The Sec system.

Proteins designated to be secreted by Escherichia coli are synthesized with an amino-terminal signal peptide and associate as nascent chains with the export-specific chaperone SecB. Translocation occurs at a multisubunit membrane-bound enzyme termed translocase, which consists of a peripheral preprotein-binding site and an ATPase domain termed SecA, a core heterotrimeric integral membrane protein complex with SecY, SecE and SecG as subunits, and an accessory integral membrane protein complex containing SecD and SecF. Major new insights have been gained into the cascade of preprotein targeting events and the enzymatic mechanism or preprotein translocation. It has become clear that preproteins are translocated in a stepwise fashion involving large nucleotide-induced conformational changes of the molecular motor SecA that propels the translocation reaction.

Isothermal Nucleation Rates of n-Propanol, n-Butanol, and n-Pentanol in Supersonic Nozzles: Critical Cluster Sizes and the Role of Coagulation.

We follow the nucleation of n-alcohols, n-propanol through n-pentanol, in two sets of supersonic nozzles having differing linear expansion rates. Combining the data from static pressure trace measurements with small-angle X-ray scattering we report the experimental nucleation rates and critical cluster sizes. For n-propanol, position resolved measurements clearly confirm that coagulation of the 2-10 nm size (radius) droplets occurs on the time scale of the experiment but that the effect of coagulation on the results is minimal. Under the conditions of the current experiments, our results suggest that alcohols have critical clusters that range from the dimer (n-pentanol) to the hexamer (n-propanol). We then compare the experimental results with classical nucleation theory (CNT), the Girshick-Chiu variant of CNT (GC), and the mean field kinetic nucleation theory (MKNT). Both CNT and MKNT underestimate the nucleation rates by up to 5 and 7 orders of magnitude, respectively, while GC theory predicts rates within 2 orders of magnitude. Correspondingly, the critical cluster size for all alcohols is overpredicted by factors of 2-9 with agreement improving with increasing chain length. An interesting byproduct of our experiments is that we find that the coagulation rate is enhanced by a factor of 3 over the value one would calculate for the free molecule regime.

Syringe HIV seroprevalence and behavioural and demographic characteristics of intravenous drug users in Sydney, Australia, 1987.

The contents of needles and syringes returned by intravenous drug users to two Sydney needle and syringe exchange centres were analysed for HIV antibodies by the enzyme-linked immunosorbent assay (ELISA). Reactive and borderline samples were further tested by the Western blot method. Basic demographic and needle sharing data were also collected from the clients of the exchanges. Of a sample of 1544 returned syringes, 48 (3%) were confirmed as containing HIV-infected blood. The proportion of infected syringes at exchange 2 was 6% (33 out of 545), which was significantly greater (P less than 0.05) than the proportion of exchange 1 at 1.5% (15 out of 999). The difference in seroprevalence between the two centres may be related to the behavioural characteristics of the client populations that attended each of the exchanges. The maintenance of a low syringe HIV seroprevalence (1-1.5%) over a 7-month period at one exchange may indicate that the availability of sterile needles and syringes prevented transmission of HIV among the clients of that exchange. HIV antibody testing of the contents of used syringes is a potentially valuable method of monitoring HIV infection among intravenous drug users. In this study, syringe exchange schemes have proved to be suitable venues for investigating the demographic characteristics and risk-taking behaviours of this population.

Thermodynamics of nucleotide binding to NBS-I of the Bacillus subtilis preprotein translocase subunit SecA.

SecA is the dissociatable nucleotide and preprotein binding subunit of the bacterial translocase. The thermodynamics of nucleotide binding to soluble SecA at nucleotide binding site I were determined by isothermal titration calorimetry. Binding of ADP and non-hydrolyzable ATPgammaS is enthalpy-driven (DeltaH(0) of -14.44 and -5.56 kcal/mol, respectively), but is accompanied by opposite entropic contributions (DeltaS(0) of -18.25 and 9.55 cal/mol/K, respectively). ADP binding results in a large change in the heat capacity of SecA (DeltaC(p)=-780 cal/mol/K). It is suggested that ADP binding promotes the interaction between the two thermodynamically discernible domains of SecA which is accompanied by a shielding of hydrophobic surface from solvent.

A state-wide assessment: marital stability and client outcomes.

This paper presents results of Missouri's first statewide evaluation of alcohol and drug treatment programs. The study utilized a 1-year follow-up sample of 242 respondents to explore the nature and patterns of post-treatment functioning. This paper focuses on the impact of client marital stability on post-treatment substance use. The data supported the expected result that marital status was related to post-treatment relapse. Further analysis suggests that transitional periods between marriage and divorce are especially important in understanding the pattern of relapse after treatment. Multivariate analysis indicates that the marital status effect is important both directly and in interaction with program completion. The data suggest that attention to transitional states and interpersonal functioning should be incorporated into client follow-up.

