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Planar bismuth compounds exhibit tunable Lewis acidity and high catalytic activity for lactone polymerization.

Reactions of the diborane(4) B2(o‐tolyl)4 and monohydridoboranes are shown to give B(o‐tolyl)3 and (o‐tolyl)BR2 (R2=(C8H14) 3, cat 4, pin 5, (C6F5)2 6) as the major products. The corresponding reaction with BH3‐sources gives complex mixtures, resulting from hydride/aryl exchange, dimerization and borane elimination. This led to the isolation of the first tetra‐substituted pentaborane(9) HB[B(o‐tolyl)(μ‐H)]4 8. The reaction pathways are probed experimentally and by computations., The diborane(4) B2(o‐tolyl)4 reacts with species with B−H bonds giving a complex mixture arising from hydride/aryl exchange, dimerization and borane elimination. Use of BH3 sources led to the isolation of the first tetra‐substituted pentaborane(9) HB[B(o‐tolyl)(μ‐H)]4.

Diazaphospholenes are widely used as hydride transfer catalysts, however their use in radical reactions is a recently emerging area. Here, we show prior stoichiometric radical cyclizations of aryl iodides mediated by diazaphospholene hydrides are made catalytic by the combination of phenylsilane and alkali metal salts to regenerate the diazaphospholene hydride. The scope was expanded to include aryl bromides, which benefit from visible light irradiation. Twenty one substrates underwent cyclization, including a dearomative cyclization. Extension to six intermolecular radical hydroarylations with arenes, thiophenes, and a pyridine was also accomplished.

Tetraarylmethanes and adamantanes are important rigid covalent connectors that play a four-way scaffolding role in molecular and materials chemistry. We report the synthesis of a new tetravalent phosphaza-adamantane cage, (PNSiMe

Sisonke is a multicentre, open-label, single-arm phase 3B vaccine implementation study of healthcare workers (HCWs) in South Africa, with prospective surveillance for 2 years. The primary endpoint is the rate of severe COVID‑19, including hospitalisations and deaths. The Sisonke study enrolled and vaccinated participants nationally at potential vaccination roll-out sites between 17 February and 26 May 2021. After May 2021, additional HCWs were vaccinated as part of a sub-study at selected clinical research sites. We discuss 10 lessons learnt to strengthen national and global vaccination strategies:(i) consistently advocate for vaccination to reduce public hesitancy; (ii) an electronic vaccination data system (EVDS) is critical; (iii) facilitate access to a choice of vaccination sites, such as religious and community centres, schools, shopping malls and drive-through centres; (iv) let digitally literate people help elderly and marginalised people to register for vaccination; (v) develop clear 'how to' guides for vaccine storage, pharmacy staff and vaccinators; (vi) leverage instant messaging platforms, such as WhatsApp, for quick communication among staff at vaccination centres; (vii) safety is paramount - rapid health assessments are needed at vaccination centres to identify people at high risk of serious adverse events, including anaphylaxis or thrombosis with thrombocytopenia syndrome. Be transparent about adverse events and contextualise vaccination benefits, while acknowledging the small risks; (viii) provide real-time, responsive support to vaccinees post vaccination and implement an accessible national vaccine adverse events surveillance system; (ix) develop efficient systems to monitor and investigate COVID‑19 breakthrough infections; and (x) flexibility and teamwork are essential in vaccination centres across national, provincial and district levels and between public and private sectors.

ObjectivesTo define the incidence of clinically-detected COVID-19 in people with HIV (PWH) in the US and evaluate how racial and ethnic disparities, comorbidities, and HIV-related factors contribute to risk of COVID-19.DesignObservational study within the CFAR Network of Integrated Clinical Systems cohort in 7 cities during 2020.MethodsWe calculated cumulative incidence rates of COVID-19 diagnosis among PWH in routine care by key characteristics including race/ethnicity, current and lowest CD4 count, and geographic area. We evaluated risk factors for COVID-19 among PWH using relative risk regression models adjusted with disease risk scores.ResultsAmong 16,056 PWH in care, of whom 44.5% were Black, 12.5% were Hispanic, with a median age of 52 years (IQR 40-59), 18% had a current CD4 count < 350, including 7% < 200; 95.5% were on antiretroviral therapy, and 85.6% were virologically suppressed. Overall in 2020, 649 PWH were diagnosed with COVID-19 for a rate of 4.94 cases per 100 person-years. The cumulative incidence of COVID-19 was 2.4-fold and 1.7-fold higher in Hispanic and Black PWH respectively, than non-Hispanic White PWH. In adjusted analyses, factors associated with COVID-19 included female sex, Hispanic or Black identity, lowest historical CD4 count ConclusionsOur results suggest that the presence of structural racial inequities above and beyond medical comorbidities increased the risk of COVID-19 among PWHPWH with immune exhaustion as evidenced by lowest historical CD4 or current low CD4:CD8 ratio had greater risk of COVID-19.

