Carvedilol--A new nonselective beta blocker.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to P Hayes.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
OBJECTIVES: National and state data on the health, social, and economic consequences of unintended pregnancy prompted Washington policy makers to identify strategies to reduce such pregnancies. Though not well known, emergency contraceptive pills (ECPs) are a safe and effective contraceptive method that can prevent pregnancy if taken within 72 hr after unprotected intercourse. A coalition conceived the idea of enabling pharmacists to prescribe ECPs directly to women through collaborative drug therapy agreements (CDTAs) with physicians. METHODS: Following a feasibility study, five agencies initiated a novel pilot project in western Washington. Key components included informing pharmacists about ECPs and CDTAs; developing tools, providing training, and developing systems to establish pharmacist/ prescriber collaborative agreements; conducting a public awareness campaign; evaluating the impact of the project; and disseminating the results. RESULTS: More than 1000 pharmacists received training in all aspects of providing ECPs and 140 pharmacies participated in the project, with more than 145 CDTA on file. In the 16 months of pharmacy service provision, 11,969 ECP prescriptions were provided, possibly preventing 700 or more unintended pregnancies. The media launch led to 200 broadcast stories and increased calls to the ECP Hotline from 116 to an average of 1160 per month. CONCLUSION: Enabling pharmacists to provide ECPs directly to women is a convenient delivery system for a time-limited therapy. It increases the chances that women will use the therapy effectively and connects women without a provider to a source of care. By increasing access to an effective contraceptive, this projects supports the Washington State goal of reducing unintended pregnancy.
Explore the source record for details and available documents.
The contributions of beat-to-beat changes in mean arterial blood pressure (MABP) and breath-by-breath fluctuations in end-tidal CO2 (EtCO2) as determinants of the spontaneous variability of cerebral blood flow velocity (CBFV) were studied in 16 normal subjects at rest. The two input variables (MABP and EtCO2) had significant cross-correlations with CBFV but not between them. Transfer functions were estimated as the multivariate least mean square finite impulse response causal filters. MABP showed a very significant effect in explaining CBFV variability (p < 10(-11), Fisher's aggregated-p test) and the model mean square error was significantly reduced (p < 0.001) by also including the contribution of EtCO2. The estimated mean CBFV step response to MABP displayed the characteristic return to baseline caused by the cerebral autoregulatory response. The corresponding response to EtCO2 showed a gradual rise taking approximately 10 s to reach a plateau of 2.5%/mmHg. This study demonstrated that spontaneous fluctuations in EtCO2 can help to explain the CBFV variability at rest if appropriate signal processing techniques are employed to address the limited power and bandwith of the breath-by-breath EtCO2 signal.
Explore the source record for details and available documents.
Heterosexual transmission of human immunodeficiency virus (HIV) is the most frequent mode of infection worldwide. However, the immediate events between exposure to infectious virus and establishment of infection are still poorly understood. This study investigates parameters of HIV infection of human female genital tissue in vitro using an explant culture model. In particular, we investigated the role of the epithelium and virucidal agents in protection against HIV infection. We have demonstrated that the major target cells of infection reside below the genital epithelium, and thus HIV must cross this barrier to establish infection. Immune activation enhanced HIV infection of such subepithelial cells. Furthermore, our data suggest that genital epithelial cells were not susceptible to HIV infection, appear to play no part in the transfer of infectious virus across the epithelium, and thus may provide a barrier to infection. In addition, experiments using a panel of virucidal agents demonstrated differential efficiency to block HIV infection of subepithelial cells from partial to complete inhibition. This is the first demonstration that virucidal agents designed for topical vaginal use block HIV infection of genital tissue. Such agents have major implications for world health, as they will provide women with a mechanism of personal and covert protection from HIV infection.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
BACKGROUND: Adequacy of delivered dialysis is important in preventing morbidity in patients on hemodialysis for end-stage renal disease. A satisfactory KT/V is often difficult to obtain in patients with a large body mass despite optimization of remediable factors. AIM: This pilot study was performed to examine the hypothesis that twin dialyzers in parallel enhance delivered KT/V. METHODS: Three compliant patients on maintenance hemodialysis with post-dialysis weights greater than 95 kg who had a KT/V between 1.0 and 1.3 despite optimization of duration of dialysis, blood flow rates and anticoagulation and absence of access recirculation were studied using twin dialyzers in parallel after in vitro experiments demonstrated the safety of this technique. After a run-in period lasting over six months, during which the technique was perfected, three study treatments with twin dialyzers were compared to three treatments before and three treatments after study treatments. Both study and control treatments were performed under identical, rigidly standardized conditions. There was a wash-out period before the control and the study treatments. KT/V was calculated using the post-dialysis blood urea nitrogen (BUN) obtained by the stop-flow technique. RESULTS: KT/V was higher with twin dialyzers in parallel than with single dialyzers (mean +/- SD 1.54 +/- 0.32 for twin dialyzers vs 1.33 +/- 0.11 for single dialyzers) despite the lack of significant differences in potentially confounding variables. CONCLUSIONS: Using twin dialyzers in parallel appears to enhance delivered KT/V and is a safe and potentially useful technique especially in patients with a large body mass.
