. Apo(a) is severalfold larger than plasminogen (molecular weight approximately 90,000) and also differs from it because it fails to be activated to plasmin. This is due to the fact that arginine is replaced by serine at the site of cleavage by streptokinase, urokinase, or tissue plasminogen activator. A single gene locus appears to control the Lp(a) polymorphism as well as the concentration of the Lp(a) phenotypes in the plasma. Patients with high plasma levels of Lp(a) have been shown to have an increased incidence of cardiovascular disease but a causal relationship has not been firmly established. The information that is being rapidly acquired on the structure of Lp(a) should facilitate the understanding of the molecular basis of the polymorphism of this genetic variant and of the role that the various Lp(a) phenotypes play in atherosclerosis and thrombosis. The potential physiologic role of Lp(a) remains open to inquiry.     

Calculating the risk of a pancreatic fistula after a pancreaticoduodenectomy: a systematic review

BackgroundA post‐operative pancreatic fistula (POPF) is a major cause of morbidity and mortality after a pancreaticoduodenectomy (PD). This systematic review aimed to identify all scoring systems to predict POPF after a PD, consider their clinical applicability and assess the study quality.MethodAn electronic search was performed of Medline (1946–2014) and EMBASE (1996–2014) databases. Results were screened according to Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines, and quality assessed according to the QUIPS (quality in prognostic studies) tool.ResultsSix eligible scoring systems were identified. Five studies used the International Study Group on Pancreatic Fistula (ISGPF) definition. The proposed scores feature between two and five variables and of the 16 total variables, the majority (12) featured in only one score. Three scores could be fully completed pre‐operatively whereas 1 score included intra‐operative and two studies post‐operative variables. Four scores were internally validated and of these, two scores have been subject to subsequent multicentre review. The median QUIPS score was 38 out of 50 (range 16–50).ConclusionThese scores show potential in calculating the individualized patient risk of POPF. There is, however, much variation in current scoring systems and further validation in large multicentre cohorts is now needed.     

Passive entry of a DNA molecule into a small pore

I consider a vesicle with an open pore of small radius rp, exposed to a DNA solution. The crucial moment is the entry, when a chain end faces the pore and enters it. I discuss qualitatively the following three characteristic times: (i) the duration of the entry of one chain end (defining the minimum lifetime of the pore) taue approximately 10(-4) sec, (ii) the transfection time taut (the time required to be sure that one chain has gone in) taut approximately hours, and (iii) the sliding time tauS (the time between entry of one end and entry of the other end) approximately 1 sec. A fortunate feature is that sliding may proceed even if the pore tends to close itself after entry.     

Changing indications for a total pancreatectomy: perspectives over a quarter of a century

Introduction

The indications for a total pancreatectomy (TP), its peri-operative management, provision of pancreatic surgical services and medical treatment of the inherent exo- and endocrine deficient states have all changed considerably over recent decades. The effects of these upon the incidence, indications for and outcomes of TP are unclear. Patients undergoing TP at a single institution over a quarter of a century were reviewed to try to address these issues.

Methods

Data on patients who underwent elective (el-) and emergency TP (em-TP) between 1987 and 2013 were reviewed. Patient demographics, indications, intra-operative details, peri-operative management and long-term outcomes were analysed. Absolute numbers of TP were reported relative to partial pancreatectomy rates.

Results

In total, 136 patients underwent TP [98 (72.1%) el-TP; 38 (27.9%) em-TP]. There was a significant change in indication for el-TP with it increasingly performed for (an intraductal papillary mucinous neoplasm (IPMN) and renal cell metastases whereas there was a decrease in the number of el-TP performed for chronic pancreatitis (P = 0.025). The relative rates of el-TP, however, did not change significantly across the study period (P = 0.225). The median length of stay after el-TP decreased from 19 days pre-1997 to 12 days post-1997 (P = 0.009). The relative use of em-TP declined by 0.28 percentage points per year [P = 0.018; 95% confidence interval (CI): 0.04–0.41].

Conclusions

The indications for el-TP have changed; it is being performed more frequently although the proportion relative to other pancreatic resections has not changed. A decrease in the rate of em-TP is likely to reflect improved peri-operative management of a pancreatic fistula and its complications after a pancreaticoduodenectomy.     

