Home treatment services for acute mental disorders: an all-Ireland survey.

OBJECTIVES: To determine the distribution, functioning and perceived impact of home-based treatment (HBT) teams for acute mental disorders on the island of Ireland. METHODS: A 28-item questionnaire exploring the structure, staffing and operation of HBT teams was emailed to all clinical directors of mental health services in Ireland (n=26) and Northern Ireland (NI) (n=5). Quantitative data was analysed using the Survey Monkey package, while free-text responses to open questions were analysed for thematic content. RESULTS: In total, 11 of 16 (68%) mental health services in Ireland and four of five (80%) in NI confirmed the presence of HBT teams. For 80% of respondents the primary function of HBT was as an alternative to inpatient admission. All NI respondents reported provision of a 24/7 HBT service. A 7 day a week service was reported by 82% of Republic of Ireland respondents. In total, 70% of respondents reported a gate-keeping role for their teams. Staffing levels and multidisciplinary representation varied widely. Most respondents perceived HBT as improving patient/carer experience and cost-effectiveness. CONCLUSIONS: Our findings suggest that the implementation of the HBT model in Ireland has not fulfilled the aspirations set out in mental health policy in both Irish jurisdictions. Many areas have no HBT services while wide variations in staffing levels and functioning persist. However, mental health services with established HBT teams appear convinced of their positive impact. An All-Ireland forum on HBT may help to define the model in an Irish context and standardise its future resourcing, operation and evaluation.

Requirement for a kinase-specific chaperone pathway in the production of a Cdk9/cyclin T1 heterodimer responsible for P-TEFb-mediated tat stimulation of HIV-1 transcription.

Tat activation of HIV-1 transcription is mediated by human transcription elongation factor P-TEFb, which interacts with Tat and phosphorylates the C-terminal domain of RNA polymerase II. The catalytic subunit of the P-TEFb complex, Cdk9, has been shown to interact with cyclin T and several other proteins of unknown identity. Consequently, the exact subunit composition of active P-TEFb has not been determined. Here we report the affinity purification and identification of the Cdk9-associated proteins. In addition to forming a heterodimer with cyclin T1, Cdk9 interacted with the molecular chaperone Hsp70 or a kinase-specific chaperone complex, Hsp90/Cdc37, to form two separate chaperone-Cdk9 complexes. Although the Cdk9/cyclin T1 dimer was exceptionally stable and produced slowly in the cell, free and unprotected Cdk9 appeared to be degraded rapidly. Several lines of evidence indicate the heterodimer of Cdk9/cyclin T1 to be the mature, active form of P-TEFb responsible for phosphorylation of the C-terminal domain of RNA polymerase II interaction with the Tat activation domain, and mediation of Tat activation of HIV-1 transcription. Pharmacological inactivation of Hsp90/Cdc37 function by geldanamycin revealed an essential role for the chaperone-Cdk9 complexes in generation of Cdk9/cyclin T1. Our data suggest a previously unrecognized chaperone-dependent pathway involving the sequential actions of Hsp70 and Hsp90/Cdc37 in the stabilization/folding of Cdk9 as well as the assembly of an active Cdk9/cyclin T1 complex responsible for P-TEFb-mediated Tat transactivation.

Single-dose ciprofloxacin for the treatment of uncomplicated gonorrhea: a worldwide summary.

BACKGROUND AND OBJECTIVES: Antibiotic therapy for Neisseria gonorrhoeae infections has evolved owing to the development of resistance to penicillin and tetracycline therapy. A variety of antimicrobials, including the fluoroquinolones, have been proposed as useful alternatives. GOAL OF THE STUDY: To evaluate the efficacy and safety of oral ciprofloxacin as single-dose treatment for urogenital and extragenital gonococcal infections. STUDY DESIGN: 1180 patients with uncomplicated gonococcal infection received single-dose ciprofloxacin regimens ranging from 100 mg to 2000 mg to demonstrate microbiologic efficacy and to determine the minimum effective dose. Eight of 18 studies were randomized, controlled trials with ampicillin/probenecid, amoxicillin/probenecid, ceftriaxone, or spectinomycin as control drugs. RESULTS: Although a ciprofloxacin dose-response was not detected, 250 mg was used in most of the studies. Among 815 patients with 910 infected sites receiving 250 mg of ciprofloxacin, bacteriologic eradication was achieved in 563 (100%) male urethral, 199 (100%) female cervical, 101 (99%) male and female rectal, and 47 (96%) male and female pharyngeal sites. CONCLUSION: Although the World Health Organization and the Centers for Disease Control and Prevention have identified 500 mg of ciprofloxacin as a single-dose treatment regimen for uncomplicated gonorrhea, the clinical data from the multinational studies indicate that a 250-mg single-dose of ciprofloxacin is equally effective in the management of uncomplicated gonorrhea, including extragenital sites of infection.

