Optimising physiotherapy for people with lateral elbow tendinopathy - Results of a mixed-methods pilot and feasibility randomised controlled trial (OPTimisE).

BACKGROUND: The OPTimisE intervention was developed to address uncertainty regarding the most effective physiotherapy treatment strategy for people with Lateral Elbow Tendinopathy (LET). OBJECTIVES: To assess the feasibility of conducting a fully-powered randomised controlled trial (RCT) evaluating whether the OPTimisE intervention is superior to usual physiotherapy treatment for adults with LET. DESIGN: A mixed-methods multi-centred, parallel pilot and feasibility RCT, conducted in three outpatient physiotherapy departments in the UK. METHOD: Patients were independently randomised 1:1 in mixed blocks, stratified by site, to the OPTimisE intervention or usual care. Outcomes were assessed using pre-defined feasibility progression criteria. RESULTS: 50 patients were randomised (22 Female, 28 Male), mean age 48 years (range 27-75). Consent rate was 71% (50/70), fidelity to intervention 89% (16/18), attendance rate in the OPTimisE group 82% (55/67) vs 85% (56/66) in usual care, outcome measure completion 81% (39/48) at six-month follow-up. There were no related adverse events. Patients and physiotherapists reported that the OPTimisE intervention was acceptable but suggested improvements to the trial design. 49 patients were recruited from physiotherapy referrals vs one from primary care records. Outcome measure return rates were higher when completed online (74%) compared to postal questionnaire (50%). Exploratory analysis showed improvements in both groups over time. CONCLUSIONS: It is methodologically feasible to conduct a fully powered RCT comparing the clinical and cost-effectiveness of the OPTimisE intervention versus usual physiotherapy treatment. Considering the similar improvements observed in both groups, careful consideration is needed regarding the priority research question to be addressed in future research.

Discovery of 4-[3-(trans-3-dimethylaminocyclobutyl)-1H-indol-5-ylmethyl]-(4S)-oxazolidin-2-one (4991W93), a 5HT(1B/1D) receptor partial agonist and a potent inhibitor of electrically induced plasma extravasation.

Utilizing a pharmacophoric model of binding of 3-(2-aminoethyl)indoles to 5HT(1B/1D) receptors, we identified the 3-aminocyclobutyl group as a potential ethylamine isostere. A novel multidimensional chemometric approach was used to predict the intrinsic activity (degree of agonism) at the receptor. A qualitative model for pharmacokinetic properties was then used to guide the synthesis toward molecules likely to have oral bioavailability in humans. A novel synthetic route to 3-(3-dimethylaminocyclobutyl)indoles was developed. Analogues showed generally lower intrinsic activity at 5HT(1B/1D) receptors than their ethylamine counterparts. 4-[3-(trans-3-Dimethylaminocyclobutyl)-1H-indol-5-ylmethyl]-(4S)-oxazolidin-2-one (4991W93, 1) was identified as a partial agonist against 5HT(1B/1D) receptors, with low intrinsic activity. This molecule also has significant activity against 5HT(1F) receptors but is selective over other 5HT receptors. In addition this compound was found to be an exceptionally potent inhibitor of electrically induced plasma extravasation. Compound 1 may have utility in the treatment and prophylaxis of migraine.

The pharmacological properties of the novel selective 5-HT3 receptor antagonist, alosetron, and its effects on normal and perturbed small intestinal transit in the fasted rat.

The purpose of this study was to investigate the pharmacological properties of the novel, selective 5-HT3 receptor antagonist, alosetron, and its effects on transit time in both the normal and perturbed small intestine of the rat. Alosetron concentration-dependently inhibited radioligand binding in membranes containing rat and human 5-HT3 receptors with estimated pKi values of 9.8 (n = 3) and 9.4 (n = 6), respectively. In selectivity studies alosetron had little or no significant affinity for any of the many other receptors and ion channels studied. Alosetron potently antagonized the depolarization produced by 5-HT in the rat vagus nerve (estimated pKB value of 9.8, n = 25). In anaesthetized rats, i. v. administration of alosetron inhibited 2-methyl-5-HT induced bradycardia (Bezold Jarisch index) at 1 and 3 microg kg-1, with an agonist dose ratio of approximately 3.0 at 1.0 microg kg-1, = 3-5). Alosetron administered via the duodenum also inhibited this reflex, with duration of action that was significantly longer than that seen with ondansetron (120-60 min, respectively, n = 6). Alosetron had no significant effect on normal small intestinal propulsion in the rat, but fully reversed the increase in intestinal propulsion (96%, n = 3) produced by egg albumin challenge. Alosetron is a highly selective 5-HT3 antagonist which normalizes perturbed small intestinal propulsion. Previous clinical data in IBS patients together with the transit data provide a good rationale for further studies with alosetron in IBS patients.

