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PubMed2001

Evolutionary engineering of industrially important microbial phenotypes.

The tremendous complexity of dynamic interactions in cellular systems often impedes practical applications of metabolic engineering that are largely based on available molecular or functional knowledge. In contrast, evolutionary engineering follows nature's 'engineering' principle by variation and selection. Thus, it is a complementary strategy that offers compelling scientific and applied advantages for strain development and process optimization, provided a desired phenotype is amenable to direct or indirect selection. In addition to simple empirical strain development by random mutation and direct selection on plates, evolutionary engineering also encompasses recombination and continuous evolution of large populations over many generations. Two distinct evolutionary engineering applications are likely to gain more relevance in the future: first, as an integral component in metabolic engineering of strains with improved phenotypes, and second, to elucidate the molecular basis of desired phenotypes for subsequent transfer to other hosts. The latter will profit from the broader availability of recently developed methodologies for global response analysis at the genetic and metabolic level. These methodologies facilitate identification of the molecular basis of evolved phenotypes. It is anticipated that, together with novel analytical techniques, bioinformatics, and computer modeling of cellular functions and activities, evolutionary engineering is likely to find its place in the metabolic engineer's toolbox for research and strain development. This review presents evolutionary engineering of whole cells as an emerging methodology that draws on the latest advances from a wide range of scientific and technical disciplines.

Biological Evolution↗

PubMed2004

Effect of menthol on the pharmacokinetics and pharmacodynamics of felodipine in healthy subjects.

OBJECTIVES: The present study was undertaken to determine whether menthol affects the metabolism of and pharmacological responses to the calcium channel antagonist felodipine in people. METHODS: Eleven healthy subjects (ten female, one male) participated in a randomized, double-blind, two-way crossover study, comparing the kinetics and effects of a single oral dose of felodipine ER tablet (Plendil, 10 mg) with menthol (test) or placebo (reference) capsules. Ten subjects completed the study. At the beginning of the study, a 10-mg felodipine ER tablet and a 100-mg menthol or placebo capsule were given. During the 2nd, 5th and 7th hours of the study, 50, 25 and 25 mg menthol or placebo capsules were given, respectively. Blood samples and cardiovascular measurements were obtained at frequent intervals. Serum felodipine and dehydrofelodipine concentrations were determined by means of gas chromatography/mass spectrometry. RESULTS: Pharmacokinetic parameters of felodipine and dehydrofelodipine (AUC0-24, Cmax, t(max), dehydrofelodipine/felodipine AUC0-24 ratio) were not markedly changed with menthol coadministration. Only eight female subjects' cardiovascular data were included in the analysis because of technical problems during the measurements. There were no statistically significant differences in blood pressures and heart rates between the two treatments. CONCLUSIONS: We conclude that the pharmacokinetics and pharmacodynamics of felodipine were essentially unaltered by menthol.

Adult↗

PubMed2003

[Brachytherapy in cervix cancers: development of techniques and concepts].

Brachytherapy plays an important role in the treatment of patients with cervical carcinoma. Technical modalities have evolved during the last years and have benefited from imaging modalities development, specially MRI. Imaging modalities contribute to a better knowledge of tumoral extension and critical organs. Ultrasound during brachytherapy has led to the almost complete eradication of uterine perforation. In the future, a more systematic use of systems allowing optimization may induce a better dose distribution in the tumor as well as in the critical organs. Recent data provided information in favor of a better analysis in the relative role of dose-rate, total dose and treated volume and their influence on the local control and complication incidence. Concomitant radiochemotherapy represents a standard in the treatment of patients with tumoral size exceeding 4 cm. Some questions still remain: is concomitant chemotherapy of benefit during brachytherapy? Is there any place for complementary surgery, specially in patients with complete response after external irradiation with concomitant chemotherapy and brachytherapy? In order to answer the former question, a phase III randomized trial is going to start, with the Fédération Nationale des Centres de Lutte Contre le Cancer as a promoter.

Antineoplastic Agents↗

PubMed1996

Attitude of physicians toward patient package inserts for medication information in Belgium.

