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Biomedical subjects

M Horton

Publications and source records attributed to M Horton.

At least 19 recordsLinked to original sources
PubMed2001

Effect of selective or combined inhibition of integrins alpha(IIb)beta(3) and alpha(v)beta(3) on thrombosis and neointima after oversized porcine coronary angioplasty.

BACKGROUND: Thrombosis and neointima formation limit the efficacy of coronary angioplasty (PTCA). Clinical trials have implicated the adhesion molecules integrin alpha(IIb)beta(3) and integrin alpha(v)beta(3) in these processes. The roles of these molecules in vascular smooth muscle cell adhesion, platelet aggregation, and the thrombotic and neointimal response to oversize porcine PTCA was investigated by use of a selective alpha(IIb)beta(3) antagonist (lamifiban), a selective alpha(v)beta(3) antagonist (VO514), and a combined alpha(IIb)beta(3)/alpha(v)beta(3) antagonist (G3580). METHODS AND RESULTS: In vitro, both alpha(v)beta(3) inhibitors caused dose-dependent inhibition of porcine vascular smooth muscle cell adhesion to vitronectin but not to collagen type IV, fibronectin, or laminin, whereas selective alpha(IIb)beta(3) inhibition had no effect. Intravenous infusions of either alpha(IIb)beta(3) inhibitor in swine profoundly inhibited ex vivo platelet aggregation to ADP, whereas selective alpha(v)beta(3) inhibition had no effect. In a porcine PTCA model, intravenous infusions of the integrin antagonists were administered for 14 days after oversized balloon angioplasty injury. After PTCA, there was regional upregulation of integrin alpha(v)beta(3) in the developing neointima, as assessed by immunohistochemistry. Six hours after PTCA, obstruction of lumen by thrombus was reduced significantly by alpha(IIb)beta(3) inhibition compared with either control or alpha(v)beta(3) inhibition (mean control, 18.7%; VO514, 18.5%; lamifiban, 6.4%; G3580, 7.9%). Twenty-eight days after PTCA, there was a significant reduction of neointima with inhibitors of either integrin (mean intima/media ratio: control, 3.08; VO514, 1.33; lamifiban, 0.97; G3580, 1.32). CONCLUSIONS: We conclude that both integrin alpha(IIb)beta(3) and integrin alpha(v)beta(3) participate in neointima development after experimental angioplasty.

Acetates↗
PubMed2001

Opinions and experiences in general practice on osteoporosis prevention, diagnosis and management.

We determined to survey the general practice population regarding their attitudes to and knowledge of osteoporosis as a baseline prior to publication of national guidelines for the management of osteoporosis. All 2515 general practitioners registered in the 10 Health Authorities of the North Thames region, London, UK were surveyed by a postal questionnaire. Responses relating to epidemiology, public health and education on osteoporosis were analyzed. The overall response was 1153 (46%). General practitioners who responded were younger, predominantly female and in group practice. There is considerable awareness of the importance of preventing osteoporosis. General practitioners are active in identifying groups at risk, particularly those who are aged 40 years and older. A prevention strategy for osteoporosis is viewed as effective. However, two thirds of general practitioners remain unconvinced about the efficacy of drug therapy. Education on osteoporosis is considered inadequate. General practitioners would welcome further information on management issues and access to osteoporosis services. In conclusion, educational initiatives will be important both at undergraduate and postgraduate levels to increase awareness and knowledge of osteoporosis. General practitioners are aware of the public health impact of this condition and express a preference for educational material of direct relevance to the care of their patients. Therefore better cooperation between primary and secondary care should lead to ways of breaking down barriers to change in clinical practice and promoting fully integrated care of patients with osteoporosis.

Attitude of Health Personnel↗
PubMed2001

The development and use of a triage protocol for patients with dental problems contacting an out-of-hours general medical practitioner cooperative.

