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Issue Addressed: Referral to supervised physical activity (PA) programs is an effective treatment for military service veterans (MSVs) suffering from a range of chronic diseases. However, many MSVs fail to maintain PA regimes once discharged from supervision. This pilot study assessed Active Choices, a stepped-down program to support MSVs in the transition from allied health treatment to self-managed PA., Methods: Participants were 34 Australian MSVs (mean [SD] age = 61 [15.8] years) who were completing supervised referral to an exercise physiologist or physiotherapist. MSVs stepped-down to Active Choices and received a 12-week, evidence-based PA support program (2020-2021). Analyses compared within-group changes in accelerometer-assessed PA at three time points (Weeks 0, 12, and 24; linear mixed model). Program retention, PA choices, and allied healthcare service costs were also evaluated., Results: Relative to baseline (64 [26] min/day), mean (SD) moderate-to-vigorous PA increased (74 [28] min/day; p < .05) and was maintained (62 [28] min/day) at weeks 12 and 24, respectively. Retention in the program was high (86% [29/34 participants] completion rate at 12 weeks), with water-based group activities the most popular PAs of choice (14/24 activities). Average allied healthcare service costs during the study were lower than typical costs for MSVs (60.51 vs. 97.06 AUD/week)., Conclusion: The findings highlight the potential of Active Choices to support MSVs in the transition from supervised to self-managed MVPA. SO WHAT?: The program could promote the health of veterans and reduce costs for ongoing referral if impact is replicated at scale., (© 2023 The Authors. Health Promotion Journal of Australia published by John Wiley & Sons Australia, Ltd on behalf of Australian Health Promotion Association.)

Objective: This study aimed to identify peripheral and salivary gland (SG) biomarkers of response/resistance to B cell depletion based on the novel concise Composite of Relevant Endpoints for Sjögren Syndrome (cCRESS) and candidate Sjögren Tool for Assessing Response (STAR) composite endpoints., Methods: Longitudinal analysis of peripheral blood and SG biopsies was performed pre- and post-treatment from the Trial of Anti-B Cell Therapy in Patients With Primary Sjögren Syndrome (TRACTISS) combining flow cytometry immunophenotyping, serum cytokines, and SG bulk RNA sequencing., Results: Rituximab treatment prevented the worsening of SG inflammation observed in the placebo arm, by inhibiting the accumulation of class-switched memory B cells within the SG. Furthermore, rituximab significantly down-regulated genes involved in immune-cell recruitment, lymphoid organization alongside antigen presentation, and T cell co-stimulatory pathways. In the peripheral compartment, rituximab down-regulated immunoglobulins  and auto-antibodies together with pro-inflammatory cytokines and chemokines. Interestingly, patients classified as responders  according to STAR displayed significantly higher baseline levels of C-X-C motif chemokine ligand-13 (CXCL13), interleukin (IL)-22, IL-17A, IL-17F, and tumor necrosis factor-α (TNF-α), whereas a longitudinal analysis of serum T cell-related cytokines showed a selective reduction in both STAR and cCRESS responder patients. Conversely, cCRESS response was better associated with biomarkers of SG immunopathology, with cCRESS-responders showing a significant decrease in SG B cell infiltration and reduced expression of transcriptional gene modules related to T cell costimulation, complement activation, and Fcγ-receptor engagement. Finally, cCRESS and STAR response were associated with a significant improvement in SG exocrine function linked to transcriptional evidence of SG epithelial and metabolic restoration., Conclusion: Rituximab modulates both peripheral and SG inflammation, preventing the deterioration of exocrine function with functional and metabolic restoration of the glandular epithelium. Response assessed by newly developed cCRESS and STAR criteria was associated with differential modulation of peripheral and SG biomarkers, emerging as novel tools for patient stratification., (© 2023 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

