Adverse events among persons with TB using in-person vs. electronic directly observed therapy.

BACKGROUND: We evaluated patient safety within a randomized crossover trial comparing electronic directly observed therapy (eDOT) to in-person DOT (ipDOT) in persons undergoing TB treatment in New York City, NY, USA.METHODS: Participant symptoms, symptom severity, and clinical management were documented. We assessed adverse event reports (AERs) by DOT method during the two-period crossover. Using Cox proportional-hazards mixed-effects models, we estimated the adjusted hazard ratio (aHR) of participants reporting an adverse event (AE) vs. not reporting an AE.RESULTS: Of 211 participants, 57 (27.0%) reported AEs during the two-period crossover; of these, 54.4% (31/57) were reported while using eDOT vs. 45.6% (26/57) while using ipDOT. Controlling for study group and period, the aHR for eDOT vs. ipDOT was 0.98 (95% CI 0.49-1.93). Although statistically not significant, the wide confidence intervals suggest that a significant association cannot be entirely ruled out. Gastrointestinal symptoms were most frequently reported (42.1%, 24/57). AER types and severity did not differ significantly by DOT method. Days from symptom onset to medical attention was similar across DOT methods (median: 1.0 day, IQR 0.0-2.0). No participants switched DOT methods due to AERs or monitoring concerns.CONCLUSION: Further evaluation to ascertain whether AERs differ when patients use eDOT vs. ipDOT is warranted.

Challenges associated with electronic and in-person directly observed therapy during a randomized trial.

BACKGROUND: Electronic directly observed therapy (eDOT) has been proposed as an alternative to traditional in-person DOT (ipDOT) for monitoring TB treatment adherence. Information about the comparative performance and implementation of eDOT is limited.METHODS: The frequency of challenges during DOT, challenge type, and effect on medication observation were documented by DOT method during a crossover, noninferiority randomized controlled trial. A logistic mixed-effects model that adjusted for the study design was used to estimate the percentage of successfully observed doses when challenges occurred.RESULTS: A total of 20,097 medication doses were scheduled for observation with either eDOT (15,405/20,097; 76.7%) or ipDOT (4,692/20,097; 23.3%) for 213 study participants. In total, one or more challenges occurred during 17.3% (2,672/15,405) of eDOT sessions and 15.6% (730/4,692) of ipDOT sessions. Among 4,374 documented challenges, 27.3% (n = 1,192) were characterized as technical, 65.9% (n = 2,881) were patient-related, and 6.9% (n = 301) were program-related. Estimated from the logistic model (n = 6,782 doses, 173 participants), the adjusted percentage of doses successfully observed during problematic sessions was 21.7% (95% CI 11.2-37.8) for eDOT and 4.2% (95% CI 1.1-14.7) for ipDOT.CONCLUSION: Compared to ipDOT, challenges were encountered in a slightly higher percentage of eDOT sessions but were more often resolved to enable successful dose observation during problematic sessions.

Challenges in LTBI care in the United States identified using a nationwide TB medical consultation database.

BACKGROUND: Identifying and treating individuals with latent TB infection (LTBI) represents a critical and challenging component of national TB elimination. Medical consultations by the Centers for Disease Control and Prevention (CDC) funded TB Centers of Excellence (COEs) are an important resource for healthcare professionals (HCPs) caring for individuals with LTBI. This study aimed to identify the most common clinical concerns regarding LTBI care and to describe epidemiologic and clinical features of patients discussed in these consultations. METHODS: This mixed-methods study randomly sampled 125 consultation inquiries related to LTBI from the COEs' medical consultation database in 2018. Text from consultation records were reviewed and coded to identify reasons for the inquiries and common epidemiologic and clinical patient characteristics. RESULTS: The most common topics of inquiry for consultation included accurate LTBI diagnosis (36%), management of LTBI treatment-related issues (22%), and choice of appropriate LTBI treatment regimen (17%). Patients for whom consultations were requested commonly had another medical condition (34%), were non-U.S. born (31%), were children (25%), and had a history of travel to TB-endemic areas (18%). CONCLUSION: Our findings emphasize the challenge of managing patients with either suspected or confirmed LTBI, highlighting the need for ongoing medical consultation support for nuanced clinical and epidemiologic scenarios.