Partitioning of a polymer into a nanoscopic protein pore obeys a simple scaling law

The dependence of the rate on polymer mass was examined for the reaction of four sulfhydryl-directed poly(ethylene glycol) reagents with cysteine residues located in the lumen of the staphylococcal alpha-hemolysin pore. The logarithms of the apparent rate constants for a particular site in the lumen were proportional to N, the number of repeat units in a polymer chain. The proportionality constant was -(a/D)(5/3), where a is the persistence length of the polymer ( approximately 3.5A) and D is the diameter of the pore. Despite some incongruencies with the assumptions of the derivation, the result suggests that the polymers partition into the lumen of the pore according to the simple scaling law of Daoud and de Gennes, c(pore)/c(solution) = exp(-N(a/D)(5/3)). Therefore, the measured reaction rates yield an estimate of the diameter of the pore and might be applied to determine the approximate dimensions of cavities within other similar proteins.     

Feasibility of a breath test with a substrate of natural 13C-abundance and isotope-selective non-dispersive infrared spectrometry: a preliminary study

BACKGROUND AND AIMS: Isotope-selective non-dispersive infrared spectrometry (NDIRS) is a cheaper alternative to isotope ratio mass spectrometry (IRMS). We checked on the efficiency of NDIRS to perform a breath test with naturally (13)C-enriched maize starch. METHODS: Fifty-six healthy volunteers were examined. After a basal fasted sample of their expiratory air was collected, the subjects ate a test breakfast of 50 g (CF50 group, n = 9) or 100 g (CF100 group, n = 47) cornflakes with 175 g yoghurt. For 6 h thereafter, exhaled air was collected every 30 min for the NDIRS measurement of (13)CO(2) concentration. RESULTS: The time-course of the curves of (13)CO(2) concentration resembled those obtained previously with IRMS. A dose-response to the amount of ingested cornflakes was observed--the maximum postprandial net increment in (13)CO(2) was statistically significantly higher in the CF100 than CF50 group: 4.78 +/- 0.13 versus 3.12 +/- 0.17 per thousand (P < 0.001), whereas the time needed to reach the maximum did not differ after the intake of 50 g (233 +/- 13 min) or 100 g (248 +/- 9 min) cornflakes. The 5-h area-under-the-curve of cumulative (13)CO(2) net recovery (AUC(60-360)) was statistically significantly greater after ingestion of 100 g compared to 50 g cornflakes (97.6 +/- 2.2 versus 61.7 +/- 2.2 micromol, P < 0.001) and it also exhibited a stable between-subject variability. CONCLUSION: The obtained proof of technical feasibility of a breath test with the use of naturally (13)C-enriched starch and NDIRS provides background for future research on the clinical usefulness of this method for a non-invasive assessment of the pancreatic exocrine function.     

Synergism of Bacillus thuringiensis toxins by a fragment of a toxin-binding cadherin

The insecticidal crystal proteins produced by Bacillus thuringiensis (Bt) are broadly used to control insect pests with agricultural importance. The cadherin Bt-R(1) is a binding protein for Bt Cry1A toxins in midgut epithelia of tobacco hornworm (Manduca sexta). We previously identified the Bt-R(1) region most proximal to the cell membrane (CR12-MPED) as the essential binding region required for Cry1Ab-mediated cytotoxicity. Here, we report that a peptide containing this region expressed in Escherichia coli functions as a synergist of Cry1A toxicity against lepidopteran larvae. Far-UV circular dichroism and (1)H-NMR spectroscopy confirmed that our purified CR12-MPED peptide mainly consisted of beta-strands and random coils with unfolded structure. CR12-MPED peptide bound brush border membrane vesicles with high affinity (K(d) = 32 nM) and insect midgut microvilli but did not alter Cry1Ab or Cry1Ac binding localization in the midgut. By BIAcore analysis we demonstrate that Cry1Ab binds CR12-MPED at high (9 nM)- and low (1 microM)-affinity sites. CR12-MPED-mediated Cry1A toxicity enhancement was significantly reduced when the high-affinity Cry1A-binding epitope ((1416)GVLTLNIQ(1423)) within the peptide was altered. Because the mixtures of low Bt toxin dose and CR12-MPED peptide effectively control target insect pests, our discovery has important implications related to the use of this peptide to enhance insecticidal activity of Bt toxin-based biopesticides and transgenic Bt crops.     

