Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “THERAPEUTICS”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 685 records · Page 38Linked to original sources
PubMed1996

Validation of a rodent model of Parkinson's Disease: evidence of a therapeutic window for oral Sinemet.

Behavioral measures of parkinsonism that are more clinically relevant than rotometry have been developed for rats with severe unilateral dopamine depletions, and the validity of these measures is supported by reports that these parkinsonian symptoms are attenuated by drugs that are effective in the clinical setting. Although the therapeutic gold standard, L-DOPA:carbidopa (Sinemet), effectively attenuates parkinsonian symptoms, the beneficial effects of this drug are limited by the dyskinesias that it produces at higher doses. The range of effective doses, from the minimum dose that produces beneficial effects to the dose that produces intolerable dyskinesias, is referred to as the "therapeutic window." It would be extremely valuable to assess, preclinically, the effects of novel treatments on the therapeutic window for Sinemet. The results of the present study support the validity of nondrug-induced measures of parkinsonian symptoms in dopamine-depleted rats. Neurological measures revealed large behavioral deficits in the affected forelimb analogous to the deficits exhibited in Parkinson's disease patients, and these deficits were significantly attenuated with some doses of oral Sinemet (30-40 mg/kg). These drug effects on measures of parkinsonism were specific to performance with the affected limb. At slightly higher doses (50 mg/ kg), the rats were untestable due to severe dyskinesias. The results of the present study suggest that it is possible to investigate the therapeutic potential of novel treatments as well as their effects on the therapeutic window of oral Sinemet in this rodent model of Parkinson's disease.

Administration, Oral↗
PubMed1991

Hematopoietic and therapeutic properties of bestatin in normal and myelosuppressed mice.

Bestatin is a potent inhibitor of aminopeptidase B, an enzyme which is found in abundance in the membrane of monocytes and macrophages. Binding of Bestatin to cells in the histiocytic linage upregulates colony stimulating activity (both in vitro and in vivo), which subsequently increases hematopoietic and hematologic values. We report that the treatment of mice with Bestatin upregulates the frequency and absolute numbers of colony forming unit--granulocyte-macrophage (CFU-GM), as well as the entry of CFU-GM into S phase (a measure of progenitor cell activity). As a result, there is an increase in bone marrow cellularity in cyclophosphamide myelosuppressed mice and an increase in the absolute neutrophil count in normal and myelosuppressed mice. The therapeutic application of this hematopoietic modulator has been demonstrated in combination cyclophosphamide and Bestatin protocols. While Bestatin has significant therapeutic activity for minimal metastatic disease, therapy models in which the hosts have greater metastatic tumor burdens requires combination chemoimmunotherapy for a significant therapeutic effect. Because myelosuppression as a therapeutic indication for Bestatin has only recently been recognized, few clinical studies have been undertaken with appropriate surrogates of hematopoietic activity. However, the preliminary clinical evidence of hematopoietic activity by this non-toxic dipeptide, as reviewed here, suggests that this may be an appropriate drug for the treatment of myelosuppressed patients. Thus, Bestatin as an orally active biological response modifier (BRM) has significant therapeutic activity for metastatic disease via multiple mechanisms including hematopoietic stimulation and macrophage activating properties.

Animals↗
PubMed2005

Individual and joint association of alpha1A-adrenergic receptor Arg347Cys polymorphism and plasma irbesartan concentration with blood pressure therapeutic response in Chinese hypertensive subjects.