The early identification of youth at risk for restraint incidents is an important next step to reducing the likelihood of such incidents. Yet, the extant research has not comprehensively investigated the idiographic factors that contribute to the restraint of youth in psychiatric residential treatment facilities (PRTFs). The current study investigated client-level predictors of restraint incidents, with specific emphasis on youth client trauma history and traumatic stress symptoms as assessed at admission. Participants were children and adolescents (N = 150; 55.3% female, 66.7% White, 33.3% Black or biracial) aged 6-17 (M = 11.8 years) admitted to a PRTF in the northeastern United States. A negative binomial regression with maximum likelihood estimation was conducted to examine the relative contributions of age, gender, length of stay, number of psychiatric diagnoses, body mass index (BMI), and traumatic stress symptoms at intake to the frequency of restraint incidents. The model was significant, χ 2 (6, N = 150) = 30.326, p < .001, and both length of stay, β = .005, p < .001, IRR = 1.005, and traumatic stress symptoms at intake, β = .072, p = .007, IRR = 1.074, were identified as significant predictors within the model. Although length of stay is an obvious predictor of restraint incidents, the current study is the first of which we are aware to identify traumatic stress symptoms at intake as a potential indicator of restraint frequency following admission. Clinical implications of these results are discussed., (© 2022 International Society for Traumatic Stress Studies.)

The coronavirus disease 2019 (COVID-19) pandemic ushered in a new era for advanced practice registered nurses, as emergency regulatory and policy changes expanded the nurse practitioner (NP) scope of practice. The legislative changes enabled NPs to bolster the national pandemic response by working to the full extent of their education and training. The changes are only temporary, and many have contemplated the permanent impact of COVID-19 when healthcare transitions to a postpandemic normal. NPs now have a unique opportunity to educate others about the merit of their role and advocate for permanent legislative changes. In this creative controversy manuscript, we build a case that national NP full practice authority increases access to care and is vital for a sustainable and resilient healthcare system that can react to future pandemic crises., (Published 2020. This article is a U.S. Government work and is in the public domain in the USA.)

Issue Addressed: Many Australian employees now regularly work from home in some capacity. This new way of working has not been widely studied in relation to the potential implications for employees' health-related behaviour or workplace health promotion. The aim of this study was to explore office-based employees' perceptions of the impact of flexible work on physical activity and sedentary behaviour; and preferences for associated interventions., Methods: Three focus groups were conducted with office-based employees (n = 28) 6 months after the introduction of a flexible work policy. A semi-structured interview format with open-ended questions was used with summary statements to check understanding. Sessions were audiotaped, and dominant themes were identified. Findings on intervention preferences were interpreted using a social cognitive framework. An overview of results was provided to a group of managers (n = 9) for comment., Results: Employees reported that physical activity was not impacted, but sedentary behaviour had increased, with flexible work. Intervention preferences focussed on occupational sedentary behaviour, self-regulation, prompts and social connections, and not the physical work environment. Managers agreed with employees' preferences and also wanted interventions to be sustainable., Conclusion: Self-directed interventions with social components and targeting occupational sedentary behaviour were more acceptable than physical activity interventions in this flexible workplace. SO WHAT?: Health promotion for workplaces with flexible work practices may benefit from prioritising strategies that promote self-regulation and social connections rather than being linked to the physical worksite., (© 2018 Australian Health Promotion Association.)

Issue addressed Smoking, risky drinking, overweight and obesity, and physical inactivity are health-risk factors (HRFs) that contribute significantly to morbidity worldwide. Several initiatives have been introduced over the past two decades to reduce these HRFs. This paper examines changes in the prevalence of HRFs in young women (aged 18-23 years) between 1996 and 2013, overall and within demographic groups. Methods Data from two cohorts of the Australian Longitudinal Study on Women's Health, born in 1973-78 (n=14247) and 1989-95 (n=17012) were weighted to provide national estimates. Prevalence ratios were used to compare HRFs in 2013 relative to 1996. Results In 1996, 32% were current smokers, 38% were risky drinkers, 22% were overweight or obese and 7% were physically inactive. In 2013, corresponding estimates were 19%, 35%, 33% and 6%. Between 1996 and 2013, overall smoking prevalence decreased, but remained over 43% among least educated women. Overweight and obesity increased in all demographic groups. Conclusions The findings suggest that only smoking, which has been the subject of changes in taxation, legislation and regulation, declined significantly, in all except the least educated women. In contrast, the prevalence of overweight and obesity, which has largely been addressed through awareness campaigns and voluntary actions by the food industry, increased markedly in all demographic sub-groups. So what? The findings show that comprehensive health promotion interventions, such as those for tobacco control, are successful (but may still be ineffective among less educated women). In contrast the measures to control population weight gain among young women have been futile so far.

