Design, synthesis, and conformational analysis of 3-cyclo-butylcarbamoyl hydantoins as novel hydrogen bond driven universal peptidomimetics.

A collection of systematically substituted 3-cyclo-butylcarbamoyl hydantoins was synthesized by a regioselective multicomponent domino process followed by easy coupling reactions. Calculations, NMR studies and X-ray analysis show that these scaffolds are able to project their side chains similar to common secondary structures, such as the α-helix and ß-turn, with favourable enthalpic and entropic profiles.

Differentiation and adaptive radiation of amphibious gobies (Gobiidae: Oxudercinae) in semi-terrestrial habitats.

During several surveys made in the region of the lower Fly River and delta, Papua New Guinea, nine species of oxudercine gobies (Gobiidae: Oxudercinae) were recorded: Boleophthalmus caeruleomaculatus, Oxuderces wirzi, Periophthalmodon freycineti, Periophthalmus darwini, Periophthalmus novaeguineaensis, Periophthalmus takita, Periophthalmus weberi, Scartelaos histophorus and Zappa confluentus. An exploratory multivariate analysis of their habitat conditions discriminated five guilds, differentially distributed in habitats with different quantities of environmental water and three guilds corresponding to different levels of salinity. A partial correspondence between phylogenetic and ecological categories suggested the presence of parallel adaptive radiations within different genera. In particular, the species found in the most terrestrial habitats (P. weberi) was also found in the widest range of conditions, suggesting that colonization of extreme semi-terrestrial and freshwater habitats by this species was facilitated by eurytypy. It is proposed that these findings provide insight into convergent adaptations for the vertebrate eco-evolutionary transition from sea to land.

[Health-related quality of life in patients with chronic kidney disease]. / Qualita' della vita nei nefropatici.

Assessment of quality of life in patients with different degrees of chronic kidney disease is an important issue because of its impact on clinical decisions and financial resource management in the health-care system. The aim of this study was to assess whether a generic instrument like the SF-36 questionnaire is able to discriminate three different populations of patients with different degrees of renal disease (pre-ESRD, ESRD, TxR). Five hundred sixty-three patients from 12 Italian nephrology units completed the SF-36 scales by themselves. The results from these samples were compared with those from the general population. Univariate analysis and multivariate regression were used. The generic SF-36 questionnaire proved to be a powerful instrument to discriminate populations with different degrees of chronic renal failure. The quality of life of patients on dialysis is significantly worse than that of the normal population and other patients with less severe renal function impairment.

The safety of single-physician procedural sedation in the emergency department.

BACKGROUND: Previous research has shown the safety of procedural sedation in the emergency department in university settings involving multiple emergency physicians. OBJECTIVE: To examine sedation in the emergency department conducted by a single emergency physician with monitoring by the emergency nurse. METHODS: The Procedural Sedation in the Community Emergency Department Registry is a prospective observational database of procedural sedation cases directed by the emergency physicians. Among other parameters, the registry tracts whether emergency physicians or emergency nurses monitored patient sedation. The incidence of complications and outcomes were compared between these two monitoring groups. RESULTS: 1028 procedural sedations were performed on 977 patients at 14 sites. In 885 (86.1%) cases the emergency physician directed the sedation, and performed the procedure with monitoring by the emergency nurse. Complications occurred in 42 (4.1%) patients, 35 (4.0%) EN monitored patients and 6 (4.2%) EP monitored patients (p>0.7). Procedures were successful in 863 (97.5%) cases monitored by emergency nurses and in 140 (97.9%) patients monitored by emergency physicians (p>0.7). CONCLUSION: Procedural sedation in the emergency department performed by a single emergency physician is safe and effective.

Release of the mitogen lysophosphatidylinositol from H-Ras-transformed fibroblasts; a possible mechanism of autocrine control of cell proliferation.

Lysophosphatidylinositol (LysoPtdIns) is formed by a constitutively-active phosphoinositide-specific phospholipase A2 in Ras-transformed cells and can stimulate cell proliferation. To evaluate whether LysoPtdIns could function as an autocrine modulator of cell growth, we examined whether LysoPtdIns can be released in the medium of Ras-transformed FRT-Fibro fibroblasts and thyroid cells. Here, we report that LysoPtdIns accumulates in the extracellular space of these lines and reaches levels up to tenfold higher than in the case of normal cells. Moreover, the ionophore A23187 increased the levels of the lysolipid in the extracellular medium. Extracellular LysoPtdIns was rapidly hydrolyzed to inositol 1:2-cyclic phosphate. LysoPtdIns induced thymidine incorporation in FRT-Fibro Ha-Ras fibroblasts, whereas inositol cyclic 1:2-cyclic phosphate did not affect cell growth per se, nor did it interfere with the LysoPtdIns mitogenic activity. We hypothesize that in Ras-transformed fibroblasts the formation and release of LysoPtdIns may function as an autocrine mechanism that participates in the Ras-dependent stimulation of cell growth.

