Potential costs and effects of the National Service Framework for Coronary Heart Disease in the UK

OBJECTIVE: To estimate the costs and effect of implementing the National Service Framework for Coronary Heart Disease (CHD) in the UK. DESIGN: Decision trees were built on the results from randomised controlled trials on improving coronary revascularisation. All costs were presented in UK pounds (1997 values). PATIENTS: Each year 6600 new patients with CHD are expected to require revascularisation in the UK. INTERVENTIONS: The new patients would be equally divided into those undergoing coronary artery bypass grafting (CABG) and those undergoing a percutaneous coronary intervention (PCI) i.e., percutaneous transluminal angioplasty (PCTA). PTCA could be administered with or without abciximab (a glycoprotein IIb/IIIa receptor antagonist), stent, or stent plus abciximab (stent+). RESULTS: CABG/stent alone has an incremental cost of more than 115,489 pounds per additional quality-adjusted life-year (QALY) gained compared with CABG/ PTCA+. This high incremental cost is not attractive because if CABG/ stent would be added to abciximab (CABG/stent+) its incremental cost-effectiveness ratio would be 2529 pounds per extra QALY compared with CABG/stent. Therefore, the debate should not be limited to the issue of stents but it should focus on the need for administering abciximab in addition to stent. The 5-year direct costs of implementing such a strategy in the UK is expected to be 50.6 million pounds (1997 values). CONCLUSIONS: Abciximab and probably any glycoprotein IIb/IIIa receptor antagonists should be added to any PCI, especially if stents are used.     

Short-term exposure of Chinook salmon (Oncoryhnchus tshawytscha) to o,p-DDE or DMSO during early life-history stages causes long-term humoral immunosuppression

We evaluated the effect of short-term exposures to a xenobiotic chemical during early life-history stages on the long-term immune competence of chinook salmon (Oncoryhnchus tshawytscha). Immersion of chinook salmon eggs in a nominal concentration of o,p-dichlorodiphenyldichloroethylene (o,p-DDE; 10 ppm) for 1 hr at fertilization followed by immersion in the same dose for 2 hr at hatch resulted in a significant reduction in the ability of splenic leukocytes from fish 1 year after treatment to undergo blastogenesis upon in vitro stimulation with lipopolysaccharide. We also observed that the vehicle, dimethyl sulfoxide (DMSO), caused a significant reduction in the ability of the splenic leukocytes to express surface immunoglobin M (SIgM) at this time. The concentration of o,p-DDE in a pooled sample of whole fry from this treatment was 0.53 microg/g lipid 1 month after first feeding but was undetectable in all other treatments. Mortality rate, time to hatch, fish length, and weight were unaffected by treatment with o,p-DDE. Similarly, sex ratios, gonadal development, and concentrations of plasma estradiol and 11-ketotestosterone were not affected by the treatment. In addition, we found no evidence that plasma lysozyme concentrations or the mitogenic responses of splenic leukocytes to concanavalin A or polyinosinic-polycytidylic acid were influenced by the treatment. In this experiment, a brief period of exposure to o,p-DDE or DMSO during early development was able to induce long-term effects on humoral immune competence of chinook salmon. Such immunosuppression may increase susceptibility to disease, which may in turn be critical to regulating the population.     

The cooling effect of liquid flow on the focussed ultrasound-induced heating in a simulated foetal brain

There is a need to investigate the thermal effects of diagnostic ultrasound (US) to assist the development of appropriate safety guidelines for obstetric use. The cooling effect of a single liquid flow channel was measured in a model of human foetal brain and skull bone heated by a focussed beam of simulated pulsed spectral Doppler US. Insonation conditions were 5.7 micros pulses, repeated at 8 kHz from a focussed transducer operating with a centre frequency of 3.5 MHz, producing a beam of -6 dB diameter of 3.1 mm at the focus and power outputs of up to 255 +/- 5 mW. Brain perfusion was simulated by allowing distilled water to flow at various rates in a 2 mm diameter wall-less channel in the brain soft tissue phantom material. This study established that the cooling effect of the flowing water; 1. was independent of the acoustic source power, 2. was more effective close to the flow channel, for example, there was a marked cooling at a distance of 1 mm and negligible cooling at a distance of 3 mm from the channel; and 3. initially increased at low flow rates, but further increase above normal perfusion had very little effect.     

