Agents In Common Use Research Articles

Multidrug Resistance in Klebsiella species Isolated from Liquid Herbal Remedies in Port Harcourt, Nigeria

Aims: Klebsiella are lactose fermenting, encapsulated, non-motile, oxidase-negative, gram negative rods; belonging to the family Enterobacteriaceae and the non-taxonomic group, coliforms. Klebsiella isolates numbering 109, recovered from three categories of liquid herbal medicines were analyzed with the intent of ascertaining the prevalence of multidrug resistance (MDR) strains.
 Study Design: The research is an observational, descriptive, prospective and cross-sectional research. The samples of herbal remedies procured from randomly selected outlets within Port Harcourt metropolis in a completely randomized block design. The analysis was conducted at the Department of Microbiology laboratory of Rivers State University, Port Harcourt, Rivers State, Nigeria.
 Methodology: The antimicrobial resistance (AMR) patterns of Klebsiella pneumoniae and Klebsiella oxytoca were determined against 15 antimicrobial agents in common use in the area, namely amoxicillin clavulanate(30ug/ul), ceftriaxone (30ug/ul), cefuroxime (30ug/ul), cephalexin (30ug/ul), chloramphenicol (30ug/ul), ciprofloxacin (5 ug/ul), cotrimoxazole (25ug/ul), doxycycline (30ug/ul), erythromycin (15 ug/ul), gentamycin (10 ug/ul), levofloxacin (5 ug/ul) norfloxacin (10 ug/ul), ofloxacin (5 ug/ul), peflacine (5 ug/ul), streptomycin (10 ug/ul) (0xoid/Thermo Fisher Scientific, UK).; by seeding the test isolates on Muellar-Hinton agar (oxoid) and incubating for 18 to 24 hours.
 Results: The cumulative resistance profile for all strains was 45.4%. Doxycycline was the least effective antimicrobial, being resisted by 63.3% of the strains, followed by cotrimoxazole (61.5%), erythromycin (58.7%), chloramphenicol (57.8%) and norfloxacin (50.0%). Overall, 82.6% of the Klebsiella strains were MDR, including extensively drug resistant-XDR, (52.3%) and pandrug resistance-PDR (1.8%). Non-multidrug resistant-NMDR strains were 16.0%. MDR strains constitute 81.6% of Klebsiella pneumoniae which includes XDR (48.8%) and PDR (2.0%); while NMDR strains were 18.4%. The MDR strains amounted to 90.9% of the Klebsiella oxytoca strains all of which were XDR.
 Conclusion: This study has contributed in establishing that liquid herbal remedies are contaminated with multidrug resistant strains of Klebsiella Species. It has also shown that multidrug resistant strains of the bacteria are on the increase and could pose a great threat to public health.

Differential Alemtuzumab Dosage Effects in T-Cell Deplete Allogeneic Haematopoietic Stem Cell Transplants for Myeloid Malignancies- King's College Hospital London Experience