A comparative EPR, infrared and Raman study of natural and deproteinated tooth enamel and dentin.

The aim of the present work was to investigate how the native signal observed in the electron paramagnetic resonance (EPR) spectrum of tooth enamel and dentin is associated with the organic content of the two tissues. This was achieved by comparing the EPR native signal and the optical bands (Raman and infrared, IR) associated with organic components of tooth enamel and dentin, in natural and deproteinated samples. The main results were: (a) in natural samples, the organic optical bands are more intense in dentin than in enamel, in contrast with the EPR native signal which shows similar intensity in the two tissues; (b) after deproteination, the optical organic bands are completely suppressed in both dentin and enamel, while the EPR native signal is eliminated only in dentin. It is suggested that the IR and Raman organic bands are originated in the bulk of the organic matrix, while the paramagnetic centres associated with the EPR native signal are located in the organic-mineral interface.

Efficient GFP mutations profoundly affect mRNA transcription and translation rates.

Green fluorescent protein (GFP) variants with higher expression efficiencies have been generated by mutagenesis. Favorable mutations often improve the folding of GFP. However, an effect on protein folding fails to explain the efficiency of several other GFP mutations. In this work, we demonstrate that mutations of the GFP open reading frame and untranslated regions profoundly affect mRNA transcription and translation efficiencies. The removal of the GFP 5' untranslated region halves the transcription rate of the GFP gene, but hugely improves its translation rate. Mutations of the GFP open reading frame or the addition of peptide sequences differentially reduce the GFP mRNA transcription rate, translation efficiency and protein stability. These previously unrecognized effects are demonstrated to be critical to the efficiency of GFP mutants. These findings indicate the feasibility of generating more efficient GFP variants, with optimized mRNA transcription and translation in eukaryotic cells.

Family member knowledge of children's medical problems: the need for universal application of an emergency data set.

OBJECTIVE: Advances in medical care have led to a growing population of special needs children who are at risk for suboptimal care when they present to a physician with no previous knowledge of their medical history. This risk may be amplified in the emergency department setting when time-sensitive interventions must be initiated without immediate access to consultants or past records. Our purpose in this study was to evaluate caretakers' knowledge of their children's chronic medical problems and their ability to relate this knowledge to unfamiliar health care providers. METHODS: Caretaker/child pairs presenting for specialty visits were surveyed. Questions focused on knowledge of the child's illness, medicine regime, and how to contact the specialist. Chart review confirmed responses of caretakers and provided sociodemographic information. Descriptive statistics and chi2 were used in data analysis. RESULTS: Of the 49 caretakers interviewed, 85% were parents, 53% were African-American, and 43% were Caucasian. One-half of the group received medical assistance. The mean age of the children was 55 months. Responses showed that 53% of caretakers were unable to provide their children's specific diagnoses. Of these, one half could provide a lay diagnosis whereas the remaining one half could only identify the organ system involved or that there was a problem. For children on medications, 29% of caretakers could not provide an accurate list. Name of the subspecialist and phone number of the subspecialty clinic was unknown by 25% of caretakers. No child wore medical identification jewelry. CONCLUSIONS: Caretakers are not always able to accurately relay vital information on their child's essential medical needs, a problem that may be compounded in emergency situations. The use of some form of independent identification and information set is needed to assure proper treatment of children with special health care needs encountering an unfamiliar health care provider.

The molecular determinants of the efficiency of green fluorescent protein mutants.

The Green Fluorescent Protein (GFP) is a spontaneously fluorescent polypeptide of 27 kD from the jellyfish Aequorea victoria that absorbs UV-blue light and emits in the green region of the spectrum. GFP has been successfully expressed both in bacteria and in eukaryotic cells and is widely used to monitor the localization of tagged proteins in living cells. Since wtGFP performs inefficiently in different cellular contexts, efforts have been devoted to the improvement of GFP expression levels and/or fluorescence. We will here review the basic characteristics of wt and mutated GFP, in particular their protein expression vs fluorescent properties. Emphasis will be given to unexpected consequences of mutations of the GFP gene, i.e. on transcription and translation rates and on protein folding in different cell types, and to how these critically reflect on the use of GFP in different cellular environments.