Utility of a repeated EUS at a tertiary-referral center

BACKGROUND: The utility of a repeated EUS by experts is not known. OBJECTIVE: To define the utility of a repeated EUS for the same indication. DESIGN: A retrospective case series. SETTING: Tertiary-referral hospital in Indianapolis, Indiana. PATIENTS: Consecutive subjects, with and without cancer, who, between January 2000 and September 2006, underwent an initial EUS elsewhere within 6 and 12 weeks of a repeated EUS at our hospital. INTERVENTIONS: A repeated EUS. MAIN OUTCOME MEASUREMENTS: Clinical impact of a repeated EUS. RESULTS: Of 8936 EUS examinations, 73 repeated procedures (0.8%) were identified, and 24 were excluded. The 49 initial EUS procedures (26 men, median age 59 years) were done in Indiana (n = 44) or another state (n = 5) by one of 15 physicians in private practice (n = 48) or at a teaching hospital (n = 1). An EUS-guided FNA (EUS-FNA) was performed during an initial EUS in 21 patients (no biopsy diagnostic for cancer) and was not attempted in 14 patients. The principle indication for a repeated EUS (n = 35) was for an EUS-FNA after the initial tissue sampling was benign, nondiagnostic, or not done. A second EUS had no clinical impact in 18 patients (37%). In the remaining 31 patients (63%), a repeated EUS provided a new or changed clinical diagnosis (n = 12), the initial diagnosis of primary pancreatic cancer (n = 5) or GI stromal tumor (GIST) (n = 1) after a previous nondiagnostic biopsy; or the initial diagnosis of primary (n = 4) or metastatic (n = 2) pancreatic cancer, metastatic esophageal cancer (n = 1), hilar cholangiocarcinoma (n = 1), GIST (n = 1), or pancreatic neuroendocrine tumor (n = 1), or an initial aspiration of a pancreatic cyst (n = 3) after a previous EUS-FNA was not able to be performed. LIMITATIONS: A retrospective design; a small number of nonpancreatic indications. CONCLUSIONS: In this study, a repeated EUS at a tertiary-referral center had a clinical impact in 63% of patients when performed by experts for a similar clinical indication.     

Rupture of a retro-esophageal diverticulum on a right aortic arch. Apropos of a case

Right aortic arch with retro-oesophageal left subclavian artery usually is an asymptomatic vascular abnormality. The evolutive potential of the associated retro-oesophageal diverticulum is unknown. Complications caused by the malformation are rare, but they may be extremely severe. A case of ruptured diverticulum in an adult patient is reported. The vascular abnormality, as well as the rupture, were confirmed by computerized tomography (CT) and angiography. Complications of retro-oesophageal diverticula are due to these formations being transformed into aneurysms, with compression of the oesophagus, dissection of the aorta or rupture. Such accidents raise the problems of detection of the abnormality, long-term surveillance of the diverticulum (facilitated by CT) and decision to be made when signs of transformation develop (resection of the diverticulum under extracorporeal circulation).     

Safety of a cardiac surgical training program over a twelve-year period

INTRODUCTION: The operative results of cardiac surgical procedures performed either by staff surgeons or trainees were compared to evaluate whether there is any additional risk to the patient in operations carried out by trainees. PATIENT AND METHODS: Between 1994 and 2006, 13 197 operations were done by 9 staff surgeons (S-group) and were compared to 1925 operations performed by 10 residents during their training program (R-group). In both groups, subgroups were defined in which patients either underwent isolated coronary artery bypass grafting (CABG) or aortic valve replacement (AVR). Isolated CABG was performed in 8725 cases (S-group) and 1706 cases (R-group). AVR was done in 1273 patients (S-group) and 191 patients in the R-group. The groups were compared with regard to length of surgery, in-hospital mortality, reexploration for bleeding, sternal wound complications, preoperative infarction and stroke. For overall risk stratification, the EuroSCORE was used. In the CABG groups, the KCH score was additionally used. RESULTS: Overall mortality was 0.5 % in the R-group (predicted mortality: 4.6 +/- 5 %) compared to 2 % in the S-group (predicted mortality: 6.9 +/- 7.9 %). Analyzing the CABG groups, mortality was 0.7 % in the R-group (predicted: 1.9 +/- 1.8 %) compared to 1.3 % in the S-group (predicted: 2.1 +/- 2.3 %). The rate of reexplorations for bleeding was 1 % in the R-group compared to 2 % in the S-group ( P < 0.05). Duration of extracorporeal circulation (ECC) was slightly longer in the R-group (95.8 +/- 33 compared to 85.5 +/- 28.3 minutes) without reaching statistical significance ( P > 0.05). Analyzing the AVR group, there was a 0.6 % mortality in the R-group (predicted: 6.5 +/- 6 %) compared to 3.1 % in the S-group (predicted: 8.8 +/- 8 %). Again, there were significantly more reexplorations for bleeding in the S-group (0.6 % vs. 2.8 %, P < 0.05). Time on ECC was longer in the R-group (101.6 +/- 21.6 vs. 96.6 +/- 35 minutes) with a resulting longer cross-clamping time (71.2 +/- 17.1 vs. 63.5 +/- 21 minutes). CONCLUSIONS: Training in cardiac surgery can be done with excellent results and no additional risk to the patients. Both groups performed similarly and had outcomes better than the predicted mortality. Training was mostly performed with isolated coronary artery bypass grafting procedures, resulting in only a small surgical spectrum at the time of board certification.     

