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PubMedDate not supplied

Laboratory and therapeutic control in the Thrombosis Centre Rotterdam using chromogenic prothrombin time tests.

Growing interest is observed in chromogenic substrate assays, because of their better precision, performance and possibilities for automation. Applied to a Cobas Bio centrifugal analyzer, we compared Nycotest-Chrom (N-test) and Thromboquant-PT (Tbq) with Thrombotest (TT). Precision tests were performed with samples from 4 plasma pools: normal (45 sec), low (100 sec), middle (150 sec) and high (200 sec) segments of the therapeutic range of TT. N-test had the best precision profile in both intraassay and interassay determinations compared with Tbq. Both chromogenic substrate assays were better than TT in this respect. By orthogonal regression a provisional therapeutic range was calculated from 312 determinations and later adjusted in a confirmation experiment with natural logarithm regression in 946 determinations. Compared with a TT range of 105-180 sec, the therapeutic ranges were 71-120 sec for N-test and 63-103 sec for Tbq. In a clinical therapeutic control phase, 110 patients were randomized in equal proportions to two groups A and B. Every 2 weeks for a period of 16 weeks, blood samples were tested for N-test, Tbq and TT. In group A, dose adjustment was based on N-test, and in group B on Tbq. The monitoring physician was blinded for Tbq and TT in group A and for N-test and TT in group B. No differences were found between the groups for mean TT, N-test, Tbq or mean dosage, nor differences were found in complication rate. A definite therapeutic range was complied using sensitivity/specificity curves together with their 95% confidence limits. Given TT 105-180 sec, the therapeutic range of N-test is from 80 (95% confidence limits: 77-82) to 110 (95% confidence limits: 108-115) sec, and of Tbq from 68 (95% confidence limits: 66-71) to 95 (95% confidence limits: 91-98) sec. It was concluded that the two chromogenic substrate assays performed equally safe in the monitoring of patients on oral anticoagulant therapy, despite differences in diagnostic correspondence with the reference TT.

Administration, Oral↗
PubMed2000

Marked acute tissue swelling following percutaneous sclerosis of low-flow vascular malformations: a predictor of both prolonged recovery and therapeutic effect.

PURPOSE: To evaluate the significance of marked, acute swelling in patients after percutaneous sclerosis of low-flow vascular malformations, as a predictor of both prolonged recovery and likelihood of therapeutic effect. MATERIALS AND METHODS: In 22 patients who underwent percutaneous ethanol sclerosis of low-flow vascular malformations, we compared the incidence of prolonged recovery and lasting therapeutic effect between those patients with and without marked soft-tissue swelling following the procedure. RESULTS: Five patients exhibited marked swelling after sclerosis. Four of these five had causes of prolonged recovery. These four recovered and all five eventually had marked therapeutic effect. Seventeen patients did not meet criteria for severe swelling. Only one of these patients had prolonged recovery. Eighteen of the 22 total patients had therapeutic effect. All 4 of the 22 total patients who had no therapeutic effect were in the group without marked swelling. CONCLUSIONS: Marked soft-tissue swelling, which occurs after percutaneous sclerosis of vascular malformations, is both a predictor of prolonged recovery and high likelihood of therapeutic effect.

Acute Disease↗
PubMed2000

Therapeutic advantages of Auger electron- over beta-emitting radiometals or radioiodine when conjugated to internalizing antibodies.

