Description of a chronic heart failure service model and review of pharmacotherapy in a district general hospital in comparison to Scottish Intercollegiate Guideline Network (SIGN) guidelines.

BACKGROUND: The Scottish Intercollegiate Guidelines Network (SIGN) guideline 95 on the management of chronic heart failure (CHF) was published in February 2007, superseding SIGN guideline 35 of February 1999. The guideline promotes evidence based management of CHE. AIMS: To describe an existing service model and to review our level of concordance with SIGN guidelines. METHODS: We describe a model of a CHF service based in a district general hospital (DGH) in Scotland. We conducted a retrospective review on consecutive new referrals between August and November 2002, and a prospective review of new attendances between September 2005 and January 2006. RESULTS: In 2002 and 2005/6, 49 and 45 patients were reviewed respectively, with 26 and 28 patients showing left ventricular systolic dysfunction on echocardiography. Median ages of patients were 81 and 79 years respectively. Angiotensin Converting Enzyme Inhibitor (ACEI) or Angiotensin II Receptor Blocker (AIIRB) therapy was in use in 23 (88.5%) and 24 (85.7%) patients respectively. The use of beta-blockers, digoxin and spironolactone was shown to have improved between both reviews. CONCLUSIONS: We have been able to demonstrate an improving level of concordance with SIGN guidelines in a district general hospital (DGH) heart failure service model run by care of the elderly physicians and supported by specialist nurses.

Outcomes of permanent pacemaker implantation for carotid sinus hypersensitivity in a district general hospital with a Falls Fits Faints and Funny Turns Clinic.

UNLABELLED: Permanent pacemaker implantation is considered for carotid sinus hypersensitivity with asystolic pause of > 3 seconds during carotid sinus massage, with or without associated systolic blood pressure drop of > 50 mmHg. AIMS: To assess the outcome of treatment with dual chamber permanent pacemaker implantation for carotid sinus hypersensitivity in a district general hospital and to compare our practice with available national data. METHODS: Patients presenting with syncope, dizziness or unexplained falls were initially assessed as outpatient and investigations, commonly cardiovascular were performed including tilt table test with carotid sinus massage to look for carotid sinus hypersensitivity, vasovagal syncope and postural hypotension. A retrospective analysis was performed on patients who had pacemaker implantations for carotid sinus hypersensitivity. RESULTS: Fifty pacemaker implantations were performed, 14 (28%) were for carotid sinus hypersensitivity. Mean follow-up period was 10 months. Age range was 56-88 (mean = 71.9) years. In the eighteen months prior to pacemaker implantation, 71.4% of patients had syncope, 64% dizziness and 50% had unexplained falls. Following pacemaker implantations, only 2 (14.3%) had symptoms. Scottish national figures show 13.6% of all new pacemaker implants were for carotid sinus hypersensitivity, and in district general hospitals this was 16%. CONCLUSIONS: Health benefits for patients presenting with syncope dizziness and falls can be achieved by cardiovascular investigations including tilt table testing. We have shown carotid sinus hypersensitivity is successfully treated with pacemaker implantation in a district general hospital setting and this type of clinic has an impact on the rate and type of new pacemaker implantation.

Analysis of six months' referrals to a "one-stop" neurovascular clinic in a district general hospital: implications for purchasers of a stroke service.

OBJECTIVE: To determine the effectiveness of a "one-stop" neurovascular clinic (NVC) in guiding the diagnosis and investigation of patients suffering a mild stroke or transient ischaemic attack (TIA). DESIGN: Six months' survey of the activity of a new neurovascular clinic (NVC). SETTING: Borders region of Scotland. SUBJECTS: Patients referred with a suspected diagnosis of stroke or TIA. RESULTS: The clinic served 23 general practices and a population of 106,000. Over a 6 month period 128 patients were referred; 93% of patients were referred by general practitioners, 5% by consultant physicians and 2% from wards in the Borders General Hospital. Most patients were independent prior to the presenting event and had minimal disability on presentation to the clinic. Patients were seen within 48 hours of referral in the majority of cases and all within five working days. However, only 52% were seen within two weeks of the onset of their symptoms. Only 50% of patients were shown to have sustained a stroke or TIA. A variety of other diagnoses mimicked vascular events including epilepsy, migraine, cranial nerve palsies and cerebral tumour. The stroke-related group differed significantly in age (P = 0.003) and in the number of patients already on aspirin (P = 0.010) but not in any other risk factor. CT scan and carotid doppler examination were considered necessary in only 47% and 24% respectively of referred patients. Only five stroke-related patients and one non-stroke-related patient needed further input from physiotherapy, occupational therapy or speech therapy. Over 90% of patients were discharged home. Patient and general practitioner satisfaction with the service received were rated at 9 (0 = very poor; 10 = excellent). CONCLUSION: Applying evidence-based medicine to patients attending a "one-stop" neurovascular clinic with minor stroke and/or transient ischaemic attack resulted in an efficient delivery of appropriate investigations and therapy to this group of patients. The NVC prevented unnecessary requests for both CT scanning and carotid doppler examination, which are valuable resources, and may have prevented admissions to hospital. Patients were anxious about their symptoms and appreciated being seen quickly and a diagnosis made. We would recommend that these clinics be set up as part of the stroke service in all district general hospitals.