Issue addressed: Smoking, risky drinking, overweight and obesity, and physical inactivity are health-risk factors (HRFs) that contribute significantly to morbidity worldwide. Several initiatives have been introduced over the past two decades to reduce these HRFs. This paper examines changes in the prevalence of HRFs in young women (aged 18-23 years) between 1996 and 2013, overall and within demographic groups. Methods: Data from two cohorts of the Australian Longitudinal Study on Women's Health, born in 1973-78 (n=14247) and 1989-95 (n=17012) were weighted to provide national estimates. Prevalence ratios were used to compare HRFs in 2013 relative to 1996. Results: In 1996, 32% were current smokers, 38% were risky drinkers, 22% were overweight or obese and 7% were physically inactive. In 2013, corresponding estimates were 19%, 35%, 33% and 6%. Between 1996 and 2013, overall smoking prevalence decreased, but remained over 43% among least educated women. Overweight and obesity increased in all demographic groups. Conclusions: The findings suggest that only smoking, which has been the subject of changes in taxation, legislation and regulation, declined significantly, in all except the least educated women. In contrast, the prevalence of overweight and obesity, which has largely been addressed through awareness campaigns and voluntary actions by the food industry, increased markedly in all demographic sub-groups. So what?: The findings show that comprehensive health promotion interventions, such as those for tobacco control, are successful (but may still be ineffective among less educated women). In contrast the measures to control population weight gain among young women have been futile so far.

Rumination, defined as repetitive, negative, self-focused thinking, is hypothesized to be a transdiagnostic factor that is associated with depression, anxiety, and posttraumatic stress disorder (PTSD). Theory has suggested that in individuals with PTSD, rumination serves as a cognitive avoidance factor that contributes to the maintenance of symptoms by inhibiting the cognitive and emotional processing of the traumatic event, subsequently interfering with treatment engagement and outcome. Little is known about the neural correlates of rumination in women with PTSD. The current study utilized functional magnetic resonance imaging (fMRI) to examine neural correlates during an emotion interference task of self-reported rumination in women with PTSD. Women with PTSD (39 participants) were recruited at a university-based trauma clinic and completed a clinical evaluation that included measures of PTSD symptoms, rumination, and depressive symptoms, as well as a neuroimaging session in which the participants were administered an emotion interference task. There was a significant relationship between self-reported rumination and activity in the right orbital frontal cortex, BA 11; t(37) = 5.62, p = .004, k = 46 during the task. This finding suggested that women with PTSD, who had higher levels of rumination, may experience greater difficulty inhibiting negative emotional stimuli compared to women with lower levels of rumination., (Copyright © 2016 International Society for Traumatic Stress Studies.)

Issue Addressed: Although pole walking (PW) has the potential to be a useful health-enhancing physical activity (PA), little is known about by whom or how it is being practised. The aims of this study were to describe (1) the characteristics of PW leaders, pole walkers and PW programs in Australia, and (2) participants' perceptions of PW and their reasons for participation., Methods: In 2012, PW leaders (n=31) and walkers (n=107) completed self-administered surveys that included questions about participants' sociodemographic and health characteristics, PW programs and perceptions of PW. Data were analysed using SPSS., Results: Leaders and walkers were generally born in Australia (leaders, 71%; walkers, 83%), older (leaders, 55 years [s.d. 11.5]; walkers, 65 years [s.d. 10.6]) and female (leaders, 77%; walkers, 79%). Most walkers (82%) walked regularly in groups, approximately once per week for about an hour, at light to moderate intensity. The program's aims most strongly endorsed by PW leaders were to increase participant enjoyment (90%), increase PA levels (81%), provide a positive social experience (77%) and increase PA confidence (71%). The most strongly endorsed motivations for PW among walkers were to remain physically active (63%), improve fitness (62%) and personal and social enjoyment (60%)., Conclusions: In Australia, PW is being practised by a health conscious, older population. It is perceived as an enjoyable and health-enhancing outdoor activity. SO WHAT?: Health and exercise practitioners may find that PW is a beneficial form of PA for older Australians.