Simple synthesis of a 4a-hydroperoxy adduct of a 1,5-dihydroflavine: preliminary studies of a model for bacterial luciferase.

The solution chemistry of N(5)-alkyl flavinium cations and radical species formed by their le- reduction are discussed. Previously unknown, the 4a-flavine hydroperoxides are established to be formed on reaction of N(5)-alkyl flavinium cations with H2O2 or on reaction of N(5)-alkyl-1, 5-dihydroflavines with 3O2. The stability of the 4a-flavine hydroperoxide species is exemplified in the isolation and characterization of 4a-hydroperoxy-N(5)-ethyl-3-methyl-lumiflavine. 4a-Flavine hydroperoxide compounds are shown to be stronger oxidants than H2O2, and to undergo a chemiluminescent reaction in the presence of an aldehyde. Preliminary observations on the chemiluminescent reaction of 4a-flavine hydroperoxides + RCHO are provided, and these are compared to those in the literature dealing with the bioluminescence of bacterial luciferase in the presence of 3O2 and RCHO.     

Clinical testing of a new, low-flux polysulfone membrane. Results of a 26-week study

In a 6-month study, a new hollow-fiber (HF) dialyzer with a modified polysulfone (PS) membrane was evaluated in 12 hemodialysis patients. Seven of them had previously used a cuprophane (CU) HF and five a polymethylmethacrylate (PMMA) HF dialyzer. The PS dialyzer reduced the concentration of serum creatinine by 54 +/- 5% (SD), that of urea by 59 +/- 5%, that of urate by 62 +/- 6% and that of phosphate by 40 +/- 12%; the mean urea index (Kt/V) was 0.9. Heparin consumption diminished with the PS dialyzer compared with the PMMA dialyzer. The serum predialysis beta-2-microglobulin (beta 2M) concentrations rose by 5.4 mg/l (mean). The intradialytic beta 2M measurements showed insignificant changes in all the membranes studied. Eosinophilia was initially observed in 4/12 (33%) of the patients, all using an ethylene oxide (ETO)-sterilized CU dialyzer. At the end of the study this figure had decreased to 1/12 (8%). The serum IgE concentrations also decreased significantly. IgE class antibodies to ETO were initially detected in 2 patients. The level decreased clearly in 1 of them after switching to the PS dialyzer. The new PS dialyzer was found to be effective, possibly less allergenic and, owing to its moderate hydraulic permeability, suitable for routine dialyses.     

Effect of a high-fiber diet vs a fiber-supplemented diet on C-reactive protein level

BACKGROUND: Diets high in fiber are associated with lower levels of inflammatory markers. This study examined the reduction in inflammation from a diet supplemented with fiber compared with a diet naturally high in fiber. METHODS: Randomized crossover intervention trial of 2 diets, a high-fiber (30-g/d) Dietary Approaches to Stop Hypertension (DASH) diet or fiber-supplemented diet (30 g/d), after a baseline (regular) diet period of 3 weeks. There were 35 participants (18 lean normotensive and 17 obese hypertensive individuals) aged 18 to 49 years. RESULTS: The study included 28 women and 7 men; 16 (46%) were black, the remainder white. The mean (SD) fiber intake on baseline diets was 11.9 (0.3) g/d; on the high-fiber DASH diet, 27.7 (0.6) g/d; and on the supplemented diet, 26.3 (0.4) g/d. Overall, the mean C-reactive protein (CRP) level changed from 4.4 to 3.8 mg/L (-13.7%; P = .046) in the high-fiber DASH diet group and to 3.6 mg/L (-18.1%) in the fiber-supplemented diet group (P = .03). However, CRP levels decreased in the 18 lean normotensive participants in either intervention diet group (2.0 mg/L [baseline] vs 1.4 mg/L [high-fiber DASH] vs 1.2 mg/L [supplemented]); P<.05) but did not change significantly (7.1 mg/L [baseline] vs 6.2 mg/L [high-fiber DASH] vs 6.5 mg/L [supplemented]; P>.05) in obese hypertensive participants. Neither age nor race influenced the response of CRP levels to the diets. No evidence of a crossover effect was detected. CONCLUSIONS: The results demonstrate that fiber intake of about 30 g/d) from a diet naturally rich in fiber or from a supplement can reduce levels of CRP. Further research is needed to more clearly elucidate the differential effect seen in lean vs obese individuals and whether modification of dietary fiber may be helpful in modulating inflammation and its consequent cardiovascular consequences.     