BACKGROUND: Individual variability in the therapeutic response to an antihypertensive drug could have a genetic basis. We investigated whether the alpha1A-adrenergic receptor (alpha1A-AR) Arg347Cys polymorphism is associated with the blood pressure (BP) therapeutic response to irbesartan and whether the association could be altered by the plasma irbesartan level. METHODS: A total of 696 hypertensive subjects were treated with a daily oral dose of 150 mg irbesartan. Baseline BP was measured before the first dose. On the 28th day, after 27 consecutive days of treatment and an overnight fast, BPs and blood samples were obtained before the morning dose (0 hours) and 6 hours after the morning dose was taken. Plasma irbesartan concentrations were measured by use of HPLC-fluorescence. RESULTS: BP therapeutic response was defined as baseline BP minus BP on the 28th day of irbesartan treatment. Relative to noncarriers, alpha1A-AR Cys347 allelic carriers had a significantly greater diastolic blood pressure (DBP) response at 0 hours (mean +/- SD, 7.5 +/- 8.4 mm Hg versus 5.5 +/- 8.4 mm Hg; P = .016) and at 6 hours (16.2 +/- 9.1 mm Hg versus 14.2 +/- 8.9 mm Hg, P = .025). Although the pattern was similar to the DBP response, alpha(1A)-AR Cys347 allelic carriers had only a moderately increased systolic blood pressure (SBP) response at the 2 time points. When subjects were stratified into subgroups with high or low plasma irbesartan concentrations (with the median value used as the cutoff point), Cys347 allelic carriers in the high-concentration group, relative to noncarriers, had a more pronounced DBP response at 0 hours (adjusted beta [+/- SE], 3.0 +/- 1.0 mm Hg; P = .004) and at 6 hours (adjusted beta, 3.0 +/- 1.2 mm Hg; P = .014), and the same was true for the SBP response at 0 hours (adjusted beta, 5.6 +/- 2.1 mm Hg; P = .006) and at 6 hours (adjusted beta, 4.7 +/- 2.0 mm Hg; P = .021). In contrast, in the low-concentration group, there was no significant association between DBP or SBP responses and Arg347Cys genotypes at 0 hours and 6 hours. CONCLUSION: Our data suggest that the alpha1A-AR Arg347Cys polymorphism is associated with BP response (particularly DBP) to short-term irbesartan treatment. Our data also showed evidence of an interaction between the alpha1A-AR Arg347Cys polymorphism and the plasma level of irbesartan in relation to BP therapeutic response. The association of the Arg347Cys polymorphism with the BP therapeutic response was more pronounced in those patients with higher plasma concentrations of irbesartan.

Aged↗
PubMed2005

Meta-analysis of therapeutic relationship variables in youth and family therapy: the evidence for different relationship variables in the child and adolescent treatment outcome literature.

This meta-analysis examines associations between therapeutic relationship variables, and the extent to which they account for variability in treatment outcomes, in 49 youth treatment studies. Correlations between therapeutic relationship variables ranged from modest to strong. Among the best predictors of youth outcomes were counselor interpersonal skills, therapist direct influence skills, youth willingness to participate in treatment, parent willingness to participate in treatment, youth participation in treatment, and parent participation in treatment. Adequacy of current approaches to conceptualizing and measuring therapeutic relationship variables, such as the therapeutic alliance, in youth and family therapy is discussed. This paper represents the most comprehensive analysis of therapeutic relationship constructs in the youth treatment literature.

Adolescent↗
PubMed2005

Therapeutic electrical stimulation of the central nervous system.

The electrical effects on the nervous system have been known for long. The excitatory effect has been used for diagnostic purposes or even for therapeutic applications, like in pain using low-frequency stimulation of the spinal cord or of the thalamus. The discovery that High-Frequency Stimulation (HFS) mimics the effect of lesioning has opened a new field of therapeutic application of electrical stimulation in all places where lesion of neuronal structures, such as nuclei of the basal ganglia, had proven some therapeutic efficiency. This was first applied to the thalamus to mimic thalamotomy for the treatment of tremor, then to the subthalamic nucleus and the pallidum to treat some advanced forms of Parkinson's disease and control not only the tremor but also akinesia, rigidity and dyskinesias. The field of application is increasingly growing, currently encompassing dystonias, epilepsy, obsessive compulsive disease, cluster headaches, and experimental approaches are being made in the field of obesity and food intake control. Although the effects of stimulation are clear-cut and the therapeutic benefit is clearly recognized, the mechanism of action of HFS is not yet understood. The similarity between HFS and the effect of lesions in several places of the brain suggests that this might induce an inhibition-like process, which is difficult to explain with the classical concept of physiology where electrical stimulation means excitation of neural elements. The current data coming from either clinical or experimental observations are providing elements to shape a beginning of an understanding. Intra-cerebral recordings in human patients with artefact suppression tend to show the arrest of electrical firing in the recorded places. Animal experiments, either in vitro or in vivo, show complex patterns mixing inhibitory effects and frequency stimulation induced bursting activity, which would suggest that the mechanism is based upon the jamming of the neuronal message, which is by this way functionally suppressed. More recent data from in vitro biological studies show that HFS profoundly affects the cellular functioning and particularly the protein synthesis, suggesting that it could alter the synaptic transmission by reducing the production of neurotransmitters. It is now clear that this method has a larger field of application than currently known and that its therapeutical applications will benefit to several diseases of the nervous system. The understanding of the mechanism has opened a new field of research, which will call for reappraisal of the basic effects of electricity on the living tissues.

