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Biomedical subjects

J M Smith

Publications and source records attributed to J M Smith.

At least 127 records · Page 7Linked to original sources
PubMed1997

Prescribing behaviour in general practice: the impact of promoting therapeutically equivalent cheaper medicines.

BACKGROUND: The volume and cost of prescribing varies considerably between practices. This variation is at least in part due to the prescribing behaviour of individual doctors, who are often faced with a range of therapeutically equivalent generic and brand-name drugs. AIM: To assess the impact on general practitioners' prescribing behaviour of promoting therapeutically equivalent lower cost prescribing in conjunction with an incentive scheme. METHOD: Annual prescribing data from before (1992-93) and after (1993-94) implementation of the incentive scheme were compared retrospectively for general practices in the former Northern Regional Health Authority. Main outcome measures were the practices' 1993-94 rates of prescribing relative to those in 1992-93 for 18 drugs prescribed by brand name, of which 10 were targeted in the promotion, and for 14 drugs or classes of drugs either with equivalent cheaper alternatives or of limited clinical value (10 targeted and four not). RESULTS: For 17 of the 18 drugs, brand name prescribing rates were significantly lower in 1993-94. Reductions in rates were greater for the 10 drugs appearing in the scheme's promotional literature. For other cost-saving measures, total prescribing rates were lower for seven classes of drugs, unchanged for one, but higher for the other six, all of which had been targeted. According to the growth in their overall per capita prescribing costs between the two study years, the 499 practices were categorized as low, average or high. Overall costs and individual prescribing rates for the majority of drugs studied were similar for these three practice groups in 1992-93. In 1993-94, practices' changes in prescribing volume differed between the groups, with the lowest increases in the low cost-growth group for all but one of the 32 classes of drugs. CONCLUSION: Generic substitution was more easily implemented than more complex hints regarding cost-saving substitutions. Practices with smaller overall cost growth were making greater use of cost-beneficial prescribing strategies, whether promoted or otherwise. Simple messages may improve the cost-effectiveness of prescribing in the UK. With information support and encouragement, many prescribers appear to have modified their prescribing habits.

Cost Control↗
PubMed1997

Carpal bone titanium implant arthroplasty. 10 years' experience.

In 1984, in an effort to address the silicone wear particle problem, titanium implants were developed for the scaphoid, lunate, and trapeziometacarpal joint. The design of these implants closely resembled their silicone counterparts, though some modifications were made to accommodate the properties of unalloyed titanium and enhance their stability. Carpal bone implants act as articulating spacers to help maintain the relationship of adjacent carpal bones after local resection procedures. Their use allows carpal stabilization procedures and provides functional mobility with good strength and pain relief. Their surgical application began in 1985. The 10-year clinical experience seems very promising to date.

Adult↗
PubMed1996

(Aryloxy)aryl semicarbazones and related compounds: a novel class of anticonvulsant agents possessing high activity in the maximal electroshock screen.

A number of (aryloxy)aryl semicarbazones and related compounds were synthesized and evaluated for anticonvulsant activities. After intraperitoneal injection to mice, the semicarbazones were examined in the maximal electroshock (MES), subcutaneous pentylenetetrazole (scPTZ), and neurotoxicity (NT) screens. The results indicated that greater protection was obtained in the MES test than the scPTZ screen. Quantitation of approximately one-third of the compounds revealed an average protection index (PI, i.e. TD50/ED50) of approximately 9. After oral administration to rats, a number of compounds displayed significant potencies in the MES screen (ED50 of 1-5 mg/kg) accompanied by very high protection indices. In fact over half the compounds had PI figures of greater than 100, and two were in excess of 300. The compounds were essentially inactive in the scPTZ and NT screens after oral administration to rats. Various compounds displayed greater potencies and PI figures in the mouse intraperitoneal and rat oral screens than three reference clinically used drugs. The data generated supported a binding site hypothesis. Quantitative structure-activity relationships indicated a number of physicochemical parameters which contributed to activity in the MES screen. X-ray crystallography of five compounds suggested the importance of certain interatomic distances and bond angles for activity in the mouse and rat MES screens.

Animals↗
PubMed1996

A prescribing incentive scheme for non-fundholding general practices: an observational study.