Introduction Alemtuzumab is a monoclonal anti-CD52 antibody, a pan-lymphodepleting immunosuppressive agent in common use as part of conditioning for allogeneic stem cell transplantation (Allo-HSCT) in United Kingdom and many other centres across the globe, with benefits related to reduced graft versus Host disease (GVHD) and lower non-relapse mortality (NRM). However, evidence for effective dose schedule in Allo-HSCT remains debatable with some concerns related to delayed immune reconstitution and increased relapses with higher dosages; but increased risk of acute and chronic GVHD observed with lower doses. We present a large single-centre UK experience evaluating differential dosage effect of Alemtuzumab on HSCT outcomes. Methods: We retrospectively evaluated 330 patients undergoing Allo-HSCTs for myeloid malignancies (AML/MDS/MPNs) during a 10-year period (Jan 2010 to April 2019) at King's College Hospital, London. Two dosage schedules of Alemtuzumab based T-cell deplete conditioning regimen using 100mg (n-96) were compared to those receiving 60mg (n-234; <100mg dose) with respect to HSCT outcomes. Alemtuzumab based T deplete conditioning regimens included Fludarabine(Flu)-Busulphan(Bu) (2 doses as reduced intensity) while Flu-Bu4 or Bu4-Cyclophosphamide used as myeloablative protocol. Standard supportive care for GVHD prophylaxis (ciclosporin), viral/bacterial and anti-fungal prophylaxis was used. Close monitoring for infections, GVHD, chimerism (included fractionated lymphoid/myeloid) and disease assessments post HSCT were undertaken as per institutional policy. The data was compared and statistically analysed using Log-rank test for overall survival (OS), Cox regression for adjusted multivariate analysis and Gray method for cumulative incidences for NRM and relapses. Results Baseline characteristics (Table-1) were similar between the 2 groups in terms of conditioning intensity, patient age, underlying disease (AML/MDS), disease risk and donor HLA matching. Median follow up of survivors was 34 months (range 01-112months) with significantly longer follow up available for 100mg dose group (median 90 months vs 28 months; p<0.001). Higher Alemtuzumab dosage (100mg) was associated with a significant improvement in GVHD & Relapse free survival (GRFS)(32% vs 20% at 12 months;p-0.003; Fig 1a) and significantly lower incidence of both grade 3-4 acute (18% vs 42% at D100;p-<0.001; Fig 1b) and chronic GVHD (all grades)(21% vs 42% at 12 months; p<0.001; Fig 1c) compared to <100mg dose. No differences in OS (66% vs 71% at 12 months; p-0.62; Fig 1d), NRM (17% vs 16% at 12 months; p-0.37; Fig 1e) and relapse incidences (24% vs 24% at 12 months;p-0.71; Fig 1f) were observed with no impact on rates of CMV/EBV reactivation, disseminated Adenoviraemia or invasive fungal disease(IFD) between the 2 cohorts. Multivariate adjusted cox analysis (MVA) confirmed older age>60 years, mismatched unrelated donor, absence of chronic GVHD, disease relapse, ITU admission event, CMV reactivation and absence of any EBV reactivation post HSCT as significant predictive factors for poor OS. This was not affected by different Alemtuzumab dosages, disease risk index or type of disease. However, GFRS was positively influenced by standard 100mg Alemtuzumab dose (HR 0.67; 95%CI: 0.51-0.86; p-0.005), no ITU admission event (HR-0.51; 95%CI:0.38-0.70; p<0.001) and EBV reactivation (HR-0.67; 95%CI:0.52-0.86; p-0.02) on multivariate analysis. NRM was worse for patients admitted in ITU, no known chronic GVHD, mismatched unrelated donor, presence of CMV and absence of EBV reactivation (p<0.001), but not affected by differential alemtuzumab dosages. Conclusions With improved supportive care, effective infection management and pre-emptive cellular therapy approaches available in current era, standard dosage (100mg) of alemtuzumab is safe and effective in both RIC and myeloablative allo-HSCTs for myeloid malignancies, with significantly lower GVHD related morbidity and overall better GFRS. Despite concerns of relapses and delayed immune reconstitution, this report on a homogenous cohort of allo-HSCTs in myeloid malignancies confirms the contrary with no impact on OS, NRM or relapses and no significant increase in opportunistic infections with 100mg dose. Disclosures Mufti: Celgene: Consultancy, Research Funding. De Lavallade:Bristol Myers Squibb: Research Funding; Bristol Myers Squibb: Research Funding.

The in vitro zebrafish heart as a model to investigate the chronotropic effects of vapor anesthetics.

In addition to their intended clinical actions, all general anesthetic agents in common use have detrimental intrasurgical and postsurgical side effects on organs and systems, including the heart. The major cardiac side effect of anesthesia is bradycardia, which increases the probability of insufficient systemic perfusion during surgery. These side effects also occur in all vertebrate species so far examined, but the underlying mechanisms are not clear. The zebrafish heart is a powerful model for studying cardiac electrophysiology, employing the same pacemaker system and neural control as do mammalian hearts. In this study, isolated zebrafish hearts were significantly bradycardic during exposure to the vapor anesthetics sevoflurane (SEVO), desflurane (DES), and isoflurane (ISO). Bradycardia induced by DES and ISO continued during pharmacological blockade of the intracardiac portion of the autonomic nervous system, but the chronotropic effect of SEVO was eliminated during blockade. Bradycardia evoked by vagosympathetic nerve stimulation was augmented during DES and ISO exposure; nerve stimulation during SEVO exposure had no effect. Together, these results support the hypothesis that the cardiac chronotropic effect of SEVO occurs via a neurally mediated mechanism, while DES and ISO act directly upon cardiac pacemaker cells via an as yet unknown mechanism.