Dental implants. 7. Basic restorative techniques.

Some restorative techniques for implant supported restorations will be familiar to dentists used to providing conventional crown and bridgework. The differences and principles involved when using implants are identified.

Advanced restorative techniques.

Many alternative techniques are available to ensure the best possible outcome for an implant restoration.

Negligible prevalence of antibodies against Trypanosoma cruzi among blood donors in the southeastern United States.

Trypanosoma cruzi, a hemoflagellate, causes Chagas' disease and is endemic throughout Latin America. Increasing Latin American immigration to the United States has enhanced concern about transmission of Chagas' disease by infected donor blood. The insect vector and parasites also have been found in the southeastern United States. Autochthonous infection of several species of wild and domesticated mammals suggests that the general human population also may be at risk. To assess the prevalence of antibodies to T cruzi in humans, randomly selected donor blood was screened. Initial screening was performed by indirect hemagglutination (1:4 initial serum dilution) and at least one of three different enzyme immunoassays. All samples testing positive by at least one screening method were tested by radioimmunoprecipitation and indirect immunofluorescence supplemental methods, which were used for confirmation and calculation of specificity. Of the 6,013 serum samples evaluated, 85 tested positive by one screening method. Only 10 of the samples tested positive by more than one method. The percentages of positive screening tests are 0.05% by indirect hemagglutination and 0.06%, 0.91%, 3.97% by Abbott Laboratories (Abbott Park, Ill), Gull (Gull Laboratories, Salt Lake City, Utah), and Polychaco (Polychaco S.A.I.C., Buenos Aires, Argentina) enzyme immunoassays, respectively. All samples were negative by radioimmunoprecipitation and indirect immunofluorescence. These results suggest that although parasite and vector are found in the southeastern United States and both infect mammals, the risk of natural infection to humans in this region seems to be negligible. There was variation in positivity among different screening methods. The highest percentage of positive results was with the enzyme immunoassay, in which the binding of serum antibodies to antigens is amplified by enzymatic reactions.

Receptor specificity and trigemino-vascular inhibitory actions of a novel 5-HT1B/1D receptor partial agonist, 311C90 (zolmitriptan).