OBJECTIVE: To examine the effects of a financial incentive scheme on prescribing in non-fundholding general practices. DESIGN: Observational study. SETTING: Non-fundholding general practices in former Northern region in 1993-4. INTERVENTION: Target savings were set for each group of practices; those that achieved them were paid a portion of the savings. MAIN OUTCOME MEASURES: Financial performance; prescribing patterns in major therapeutic groups and some specific therapeutic areas; rates of generic prescribing; and performance against a measure of prescribing quality. SUBJECTS: 459 non-fundholding general practices, grouped into three bands according to the ratio of their indicative prescribing amount to the local average (band A > or = 10% above average, B between average and 10% above, C below average). RESULTS: 102 (23%) of 442 practices achieved their target savings (18%, 19%, and 27% of bands A, B, and C respectively). Band C practices that achieved their target had a lower per capita prescribing frequency for gastrointestinal drugs, inhaled steroids, antidepressants, and hormone replacement therapy. There were no other significant differences in prescribing frequency, and no reduction in the quality of prescribing in achieving practices. Total savings of pounds 1.54 m on indicative prescribing amounts were achieved. Payments from the incentive scheme and discretionary quality awards resulted in pounds 463,000 being returned to practices for investment in primary care. CONCLUSIONS: The prescribing behaviour of non-fundholding general practitioners responded to financial incentives in a similar way to that of fundholding practitioners. The incentive scheme did not seem to reduce the quality of prescribing.

Budgets↗
PubMed1996

ATP-sensitive potassium channels are altered in ventricular myocytes from diabetic rats.

Hypoxia-induced shortening of the action potential duration, attributed to activation of the ATP-sensitive potassium (KATP) channels, occurs to a much greater extent in ventricular cells from diabetic rats. This study examined whether the KATP channels are altered in streptozotocin-diabetic myocardium. In inside-out patches from ventricular myocytes (with symmetrical 140 mM [K+]), inward KATP currents (at potentials negative to the K+ reversal potential) were similar in amplitude in control and diabetic patches (slope conductances: 69 and 74 pS, respectively). However, outward single-channel currents were larger for channels from diabetic heart cells than from control cells (e.g., at +75 mV the diabetic channel currents were 3.7 +/- 0.3 pA vs. 2.7 +/- 0.1 pA for control currents, p < 0.05), due to reduced inward rectification of diabetic channel currents. There was no difference in open and closed times between control and diabetic channels. The IC50 for ATP inhibition of the KATP channel single-channel currents was 11.4 microM for control currents and 4.7 microM for diabetic channel currents. Thus, the major difference found between KATP channels from control and diabetic hearts was the greater outward diabetic single-channel current, which may contribute to the enhanced sensitivity to hypoxia (or ischemia) in diabetic hearts.

Action Potentials↗
PubMed1996

Quantitative assessment of the spatial organization of atrial fibrillation in the intact human heart.

BACKGROUND: Atrial activation during atrial fibrillation (AF) is frequently described as random or chaotic. We propose that activation during AF is constrained by the principles of reentrant excitation; that these constraints impart a measurable spatial organization to activation during AF; and that the distance over which activation sequences remain well correlated can be readily measured and related both to the propensity of AF to sustain itself as well as to atrial tissue wavelength. METHODS AND RESULTS: We describe a novel signal-processing technique that quantifies the correlation in activation sequences recorded from five equally spaced sites in the right atrium in patients undergoing electrophysiology studies. In 20 patients in AF (12 with paroxysmal AF, 5 with chronic AF, and 3 with no clinical history of AF), the average correlation was 0.54 +/- 0.12 at 11 mm and 0.32 +/- 0.11 at 44 mm, compared with 0.95 +/- .023 and 0.91 +/- .023 in sinus rhythm. In AF, the correlation versus distance relation was monotonically decreasing, well fit by a decaying exponential function. The space constant of this exponential function, termed the activation space constant, provides a single objective metric of the spatial organization of activation during AF. The mean activation space constant for the group was 2.6 +/- 1.15 cm. Chronic AF had the lowest mean activation space constant (1.84 +/- 0.36 cm) and AF in patients with no prior history of AF had the highest (3.06 +/- 0.40 cm) (P < .05), with paroxysmal AF characterized by intermediate values (2.80 +/- 1.4 cm). CONCLUSIONS: Using a novel method to measure the spatial organization of atrial activation during AF, we have demonstrated that AF in the intact human heart is organized over a length scale consistent with reentrant excitation. Preliminary results suggest a relationship between measured spatial organization and the clinical course of the arrhythmia. Further work is needed to determine whether measurement of spatial organization may be useful in prospective patient-specific selection of therapeutic options.