Issue Addressed: There is limited evaluation on the impact of community-based walking groups on physical activity (PA). This study examined the amount of walking and total PA minutes when adults joined the Just Walk It (JWI) program in Queensland, and changes over time., Methods: All adult participants (n=1258) were sent a survey on registration with the JWI program between April 2002 and December 2003, and after 6 and 12 months. Outcomes included self-reported minutes of walking and total PA in the past week and the proportion meeting PA recommendations., Results: Of the 1,258 registrants, 601 returned the 12-month survey; 423 of these confirmed they still participated. At baseline, 36 (8.5%) of these were inactive, 280 (66.2%) were insufficiently active to meet PA recommendations and 107 (25.3%) met PA recommendations. Among these groups, the largest 12-month increases in walking and total PA were in participants who were inactive (177 minutes, 95% CI 144-210, p<0.001 and 233 minutes, 95% CI 169-297, p<0.001, respectively) and in participants who were insufficiently active (63 minutes, 95% CI 39-86, p<0.001 and 122 minutes, 95% CI 81-162, p<0.001, respectively). Walking minutes increased more for men (n=92) [100 minutes, 95% CI 51-150] than for women (n=331) [52 minutes, 95% CI 32-72, p=0.044], as did total PA minutes (158 minutes, 95% CI 61-247 compared to 67 minutes, 95% CI 31-103, p=0.038). Furthermore, compared with participants aged 18-44 years (n=41) [-12 minutes, 95% CI -75-50] and 65 and older (n=183) [57 minutes, 95% CI 27-87], walking increased more in those aged 45-64 years (n=199) [83 minutes, 95% CI 56-110, p=0.018)., Conclusions: Participation in a community-based walking group for 12 months increased both walking and total PA, especially in men, mid-aged participants and those who were inactive or insufficiently active at registration.

Issue Addressed: There is increasing interest in the potential association between sedentary behaviour and poor health. This study examined office-based employees' perceptions of the health risks associated with prolonged sitting at work, and strategies to interrupt and reduce occupational sitting time., Methods: Four focus groups were conducted with a convenience sample of Australian government personnel (20 women and two men). Open-ended questions concerning health risks and sitting reduction strategies were posed by lead researchers and focus group participants invited to express opinions, viewpoints and experiences. Audio recordings and summary notes of focus group discussions were reviewed by researchers to identify key response themes., Results: Employees associated prolonged occupational sitting with poor health, primarily in terms of musculoskeletal issues, fatigue and de-motivation.This risk was seen as independent of physical activity. Workplace interventions tailored to occupational roles were viewed as important and considered to be the joint responsibility of individuals and organisations. Strategies included workload planning (interspersing sedentary and non-sedentary tasks), environmental change (e.g. stairwell access, printers away from desks), work tasks on the move (e.g. walking meetings) and purposive physical activity (e.g. periodic breaks, exercise/walking groups).The perception that these strategies would compromise productivity was identified as the primary barrier to implementation; team leaders were subsequently considered vital in enabling integration and acceptance of strategies into everyday workplace practices., Conclusions: Prolonged occupational sitting was perceived as detrimental to health. Suggested strategies targeted individuals, workplaces, organisations and environments.

Little is known about cancer survivors' experiences with and preferences for exercise programmes offered during rehabilitation (immediately after cancer treatment). This study documented colorectal cancer survivors' experiences in an exercise rehabilitation programme and their preferences for programme content and delivery. At the completion of 12 weeks of supervised exercise, 10 participants took part in one-on-one semi-structured interviews. Data from these interviews were coded, and themes were identified using qualitative software. Key findings were that most participants experienced improvements in treatment symptoms, including reduced fatigue and increased energy and confidence to do activities of daily living. They also reported that interactions with the exercise trainer and a flexible programme delivery were important aspects of the intervention. Most participants reported that they preferred having a choice of exercise, starting to exercise within a month after completing treatment, having supervision and maintaining a one-on-one format. Frustrations included scheduling conflicts and a lack of a transition out of the programme. The findings indicate that colorectal cancers experience benefits from exercise offered immediately after treatment and prefer individual attention from exercise staff. They further indicate directions for the implementation of future exercise programmes with this population., (© 2010 Blackwell Publishing Ltd.)

We have investigated the role of phospholipase A(2) (PLA(2) ) enzymes in generating membrane tubules at the trans-Golgi network (TGN). Constitutive TGN membrane tubules and those induced by over-expressing kinase dead protein kinase D were inhibited by the PLA(2) inhibitors ONO-RS-082 (ONO) and bromoenol lactone. These antagonists also inhibited secretory delivery of both soluble and transmembrane cargoes. Finally, use of the reversible antagonist ONO and time-lapse imaging revealed for the first time that PLA(2) antagonists inhibit the initiation of membrane tubule formation at the TGN. Thus, PLA(2) enzymes appear to have an important role in the earliest steps of membrane tubule formation at the TGN, which are utilized for membrane trafficking., (© 2010 John Wiley & Sons A/S.)

