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Affordable thin-film composite (TFC) membranes are a potential alternative to more expensive ion exchange membranes in saltwater electrolyzers used for hydrogen gas production. We used a solution-friction transport model to study how the induced potential gradient controls ion transport across the polyamide (PA) active layer and support layers of TFC membranes during electrolysis. The set of parameters was simplified by assigning the same size-related partition and friction coefficients for all salt ions through the membrane active layer. The model was fit to experimental ion transport data from saltwater electrolysis with 600 mM electrolytes at a current density of 10 mA cm -2 . When the electrolyte concentration and current density were increased, the transport of major charge carriers was successfully predicted by the model. Ion transport calculated using the model only minimally changed when the negative active layer charge density was varied from 0 to 600 mM, indicating active layer charge was not largely responsible for controlling ion crossover during electrolysis. Based on model simulations, a sharp pH gradient was predicted to occur within the supporting layer of the membrane. These results can help guide membrane design and operation conditions in water electrolyzers using TFC membranes.

Hydrogen gas evolution using an impure or saline water feed is a promising strategy to reduce overall energy consumption and investment costs for on-site, large-scale production using renewable energy sources. The chlorine evolution reaction is one of the biggest concerns in hydrogen evolution with impure water feeds. The "alkaline design criterion" in impure water electrolysis was examined here because water oxidation catalysts can exhibit a larger kinetic overpotential without interfering chlorine chemistry under alkaline conditions. Here, we demonstrated that relatively inexpensive thin-film composite (TFC) membranes, currently used for high-pressure reverse osmosis (RO) desalination applications, can have much higher rejection of Cl - (total crossover of 2.9 ± 0.9 mmol) than an anion-exchange membrane (AEM) (51.8 ± 2.3 mmol) with electrolytes of 0.5 M KOH for the anolyte and 0.5 M NaCl for the catholyte with a constant current (100 mA/cm 2 for 20 h). The membrane resistances, which were similar for the TFC membrane and the AEM based on electrochemical impedance spectroscopy (EIS) and Ohm's law methods, could be further reduced by increasing the electrolyte concentration or removal of the structural polyester supporting layer (TFC-no PET). TFC membranes could enable pressurized gas production, as this membrane was demonstrated to be mechanically stable with no change in permeate flux at 35 bar. These results show that TFC membranes provide a novel pathway for producing green hydrogen with a saline water feed at elevated pressures compared to systems using AEMs or porous diaphragms.

Low-cost polyamide thin-film composite membranes are being explored as alternatives to expensive cation exchange membranes for seawater electrolysis. However, transport of chloride from seawater to the anode chamber must be reduced to minimize the production of chlorine gas. A double-polyamide composite structure was created that reduced the level of chloride transport. Adding five polyamide layers on the back of a conventional polyamide composite membrane reduced the chloride ion transport by 53% and did not increase the applied voltage. Decreased chloride permeation was attributed to enhanced electrostatic and steric repulsion created by the new polyamide layers. Charge was balanced through increased sodium ion transport (52%) from the anolyte to the catholyte rather than through a change in the transport of protons and hydroxides. As a result, the Nernstian loss arising from the pH difference between the anolyte and catholyte remained relatively constant during electrolysis despite membrane modifications. This lack of a change in pH showed that transport of protons and hydroxides during electrolysis was independent of salt ion transport. Therefore, only sodium ion transport could compensate for the reduction of chloride flux to maintain the set current. Overall, these results prove the feasibility of using a double-polyamide structure to control chloride permeation during seawater electrolysis without sacrificing energy consumption.

Low-cost polyamide thin-film composite (TFC) membranes are being explored as alternatives to cation exchange membranes for seawater electrolysis. An optimal membrane should have a low electrical resistance to minimize applied potentials needed for water electrolysis and be able to block chloride ions present in a seawater catholyte from reaching the anode. The largest energy loss associated with a TFC membrane was the Nernstian overpotential of 0.74 V (equivalent to 37 Ω cm 2 at 20 mA cm -2 ), derived from the pH difference between the anolyte and catholyte and not the membrane ohmic overpotential. Based on analysis using electrochemical impedance spectroscopy, the pristine TFC membrane contributed only 5.00 Ω cm 2 to the ohmic resistance. Removing the polyester support layer reduced the resistance by 79% to only 1.04 Ω cm 2 , without altering the salt ion transport between the electrolytes. Enlarging the pore size (∼5 times) in the polyamide active layer minimally impacted counterion transport across the membrane during electrolysis, but it increased the total concentration of chloride transported by 60%. Overall, this study suggests that TFC membranes with thinner but mechanically strong supporting layers and size-selective active layers should reduce energy consumption and the potential for chlorine generation for seawater electrolyzers.