The organization and structure of the murine GH gene encoding gamma-glutamyl hydrolase were determined. The murine GH gene spans 24kb and was found to be distributed in nine exons. The intron/exon coding junctions delineated conformed to the GT-AG rule. The 5' UTR and 3' UTR along with some coding sequences were incorporated in exons 1 and 9, respectively, whereas exons 2-8 incorporated only coding sequence. A relatively GC-rich region of the genome 5' of exon 1 was distinctly promoter-like and encoded a number of putative cis-acting elements, including six Sp1 sites known to be involved in the regulation of transcription but no TATA sequence motif. Primer extension analysis of this region with mouse liver and S180 cell mRNA revealed several tsps within the region encompassing the Sp1 sites. Functional analysis of this 5' upstream region of sequence was carried out by inserting it into the pGL3 reporter gene vector for transfection into NIH3T3 cells. The transcription of the luciferase gene that resulted in these cells established the identity of this region as an active promoter for the mouse GH gene.
Explore the source record for details and available documents.
BACKGROUND: Although microembolization may not be associated with focal neurological events following carotid endarterectomy (CEA), it might contribute towards cognitive impairment. METHODS: Forty-nine patients undergoing CEA underwent 30 min of preoperative ipsilateral transcranial Doppler (TCD) monitoring and a battery of tests of cognitive function, and the results were compared with those of age-matched normal controls. RESULTS: Seven patients who were spontaneously embolizing had significantly worse preoperative cognitive function scores than 42 patients with no recorded emboli (P = 0.03). Overall, patients undergoing CEA had a significant cognitive deficit compared with age-matched normal controls. CONCLUSION: Patients who have evidence of spontaneous preoperative embolization on TCD monitoring have a greater degree of preoperative cognitive impairment. This finding underlines the potential clinical importance of microembolization and suggests that this phenomenon should be investigated further.
BACKGROUND: Evidence suggests that embolization precedes carotid thrombosis, a previously unpredictable event complicating 2-3 per cent of all carotid endarterectomies. It was hypothesized that dextran 40 therapy might prevent progression to complete thrombosis in high-risk patients. METHODS: Between October 1995 and July 1998, 400 consecutive patients were monitored following carotid endarterectomy using transcranial Doppler ultrasonography. Those with sustained embolization (more than 25 in 10 min) or those with emboli that distorted the middle cerebral artery waveform were commenced on an incremental dextran 40 infusion. RESULTS: Two hundred and sixteen patients (54 per cent) had one or more emboli detected (96 per cent within 2 h of flow restoration) but only 15 (4 per cent) required dextran therapy. Embolization ceased in each case although the dextran dose had to be adjusted in four. In one of the latter patients, embolization recurred on day 5 but was again controlled with high-dose dextran. Overall, the death and any stroke rate was 2 per cent and no patient suffered a stroke due to carotid thrombosis. CONCLUSION: A few patients develop sustained embolization following carotid endarterectomy which, in previous studies, has been shown to be highly predictive of carotid thrombosis. The authors' experience to date suggests that dextran can stop this phase of embolization and prevent progression to complete carotid thrombosis. However, the dose of dextran has to be adjusted in 25 per cent of patients (i.e. blind administration of dextran may not be effective) and, very rarely, embolization may recur later.
BACKGROUND: Prosthetic graft infection following abdominal aortic aneurysm (AAA) surgery is life threatening. Treatment options include total graft excision and extra-anatomic bypass or in situ replacement of the graft. The latter option is gaining popularity but the long-term outcome remains uncertain, particularly in light of the increasing prevalence of methicillin-resistant Staphylococcus aureus (MRSA) infection. A retrospective study was undertaken to assess the outcome after graft excision and in situ replacement with a rifampicin-bonded prosthesis for the treatment of major aortic graft infection. The prevalence of MRSA and its influence on outcome was also assessed. METHODS: Over 6 years between January 1992 and December 1997, 11 patients (eight men) with major aortic graft infection underwent total graft excision and in situ replacement with a rifampicin-bonded prosthesis. RESULTS: The median age was 66 (range 49-78) years. Four patients presented with haemorrhage from an aortoenteric fistula, three had retroperitoneal abscess, two had graft occlusion, one had a perigraft collection on computed tomography and one presented with a ruptured suprarenal false aneurysm. Organisms were cultured from ten patients. Staphylococcus epidermidis and Streptococcus faecalis were predominant. MRSA was isolated from two patients, both of whom had originally undergone ruptured AAA repair. Two patients died and three suffered non-fatal complications. Two patients died during follow-up, one from suspected ongoing MRSA infection and the other from recurrent graft infection. Seven patients remain alive and clinically free from infection, although two were lost to follow-up at 12 and 15 months. CONCLUSION: The long-term results following total graft excision and in situ replacement with a rifampicin-bonded prosthesis appear to be favourable. MRSA infection seems to be associated with a poor prognosis.