The mechanism of coat protein (COP)II vesicle fission from the endoplasmic reticulum (ER) remains unclear. Lysophospholipid acyltransferases (LPATs) catalyze the conversion of various lysophospholipids to phospholipids, a process that can promote spontaneous changes in membrane curvature. Here, we show that 2,2-methyl-N-(2,4,6,-trimethoxyphenyl)dodecanamide (CI-976), a potent LPAT inhibitor, reversibly inhibited export from the ER in vivo and the formation of COPII vesicles in vitro. Moreover, CI-976 caused the rapid and reversible accumulation of cargo at ER exit sites (ERESs) containing the COPII coat components Sec23/24 and Sec13/31 and a marked enhancement of Sar1p-mediated tubule formation from ERESs, suggesting that CI-976 inhibits the fission of assembled COPII budding elements. These results identify a small molecule inhibitor of a very late step in COPII vesicle formation, consistent with fission inhibition, and demonstrate that this step is likely facilitated by an ER-associated LPAT.

Issue Addressed: The evaluation of an earlier 10,000 Steps community-based intervention program indicated that men were less likely than women to have used a pedometer or increased their physical activity (PA). This study aimed to explore men's reactions to the 10,000 Steps a Day message, the use of pedometers, and other strategies for increasing PA., Method: Five focus groups were conducted with 39 men aged 45-65 years., Results: Although many were familiar with the 10,000 Steps message, the majority of men did not like it. Pedometers were seen as useful for assessing PA in the short term, but not for ongoing use. Participants were generally aware of PA recommendations. Walking was considered a good option for this age group, but there was varying interest in this type of activity. Weight and stress management were commonly identified benefits of PA. Common barriers to PA were lack of time and motivation, health and weight restrictions, cost, and disinterest. Suggestions of how to promote PA to mid-aged men included workplace initiatives, making PA "fun", and creating opportunities for men to do PA with their family or same-aged peers., Conclusions: PA promotion using the 10,000 Steps message, walking, and pedometers may not appeal to mid-aged men.

Since the mid-1990s, there have been tremendous advances in our understanding of the roles that lipid-modifying enzymes play in various intracellular membrane trafficking events. Phospholipases represent the largest group of lipid-modifying enzymes and accordingly display a wide range of functions. The largest class of phospholipases are the phospholipase A(2) (PLA2) enzymes, and these have been most extensively studied for their roles in the generation lipid signaling molecules, e.g. arachidonic acid. In recent years, however, cytoplasmic PLA2 enzymes have also become increasingly associated with various intracellular trafficking events, such as the formation of membrane tubules from the Golgi complex and endosomes, and membrane fusion events in the secretory and endocytic pathways. Moreover, the ability of cytoplasmic PLA2 enzymes to directly affect the structure and function of membranes by altering membrane curvature suggests novel functional roles for these enzymes. This review will focus on the role of cytoplasmic PLA2 enzymes in intracellular membrane trafficking and the mechanisms by which they influence membrane structure and function.

Eukaryotic cells contain a variety of cytoplasmic Ca(2+)-dependent and Ca(2+)-independent phospholipase A2s (PLA2s; EC 2.3.1.2.3). However, the physiological roles for many of these ubiquitously-expressed enzymes is unclear or not known. Recently, pharmacological studies have suggested a role for Ca(2+)-independent PLA2 (iPLA2) enzymes in governing intracellular membrane trafficking events in general and regulating brefeldin A (BFA)-stimulated membrane tubulation and Golgi-to-endoplasmic reticulum (ER) retrograde membrane trafficking, in particular. Here, we extend these studies to show that membrane-permeant iPLA2 antagonists potently inhibit the normal, constitutive retrograde membrane trafficking from the trans-Golgi network (TGN), Golgi complex, and the ERGIC-53-positive ER-Golgi-intermediate compartment (ERGIC), which occurs in the absence of BFA. Taken together, these results suggest that iPLA2 enzymes play a general role in regulating, or directly mediating, multiple mammalian membrane trafficking events.