Heart failure (HF) is characterized by poor survival, a loss of catecholamine reserve and cellular structural remodeling in the form of disorganization and loss of the transverse tubule network. Indeed, survival rates for HF are worse than many common cancers and have not improved over time. Tadalafil is a clinically relevant drug that blocks phosphodiesterase 5 with high specificity and is used to treat erectile dysfunction. Using a sheep model of advanced HF, we show that tadalafil treatment improves contractile function, reverses transverse tubule loss, restores calcium transient amplitude and the heart's response to catecholamines. Accompanying these effects, tadalafil treatment normalized BNP mRNA and prevented development of subjective signs of HF. These effects were independent of changes in myocardial cGMP content and were associated with upregulation of both monomeric and dimerized forms of protein kinase G and of the cGMP hydrolyzing phosphodiesterases 2 and 3. We propose that the molecular switch for the loss of transverse tubules in HF and their restoration following tadalafil treatment involves the BAR domain protein Amphiphysin II (BIN1) and the restoration of catecholamine sensitivity is through reductions in G-protein receptor kinase 2, protein phosphatase 1 and protein phosphatase 2 A abundance following phosphodiesterase 5 inhibition.

Background: Vascular calcification is associated with increased cardiovascular morbidity and mortality in patients with atherosclerosis, diabetes and chronic kidney disease. However, no viable treatments for this condition have been identified. This study aimed to determine whether farnesyl transferase inhibitors (FTIs) can reduce vascular calcification and the mechanism by which this reduction occurs., Results: We demonstrate that FTI-277 significantly inhibits phosphate-induced mineral deposition by vascular smooth muscle cells (VSMC) in vitro, prevents VSMC osteogenic differentiation, and increases mRNA expression of matrix Gla protein (MGP), an inhibitor of mineralization. FTI-277 increases Akt signaling in VSMC in short-term serum-stimulation assays and in long-term mineralization assays. In contrast, manumycin A has no effect on Akt signaling or mineralization. Co-incubation of VSMC with FTI-277 and SH6 (an Akt inhibitor) significantly reduces the inhibitory effect of FTI-277 on mineralization, demonstrating that FTI-277 inhibits calcification by activating Akt signaling. Over-expression of the constitutively active p110 sub-unit of PI3K in VSMC using adenovirus activates Akt, inhibits mineralization, suppresses VSMC differentiation and significantly enhances MGP mRNA expression. FTI-277 also inhibits phosphate-induced activation of caspase 3 and apoptosis of VSMC, and these effects are negated by co-incubation with SH6. Finally, using an ex vivo model of vascular calcification, we demonstrate that FTI-277 inhibits high phosphate-induced mineralization in aortic rings derived from rats with end-stage renal failure., Conclusions: Together, these results demonstrate that FTI-277 inhibits VSMC mineral deposition by up-regulating PI3K/Akt signaling and preventing apoptosis, suggesting that targeting farnesylation, or Akt specifically, may have therapeutic potential for the prevention of vascular calcification.

Rationale: Transverse tubules (t-tubules) regulate cardiac excitation-contraction coupling and exhibit interchamber and interspecies differences in expression. In cardiac disease, t-tubule loss occurs and affects the systolic calcium transient. However, the mechanisms controlling t-tubule maintenance and whether these factors differ between species, cardiac chambers, and in a disease setting remain unclear., Objective: To determine the role of the Bin/Amphiphysin/Rvs domain protein amphiphysin II (AmpII) in regulating t-tubule maintenance and the systolic calcium transient., Methods and Results: T-tubule density was assessed by di-4-ANEPPS, FM4-64 or WGA staining using confocal microscopy. In rat, ferret, and sheep hearts t-tubule density and AmpII protein levels were lower in the atrium than in the ventricle. Heart failure (HF) was induced in sheep using right ventricular tachypacing and ferrets by ascending aortic coarctation. In both HF models, AmpII protein and t-tubule density were decreased in the ventricles. In the sheep, atrial t-tubules were also lost in HF and AmpII levels decreased. Conversely, junctophilin 2 levels did not show interchamber differences in the rat and ferret nor did they change in HF in the sheep or ferret. In addition, in rat atrial and sheep HF atrial cells where t-tubules were absent, junctophilin 2 had sarcomeric intracellular distribution. Small interfering RNA-induced knockdown of AmpII protein reduced t-tubule density, calcium transient amplitude, and the synchrony of the systolic calcium transient., Conclusions: AmpII is intricately involved in t-tubule maintenance. Reducing AmpII protein decreases t-tubule density, reduces the amplitude, and increases the heterogeneity of the systolic calcium transient., (© 2014 American Heart Association, Inc.)

Chronic kidney disease (CKD) is defined as the progressive loss of renal function often involving glomerular, tubulo-interstitial and vascular pathology. CKD is associated with vascular calcification; the extent of which predicts morbidity and mortality. However, the molecular regulation of these events and the progression of chronic kidney disease are not fully elucidated. To investigate the function of Axl receptor tyrosine kinase in CKD we performed a sub-total nephrectomy and fed high phosphate (1%) diet to Axl+/+ and Axl-/- mice. Plasma Gas6 (Axl' ligand), renal Axl expression and downstream Akt signalling were all significantly up-regulated in Axl+/+ mice following renal mass reduction and high phosphate diet, compared to age-matched controls. Axl-/- mice had significantly enhanced uraemia, reduced bodyweight and significantly reduced survival following sub-total nephrectomy and high phosphate diet compared to Axl+/+ mice; only 45% of Axl-/- mice survived to 14 weeks post-surgery compared to 87% of Axl+/+ mice. Histological analysis of kidney remnants revealed no effect of loss of Axl on glomerular hypertrophy, calcification or renal sclerosis but identified significantly increased tubulo-interstitial apoptosis in Axl-/- mice. Vascular calcification was not induced in Axl+/+ or Axl-/- mice in the time frame we were able to examine. In conclusion, we identify the up-regulation of Gas6/Axl signalling as a protective mechanism which reduces tubulo-interstitial apoptosis and slows progression to end-stage renal failure in the murine nephrectomy and high phosphate diet model of CKD.