CONTEXTE: L'identification et le traitement des personnes atteintes d'infection tuberculeuse latente (LTBI) sont des composantes essentielles et difficiles de la stratégie nationale d'élimination de la TB. Les consultations médicales des TB Centers of Excellence (COE), financés par les Centres pour le contrôle et la prévention des maladies (CDC), sont d'importantes ressources pour les professionnels de santé qui prennent en charge les personnes atteintes de LTBI. Cette étude avait pour objectif d'identifier les problèmes cliniques les plus fréquents en matière de prise en charge de la LTBI, et de décrire les caractéristiques épidémiologiques et cliniques des patients évoquées lors de ces consultations. MÉTHODES: Cette étude à méthodes mixtes a sélectionné de manière aléatoire 125 demandes de consultations relatives à la LTBI à partir de la base de données des consultations médicales du COE en 2018. Les notes des dossiers de consultation ont été revues et codées pour identifier les raisons des demandes, ainsi que les caractéristiques cliniques et épidémiologiques fréquentes des patients. RÉSULTATS: Les raisons les plus fréquentes de demandes de consultation étaient diagnostic précis de LTBI (36%), prise en charge des problèmes liés au traitement de la LTBI (22%) et choix d'un schéma thérapeutique approprié de la LTBI (17%). Les patients pour lesquels des consultations étaient demandées avaient fréquemment une autre pathologie (34%), n'étaient pas nés aux États-Unis (31%), étaient des enfants (25%) et avaient des antécédents de voyage dans des zones où la TB est endémique (18%). CONCLUSION: Nos résultats mettent l'accent sur les défis de la prise en charge des patients avec une LTBI présumée ou confirmée, soulignant le besoin d'aide continue aux consultations médicales pour des scénarios épidémiologiques et cliniques nuancés.

Physical therapy affects endothelial function in lymphedema patients.

Lymphedema arises due to a malfunction of the lymphatic system and can lead to massive tissue swelling. Complete decongestive therapy (CDT), consisting of manual lymphatic drainage (MLD) and compression bandaging, is aimed at mobilizing fluid and reducing volume in affected extremities. Lymphatic dysfunction has previously been associated with chronic inflammation processes. We investigated plasma ADMA as an indicator of endothelial function/inflammation before-, during- and after-CDT. Also assessed were vascular function parameters such as carotid-femoral pulse wave velocity (PWVcf), flow-mediated dilata-tion (FMD) and retinal microvasculature analysis. 13 patients (3 males and 10 females, 57 ± 8 years old (mean ± SD), 167.2 ± 8.3 cm height, 91.0 ± 23.5 kg weight), with lower limb lymphedema were included. Vascular function parameters were assessed on day 1, 2, 7, 14 and 21 of CDT, pre- and post-MLD. ADMA was significantly lower post-MLD (p=0.0064) and tended to reduce over three weeks of therapy (p=0.0506). PWVcf weakly correlated with FMD (r=0.361, p=0.010). PWVcf, FMD and retinal microvasculature analysis did not show changes due to physical therapy. The novel results from this study indicate that lymphedema does not affect endothelial func-tion and lymphedema patients may therefore not have a higher risk of cardiovas-cular diseases. Our results further suggest that manual lymphatic drainage with or without full CDT could have potentially beneficial effects on endothelial function in lymphedema patients (by reducing ADMA levels), which has not been reported previously.

Tryptic digestion of human serum for proteomic mass spectrometry automated by centrifugal microfluidics.

Mass spectrometry has become an important analytical tool for protein research studies to identify, characterise and quantify proteins with unmatched sensitivity in a highly parallel manner. When transferred into clinical routine, the cumbersome and error-prone sample preparation workflows present a major bottleneck. In this work, we demonstrate tryptic digestion of human serum that is fully automated by centrifugal microfluidics. The automated workflow comprises denaturation, digestion and acidification. The input sample volume is 1.3 µl only. A triplicate of human serum was digested with the developed microfluidic chip as well as with a manual reference workflow on three consecutive days to assess the performance of our system. After desalting and liquid chromatography tandem mass spectrometry, a total of 604 proteins were identified in the samples digested with the microfluidic chip and 602 proteins with the reference workflow. Protein quantitation was performed using the Hi3 method, yielding a 7.6% lower median intensity CV for automatically digested samples compared to samples digested with the reference workflow. Additionally, 17% more proteins were quantitated with less than 30% CV in the samples from the microfluidic chip, compared to the manual control samples. This improvement can be attributed to the accurate liquid metering with all volume CVs below 1.5% on the microfluidic chip. The presented automation solution is attractive for laboratories in need of robust automation of sample preparation from small volumes as well as for labs with a low or medium throughput that does not allow for large investments in robotic systems.