Intravenous ascorbic acid in hemodialysis patients with functional iron deficiency: a clinical trial.

BACKGROUND: Hemodialysis (HD) patients with functional iron deficiency (FID) often develop resistance to recombinant human erythropoietin (rHuEpo). In these patients, iron therapy may be a hazard, leading to iron overload and consequently to hemosiderosis. Recent studies suggest that intravenous ascorbic acid (IVAA) may circumvent rHuEpo resistance. The aim of our study was to show the effects of IVAA on FID and whether this results in a better correction of anemia in HD patients with stable hemoglobin (Hb) concentration and FID. METHODS: Twenty-seven HD patients with serum ferritin >300 microg/l, transferrin saturation (TS) <20% and hemoglobin (Hb) <10 g/dL were selected andrandomly divided into two groups to enter a cross-over trial with IVAA. In group I IV vitamin C 500 mg was administered three times a week for three months and discontinued in the next three months of the study. Vitamin C was not given the first three months in group II (control group, first three months of the study), who then received 500 mg IV three times a week for the next three months. RESULTS: Hb and TS% significantly increased (baselines vs 3 months, Hb 9.2 +/- 0.2 vs 10.0 +/- 0.3 g/dL, TS% 17.5 +/- 0.6 vs 25.7 +/- 1.7, respectively p < 0.01 and p <0.001) in group I after three months; ferritin fell significantly from 572 +/- 40 to 398 +/- 55 microg/L (p<0.004). Ten patients completed the study: mean Hb and TS% fell significantly (3 months vs final, Hb 9.9 +/- 0.3 vs 8.9 +/- 0.2 g/dL, TS% 25.1 +/- 1.2 vs 19.1 +/- 1.1, respectively p < 0.01 and p <0.001), while mean ferritin did not change. Mean Hb, ferritin and TS% remained unchanged in group II after three months. Hb and TS% mean values rose significantly (3 months vs final, Hb 9.0 +/- 0.2 vs 9.9 +/- 0.2 g/dl, TS% 18.4 +/- 1.0 vs 27.0 +/- 1.0, respectively p < 0.005 and p <0.001), and ferritin markedly decreased from 450 +/- 50 to 206 +/- 24 microg/L (p < 0.001) at the end of the study. The rHuEpo dose was kept unchanged throughout the study. Differences were analyzed after three months. Mean Hb rose (0.8 +/- 0.2 g/dL) in group I but dropped (-0.1 +/- 0.1 g/dL) (p< 0.009) in group II. Ferritin dropped in both groups (group I vs group II, -173 + /-48 vs - 33 +/- 21 microg/L) (p < 0.01) while TS% increased (group I vs group II, 8.2 +/- 1.5 vs 0.4 +/- 0.7) (p < 0.001). CONCLUSION: IVAA may partially correct FID and consequently help rHuEpo hyporesponsive anemia.

Subcutaneous lidocaine does not affect the success rate of intravenous access in children less than 24 months of age.

OBJECTIVE: To determine whether subcutaneous lidocaine (SQL), when used to decrease the pain of IV catheter insertion, adversely affects IV access in children < 24 months of age. METHODS: A historically controlled comparison of IV access successes with and without SQL in children < 2 years of age was performed in a 30,000-annual-visit community hospital ED. On-site data collected at the time of IV placement included: patient age, weight, hydration status, number of attempts, and location of attempts. All patients had IV attempts made by the same emergency physician. RESULTS: A total of 110 children, mean age 9.6 +/- 6.9 months, were included in the study analysis. Of the 110, 70 had an IV catheter placed with no pretreatment, while 40 had SQL pretreatment. The average number of attempts for all patients was 1.36 +/- 0.73, with 83 (75%) performed successfully in 1 attempt and 101 (91%) within 2 attempts. The mean numbers of attempts were similar for the control and SQL groups: 1.34 vs 1.40, respectively (p = 0.68), as were the proportions successful in 1 attempt (77% vs 73%; p = 0.58) and within 2 attempts (91% vs 90%; p = 0.84). CONCLUSION: SQL use prior to an IV attempt in children < 2 years of age does not impact vascular access. A secondary finding was that vascular access with and without SQL in infants and small children generally can be accomplished in 1 attempt.

The potential for errors in children with special health care needs.