Recent studies support a role for FGF23 and its co-receptor Klotho in cardiovascular pathology, yet the underlying mechanisms remain largely elusive. Herein, we analyzed the expression of Klotho in mouse arteries and generated a novel mouse model harboring a vascular smooth muscle cell specific deletion of Klotho (Sm22-KL(-/-) ). Arterial Klotho expression was detected at very low levels with quantitative real-time PCR; Klotho protein levels were undetectable by immunohistochemistry and Western blot. There was no difference in arterial Klotho between Sm22-KL(-/-) and wild-type mice, as well as no changes in serum markers of mineral metabolism. Intravenous delivery of FGF23 elicited a rise in renal (0.005; p<0.01) but not arterial Egr-1 expression, a marker of Klotho-dependent FGF23 signaling. Further, the impact of FGF23 on vascular calcification and endothelial response was evaluated in bovine vascular smooth muscle cells (bVSMC) and in a murine ex vivo model of endothelial function, respectively. FGF23 treatment (0.125-2 ng/mL) did not modify calcification in bVSMCs or dilatory, contractile and structural properties in mice arterial specimen ex vivo. Collectively, these results demonstrate that FGF23-Klotho signaling is absent in mouse arteries and that the vascular response was unaffected by FGF23 treatment. Thus, our data do not support Klotho-mediated FGF23 effects in the vasculature although confirmative studies in humans are warranted.

We investigated autonomic control of cardiovascular function in able-bodied (AB), paraplegic (PARA), and tetraplegic (TETRA) subjects in response to head-up tilt following spinal cord injury. We evaluated spectral power of blood pressure (BP), baroreflex sensitivity (BRS), baroreflex effectiveness index (BEI), occurrence of systolic blood pressure (SBP) ramps, baroreflex sequences, and cross-correlation of SBP with heart rate (HR) in low (0.04-0.15 Hz)- and high (0.15-0.4 Hz)-frequency regions. During tilt, AB and PARA effectively regulated BP and HR, but TETRA did not. The numbers of SBP ramps and percentages of heartbeats involved in SBP ramps and baroreflex sequences increased in AB, were unchanged in PARA, and declined in TETRA. BRS was lowest in PARA and declined with tilt in all groups. BEI was greatest in AB and declined with tilt in all groups. Low-frequency power of BP and the peak of the SBP/HR cross-correlation magnitude were greatest in AB, increased during tilt in AB, remained unchanged in PARA, and declined in TETRA. The peak cross-correlation magnitude in HF decreased with tilt in all groups. Our data indicate that spinal cord injury results in decreased stimulation of arterial baroreceptors and less engagement of feedback control as demonstrated by lower 1) spectral power of BP, 2) number (and percentages) of SBP ramps and barosequences, 3) cross-correlation magnitude of SBP/HR, 4) BEI, and 5) changes in delay between SBP/HR. Diminished vasomotion and impaired baroreflex regulation may be major contributors to decreased orthostatic tolerance following injury.

This study quantified the effect of interrupting the descending input to the sympathetic preganglionic neurons on the dynamic behavior of arterial blood pressure (BP) in the unanesthetized rat. BP was recorded for approximately 4-h intervals in six rats in the neurally intact state and in the same animals after complete spinal cord transection (SCT) between T(4) and T(5). In the intact state, power within the frequency range of 0.35-0.45 Hz was 1.53 +/- 0.38 mmHg(2)/Hz (mean +/- SD by fast Fourier transform). One week after SCT, power within this range decreased significantly (P < 0.05) to 0.43 +/- 0.62 mmHg(2)/Hz. To test for self-similarity before and after SCT, we analyzed data using a wavelet (i.e., functionally, a digital bandpass filter) tuned to be maximally sensitive to fluctuations with periods of approximately 2, 4, 8, 16, 32, or 64 s. In the control state, all fluctuations with periods of >/=4 s conformed to a "self-similar" (i.e., fractal) distribution. In marked contrast, the oscillations with a period of approximately 2 s (i.e., approximately 0.4 Hz) were significantly set apart from those at lower frequencies. One day and seven days after the complete SCT, however, the BP fluctuations at approximately 0.4 Hz now also conformed to the same self-similar behavior characteristic of the lower frequencies. We conclude that 1) an intact sympathetic nervous system endows that portion of the power spectrum centered around approximately 0.4 Hz with properties (e.g., a periodicity) that differ significantly from the self-similar behavior that characterizes the lower frequencies and 2) even within the relatively high frequency range at 0.4 Hz self-similarity is the "default" condition after sympathetic influences have been eliminated.