Tetraarylmethanes and adamantanes are very rare examples of rigid, four-way, anionic connectors that play a scaffolding role in multiple areas of molecular and materials chemistry. We report the synthesis of a tetravalent phosphaza-adamantane cage, (PNSiMe3)4(NMe)6 (2), that shows unusually high ambient, thermal, and redox stability due to its unique geometry. It nevertheless participates in four-fold functionalization reactions on its periphery. The combination of a robust core but a reactive corona makes 2 a convenient inorganic scaffold upon which tetrahedral molecular and macromolecular chemistry can be reliably constructed. This potential is exemplified by the unprecedented synthesis of a tetracationic tetraphosphinimine (3) and the first porous all-P/N polyphosphazene network (5).

The synthesis and isolation of the first stable C-B-N-substituted borinium [MesBNiPr2][B(C6F5)4] (2) is described. Compound 2 was shown to react with isothiocyanate and carbodiimides, effecting B-C insertion to afford nitrilium (4) and borenium amidinate salts, respectively. The borinium cation [MesBNiPr2]+ (2+) was also generated from reactions of MesB(Cl)NiPr2 (1) and GaCl3, and used to prepare stable borenium amidinate salts (5-6), while the triflate borane MesB(OTf)NiPr2 (7) reacts with carbodiimide to give the bis(amidinate) boronium salt [MesC(NiPr)2B((NiPr)2C)NiPr2][OTf] (8).

The mechanochemical synthesis of tertiary and secondary alanes AlR3 (R = Np 1 or Mes 2; HAlR2 R = Np 3 or Mes 4) is described. These species are reacted with several α-diimines to give a series of aluminium-derived radicals of the form [(diimine)AlR2]˙ (6–11). EPR and several crystallographic studies are reported. These species are thought to form via hydro- or carboalumination and subsequent elimination reactions. This view is supported by the structural data for minor products C12H7(NHDipp)(NDipp)AliBu25 and C13H8(C(iBu)N(m-Xy)(NH(m-Xy)))AliBu212. In addition, the characterization of (C6F5)2B(OC(C6F5)OC12H8) indicates that such a carboboration pathway also provides access to related boron-derived radicals.

The reactions of CO2 with a series of phosphinoboranes, including R2PBpin (R=Ph, tBu; pin=pinacol), R2PBMes2 (R=Ph, tBu; Mes=2,4,6‐Me3‐C6H2), and R2PBcat (R=Ph, tBu, Mes; cat=catechol) are described. Although R2PBpin and R2PBMes2 afford products of the form R2PCO2Bpin (R=Ph 1, tBu 4) and R2PCO2BMes2 (R=Ph 2, tBu 3), respectively, R2PBcat lead to further reaction affording the diphospha‐ureas, (R2P)2CO (R=Ph 5, tBu 6, Mes 7), together with O(Bcat)2. Computational studies provide insight into the mechanism, revealing an intermediate derived from double phosphinoboration of CO2., From CO2 to urea: The reactions of CO2 with a series of phosphinoboranes afford compounds of the form R2PCO2BR′2 and diphospha‐ureas, (R2P)2CO. Computational data reveals a mechanism, involving a double phosphinoboration of CO2.

Reaction of dihydrogen and the borinium cation salt [Mes2B][B(C6F5)4] gave an arene-stabilized mesityl-borenium cation, which isotopically scrambles HD. Similarly, reaction with triethylsilane gave the diboranium cation [MesB(μ-H)2(μ-Mes)BMes]+ featuring three bridge-bonds between two boron centers. Reaction of same (Mes2BH)2 with Bronsted acid also afforded the same diboranium whereas the corresponding reaction with (MesBH2)2 yielded the triboron cation [H2B(μ-H)(μ-Mes)B(μ-Mes)(μ-H)BH2]+.