In Belgium, the distribution of medications to outpatients in community pharmacies is almost exclusively by branded unit-of-use packages, with a package insert inside every package. At the time of the study (spring 1990), the implementation of legislation that mandated a shift from highly technical documents to patient package inserts (PPIs), understandable by the lay person, had begun. This study explores the attitude of practising physicians toward written medication information for patients. A mail questionnaire was sent to 1500 (8% random sample) Belgian general practitioners and to 500 (22% random sample) internal medicine specialists. A total of 543 usable questionnaires were returned (27.5% return rate). Ninety-two percent of the physicians stated that their patients seldom or never requested additional information on drug efficacy or side effects, during routine consultation; 30% estimated that more than half of their patients read the PPI; 75% expect that a patient would experience side effects after reading about them in the PPI; 59% agreed that the PPI could help the patient react more adequately in unforeseen situations. It was possible to cluster the respondents in a stable segmentation of three clusters: moderately positive physicians (20%), ambiguous to neutral physicians (44%), physicians overtly negative to written drug information (36%). The low response rate to this extensive postal questionnaire limits the conclusions to a qualitative description of relevant clusters of respondents. In contrast with the opinion of physicians about patient readership, results from other studies indicate that the vast majority of patients read the package inserts.

Adult↗

PubMed2001

CLT and CLS job responsibilities: current distinctions and updates.

OBJECTIVE: This study was undertaken to address the following questions: 1. What tasks distinguish the job of a clinical laboratory scientist (CLS) from that of a clinical laboratory technician (CLT)? 2. What changes in role distinctions, have occurred for entry-level CLS and CLT practitioners over the five-year period 1993-98? 3. What tasks have been deleted from the CLT and CLS content outlines because they were not frequently performed or not considered entry-level? 4. What changes in practice are reflected in the current job analyses? DESIGN: A national job analysis of tasks constituting the job of clinical laboratory scientists (CLSs) and clinical laboratory technicians (CLTs) was conducted in 1998-99 as part of a standard setting process for the certifying examinations of the National Credentialing Agency for Laboratory Personnel (NCA). The job analyses relied upon mail surveys to 1200 individuals for each job level asking respondents to identify tasks significant to effective practice at job entry. The task lists resulting from statistical analysis of those surveys were examined to answer the study questions. PARTICIPANTS: The sample for each survey included 1200 practitioners, educators and laboratory managers selected at random from membership in professional organizations or from NCA certificant lists. Sampling was stratified to insure adequate practitioner representation. MAIN OUTCOME MEASURES: The mean rating on a four point scale for each item on the surveys was evaluated for overall significance as well as significance across geographic regions. The tasks meeting specified criteria were retained in the final task lists. Tasks were counted and their content evaluated to compare CLS and CLT job tasks. RESULTS: The response rates to the surveys were 33% for CLT and 21% for CLS. Reliability was judged based on average intraclass correlation coefficients of .86 and .82 for the CLT and CLS surveys, respectively. There were 952 tasks retained on the CLS content outline and 725 retained on the CLT content outline of the 1151 tasks on the original survey. Seven hundred and twenty two tasks were found on content outlines of both job levels, representing a 76% overlap. Tasks found only on the CLS outline included advanced technical tasks, a few management tasks, and more communication tasks. CONCLUSIONS: The jobs of CLS and CLT practitioners are distinct at job entry level with CLSs performing a broader array of technical and communication tasks as well as some management tasks. Though CLS staff uses few management skills at job entry, those tasks are performed by CLS staff in the laboratory and curricula must help prepare graduates for these tasks expected of experienced staff. CLTs perform tasks requiring problem solving and high level reasoning. CLT curricula must address the need for CLTs to perform these tasks.

Data Collection↗

PubMed1994

Current status of neoadjuvant therapy for non-small cell lung cancer.

Any program of therapy for clinically advanced non-small cell lung cancer (NSCLC) that would increase the incidence of local tumor control and decrease the likelihood of distant metastatic disease would be of obvious benefit. The objective of neoadjuvant therapy is to eradicate the primary tumor and micrometastatic disease. In the past 10 years, many trials have been completed to evaluate neoadjuvant therapy and they have included sequential chemoradiotherapy, concurrent chemoradiotherapy, chemotherapy/surgery, and chemoradiation/surgery. These trials have predominately been phase 2 trials and have demonstrated that chemotherapy is generally well tolerated, surgery is technically feasible, and operative morbidity and mortality are not excessive. Long-term survival for patients with clinically advanced NSCLC is improved when compared with historic controls. These trials have demonstrated a greater than 50% clinical response rate and in approximately 20% of patients who have undergone resections, the tumor is sterilized. This latter group of patients demonstrate significantly improved survival. Cost-benefit ratios and quality of life have yet to be evaluated. Final determination of the effectiveness of neoadjuvant therapy for NSCLC awaits completion of phase 3 trials.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1994

Continuous invasive cardiac output monitoring--the Baxter/Edwards Critical-Care Swan Ganz IntelliCath and Viligance system.