This experiment quantified the initial disruption and subsequent adaptation of the blood pressure (BP)-heart rate (HR) relationship after spinal cord transection (SCT). BP and HR were recorded for 4 h via an implanted catheter in neurally intact, unanesthetized rats. The animals were then anesthetized, and their spinal cords were severed at T(1)-T(2) (n = 5) or T(4)-T(5) (n = 6) or sham lesioned (n = 4). BP was recorded for 4 h daily over the ensuing 6 days. The neurally intact rat showed a positive cross correlation, with HR leading BP at the peak by 1.8 +/- 0.8 (SD) s. The cross correlation in unanesthetized rats (n = 2) under neuromuscular blockade was also positive, with HR leading. After SCT at T(1)-T(2), the cross correlation became negative, with BP leading HR, and did not change during the next 6 days. The cross correlation also became negative 1-3 days after SCT at T(4)-T(5), but in four rats by day 6 and thereafter the cross correlation progressively reverted to a positive value. We propose that the positive cross correlation with HR leading BP in the intact rat results from an open-loop control that depends on intact supraspinal input to sympathetic preganglionic neurons in the spinal cord. After descending sympathetic pathways were severed at T(1)-T(2), the intact vagal pathway to the sinoatrial node dominated BP regulation via the baroreflex. We suggest that reestablishment of the positive correlation after SCT at T(4)-T(5) was attributable to the surviving sympathetic outflow to the heart and upper vasculature reasserting some effective function, perhaps in association with decreased spinal sympathetic hyperreflexia. The HR-BP cross correlation may index progression of sympathetic dysfunction in pathological processes.

Purpose: To determine the incidence of bacterial contamination of the anterior chamber after phacoemulsification cataract surgery with intraocular lens (IOL) implantation., Setting: Department of Ophthalmology, Royal Prince Alfred Hospital, Sydney, Australia., Methods: Ninety-eight consecutive eyes of 96 patients having phacoemulsification cataract surgery with IOL implantation were included in this prospective study. Two intraoperative anterior chamber aspirates were obtained from each patient, 1 taken at the start and the other at the conclusion of surgery. In addition, preoperative and postoperative conjunctival swabs were acquired. The 4 specimens were cultured using direct culturing techniques under aerobic and anaerobic conditions for 14 days. No preoperative antibiotics were used., Results: The incidence of intraoperative anterior chamber contamination was 0% (95% confidence interval, 0%-3.7%) as all intraoperative anterior chamber samples proved culture negative. Sixty-five percent of the preoperative conjunctival swabs were positive for growth, with corynebacteria, coagulase-negative staphylococci, and Propionibacterium acnes being the most frequently cultured organisms. Sixteen percent of the postoperative conjunctival swabs were positive for growth, with corynebacteria and coagulase-negative staphylococci being the most common bacteria. One patient developed culture-positive postoperative endophthalmitis; using pulsed-field gel electrophoresis for further typing, the implicated Staphylococcus epidermidis was indistinguishable from that isolated from the patient's preoperative conjunctival swab., Conclusions: The bacterial contamination rate of the anterior chamber after phacoemulsification and IOL implantation was extremely low. Additional findings support the conjunctiva as being a primary source of bacteria causing postoperative endophthalmitis as well as the ability of povidone-iodine to reduce the conjunctival bacterial load.

Objective: To assess the safety and efficacy of upper eyelid gold weight implants in managing paralytic lagophthalmos and to compare two surgical techniques for their insertion., Study Design: Retrospective case series., Setting: Tertiary referral center., Patients: One hundred four patients had a gold weight implanted for paralytic lagophthalmos between 1982 and 1996 at the Royal Prince Alfred Hospital in Sydney. Each patient had more than 2 years of follow-up of lid load function., Main Outcome Measures: The effectiveness of gold weights in reanimating eyelid closure, mean duration of gold weight retention, reasons for removal, and complications resulting from a gold weight; these outcomes were also compared using two surgical techniques for gold weight insertion., Results: One hundred three patients maintained corneal integrity. At the time of assessment, 46 patients had had their lid loads removed from their eyelids, and 58 lid loads remained in situ. Of the lid loads that were removed, 78% were because the facial nerve had recovered. The remaining 22% were removed because of cosmetic dissatisfaction (7 patients), the lid load becoming too superficial (6 patients), migration (3 patients), partial extrusion (1 patient), and ptosis resulting from too heavy a weight (1 patient)., Conclusion: Gold weights are well tolerated and effective in managing paralytic lagophthalmos. An open surgical technique with direct suture fixation of the gold weight to the tarsal plate produced fewer complications than inserting the lid load into a prefashioned tissue pocket in the preseptal space through a small lateral skin incision.