Multidrug-resistant tuberculosis care in the United States.

BACKGROUND: To examine the utilization of the Tuberculosis (TB) Centers of Excellence (COE) medical consultation service and evaluate how these services were being employed for patients in relation to multidrug-resistant TB (MDR-TB).METHODS: Medical consults are documented in a secure database. The database was queried for MDR-TB consultations over the period 1 January 2013-31 December 2017. All were analyzed to assess provider type, center, setting, year of call, and type of patient (pediatric vs. adult). A subgroup was randomly selected for thematic analysis.RESULTS: The centers received 1560 MDR-TB consultation requests over this period. Providers requesting consults were primarily physicians (55%). The majority of requests were from public health departments (64%) and for adult patients (80%). Four major topic areas emerged: 1) initial management of MDR-TB, 2) MDR-TB longitudinal treatment and complications, 3) management of persons exposed to MDR-TB, and 4) MDR-TB treatment completion.CONCLUSIONS: Analysis of these consultations provides insight into the type of expert advice about MDR-TB that was provided. These findings highlight topics where increased medical training and education may help to improve MDR-TB-related practices.

Sex differences in cardiovascular responses to orthostatic challenge in healthy older persons: A pilot study.

BACKGROUND: Premenopausal women show a higher incidence of orthostatic hypotension than age-matched men, but there are limited data available on sex differences in cardiovascular responses to orthostatic challenge in healthy older persons. We investigated sex differences in hemodynamic and autonomic responses to orthostatic challenge in healthy older males and females. MATERIALS AND METHODS: Fourteen older healthy women and 10 age-matched men performed a sit-to-stand test (5 min of sitting followed by 5 min of standing). A Task Force® Monitor continuously measured the following beat-to-beat hemodynamic parameters: heart rate, systolic blood pressure, diastolic blood pressure, mean blood pressure, stroke index, cardiac index, and total peripheral resistance index. Cardiac autonomic activity, low-frequency (LF: 0.04-0.15 Hz) normalized (LFnuRRI) and high-frequency (HF: 0.15-0.4 Hz) normalized (HFnuRRI) components, and the ratio between LF and HF power (LF/HF) were calculated using power spectral analysis of heart rate variability. RESULTS: Across all hemodynamic parameters, there were no significant differences between the sexes at baseline and during standing. LFnuRRI (median: 70.2 vs. 52.3, p < 0.05) and LF/HF ratio (median: 2.4 vs. 1.1, p < 0.05) were significantly higher, whereas HFnuRRI (median: 29.8 vs. 47.7, p < 0.05) was lower among women at baseline. All other heart rate variability measures did not differ between the sexes. CONCLUSIONS: The data indicate that older women showed higher sympathetic and lower parasympathetic activity at rest compared to age-matched men. These results are contradictory to the observations from previous studies, which showed a reduced sympathetic and enhanced parasympathetic activity in women in all ages. Further studies are required to determine the underlying mechanisms contributing to higher incidence of orthostatic hypotension in older females.

Homeless shelter context and tuberculosis illness experiences during a large outbreak in Atlanta, Georgia.

Setting: Persons experiencing homelessness (PEH) represent a population at high risk for tuberculosis (TB). While quantitative studies have characterized some important features of this key group, less has been captured directly from PEH about how they experience TB illness itself and the prevention and control measures implemented in response to an outbreak. This qualitative study aimed to explore PEH's TB disease experiences in the context of a large TB outbreak involving homeless shelters in Atlanta, Georgia, USA. Design: This was a qualitative cross-sectional study involving in-depth interviews with 10 PEH with active TB disease. Key themes were identified through coded data analysis. Results: The central theme to emerge was that stressful social environments of homeless shelters shape illness experiences and health care seeking behaviors, and limit the influence of shelter-based prevention and control measures implemented in response to a TB outbreak. Despite availability, shelter-based latent tuberculous infection (LTBI) testing and education services were minimally engaged. Furthermore, hardships inherent to homelessness were interrelated with disease normalization and symptom minimization. Conclusions: Homeless shelter-related stress may have important implications for the prevention and control of TB outbreaks in this setting. This stress may hinder case finding; a model of supplemental TB education and testing for LTBI at proximal community venues is necessary.