The synthesis and isolation of the first stable C-B-N-substituted borinium [MesBNiPr2][B(C6F5)4] (2) is described. Compound 2 was shown to react with isothiocyanate and carbodiimides, effecting B-C insertion to afford nitrilium (4) and borenium amidinate salts, respectively. The borinium cation [MesBNiPr2]+ (2+) was also generated from reactions of MesB(Cl)NiPr2 (1) and GaCl3, and used to prepare stable borenium amidinate salts (5-6), while the triflate borane MesB(OTf)NiPr2 (7) reacts with carbodiimide to give the bis(amidinate) boronium salt [MesC(NiPr)2B((NiPr)2C)NiPr2][OTf] (8).

The mechanochemical synthesis of tertiary and secondary alanes AlR3 (R = Np 1 or Mes 2; HAlR2 R = Np 3 or Mes 4) is described. These species are reacted with several α-diimines to give a series of aluminium-derived radicals of the form [(diimine)AlR2]˙ (6-11). EPR and several crystallographic studies are reported. These species are thought to form via hydro- or carboalumination and subsequent elimination reactions. This view is supported by the structural data for minor products C12H7(NHDipp)(NDipp)AliBu25 and C13H8(C(iBu)[double bond, length as m-dash]N(m-Xy)(NH(m-Xy)))AliBu212. In addition, the characterization of (C6F5)2B(OC(C6F5)OC12H8) indicates that such a carboboration pathway also provides access to related boron-derived radicals.

The borinium cation [(iPr2N)2B]+ (1+) is shown to react with PhCCH, PhCN, Ph2CO, and Ph2CN2 to effect a net hydroboration, affording borenium complexes of the form [(iPr2N)B(iPrNCMe2)(L)][B(C6F5)4] (L = CHCHPh 2, NCHPh 3, OCHPh24, NHNCPh25). The nature and reaction of 1+ with PhCCH was probed computationally and the reduction of these unsaturates is shown to occur via hydride transfer from an isopropyl group to the alkyne, thus effecting hydroboration without a B–H bond.

The stoichiometric reactions of the alkylfluorides 1-fluoroadamantane (Ad-F), fluorocyclohexane (Cy-F), 1-fluoropentane (Pent-F) and benzyl fluorides with secondary boranes pinacolborane (HBpin), catecholborane (HBcat), 9-borabicyclo(3.3.1)nonane (9-BBN) and Piers' borane (HB(C6 F5 )2 ) are described. While HBcat, 9-BBN and HB(C6 F5 )2 reduce Ad-F to Ad-H, the latter borane was shown to react with secondary and primary fluoroalkanes, affording C-F borylation, while benzyl fluorides undergo Friedel-Crafts chemistry.

Metal-free hydroarylation of alkynes with N-substituted pyrroles is shown to be most efficiently mediated by B(C6F5)3 to yield 12 variants of dipyrrole-alkanes, a mono-hydroarylation product and a tetrahydroarylation product of a bis-alkyne. These products were generally obtained in good to excellent yields (up to 95%). Control experiments suggest a mechanism involving FLP addition of the borane and pyrrole to alkyne.

A rigid naphthalenediamine framework has been used to prepare antimony hydrides that feature LUMO shapes and energies strikingly similar to those of secondary boranes. Exploiting this feature, we report the first example of uncatalyzed hydrostibination of robust CC double and triple bonds, as well as C=O, and N=N bonds as a new elementary hydrometallation reaction analogous to hydroboration. In the alkyne case, a Z-olefin is formed and in the reaction with N=N bonds, hydrostibination and hydrogenation are both observed. These results endorse the notion of a diagonal relationship between the lightest p-block element and the heaviest Group 15 elements and may lead to the realization of novel reaction chemistry.

Friedel-Crafts benzylation of arenes with benzyl fluorides using 9-borabicyclo[3.3.l]nonane (9-BBN) as a mediator has been developed. This provides a simple and cheap route to the activation of C-F bonds to synthesize 1,1-diarylmethanes in good to excellent yields (up to 98%) under mild conditions. Functional group tolerance and the mechanism are considered.

Reaction of dihydrogen and the borinium cation salt [Mes

Redox active, or non-innocent, ligands containing O or N heteroatoms are frequently used in transition metal complexes, imparting unique catalytic properties, but have seen comparatively limited use in the chemistry of group 13 elements. In this article we report the frustrated Lewis pair (FLP) hydrogenation and hydroboration of an N-aryl-phenanthrene-o-iminoquinone and two N,N′-diaryl-phenanthrene α-diimines. These reactions exploit B(C6F5)3/H2, HB(C6F5)2 and H2BC6F5·SMe2 to give a series of derivatives including 1,3,2-oxaza- and diazaboroles and borocyclic radicals. The reaction pathways leading to these products are outlined and supported by DFT-calculations and experimental insight. The modular and unusual synthetic strategies described herein give access to new boroles as well as air-stable boron-containing radicals, thus extending the chemistry of redox active ligands in main group systems.