A 45-year-old man with primary systemic amyloidosis was found to have bilateral uveal effusions secondary to thickened sclera according to magnetic resonance imaging of the orbits. The patient was treated with bilateral sclerectomies and vortex vein decompression, and had an excellent outcome. Light microscopy of excised sclera revealed severe infiltration of the tissue by amyloid. To our knowledge, this is the first report of amyloid infiltration of the sclera leading to uveal effusion. Arch Ophthalmol. 2000;118:1293-1295

The symptoms of urinary incontinence, ataxia, and mental confusion are an integral part of the clinical presentation of normal pressure hydrocephalus (NPH). They are also common presentations in the rehabilitation setting of patients who have had a cerebral vascular accident. The concurrence of these entities challenges the physiatrist to carefully diagnose and properly manage the patient to maximize the rehabilitation outcome. In the older population the clinical picture may be clouded by several overlapping conditions such as dementia, deconditioning, and age-related decline in bladder control. A case is presented in which the diagnosis of NPH was made after the patient showed a lack of progress in ambulation despite dramatic improvement in strength of the lower extremities.

Background: Significant morbidity and mortality result from the ineffective evacuation of empyema. Failure of conventional first line treatment with closed intercostal tube drainage and antibiotic therapy may result in fibrin deposition and loculated empyema. Enzymatic debridement using intrapleural instillation of streptokinase is a non-invasive therapeutic option which may obviate the need for surgical intervention., Methods: Eleven adults with multiloculated post-pneumonic empyemas who had failed to respond satisfactorily to intercostal tube drainage and antibiotic therapy were treated with intrapleural streptokinase between November 1992 and January 1994. A small catheter was inserted under ultrasound guidance into a loculation within the pleural space. Aliquots of 250,000 units of streptokinase in 100 ml normal saline were instilled into the pleural cavity and the tube clamped for four hours. Response was assessed by clinical outcome, measurement of drain output after unclamping, and subsequent pleural ultrasound, chest radiography, or both., Results: Streptokinase enhanced drainage in all patients. Complete resolution of the empyema with re-expansion of the underlying lung was effected in eight patients, all of whom remain well. Further resolution of minimal pleural thickening was shown on subsequent chest radiographs. Two patients with considerably thickened visceral pleura following empyema drainage underwent successful decortication. The other, with myocarditis and a pyopneumothorax, underwent surgery for non-resolution of the pneumothorax but died perioperatively from cardiac failure. The number of streptokinase instillations per patient ranged from two to six (median three), and the volume of empyema fluid drained per patient ranged from 100 ml to 4870 ml (median 900 ml). Streptokinase was well tolerated in all patients., Conclusions: Intrapleural streptokinase is an effective adjunct in the management of complicated empyema and may reduce the need for surgery.

The antimicrobial prescribing practices of 26 physicians from the U.K. and Eire who care for patients with cystic fibrosis (CF) were assessed by postal questionnaire. Our main aim was to delineate divergent practices which may reveal a need for controlled prospective studies. For first-line intravenous (i.v.) therapy of acute exacerbations associated with Pseudomonas aeruginosa, 20 physicians (76.9%) combine a penicillin derivative with an aminoglycoside, in contrast to five (19.2%) who regularly use i.v. monotherapy with ceftazidime and one who combines i.v. ceftazidime with an aminoglycoside. When i.v. therapy is considered inappropriate, oral ciprofloxacin is sometimes used by all clinicians and oral broad spectrum agents are used in addition by 13, chloramphenicol being prescribed most often. Excluding allergy, the most important factor influencing choice of agents by 19 (73.1%) physicians is the most recent sputum susceptibility results. For maintenance therapy, 21 prescribe oral anti-staphylococcal agents if Staphylococcus aureus is isolated; of these, eight do so only if lung function deteriorates, nine after repeated isolation and four after first isolation of S. aureus. The remaining five physicians give anti-staphylococcal drugs to all patients once the diagnosis of CF is made. For maintenance of lung function in patients with persistent P. aeruginosa, all physicians used nebulized antibiotics, the indications for which vary between units. There was general concordance in the therapy of exacerbations associated with P. aeruginosa, whereas the use of agents to maintain lung function is more varied. We suggest that prospective studies address practices which vary greatly, such as the route, the duration and the timing of initiating antibiotic therapy given to maintain lung function.

Background: Pseudomonas aeruginosa has been located in the endobronchiolar spaces of patients with cystic fibrosis where nutrients may be limited. In these sites it is thought that adaptation of the pathogen might occur and growth factors, present in relative excess, may thus promote survival of the organism. Auxotrophy of pulmonary isolates of P aeruginosa has previously been shown to be a feature of cystic fibrosis and chronic lung sepsis; auxotrophic isolates have additional nutritional requirements to the prototrophic "wild types" of the species. A study was therefore carried out to determine whether the proportion of auxotrophs differs between stable and acutely ill patients, or correlates with the extent of underlying disease., Methods: Sputum samples were cultured for P aeruginosa and tested for auxotrophy by spreading serial dilutions of homogenised sputum on to a minimal medium which supports only prototrophs, and a complete medium which supports both nutritional types. The proportion of auxotrophs to prototrophs was determined and growth factors of confirmed auxotrophs were identified., Results: Thirty two (86%) of 37 adults with cystic fibrosis infected with P aeruginosa harboured auxotrophs; methionine dependent mutants were isolated from seven of 16 patients tested (44%). More than 50% of the total number of colonies were auxotrophic in 19 of 26 samples (73%) from patients with acute exacerbations and in only six of 15 samples (40%) from clinically stable patients. In four patients from whom samples in both the acute and stable states were available, the proportion of auxotrophs fell in the sample taken when stable. Auxotrophs predominated in all samples from 11 of those patients with very severe underlying lung disease, in contrast to 13 of 30 samples from patients with less severe disease. There was no association between the percentage of auxotrophs and the presence of other respiratory pathogens., Conclusions: The majority of adults with cystic fibrosis infected with P aeruginosa harbour auxotrophs in the sputum. A significant proportion of acutely ill patients and those with severe underlying disease have a preponderance of auxotrophs in the sputum compared with stable patients and those with less severe disease.