We evaluated the Baxter/Edwards Critical-Care Swan Ganz IntelliCath continuous cardiac output catheter and Vigilance continuous cardiac output monitor in critically ill adult intensive care patients, and compared cardiac output measurements obtained from this new system with those from a standard bolus thermodilution technique using cold normal saline. Nine Swan Ganz IntelliCath catheters were inserted into patients selected at random, following the decision that pulmonary artery catheter monitoring was required. A total of 100 comparisons were made in nine patients. We found the Swan Ganz IntelliCath catheter to be both easy to insert and position, and simple to use. There were no complications or technical difficulties. The mean cardiac output measured by the continuous system was 8.00 l/min (SD 1.66/min) compared to 8.02 1/min (SD 1.74 l/min) using bolus techniques. Continuous cardiac output values correlated well with bolus measurements (r = 0.87), there was excellent accuracy (bias of 0.02 l/min) and precision was acceptable (limits of agreement of -1.71 to 1.75 l/min). These larger than anticipated limits of agreement may not reflect any inaccuracy in the continuous measurement system, rather they may highlight the extent of well recognised potential errors inherent in the intermittent bolus technique. The availability of a system to measure cardiac output continuously provides a major improvement in intensive care monitoring. This system will permit the rapid and accurate assessment of the response of patients to therapy while providing increased diagnostic facilities and a new research tool.

Adult↗

PubMed2000

'of Mice and men' (John steinbeck)-How do we determine the potential for immunotoxicity in humans?

PURPOSE: Immunotoxicology is most simply defined as the study of adverse effects on the immune system resulting from exposure to drugs, environmental and industrial chemicals, and in some instances, biological materials. The science of immunotoxicology has validated animal models to conduct risk assessment. However, approaches to characterize immunotoxicity in humans are poorly defined. Animal models have indicated that a primary immune response is most predictive of immunotoxicity. Because vaccines can trigger a primary immune response, this approach may have utility in humans. The purpose of this project was to determine if the response to the influenza vaccine can be validated as an objective measurement of immune status in the workplace.METHODS: We randomly selected employees to receive the influenza vaccine and employees, matched according to age and gender, to receive the placebo. The participants (32 test group and 19 placebo group) completed a brief questionnaire to identify potential confounding factors. Specific anti-influenza antibodies were measured in the serum via an ELISA 30 days after administering the vaccine or placebo.RESULTS: Only 50% (16 of 32 subjects) produced a positive response which is defined by the Centers for Disease Control as a four-fold increase in serum titers. Not unexpectedly, all samples contained antibody to influenza prior to vaccination, and a number of the participants who did not achieve a positive response started with high serum titers.CONCLUSIONS: The influenza vaccine was originally selected for this study because of costs, acceptability to the population and proven safety and efficacy. However, the results of the present investigation suggest that this approach will have little utility as a workplace monitor of human immunotoxicity because most individuals would not be making a primary antibody response. Other technical limitations with the influenza vaccine will be presented; and the alternatives for other biomonitors of human immunotoxicity will be discussed.

Journal Article↗

PubMed1987

Threshold characteristics of the human auditory brain stem response.

Auditory brain stem responses (ABRs) were recorded from ten normal-hearing subjects in response to 100-microseconds clicks from a TDH 49 earphone at a rate of 48 pps and at levels randomly varied in 2-dB steps between 34 and 52 dB p.e. SPL. At each level, 10 000 epochs were averaged with use of a weighted concept and a running estimate was made of the signal-to-noise ratio (SNR). This quantity was used to detect the presence of the ABR and the median threshold was found at 38 dB p.e. SPL. The mean averaged background noise level was 11.3 nVrms, and the "true" ABRrms amplitude function crossed this value at 35.5 dB p.e. SPL, which indicates the level where the SNR = 1. By extrapolation, it was found that the ABR amplitude became zero at 32 dB p.e. SPL. The perceptual thresholds of the click were estimated by means of a modified block up-down procedure, and the median value was found at 33 dB p.e. SPL. The slope of the amplitude function and the magnitude of the averaged background noise are the two factors responsible for the ABR threshold sensitivity, which thus depends on both physiological and technical parameters. Therefore, these have to be considered together with the method of detection when the ABR is used to indicate the hearing sensitivity.