Contexte: Les personnes sans domicile fixe (SDF) représentent une population à haut risque de tuberculose (TB). Si les études quantitatives ont caractérisé certains traits importants de ce groupe clé, moins d'informations ont été obtenues directement des SDF sur la façon dont ces personnes expérimentent la TB maladie elle-même et les mesures de prévention et de lutte mises en œuvre en réponse à l'épidémie. Cette étude qualitative visait à explorer l'expérience des SDF en matière de TB maladie dans le contexte d'une vaste flambée épidémique impliquant des centres d'hébergement de SDF à Atlanta, Georgie.Schéma : Une étude qualitative transversale impliquant des entretiens approfondis avec dix SDF atteints de TB active. Les thèmes clés ont été identifiés grâce à une analyse des données codées.Résultats : Le thème central qui a émergé est que l'environnement social stressant des centres d'hébergement façonne les expériences de la maladie et les comportements de recherche de soins et limite l'influence des mesures de prévention et de lutte basées dans ces centres et mises en œuvre en réponse à une flambée de TB. En dépit de leur disponibilité dans les centres d'hébergement, le dépistage de l'infection tuberculeuse latent (ITL) et les services d'éducation ont été très peu engagés. Plus encore, les difficultés inhérentes à l'absence de domicile fixe ont été indissociables de la normalisation de la maladie et de la minimisation des symptômes.Conclusions: Le stress lié à l'hébergement dans un refuge pour SDF peut avoir des implications majeures dans la prévention et la lutte contre les flambées de TB dans ce contexte. Ce stress peut entraver la découverte des cas et soutenir un modèle d'éducation supplémentaire à la TB et une recherche de l'ITL dans les lieux communautaires proches.

Marco de referencia: Las personas que carecen de vivienda constituyen una población con alto riesgo de contraer la tuberculosis (TB). Los estudios cuantitativos han caracterizado algunos aspectos importantes de este grupo poblacional, pero poco se ha captado directamente de su forma de vivenciar la enfermedad tuberculosa y las medidas de prevención y de control que se instauran en respuesta a un brote epidémico. El presente estudio cualitativo tuvo por objeto analizar las vivencias de la enfermedad tuberculosa por parte de las personas que carecen de vivienda, en el contexto de un amplio brote epidémico de TB que ocurrió en los albergues para personas sin techo en Atlanta, Georgia.Método: Fue este un estudio cualitativo transversal, que comportó entrevistas exhaustivas a 10 personas sin vivienda, con enfermedad tuberculosa activa. Se reconocieron los principales temas mediante un análisis temático con datos codificados.Resultados: El principal tema que surgió en el análisis fue que los entornos sociales estresantes de los albergues determinan las experiencias de la enfermedad y el comportamiento de búsqueda de atención y limitan la repercusión de las medidas de prevención y control que se aplican en los albergues en respuesta a un brote epidémico de TB. Pese a su disponibilidad, las pruebas diagnósticas de la infección tuberculosa latente y los servicios educativos prestados en los albergues se utilizaban poco. Además, las adversidades inherentes a la falta de vivienda se correlacionaron con una normalización de la enfermedad y la minimización de los síntomas.Conclusión: El estrés generado en los albergues destinados a las personas sin vivienda puede tener repercusiones importantes en la prevención y el control de los brotes de TB en estos entornos. Este estrés puede obstaculizar la búsqueda de casos y su demostración respalda la aplicación de un modelo de educación complementaria en materia de TB y de pruebas diagnósticas de la infección latente en los centros comunitarios próximos.

Building Bridges for Innovation in Ageing: Synergies between Action Groups of the EIP on AHA.