In a previous study, we reported that inspiratory tracheal occlusion (TO) significantly inhibited the motor drive to the diaphragm in a decerebellated bilaterally vagotomized preparation (J. Appl. Physiol. 75:675-681, 1993). The hypothesis to be tested in the present study was that respiratory muscle afferents activated by inspiratory TO provided the inputs responsible for the observed inhibition. Adult cats were anesthetized, tracheotomized, and instrumented with diaphragm electromyographic (EMGdi) recording electrodes. The cerebellum, vagi, and dorsal spinal cord (C2-T2) were surgically exposed. Inspiratory TO was applied before and after cold blockade of the dorsal cord (C6) or dorsal root (C3-6) transection in the intact and decerebellated vagotomized cat. Respiratory timing (inspiratory and expiratory duration) was determined from the EMGdi record, and the peak integrated EMGdi (integral of EMGdi) response was used as an index of respiratory motor drive. Our results showed that 1) cold blockade at the dorsal C6 level in an intact preparation significantly increased the peak of the integral of EMGdi response to TO and was reversible upon rewarming; 2) as previously reported, decerebellation coupled with bilateral vagotomy significantly decreased the peak integral of EMGdi response to TO with no effect on timing; 3) cold blockade (-1 degree C) of the dorsal cord at C6 significantly attenuated this inhibition, and subsequent dorsal rhizotomy at C3-6 completely abolished this inhibition; and 4) decerebellation, cold blockade of the dorsal cord (C6), and dorsal rhizotomy (C3-6) did not significantly affect baseline values in bilaterally vagotomized cats.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of inspiratory tracheal occlusion (TO) on respiratory duration (inspiratory and expiratory duration), ventilation, and the peak integrated diaphragm electromyographic (integral of EMGdi) response were tested in 16 anesthetized cats before and after decerebellation with and without vagal input. The same protocols were repeated in the decerebrate preparation. Decerebellation did not significantly affect the baseline or the loaded values [tracheal occlusion (TO)] for respiratory duration, tidal volume, or magnitude of the integral of EMGdi response. Vagal blockade eliminated the load-compensating responses in the intact and the decerebrate preparation. However, vagal blockade in concert with decerebellation resulted in a significant (P < 0.05) reversible inhibition of the peak integral of EMGdi response during inspiratory TO. This suggests that removal of vagal and cerebellar influences during loaded breathing unmasked inhibitory inputs to the respiratory pattern generator. With vagus intact, decerebellation before or after decerebration abolished the attenuation of the peak integral of EMGdi response to TO observed with decerebration alone. We conclude that the cerebellum does play a role in determining the pattern of the respiratory response to TO. This influence may be direct and/or indirect via interaction with information emanating from suprapontine, vagal, and nonvagal sources.

This retrospective study reviews the patterns of P. cepacia pulmonary infection in 75 of a total of 872 mainly adults with cystic fibrosis, registered here during the 4 years 1987-1990; 35 (47%) were female. During this period, 55 patients acquired P. cepacia and the annual incidence and prevalence rates have remained between 1.6 and 3.1%, and 4.1 and 5.9%, respectively. The mean age at the time of the first isolation of P. cepacia was 23 years, ranging 11-45 years. Sixty-eight percent of the initial isolates were multi-resistant (sensitive to fewer than three of 15 anti-pseudomonal agents). Prior to acquisition of P. cepacia, 28 (50.9%) patients already had severe lung disease and only three had normal lung function. Infection was transient in 39.1% of patients. Initial multi-resistance of P. cepacia to anti-pseudomonal agents was significantly associated with persistent infection. Clinical outcome was unaffected by age, sex and early intravenous antibiotic therapy but was significantly adversely affected by increasing severity of lung disease at the onset of P. cepacia infection and by initial multi-resistance, and persistence of the organism. Thus, all patients with normal or mild lung disease at the outset of infection have remained clinically stable, whereas, only six of 28 patients with severe disease remained stable, three of whom were transiently infected with P. cepacia. The prevalence of P. cepacia at the time of death fluctuated between 12.5% and 26.9% during the study period.