PURPOSE OF THE STUDY: The number of patients contacting general medical practitioner (GMP) out-of-hours services with dental problems is perceived to be a significant problem by the medical profession. This study was undertaken to design and pilot a triage protocol that could be used by non-dental staff to refer callers with dental complaints for appropriate treatment. BASIC PROCEDURES: A triage protocol was designed to address the patient conditions considered to be relevant to emergency dental care. The triage protocol was piloted for three months at a GMP cooperative in North Wales, which provided an out-of-hours service for 61 GMPs. Baseline data were collected for three months prior to the introduction of the triage protocol. MAIN FINDINGS: The study showed that the number of dental callers contacting the out-of-hours service was not as great as GMPs imagined, and was similar to other studies. The introduction of the triage protocol resulted in a rise in the number of callers asked to call the general dental practitioner (GDP) support line. The number of unregistered patients given the name of a dentist also increased. The need to make a second telephone call seemed not to affect patient satisfaction since when patients were later questioned on their experience, those who had used the service since the introduction of the triage protocol were more likely to be satisfied with the service. PRINCIPAL CONCLUSIONS: This study provides some evidence that a triage protocol can be used successfully by non-dental staff to sift requests for out-of-hours emergency dental care.

Dental Care↗
PubMed2001

Cell adhesion molecules in human osteoblasts: structure and function.

Osteoblasts and bone lining cells form a near continuous layer covering the bone surface and interactions between these cells and the organic matrix of bone are important determinants of osteoblast proliferation and differentiation. In addition, cells of the osteoblast-lineage form functional communications with each other, with the extra-cellular matrix and with osteocytes through cytoplasmic processes extending through canaliculi in the bone. Together, these cells form a network of putative importance in the regulation of skeletal homeostasis. Cell-cell and cell-matrix interactions are mediated by members of several families of cell adhesion molecules, and knowledge of their interactions will be of fundamental importance in understanding the role of osteoblast in skeletal turnover. Here, the expression pattern of members of the major families of cell adhesion molecules by cells of the osteoblast lineage is reviewed. Special emphasis has been placed on human tissues. In addition, the possibility that cells at progressive stages of the osteoblast lineage have different profiles of cell adhesion molecule expression is explored, and the putative significance of cell-matrix interactions in human skeletal disease briefly discussed.

Cadherins↗
PubMed2000

Mechanical bridge to recovery in fulminant myocarditis.

A patient with acute fulminant lymphocytic myocarditis and cardiogenic shock was successfully treated by mechanical off loading of the left ventricle. A nonpulsatile left-heart bypass was undertaken with an implantable centrifugal blood pump. Careful weaning resulted in device removal on the seventh day. Left and right ventricular function is sustained at 7 months. Widespread application of this method depends on the availability of an inexpensive user friendly blood pump, appropriate weaning protocols and emerging strategies to promote sustainable myocardial recovery.

Adult↗
PubMed2000

Survival advantage of stentless aortic bioprostheses.

BACKGROUND: Bioprostheses (BPs) are used to avoid anticoagulation after aortic valve replacement (AVR) in patients over 65 years of age. Stentless BPs offer established hemodynamic benefits. We sought to determine whether these advantages translate into improved survival. METHODS: Between 1993 and 1997, follow-up data (for Food and Drug Administration submission) were collected prospectively for 160 consecutive, unselected hospital survivors who received the Freestyle valve (FS). Equivalent data were collected for 247 Carpentier-Edwards (CE) porcine xenograft patients. Detailed comparative statistical analysis was used to compare events and survival between the groups. Follow-up was 100% complete for the FS (5.2 years maximum; mean 3.2+/-1.0 years) group and 98% (7.2 years maximum; mean 3.8+/-2.0 years) for CE. RESULTS: The groups were well matched in age (FS, 73+/-6 years; CE, 74+/-6 years), gender (FS, 58% male; CE, 62% male), ventricular function, and number of patients requiring coronary grafts (FS, 41%; CE, 37%). Actuarial survival at 5 years was 84% for FS versus 69% for CE (p = 0.023 Kaplan Meier, p = 0.009 Cox). Annual mortality rates were 3.6% for FS versus 7.1% for CE (p = 0.001). Thromboembolic rate was 0.8% per year for FS and 2.4% for CE (p = 0.024) without a difference in cardiac rhythm. Incidence of nonstructural dysfunction (paravalvular leak) was 0.2% for FS versus 1.3% for CE (p = 0.020). CONCLUSIONS: By 5 years, the stentless valve patients had improved survival and reduced adverse events. Though differences in durability are yet to be proved, our findings support the use of stentless bioprostheses in this age group.

Adult↗
PubMed2000

The pharmacokinetics of ziprasidone in subjects with normal and impaired renal function.