Tartaric Acid Cross-Linking of Starch: Effect of Reaction Conditions on the Maximum Tensile Strength of Cast Plastic Films

Modification of starch by cross-linking is used in many fields, as the process improves many of the properties of starch, yet most cross-linking agents in common use tend to be toxic, expensive, or both. Polycarboxylic acids could function as nontoxic alternatives to these – some, such as tartaric acid (TA) being also of low cost. This study presents a method to cross-link thermoplastic starch films with TA, as well as the effect of this modification on the tensile strength of the material when films are prepared using different reaction conditions. An increase in strength was observed, which is believed to occur due to an increase in the London dispersion forces acting within the cross-linked starch (CLS). The greatest observed increase in the maximum tensile strength of the plastic was 6%. Monosodium tartrate was used as a catalyst for the cross-linking reaction. The maximum tensile strengths of the plastics produced were determined by using adapted binder clips, a hook (total mass 10g) and hanging masses to subject films of the plastics to progressively greater tension. Incremental weights of 10g were used, with recorded tensions at fracture of 1.2~8.9 N.

Mitomycin C versus 5-Fluorouracil for wound healing in glaucoma surgery.

Raised intraocular pressure is a risk factor for glaucoma. One treatment option is glaucoma drainage surgery (trabeculectomy). Antimetabolites are used during surgery to reduce postoperative scarring during wound healing. Two agents in common use are mitomycin C (MMC) and 5-Fluorouracil (5-FU). To assess the effects of MMC compared to 5-FU as an antimetabolite adjunct in trabeculectomy surgery. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2015 Issue 9), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to October 2015), EMBASE (January 1980 to October 2015), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to October 2015), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 2 October 2015. We included randomised controlled trials where wound healing had been modified with MMC compared to 5-FU. Two review authors independently selected trials and collected data. The primary outcome was failure of a functioning trabeculectomy one year after surgery. Secondary outcomes included mean intraocular pressure at one year. We considered three subgroups: high risk of trabeculectomy failure (people with previous glaucoma surgery, extracapsular cataract surgery, African origin and people with secondary glaucoma or congenital glaucoma); medium risk of trabeculectomy failure (people undergoing trabeculectomy with extracapsular cataract surgery) and low risk of trabeculectomy failure (people who have received no previous surgical eye intervention). We identified 11 trials that enrolled 687 eyes of 679 participants. The studies were conducted in the United States, Europe, Asia and Africa. Five studies enrolled participants at low risk of trabeculectomy failure, five studies enrolled participants at high risk of failure, and one study enrolled people with both high and low risk of failure. None of the included trials enrolled participants with combined trabeculectomy/cataract surgery.We considered one study to be at low risk of bias in all domains, six studies to be at high risk of bias in one or more domains, and the remaining four studies to be at an unclear risk of bias in all domains.The risk of failure of trabeculectomy at one year after surgery was less in those participants who received MMC compared to those who received 5-FU, however the confidence intervals were wide and are compatible with no effect (risk ratio (RR) 0.54, 95% confidence interval (CI) 0.30 to 1.00; studies = 11; I(2) = 40%). There was no evidence for any difference between groups at high and low risk of failure (test for subgroup differences P = 0.69).On average, people treated with MMC had lower intraocular pressure at one year (mean difference (MD) -3.05 mmHg, 95% CI -4.60 to -1.50), but the studies were inconsistent (I(2) = 52%). The size of the effect was greater in the high-risk group (MD -4.18 mmHg, 95% CI -6.73 to -1.64) compared to the low-risk group (MD -1.72 mmHg, 95% CI -3.28 to -0.16), but again the test for interaction was not statistically significant (P = 0.11).Similar proportions of eyes treated with MMC lost 2 or more lines of visual acuity one year after surgery compared to 5-FU, but the confidence intervals were wide (RR 1.05, 95% CI 0.54 to 2.06).Adverse events occurred relatively rarely, and estimates of effect were generally imprecise. There was some evidence for less epitheliopathy in the MMC group (RR 0.23, 95% CI 0.11 to 0.47) and less hyphaema in the MMC group (RR 0.62, 95% CI 0.42 to 0.91).None of the studies reported quality of life.Overall, we graded the quality of the evidence as low largely because of risk of bias in the included studies and imprecision in the estimate of effect. We found low-quality evidence that MMC may be more effective in achieving long-term lower intraocular pressure than 5-FU. Further comparative research on MMC and 5-FU is needed to enhance reliability and validity of the results shown in this review. Furthermore, the development of new agents that control postoperative scar tissue formation without side effects would be valuable and is justified by the results of this review.