Recent studies suggest a higher anti-tumour efficacy of internalizing monoclonal antibodies (MAbs) when labelled with Auger electron emitters, as compared with beta-emitters. The aim of this study was to compare the anti-tumour efficacy and toxicity of the internalizing MAb, CO17-1A, labelled with Auger electron emitters (125I, (111)In) versus conventional beta(-)-emitters (131I, 90Y) in a colon cancer model, and to assess whether the residualizing radiometals may have therapeutic advantages over the conventionally iodinated conjugates. Biodistribution studies of 125I-, (111)In- or 88Y-labelled CO17-1A were performed in nude mice bearing subcutaneous human colon cancer xenografts. For therapy, the mice were injected with either unlabelled or 125I-, 131I-, (111)In- or 90Y-labelled CO17-1A IgG2a, whereas control groups were left untreated or were given a radiolabelled isotype-matched irrelevant antibody. The influence of internalization was assessed by comparing the results with those obtained with an anti-carcinoembryonic antigen (CEA) antibody which does not internalize to a relevant extent. The maximum tolerated activities (MTA) and doses (MTD) of each agent were determined. Myelotoxicity and potential second-organ toxicities, as well as tumour growth, were monitored. Bone marrow transplantation (BMT) was performed in order to enable dose intensification. Radiometals showed significantly better tumour-to-blood ratios than the respective iodinated conjugates. The MTAs of 131I- and 125I-CO17-1A without artificial support were 11.1 MBq (300 microCi) and 111 MBq (3 mCi), respectively; the MTA of the metals was reached at 4 MBq (100 microCi) for 90Y-, and at 85 MBq (2.3 mCi) for (111)In-CO17-1A. Myelotoxicity was dose limiting in all cases. BMT enabled an increase in the MTA to 15 MBq (400 microCi) of 131I-labelled CO17-1A, to 4.4 MBq (120 microCi) of 90Y-labelled CO17-1A, and to 118 MBq (3.2 mCi) of (111)In-labelled CO17-1A, while the MTA of 125I-CO17-1A had not been reached at 185 MBq (5 mCi) with BMT. Whereas no significant therapeutic effects were seen with unlabelled CO17-1A, tumour growth was retarded significantly with its radiolabelled forms. The therapeutic results were significantly (P<0.01) better with both Auger electron emitters (125I and (111)In) than with the beta-emitters, and, in accordance with the biodistribution data, a trend towards better therapeutic results was found with radiometals (more complete remissions) as compared with radioiodine. In contrast, at equitoxic doses, no significant difference was observed in the therapeutic efficacy of 131I- versus 125I-labelled non-internalizing anti-CEA antibody, F023C5. These data suggest that, at equitoxic doses, the therapeutic efficacy of internalizing MAbs labelled with Auger electron emitters, such as 125I or (111)In, is superior to that of internalizing MAbs labelled with conventional beta-emitters. The lower toxicity of Auger electron emitters may be due to the short path length of their low-energy electrons, which can reach the nuclear DNA only if the antibody is internalized (as is the case in antigen-expressing tumour tissue, but not in the stem cells of the red marrow).

Animals↗
PubMed1989

Controlling drug effects through improved oral formulations. The pharmacokinetics of the prazosin gastrointestinal therapeutic system.

Influences that determine a drug's effects include pharmacokinetic factors (the serum concentrations of drug as determined by the drug dose, absorption, distribution, and excretion) and pharmacodynamic factors (the intensity of drug effect). Most assessments of drug effect focus on the therapeutic range, i.e., the serum concentrations below which therapeutic effects are unlikely and above which toxic effects may be seen. A goal for many treatment regimens is to maintain serum drug concentrations within the therapeutic range. Maintenance of drug concentrations within the therapeutic range can be difficult with many traditional oral dosage formulations. Soon after administration of standard tablets, capsules, or liquids, a pronounced peak level is observed in serum. At the end of a dosage interval, serum concentrations are frequently below those needed to exert therapeutic effect. One reason for the wide range in serum concentrations with standard oral formulations is that these products usually exhibit first-order drug absorption, in which the rate of absorption from the gastrointestinal tract continually varies following a dose (from high to low) and is directly determined by the amount of drug remaining in the gastrointestinal tract. First-order absorption, therefore, results in changing absorption rates, wide swings in serum drug concentrations, a relatively short duration of action, and often, inconsistent drug effects over a dosage interval. One way to address the problems with standard oral products that have first-order absorption is to produce products that control drug release and absorption. A large number of controlled-release oral products are now on the market and use a variety of technologies. The ideal controlled-release formulation would result in zero-order drug absorption, in which the rate of drug absorption from the gastrointestinal tract would be constant and not determined by the amount of drug in the gastrointestinal tract. Zero-order absorption, therefore, results in an unchanging absorption rate, consistent serum levels, a longer duration of action, and more steady drug effect. Zero-order absorption is particularly preferable in situations that require a consistent, long-term therapeutic effect, e.g., in patients with hypertension, asthma, or arrhythmias. Of all the controlled-release preparations on the market, however, very few exhibit zero-order absorption; most can be categorized somewhere between first- and zero-order kinetics. An advanced-technology tablet has been invented to produce zero-order drug absorption for prazosin and nifedipine.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Oral↗
PubMedDate not supplied

Therapeutic uses of contact lenses.