Animals↗
PubMed2005

Tumor therapeutics by design: targeting and activation of death receptors.

Due to their strong apoptosis-inducing capacity, the death receptor ligands CD95L, TNF and TRAIL have been widely viewed as potential cancer therapeutics. While clinical data with CD95L and TRAIL are not yet available, TNF is a registered drug, albeit only for loco-regional application in a limited number of indications. The TNF experience has told us that specific delivery and restricted action is a major challenge in the development of multifunctional, pleiotropically acting cytokines into effective cancer therapeutics. Thus, gene-therapeutic approaches and new cytokine variants have been designed over the last 10 years with the aim of increasing anti-tumoral activity and reducing systemic side effects. Here, we present our current view of the therapeutic potential of the death receptor ligands TNF, CD95L and TRAIL and of the progress made towards improving their efficacy by tumor targeting, use of gene therapy and genetic engineering. Results generated with newly designed fusion proteins suggest that enhanced tumor-directed activity and prevention of undesirable actions of death receptor ligands is possible, thereby opening up a useful therapeutic window for all of the death receptor ligands, including CD95L.

Animals↗
PubMed2005

Echo-Doppler and clinical evaluations to define hemodynamic profile in patients with chronic heart failure: accuracy and influence on therapeutic management.

BACKGROUND: Correct classification of chronic heart failure (CHF) patients by dual evidence of congestion and adequate perfusion is the primary clinical focus for management. OBJECTIVES: To evaluate the accuracy of echo-Doppler compared with clinical evaluation in determining the hemodynamic profile of patients with CHF; and to compare therapeutic changes based on hemodynamic or echo-Doppler findings. METHODS: Three hundred and sixty-six consecutive CHF patients (ejection fraction 25+/-7%) in sinus rhythm, undergoing evaluation for cardiac transplantation, underwent physical examination prior to right heart catheterization and echo-Doppler studies. Subsequently, patients were randomized to therapeutic optimization using either right heart catheterization or echo-Doppler data. The end-points were: identification of low cardiac output (cardiac index <2.2 l/min/m(2)); high pulmonary wedge pressure (PWP >18 mm Hg); high right atrial pressure (RAP >5 mm Hg) and analysis of therapeutic changes made in response to the right heart catheterization and echo-Doppler studies. RESULTS: Echo-Doppler showed better accuracy in estimating abnormal hemodynamic indices than clinical variables (cardiac index <2.2 l/min/m(2): echo positive predictive accuracy (PPA) 98% vs. clinical PPA 52% p<0.00001; PWP >18 mm Hg: echo PPA 85% vs. clinical PPA 76% p=0.0011; RAP >5 mm Hg: echo PPA 82% vs. clinical PPA 57% p<0.00001). When applied to individual patients, the echo-Doppler assessment was more accurate than clinical evaluation in defining the different hemodynamic profiles: wet/cold (89% vs. 13%, p<0.0001); wet/warm (73% vs. 30%, p<0.0001); dry/cold (68% vs. 12%, p<0.0001); dry/warm (88% vs. 51%, p<0.0001). Therapeutic decision-making based on echo-Doppler findings was similar to that based on hemodynamics. CONCLUSION: Echo-Doppler hemodynamic monitoring proved accurate in estimating hemodynamic profiles and influenced therapeutic management.

Adrenergic beta-Antagonists↗
PubMed2004

Therapeutic advantage of grid irradiation for large single fractions.