A nomogram to calculate the maximum dose of local anaesthetic in a paediatric dental setting.

While local anaesthetic agents are usually safe and are used ubiquitously, inadvertent overdoses may have potentially fatal consequences. Errors in the dosing of local anaesthetics frequently occur due to inherent difficulties in remembering the toxic dosage limits, difficulties in performing the appropriate calculations correctly, and errors in estimating patient weight. We have developed a simple graphical calculation aid (nomogram) to overcome these problems and facilitate rapid cross-checking of the maximum safe dose for a variety of local anaesthetic agents in common use. Standard mathematical techniques were used to draft the nomogram. A randomised blinded study using simulated patient data and Bland-Altman analysis was used to assess the accuracy and precision of the nomogram. The nomogram was found to have a bias of 0.0 ml, with limits of agreement -0.05-0.04 ml. It was found to be easy to use and suitably accurate for clinical use.

Tartaric acid cross-linking of starch: effects of reaction conditions on the maximum tensile strength of cast plastic films

Modification of starch by cross-linking is used in many fields, as the process improves many of the properties of starch, yet most cross-linking agents in common use tend to be toxic, expensive, or both. Polycarboxylic acids could function as nontoxic alternatives to these – some, such as tartaric acid (TA) being also of low cost. This study presents a method to cross-link thermoplastic starch films with TA, as well as the effect of this modification on the tensile strength of the material when films are prepared using different reaction conditions. An increase in strength was observed, which is believed to occur due to an increase in the London dispersion forces acting within the cross-linked starch (CLS). The greatest observed increase in the maximum tensile strength of the plastic was 6%. Monosodium tartrate was used as a catalyst for the cross-linking reaction. The maximum tensile strengths of the plastics produced were determined by using adapted binder clips, a hook (total mass 10g) and hanging mass...

Management of Benign Head and Neck Tumors

: Endovascular procedures for benign head and neck tumors include embolization, stenting, and balloon test occlusion. A transarterial (or endovascular) approach forms the mainstay of treatment for head and neck bleeding as well as for transarterial chemotherapy for head and neck neoplasms. A combination of percutaneous and transarterial approaches may be needed in the embolization of high-flow craniofacial vascular malformations (VMs) and hypervascular tumors. This is a review of the current clinical applications of a variety of percutaneous and endovascular interventional procedures of the extracranial head and neck. The tumors that require embolization in the head and neck most commonly include glomus tumors, angiofibromas, and meningiomas. Many other types of tumors that may also require preoperative embolization include the following: hypervascular metastases, esthesioneuroblastomas, schwannomas, rhabdomyosarcomas, plasmacytomas, chordomas, and hemangiopericytomas. The goal of tumor embolization is to selectively occlude the external carotid artery (ECA) feeders through intratumoral deposition of embolic material. The embolic agents in common use are polyvinyl alcohol (PVA), Embospheres (BioSphere Medical, Rockland, Mass), liquid embolic agents (glue, ethylvinyl alcohol copolymer [EVOH], or Onyx [ev3, Irvine, Calif]), gelatin sponge (Gelfoam; Phadia, Uppsala, Sweden), and coils. The embolization is ideally performed 24-72 hours before surgical resection to allow maximal thrombosis of the occluded vessels and prevent recanalization of the occluded arteries or formation of collateral arterial channels. Preoperative embolization is cost-effective and tends to shorten operation time by reducing blood loss and the period of recovery.

Complementary and Alternative Medicines in Prostate Cancer: From Bench to Bedside?

Complementary and alternative medicine (CAM) use is common among adults, and recent reports suggest that 25%-50% of prostate cancer (PCa) patients use at least one CAM modality. The most common CAM modalities used by PCa patients are vitamin and herbal preparations with purported antitumor effects despite only modest underlying preclinical or clinical evidence of efficacy. In this review we provide a brief overview of the basic scientific and clinical studies underlying the most common herbal and vitamin preparations including common antioxidants, pomegranate extract, green tea, turmeric, resveratrol, silibinin, and herbal combination preparations. When available, prostate cancer clinical trial data are reviewed. Importantly, we have compared the concentration of these agents used in in vitro experiments to that likely to be achievable in humans. From the available data we conclude that there is insufficient evidence to support the use of CAMs for the treatment of prostate cancer patients outside of a clinical trial. The purpose of this review is to more rigorously evaluate CAM therapy in prostate cancer and educate oncologists and patients. This review focuses on examples from the general classes of agents in common use.