Therapeutic use of contact lenses is an essential element in ophthalmic care. Materials currently in use include polymethyl methacrylate (PMMA), cellulose acetate butyrate, siloxane-containing polymethacrylates, silicones, and hydrogels. Suitability of a material for therapeutic contact lens use is determined by the physical, chemical, and mechanical properties (notably gas permeability and hydrophilicity, but also lipid absorption and lens movement, among others) and the condition to be treated; fabrication techniques are likewise important, affecting lens diameter and base curve. Selection and fitting of therapeutic contact lenses requires knowledge of how different contact lenses affect corneal physiology, as well as an understanding of the mechanisms whereby a contact lens can be therapeutic. In addition to these topics, general fitting guidelines are discussed, and results of therapeutic lens use in selected clinical situations (including recurrent erosion, metaherpetic ulcers and other epithelial defects, and keratitis sicca, and other dry eye states). Common therapeutic contact lens complications and their treatment are also discussed.

Contact Lenses↗
PubMed1994

The development of a [211At]-astatinated endoradiotherapeutic drug: Part II. Therapeutic results for transplanted adenocarcinoma of the rectum in mice and associated studies.

PURPOSE: 6-[211At]-astato-MNDP is of a class of a high linear energy transfer endoradiotherapeutic drug, which selectively targets to an onco-APase isoenzyme expressed by certain epithelial and germ cell tumors. The therapeutic efficacy and acute toxicity of its endogenous alpha-particle emissions have been studied in a murine tumor model. METHODS AND MATERIALS: 211At was produced by the 207Bi(alpha,2n)211 At cyclotron-based nuclear reaction. High specific activity 6-[211At]-astato-MNDP was rapidly synthesized by in vacuo thermal heterogeneous isotopic exchange. The therapeutic potential of 6-[211At]-astato-MNDP and 211At- was determined in mice bearing a transplanted CMT-93 rectal carcinoma which exhibited onco-APase activity. RESULTS: Significant therapeutic effects due to targeted alpha-particle emissions have been confirmed for the activity dose range, 10-750 kBq 6-[211At]-astato-MNDP. A therapeutic window has been identified, whereby cure rates of approximately 45-65% were achieved following administration of 55-300 kBq 6-[211At]-astato-MNDP. Estimated tumor absorbed radiation doses were not inconsistent with clinical response. Irreversible hematoxicity or stigmata of acute radiation damage in other critical normal tissues were not encountered. Nonspecifically internalized 211At- exerted no therapeutic effect. CONCLUSION: Therapeutic results for 6-[211At]-astato-MNDP have confirmed the profound in vivo cytotoxicity of its targeted alpha-radiations in the CMT-93 tumor. Acute normal tissue toxicity was acceptable. A rationale for optimal fractionation of targeted 6-[211At]-astato-MNDP endoradiotherapy is discussed, and its putative role in the possible individualized management of certain human tumors has been proposed.

Adenocarcinoma↗
PubMed1996

Cumulative reduction in serum cholinesterase following repeated therapeutic plasma exchange.

STUDY OBJECTIVE: To investigate the magnitude of serum cholinesterase reduction following repeated therapeutic plasma exchange in patients with neuromuscular disease. DESIGN: Serum cholinesterase activity was measured immediately before and after each plasma exchange in open-label fashion and then analyzed using an analysis of variance model. SETTING: Inpatient neurology and allergy and immunology clinics at a university-affiliated hospital. PATIENTS: 50 consecutive patients with neuromuscular disease. INTERVENTIONS: All patients underwent repeated therapeutic plasma exchange, with each subject receiving up to a maximum of six plasma exchanges. MEASUREMENTS AND MAIN RESULTS: Serum cholinesterase activity was determined spectrophotometrically. Analysis of variance revealed a significant reduction in serum cholinesterase following each therapeutic plasma exchange (p < 0.0001), a significant and consistent reduction across the six treatments (p < 0.0001), and a significant interaction between (before versus after exchange) and treatment number (p < 0.0001). Mean serum cholinesterase before repeated therapeutic plasma exchange was 4817 U/L, but it decreased to a mean of 929 U/L following six plasma exchanges. CONCLUSIONS: There is a significant reduction in serum cholinesterase following repeated therapeutic plasma exchange. It is suggested that drugs metabolized by serum cholinesterase (e.g., succinylcholine, mivacurium) be used with caution in the period immediately following repeated therapeutic plasma exchange.

Anesthesia↗
PubMed2004

Therapeutic penetrating keratoplasty for microbial keratitis in Taiwan from 1987 to 2001.