A series of phosphinophosphonium cations ([R2PPMe3]+; R = Me, Et, iPr, tBu, Cy, Ph and NiPr2) have been prepared and examined by collision-induced dissociation (CID) to determine the fragmentation pathways accessible to these prototypical catena-phosphorus cations in the gas-phase. Experimental evidence for fission of P–P and P–E (E = P, C) bonds, and β-hydride elimination has been obtained. Comparison of appearance potentials for the P–P bond dissociation fragments [R2P]+ (P–P heterolysis) and [PMe3]+˙ (P–P homolysis) shows that heterolytic P–P cleavage is more sensitive than P–P homolysis towards changes in substitution at the trivalent phosphorus center. The facility of β-hydride elimination increases with the steric bulk of R in [R2PPMe3]+. A density functional theory (DFT) study modelling these observed processes in gas-phase, counterion- and solvent-free conditions, to mimic the mass spectrometric environment, was performed for derivatives of [R2PPMe3]+ (R = Me, Et, iPr, tBu, Ph and NiPr2), showing good agreement with experimental trends. The unusual observation of both homolytic and heterolytic cleavage pathways for the P–P and P–C bonds reveals new insight into the fundamental aspects of bonding in monocations and undermines the use of simplistic bonding models.

The position of the spray-head, the solvent, and a variety of additional instrumental parameters were independently adjusted during electrospray ionization mass spectrometric (ESI-MS) analysis of an equimolar mixture of two different ions. These parameters were found to have drastic effects on the distribution of signal intensity from one ion to another, and therefore the resulting usefulness of acquired spectra. The analytes studied were bis(triphenylphosphine)iminium (PPN) chloride and tetramethylammonium (TMA) chloride, two chemically distinct ions. The use of these two ions in a test solution yielded information regarding ESI probe spatial effects for two very different analytes, while probing the issue of sampling efficiency. Each experimental parameter was individually adjusted prior to rastering the spray head across the operational plane in order to observe how adjustment to a particular parameter affects analyte signal in relation to the distance from the MS aperture. Following acquisition, the intensities of both ions were plotted as ion contour maps demonstrating the intensity change with respect to capillary position in relation to the mass spectrometer aperture. The sharp contrast in ion intensity, and even differential ion activity, with relatively minor instrument changes (such as temperature programming, gas flow rates and solvent choice) clearly demonstrates the importance of finding the “sweet spot” for the ESI spray head, especially when signal intensity and a quality analysis are key.

Three series of phosphine chalcogenide complexes of the antimony(III) halides SbX3 (X = F, Cl, Br, or I) have been synthesized and characterized by spectroscopic and crystallographic methods. Complexes of the generic formulae (Cy3PO)SbX3 (X = F (1a), Cl (1b), or Br (1c)), (Cy3PO)2SbX3 (X = F (2a), Cl (2b), or Br (2c)), and (Cy3PS)SbX3 (X = Cl (3b), Br (3c), or I (3d)) were synthesized via the treatment of solutions of SbX3 with OPCy3 and SPCy3, respectively. Derivatives of (Cy3PO)SbX3 were characterized by single crystal X-ray diffraction for 1a and 1b and crystallize as dimers through symmetry related intermolecular Sb–X interactions, providing the first structurally characterized examples of this class of complex. Derivatives of (Cy3PS)SbX3 (3b–3c) adopt analogous dimeric structures in the solid state. The solid-state structure of (Cy3PO)2SbCl3 (2b) is consistent with the previously reported structures of bis-phosphine oxide complexes of antimony(III), with a square pyramidal Sb center and cis-configured OPCy3 ligands. The phosphine chalcogenide complexes of SbX3 display configurations that are consistent with the perceived trans-labilizing properties of the ligands/substituents.