Chlamydiae are obligate intracellular pathogens that spend their entire growth phase sequestered in a membrane-bound vacuole called an inclusion. A set of chlamydial proteins, labelled Inc proteins, has been identified in the inclusion membrane (IM). The predicted IncA, IncB and IncC amino acid sequences share very limited similarity, but a common hydrophobicity motif is present within each Inc protein. In an effort to identify a relatively complete catalogue of Chlamydia trachomatis proteins present in the IM of infected cells, we have screened the genome for open reading frames encoding this structural motif. Hydropathy plot analysis was used to screen each translated open reading frame in the C. trachomatis genome database. Forty-six candidate IM proteins (C-lncs) that satisfied the criteria of containing a bilobed hydrophobic domain of at least 50 amino acids were identified. The genome of Chlamydia pneumoniae encodes a larger collection of C-lnc proteins, and only approximately half of the C-lncs are encoded within both genomes. In order to confirm the hydropathy plot screening method as a valid predictor of C-lncs, antisera and/or monoclonal antibodies were prepared against six of the C. trachomatis C-lncs. Immunofluorescence microscopy of C. trachomatis-infected cells probed with these antibodies showed that five out of six C-lncs are present in the chlamydial IM. Antisera were also produced against C. pneumoniae p186, a protein sharing identity with Chlamydia psittaci lncA and carrying a similar bilobed hydrophobic domain. These antisera labelled the inclusion membrane in C. pneumoniae infected cells, confirming that proteins sharing the unique secondary structural characteristic also localize to the inclusion membrane of C. pneumoniae. Sera from patients with high-titre antibodies to C. trachomatis were examined for reactivity with each tested C-lnc protein. Three out of six tested C-lncs were recognized by a majority of these patient sera. Collectively, these studies identify and characterize novel proteins localized to the chlamydial IM and demonstrate the existence of a potential secondary structural targeting motif for localization of chlamydial proteins to this unique intracellular environment.

Quinidine gluconate 324 mg sustained release tablets (Quinaglute) was administered as a single dose to 15 healthy male subjects following an overnight fast, immediately following a high fat (HF) breakfast or immediately following a low fat (LF) breakfast. Serum samples were obtained over a 48 h period and analyzed for quinidine content using a high performance liquid chromatographic assay. Under the conditions of the study, both the rate and extent of quinidine bioavailability was significantly affected by food. The extent of bioavailability was statistically significantly greater (p less than 0.05) following both the HF and LF meals as compared to that in the fasted state. Rate of bioavailability was significantly enhanced following the LF meal as compared to that of the other two treatment groups. Although peak concentrations were greater and time to peak concentrations somewhat later following the HF meal versus those under fasting conditions, these differences were not statistically significant. In addition, the characteristics of the serum concentration-time profile (as defined by the number, magnitude, and time of occurrence of the multiple absorption maxima) was unique for each of the three treatment groups. Possible mechanisms underlying these results are explored.

Data from a five-way crossover study in human subjects using four talented promethazine products and a promethazine solution are presented. All products were administered as a single oral dose. The five objectives of the study were to investigate bioequivalency, to estimate dose proportionality at two dose levels, to establish validity of a reference production solution for future bioequivalency studies, to estimate intersubject variation, and to compare bioavailability/tablet dissolution data. Blood samples were collected at given intervals over a 24-hour period and analysed for promethazine using an HPLC technique. Pharmacokinetic parameters were calculated using standard procedures and a two-way analysis of variance (ANOVAR) was used to assess whether the differences were statistically significant. The AUC0----infinity data from the ANOVAR analysis showed that the 50 mg innovator and generic products and the 50 mg solution were not significantly different. However, the innovator product had a significantly lower Cmax and longer tmax than the solution. The generic product did not differ significantly from the solution. Promethazine was found to exhibit linear dose proportionality in the range and product studied. Intersubject variation was high for all parameters (23 to 63 per cent) and the in vivo and in vitro data showed a positive relationship.

As can be seen from the tables, the terminal half-life of clobazam is about 50 hours, and from a solid dosage form the peak plasma level occurs approximately 1.5 hours after ingestion. Thus, there is a significant, yet relatively short, dosage form delay effect when the solid dosage forms are compared to the rapidly available solution of the drug. However, based on the areas under the curve, comparison of the solid dosage forms with the solution indicates that the fraction of clobazam absorbed is 1. Pupil diameter measurement at 2, 4, and 6 hours after ingestion of clobazam correlated well with the plasma levels at these times. Pupils were constricted to the highest degree at 2 hours and approached the initial pupillary diameter at the 6-hour measurement.