PURPOSE: In the present work, we used model calculations of cell survival to compare the effects of single fraction high-dose grid therapy with those of uniform dose delivery on tumor and normal tissues. METHODS AND MATERIALS: The grid consisted of a hexagonal pattern of divergent holes in a Cerrobend block. A linear-quadratic model was used to find the surviving fraction of tumor and normal tissue cells after high-dose irradiation. Equivalent uniform doses were determined according to the tumor cell kill. The ratio of the normal tissue surviving fraction under grid irradiation to that obtained under equivalent uniform dose irradiation was taken as a measure of therapeutic gain. RESULTS: The therapeutic ratio varied from 0.80 to 13.22 for the range of cell sensitivities investigated, with single fraction doses of 10.0-20.0 Gy. Optimization studies showed no significant dependence of therapeutic gain on hole spacing. CONCLUSION: With high, single-fraction doses, grid irradiation revealed a therapeutic advantage over uniform dose irradiation whenever the tumor and surrounding normal tissues cells were equally radiosensitive, or, particularly, if the tumor cells were more radioresistant than the normal cells. The therapeutic gain did not appear to be a strong function of grid design.

Algorithms↗
PubMed2006

The role of the Therapeutic Goods Administration and the Medicine and Medical Devices Safety Authority in evaluating complementary and alternative medicines in Australia and New Zealand.

Currently, the regulation of complementary and alternative medicines and related health claims in Australia and New Zealand is managed in a number of ways. Complementary medicines, including herbal, minerals, nutritional/dietary supplements, aromatherapy oils and homeopathic medicines are regulated under therapeutic goods/products legislation. The Therapeutic Goods Administration (TGA), a division of the Commonwealth Department of Health and Ageing is responsible for administering the provisions of the legislation in Australia. The New Zealand Medicines and Medical Devices Safety Authority (Medsafe) administers the provision of legislation in New Zealand. In December 2003 the Australian and New Zealand governments signed a Treaty to establish a single, bi-national agency to regulate therapeutic products, including medical devices prescription, over-the-counter and complementary medicines. A single agency will replace the Australian TGA and the New Zealand Medsafe. The role of the new agency will be to safeguard public health through regulation of the quality, safety and efficacy or performance of therapeutic products in both Australia and New Zealand. The major activities of the new joint Australia New Zealand therapeutic products agency are in product licensing, specifying labelling standards and setting the advertising scheme, together with determining the risk classes of medicines and creating an expanded list of ingredients permitted in Class I medicines. A new, expanded definition of complementary medicines is proposed and this definition is currently under consultation. Related Australian and New Zealand legislation is being developed to implement the joint scheme. Once this legislation is passed, the Treaty will come into force and the new joint regulatory scheme will begin. The agency is expected to commence operation no later than 1 July 2006 and will result in a single agency to regulate complementary and alternative medicines.

Australia↗
PubMed2006

Analysis of prognostic factors in therapeutic responses to interferon in patients with chronic hepatitis C.

The genotype of hepatitis C virus (HCV) and the amount of HCV RNA are often used to predict the efficacy of interferon (IFN) therapy on chronic hepatitis C. In addition to these factors, there may be several factors related to the host. Therefore, the authors undertook a retrospective study in which physical findings and laboratory data before therapy were evaluated by multiple logistic analysis. Two-hundred and five cases with chronic hepatitis C treated with interferon were analyzed in this study. Sustained virological response was observed with 68 cases. Multiple logistic analysis was performed with 29 explanatory variables including HCV genotype, HCV RNA, IFN types, and total dose, along with gender, age, alcohol consumption, body mass index (BMI), histological findings of liver biopsy, platelet counts, and laboratory data of serum enzymes. Analysis on the factors that correlated well with therapeutic efficacy revealed that genotype 2a, 2b showed higher therapeutic responses than genotype 1b with reference to HCV genotypes, and higher IFN dose or lower HCV RNA levels gave better results. With reference to host factors, higher total protein level, lower levels of BMI, total bilirubin, and aspartate aminotransferase were highly correlated with therapeutic efficacy. HCV genotypes and HCV RNA levels have been already identified as prognostic factors. However, the high correlation values of BMI and the total protein level are new findings. It is suggested that probability estimation of therapeutic effects using the logistic regression equation may be a good tool for predicting therapeutic efficacy of IFN therapy on individual cases.

Adult↗
PubMed1995

Diagnosis and therapeutic monitoring of invasive candidiasis by rapid enzymatic detection of serum D-arabinitol.