Reactions of [Cp*2 Fe] with the Lewis acid [Zn(C6 F5 )2 ] in the presence of [(PhC(S)S)2 ], 9,10-phenanthrenedione or 4,5-pyrenedione yield the salt [Cp*2 Fe][(PhC(S)S)Zn(C6 F5 )2 ] 1, [Cp*2 Fe][((C14 H8 O2 )Zn(C6 F5 )2 )⋅] 4, and [Cp*2 Fe][((C16 H8 O2 )Zn(C6 F5 )2 )⋅] 5, respectively. The latter two species represent the first examples of isolable zinc-containing radical anions. While [(PhC(S)S)2 ] binds weakly to [Zn(C6 F5 )2 ], the diones afford the isolable adducts [(C14 H8 O2 )Zn(C6 F5 )2 ] 2 and [(C16 H8 O2 )Zn(C6 F5 )2 ] 3. Cyclic voltammetry and computational studies support the view that 4 and 5 are formed via single electron transfer (SET) to the donor-acceptor adducts, 2 and 3, respectively. Subsequent treatment of 4 and 5 with [NC5 H4 NMe2 ] affords [Zn(C6 F5 )2 (NC5 H4 NMe2 )2 ] with liberation of the dione, and regeneration of [Cp*2 Fe].

BACKGROUND: Acid gastroesophageal reflux is a common problem in non-cystic fibrosis bronchiectasis and COPD. Invasive methods are used to diagnose gastroesophageal reflux, but the ability to detect pulmonary microaspiration of gastric contents using this method is unclear. A noninvasive option to detect pulmonary microaspiration is to measure pepsin in exhaled breath condensate (EBC), but this has not been related to esophageal pH monitoring in these lung conditions. This study aimed to measure pepsin concentrations and pH in EBC and to determine the relationship to gastroesophageal reflux in bronchiectasis or COPD. METHODS: Subjects with bronchiectasis ( n = 10) or COPD ( n = 10) and control subjects ( n = 10) completed 24-h esophageal pH monitoring for detection of acid gastroesophageal reflux, measuring the percentage of reflux time in the proximal esophagus and the DeMeester score (DMS). Concurrently, 3 samples of EBC were collected from each subject, and pH was measured and pepsin concentrations were analyzed by enzyme-linked immunosorbent assay. RESULTS: EBC pepsin was detected in subjects with bronchiectasis (44%) or COPD (56%) and in control subjects (10%). A diagnosis of gastroesophageal reflux was not associated with a higher concentration of EBC pepsin in bronchiectasis ( P = .21) or COPD ( P = .11). EBC pepsin concentration did not correlate with DMS (rs = 0.36) or proximal reflux index (rs = 0.25) in subjects with bronchiectasis or with DMS (rs = 0.28) or proximal reflux index (rs = 0.21) in patients with COPD. EBC and sputum pepsin concentrations were moderately correlated in bronchiectasis (rs = 0.56) and in COPD (rs = 0.43). CONCLUSIONS: Pepsin is detectable in EBC samples in bronchiectasis and COPD. Although no association was found between pepsin concentrations and a diagnosis of gastroesophageal reflux, a moderate relationship between sputum and EBC pepsin concentrations suggests that EBC pepsin may be a useful noninvasive marker of pulmonary microaspiration.

Background and objective The aims of this observational study were (i) to examine the prevalence of symptomatic and clinically silent proximal and distal gastro-oesophageal reflux (GOR) in adults with chronic obstructive pulmonary disease (COPD) or bronchiectasis, (ii) the presence of gastric aspiration, and (iii) to explore the possible clinical significance of this comorbidity in these conditions. Methods Twenty-seven participants with COPD, 27 with bronchiectasis and 17 control subjects completed reflux symptom evaluation and dual-channel 24 h oesophageal pH monitoring. In those with lung disease, pepsin levels in sputum samples were measured using enzyme-linked immunosorbent assay, with disease severity (lung function and high-resolution computed tomography) also measured. Results The prevalence of GOR in COPD was 37%, in bronchiectasis was 40% and in control subjects was 18% (P = 0.005). Of those diagnosed with GOR, clinically silent reflux was detected in 20% of participants with COPD and 42% with bronchiectasis. While pepsin was found in 33% of COPD and 26% of bronchiectasis participants, the presence of pepsin in sputum was not related to a diagnosis of GOR based on oesophageal pH monitoring in either condition. Neither a diagnosis of GOR nor the presence of pepsin was associated with increased severity of lung disease in COPD or bronchiectasis. Conclusions The prevalence of GOR in COPD or bronchiectasis is twice that of the control population, and the diagnosis could not be based on symptoms alone. Pepsin was detected in sputum in COPD and bronchiectasis, suggesting a possible role of pulmonary aspiration, which requires further exploration.