AIMS: To assess whether renal impairment influences the pharmacokinetics of ziprasidone, and to determine whether ziprasidone is cleared via haemodialysis. METHODS: Thirty-nine subjects with varying degrees of renal impairment were enrolled into an open-label, multicentre, multiple-dose study and assigned to four groups according to their renal function: normal (group 1, creatinine clearance > 70 ml min(-1); mildly impaired (group 2, creatinine clearance 30-60 ml min(-1); moderately impaired (group 3, creatinine clearance 10-29 ml min(-1), and severely impaired (group 4, requiring haemodialysis three times-a-week). Subjects received ziprasidone 40 mg day(-1), given orally with food, as two divided daily doses for 7 days and a single 20 mg dose on the morning of day 8. Pharmacokinetic variables were determined from multiple venous blood samples collected on days 1 and 8 (haemodialysis day for subjects with severe renal impairment). Additional samples were collected from subjects with severe renal impairment on day 7 (nonhaemodialysis day). RESULTS: On day 1 there were no statistically significant differences in the pharmacokinetics (AUC(0, 12 h), Cmax, tmax) of ziprasidone among subjects with normal renal function and those with mild, moderate and severe renal impairment. The AUC(0,12 h) and Cmax in subjects with mildly impaired renal function were statistically significantly greater than in those with moderately impaired renal function (P = 0.0163-0.0385). The mean AUC(0,12 h) was 272, 370, 250 and 297 ng ml(-1) h in groups 1, 2, 3 and 4, respectively. Corresponding mean Cmax values were 47, 61, 41 and 50 ng ml(-1) and corresponding mean tmax values were 5, 6, 5 and 5 h. On day 8 there were no statistically significant differences in the pharmacokinetics (AUC(0,12 h), Cmax, tmax, lambda(z), Fb) of ziprasidone among subjects with normal renal function and those with moderate or severe renal impairment. The AUC(0,12 h) in subjects with mild renal impairment was statistically significantly greater than those in the other three groups (P = 0.0025-0.0221), but this was not considered clinically significant. The mean AUC(0,12 h) were 446, 650, 389 and 427 ng ml(-1) h in groups 1, 2, 3 and 4, respectively. Corresponding mean Cmax values were 68, 93, 54 and 70 ng ml(-1), corresponding mean tmax values were 4, 5, 4 and 5 h and corresponding mean lambda(z) were 0.14, 0.11, 0.14 and 0.17 h(-1). The mean percentage Fb was 99.84-99.88% across all groups and the mean t(1/2),z ranged from 4.2 to 6.4 h. Comparison of the mean AUC(0,12 h) and Cmax values in subjects with severe renal impairment on day 7 with those on day 8 suggested that haemodialysis does not have a clinically significant effect on the pharmacokinetics of ziprasidone. CONCLUSIONS: The findings of this study indicate that mild-to-moderate impairment of renal function does not result in clinically significant alteration of ziprasidone pharmacokinetics and therefore does not necessitate dose adjustment.

Adolescent↗
PubMed2000

Smooth muscle cell matrix metalloproteinase production is stimulated via alpha(v)beta(3) integrin.

This study tests the hypothesis that alpha(v)beta(3) integrin receptors play a critical role in smooth muscle cell (SMC) migration after arterial injury and facilitate migration through the upregulation of matrix metalloproteinase (MMP) activity. We showed that beta(3) integrin mRNA was upregulated by SMCs in the balloon-injured rat carotid artery in coincidence with MMP-1 expression and early SMC migration. Treatment with the beta(3) integrin-blocking antibody F11 significantly decreased SMC migration into the intima at 4 days after injury, from 110.8+/-30.8 cells/mm(2) in control rats to 10.29+/-7.03 cells/mm(2) in F11-treated rats (P=0.008). By contrast, there was no effect on medial SMC proliferation or on medial SMC number in the carotid artery at 4 days. In vitro, we found that human newborn SMCs produced MMP-1 but that adult SMCs did not. This was possibly due to the fact that newborn SMCs expressed alpha(v)beta(3) integrin receptors, whereas adult SMCs did not. Stimulation of newborn (alpha(v)beta(3)+) SMCs with osteopontin, a matrix ligand for alpha(v)beta(3), increased MMP-1 production from 114.4+/-35.8 ng/mL at 0 nmol/L osteopontin to 232.5+/-57.5 ng/mL at 100 nmol/L osteopontin. Finally, we showed that stimulation of newborn SMCs with platelet-derived growth factor-BB and osteopontin together increased the SMC production of MMP-9. Thus, our results support the hypothesis that SMC alpha(v)beta(3) integrin receptors play an important role in regulating migration by stimulating SMC MMP production.