Compound rejuvenation of polymer modified asphalt binder

The objective of this research was to show a way to conduct rejuvenation of aged polymer modified asphalt binder (PMB) successfully. To fully evaluate and understand the rejuvenation of aged PMB, the Penetration grade tests including penetration, soften point, ductility and elastic recovery and Superpave™ PG grade tests including DSR, BBR and DDT were conducted. The rejuvenation effect of aged PMB by utilizing a fluid recycling agent in common use for binder rejuvenation was evaluated. And then the compound rejuvenation effect of aged PMB by utilizing the recycling agent with a new modifying additive for binder modification was evaluated. The experimental results indicated that the recycling agent in common use currently does not apply to polymer modified asphalt binder rejuvenation. But the recycling agent together with the modifying additive can restore the characteristics of aged polymer modified binder very well. Therefore, compound rejuvenation of polymer modified asphalt binder is recommended.

Elimination of persistent toxicants from the human body

There is compelling evidence that various chemical agents are important determinants of myriad health afflictions--several xenobiotics have the potential to disrupt reproductive, developmental, and neurological processes and some agents in common use have carcinogenic, epigenetic, endocrine-disrupting, and immune-altering action. Some toxicants appear to have biological effect at miniscule levels and certain chemical compounds are persistent and bioaccumulative within the human body. Despite escalating public health measures to preclude further exposures, many people throughout the world have already accrued a significant body burden of toxicants, placing them at potential health risk. As a result, increasing discussion is underway about possible interventions to facilitate elimination of persistent toxicants from the human organism in order to obviate health affliction and to potentially ameliorate chronic degenerative illness. An overview of the clinical aspects of detoxification is presented with discussion of established and emerging interventions for the elimination of persistent xenobiotics. Potential therapies to circumvent enterohepatic recirculation and a case report highlighting a clinical outcome associated with detoxification are also presented for consideration.

An anesthesiologist’s perspective on inhaled anesthesia decision-making

To describe the culture and content of anesthesia practice; the stages, types, and goals of anesthesia; nomenclature and factors that can affect dosing of inhaled anesthesia; basis for anesthesiologist choices among inhaled anesthesia agents; and special considerations in using inhaled anesthesia in bariatric surgery patients, pediatric patients, and cardiac surgery patients; and to provide insights into myths associated with inhaled anesthesia. The practice of anesthesiology requires complex monitoring, detailed knowledge of pharmacology, and the ability to make quick decisions about patient management. Four stages of anesthesia have been characterized on the basis of patient responsiveness to surgical stimuli. The second stage ("excitement") occurs during induction of or emergence from anesthesia; patients in this stage are particularly vulnerable to problems with laryngospasm, airway obstruction, uncontrolled motor movements, regurgitation, vomiting, and aspiration. In the United States, most general anesthesia involves inhaled agents. The minimum alveolar concentration (MAC) of inhaled anesthetic agents, which anesthesiologists use in dosing these drugs, can be affected by age, a variety of medications, and other patient-specific factors. MAC can be thought of as a measure of drug potency. Both MAC and solubility in blood and tissues differ among inhaled anesthetic agents. Agents with low solubility have a rapid onset and offset of effect and may allow for faster recovery. The choice among inhaled anesthetic agents may depend on their solubility, as well as the propensity to cause airway irritation and coughing, drug cost, and characteristics such as patient age, obesity, and duration of surgery. Anesthesia care providers' experience and habits may also influence drug choice. Emergence delirium (i.e., agitation) can occur with all three inhaled anesthetic agents in common use (isoflurane, desflurane, and sevoflurane). Other potential issues such as hepatotoxicity and nephrotoxicity are of minimal concern with these agents. Using low flow rates of fresh gas is one strategy for minimizing inhaled anesthesia costs, but it is not always feasible. Experience and careful consideration of the characteristics of inhaled anesthesia agents and surgery- and patient-specific factors allow anesthesia care providers to meet the rapidly changing needs of patients receiving inhaled anesthesia in a safe and cost-effective manner.