Adult↗
PubMed1996

The tetracycline resistance gene tet(M) exhibits mosaic structure.

Tetracycline resistance genes of the M class, tet(M), are typically found on mobile genetic elements as the conjugative transposons of gram-positive bacteria. By comparing the sequences of eight different tet(M) genes (from Enterococcus faecalis, Streptococcus pneumoniae, Staphylococcus aureus, Ureaplasma urealyticum, and Neisseria), a mosaic structure was detected which could be traced to two distinct alleles. The two alleles displayed a divergence of 8% and a different G/C content. The block structure of these genes provides evidence for the contribution of homologous recombination to the evolution and the heterogeneity of the tet(M) locus. Unlike described cases of chromosomally located mosaic loci, tet(M) is a relatively recently acquired determinant in the species examined and it would appear that mosaic structure within tet(M) has evolved after acquisition of the gene by the mobile genetic elements upon which it is located.

Bacterial Proteins↗
PubMed1996

Catheter ablation of clinical intraatrial reentrant tachycardias resulting from previous atrial surgery: localizing and transecting the critical isthmus.

OBJECTIVES: We sought to evaluate the efficacy of anatomically based radiofrequency catheter ablation for the treatment of intraatrial reentrant tachycardia in patients with previous atrial surgery. BACKGROUND: Intraatrial reentrant tachycardias, a common late complication of atrial surgery, are often refractory to standard medical management. Data from experimental animals and from humans indicate that anatomic barriers resulting from residual atrial scars provide a substrate for intraatrial reentry. We speculated that these tachycardias require a narrow isthmus of tissue between surgical scars and native nonconductive boundaries and that transection of this isthmus with radiofrequency ablation would therefore constitute an effective treatment. METHODS: Fourteen patients with a history of atrial surgery and clinical intraatrial reentrant tachycardia underwent electrophysiologic testing. From activation mapping, putative surgical scars and patches that served as boundaries of reentrant circuits were identified. Radiofrequency lesions were then placed to transect the narrowest isthmus of conducting tissue between a surgical scar and an anatomic barrier. Catheter ablation was attempted only for tachycardias consistent with the patient's clinical arrhythmias. RESULTS: Radiofrequency catheter ablation was attempted for 17 (55%) of 31 tachycardias identified; it successfully terminated tachycardias in 13 (93%) of 14 patients (95% confidence interval [CI] 79% to 99%). There were clinical recurrences in six patients (46%, 95% CI 19% to 73%), each of whom underwent a repeat ablation that was successful. Twelve (86%) of 14 patients (95% CI 67% to 99%) have remained free of intraatrial reentrant tachycardia for a mean of 7.5 +/- 5.3 months. CONCLUSIONS: Anatomically guided radiofrequency catheter ablation is an effective technique for definitive management of intraatrial reentrant tachycardia in patients with previous atrial surgery.

Adult↗
PubMed1996

Analysis of autogenous vein femoral-infrapopliteal bypass for limb salvage in the elderly.

The hypothesis that older patients undergoing femoral-infrapopliteal bypass have a similar outcome as a matched younger group of patients undergoing the same operation was tested. Seventy-six femoral-infrapopliteal autogenous saphenous vein bypasses for critical limb ischemia were performed from 1985 to 1990. By using the life-table method, the primary and secondary patency, limb salvage and survival rates are analyzed and compared for older and younger age groups. Forty cases (53%) were performed in an elderly group, defined as age 70 or older. At 4 years, there was no significant difference between age groups in limb salvage and patency rates. However, operative mortality for the older age group was 12%, compared with 0% in the younger group (P = 0.0004). Thus, femoral-infrapopliteal autogenous vein bypass can be performed with comparable limb salvage and patency rates for an older age group, but the risk of operative mortality appears to be increased with age.

Adult↗
PubMed1996

Randomized comparison of ultrasonic aspiration versus conventional electrocautery for dissection of the human internal thoracic artery.