PURPOSE: To determine the surgical outcomes of therapeutic penetrating keratoplasty (PKP) and its role in the management of microbial keratitis. DESIGN: Interventional case series. METHODS: We retrospectively performed a chart review of the hospital records of all 151 patients undergoing therapeutic PKP for culture-proven microbial keratitis at the National Taiwan University Hospital during a 14 year-period (1987-2001). Patients were divided into three categories: (1) bacterial keratitis; (2) fungal keratitis; and (3) acanthamoebic keratitis. Each of the following criteria was evaluated: (1) graft clarity 1 month and 1 year postoperatively; (2) cure of the disease; and (3) anatomical success rate. RESULTS: A total of 108 therapeutic PKP met the criteria. Therapeutic PKP eradicated the infection in 37/41 of patients with bacterial keratitis, 36/52 of patients with fungal keratitis, and 13/15 of patients with acanthamoebic keratitis. 22/32 of grafts of bacterial keratitis, 20/39 of fungal keratitis, and 11/14 of acanthamoebic keratitis remained clear at 1 year postoperatively. A higher percentage of graft clarity at 1 year postoperatively was achieved in all three categories when grafts were 8.5 mm or less compared with larger grafts. All five patients with secondary endophthalmitis observed at the time of therapeutic PKP experienced a progression of infection despite aggressive surgical treatment, and had to be enucleated. CONCLUSIONS: Therapeutic PKP is valuable in the management of microbial keratitis that is unresponsive to medical therapy. A higher percentage of clear graft was found when grafts were smaller in all three categories. Surgical results are worse for patients with fungal keratitis, regardless of graft clarity, anatomical success, or infection eradication rate.

Acanthamoeba Keratitis↗
PubMed2006

Therapeutic bronchoscopy interventions before surgical resection of lung cancer.

BACKGROUND: Therapeutic bronchoscopy is used for endobronchial staging of lung cancer and symptomatic relief of central airway obstruction or postobstructive pneumonia. The aim of this study was to assess the utility of therapeutic bronchoscopy as a complementary tool in the combined bronchoscopic and surgical management of malignant airway lesions before curative lung surgery. METHODS: Seventy-four consecutive patients with nonsmall cell lung carcinoma undergoing a therapeutic bronchoscopy procedure followed by surgery with a curative intent were included. RESULTS: A single interventional bronchoscopic method was used in 27 patients (36%) and a combination of methods in 47 patients (64%). Median forced expiratory volume in 1 second (FEV1) before and after bronchoscopy were 1.7 L and 2.2 L, respectively, and forced vital capacity (FVC) was 2.5 L and 3.3 L, respectively. Sleeve upper lobectomy was performed in 22 patients (30%), sleeve upper bilobectomy in 16 patients (22%), lower bilobectomy in 2 patients (3%), pneumonectomy with sleeve resection in 2 patients (3%), and pneumonectomy in 28 patients (38%). The following surgeries were performed in 1 patient each: sleeve middle lobectomy, sleeve lower lobectomy, carina resection and complex reconstruction, and exploratory thoracotomy. Overall, parenchyma-sparing surgery (lobectomy or bilobectomy) could be performed in 57% patients after therapeutic bronchoscopy. There were no in-hospital deaths or deaths in the first 30 days after surgery. CONCLUSIONS: Therapeutic bronchoscopy can be used as a complementary tool in the combined bronchoscopic and surgical management of malignant airway obstruction before curative lung surgery. Therapeutic bronchoscopy might permit parenchyma-sparing surgery in patients with lung cancer.

Adenocarcinoma↗
PubMed2005

Therapeutic inhibition of hepatitis B virus surface antigen expression by RNA interference.