Efficacy of chest CT in a pediatric ICU: a prospective study

STUDY OBJECTIVES: (1) To determine whether chest CT provides additional information compared with chest radiography regarding the nature of intrathoracic disease in critically ill children, (2) to determine whether such information alters clinical management, (3) to assess the role of a low-dose high-resolution CT (HRCT) protocol in pediatric ICU (PICU) patients. DESIGN: Prospective study. SETTING: Specialized PICU in a teaching hospital serving London and the south of England. PATIENTS: Twenty children (age range, 3 weeks to 12 years; median, 11 months) underwent chest CT during a 33-month period. Inclusion criteria were (1) inconclusive diagnosis from chest radiograph (CXR) or (2) CXR appearances inconsistent with high oxygenation or ventilatory requirements (PaO(2) to fraction of inspired oxygen ratio < 30 or mean airway pressure > 15 cm H(2)O). INTERVENTIONS: Low-dose HRCT scans (50 mA, 2-mm slice thickness at intervals of 10 or 15 mm) were performed on 12 patients, and helical CT (50 to 250 mA; pitch, 1 to 1.5) performed on 8 patients. MEASUREMENTS AND RESULTS: CT provided additional information regarding the nature of intrathoracic disease in 17 of 20 patients (85%) and resulted in changes to subsequent clinical management in 12 of 20 patients (60%). CONCLUSIONS: Chest CT can add to the accuracy of intrathoracic diagnosis provided by the CXR and may directly influence the acute management of critically ill children. The CT protocol should be tailored to the clinical and radiologic question posed for each individual patient. Noncontiguous HRCT can often provide accurate assessment of pulmonary parenchymal and pleural disease at a reduced radiation dose compared with helical CT.     

Comparison of musculoskeletal ultrasound practices of a rheumatologist and a radiologist

OBJECTIVE: There is considerable debate regarding the role of the rheumatologist ultrasonographer and how this development will impact on musculoskeletal ultrasound (MSUS) performed by radiologists. We compared the MSUS practices of a rheumatologist and a radiologist working within the same National Health Service Trust. METHODS: A retrospective review of MSUS reports of consecutive scans performed by a consultant rheumatologist with a special interest in MSUS and a consultant musculoskeletal radiologist. Reports were analysed for referring specialties, indications for MSUS, joint regions scanned, MSUS findings, frequency with which patients were referred for injection and how often injection was performed. RESULTS: A total of 170 patients were referred to the rheumatologist for MSUS of 282 joint regions (91% referred by rheumatologists). Of those, 84 (49%) patients had MSUS examination of more than one joint region, with up to five regions scanned per sitting. One hundred patients were referred to the radiologist for MSUS of 111 joint regions (49% referred by orthopaedic surgeons). The most frequently requested primary indication for MSUS performed by the rheumatologist was detection of synovitis [74 (44%) patients] while MSUS performed by the radiologist was most frequently for assessment for major structural changes [44 (44%) patients]. The rheumatologist performed MSUS-guided injection in 59 of 170 (35%) patients scanned and the radiologist in 13 of 100 (13%). CONCLUSION: MSUS performed by the rheumatologist was predominantly requested by rheumatologists to aid diagnosis of synovial and tendon inflammation and to guide injections, while MSUS performed by the radiologist was predominantly requested by orthopaedic surgeons to aid diagnosis of structural pathology. Curriculums in MSUS designed for rheumatologists may need to place appropriate emphasis on the identification of synovial and tendon inflammation, and injection guidance.     