A total of 452 broiler chickens, naturally infected with Raillietina cesticillus, were allotted into six treatment groups. One group was fed unmedicated broiler ration (Group 1), and the other five groups were fed broiler ration containing fenbendazole at 180 ppm for 3 days (38.5 mg/kg body weight [BW]), 240 ppm for 3 days (50.9 mg/kg BW), 120 ppm for 6 days (52.2 mg/kg BW), 180 ppm for 6 days (79.9 mg/kg BW), or 240 ppm for 6 days (104.3 mg/kg BW). Fenbendazole was 100.0% efficacious against R. cesticillus when administered in the diet at 240 ppm for 6 days; 99.9% at 240 ppm for 3 days and at 180 ppm for 6 days; 99.5% at 120 ppm for 6 days; and 96.9% at 180 ppm for 3 days. Fenbendazole treatment had no adverse effect on weight gain or feed intake.

Ribotyping of 25 isolates of Pseudomonas cepacia taken from the sputum of 21 adults with cystic fibrosis (CF) who were registered at the Royal Brompton Hospital between 1987 and 1991, revealed that seven patients (33.3%) shared strains of a similar ribotype pattern with others, while 14 patients (63.7%) harboured strains unique to each individual. Constancy of sputum strain carriage was seen in two of three patients sampled twice over a 3-month period. Although no evidence for patient-to-patient transmission of P. cepacia within this group of patients was found, the fact that one third of CF patients shared strains of the same ribotype with others, suggests that nosocomial acquisition of this organism may have occurred.

Background: Pseudomonas aeruginosa infection is seldom eradicated in patients with cystic fibrosis despite intensive antipseudomonal treatment. Upper airway sites of infection may contribute to perpetuation of lower airways infection. This study was designed to find out which extrapulmonary sites are infected and whether the strains at these sites are identical to those in the lungs., Methods: Sputum and upper airway samples from 42 patients were cultured for P aeruginosa and stool samples from 20 patients were also tested. Nineteen isolates from sputum and extrapulmonary sites from four patients were genotyped with the pCM tox probe., Results: P aeruginosa was isolated from the sputum of 36 patients, 34 of whom had infection in the upper airways. Six of the 20 patients tested were positive for P aeruginosa in the stool. The nasopharynx was colonised in 30 patients, the oropharynx in 29, the middle meatus in 13, the external nares in six, and the inferior turbinate in four. Three of four patients tested had the same strain of P aeruginosa (a different one in each individual) in the sputum and the upper airways, and in two of the three the stool isolate was a different strain., Conclusion: Most adults with cystic fibrosis and P aeruginosa pulmonary infection have upper airway reservoirs of the organism and strains from these sites are identical to those in the lungs.

Two Asian patients admitted to hospital with acute severe asthma had been chewing betel nut immediately before the attacks. Arecoline, a cholinergic alkaloid, is a major constituent of Areca catechu (betel) nut and causes the euphoric effects. We sought an association between betel-nut chewing and bronchoconstriction in asthmatic patients. In vitro, arecoline caused dose-related contraction of human bronchial smooth-muscle strips, with one-tenth the potency of methacholine. In a double-blind challenge study, inhalation of arecoline caused bronchoconstriction in six of seven asthmatic patients and one of six healthy subjects; methacholine caused bronchoconstriction in all the asthmatic patients and in five controls. The geometric mean concentrations of arecoline and methacholine that caused 20% falls in the forced expiratory volume in 1 s (PC20 FEV1) in the asthmatic subjects were 5.2 mg/ml and 1.6 mg/ml, respectively. We then studied four Bengali asthmatic patients, regular users of betel nut, during a betel-nut challenge. Three showed no adverse effects, but one showed a 30% fall in FEV1 by 150 min after chewing; the effect was reproducible. In the UK, the rate of hospital admission for acute asthma is higher among Asians than among other groups in the population; betel-nut chewing may be one of several factors that affect asthma control and severity of attacks.

Seventy-four of 403 (18.4%) sputum isolates of Pseudomonas aeruginosa from 49 of 136 (36.0%) adults with cystic fibrosis (CF) were auxotrophic mutants. Two of 11 (18.2%) isolates of P. aeruginosa taken from patients with non-CF bronchiectasis were also auxotrophic. All 99 strains taken from non-bronchiectatic sources were prototrophic. Forty-six of 55 (83.6%) CF auxotrophs required one or more of 36 growth factors tested; the requirements for the remaining 9 isolates were not identified. Methionine was the sole factor required by 17 of 22 (77.3%) isolated which depended on a single factor. We conclude that auxotrophy is a feature of P. aeruginosa infection in cystic fibrosis.

Twelve courses of intravenous temocillin were given in combination with an intravenous aminoglycoside to five patients with cystic fibrosis (CF) for pulmonary exacerbations associated with Pseudomonas cepacia. All patients were infected concurrently with Pseudomonas aeruginosa in addition to P. cepacia. Improvement occurred after six of seven courses given to three patients in which temocillin was used as first-line therapy and following three of five courses given to two patients after failure of other antipseudomonal agents. All ten pre-treatment isolates of P. cepacia were resistant to aminoglycosides and eight were sensitive to temocillin. Clinical improvement was seen on both occasions in which the pre-treatment isolates were resistant to temocillin.