The Strategic Implementation Plan of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) proposed six Action Groups. After almost three years of activity, many achievements have been obtained through commitments or collaborative work of the Action Groups. However, they have often worked in silos and, consequently, synergies between Action Groups have been proposed to strengthen the triple win of the EIP on AHA. The paper presents the methodology and current status of the Task Force on EIP on AHA synergies. Synergies are in line with the Action Groups' new Renovated Action Plan (2016-2018) to ensure that their future objectives are coherent and fully connected. The outcomes and impact of synergies are using the Monitoring and Assessment Framework for the EIP on AHA (MAFEIP). Eight proposals for synergies have been approved by the Task Force: Five cross-cutting synergies which can be used for all current and future synergies as they consider overarching domains (appropriate polypharmacy, citizen empowerment, teaching and coaching on AHA, deployment of synergies to EU regions, Responsible Research and Innovation), and three cross-cutting synergies focussing on current Action Group activities (falls, frailty, integrated care and chronic respiratory diseases).

Public health costs for tuberculosis suspects in Wake County, North Carolina, United States.

SETTING: As the incidence of tuberculosis (TB) declines in high-income countries, resources to control TB are also declining. A portion of these resources are utilized for the evaluation and treatment of persons initially suspected of, but who do not actually have, TB (TB suspects). OBJECTIVE: To describe the cost of TB suspects to public health departments, and determine whether part of this cost can be averted using improved diagnostic tools. DESIGN: We evaluated resource utilization for all TB suspects as well as a random sample of TB cases managed at the Wake County public health clinic during 2008-2010. The proportion of total health department costs attributable to TB suspects was estimated. A sensitivity analysis assessed the potential impact of a rapid, accurate diagnostic test to avert suspect-associated costs. RESULTS: Of 135 patients evaluated for TB, 36 (27%) were suspects, accounting for 14% (US5,885) of the total estimated costs for managing all patients. A perfect diagnostic test with a 3-day turnaround would have averted US27,975 (53%) of the costs attributable to suspects. CONCLUSION: A substantial proportion of public health resources is utilized to manage persons whose final diagnosis is not TB. Efficient implementation of novel rapid tests could avert substantial public health costs.

Protein-encapsulated gold cluster aggregates: the case of lysozyme.

We report the evolution and confinement of atomically precise and luminescent gold clusters in a small protein, lysozyme (Lyz) using detailed mass spectrometric (MS) and other spectroscopic investigations. A maximum of 12 Au(0) species could be bound to a single Lyz molecule irrespective of the molar ratio of Lyz : Au(3+) used for cluster growth. The cluster-encapsulated protein also forms aggregates similar to the parent protein. Time dependent studies reveal the emergence of free protein and the redistribution of detached Au atoms, at specific Lyz to Au(3+) molar ratios, as a function of incubation time, proposing inter-protein metal ion transfer. The results are in agreement with the studies of inter-protein metal transfer during cluster growth in similar systems. We believe that this study provides new insights into the growth of clusters in smaller proteins.

Luminescent, bimetallic AuAg alloy quantum clusters in protein templates.

We report the synthesis of luminescent AuAg alloy quantum clusters (QCs) in bovine serum albumin (BSA), for the first time, with experimentally determined atomic composition. Mixing of the as-synthesized protein-protected Au and Ag clusters resulted in the formation of alloy AuAg clusters within the BSA. Mass spectrometric analysis of the product of a 1 : 1 molar ratio reaction mixture of Au(QC)@BSA and Ag(QC)@BSA suggested that the alloy clusters could be Au(38-x)Ag(x)@BSA. Further analyses by standard techniques revealed that the alloy cluster core of ∼1.2 nm diameter is composed of nearly zero valent Au and Ag atoms that exhibit distinctly different steady state and time resolved excited state luminescence profiles compared to the parent clusters. Tuning of the alloy composition was achieved by varying the molar ratio of the parent species in the reaction mixture and compositional changes were observed by mass spectrometry. In another approach, mixing of Au(3+) ions with the as-synthesized Ag(QC)@BSA also resulted in the formation of alloy clusters through galvanic exchange reactions. We believe that alloy clusters with the combined properties of the constituents in versatile protein templates would have potential applications in the future. The work presents interesting aspects of the reactivity of the protein-protected clusters.

Presyncopal cardiac contractility and autonomic activity in young healthy males.