Animals↗
PubMed2000

Community control of Chlamydia trachomatis.

UNLABELLED: In order to determine the amount of Chlamydia trachomatis that is diagnosed outside genitourinary medicine (GUM) clinics in a large university city, a review of all positive chlamydial infections diagnosed on specimens received from hospitals (non-GUM) and community sources in 1996 was performed. It was also ascertained whether these patients subsequently attended at GUM. Eight hundred and nine cases of C. trachomatis were diagnosed during the study period. Three hundred and ninety-seven (49%) were initially diagnosed outside GUM of which 264 (66.5%) were referred, giving an overall involvement of GUM in 667 (83.6%) of all cases. The proportion of cases referred varied according to service: Family Planning Clinics 94.5%, Obstetrics and Gynaecology 73%, General Practice 52.5%. Referral rates also showed within service variation, with University Health Services referring 19% vs 73% (P < 0.001). High levels of referral to GUM of patients diagnosed with C. trachomatis are achievable, but referrals show inter- and intra-service variations. Efforts should be made to improve referral rates from those services with the lowest rates. IN CONCLUSION: (1) The proportion of cases of C. trachomatis diagnosed in the community who are referred to a GUM clinic, varies according to service type. (2) Referral rates vary within services and (3) Distance of services from a GUM clinic does not appear to influence referral rates.

Chlamydia Infections↗
PubMed1998

Unusual abscess patterns following dropped gallstones during laparoscopic cholecystectomy.

BACKGROUND: Laparoscopic cholecystectomy has become the standard treatment for symptomatic cholelithiasis. Numerous clinical trials have deemed it a safe procedure, regardless of the known increased risk of bile duct injury. However, the consequences and incidence of less well-known complications are still being addressed. METHODS: Between 1993 and 1995, 1,130 laparoscopic cholecystectomies were performed at two major metropolitan medical centers. Of these patients, we know of 3 (0.3%) who subsequently developed abscesses as a consequence of dropped stones during the laparoscopic cholecystectomy. One additional patient who underwent prior laparoscopic cholecystectomy at another institution developed late infection as well. RESULTS: All 4 patients developed late purulent abscesses that ultimately required open surgical drainage, and 1 patient developed trocar site "tumor" masses that were secondary to inflammatory tissue around gallstone fragments. All patients were successfully treated by surgical drainage, stone removal, and antibiotics. Trocar site inflammatory masses required excision only. Significant costs were involved in the diagnosis, management, and duration of therapy for these problems. CONCLUSIONS: This experience closely resembles that of other centers and points out the existence of a late postoperative complication following laparoscopic cholecystectomy that was rarely encountered with open cholecystectomy. Strategies for avoiding this problem are discussed. Whether dropped stones are an indication for conversion to open cholecystectomy remains unclear. Thorough irrigation at time of laparoscopic cholecystectomy with or without placement of a drain in the subhepatic space does not prevent this complication.

Abdominal Abscess↗
PubMed1998

Transport in vitro fertilization and intracytoplasmic sperm injection: results of a collaborative trial.

OBJECTIVE: To determine whether the use of a central assisted reproduction laboratory, with gamete transport to the facility (transport assisted reproduction), would decrease oocyte quality or performance in IVF-ET and intracytoplasmic sperm injection (ICSI). DESIGN: Retrospective clinical study. SETTING: Public and private fertility clinics. PATIENT(S): A total of 467 couples underwent transport IVF, whereas 108 underwent transport ICSI. A group of 60 couples underwent conventional IVF during the same period. All methods and protocols used were similar among centers. Oocyte pick-up was performed by ultrasound-guided vaginal puncture. INTERVENTION(S): Oocytes were transported under controlled conditions, from the site of follicular aspiration to a central laboratory. MAIN OUTCOME MEASURE(S): The fertilization and cleavage rates and clinical pregnancies were compared among the study populations. RESULT(S): The differences between the fertilization and cleavage rates of ova and the rates of clinical pregnancies produced by transport and conventional methods were not statistically significant. CONCLUSION(S): Gamete transport to a central laboratory was not harmful for oocytes or for the outcome of assisted reproduction. Transport makes the use of IVF and ICSI available to physicians who are not affiliated with an assisted reproduction program, reduces costs, and increases acceptability of the procedures to patients.

Adult↗
PubMed1998

Pharmacokinetics of oral and intravenous dolasetron mesylate in patients with renal impairment.