BACKGROUND: Six hours' monitoring by transcranial Doppler (TCD) has been successful in directing Dextran therapy in patients at high risk of thrombotic stroke after carotid endarterectomy (CEA). OBJECTIVES: Is 3 h of routine monitoring as effective as 6 h in the prevention of early postoperative thrombotic stroke? DESIGN: Prospective, consecutive study in all patients with an accessible cranial window. METHODS: One hundred and sixty-six patients undergoing CEA underwent 3 h of postoperative monitoring by TCD. Any patient with > 25 emboli detected in any 10 min period or those with emboli that distorted the arterial waveform were commenced on an incremental infusion of dextran 40. RESULTS: The majority of patients destined to embolise will do so within the first 2 postoperative hours. Dextran therapy was instituted in nine patients (5%) and rapidly controlled this phase of embolisation although the dose had to be increased in three (33%). No patient suffered a postoperative carotid thrombosis but one suffered a minor stroke on day 5 and was found to have profuse embolisation on TCD; high dose dextran therapy was again instituted, the embolus count rate fell rapidly and he made a good recovery thereafter. Overall, the death and disabling stroke rate was 1.2% and the death/any stroke rate was 2.4%. CONCLUSION: Three hours of postoperative TCD monitoring is as effective as 6 h in the prevention of postoperative carotid thrombosis.
Arterial pCO2 is known to influence cerebral autoregulation but its effect on the dynamic relationship between mean arterial blood pressure (ABP) and mean cerebral blood flow velocity (CBFV), obtained from spontaneous fluctuations in ABP, has not been established. In 16 normal subjects, ABP was measured non-invasively (Finapres), CBFV was estimated with Doppler ultrasound in the middle cerebral artery, and end-tidal CO2 (EtCO2) was measured with an infrared capnograph. Recordings were made before, during and after breathing a mixture of 5% CO2 in air. The coherence function, amplitude and phase frequency responses, and impulse and step responses for the effects of ABP on CBFV were calculated by spectral analysis of beat-to-beat changes in mean ABP and CBFV before (mean CO2 5.55 +/- 0.38 kPa), during (6.43 +/- 0.31 kPa) and after 5% CO2 (5.43 +/- 0.26 kPa). During 5% CO2, the coherence function and the amplitude frequency response were significantly increased for frequencies below 0.05 Hz and the phase was reduced for the frequency range 0.02-0.1 Hz. The impulse and step responses indicated that 5% CO2 reduces the efficiency of the autoregulatory mechanism. A 20.7% average increase in CBFV induced by a 14.4% increase in EtCO2 was found to be mediated by a 25.9% reduction in critical closing pressure, while the change in resistance area product was non-significant.
UNLABELLED: We performed a prospective study to examine the impact of dialyzer reuse on KT/V under rigidly standardized conditions on 3 membrane types. Heparin dosage was standardized with ACT during an eight week run-in period and remained unchanged through the study. Post dialysis BUN and weight were obtained at five minutes after exactly 80 +/- 0.5 l of blood were processed through the dialyzer. Dialyzers were reused after automated glutaraldehyde processing and after ensuring >80% open fiber bundles. Each membrane type was utilized 3 times on a set of 3 patients; each individual dialyzer was reused 8 times. KT/V was done on the 1st, 2nd, 4th and 8th uses of each dialyzer (36 measurements) starting mid week; BUN measurements were grouped. The KT/V (mean +/- SD) for the 1st, 2nd, 4th, and 8th uses of the cellulose acetate dialyzer were 1.3 +/- 0.2, 1.3 +/- 0.3, 1.3 +/- 0.2, 1.3 +/- 0.2 respectively; the corresponding values of the cuprophane dialyzer were 1.4 +/- 0.3, 1.4 +/- 0.3, 1.3 +/- 0.4, 1.3 +/- 0.3 respectively; and those of the polysulfone dialyzer 1.7 +/- 0.3, 1.6 +/- 0.2, 1.6 +/- 0.2 respectively. By a 3 way ANOVA there were no significant differences between the 1st and subsequent uses of any of the dialyzers tested. CONCLUSIONS: Reuse of dialyzers up to 8 times does not result in a loss of urea clearance. We believe this model is useful for further studies on reuse and quality assurance.