Asthma is characterized by chronic airways inflammation, airway wall remodeling, and airway hyperresponsiveness (AHR). An increase in airway smooth muscle has been proposed to explain a major part of AHR in asthma. We have used unbiased stereological methods to determine whether airway smooth muscle hyperplasia and AHR occurred in sensitized, antigen-challenged Brown Norway (BN) rats. Ovalbumin (OA)-sensitized BN rats chronically exposed to OA aerosol displayed airway inflammation and a modest level of AHR to intravenously administered ACh 24 h after the last antigen challenge. However, these animals did not show an increase in smooth muscle cell (SMC) number in the left main bronchus, suggesting that short-lived inflammatory mechanisms caused the acute AHR. In contrast, 7 days after the last aerosol challenge, there was a modest increase in SMC number, but no AHR to ACh. Addition of FCS to the chronic OA challenge protocol had no effect on the degree of inflammation but resulted in a marked increase in both SMC number and a persistent (7-day) AHR. These results raise the possibility that increases in airway SMC number rather than, or in addition to, chronic inflammation contribute to the persistent AHR detected in this model.

Older people may struggle to adhere to complex drug regimens, but are commonly prescribed multiple medications. Geriatricians require practical knowledge of strategies and aids that maximise patients' ability to implement their treatment.

Staphylococcus aureus (S. aureus) is responsible for a small proportion of acute respiratory infections in children. Nevertheless a high index of suspicion is required because of the potential for rapid progression, the need for antibiotics different to those routinely administered in the treatment of pneumonia, and the high incidence of complications. There are few data from developing countries. The objective of this retrospective review was to document the natural history of primary staphylococcal pneumonia at Red Cross Childrens' Hospital in Cape Town over a 7-year period (1989-1995). Staphylococcal pneumonia was defined as acute pneumonia with microbiological evidence of S. aureus or with characteristic radiological features. One hundred patients were identified. The median age was 5 months, 78 patients being below one year of age. Cough and fever were present in almost all patients at the time of presentation. Tachypnoea, recession, dullness, and crepitations were commonly elicited signs. Initial chest radiographs revealed empyema, pleural effusion, or pyopneumothorax in 67 patients. A further 26 patients developed such changes on subsequent chest radiographs. Pneumatocoeles were identified in 37 patients--most of these were only noted on radiographs taken some days after admission. Microbiological confirmation was obtained in 92 cases. S. aureus was isolated in 23/98 blood cultures, 62/67 pleural aspirates, and from tracheal aspirates in 16 cases. Intercostal drains were inserted in 67 cases and 20 children underwent thoracotomy. The case fatality rate was 7 per cent. This study shows that primary staphylococcal pneumonia is chiefly a disease of infants. Symptoms and signs were similar as for other forms of acute pneumonia, although in the majority of cases chest radiographs taken at the time of admission suggested the diagnosis. Treatment with antibiotics and drainage of empyema resulted in a good outcome in the majority of cases.

BACKGROUND: Bronchial hyperresponsiveness (BHR) to methacholine has been reported to occur in most lung transplant recipients. BHR to physical stimuli such as exercise and non-isotonic aerosols has not been as extensively studied in this subject population. This report aims to assess the presence and degree of BHR to methacholine and hypertonic saline in stable lung transplant recipients and to relate it to the presence of airway inflammation. METHODS: Ten patients undergoing bilateral sequential lung transplantation and six heart-lung transplant recipients, all with stable lung function, were recruited 66- 1167 days following transplantation. Subjects underwent a methacholine challenge and bronchoscopy for sampling of bronchoalveolar lavage fluid, transbronchial and endobronchial biopsy tissues. Hypertonic saline challenge was performed six days later. RESULTS: Nine of the 16 transplant recipients had positive methacholine challenges (geometric mean PD20 0.18 mg, interquartile range 0.058-0.509) and three of these subjects also had positive hypertonic saline challenges (PD15 = 2.3, 33.0, and 51.5 ml). No clear relationship was found between BHR to either methacholine or hypertonic saline and levels of mast cells, eosinophils or lymphocytes in samples of biopsy tissue or lavage fluid. CONCLUSIONS: Most of the lung transplant recipients studied were responsive to methacholine and unresponsive to hypertonic saline. BHR was not clearly related to airway inflammation, suggesting an alternative mechanism for BHR following lung transplantation from that usually assumed in asthma.