BACKGROUND: Using a rapid automated enzymatic assay, we prospectively investigated serum D-arabinitol (DA), a biochemical marker of invasive candidiasis, in a large population of high-risk patients to determine its potential diagnostic, therapeutic, and prognostic significance in invasive candidiasis. PATIENTS AND METHODS: A total of 3,223 serum samples were collected from 274 patients with cancer. Serum DA concentrations were determined in coded serum samples analyzed by rapid enzymatic assay. Creatinine also was analyzed in the same system to determine a serum DA and creatinine ratio (DA/Cr). The sensitivity, specificity, correlation with therapeutic response, and prognostic significance were analyzed for all patient study groups. RESULTS: A DA/Cr of > or = 4.0 mumol/L per mg/dL was detected in 31 (74%) of all 42 cases of fungemia and 25 (83%) of the 30 cases of the subset of persistent fungemia. Elevated DA/Cr was detected in 4 (40%) of 10 patients with tissue-proven, deeply invasive candidiasis and negative blood cultures (eg, hepatosplenic candidiasis or localized abscess) and 7 (44%) of 16 cases of deep mucosal candidiasis (eg, esophageal candidiasis). Elevated serial DA/Cr levels also were detected in persistently febrile and granulocytopenic patients requiring empirical amphotericin B. Among 26 assessable cases of fungemia, abnormally elevated DA/Cr values were detected in 14 (54%) before, 10 (38%) after, and 2 (8%) simultaneously with the first microbiologic report of fungemia. The trends of serial DA/Cr values correlated with therapeutic response in 29 (85%) of 34 patients with assessable cases of fungemia, decreasing in 8 (89%) of 9 patients with clearance of fungemia and increasing in 21 (84%) of 25 patients with persistence of fungemia. Among the 34 assessable patients with fungemia, mortality was directly related to the trend of serial DA/Cr determinations over time: 71% among fungemic patients who had persistently elevated or increasing DA/Cr, and 18% among the fungemic patients who had resolving DA/Cr or never had elevated DA/Cr (P < 0.01). CONCLUSIONS: Rapid enzymatic detection of DA in serially collected serum samples from high-risk cancer patients permitted detection of invasive candidiasis, early recognition of fungemia, and therapeutic monitoring in DA-positive cases. Serially collected serum DA determinations complement blood cultures for improving detection and monitoring therapeutic response in patients at risk for invasive candidiasis.

Candidiasis↗
PubMedDate not supplied

Bacteremia following diagnostic and therapeutic ERCP.

The occurrence of bacteremia in association with diagnostic or therapeutic ERCP was studied in 180 patients undergoing a total of 194 examinations. Nineteen (15%) of 126 diagnostic procedures and 18 (27%) of 68 therapeutic procedures were associated with bacteremia (p less than 0.1). Nine patients had polymicrobial bacteremia and a total of 16 species were detected. Different streptococci, mainly alpha-hemolytic, were the most common bacteria which were identified in 38% of the bacteremic patients. There were no significant differences with regard to the occurrence of fever, pancreatitis, or septic complications between the diagnostic and therapeutic groups of patients. Neither did the complication rate in patients with bacteremia differ from that in patients without bacteremia, whether the procedure was diagnostic or therapeutic. Complication rates did not differ between patients with and patients without pancreaticobiliary obstruction. However, the majority of patients with biliary stasis had drainage with relief of the obstruction at the time of the diagnostic ERCP. We conclude that general routine antibiotic prophylaxis is not indicated in patients undergoing diagnostic or therapeutic ERCP. The question whether such prophylaxis should be given with certain diagnoses or treatments, or in patients with valvular heart disease, remains to be answered in controlled randomized studies.

Aged↗
PubMed1997

Therapeutic ERCP: a cost-prohibitive procedure?

BACKGROUND: ERCP is increasingly being performed for therapeutic purposes and engenders a proliferation of disposable equipment without a clear indication of cost-effectiveness. METHODS: We analyzed the financial impact of ERCP by prospectively analyzing ERCPs performed in our institution from June 1, 1994, to September 30, 1994, by calculating charges related to indirect costs, disposable equipment costs, and overall reimbursement. The data were analyzed according to insurance payor as well. RESULTS: Disposable equipment costs a mean of $149 per diagnostic ERCP and $532 per therapeutic ERCP. For diagnostic ERCP, disposable equipment accounted for 27% of reimbursement; for therapeutic ERCP, disposable equipment accounted for 68% of reimbursement. Although overall reimbursement was higher for therapeutic ERCP, the very high direct costs related to disposable equipment limited the ability of reimbursement to cover indirect costs. CONCLUSIONS: Depending on the complexity of cases, quantity of disposable equipment used, and patient-insurance mix, therapeutic ERCP may be cost prohibitive for a given endoscopy unit. Indirect costs should be more carefully and quantitatively analyzed. Disposable equipment should be evaluated in terms of cost, safety, and patient outcome.