In an open-label, randomized, two-way complete crossover study, the influence of renal impairment on the pharmacokinetics of dolasetron and its primary active metabolite, hydrodolasetron, were evaluated. Patients with renal impairment were stratified into three groups of 12 based on their 24-hour creatinine clearance (Cl(cr)): group 1, mild impairment (Cl(cr) between 41 and 80 mL/min); group 2, moderate impairment (Cl(cr) between 11 and 40 mL/min); and group 3, endstage renal impairment (Cl(cr) < or = 10 mL/min). Twenty-four healthy volunteers from a previous study served as the control group. Each participant received a single intravenous or oral 200-mg dose of dolasetron mesylate on separate occasions. Serial blood samples were collected up to 60 hours after dose for determination of dolasetron and hydrodolasetron, and urine samples were collected in intervals up to 72 hours for determination of dolasetron, hydrodolasetron, and the 5' and 6'-hydroxy metabolites of hydrodolasetron. Because plasma concentrations were low and sporadic, pharmacokinetic parameters of dolasetron were not calculated after oral administration. Although some significant differences in area under the concentration-time curve (AUC0-infinity), volume of distribution (Vd), systemic clearance (Cl), and elimination half-life (t1/2) of the parent drug were observed between control subjects and patients with renal impairment, there were no systematic findings related to degree of renal dysfunction. The elimination pathways of hydrodolasetron include both hepatic metabolism and renal excretion. Consistent increases in mean Cmax, AUC0-infinity, and t1/2 and decreases in renal and total apparent clearance of hydrodolasetron were seen with diminishing renal function after intravenous administration of dolasetron mesylate. No consistent changes were found after oral administration. Urinary excretion of hydrodolasetron and its metabolites decreased with decreasing renal function, but the profile of metabolites remained constant. Dolasetron was well tolerated in all three groups of patients. Based on these findings, no dosage adjustment for dolasetron is recommended in patients with renal impairment.

Administration, Oral↗
PubMed1997

Renal dysfunction does not alter the pharmacokinetics or LDL-cholesterol reduction of atorvastatin.

The objective of this study was to determine the effects of renal dysfunction on the steady-state pharmacokinetics and pharmacodynamics of atorvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor. Nineteen subjects with calculated creatinine clearances ranging from 13 mL/min to 143 mL/min were administered 10 mg atorvastatin daily for 2 weeks. Pharmacokinetic parameters and lipid responses were analyzed by regression on calculated creatinine clearance. Correlations between steady-state atorvastatin pharmacokinetic or pharmacodynamic parameters and creatinine clearance were weak and, in general, did not achieve statistical significance. Although the elimination rate constant, lambda z (0.579), was significantly correlated with creatinine clearance, neither maximum plasma concentration (Cmax, -0.361) nor oral clearance (Cl/F, 0.306) were; thus, steady-state exposure is not altered. Renal impairment has no significant effect on pharmacodynamics and pharmacokinetics of atorvastatin.

Adult↗
PubMed1996

Breast cancer in Nebraska: recent trends in incidence, mortality, and screening.

Data from the Nebraska Cancer Registry indicate that the State's female breast cancer incidence rate did not increase or decrease significantly during the period 1987-1993, although the percentage of in situ diagnoses increased from 8% to 13%. Similarly, breast cancer mortality among Nebraska women has remained relatively constant during the past decade (1985-1994). According to Nebraska's Behavioral Risk Factor Survey, screening mammography rates among Nebraska women have shown striking increases in recent years: in 1994, nearly half (48%) of all women 50 and older reported that they had had a mammogram within the past year, up from 24% in 1988. Nebraska's breast cancer incidence, mortality, and screening rates remain lower than U.S. rates.

Adult↗
PubMed1995

Hepatic cryotherapy: double-freeze cycles achieve greater hepatocellular injury in man.

Hepatic cryotherapy is a relatively new technique used to treat both primary and secondary tumors. This paper concerns the changes in serum aspartate transaminase (AST) in 45 patients following both single and double freeze with partial thaw cycles. There was considerable elevation in serum AST, greatest on the day of operation, and there was a significantly higher peak AST following the double-freeze cycles (1159; SE, 117.5) compared with single-freeze/thaw procedures (437; SE, 61.7). This finding indicates greater hepatocellular disruption which may be important both in planning clinical hepatic cryosurgery to achieve adequate destruction and also to avoid the morbidity of the cryoshock phenomenon.

Aspartate Aminotransferases↗