The aims of this observational study were (i) to examine the prevalence of symptomatic and clinically silent proximal and distal gastro-oesophageal reflux (GOR) in adults with chronic obstructive pulmonary disease (COPD) or bronchiectasis, (ii) the presence of gastric aspiration, and (iii) to explore the possible clinical significance of this comorbidity in these conditions.Twenty-seven participants with COPD, 27 with bronchiectasis and 17 control subjects completed reflux symptom evaluation and dual-channel 24 h oesophageal pH monitoring. In those with lung disease, pepsin levels in sputum samples were measured using enzyme-linked immunosorbent assay, with disease severity (lung function and high-resolution computed tomography) also measured.The prevalence of GOR in COPD was 37%, in bronchiectasis was 40% and in control subjects was 18% (P = 0.005). Of those diagnosed with GOR, clinically silent reflux was detected in 20% of participants with COPD and 42% with bronchiectasis. While pepsin was found in 33% of COPD and 26% of bronchiectasis participants, the presence of pepsin in sputum was not related to a diagnosis of GOR based on oesophageal pH monitoring in either condition. Neither a diagnosis of GOR nor the presence of pepsin was associated with increased severity of lung disease in COPD or bronchiectasis.The prevalence of GOR in COPD or bronchiectasis is twice that of the control population, and the diagnosis could not be based on symptoms alone. Pepsin was detected in sputum in COPD and bronchiectasis, suggesting a possible role of pulmonary aspiration, which requires further exploration.

Airway mesenchymal cells, such as myofibroblasts and airway smooth muscle cells, contribute to inflammation, airway remodelling and hyperresponsiveness in asthma by excessive proliferation and inflammatory mediator production. Using endobronchial biopsies obtained from both nonasthmatic and asthmatic subjects, in situ proliferation was assessed by immunostaining for cyclin D1. The number of immunoreactive cells increased with asthma severity and was restricted to the epithelium and subepithelial connective tissue. Despite increases in smooth muscle area, cyclin D1 was not detected in cells in intact muscle bundles. Biopsy-derived cell cultures were characterised as predominantly myofibroblasts, and were assessed to determine whether proliferation and cytokine production varied with asthma status. Cell enumeration showed that basal proliferation was similar in cells from nonasthmatics and asthmatics, and mitogenic responses to fibroblast growth factor-2, thrombin or serum were either reduced or unchanged in cells from asthmatics. Interleukin (IL)-1-dependent granulocyte-macrophage colony-stimulating factor and IL-8 release was increased in cell supernatants from asthmatics. Thus, increased rates of cellular proliferation identified in situ in the asthmatic airway occurred outside the expanded smooth muscle compartment. Although reduced proliferative responses were observed in cultured myofibroblasts from asthmatics, the increased cytokine production by these cells suggests that this contributes to and may perpetuate ongoing inflammation in asthma.

The expression of a primary initiator of tumor angiogenic responses, vascular endothelial growth factor (VEGF), may be induced by nitric oxide (NO) in carcinoma cells. However, the net impact of NO on carcinogenesis remains unclear, because manipulation of NO levels has been shown to either stimulate or inhibit tumor growth. We have investigated the relationship between inducible NO synthase (NOS II), VEGF expression, and growth of B16-F1 melanoma over 14 days in wild-type (NOS II+/+) mice and in those in which the gene for NOS II has been deleted (NOS II-/-). B16-F1 tumor growth was measured as wet weight of the excised tissue. Tumor NOS II and VEGF localization were evaluated by immunohistochemistry, and VEGF mRNA levels were measured by Northern blot analysis. In NOS II+/+ mice inoculated with B16-F1 melanoma cells, macroscopic tumors were always observed at 14 days; however, 22% of NOS II-/- mice had no detectable tumor mass. Immunoreactive NOS II was detected in tumor cells of tumors grown in NOS II+/+ but not in NOS II-/- mice. Although immunoreactive VEGF was detected in the granules of tumor-associated mast cells from both NOS II+/+ and NOS II-/- mice, VEGF mRNA expression in tumors from NOS II-/- was half that in NOS II+/+ mice. Neither NOS II inhibition, exogenous NO, nor peroxynitrite influenced DNA synthesis in culture B16-F1 melanoma cells. The NO donor did not alter either VEGF mRNA levels or degranulation in cultures of the mast cell line RBL-2H3, but peroxynitrite increased both VEGF mRNA expression and degranulation. We conclude that host expression of NOS II contributes to induction of NOS II in the tumor and to melanoma growth in vivo, possibly by regulating the amount and availability of VEGF.