Children with special health care needs (CSHCN) are at risk for suboptimal treatment when presenting for emergent care to unfamiliar health care providers. Errors in their management may stem from failure to recognize occult conditions, lack of familiarity with rare or complex medical problems, or lack of prior knowledge of baseline physical findings. An emergency information form (EIF) that contains patient-specific information on essential diagnostic and therapeutic interventions may provide a ready personal reference for the emergent care of CSHCN. Coupled with the use of medical identification jewelry and an electronic transmission system, an EIF has the potential to eliminate management errors in the care of these patients.

Bi-level positive airway pressure support system use in acute congestive heart failure: preliminary case series.

OBJECTIVE: To describe the use of a noninvasive bi-level positive airway pressure (PAP) support system for ED patients with acute congestive heart failure (CHF). METHODS: Retrospective case series analysis of ED patients presenting with acute CHF in imminent need of endotracheal intubation (ETI) managed with a bi-level PAP system. The bi-level PAP system was applied at the discretion of the treating emergency physician. Management of the bi-level PAP system, including setting of inspiratory PAP (IPAP) and expiratory PAP (EPAP), weaning, adjunct pharmacologic therapy, and failure of bi-level PAP support, was determined by the treating physician. RESULTS: Only two (9%) of 22 patient presentations necessitated ETI. The mean duration of bi-level PAP therapy was 7.9 hours. The mean maximum IPAP and EPAP settings were 10.8 and 5.8 cm H2O, respectively. Mean intensive care unit length of stay (LOS) was 2.4 days, with a median LOS of only 1 day. There were three deaths in the series; none were attributed to the bi-level PAP system. No technical difficulty with the bi-level PAP system was noted. CONCLUSION: Noninvasive pressure support ventilation with a bi-level PAP support system may avert ETI in acute CHF patients. This device can be effectively used by ED personnel.

Should pediatric emergency care be decentralized?: an out-of-hospital destination model for critically ill children.

OBJECTIVES: A time-to-initial-stabilization model for out-of-hospital destinations of critically ill children (CICs) was developed. Application of this model to assess the impact of changes in different parameters of an emergency medical services for children (EMSC) system is described. METHODS: A computer model created a 2,500-square-mile community containing ten community hospitals (CHs) and one pediatric critical care center (PCC). Community hospitals capable of providing initial immediate stabilization of CICs were defined as emergency departments accepting pediatrics (EDAPs). Critically ill children were randomly selected in proportion to population densities across the modeled community. Time to initial stabilization (TIS) was defined as the time to arrival at either an EDAP or a PCC or time to arrival at a non-EDAP CH + travel time for a team from the PCC to the non-EDAP CH + preparation/dispatch (P/D) time. The following parameters of the model were varied and their effect on TIS was evaluated: location of CHs, location of PCC, primary destinations for CICs, percent of CHs meeting EDAP standards, out-of-hospital compliance with designated hospitals for CICs, P/D time, and ambulance speed. RESULTS: The computer model selected 1,000 CICs in accordance with the population densities of the community. The scenario with the shortest TIS was one in which every CH achieved EDAP designation (9.8 +/- 0.5 minutes). The scenario with the longest TIS involved a model in which every CIC was transported directly to the PCC (28.6 +/- 0.33 minutes). The number of EDAPs in a community and out-of-hospital compliance with use of EDAPs produced comparable effects on the TIS. Travel speeds had a direct effect on TIS but also exaggerated inefficiencies between scenarios. The P/D time had little effect on the TIS. CONCLUSIONS: An out-of-hospital destination model has been developed with the ability to modify multiple EMSC system variables. Application of this model demonstrates the shortest times to stabilization of critically ill children occur in systems that maximize the number of hospitals that meet EDAP standards and decentralize pediatric emergency care.

Can sick children tell time?: emergency department presentation patterns of critically ill children.