A newly recognized cause of wheezing: AIDS-related bronchial leiomyomas.

We present two human immunodeficiency virus-infected children who developed wheezing and radiological evidence of pulmonary air trapping due to intra- and peribronchial leiomyomas. At autopsy, leiomyomas were also found in their spleens, which to our knowledge, has never been reported. The smooth muscle tumors were strongly positive for the Epstein-Barr virus, as demonstrated by in situ hybridization to Epstein-Barr virus-encoded ribonucleic acid, confirming the findings of recent investigators and linking these tumors to the Epstein-Barr virus.

Waterhouse-Friderichsen syndrome secondary to Capnocytophaga canimorsus septicemia and demonstration of bacteremia by peripheral blood smear.

Waterhouse-Friderichsen syndrome caused by Capnocytophaga canimorsus septicemia was fatal in a previously healthy 47-year-old woman. The patient died suddenly in less than 12 hours after presentation, in spite of supportive measures, including ventilation, antibiotic coverage, pressor therapy, and multiple transfusions of blood products. The diagnosis of infection due to an unusual organism was suspected earlier in the course of management after review of the peripheral blood smear. The importance of the findings in the blood smear and their correlation with infection due to this organism are discussed.

Prostate brachytherapy--the community hospital experience.

One of the options for treating localized carcinoma of the prostate includes the implantation of radioactive seeds under ultrasound guidance (brachytherapy). A community hospital-based prostate brachytherapy program was started in 1992. The overall survival and disease-free survival figures for the initial 100 patients treated in this program seem comparable to patients treated by radical prostatectomy or brachytherapy in larger series. The main side effects of brachytherapy included nocturia, daytime urinary frequency, dysuria, and proctitis. These side effects were transient and decreased to less than 10% by 12 to 24 months following implantation. Prostate brachytherapy can be effectively and safely provided in a community hospital setting.

The management of dementia in general practice. A field test of guidelines.

INTRODUCTION: Guidelines for the management of dementia in non-institutionalized patients living in the community were developed by a broadly representative group. We assessed their usefulness. METHOD: The draft guidelines included emphasis on psychosocial issues. They were field tested by 17 general practitioners with 119 dementia patients. RESULTS: There was a high prevalence of comorbidity in the patients and frequent psychosocial issues in their management that were often not addressed. The guidelines were rated as very helpful for at least one aspect of care for 50% of the patients. DISCUSSION: The guidelines were found to be useful to GPs.

Benzodiazepine prescribing by GP registrars. A trial of educational outreach.

BACKGROUND: Despite ongoing concern about adverse effects and dependence on benzodiazepines, approximately 2% of Australians are still taking them on a regular basis. The aim of this study was to evaluate the effectiveness of an educational outreach or 'academic detailing' program about prescribing of benzodiazepines. METHOD: In this randomised trial general practice registrars (n = 157) in New South Wales were allocated to an intervention group (n = 79), which received a 20 minute educational outreach visit; or a control group (n = 78) which received an intervention on an unrelated topic. Prescribing behaviour was monitored by a pre-intervention and two post-intervention practice activity surveys. MAIN OUTCOME MEASURES: These were the rate of benzodiazepine prescribing for all indications, for anxiety and for sleep disorders. RESULTS: Overall benzodiazepine prescribing by the intervention group declined from 2.3 to 1.7 per 100 encounters, while the control group also declined from 2.2 to 1.6 per 100 encounters. Analysis of variance showed this was a significant drop over time (P = 0.042) but there was no difference between groups (P = 0.99). The prescribing decrease observed was in continuing rather than initial prescriptions. CONCLUSIONS: A marked decrease in benzodiazepine prescribing was seen over the course of the study in both intervention and control groups but no differential effect due to the educational outreach visit was found.

Elective admission policies in New South Wales public hospitals.

OBJECTIVE: To assess the existence and content of elective admission policies in New South Wales acute public hospitals. METHODS: A questionnaire was sent to managers of all acute public hospitals (n = 76). Copies of elective admission policies were sought from respondents. Results were analysed with EpiInfo 5.01b and policy content by thematic analysis. RESULTS: Survey response was 91% (69/76). Policies existed in 71% (49/69) of hospitals. Of these, 96% (47/49) disseminated their policy, with 23% (11/47) disseminating it at least annually, 41% (19/47) only when updated, and 32% (15/47) infrequently, with one policy being new (2%) and one hospital not stating its frequency (2%). Policy compliance was assessed in 86% (42/49) of hospitals and guidelines reviewed periodically in 92% (45/49) of hospitals. Twenty per cent (10/49) of the policies had been developed since a departmental instruction of May 1994. Of the 20 acute hospitals with no policy, 75% (15/20) were rural and 85% (17/20) thought they should have a policy. Analysis of policy content revealed emphases on resource availability and clinical need as determinants of elective admission, an institutional rather than a patient focus, and a high level of senior nurse manager involvement in admission decisions in rural hospitals. CONCLUSIONS: Despite a specific departmental instruction, nearly one-third of hospitals still had no admission policy 18 months later. This could be indicative of miscommunication between hospitals and NSW Health or perceived irrelevance of department guidelines by hospital managers. Existing policies were mostly institutionally focused and dominated by perceived resource limitations. NSW Health might consider other medico-social factors and manager involvement in future policy development.

