Laser-based spectroscopy of FeD: Excitations to the g 6Φ electronic state.

Bands of the g 6Φ-X 4Δ, g 6Φ-A 4Π, g 6Φ-a 6Δ, and g 6Φ-b 6Π electronic transitions of iron monodeuteride (FeD) have been measured in laser excitation and in dispersed fluorescence. The molecules were produced both in a cold supersonic molecular jet source and in a chemical reaction between iron pentacarbonyl [Fe(CO5)] and a microwave discharge of argon and hydrogen gases. Dispersed fluorescence from the latter source was detected at high resolution with a Fourier transform spectrometer, yielding a large number of the transitions observed. The data reveal that FeD experiences strong interstate couplings that compromise fitting of the data with traditional Hamiltonians but that the problem is less severe than in corresponding spectra of FeH. This work greatly expands the available data on FeD, which were previously characterized only through the F 4Δ-X 4Δ spectrum and pure rotational data in the ground state.

Do we need post-pregnancy screening with human chorionic gonadotrophin after previous hydatidiform mole to identify patients with recurrent gestational trophoblastic disease?

OBJECTIVE: To determine whether post-pregnancy human chorionic gonadotrophin screening after previous hydatidiform mole identifies patients with recurrent gestational trophoblastic disease. STUDY DESIGN: A retrospective evaluation of 9315 patients who underwent post-pregnancy screening from 2000 to 2009, as part of the National Gestational Trophoblastic Disease Service in the UK. RESULTS: Patients with previous hydatidiform mole, who had human chorionic gonadotrophin screening after one or more subsequent pregnancies, were identified (n = 9315). Of these, 8630 patients had an initial hydatidiform mole that did not require chemotherapy. In 12,329 subsequent pregnancy events, screening with human chorionic gonadotrophin identified 3 cases of gestational trophoblastic neoplasm. The remaining 685 patients developed gestational trophoblastic neoplasm, following their initial hydatidiform mole and required chemotherapy. In this group there were 1012 further pregnancy events, human chorionic gonadotrophin screening identified 3 patients with gestational trophoblastic neoplasm. The overall recurrence rate was 6 in 13,341 events (risk 1: 2227). The rate was 3 in 12,329 (risk 1:4110) for HM that did not require chemotherapy and 3 in 1012 (1:337) for previously treated gestational trophoblastic neoplasm. All 6 patients with recurrent disease were successfully treated with chemotherapy. CONCLUSION: Routine post-pregnancy human chorionic gonadotrophin screening may be safely discontinued in patients with one previous uncomplicated hydatidiform mole.

Gastric myoelectrical and neurohormonal changes associated with nausea during tilt-induced syncope.

BACKGROUND: Nausea is a common prodromal symptom of neurally mediated syncope, but the biological factors linking nausea with syncope have not been studied. We aimed to characterize nausea during tilt-induced syncope by exploring related changes in gastric myoelectrical activity and plasma epinephrine, norepinephrine, and vasopressin concentrations across study phases of recumbency, tilt, syncope, and recovery. METHODS: Electrogastrographic and plasma hormone changes were compared between patients with tilt-induced syncope and nausea (n = 18) and control subjects (n = 6) without symptoms or hemodynamic changes during tilt-table testing. KEY RESULTS: Over a 4-minute period preceding syncope, sequential electrogastrography epochs demonstrated an increase over time in bradygastria (P = .003) and tachygastria (P = .014) power ratios, while the dominant frequency (P < .001) and the percent normogastria (P = .004) decreased. Syncope led to significant differences between cases and controls in electrogastrographic power ratios in each frequency range: bradygastria (P = .001), tachygastria (P = .005), and normogastria (P = .03). Nausea always followed electrogastrographic changes, and nausea resolution always preceded electrogastrographic normalization. Plasma vasopressin (676.5 ± 122.8 vs 91.2 ± 15.3 pg/mL, P = .012) and epinephrine (434 ± 91.3 vs 48.7 ± 2.5 pg/mL, P = .03), but not norepinephrine (P > .05), also differed with syncope between cases and controls. CONCLUSIONS AND INFERENCES: The nausea related to tilt-induced syncope is temporally associated with changes in gastric myoelectrical activity and increases in plasma vasopressin and epinephrine. The biological mechanisms that induce syncope are physiologically distinct from other experimental models of nausea such as illusory self-motion, yet nausea with syncope appears to have similarly associated electrogastrographic and hormone changes. Thus, tilt-induced syncope could serve as an informative experimental model for nausea research.