The objective of the study was to assess what differences exist between individuals who are dependent on opiates and benzodiazepines and compare to those who are dependent on opiates. A questionnaire was compiled and administered to patients who had been consecutively admitted to an inpatient drug treatment unit. The prevalence of benzodiazepine dependency was 54 per cent [n = 34]. Patients dependent on benzodiazepines and opiates were significantly older, had been admitted for methadone stabilisation and were more likely to have been prescribed a methadone maintenance programme prior to admission. They had used heroin longer, benzodiazepines more frequently, at larger doses for a longer duration of time and tended to use more drugs in general. They were found to be more psychologically vulnerable than those not dependent on benzodiazepines as they were significantly more likely to have described a past experience of depression and a past episode of deliberate self harm.

The Belfast Breast Screening Programme serves a population of approximately 25,000 patients. We aimed to analyse radiological and pathological trends between screen-detected and interval breast cancers, and determine our screening lesion miss rate.

An open crossover study was carried out in 6 normal volunteers to measure faecal blood loss caused by tilcotil (Ro 12-0068), a new anti-inflammatory drug, compared with that caused by enteric-coated aspirin. Subjects were allocated at random to receive either single doses of 20 mg tilcotil daily or 900 mg aspirin 4-times daily, reducing to a maximum tolerated dose, over a period of 2 weeks before being crossed over to the alternative medication for a further 2 weeks. Faecal specimens passed during 4 consecutive days in a run-in-period of 1 week, in each treatment period, and in the 2 weeks after the finish of drug therapy were analyzed for blood using a radioactive labelling method. The results showed that faecal blood loss was lower and it did not produce any haematological or biochemical abnormalities or any increase in urinary N-acetyl-beta-glucosaminidase activity indicative of renal damage. It is suggested that the method described provides a simple and reliable means of comparing faecal blood loss with different anti-inflammatory drugs.

Ten psychotic and 10 normal children, paired for age and sex, were compared for respiratory sinus arrhythmia differences under conditions of spontaneous and 5, 10, and 15 sec interval breathing. Cardiac rate and respiratory changes were simultaneously recorded. Parameters of degree of change and timing for each respiratory-cardiac cycle and its associated changes in heart rate were measured and compared statistically. Results show significant differences between psychotics and normal controls as follows: 1 The psychotics did not sustain the acceleratory phase of the cardiac cycle as did the controls. 2 The lag intervals (interval between onset of inspiration and onset of cardiac acceleration, interval between onset of expiration and onset of cardiac deceleration) were more consistent for the normal controls than for the psychotics. 3 At maximum respiratory depths the psychotics no longer demonstrated a direct relationship between depth of respiration and degree of cardiac rate change as did the controls. We conclude that there is a different or less well-coordinated combination of operative forces in the sinus arrhythmia mechanism of the psychotics as compared to the controls.

This study was based on two assumptions. The first is that the hierarchy of motives is learned. “Hierarchy of Motives” is a concept denoting those largely unconscious systems which enable the selection of alternative behavior. The second assumption is that learning the hierarchy of motives requires an aptitude which varies widely in the population. The working hypotheses were: (1) presently measured aptitudes and environmental influences are insufficient to account for the observed variance in performance, and (2) that a discriminative learning task which requires a differential physiological response of the autonomic nervous system can measure the aptitude for learning social motives. Sixty-three Negro subjects were classified into two relatively higher and lower motivation groups based on their history of employment (from interview data) or on vocational training school teachers’ ratings. They were subjected to a single session of discriminative classical autonomic conditioning involving tones and pain, and given intelligence, personality, and level of aspiration tests. It was found that 18 variables, each individually statistically significant, when combined by means of a discriminant function analysis, classified 92% of the subjects into their correct criterion (motivation) groups. It was concluded that the working hypotheses were strongly confirmed and that the two assumptions were supported. Implications of these findings if confirmed by replication are (1) that a fundamental human aptitude for learning motives exists and can be measured; (2) having measures of the aptitude enables exploration of its relationships to other aptitudes and characteristics; (3) knowledge of these relationships will make it possible (a) to more accurately predict human performance involving motivation, (b) to more appropriately select and place personnel, (c) to devise more practicable training procedures for developing socially desirable motives, and (d) to provide persons unprepared for self-support with more appropriate vocational training.