Environmental stress cracking (ESC) of plastics caused by non‐ionic surfactants

AbstractThe susceptibility of various plastics to environmental stress cracking (ESC) was studied using a variety of agents in common use. It was found that styrenic polymers are susceptible to ESC by many kinds of agents, including detergents, that have non‐ionic surfactants as their components. The ESC of acrylonitrile‐butadiene‐styrene (ABS) copolymer caused by non‐ionic surfactants was studied intensively, and the dependence of crack propagation behavior on temperature and on the kind of non‐ionic surfactants was investigated by edge crack tension (ECT) tests. The morphology at the crack tip of ECT specimens was investigated by a transmission electron microscope (TEM). It was found that crack propagation behavior was closely related to the morphology at the crack tip and the morphology was affected by temperature and type of surfactants. The change in morphology at different experimental conditions was attributable to the difference in the solubility and diffusivity of surfactants at the crack tips.

Severe, intractable headache after injection with botulinum a exotoxin: Report of 5 cases

Background: Botulinum A exotoxin is a safe agent in common use in dermatology. Occasionally, patients receiving botulinum toxin injections report postprocedure discomfort, including headaches. Objective: Our purpose was to estimate the rate of severe headaches occurring after injection with botulinum toxin for dermatologic indications. Methods: We used prospective monitoring of botulinum toxin injection outcomes in a single-site, 3-dermatologist practice. There was in-office and telephone follow-up of patients experiencing severe headaches. Results: Approximately 1% of patients (4/320) receiving botulinum A exotoxin injections may experience severe, debilitating headaches. These may persist at high intensity for 2 weeks to 1 month before gradually fading. Conclusion: Botulinum A exotoxin injection may be associated with the development of life-altering headaches. Patients should be informed of this possibility. (J Am Acad Dermatol 2002;46:62-5.)

Embolization agents: A review

Embolotherapy is an integral part of the practice of interventional radiology. Although many of the embolic agents in common use are well established, advances in microcatheter design, as well as microcatheter-compatible embolic agents, have expanded the role of embolotherapy. This article reviews common embolic agents for use with both standard and microcatheter systems and their roles in embolotherapy.

Management of the adverse effects of antiretroviral therapy and medication adherence.

A commonly cited cause of poor adherence to highly active antiretroviral therapy (HAART) is adverse drug reactions. Short-term adverse effects are potential threats to successful introduction and maintenance of HAART. The long-term toxicities of HAART are still emerging and being defined, as evidenced by the recently described metabolic disorders (i.e., the syndrome of maldistribution, hyperlipemia, glucose intolerance and insulin resistance). With 14 licensed agents in 2000, other agents in common use, and numerous combinations of >/=3 drugs, awareness and recognition of adverse effects are increasingly important for clinicians and patients. The common adverse drug reactions encountered with HAART, including new agents and their impact on patient adherence, are reviewed. Current strategies to anticipate and mitigate adverse effects are summarized.

Feasibility of mitral flow assessment by echo-contrast ultrasound, part I: determination of the properties of echo-contrast agents

Data on the ultrasonic properties of commercially available contrast agents are limited by being instrument-dependent, especially with regard to their backscattering properties. The present work describes methods of measurements that provide instrument-independent estimations of a contrast agent’s attenuation coefficient and integrated backscatter index and provide them as functions of its concentration. The two studied commercially available contrast agents were Albunex® and Levovist® SHU 508-A, both representative of agents in common use for echocardiography. The attenuation coefficients and integrated backscatter indices of both agents were found to be a linear function of their concentrations. Proportionality coefficients ± their standard deviations are provided. Actually, square root values of the averaged backscatter indices normalized with respect to the rms of the reference signal were determined. The coefficients of proportionality were found to be: C A = 3.11 ± 0.1813 dB/mm; C L = 0.07 ± 0.005 dB/mm for attenuation coefficients of the Albunex® and Levovist® contrast agents, respectively, and the corresponding values for backscattering were: D A = 0.07 ± 0.0054; D L = 0.02 ± 0.0012. Being apparatus-independent, the findings of the study are important prerequisites for the use of these echo-contrast agents as an indicator in research for a quantitative assessment of blood flow.