Comparison of scars and resulting hypoaesthesia between the medial parapatellar and midline skin incisions in total knee arthroplasty.

The two most common skin incisions in total knee arthroplasty (TKA) are the medial parapatellar and midline. As the medial parapatellar incision is predominantly parallel to the Langer's lines of the knee, this may give a better cosmetic appearance. The aim of this study was to assess patient satisfaction of the surgical scar and resulting hypoaesthesia following TKA. Two groups of patients who underwent primary TKA were reviewed. Group 1 consisted of 91 patients who underwent primary TKA using a medial parapatellar incision and trivector arthrotomy with a mean follow up of 2.8 years. Group 2 consisted of 76 patients who underwent primary TKA using a midline incision and medial parapatellar arthrotomy with a mean follow up of 2.7 years. The scars were assessed using the validated Manchester Scar Proforma (MSP) and Visual Analogue Scales (VAS). The resulting hypoaesthesia was assessed using VAS. The mean MSP for Group 1 and Group 2 was 11.7 and 11.9 respectively. The mean area of hypoaesthesia for Group 1 and Group 2 was 28.9 cm(2) and 23.8 cm(2) respectively. There was no statistical significance in any of the parameters measured. The mean length of the incision scar was 19.5 cm for Group 1 and 19.4 cm for Group 2. Both produced equal and excellent cosmetic results. Patients in both groups had hypoaesthesia around the knee at 7 years following their TKA. Hypoaesthesia was not found to be of significant concern to patients. This information may be useful when consenting patients for TKA.

Binding of tissue plasminogen activator to vascular grafts.

Tissue plasminogen activator labeled with radioactive iodine (125I-tPA) was immobilized on vascular prostheses chemically modified with a thin coating of water-insoluble surfactant, tridodecylmethylammonium chloride (TDMAC). Surfactant-treated Dacron, polytetrafluoroethylene (PTFE), silastic, polyethylene and polyurethane bound appreciable amounts of 125I-tPA (5-30 micrograms 125I-tPA/cm2). Upon exposure to human plasma, the amount of 125I-tPA bound to the surface shows an initial drop during the first hour of incubation, followed by a slower, roughly exponential release with a t 1/2 of approximately 75 hours. Prostheses containing bound tPA show fibrinolytic activity as measured both by lysis of clots formed in vitro, and by hydrolysis of a synthetic polypeptide substrate. Prior to incubation in plasma, tPA bound to a polymer surface has an enzymic activity similar, if not identical to that of the native enzyme in buffered solution. However, exposure to plasma causes a decrease in the fibrinolytic activity of both bound tPA and enzyme released from the surface of the polymer. These data demonstrate that surfactant-treated prostheses can bind tPA, and that these chemically modified devices can act as a slow-release drug delivery system with the potential for reducing prosthesis-induced thromboembolism.

Sensitivity of mononuclear leucocytes to glucocorticoids in elderly hip-fracture patients resistant to suppression of plasma cortisol by dexamethasone.