PIP: Between 1983 and 1990, an international review of 18 clinical trials was conducted to identify a single-dose regimen of ciprofloxacin that will attain at least a 95% efficacy rate for urogenital and extragenital uncomplicated Neisseria gonorrhoeae infections. The trials took place in the US, Argentina, the UK, Finland, Thailand, South Africa, Spain, Belgium, Poland, and the Netherlands. The studies consisted of 1180 patients who received a single-dose of 100-2000 mg ciprofloxacin. 8 studies compared the single-dose ciprofloxacin regimen with ampicillin/probenecid, amoxicillin/probenecid, ceftriaxone, or spectinomycin. 15 studies used, at least, a single-dose of 250 mg ciprofloxacin to treat 815 patients with 910 infected sites. This dose eradicated N. gonorrhoeae from 100% of male urethral, 100% of female cervical, 99% of male and female rectal, and 96% of male and female pharyngeal sites. In all 18 studies, ciprofloxacin was well tolerated. The leading side effects were headache and nausea. The wholesale cost of a single dose of 250 mg ciprofloxacin is lower than that of other antibiotics used to treat uncomplicated gonorrhea ($2.53 vs. $3.36 for 400 mg ofloxacin, $3.84 for 125 mg ceftriaxone, and $5.60 for 400 mg cefixime). Even though WHO and the US Centers for Disease Control recommend a single-dose of 500 mg ciprofloxacin to treat uncomplicated gonorrhea, the findings of the international studies suggest that a single dose of 250 mg ciprofloxacin effectively treats uncomplicated gonorrhea, even extragenital sites of infection.

Comparative crossover assessment of serum bactericidal activity and pharmacokinetics of ciprofloxacin and ofloxacin.

The study compared the pharmacokinetics and pharmacodynamics of ciprofloxacin and ofloxacin in 12 healthy male volunteers with normal renal function. Each volunteer received oral ciprofloxacin 500 mg, intravenous (i.v.) ciprofloxacin 400 mg, oral ofloxacin 400 mg, or i.v. ofloxacin 400 mg in a randomized, double-blind, crossover design with a one-week 'washout' period between doses. Mean peak serum concentrations were 4.48 and 5.44 mg/L for i.v. ciprofloxacin and ofloxacin, respectively. For the oral regimens, mean peak serum concentrations were 2.45 mg/L for ciprofloxacin and 4.44 mg/L for ofloxacin. Minimum bactericidal concentrations (MBC) and serum bactericidal activity (SBA) for each drug were measured against five strains of each of the following species: Escherichia coli, Klebsiella pneumoniae, Enterobacter aerogenes, Pseudomonas aeruginosa, Acinetobacter anitratus, Haemophilus influenzae, Staphylococcus aureus, and Streptococcus pneumoniae, using the microdilution method of the National Committee for Clinical Laboratory Standards (NCCLS). Ciprofloxacin was more active in vitro than ofloxacin against the tested species of Enterobacteriaceae and P. aeruginosa, while ofloxacin was slightly more active against A. anitratus. MBCs for the two drugs were similar for H. influenzae and S. aureus. Oral and i.v. ciprofloxacin in the doses given resulted in nearly equivalent SBA. Similarly, oral and i.v. ofloxacin had nearly equivalent SBA. For the i.v. and oral regimens of both agents, peak SBA was > or = 2 throughout the 12-hour test period against the Enterobacteriaceae and H. influenzae. At peak concentrations, both drugs had modest SBA against P. aeruginosa, A. anitratus, and S. aureus but little or no activity 8 and 12 h after dosing.(ABSTRACT TRUNCATED AT 250 WORDS)

Functional assessment of patients treated with permanent dual chamber pacing as a primary treatment for hypertrophic cardiomyopathy.

Patients with severe hypertrophic cardiomyopathy pose a difficult management problem. Between 1984 and 1986, 11 such patients have been treated by dual chamber pacing. (DDD). Subjectively all patients improved and objectively there was an increase in exercise tolerance during paced rhythm.

Family care in the coronary care unit: an analysis of clinical nurse specialist intervention.

A sudden and life-threatening illness requiring hospitalization and admission to the coronary care unit (CCU) can result in serious disorganization for the patient's family. This disorganization can become obvious to staff when family members are too anxious to hear important information about the patient or when families are unable to make decisions about the patient's treatment or disposition. Although CCU care is highly technical, it is not exclusively technical. Patients and their families need care that is considerate of the family group. In a case report, the Lazarus stress and coping framework is used to assess, intervene in, and evaluate care given to one family during an admission of a family member to the CCU. Although this framework is individually oriented and is particularly dependent on individual cognition, it proved useful for work with the described family.

Successful management of serious disopyramide poisoning.

A case of deliberate disopyramide overdosage is described. Circulatory collapse was treated by means of a large dose of isoprenaline, and charcoal haemoperfusion was used in an attempt to enhance the elimination of disopyramide. The suitability of this treatment regime is discussed in the light of findings from animal studies and the implications for the management of the disopyramide-poisoned patient are considered.

Cardiac consequences and treatment of disopyramide intoxication: experimental evaluation in dogs.

A slow (1.18 mumol.kg-1.mm-1) intravenous infusion of disopyramide (mol.wt 339) was given to 8 adult Beagle dogs. An initial phase of slow decline in cardiac output and broadening of the QRS complex on the ECG, with systolic blood pressure maintained above 13.5 kPa (100 mmHg), was followed by a phase of rapid circulatory failure without a correspondingly dramatic change in ECG appearances. Underventilation and cardiac arrhythmias were observed only in the agonal phase after several minutes of circulatory arrest. They were not therefore the primary cause of death, which was due to failure of myocardial contractility. Three positively inotropic drugs (isoprenaline, dopamine, and glucagon) are shown to be capable of restoring the failing circulation, provided they are given before the phase of complete circulatory standstill. In this respect isoprenaline appears superior to dopamine and glucagon.