In 1986, 292 patients were admitted to a joint medical-surgical gastrointestinal unit with upper gastrointestinal haemorrhage. Fourteen patients died (4.8%) a mortality considerably lower than recorded in most series. The low mortality may result from the use of a specialized gastrointestinal unit to which all patients with upper gastrointestinal haemorrhage are admitted and managed with strict protocols for resuscitation, transfusion and surgery.

Although it is well established that patients with cervical spinal cord injury are prone to acute, marked, hypertensive episodes, i.e., autonomic hyperreflexia, the specific mechanisms mediating this sometimes-fatal phenomenon are not completely understood. In this report, we describe the preparation and characterization of a rat model of chronic cervical spinal cord injury and autonomic hyperreflexia. Adult male Sprague-Dawley rats were chronically instrumented with arterial, venous, and gastric catheters. Beginning the first day after a complete cervical spinal transection (CST) and continuing for 1 wk, acute hypertensive responses to a modest increase of urinary bladder pressure (0-20 mmHg) were studied. Mean arterial pressure increased 25.9 +/- 4.8 mmHg during bladder distension the first day after CST. This response was not significantly different 3, 5, and 7 days after CST (overall average = 18.0 +/- 2.3 mmHg). The pressor response to bladder distension was completely abolished by intravesical lidocaine and autonomic ganglionic blockade (atropine + hexamethonium). Responses to bladder distension were not observed after the administration of chloralose anesthesia. We conclude that after cervical spinal transection the rat exhibits autonomic hyperreflexia similar to that seen in humans with spinal injury. Furthermore, autonomic hyperreflexia is completely established within 24 h after CST in the rat. Finally, some spinal autonomic reflexes are suppressed by chloralose anesthesia in the rat.

We have developed a technique for growing endothelial monolayers on micropore filters. These monolayers demonstrate confluence by phase and electron microscopy and provide a functional barrier to passage of radiolabeled albumin. Neutrophils readily penetrate the monolayer in response to chemotaxin, whereas there is little movement in the absence of chemotaxin. This system offers unique advantages over available chemotaxis assays and may have wider applications in the study of endothelial function.

The binding characteristics of the cancer chemotherapeutic Cain's quinolinium 6-amino-1-ethyl-4-[p-[[p-[(1-ethylpyridinium-4-yl) amino] phenyl] carbamoyl]-anilino]-quinolinium dibromide (NSC 113089) to lipid extracts from rat kidney, liver, heart and skeletal muscle has been studied. Such binding is saturable with an apparent KD congruent to 1.6 microM. Drug binding to the lipid extracts is displaceable by spermine, spermidine, calcium ions and protons. Spermine is the best displacing agent, achieving half drug displacement from the lipid extracts at approximately 6.3 microM regardless of tissue. The inability of the displacing agents to displace all the NSC 113089 bound to the lipid extracts as well as differences in the amount of agent bound to as compared to amount of drug displaced from the lipid extracts indicate that a number of drug binding sites may be present in the lipid extracts. The similarities of drug binding by rat tissue lipids to similar lipids extracted from normal animal and tumor tissues is discussed.

It has recently been demonstrated that slowly adapting stretch receptors (SASRs) in the airways of the dog respond directly to nicotine (Federation Proc. 43: 318, 1984). The purpose of the present experiment was to investigate this chemical effect on an isolated stretch receptor. The crayfish muscle receptor organ was chosen, since crayfish muscle is reported to be insensitive to nicotine or acetylcholine and therefore permits the testing of any direct chemical effect of nicotine on the muscle stretch receptors. The tail was removed and pinned out in a tissue bath, and a stretch receptor organ was surgically isolated. Single-unit SASR extracellular nerve recordings were made while simultaneously measuring tension in the tail. Drugs were prepared in Van Harreveld's solution and administered into the bath kept at 18 degrees C. When resting muscle tension was essentially reduced to zero by cutting both ends of the receptor organ muscle, nicotine (0.07 microM) added to the bath increased receptor activity fourfold. This response was abolished by treatment with hexamethonium (690 microM). In a second group of animals in which the muscle was left intact, nicotine was shown to significantly increase receptor sensitivity to step changes in muscle tension. Once again hexamethonium blocked the response to nicotine. These results demonstrate that the sensitivity of mechanoreceptor can be altered by chemical interaction with nicotinic receptors, which dramatically alter sensory receptor activity.

Four wallaroos (Macropus robustus) from a central California zoo colony of 22 died within a three week period. Histopathologic findings in all four cases were suggestive of toxoplasmosis. Brain, lung and heart were the most frequently involved organs. Within 4 months of the last death sera from nine colony members were tested for antibodies against Toxoplasma gondii using the indirect hemagglutination test. All nine had serological titers ranging from 1:64 to 1:131,072.

An 8-year-old boy with severe recurrent bacterial infections was found to lack the cell-surface multimeric polypeptide complex defined by murine monoclonal antibody 60.3. This complex is expressed on the surface of all normal polymorphonuclear leucocytes (PMN), monocytes, and lymphocytes. Incubation of normal lymphocytes or PMN with antibody 60.3 produced functional abnormalities comparable with those observed in the patient's cells, suggesting that the polypeptide complex plays a significant part in several membrane-dependent leucocyte functions.