We investigated non-invasively cardiac contractility and autonomic nervous activity during presyncopal orthostatic stress induced in healthy humans. A graded orthostatic stress (GOS) paradigm, consisting of head-up tilt (HUT) combined with lower body negative pressure (LBNP) of increasing magnitude, was used to reach a presyncopal end-point in 15 healthy adults. Continuous beat-to-beat hemodynamic and autonomic parameters were recorded. From supine control (C1) to presyncope (PS), total peripheral resistance index (TPRI) decreased from 2300+/-500 to 1910+/-320 dyne*s*m(2)/cm(5) (p=0.004), index of contractility (IC) from 59+/-14 to 27+/-6 1000/s (p<0.0001), left ventricular working index (LVWI) from 5.2+/-1.3 vs. 3.6+/-0.6 mmHg*L/(min*m(2)) (p=0.0001) and acceleration index (ACI) from 65+/-18 vs. 54+/-15 100/s(2) (p=0.04). Low frequency variation of diastolic blood pressure (LF(nu)dBP) increased from 51+/-14 to 67+/-11 % (p=0.0006) and of systolic blood pressure (LF(nu)sBP) from 50+/-6 vs. 67+/-8 % (p<0.0001). High frequency variation of RR-interval (HF(ms(2))RRI) decreased from 385+/-320 to 38+/-43 ms(2) (p=0.001). From late GOS (G3) to PS, TPRI decreased from 2540+/-640 to 1910+/-320 dyne*s*m(2)/cm(5) (p=0.003), IC from 35+/-6 to 27+/-6 1000/s (p=0.003), LVWI from 4.6+/-0.9 to 3.6+/-0.6 mmHg*L/(min/m(2)) (p=0.003), LF(nu)sBP from 71+/-8 to 67+/-8 % (p=0.03), LF(mmHg(2))dBP from 6.6+/-4.0 to 4.8+/-2.9 mmHg(2) (p=0.0001), LF(mmHg(2))sBP from 9.7+/-7.8 to 7.4+/-4.8 mmHg(2) (p=0.01). HF(nu)RRI increased from 19+/-8 to 28+/-13 % (p=0.008). Myocardial contractility indices and parameters of sympathetic activity were reduced in the presyncopal state, while parasympathic activity was increased. This suggests a decrease in cardiac contractility during orthostatically induced presyncope in healthy subjects.

The cardiovascular response to lower body negative pressure in humans depends on seal location.

We tested whether seal location at iliac crest (IC) or upper abdomen (UA), before and during lower body negative pressure (LBNP), would affect thoracic electrical impedance, hepatic blood flow, and central cardiovascular responses to LBNP. After 30 min of supine rest, LBNP at -40 mm Hg was applied for 15 min, either at IC or UA, in 14 healthy males. Plasma density and indocyanine green concentrations assessed plasma volume changes and hepatic perfusion. With both sealing types, LBNP-induced effects remained unchanged for mean arterial pressure (-3.0+/-1.1 mm Hg), cardiac output (-1.0 l min(-1)), and plasma volume (-11 %). Heart rate was greater during UA (80.6+/-3.3 bpm) than IC (76.0+/-2.5 bpm) (p<0.01) and thoracic impedance increased more using UA (3.2+/-0.2 Omega) than IC (1.8+/-0.2 Omega) (p<0.0001). Furthermore, during supine rest, UA was accompanied by lower thoracic impedance (26.9+/-1.1 vs 29.0+/-0.8 Omega, p<0.001) and hepatic perfusion (1.6 vs 1.8 l.min(-1), p<0.05) compared to IC. The data suggest that the reduction in central blood volume in response to LBNP depends on location of the applied seal. The sealing in itself altered blood volume distribution and hepatic perfusion in supine resting humans. Finally, application of LBNP with the seal at the upper abdomen induced a markedly larger reduction in central blood volume and greater increases in heart rate than when the seal was located at the iliac crest.

Product development studies for stabilization of oral liquid enzyme preparations containing diastase and papain.

A product development study was undertaken with a view to stabilize acid sensitive amylolytic enzyme diastase and alkali sensitive proteolytic enzyme papain. An unique high technology method was adopted for both enzymes with enteric coating and non-enteric film forming materials respectively to achieve site specificity of action, better stability and to protect diastase from the adverse acid pH of the stomach. Feasibility of incorporating various excipients like thickening agents, surfactants, preservatives, etc., to produce stable elegant oral liquid suspension was also studied. Release studies of the enzymes both in simulated gastric and simulated intestinal juices showed steady and consistent release. The proteolytic and amylolytic activities were assessed by standard pharmacopoeial methods. The stability of the product during the studies was satisfactory. Reduction in addition of overages of costly enzymes met the project technically feasible and economically viable.