Cholangiopancreatography, Endoscopic Retrograde↗
PubMed1999

Outpatient therapeutic ERCP with endobiliary stent placement for malignant common bile duct obstruction.

BACKGROUND: Since 1996 patients in stable condition who need therapeutic endoscopic retrograde cholangiopancreatography (ERCP) at our institution have been treated as outpatients whenever possible. We reviewed our institution's experience and compared outpatient versus inpatient therapeutic ERCP for endobiliary stent placement in the care of patients with malignant common bile duct obstruction. METHODS: A retrospective review of all therapeutic ERCPs for the palliation of malignant common bile duct obstruction with endobiliary stents was performed from March 1, 1996, through December 1, 1997. RESULTS: One hundred nine therapeutic ERCPs were performed on 84 patients to place a polyethylene endobiliary stent for malignant common bile duct obstruction. Forty-three procedures were performed on 31 outpatients, 66 on 53 inpatients. There was no significant difference between outpatient and inpatient groups with regard to age, gender, procedure success rate, complication rate, need for endoscopic sphincterotomy, or whether the procedure was for initial stent placement or stent exchange. Inpatients had no procedure-related complications; outpatients had two. There was no procedure-related mortality in either group. CONCLUSION: Therapeutic ERCP for palliation of malignant common bile duct obstruction can be safely and successfully performed on an outpatient basis for selected patients. This should result in better quality of life for these patients with advanced cancer and substantial cost savings.

Aged↗
PubMed2004

[Therapeutic compliance in the prevention of primary cardiovascular diseases with lovastatine. PRELOVAS study].

BACKGROUND AND OBJECTIVE: Our objective was to compare the therapeutic compliance in two groups of patients treated with lovastatine for the prevention of cardiovascular diseases in clinical practice. PATIENTS AND METHOD: Observational, prospective and multi-centre study carried out in patients who attended primary care and had a clinical indication to follow treatment with lovastatine for the prevention of cardiovascular diseases. Four visits were carried out (baseline, at 4-6 weeks, at 6 and 12 months). In the baseline visit, clinical and sociodemographic variables were registered. In visit 2, the investigator counted the number of pills the patients had taken, which together with the results of the Morisky Green Questionnaire allowed him to classify the patients into two groups: Group A (non-compliant patient) and B (compliant patient). Group A received medical advice in order to increase the adherence to treatment. RESULTS: A total of 815 subjects with indication of lipid-lowering treatment were involved. At the 6 month of follow up, 22% of the subjects from Group A and 63% from Group B had improved their adherence, 38% of the subjects of the group B maintained a good therapeutic compliance during the whole study and 12% of the group A subjects who came up to the final visit improved their compliance during the whole study (p < 0.05). Subjects who showed good compliance with the lipid-lowering treatment along 12 months registered lesser values of cholesterol (128 mg/dl) (p < 0.005). CONCLUSIONS: It is important to identify non-compliant patients at the beginning of the treatment with lipid-lowering treatment. That makes possible to implement from the very beginning therapeutic measures aimed at improving the therapeutic compliance and allows at the same time to achieve a greater therapeutic effectiveness.

Anticholesteremic Agents↗
PubMed2002

Monitoring of unfractionated heparin with the activated partial thromboplastin time: determination of therapeutic ranges.

The purpose of the present study was to determine therapeutic ranges for unfractionated heparin therapy using the activated partial thromboplastin time (APTT) by calibration against anti-Xa concentration. APTT assays were performed locally, i.e. at the institution of blood collection, on fresh plasma samples from patients treated with intravenous unfractionated heparin. The measurements were performed by 25 Dutch clinical laboratories using 11 different APTT reagents and 10 different types of coagulometers. After the local APTT measurement, the samples were frozen and transported to a central laboratory for measurement of anti-Xa activity. The number of samples from the participating laboratories ranged from 10 to 48. Local APTT results were correlated with the central anti-Xa measurements. Orthogonal regression analysis of log-transformed values was used to calculate APTT therapeutic ranges corresponding to anti-Xa concentrations of 0.29-0.47 IU/ml. The calculated APTT ranges were different between laboratories, even when the same reagent was used. In many laboratories, the therapeutic APTT range in use was much wider than the calculated range. Imprecision of the calculated APTT range was influenced by the wide scatter of the measurement points and by the selection of samples for the orthogonal regression equation. The present results show that, if anti-Xa concentrations of 0.29-0.47 IU/ml reflect the true therapeutic range, many laboratories do not use the proper therapeutic APTT range.