Capturing the multiple contributions of the CNS role: a criterion-based evaluation tool.

The CNSs at a community hospital found that tools used to evaluate their performance did not reflect the wide variety of activities native to the CNS role within the institution. A six-member working group came to consensus on practice behaviors, and ordered them into a hierarchy of performance levels. The resulting role description and evaluation tool provides flexibility in application to unit-based, centralized, and specialty-based positions. The benefits of the new role description and evaluation tool to the organization and individual are multiple and serve to highlight the unique talents the role can bring to nursing.

Human service management: the art of interpersonal relationships.

The authors focus on the importance of interpersonal skills for the human service manager. Utilizing the significant replication of Mintzberg's study, with eight human services managers, the primacy of communication skills is emphasized. The authors conclude that management is a contingency activity; that personnel require contact to verify their feelings, attitudes, and decisions; and that organizational issues are essentially political in nature and respond to political solutions. Counsel, negotiation, persuasion, and consensus-building are viewed as corollaries of sound interpersonal skills.

Argon nucleation: bringing together theory, simulations, and experiment.

We present an overview of the current status of experimental, theoretical, molecular dynamics (MD), and density functional theory (DFT) studies of argon vapor-to-liquid nucleation. Since the experimental temperature-supersaturation domain does not overlap with the corresponding MD and DFT domains, separate comparisons have been made: theory versus experiment and theory versus MD and DFT. Three general theoretical models are discussed: Classical nucleation theory (CNT), mean-field kinetic nucleation theory (MKNT), and extended modified liquid drop model-dynamical nucleation theory (EMLD-DNT). The comparisons are carried out for the area below the MKNT pseudospinodal line. The agreement for the nucleation rate between the nonclassical models and the MD simulations is very good--within 1-2 orders of magnitude--while the CNT deviates from simulations by about 3-5 orders of magnitude. Perfect agreement is demonstrated between DFT results and predictions of MKNT (within one order of magnitude), whereas CNT and EMLD-DNT show approximately the same deviation of about 3-5 orders of magnitude. At the same time the agreement between all theoretical models and experiment remains poor--4-8 orders of magnitude for MKNT, 12-14 orders for EMLD-DNT, and up to 26 orders for CNT. We discuss possible reasons for this discrepancy and the ways to carry out experiment and simulations within the common temperature-supersaturation domain in order to produce a unified picture of argon nucleation.

Difficulties in admitting patients to metropolitan public hospitals: the view of medical practitioners.

OBJECTIVE: To investigate difficulties in public hospital admissions from the perspective of referring medical practitioners. METHODS: Referring surgeons, physicians and general practitioners (GPs) were randomly selected from three metropolitan (Sydney) health areas and formed into focus groups. Thematic analyses were undertaken of the groups' discussion transcripts to explore the problems of securing patient admissions, practitioners' perceptions of the reasons for these problems and the strategies they used to overcome them. RESULTS: Surgeons in two health areas reported major constraints affecting patient admissions. Physicians experienced fewer difficulties as this group was able to utilise outpatient services but was not always satisfied with such arrangements. GPs reported difficulties in communicating with full-time hospital medical staff. All practitioners felt that limited bed availability, restricted operating times, redefinition of many conditions as "non-urgent" and hospital budgetary constraints resulted in long waiting times for admission to public hospitals. This has led to an increasing move to use private hospitals for elective admissions, and to investigate patients in the community. CONCLUSIONS: Medical practitioners experienced difficulty in having their patients admitted to metropolitan public hospitals for both elective and non-elective procedures, and this was perceived to result in clinical and personal costs to patients.

Inpatient and outpatient outcomes in Missouri's alcohol and drug treatment programs.

A comparison of the effectiveness of inpatient and outpatient services for alcohol and drug clients is presented. Controls for program completion and severity of substance use on entry to treatment are included. While inpatients do only as well as outpatients overall, inpatient services show significant advantage for particular classes of clients. Results, though preliminary, suggest that the recent call for a cutback in inpatient services is premature.