RNA interference (RNAi) mediated inhibition of virus-specific genes has emerged as a potential therapeutic strategy against virus induced diseases. Human hepatitis B virus (HBV) surface antigen (HBsAg) has proven to be a significant risk factor in HBV induced liver diseases, and an increasing number of mutations in HBsAg are known to enhance the difficulty in therapeutic interventions. The key challenge for achieving effective gene silencing in particular for the purpose of the therapeutics is primarily based on the effectiveness and specificity of the RNAi targeting sequence. To explore the therapeutic potential of RNAi on HBV induced diseases in particular resulted from aberrant or persistent expression of HBsAg, we have especially screened and identified the most potent and specific RNAi targeting sequence that directly mediated inhibition of the HBsAg expression. Using an effective DNA vector-based shRNA expression system, we have screened 10 RNAi targeting sequences (HBsAg-1 to 10) that were chosen from HBsAg coding region, in particular the major S region, and have identified four targeting sequences that could mediate sequence specific inhibition of the HBsAg expression. Among these four shRNAs, an extremely potent and highly sequence specific HBsAg-3 shRNA was found to inhibit HBsAg expression in mouse HBV model. The inhibition was not only preventive in cotransfection experiments, but also had therapeutic effect as assessed by post-treatment protocols. Moreover, this HBsAg-3 shRNA also exhibited a great potency of inhibition in transgenic mice that constitutively expressed HBsAg. These results indicate that HBsAg-3 shRNA can be considered as a powerful therapeutic agent on HBsAg induced diseases.

Animals↗
PubMed2004

Efficacy of continuous wear PureVision contact lenses for therapeutic use.

PURPOSE: To evaluate the Bausch and Lomb PureVision contact lens as continuous wear contact lens for therapeutic and medical indications in a prospective open-ended non-randomized trial. METHODS: Patients who required therapeutic contact lens wear for various indications such as pain relief, corneal protection, persistent epithelial defects, corneal perforation and chemical burns were fitted with PureVision continuous wear contact lenses (balafilcon A, 36% water content). Success or failure of specific treatment indication was assessed in each case with evaluation of ocular and lens related complications. RESULTS: 30 eyes of 28 patients were fitted with PureVision continuous wear contact lenses. A successful fit was seen in 27 of 30 eyes with therapeutic success in 26 of 30 eyes. However, all patients reported symptomatic relief. Duration of lens use ranged from 3 days to 3 months. Dry eye was the most frequent cause of contact lens associated therapeutic failure. Complications included lens loss (two eyes), tight lens (one eye) and infective keratitis (two eyes). CONCLUSIONS: PureVision contact lenses were found to be safe and efficacious for continuous wear therapeutic use to a maximum of 90 days. The contact lens was also easier to handle by virtue of its resilient nature. There were no significant corneal complications of hypoxia, i.e. corneal oedema. Lens losses and deposits were minimal. The lens performance and fitting characteristics compares favorably with previous therapeutic lenses used by the investigators. This new lens may be considered as a safe and effective alternative for use as bandage contact lens.

Journal Article↗
PubMed2006

Efficacy and safety of therapeutic ERCP in patients 90 years of age and older.

BACKGROUND: Therapeutic ERCP has an established role in the treatment of pancreatobiliary diseases, but little information is available on the outcomes of this procedure in patients 90 years of age and older. OBJECTIVE: To evaluate the efficacy and the safety of therapeutic ERCP in an extremely elderly cohort. DESIGN: Retrospective study. SETTING: Two Greek cohorts of patients > or =90 and 70 to 89 years of age who underwent therapeutic ERCPs. PATIENTS: Sixty-three patients aged 90 years and older (group A) and 350 patients 70 to 89 years of age (group B). INTERVENTIONS: A retrospective review of therapeutic ERCPs was performed between 1994 and 2000 on both groups, identified by using a database linked to the endoscopy reporting system in our department. MAIN OUTCOME MEASUREMENTS: Efficacy and safety of therapeutic ERCPs. Concomitant diseases, complications, and outcome were also evaluated. RESULTS: Group A patients had a higher incidence of concomitant diseases than group B patients (100% vs 72.8%, respectively). The rate of post-ERCP early complications was low in both groups: 6.3% in group A and 8.4% in group B. The frequency of ERCP-related mortality was 1.6% (1 patient) in group A and 0.6% (2 patients) in group B. Group A required endoscopic sessions for stone clearance and mechanical lithotripsy more frequently than group B (20.6% vs 11.4% and 17.5% vs 10.3%, respectively). No patient in either group experienced subjective deterioration in mental status, and the 3 patients who died required ventilatory support before death. Late complications occurred in 2.3% of patients in group B. CONCLUSIONS: Therapeutic ERCP is safe and effective for the treatment of pancreatobiliary diseases in extremely elderly patients, and advanced age per se should not impinge on decisions relating to its use.

Age Factors↗
PubMed2005

Adherence to therapeutic guidelines for acute otitis media in children younger than 2 years.