Joining forces: a realistic approach for gynecologic oncology services in a midsize community.

In summary, the team approach model to problem-solving worked to meet some of the gynecologic oncology needs for women in northern Indiana. The steps of clarifying the issue, identifying potential problems and needs, setting goals and a timetable, establishing an implementation plan and assigning accountability for the steps helped to successfully bring a Gynecologic Oncology Clinic to South Bend. The final step, that oftentimes sets up another chain of events, is re-evaluating the clinic from cost, quality and service delivery perspectives. This will be done prior to the end of the year.

Aortic stenosis in elderly people: an evaluation of clinical and echocardiographic diagnosis.

In a prospective study to assess the sensitivity and specificity of clinical diagnosis against echocardiographic diagnosis in elderly people, 41 patients were studied in two 6-month periods. Overall clinical and echo diagnosis agreed in 75% of cases, but the clinical diagnosis of aortic stenosis was poor in the initial period. Adapting the lessons which were learnt in this initial period in a repeat of the study, the sensitivity of clinical diagnosis of aortic stenosis improved from 0.38 to 0.75. Additional information was gained in 50% of cases by echocardiography, and enabled the clinician to modify treatment in 50% of cases. Aortic stenosis in elderly people may be without clinical signs. Routine echocardiography increases the sensitivity of the clinical diagnosis, and may have major therapeutic implications for the elderly patient.

Two regions within the human IL-2 gene promoter are important for inducible IL-2 expression.

We have examined regulatory domains of the human IL-2 gene promoter by transfection and transient expression of rDNA constructs in which the chloramphenicol acetyl transferase gene shows T cell-specific inducible expression and cyclosporin A-mediated inhibition when placed downstream of 587 bp of the human IL-2 5'-flanking region. A series of 5'-deletion constructs transfected into the Jurkat T lymphoid line demonstrates that a region encompassing 370 bp 5' of the transcription start site is sufficient for inducible chloramphenicol acetyl-transferase expression. Further dissection of this region with internal deletion (linker-scanner) mutants revealed that portions of at least two discrete regions from -42 to -169 and -289 to -361 bp relative to the transcription start site are critical for inducible expression of the IL-2 gene. T cell-specific expression of wild-type and mutant IL-2 promoter constructs could be increased severalfold by the insertion of an upstream SV40 enhancer. With use of a battery of IL-2 promoter constructs, we could not identify subregions within IL-2 5'-flanking sequences which are crucial for cyclosporin A inhibition of the IL-2 gene or deletion of which resulted in loss of T cell-specific expression, suggesting that such functions may be mediated at pre-transcriptional levels.

Retroviral activation of interleukin 2 gene in a gibbon ape T cell lymphoma line.

The gibbon ape leukemia virus (GaLVSF)-infected T cell line, MLA 144, was established from the lymphoma of a gibbon ape. The cell line constitutively expresses IL-2 and its receptor, implying that an autocrine mechanism could be responsible for or contribute toward its growth. To explore the mechanism of constitutive IL-2 expression in MLA 144, we have isolated and characterized cosmid clones representing a normal and a doubly inserted IL-2 allele in this cell line. The map of the normal MLA 144 IL-2 allele closely resembles that of the normal human IL-2 gene. The abnormal allele contains a 3' insertion that is a GaLVSF provirus with two long terminal repeats (LTR) and an internal 3.25 kb deletion. At the 5' end of the abnormal allele is a second insertion that DNA sequencing showed to be an isolated GaLVSF LTR with a transcriptional orientation opposing that of the IL-2 gene. We demonstrate by Northern blotting analysis that the vast majority of transcripts are from the abnormal allele, implying that one or both retroviral insertions are responsible for constitutive expression of the allele.

Promoter region of interleukin-2 gene undergoes chromatin structure changes and confers inducibility on chloramphenicol acetyltransferase gene during activation of T cells.

The chromatin structure of the interleukin-2 (IL-2) gene was probed by DNase I treatment of isolated nuclei. The 5' region of the IL-2 gene contains three regions of hypersensitivity to DNase I. When peripheral blood T cells or Jurkat T cells are stimulated with mitogens, IL-2 message is induced, and the promoter region of the IL-2 gene develops an additional hypersensitive site. This suggests that a DNA sequence close to the transcriptional start site is involved in the transduction of the extracellular signal. Such a conclusion is further supported by DNA transfection experiments. A short segment of DNA, which includes the region of induced hypersensitivity, confers inducibility on the linked chloramphenicol acetyltransferase gene in transiently transfected Jurkat cells. In addition, cells of nonhematopoietic origins exhibit a strikingly different chromatin pattern of IL-2, suggesting a role during differentiation for some of the hypersensitive sites.