Quality control of a national bone marrow donor registry: results of a pilot study and proposal for a standardized approach

Unrelated hematopoietic stem cell transplantation (HSCT) is a recognized therapy for hematological diseases and over 8 million HLA-typed donors are ready to donate. Increased international exchanges and rapid requests through the Bone Marrow Donor Worldwide (BMDW) ask for standardized quality assurance. Since no such standards have been established to date, we tested a pilot program in order to evaluate donor availability and quality of HLA typing of the Swiss Registry.The 18500 donors of the registry have been analyzed by serology for HLA-AB and by molecular typing for HLA-DR. Through three successive annual quality control (QC) exercises, a total of 114 donor requests were sent to 13 blood transfusion centers responsible for donor recruitment asking for a blood sample. Donors were randomly selected according to recruitment periods (1988-1993; 1994-1997; 1998-2000), and to homozygosity for HLA-A and/or -B antigens. An additional 80 frozen blood samples from the repository corresponding to the three periods (n=26) and to the 2001 period (n=54) were also included in the HLA study. HLA-AB typings were done by polymerase chain reaction-sequence specific primers (PCR-SSP) and all discrepancies were retyped. The results showed that 79 samples provided by 69.3% of the requested donors were received within 14 days, and 19 samples (16.7%) were received in >14 days. Altogether, an 86% rate of donor availability was observed, independent of the recruitment period. Among the requested donors, 16 (14%) were not available: for medical reasons (two), for personal reasons (eight), for loss (one), and for an unknown reason (five). The HLA-A/B DNA typing results of 166 homozygous and 12 heterozygous blood samples showed that 437/439 (99.5%) of the assigned A/B antigens were correct. However in 36/178 donors (20.2%) an HLA-A or -B antigen had been missed (34 donors) or misassigned (two donors) by serology, with a decreasing discrepancy rate of 30% (1988-1993) to 18.5% in 2001. Assuming that HLA-A or -B homozygotes are found in 10-15% of the donors and that correct assignments have been observed in nearly 100% of the donors, an overall error rate of 4-5% would be expected for the national registry HLA-AB typing. These data show that standardized quality control for donor availability and HLA typing is feasible, and we propose that this model could be applied to the registries participating in bone marrow donor worldwide.     

Use of recombinant activated factor VII for treatment of a retropharyngeal hemorrhage in a hemophilic patient with a high titer inhibitor

Treatment options during an acute hemorrhage for a hemophilic patient who has an inhibitor (antibody) to factor VIII (FVIII) are limited. If the inhibitor titer is high, even massive doses of FVIII are not sufficient to neutralize the antibody. Likewise, immunoadsorption techniques or plasmapheresis cannot remove enough antibody to permit treatment with FVIII. Allergic reactions and cross-reacting inhibitors complicate therapy with porcine FVIII. Prothrombin complex concentrates (PCC) may be effective but the mechanism is unclear. The theory that activated factor VII (FVIIa) is the active principle in PCC prompted our treatment of a patient with a recombinant FVIIa (rFVIIa) product (NOVO Industries). The patient presented with a large retropharyngeal hemorrhage and an initial inhibitor titer of 129 Bethesda units (BU). Despite Autoplex therapy (100U/kg), tracheal compression by the hematoma increased and asphyxiation was imminent. RFVIIa therapy (60 micrograms/kg) was substituted for Autoplex and nine doses were given without complication. The hemorrhage was controlled. By 18 hr breathing was normal and swallowing and speech were greatly improved. Clinically, the patient dramatically responded to rFVIIa. In addition, the purity, the lack of known infectious agents, and the ease of administration make rFVIIa a potentially attractive new therapy. Use of this product also promises to further our understanding of in vivo hemostasis.     

Structure of a guinea pig common precursor to a MSEL-type neurophysin and copeptin

From guinea pig posterior pituitaries, a MSEL-type neurophysin (neurophysin containing methionine-2, serine-3, glutamic acid-6 and leucine-7), a glycopeptide referred to as copeptin and their common precursor have been purified to homogeneity and sequenced. The performed acid-oxidized precursor, subjected to trypsin hydrolysis, has given 9 peptides, 6 of which (T1-T6) identical to those given by oxidized MSEL-neurophysin except that T6 has an additional C-terminal arginine residue when compared to its homologue. The other 3 tryptic peptides (T7-T9) are identical to those given by copeptin. The 132-residue precursor therefore comprises a MSEL-type neurophysin (93 residues) and copeptin (38 residues) linked by an arginine residue. The molar proportion of this bound form compared with the free polypeptides is approximately 20%. It is believed that this precursor is a part of the vasopressin-MSEL-neurophysin-copeptin precursor incompletely processed during the transport from hypothalamus to neurohypophysis.