OBJECTIVES: to analyze adherence to therapeutic guidelines for AOM. METHODS: Descriptive retrospective study of community primary care providers in southern Israel. Study population (n = 590) included all children aged 0-48 months diagnosed with AOM in PED during the year 2000 who had a referral letter from a community physician and an AOM diagnosis confirmed by tympanocentesis. AOM antibiotic treatment was considered appropriate when in accord with CDC and local therapeutic guidelines. RESULTS: Referral letter data allowing characterization of AOM by category were available in 471 (79.8%) children, 320 (68%) with simple AOM and 151(32%) with complicated AOM. AOM diagnosis made by the primary care physician was in accord with PED diagnosis in 365/590 (62%) patients. Three hundred and fifty-five (60.2%) patients did not receive antibiotics in the community. Of 365 (62%) children diagnosed with AOM in the community, 235 (64.4%) were treated with antibiotics prior to arrival to PED. Amoxicillin was prescribed to 109 (46.4%), cefuroxime axetil to 48 (20.4%), amoxicillin/clavulanate to 31 (13.2%) and i.m. ceftriaxone to 20 (8.5%) of the patients. Eighty-three (25.9%) patients with simple AOM were treated with antibiotics in the community and only 46 (55.4%) received amoxicillin according to the therapeutic guidelines. Eighty-one (53.6%) patients with complicated AOM were treated with antibiotics in the community and only 41 (50.6%) of them received antibiotics according to AOM therapeutic guidelines. More antibiotics were prescribed in the community to patients with complicated AOM than to patients with simple AOM (81/151, 53.6% versus 83/320, 25.9%, respectively, p < 0.001). Adherence to therapeutic guidelines was similar between the simple and the complicated AOM groups (46/83, 55.4% versus 41/81, 50.6%, respectively, p = 0.5). CONCLUSION: We found partial adherence to AOM therapeutic guidelines among primary care providers in the community in Southern Israel.

Acute Disease↗
PubMed2005

Botulinum toxin type A injections: adverse events reported to the US Food and Drug Administration in therapeutic and cosmetic cases.

BACKGROUND: Botulinum toxin type A (BTA) (Botox) received Food and Drug Administration (FDA) approval for therapeutic treatment of strabismus and blepharospasm in 1989, cervical dystonia in 2000, and cosmetic treatment of glabellar wrinkles (Botox Cosmetic) in 2002. In 2002 alone there were approximately 1.1 to 1.6 million patients using cosmetic BTA. Our objective was to review adverse event (AE) reporting to the FDA after BTA administration. METHODS: We reviewed all (therapeutic and cosmetic use) serious (per FDA regulations) AEs reported to the FDA for the 13.5 years since licensure of the product (December 1989-May 2003) and nonserious AEs reported from December 2001 to November 2002. AEs are reported to the FDA through the MedWatch system. RESULTS: We reviewed 1437 AE reports; 406 followed therapeutic use of BTA (217 serious and 189 nonserious) and 1031 followed cosmetic use (36 serious and 995 nonserious). Reported AEs occurred predominantly in female patients, with a median age of 50 years. In the year December 2001 to November 2002, when both serious and nonserious reports were evaluated, the proportion of reports classified as serious was 33-fold higher for therapeutic than for cosmetic cases. The 217 serious AEs reported in therapeutic cases involved a wide spectrum of events and included all 28 reported deaths. Among cosmetic users, no deaths were reported and, of the 36 serious AEs, 30 were included as possible complications in the FDA-approved label. The remaining 6 serious AEs did not display a pattern suggesting a common causal relationship to BTA. Among the 995 cosmetic cases reported to have nonserious AEs, most commonly noted were lack of effect (623, 63%), injection site reaction (190, 19%), and ptosis (111, 11%). CONCLUSIONS: Serious AEs were more likely to be reported for therapeutic than for cosmetic use, which may be related to higher doses, complicated underlying diseases, or both. Among cosmetic cases, few serious AEs were reported, and these were predominantly events that were previously recognized in clinical trials of BTA for the labeled use. This study is limited primarily by the incomplete nature of AE reporting by clinicians. Numerous departures from FDA-approved recommendations for drug dose, dilution, handling, site of injection, and storage were noted in these AE reports.

Adult↗
PubMed2004

[Revaluation of chloroquine therapeutic efficacy on children with uncomplicated Plasmodium falciparum malaria in eastern Ivory Coast (1999-2002)].