VIRAL LOAD CHANGES IN PATIENTS UNDERGOING CHEMOTHERAPY FOR AIDS-KS

Manome et al (JAIDS 11:109-116, 1996) showed several chemotherapy agents in common use, including anthracyclines, can activate HIV long terminal repeat (LTR). Doxorubicin at concentrations of 5 ng/ml and 30 ng/mg can increase LTR-driven CAT activity by 1.6 fold and 4.1 fold, respectively. Liposomal doxorubicin given at 20 mg/m2 achieves a peak plasma concentration of 8.34 µg/ml and area under the curve (AUC) of 590± 58.7 µg/ml•h which are much higher than the concentration used by Manome et al. Increase production of HIV virus was further demonstrated in chronically as well as in acutely HIV-infected T -cell lines treated with cisplatin and mitomycin C. We therefore conducted this pilot study to evaluate HIV viral load changes in patients with AIDS-KS receiving chemotherapy. Plasma samples for HIV RNA PCA by Roche method were collected before each treatment. All viral load assessments were performed in the UCLA Virology Research Laboratory using the same quantitative methods. Six patients who were being treated with systemic chemotherapy for their AIDS-KS were evaluated. Patients received chemotherapy every two to four weeks. While the antiviral therapy differed among the patients, treatment regimen for individual patients was not changed during the care of chemotherapy administration. All subjects were male. All but one patient had CD4+ cell counts less than 200. Patients 1, 2 and 3 were treated with Liposomal doxorubicin at 20 mg/m2. Patient 4 was treated with Taxol at 125 mg/m2. Patients 5 and 6 were treated with a combination of liposomal doxorubicin at 20 mg/m2, bleomycin 10 units/m2, and vincristine I mg. All but patient 2 are alive at this time. Both increases and decrease in HIV viral load were seen in these patients over the first 305 courses of chemotherapy. These data do not indicated a significant increase in HIV viral load in patients undergoing chemotherapy for AIDS-KS. No consistent trends in changes in plasma HIV viral loads were seen in this small sample of patients. Increased HIV replication as observed by Manome et al in vitro may have little clinical effect in patients receiving antiviral therapy.

A National Survey of the Use of Local Anaesthesia for Cataract Surgery

OBJECTIVE: To ascertain indications for local anaesthesia (LA) for cataract surgery, and also to survey the techniques and agents in common use. STUDY DESIGN AND SETTING: A postal questionnaire was devised inquiring about attitudes, practices and techniques in local anaesthesia for cataract surgery. It was sent to all consultant ophthalmologists in England, Wales and Scotland during the period April to July 1989. RESULTS: The response rate was 80%. The results indicated that most surgeons prefer to operate under general anaesthesia. Expense, unavailability of anaesthetists and speed of turnover were not considered to be common indications for LA. Sedation was used by 61% of cataract surgeons, benzodiazepines being the most popular agents. Most surgeons did not routinely request the prsence of an anaesthetist during LA but 86% designated a member of the theatre staff to monitor the patient. Retrobulbar injection was the most popular local anaesthetic technique, almost invariably given by the surgeon. Some form of compression following injection was used by 61% of surgeons. The great majority of cataract operations were performed as inpatients.

Tissue-directed pharmacokinetics

Azalide antibiotics demonstrate pharmacokinetics distinct from all antibacterial agents in common use. Following oral absorption, conventional oral antibiotics diffuse through serum and interstitial compartments and are eliminated rapidly. A minimal to moderate degree of intracellular penetration may be observed. The pharmacokinetics of azithromycin, the first azalide, are characterized by a rapid and extensive movement of the drug from the serum into intracellular compartments. A dynamic equilibrium exists between the intracellular, interstitial, and serum compartments, with predominant flux into tissue sites. Azithromycin is concentrated to a high degree within phagocytes and transported by chemotactic mechanisms to the site of infection. High concentrations of azithromycin are found in pulmonary, genital, and lymphatic tissues. Azithromycin's serum levels decline in a polyphasic manner with a terminal half-life of approximately 60 hours. These kinetics allow azithromycin to be administered once daily. It is predicted that after drug administration for 5 days, therapeutic levels of azithromycin will be maintained at the tissue sites of infection for an additional 4–7 days. Consideration of the extravascular pharmacodynamics of azithromycin is necessary when making predictions regarding its therapeutic application.