OBJECTIVE: Children show a consistent pattern of ED use, with the majority of patients presenting during the late afternoon and evening hours. This study evaluated whether such a diurnal pattern also exists for critically ill children and the implications of such a presentation pattern on ED staffing. METHODS: A review was performed of the ED diagnoses and times of presentation for children less than 12 years of age at 28 nonpediatric hospitals over the six-year period from July 1990 to October 1996. In addition to total ED pediatric visits, a subset of critically ill children (CIC) were identified as those with an ED diagnosis of: meningitis, cardiac arrest, diabetic ketoacidosis, status epilepticus, meningococcemia, or epiglottitis, or those undergoing endotracheal intubation in the ED. A second group of non-critically ill children (NCIC) was composed of children with an ED diagnosis of otitis media, tonsillitis, or pharyngitis. Data collected on each patient included age, diagnosis, site of care, and time of service. Presentation patterns for all three groups were compared for time of day, with statistical analysis through chi-square, ANOVA, and Spearman's rho correlation. RESULTS: A total of 409,820 pediatric ED visits were examined, with 688 CIC children and 28,344 NCIC identified. Presentation patterns for NCIC visits mirrored those of the total pediatric population, with the traditional increase in the late afternoon and evening hours (correlation 0.96). CIC presented much more erratically, with a distribution spread more uniformly throughout the day compared with the total pediatric population (correlation 0.72). Thirty-seven percent of CIC presented during the evening hours of 16:00 to 24:00, compared with 49% for NCIC and 53% for the total pediatric population, while 22% of CIC presented from 24:00 to 08:00 compared with only 13% of NCIC and 10% of total pediatric patients (p < 0.001). CONCLUSION: Critically ill children present more uniformly throughout the day and do not have the same presentation patterns as ambulatory children. ED staffing should reflect this difference and not focus pediatric ED services simply on hours of peak pediatric visits.

Multiwire proportional chamber system of the Fermilab single arm spectrometer.

We describe a system of two groups of multiwire proportional chambers and its special purpose interface used in the Single Arm Spectrometer (SAS) facility at Fermilab. The first set measures the coordinates of the fast particle going into the spectrometer arm with a space resolution down to +/-0.5 mm. The second set, close to the target, measures the multiplicity and angular distributions of charged particles coming from the interaction. The chambers of this set have three sensitive planes with wires at 120 degrees in the same gas volume to measure three coordinates for each physical point, two readout channels per wire to minimize the inefficiency due to the very high flux and insensitive regions at the center of the chambers where they are crossed by the beam.

Nonclassic history in children with radial head subluxations.

Radial head subluxation (RHS) is a common pediatric orthopedic injury, frequently diagnosed through the classic history of axial traction to the upper extremity of a child. However, not all children with RHS will present with this classic history. This may result in misdiagnosis and delay of appropriate treatment. To evaluate the prevalence of non-classic presentations, a retrospective study was conducted of 45 emergency department patients with RHS. Of these patients, 15 presented with an atypical history. All patients were in minimal distress, holding their affected arms semiflexed and pronated (the nursemaid's position). The classic and nonclassic history groups were equivalent in patient age, spontaneous reductions, and physician reductions. A trend towards more radiographs was noted in the nonclassic group. This study suggests that even in the absence of the classic history of upper extremity traction, radial head subluxation should be suspected in any pediatric patient with an upper extremity complaint who presents with the affected arm in the nursemaid's position.

Emergency department presentation of renal dialysis patients: indications for EMS transport directly to dialysis centers.

To determine the pattern of emergency department (ED) utilization by renal dialysis (RD) patients, a prospective study was conducted of dialysis patients presenting to the ED of a regional dialysis center. The most common presenting complaints were shortness of breath (SOB), chest pain, abdominal pain, and vomiting; the most common diagnoses were congestive heart failure, chest wall pain, and electrolyte abnormalities. Interventional dialysis (ID), defined as emergent dialysis required to treat the patient's presenting complaint, was required for 30 patients, with the most common presenting complaints of these patients being shortness of breath, weakness, and chest pain. Only SOB was statistically significant in predicting the need for ID (P less than 0.001), with a positive predictive value of 0.63 and a negative predictive value of 0.85. Prehospital implications of these data suggest that RD patients with a chief complaint of SOB should be transported directly to a facility capable of dialysis on an emergent basis.

Leukocyte larceny: spurious hypoxemia confirmed with pulse oximetry.

Leukemic patients with extremely high white blood counts may exhibit the phenomenon of leukocyte larceny, in which white blood cells metabolize plasma oxygen in arterial blood gas samples (ABG) producing a spuriously low oxygen tension. We report the case of a leukemic patient with a white blood count in excess of 500,000 in whom multiple ABGs documented hypoxemia out of proportion to his clinical picture. Pulse oximetry was used to confirm higher hemoglobin oxygen saturation to establish the leukocyte larceny.

Hypoventilation and hypoxia in reversal of cardiogenic shock in an infant with congenital heart disease.

The case is presented of a child in cardiogenic shock in whom oxygen administration exacerbated a systemic to pulmonary shunt that caused a critical deterioration in his cardiovascular status requiring hypoventilation and restoration of baseline hypoxia for reversal.