OBJECTIVE: A prospective study was made from November 1999 to May 2002 in order to revaluate the therapeutic efficacy of chloroquine in pediatric Plamodium falciparum malaria in Ivory Coast. DESIGN: This study was included in the national Plasmodium falciparum-susceptibility supervision program. Two hundred and fifty-six out of 594 patients from six to 59 months of age were included. Chloroquine was administered in accordance with the standard 14 day WHO protocol; i.e. administered dose of 25 mg/kg, in split doses, over three days. RESULTS: Two hundred and forty-seven patients completed the treatment. Among these, 217 presented with adequate clinical response (87.8%). The percentage of therapeutic failure was 12.2% with 12 early cases of therapeutic failure and 18 late cases of therapeutic failure. Chloroquine was more efficacious in Agnibilékrou (11.3% of therapeutic failure), Bondoukou (10.4%), and Tanda (10%), than in Abengourou (16.4%). Parasitic reduction on patients with resistant Plasmodium was superior to 90%, from day 0 to day 3. The risk of therapeutic failure was significantly linked to patient age. CONCLUSION: Considering these results, the authors suggest that the first-line treatment with chloroquine must be continued for uncomplicated malaria in humans.

Antimalarials↗
PubMed2006

Therapeutic hypothermia.

Therapeutic hypothermia has been used for millennia, but in recent years was not in much clinical use due to an apparent high risk of complications. More recently, the benefits of induced therapeutic hypothermia have been rediscovered, mainly with the improvement in neurological outcome in out-of-hospital cardiac arrest victims. In addition, therapeutic hypothermia has been suggested to improve outcome in other neurological conditions such as traumatic brain injury, neonatal asphyxia, cerebrovascular accidents and intracranial hypertension. This article reviews the history of the discovery of therapeutic hypothermia, as well as the current therapeutic applications and ways to deliver this treatment. Cooling techniques and recovery processes, as well as potential complications are also reviewed. Clinicians caring for a wide variety of critically ill patients should be familiar with the use of therapeutic hypothermia.

Heart Arrest↗
PubMed2005

Genetically based therapeutics for cancer: similarities and contrasts with traditional drug discovery and development.

The field of molecular therapeutics is in its infancy and represents a promising and novel avenue for targeted cancer treatments. Like the small-molecule and antibody therapeutics before them, however, the genetic-based therapies will face significant research and development challenges in their maturation toward an approved cancer therapy. To facilitate this process, we outline and examine in this review the drug development process, briefly summarizing the research and development paradigms that have accompanied the recent successes of the small-molecule and antibody-based cancer therapeutics. Using this background, we compare and contrast the research and development experiences of small-molecule and antibody therapeutics with genetic-based cancer therapeutics, using oncolytic viruses as a defined example of an experimental molecular therapeutic for cancer.

Antineoplastic Agents↗
PubMed2003

Rational design and engineering of delivery systems for therapeutics: biomedical exercises in colloid and surface science.

Engineering delivery systems of therapeutic agents has grown into an independent field, transcending the scope of traditional disciplines and capturing the interest of both academic and industrial research. At the same time, the acceleration in the discovery of new therapeutic moieties (chemical, biological, genetic and radiological) has led to an increasing demand for delivery systems capable of protecting, transporting, and selectively depositing those therapeutic agents to desired sites. The vast majority of delivery systems physically reside in the colloidal domain, while their surface properties and interfacial interactions with the biological milieu critically determine the pharmacological profiles of the delivered therapeutic agents. Interestingly though, the colloidal and surface properties of delivery systems are commonly overlooked in view of the predominant attention placed on the therapeutic effectiveness achieved. Moreover, the development and evaluation of novel delivery systems towards clinical use is often progressed by serendipity rather than a systematic design process, often leading to failure. The present article will attempt to illustrate the colloid and interfacial perspective of a delivery event, as well as exemplify the vast opportunities offered by treating, analysing and manipulating delivery systems as colloidal systems. Exploring and defining the colloid and surface nature of the interactions taking place between the biological moieties in the body and an administered delivery vehicle will allow for the rational engineering of effective delivery systems. A design scheme is also proposed on the way in which the engineering of advanced delivery systems should be practiced towards their transformation from laboratory inventions to clinically viable therapeutics. Lastly, three case studies are presented, demonstrating how rational manipulation of the colloidal and surface properties of delivery systems can lead to newly engineered systems relevant to chemotherapy, gene therapy and radiotherapy.

Biomedical Engineering↗