1. 311C90 (zolmitriptan zomig: (S)-4[[3-[2-(dimethylamino)ethyl]-1H-indol-5-yl]methyl]-2-oxazolidinone) is a novel 5-HT1B/1D receptor agonist with proven efficacy in the acute treatment of migraine. Here, we describe the receptor specificity of the drug and its actions on trigeminal-evoked plasma protein extravasation into the dura mater of the anaesthetized guinea-pig. 2. At the "5-HT1B-like' receptor mediating vascular contraction (rabbit saphenous vein), the compound was a potent (p[A50] = 6.79 +/- 0.06) partial agonist achieving 77 +/- 4% of the maximum effect to 5-hydroxytryptamine (5-HT). In the same experiments, sumatriptan (p[A50] = 6.48 +/- 0.04) was half as potent as 311C90 and produced 97 +/- 2% of the 5-HT maximum effect. Studies in which receptor inactivation methods were used to estimate the affinity (pKA) and efficacy relative to 5-HT (tau rel) for each agonist confirmed that 311C90 exhibits higher affinity than sumatriptan (pKA = 6.63 +/- 0.04 and 6.16 +/- 0.03, respectively) and that both drugs are partial agonists relative to 5-HT (tau rel = 0.61 +/- 0.03 and 0.63 +/- 0.10, respectively, compared to 5-HT = 1.0). 3. Consistent with its effects in rabbit saphenous vein, 311C90 also produced concentration-dependent contractions of primate basilar artery and human epicardial coronary artery rings. In basilar artery, agonist potency (p[A50] = 6.92 +/- 0.07) was similar to that demonstrated in rabbit saphenous vein, again being 2-3 fold higher than for sumatriptan (p[A50] = 6.46 +/- 0.03). Both agonists produced about 50% of the maximum response obtained with 5-HT in the same preparations. In rings of human coronary artery, the absolute potency of 311C90 and sumatriptan was higher than in primate basilar artery (p[A50] = 7.3 +/- 0.1 and 6.7 +/- 0.1, respectively), but maximum effects relative to 5-HT were lower (37 +/- 8% and 35 +/- 7%, respectively). In both types of vessel, the inability of 5-HT1B/1D agonists to achieve the same maximum as the endogenous agonist 5-HT is explained by the additional presence of 5-HT2A receptors. 4. 311C90 displayed high affinity at human recombinant 5-HT1D (formerly 5-HT1D alpha) and 5-HT1B (formerly 5-HT1D beta) receptors in transfected CHO-K1 cell membranes (pIC50 values = 9.16 +/- 0.12 and 8.32 +/- 0.09, respectively). In intact cells, the drug produced concentration-dependent inhibition of forskolin-stimulated adenylyl cyclase (p[A50] = 9.9 and 9.5, respectively) achieving the same maximum effect as 5-HT. Excepting human recombinant 5-HT1A and 5-ht1F receptors at which the drug behaved as an agonist with modest affinity (pIC50 = 6.45 +/- 0.11 and 7.22 +/- 0.12, respectively), 311C90 exhibited low, or no detectable affinity (pKi or pKB < or = 5.5) at numerous other monoamine receptors, including other 5-HT receptor subtypes. 5. When administered to anaesthetized guinea-pigs ten minutes before unilateral electrical stimulation of the trigeminal ganglion (1.2 mA, 5 Hz, 5 ms, 5 min), 311C90 (3-30 micrograms kg-1, i.v.) caused a dose-dependent inhibition of [125I]-albumin extravasation within the ipsilateral dura mater. At the same doses, the drug also produced dose-dependent falls in cranial vascular conductance (32.3 +/- 7.5% at 30 micrograms kg-1), as measured in the ear by laser doppler flowmetry. 6. These results show that 311C90, a novel member of the 5-HT1B/1D agonist drug class, exhibits a high degree of pharmacological specificity. Its potent partial agonist action at "5-HT1B-like' receptors in intracranial arteries, coupled with potent agonism at 5-HT1D and 5-HT1B receptors and an ability to inhibit neurogenic plasma protein extravasation in the dura, are consistent with its utility as an effective acute treatment for migraine.

Home health care and quality of life of patients with Alzheimer's disease.

BACKGROUND: Little is known about the quality of life (QOL) of people with Alzheimer's disease (AD). The formal home care sector plays an increasingly large role in care for this population, but home care agencies do not routinely collect QOL information or use this information in care planning. METHODS: A series of roundtable discussions with representatives of the home care industry were held to document current practices by home care providers regarding the elicitation, recording, and use of QOL information; to derive indicators of QOL in AD patients; and to develop standardized procedures for using QOL information. Results from this investigation were incorporated into an epidemiological investigation of community-dwelling AD patients, comparing formal sector home attendants to family caregivers regarding efforts to enhance patient QOL. RESULTS: Twenty representatives of the home care industry met over three sessions to discuss these issues. Patient QOL indicators were derived, showing divergence of patient and caregiver perspectives. A survey of 240 AD patients compared family and formal home attendant caregivers and showed that home attendants underutilize opportunities to enhance patient QOL, as referenced by patient participation in activities that require supervision. CONCLUSIONS: Collaboration with home care agencies allowed a better understanding of quality of life for this vulnerable patient population. More research will be required to refine QOL outcomes and develop quality assurance tools for dementia care. Medical Subject Headings (MeSH): Alzheimer's disease, quality of life, home care, paraprofessional care.

Anti-Holley detected in a primary immune response.

Anti-Holley (Hy) has been reported as an IgG antibody occurring in previously transfused or multiparous black patients. In this case anti- Hy was identified in a 16-year-old black, primigravida female admitted at 32 weeks gestation because of premature rupture of the membranes. On admission, her blood type was determined to be A2B, D-positive and an antibody screen was negative. A second antibody screen, performed 4 days later, was positive in all three cells. Anti-Hy was subsequently identified. The antibody was reactive at room temperature, 37 degrees C, and in the antiglobulin phase. IgG and IgM components of anti-Hy were demonstrated in the maternal serum, documenting a primary immune response. This resulted in serologic findings not previously described for anti-Hy. A direct antiglobulin test on the newborn red cells was negative and there was no clinical evidence of hemolytic disease of the newborn (HDN). A monocyte monolayer assay performed with maternal serum yielded negative results. Recent scientific information has resulted in the placement of Hy in the Dombrock blood group system. Alloantibodies to Dombrock system antigens have not been associated with severe HDN.