Preparation and in vitro dissolution of isoniazid from ethylcellulose microcapsules.

Microcapsules of isoniazid were prepared by phase separation coacervation process induced by non-solvent addition and using ethylcellulose (EC) as coating polymer. When polyisobutylene (PIB)--a protective colloid was present at sufficient concentration, film coated drug particles were formed. At 0-6% PIB concentration, the microcapsules were aggregated. Increase of colloid concentration produced microcapsules of less aggregation and higher drug content because coating became progressively thinner. PIB concentration also controlled the particle size and the release rate of drug from microcapsules. Wall thickness and EC loss were calculated from drug content. Microcapsules coated with EC were prepared with 7-9% PIB. Scanning Electron Microscopy was used to study the nature of aggregation and coating behaviour. The in vitro dissolution study confirmed the first order release pattern and also the Higuchi Matrix model.

Structure, physical, and photophysical properties of platinum(II) complexes containing bidentate aromatic and bis(diphenylphosphino)methane as ligands.

This study focuses on a series of PtII(L-L')(dppm)n+ complexes, where dppm is bis(diphenylphosphino)methane and L-L' are C-C' (n = 0), C-N (n = 1), and N-N' (n = 2) aromatic ligands. Structural characteristics are as follows: for [Pt(phen)(dppm)](PF6)2, a N-N' derivative, monoclinic, C2/c, a = 33.583(6) A, b = 11.399(2) A, c = 22.158(4) A, Z = 8; for [Pt(phq)(dppm)](PF6), a C-N derivative, triclinic, P1, a = 11.415(3) A, b = 13.450(3) A, c = 14.210(4) A, Z = 2; for [Pt(phpy)(dppm)](PF6), a C-N derivative, triclinic, P1, a = 10.030(3) A, b = 13.010(2) A, c = 15.066(4) A, Z = 2; and for [Pt(bph)(dppm)], a C-C' derivative, P2(1)/c, a = 17.116(7) A, b = 21.422(6) A, c = 26.528(6) A, Z = 12, where phen is 1,10-phenanthroline, phq is 2-phenylquinoline, phpy is 2-phenylpyridine, and bph is 2,2'-biphenyl. Structural features indicate that the Pt-C bond distance is shorter than the Pt-N bond distance in symmetrical complexes and that the Pt-P bond distance trans to N is shorter than the Pt-P bond trans to C. This is consistent with the 31P NMR spectra where the chemical shift of the P trans to C is approximately 10 ppm less than found for P trans to N. The energy maxima of the metal-to-ligand charge-transfer band for the complexes containing various L-L' ligands occur in the near-UV region of the spectrum and fall into the energy series bpy > bph > phen > 2-phpy > 2-ptpy > 2-phq > 7,8-bzq, where bpy is 2,2'-bipyridine, 2-phpy is 2-phenylpyridine, 2-ptpy is 2-p-tolylpyridine, and 7,8-bzq is 7,8-benzoquinoline. The emission energy maxima, ascribed to variance in metal-perturbed triplet ligand centered emission, commence near 500 nm and follow the series phen > bpy > 7,8-bzq > 2-phpy > 2-ptpy > bph > 2-phq. In general, emission is observed at 77 K and in solution at low temperatures, but the temperature dependence of the emission lifetimes indicates thermal activation to another state occurs with an energy of approximately 1800 cm-1 for the complexes, with the exception of [Pt(bph)(dppm)], which has an activation energy of approximately 2300 cm-1.

Rhodium-105 tetrathioether complexes: radiochemistry and initial biological evaluation.

105Rhodium(III) complexes with three different acyclic tetrathioether ligands containing pendant carboxylic acid groups have been synthesized and characterized. The complexes were evaluated for stability under physiological conditions and the most promising complexes were evaluated in vivo in normal mice. The primary route of clearance for these complexes was the renal/urinary system, consistent with the presence of pendant carboxylate groups. The results indicate that the cis-[Rh(III)Cl2(2,5,8,11-tetrathiadodecane-1,12-dicarboxylic acid)]+ complex shows the most promising in vivo characteristics on which to base a potential therapeutic radiopharmaceutical.