Construction and biological characterization of an infectious molecular clone of HIV type 1GB8

Here we report the construction, sequencing, and repair of a molecular clone of HIV-1GB8, a virus representative of HIV-1 subtype B strains circulating in the UK. The phenotype of virus produced by the clone matches that of the parental virus. The molecular clone will be used in the production of attenuated virus stocks for chemical inactivation to allow development of faccines based on killed whole virus preparations.     

The value of cystoscopy and bladder biopsy taken at the time of tension-free vaginal tape insertion.

The primary aim of this study was to determine if a cystoscopy performed at the time of a tension-free vaginal tape (TVT) insertion is useful in finding unexpected pathology. A secondary outcome measure was to assess whether a bladder biopsy and cystoscopy performed during the TVT operation provide useful information about the outcome of surgery. The findings in 100 consecutive women were reviewed. A total of 42 women demonstrated mixed detrusor overactivity (DO) and urodynamic stress incontinence (USI); 32 women had abnormal biopsies. Women with DO were no more likely to have abnormal bladder biopsies than women without DO (p > 0.05). An abnormal bladder biopsy or cystoscopy failed to predict postoperative irritable symptoms (p > 0.05). The presence of preoperative DO correctly predicted postoperative irritable symptoms (p < 0.01). Cystoscopic abnormalities were noted in 14 women including one carcinoma, and one case of dysplasia was discovered on biopsy. In five women, the cystoscopy showed a bladder perforation. Cystoscopy should be performed in all women undergoing continence procedures.     

Twenty-four-hour heart rate variability to assess autonomic function in Parkinson's disease

OBJECTIVES: To evaluate the autonomic dysfunction in Parkinson's disease patients by means of a 24-h heart rate variability (HRV) method. MATERIAL AND METHODS: Thirteen patients with a diagnosis of Parkinson's disease were compared with 13 age-matched healthy persons (control group). The 13 patients had a mean age of 70.5 years, and mean disease duration of 10.9 years. The autonomic function was evaluated by HRV analysis using a continuous 24-h ECG. The parameters of SDNN (standard deviation of the normal-to-normal intervals between adjacent QRS complexes), of LF (power in low frequency) and of HF (power in high frequency) were studied during the following 3 periods: 24 h, night and day. RESULTS: The data show a statistically significant difference between groups for SDNN and LF in all the periods, while for HF parameters the difference is statistically significant only in the night period. CONCLUSION: The use of the 24-h HRV method can provide more accurate and reproducible data than other conventional cardiovascular tests.     

Grafting an RGD motif onto an epidermal growth factor-like module: chemical synthesis and functional characterization of the chimeric molecule

Abstract: A novel protein was engineered by inserting the GRGDS motif of fibronectin within the 14-residue loop of the EGF-like module from human complement protease C1r. The resulting chimeric EGF-RGD module (52 residues, three disulfide bridges) was assembled by automated solid-phase synthesis using the t-Boc strategy. Using reduced/oxidized glutathione, the EGF-RGD module was folded as efficiently as the natural C1r-EGF module, resulting in formation of the appropriate disulfide bridge pattern as shown by mass spectrometry and N-terminal sequence analyses of thermolytic fragments. Circular dichroism and NMR measurements provided further indication that introduction of the GRGDS motif had no significant effect on the folding. Using Chinese Hamster Ovary (CHO) cells bearing the integrin receptors specific for fibronectin and vitronectin, EGF-RGD was shown to induce cell adhesion via the introduced GRGDS motif. Cell binding was inhibited specifically and efficiently by the synthetic peptide GRGDSP and by fibronectin, and to a much lesser extent by vitronectin, whereas the monoclonal antibody PB1 directed to the α5 subunit of α5β1 integrin had no effect. The ability of EGF-RGD to trigger significant cell spreading and intracellular signaling was also demonstrated using immunofluorescence and confocal microscopy.     

A Reappraisal of Storage and Voiding Dysfunction

Lower urinary tract symptoms are common in women. They may be more broadly classified into storage and voiding disorders. Recent literature has focussed on the management of voiding dysfunction and the spectrum of symptoms presented by women with such disorders. Symptoms of voiding dysfunction and storage symptoms may coexist, making diagnosis and management even more challenging. The purpose of this paper is to review the literature regarding the definition and management of voiding dysfunction with and without associated storage symptoms.