Reproductive health in the American workplace.

Helping workers understand their risk of reproductive and developmental hazard exposure can be demanding for the occupational health nurse. The lack of conclusive information about most suspected hazards, as well as concern over job security and advancement, make this issue doubly challenging. Further research is needed to verify or rule out the suspected toxic effects of a hazard. The occupational health nurse must make every effort to keep abreast of new research findings and federal or state requirements related to reproductive hazards. The key to promoting the reproductive health of American workers is primary prevention (Bernhardt, 1990). Educating and counseling workers about reproductive hazards so that they can make informed decisions about their reproductive health, along with implementing engineering controls or ergonomic changes to reduce the risk of exposure, should be the goal of all occupational health programs.

Analysis of the routine use of polyethylene glycol (PEG) as an enhancement medium.

This study compared the performance of polyethylene glycol (PEG) and low-ionic saline solutions (LISS) as enhancement media for routine use in a large transfusion service. A PEG additive solution (PEG plus LISS) was compared to a LISS additive (LISS plus polymers) and to an albumin-indirect antiglobulin test (A-IAT). Fifty serum samples containing clinically significant alloantibodies and fifty samples without alloantibodies were tested. Following an acute hemolytic transfusion reaction (HTR) involving an anti-K that was not detected with LISS but was retrospectively found to be reactive with PEG, an additional 151 samples received for antibody screening were prospectively evaluated in parallel using PEG and LISS. PEG detected all clinically significant antibodies in the 50 previously tested samples, with mean reactivity scores greater than LISS or A-IAT. In the prospective study, PEG detected 35 clinically significant antibodies and 10 clinically insignificant antibodies, while LISS detected only 15 clinically significant antibodies and 33 clinically insignificant antibodies. PEG appears to increase detection of significant antibodies while decreasing detection of insignificant antibodies. PEG was therefore substituted for LISS as an enhancement medium and has been in routine use for 12 months, with no reported acute or anamnestic HTRs in 6,353 transfusions.

Market testing. What am I bid?

Walsall's experience of marketing testing for urology services was that it is a difficult, time-consuming but thoroughly worthwhile process. We believe that a much improved level of service will be available to Walsall residents, representing excellent value for money. Turning the spotlight on to this particular specialty resulted in local provider trusts showing increased willingness to address the clinical management and quality issues about which the HA had expressed concern.

Binding and elution of EGTA to anion exchange columns: implications for study of (Ca+Mg)-ATPase inhibitors.

EGTA bound to DEAE-Sephadex and DEAE-cellulose at low ionic strength in the presence and absence of applied protein. It remained bound when the column was washed at low ionic strength, but was eluted as the ionic strength was increased. The amount of EGTA recovered at high ionic strength was 60 to 90% of that applied to the column. At the peak of its elution, the concentration of EGTA in the eluted fractions was 25 mM, over 10-fold higher than the concentration of EGTA applied to the column. Eluted fractions containing EGTA inhibited the (Ca+Mg)-ATPase by two mechanisms: (1) by chelating the Ca and (2) by affecting activity even when the free Ca was held constant. We suggest that at least some of the inhibitory effects previously attributed to a cytoplasmic inhibitor of the (Ca+Mg)-ATPase may in fact be due to contaminating amounts of EGTA.

A primary care nursing model in long-term care facilities: evaluation of impact on affect, behavior, and socialization.

A primary care model of delivery of nursing aide care was implemented and evaluated in one small, rural nursing home and one large, urban facility. Experimental unit residents received primary care consisting of permanent assignment of nursing aide, a team approach and enhanced communication. The urban experimental residents improved significantly in behavior and affect as measured across several sources, while the comparison group declined or remained the same. Significant improvements in behavior and social activities were observed among the experimental rural nursing home residents as contrasted with the comparison group after implementation of primary care nursing. It was concluded that primary care nursing as applied to nursing attendants in long-term care is beneficial to residents in terms of decreasing disturbed behavior and improved affect.