Dose-Response Relationship, Drug↗
PubMed2002

Prophylactic versus therapeutic alpha-blockers after permanent prostate brachytherapy.

OBJECTIVES: To evaluate the influence of prophylactic versus therapeutic alpha-blockers on urinary morbidity after permanent prostate brachytherapy. Multiple clinical and treatment parameters were evaluated to identify the factors associated with acute urinary morbidity. METHODS: A total of 234 consecutive patients underwent permanent prostate brachytherapy in one of two prospective randomized studies from October 1999 through February 2001 using either palladium-103 or iodine-125 for clinical Stage T1b-T2b (1997 American Joint Commission on Cancer staging system) prostate cancer at either the Schiffler Cancer Center or Puget Sound Health Care System. The mean and median follow-up was 8.8 +/- 4.6 months and 6 months, respectively. In 142 patients, an alpha-blocker was initiated before implantation and continued at least until the International Prostate Symptom Score (IPSS) returned to baseline levels; 92 patients either did not receive an alpha-blocker or received a therapeutic alpha-blocker after implantation because of urinary obstructive symptoms. The clinical and treatment parameters evaluated for urinary morbidity included prophylactic versus therapeutic alpha-blockers, age, preimplant IPSS, ultrasound volume, use of neoadjuvant hormones, use of supplemental external beam radiotherapy, isotope, urethral dose, and multiple dosimetric quality indicators (minimal dose received by 90% of the prostate gland and percentage of prostate volume receiving 100% or 200% of the prescribed minimal peripheral dose). Catheter dependency and the duration of alpha-blocker dependency were also evaluated. RESULTS: In both the prophylactic and the therapeutic cohorts, the IPSS peaked 1 month after implantation. Patients receiving a prophylactic alpha-blocker returned to baseline at a mean of 4 months and a median of 3 months postoperatively. For those patients not receiving prophylactic alpha-blockers, the IPSS returned to the antecedent value at a mean and median of 10 months and 6 months, respectively. Of the 125 patients receiving prophylactic alpha-blockers, 102 (81.2%) remained medication dependent at the conclusion of the study, and 140 (78.2%) of 179 patients receiving alpha-blockers other than for hypertensive purposes did so. The incidence of prolonged urinary catheter dependency (greater than 3 days) and the need for postimplant transuretheral incision of the prostate/transurethral resection of the prostate were not affected by alpha-blocker use. Cox regression analysis revealed that only the prophylactic use of alpha-blockers and the difference between the preimplant IPSS and the 1-month IPSS were predictive of the time to return to the referent zone. CONCLUSIONS: Prophylactic use of alpha-blockers results in significantly less urinary morbidity than either the absence or therapeutic use of alpha-blockers. In patients receiving prophylactic alpha-blockers, the IPSS normalized significantly faster but had no impact on urinary retention or the ultimate need for postimplant surgical intervention.

Adenocarcinoma↗
PubMed1997

Dynamic compaction: a new process to compact therapeutic agent-loaded calcium phosphates.

The sintering stage in the classical process of preparing bone substitution materials prevents therapeutic agents from being loaded into calcium phosphate powder. However, dynamic compaction, a new process, requires no external heat, allowing the therapeutic agent to be incorporated into ceramics. This report presents the results of an in vitro study of therapeutic agents associated with calcium phosphate powder and involving this new process. A mixture of vancomycin lyophilized powder (0.15 g) and biphasic calcium phosphate (BCP) powder (1.85 g) was compacted. In addition, 2 ml of human growth hormone (1 mg ml-1) were associated with BCP powder by physical adsorption on bead surfaces before compaction. Detection by monoclonal antibodies and sodium dodecyl sulphate polyacrylamide gel electrophoresis demonstrated the structural integrity of the two therapeutic agents after consolidation. This new compaction process should be useful in developing ceramics that contain a therapeutic agent.

Adsorption↗