OBJECTIVE: Elderly women with proximal femur fracture show a prolonged increase in plasma cortisol, which could have undesirable catabolic effects. Suppression of cortisol by dexamethasone is impaired, suggesting resistance to glucocorticoid effects at feedback inhibitory sites. We therefore wished to find out whether peripheral glucocorticoid sensitivity is normal. DESIGN: Peripheral blood mononuclear leucocytes were used as a model tissue. Blood samples were taken from elderly women about 2 weeks after hip fracture and from elderly control women. Each patient was then given 1 mg dexamethasone at 2300 h followed by further sampling at 0800 and 1600 h the next day. METHODS: Glucocorticoid-receptor binding parameters were measured by incubating whole cells with [3H]dexamethasone for 2 h at 37 degrees C. Inhibition of cell proliferation by dexamethasone was assessed by addition of [3H]thymidine to cells cultured for 65 h with concanavalin A. Cortisol and dexamethasone concentrations were measured in the dexamethasone suppression test. RESULTS: As expected, the hip-fracture patients had raised morning cortisol concentrations and impaired suppression by dexamethasone. The cells of the patients had similar numbers of glucocorticoid receptors to those of the control subjects but higher values for Kd (i.e. a lower binding affinity). The cells of the patients incorporated less [3H]thymidine than the control cells in the absence of dexamethasone. The percentage inhibition by a saturating concentration of dexamethasone was unchanged but the concentration giving half-maximal inhibition was decreased (sensitivity was increased) at the higher of the two concanavalin A concentrations used. CONCLUSIONS: These experiments in mononuclear leucocytes give no evidence of peripheral resistance to glucocorticoids in hip-fracture patients with impaired suppression of cortisol by dexamethasone.

Antibiotic bonding to polytetrafluoroethylene with tridodecylmethylammonium chloride.

Polytetrafluoroethylene (PTFE) treated with the cationic surfactant, triodecylmethylammonium chloride (TDMAC), binds 14C-penicillin (1.5 to 2 mg antibiotic/cm graft), whereas untreated PTFE or PTFE treated with anionic detergents shows little binding of antibiotic. TDMAC-treated PTFE concomitantly binds penicillin and heparin, generating a surface that potentially can resist both infection and thrombosis. The retention of these biologically active molecules is not due to passive entrapment in the PTFE but reflects an ionic interaction between the anionic ligands and surface-bound TDMAC. Penicillin bound to PTFE is not removed by exhaustive washing in aqueous buffers but is slowly released in the presence of plasma or when the PTFE is placed in a muscle pouch in the rat. Muscle tissue adjacent to the treated PTFE shows elevated levels of antibiotic following implantation. PTFE treated with TDMAC and placed in a muscle pouch binds 14C-penicillin when it is locally irrigated with antibiotic or when penicillin is administered intravenously. Thus, the TDMAC surface treated either in vitro or in vivo with penicillin provides an effective in situ source for the timed release of antibiotic.

Prevention of catheter sepsis by antibiotic bonding.

The techniques of antibiotic bonding were applied to the problem of hyperalimentation catheter sepsis. Pretreatment with tridodecylmethylammonium chloride (TDMAC) increased the bonding of 14C-penicillin to polyethylene catheter segments from 3.1 to 212 micrograms/cm and to silicone elastomer catheter segments from 0.09 to 181 micrograms/cm. The elution of the bound ligands from silicone elastomer catheter segments in the presence of plasma was studied. At 2 weeks more than 60% of the bound TDMAC remained adherent to the catheter. The elution of the bonded penicillin from the silicone elastomer catheters was biphasic, initially 95% dissociated after 48 hours of incubation. A bioassay revealed that the dissociated penicillin was bacteriocidal. Polyethylene catheters were placed in the jugular vein of rats and positioned in the right atrium. The catheters were tunneled posteriorly, exited between the forelimb shoulder girdles, and connected to a swivel mechanism. The exit site was inoculated before closure with 1 X 10(8) Staphylococcus aureus. Five days after insertion the catheters were removed via sterile thoracotomy and the tips cultured. Untreated control catheters, catheters treated by antibiotic soaking, and catheters pretreated with TDMAC all had high rates of catheter colonization (60% to 80)%. TDMAC-penicillin-bonded catheters did not become colonized. This difference was significant (p less than 0.005). Antibiotic bonding may prove effective in preventing hyperalimentation catheter sepsis.

The application of antibiotic bonding to the treatment of established vascular prosthetic infection.