It is evident that substantial intersubject and intrasubject varition in the bioavailability of clobazam exists following ingestion of 10, 20 and 40 mg doses in these 12 volunteers. Peak concentrations and area under the plasma level-time curve were directly proportional to the dose of clobazam and the mean plasma half-life of clobazam was about 18 hours regardless of dose administered. The t1/2 value was less than that previously reported, as the current results allow differentiation of parent drug from metabolites. This 18 hr t1/2 compares favorably with the half-life of other benzodiazepines.

Promethazine in doses of 50 mg has demonstrated detrimental effects upon the performance of visual tasks. The purpose of the study was to examine the relationship between the blood concentration levels of promethazine and two human performance tasks. Fifteen paid healthy male volunteers completed a randomized five-way crossover design which included a 25 mg and 50 mg dose of the innovator dosage form, a 50 mg dose of a generic dosage form, a 50 mg solution dosage form, and a placebo. Serial blood samples were obtained in addition to performance measures of rotary pursuit and a simple force choice reaction time. Analysis of the forced choice reaction depicted a mild relationship with the blood concentration levels of promethazine. However, the measures of rotary pursuit, a more sensitive determinant of human motor performance, proved to be more related to both the promethazine blood concentration and the inherent learning which was confounded in the experiment. The degree of impaired pursuit performance and reaction time differences could be defined in terms of a linear relationship to the promethazine concentration.

An unusual neurilemmoma of the trigeminal nerve in a 31-year-old woman is described. The neoplasm was roentgenographically calcified and contained various types of mesenchymal tissue, including a cavernous angioma, cartilage, bone, and adipose tissue. Angioma in combination with neurilemmoma occurs more frequently than other forms of mesenchymal tissue. Lipoma is an uncommon component of neoplasms affecting the cranial nerves. Cartilage and bone are rarely encountered in benign intracranial neurilemmomas. The histogenesis of this combined neoplasm is discussed in relation to the ectomesenchymal properties of the neural crest.

The purpose of the study was to examine the bioequivalence of five commercially available oral prednisone products. The in vivo study utilized 18 healthy males, each of whom was administered 20 mg of prednisone as a reference solution or as a tablet in a 6-week, six-way crossover design. Blood was collected and serum was assayed, using an HPLC procedure specific for prednisone and prednisolone. Mean pharmacokinetic parameters (t 1/2, ke, Cmax, tmax, and AUC) were determined. ANOVA was performed on the prednisone and prednisolone data (F-test, p less than 0.05) as well as Duncan's multiple range analysis. Dissolution tests were also performed on each of the five products in order to test the relationship between dissolution and bioequivalence among prednisone products. The in vitro study consisted of a standard USP dissolution test which included tablets from the same lots as the tablets used in the in vivo study. The data showed no statistical difference in any of the pharmacokinetic parameters among tableted products, subjects, or dosing periods in the study. There was also no statistical difference in the dissolution study among the five commercial tablet forms.

An examination of steady-state performance of chlorpheniramine conventional versus controlled release products was conducted using 15 male subjects in a 3-way crossover study with a 2-week washout period between studies. The study was designed to determine if chlorpheniramine formulations provide consistent pharmacokinetic performance between individual units upon going from single dose to multiple dose therapy. In addition, the validity of predicting steady-state levels for these kinds of products using only single oral dose data was examined. The dosage forms evaluated were a conventional 4 mg tablet, and 8 mg barrier coated-bead capsule, and an 8 mg repeat action tablet. Multiple doses of each product were orally administered to each subject for 6 days prior to the study day to achieve steady-state levels and on the actual study day. Serum samples were collected at specific time intervals on the study day, and chlorpheniramine levels assayed by HPLC. Pharmacokinetic analysis was based on a two-compartment open model. The mean plasma elimination half-lives of the various dosage forms were in the range 24.5-25.4 h. There was no rapid release of drug from the controlled release products nor did they have drug release problems during the dosing interval. Good agreement was obtained between predicted average drug concentration at steady-state and drug concentration actually present for all the formulations studied. Based upon comparative examination of AUC, Cmax, and fraction of dose absorbed data, the controlled release products administered every 12 h were comparable in performance to a conventional release tablet administered every 6 h. Since the half-life of chlorpheniramine is approximately 1 day, therapeutic management may possibly be gained with dosing the patient once daily with a controlled release product or twice daily with a conventional tablet.