The most common technique currently employed to harvest the internal thoracic artery for coronary artery bypass grafting is conventional electrocautery. This study compared an alternative method, electrocautery with an ultrasonic aspirator, for harvesting the internal thoracic artery. Patients were randomly assigned to one of six experimental groups (conventional electrocautery, ultrasonic aspirator at settings of 60%, 80%, and 100% power output, and ultrasonic aspirator in 100% CAVI-Pulse modes 1 and 3). Ring segments of internal thoracic artery were studied in an organ bath. Contraction responses were elicited with 123 mmol/L potassium physiologic salt solution, KPSS, KPSS solution containing noradrenaline, and a cumulative noradrenaline dose-contraction curve. Relaxation studies were performed with the vasodilators acetylcholine, bradykinin, and sodium nitroprusside. Forty percent of the electrocauterized vessels were traumatized or damaged and failed to respond to contractile stimuli, whereas only 10% of the vessels in ultrasonic aspirator groups 60%, 80%, and 100% failed to respond. All vessels in the group harvested by ultrasonic aspirator in 100% CAVI-Pulse mode 1 responded, whereas 20% of the vessels in the group harvested by ultrasonic aspirator in 100% CAVI-Pulse mode 3 failed to respond. All settings of electrocautery with an ultrasonic aspirator produced a greater contractile response to KPSS and noradrenaline. Acetylcholine and sodium nitroprusside produced similar relaxations in all groups, but the bradykinin responses were significantly improved in all groups undergoing 100% electrocautery with an ultrasonic aspirator. These results suggest that 100% electrocautery with an ultrasonic aspirator, particularly in 100% CAVI-Pulse mode 1, resulted in less damage and trauma than conventional electrocautery during harvesting of the internal thoracic artery.

Adult↗
PubMed1996

Electrophysiologic aspects of human atrial fibrillation.

This article reviews the important developments that have led to current understanding of atrial fibrillation, the data that support its mechanistic dependence on various forms of reentrant excitation, and the resultant electrophysiologic and clinical implications of clinicians' evolving understanding.

Alcohol Drinking↗
PubMed1996

Investigation of calmodulin and basic fibroblast growth factor (bFGF) in idiopathic myelofibrosis: evidence for a role of extracellular calmodulin in fibroblast proliferation.

The urinary concentration of calmodulin and basic fibroblast growth factor (bFGF) was determined in a total of 53 patients with various chronic myeloproliferative disorders (CMPD), including 22 patients with idiopathic myelofibrosis (IMF). Calmodulin excretion was significantly elevated in IMF (0.29 +/- 0.04 microgram/mmol creatinine) (P < 0.001), when compared to polycythaemia vera (PV) (0.14 +/- 0.02), essential thrombocythaemia (ET) (0.13 +/- 0.04), chronic myeloid leukaemia (CML) (0.16 +/- 0.02), unclassified myeloproliferative disorders (UMPD) (0.11 +/- 0.02) and age-matched controls (0.1 +/- 0.02) (P < 0.001). In contrast, bFGF was slightly elevated in all CMPD conditions when compared to age-matched controls. A neutralizing antibody to calmodulin was demonstrated to significantly influence the in vitro proliferation of normal human fibroblasts, an effect dependent on both cell density and the presence of fetal calf serum (FCS). Essentially, the antibody reduced FCS-induced proliferation of low-density fibroblasts but had little or no inhibitory effect on high-density fibroblasts in the absence of FCS. In addition, extracellular calmodulin was shown not to interact with known fibroblast mitogens, namely, IFG-1, EGF, bDGF and PDGF. We conclude that extracellular calmodulin should be considered, in addition to PDGF, TFG-beta and EGF, as a potential mitogen involved in the stromal reaction of idiopathic myelofibrosis.

Adult↗
PubMed1996

Synonymous nucleotide divergence: what is "saturation"?

The nucleotide divergence at synonymous third sites between two lineages will increase with time since the latest common ancestor, up to some saturation level. The "null-hypothesis divergence" is defined as the percentage of difference predicted at synonymous third sites, allowing for amino acid composition and codon bias, but assuming that codon bias is the same at all sites occupied by a given amino acid, when equilibrium has been reached between forward and backward substitutions. For two highly expressed genes, gapA and ompA, in the enterobacteria, the estimated values of the null-hypothesis divergence are 39.3 and 38.15%, respectively, compared to estimated values of saturation divergence of 19.0 and 25.4%. A possible explanation for this discrepancy is that different codons for a given amino acid are favored at different sites in the same gene.

Codon↗