We used surfactant-mediated antibiotic bonding to treat established vascular prosthetic infections in an animal model. The infrarenal aorta of dogs was replaced with a polytef (PTFE) graft locally contaminated with Staphylococcus aureus. Infected grafts were then replaced with control polytef or polytef bonded with benzylkonium chloride and penicillin G tagged with radioactive carbon, or polytef bonded with tridodecylmethylammonium chloride and penicillin G tagged with radioactive carbon. Both types of antibiotic-bonded grafts had significantly fewer infections than control grafts did. The labeled penicillin G remained bound to both groups of antibiotic-bonded grafts for at least three weeks. In a second group of studies, surfactant-treated polytef adsorbed parenterally administered labeled penicillin G in highly significant concentrations compared with control grafts. These studies suggest the possibility that human vascular prosthetic infection may be treated with an antibiotic-bonded graft.

Noncovalent bonding of penicillin and cefazolin to dacron.

Dacron grafts treated with the surfactant, benzalkonium chloride or TDMAC bind significant quantities of penicillin-14C or cefazolin-14C. The treated grafts showed strong antibacterial activity which indicated that bound radioactivity corresponds to the reversible adsorption of biologically active molecules. Bound penicillin-14C or cefazolin-14C slowly dissociates when the grafts are placed in a surgically prepared muscle pouch in the rat. This slow release of antibiotic produces therapeutic levels of antibiotic in the adjacent tissue. Binding can also be achieved by in situ irrigation of surfactant treated grafts with antibiotic or by injection of the antibiotic.

Diffusion of antibiotics from a polytetrafluoroethylene-benzalkonium surface.

The ability to bond antibiotics non-covalently to polytetrafluoroethylene surfaces was evaluated in an animal model. Grafts soaked or bonded in (14)C-penicillin were placed in subcutaneous pockets in rats and harvested at various time intervals. The amount of antibiotic present on grafts and in local tissue were evaluated by liquid scintillation counting. Antibiotic bonding resulted in higher concentrations of antibiotic present on the graft at implantation. Diffusion of antibiotics from the graft into surrounding tissues was also slowed by the bonding process. However, all grafts retained minimal activity at the end of 24 hours. The possibility of managing vascular prostheses with antibiotic bonding and local antibiotic irrigation is raised.

Failure of demonstrated clinical efficacy of antibiotic-bonded continuous ambulatory peritoneal dialysis (CAPD) catheters.

Previous in vitro, in vivo, and a preliminary clinical report have demonstrated efficacy of noncovalently bonding antibiotics to the surface of continuous ambulatory peritoneal dialysis (CAPD) catheters in decreasing infectious complications. A larger prospective randomized clinical trial was completed. Eighty-six patients with chronic renal failure were enrolled in the study and randomized to receive either a surfactant treated or untreated control catheter. All catheters were soaked in cefoxitin at the time of insertion. Groups were comparable in terms of pre-existing illnesses, age, and gender. No differences were shown in the incidence of catheter-tract infections, peritonitis or mechanical complications. There was also no differences in microbiologic culture results. Therefore, it is concluded that this clinical trial did not demonstrate a reduction in catheter-related infectious complications by antibiotic bonding.

Light and electron microscopic studies of an antibiotic bonded vascular graft.

Polytetrafluoroethylene grafts were bonded to oxacillin with the cationic surfactant, benzalkonium chloride. Grafts were placed in the canine aorta and harvested six and twelve weeks after implantation. Light and scanning and transmission electron microscopy were performed in all specimens. No histological differences could be demonstrated between control and antibiotic bonded grafts. Significant antibacterial activity was demonstrated at the time of graft implantation. However, none remained six and twelve weeks later.

The "S" Quattro in the management of fractures in the hand.

The "S" Quattro has shown its value in the management of displaced comminuted intra-articular phalangeal fracture dislocations. Since then the system has been used as a dynamic flexible external fixator in the treatment of five maluniting phalangeal fractures, five comminuted condylar and four severe compound fractures. These challenging fractures have been dealt with by easy operations, taking full advantage of the versatility of the "S" Quattro to achieve good results.

The dynamic nature of ST-segment and T-wave changes during acute MI.

Obtaining a prehospital 12-lead electrocardiogram (ECG) diagnostic of acute myocardial injury has been demonstrated to hasten the administration of thrombolytic agents in the emergency department. This case demonstrates that a prehospital electrocardiogram diagnostic of acute anterior wall infarction can become non-diagnostic following routine administration of oxygen, nitroglycerin, and morphine by paramedics. Although this phenomenon has been observed in the in-hospital setting, it has not been reported in patients with a prehospital ECG.

Reduced levels of plasma kisspeptin during the antenatal booking visit are associated with increased risk of miscarriage.

CONTEXT: Kisspeptin is a recently identified hormone encoded by the KISS1 gene, playing a critical role in human reproduction. Plasma kisspeptin levels rise dramatically during normal pregnancy due to placental synthesis, which implicates it as a potential tool for assessing risks of pregnancy complications. No previous prospective study has investigated the association between plasma kisspeptin and risk of miscarriage. OBJECTIVE: The objective of the study was to determine whether a single plasma kisspeptin or serum human chorionic gonadotropin (hCG) measurement in asymptomatic women attending their booking antenatal visit is associated with miscarriage. DESIGN: This was a prospective cohort study. SETTING: The study was conducted at a tertiary obstetric center. PARTICIPANTS: A total of 993 asymptomatic pregnant women with a gestation of 6 weeks or longer attending routine antenatal booking visit were recruited between January 2010 and December 2012. MAIN OUTCOME MEASURES: Plasma kisspeptin and serum hCG were measured during the antenatal booking visit. Pregnancy outcome was recorded prospectively. RESULTS: Plasma kisspeptin correlated with gestation (r(2) = 0.57; P < .0001). Gestational age-corrected (multiples of median) plasma kisspeptin was 60.4% lower (P < .001), and multiples of median-hCG was 36.1% lower (P < .001) in women later diagnosed with miscarriage compared with women without miscarriage. Increased plasma kisspeptin was associated with reduced miscarriage risk, even after adjusting for age, body mass index, gestational age, smoking, and blood pressure [odds ratio 0.13 (95% confidence interval 0.08-0.22), P = .0001]. Kisspeptin had a higher diagnostic performance for miscarriage than hCG (receiver-operator characteristic-area under the curve 0.899 ± 0.025 plasma kisspeptin; 0.775 ± 0.040, serum hCG, P < .01 vs plasma kisspeptin). CONCLUSION: Our data suggest for the first time that a single plasma kisspeptin measurement taken during the antenatal booking visit provides a potential novel marker for identifying asymptomatic pregnant women at a gestation of 6 weeks or greater at increased risk of miscarriage.

Distribution-based sensitivity metric for highly variable biochemical systems.

Classical sensitivity analysis is routinely used to identify points of fragility or robustness in biochemical networks. However, intracellular systems often contain components that number in the thousands to tens or less and consequently motivate a stochastic treatment. Although methodologies exist to quantify sensitivities in stochastic models, they differ substantially from those used in deterministic regimes. Therefore it is not possible to tell whether observed differences in sensitivity measured in deterministic and stochastic elaborations of the same network are the result of methodology or model form. The authors introduce here a distribution-based methodology to measure sensitivity that is equally applicable in both regimes, and demonstrate its use and applicability on a sophisticated mathematical model of the mouse circadian clock that is available in both deterministic and stochastic variants. The authors use the method to produce sensitivity measurements on both variants. They note that the rank-order sensitivity of the clock to parametric perturbations is extremely well conserved across several orders of magnitude. The data show that the clock is fragile to perturbations in parameters common to the cellular machinery ('global' parameters) and robust to perturbations in parameters that are clock-specific ('local' parameters). The sensitivity measure can be used to reduce the model from its original 73 ordinary differential equations (ODEs) to 18 ODEs and to predict the degree to which parametric perturbation can distort the phase response curve of the clock. Finally, the method is employed to evaluate the effect of transcriptional and translational noise on clock function. [Includes supplementary material].