Auditory Threshold↗

PubMed2004

Artificial neural networks for adolescent marijuana use and clinical features of marijuana dependence.

This article compares the performance of multiple logistic regression (MLR) with feed-forward, artificial neural network (ANN) models for the assessment of adolescent marijuana use and clinical features of dependence based on self-evaluation from recent National Household Surveys on Drug Abuse (NHSDA). The effect of training and testing the neural networks with randomly selected data was compared to data selected as a function of survey year. The technical aim of the study was to account for adolescent marijuana use and features of marijuana dependence based on experiences with alcohol and tobacco. Similarities observed in MLR and ANN model performance may indicate no major complex or nonlinear relationships in cross-sectional epidemiological data selected to model adolescent drug use and dependence in this specific application. We concluded that ANNs should be further studied in future longitudinal research, perhaps with modeling of recursive networks, allowing feedback from drug dependence to levels of marijuana use. The ANN models also have the potential to model drug use and dependence based on input parameters with no obvious direct link to drug involvement--e.g., polymorphisms associated with "openness to experience" or other personality traits hypothesized to function as distal antecedents, and could thus be implemented to identify higher risk youths using assessments indirectly related or nonlinearly associated to adolescent drug use and dependence but less sensitive to survey-related response tendencies.

Adolescent↗

PubMed1997

Active voluntary euthanasia or physician-assisted suicide?

OBJECTIVE: To find out why Dutch general practitioners (GPs) and nursing home physicians (NHPs), and patients (according to their physician) opt for active voluntary euthanasia rather than for physician-assisted suicide, or vice-versa. DEFINITIONS: The following definitions were used in the study: Euthanasia is the intentional termination of life, by someone other than the patient, at the patient's request; physician-assisted suicide is intentionally helping a patient to terminate his or her life at his or her request. DESIGN: Two descriptive, retrospective studies. SETTING: The Netherlands. METHOD: Data were collected by means of anonymous questionnaires sent to a random sample of 521 GPs from the province of North Holland, 521 GPs from the rest of the Netherlands, and all 713 NHPs who were members of the Dutch Association of Nursing Home Physicians. Data were collected over the period 1986-1989 (inclusive) for GPs and the period 1986-June 1990 (inclusive) for NHPs. RESULTS: Forty-eight percent of the Gps, 78% of the NHPs, and about half of the patients who opted for euthanasia did so because of the physical condition of the patient. The reason GPs, NHPs, and patients gave most often for opting for physician-assisted suicide was that they wanted 'as far as possible to let the patient bear the responsibility.' CONCLUSION: In 38% of all cases for GPs and 57% of all cases for NHPs, only active voluntary euthanasia could be performed because of the patient's condition. In the other cases, where there was a choice, most GPs performed euthanasia, while most NHPs assisted in suicide. Active voluntary euthanasia was chosen primarily for medico-technical reasons, whereas physician-assisted suicide was selected primarily for moral reasons.

Adult↗

PubMed2001

Effects of multisite biventricular pacing in patients with heart failure and intraventricular conduction delay.

BACKGROUND: One third of patients with chronic heart failure have electrocardiographic evidence of a major intraventricular conduction delay, which may worsen left ventricular systolic dysfunction through asynchronous ventricular contraction. Uncontrolled studies suggest that multisite biventricular pacing improves hemodynamics and well-being by reducing ventricular asynchrony. We assessed the clinical efficacy and safety of this new therapy. METHODS: Sixty-seven patients with severe heart failure (New York Heart Association class III) due to chronic left ventricular systolic dysfunction, with normal sinus rhythm and a duration of the QRS interval of more than 150 msec, received transvenous atriobiventricular pacemakers (with leads in one atrium and each ventricle). This single-blind, randomized, controlled crossover study compared the responses of the patients during two periods: a three-month period of inactive pacing (ventricular inhibited pacing at a basic rate of 40 bpm) and a three-month period of active (atriobiventricular) pacing. The primary end point was the distance walked in six minutes; the secondary end points were the quality of life as measured by questionnaire, peak oxygen consumption, hospitalizations related to heart failure, the patients' treatment preference (active vs. inactive pacing), and the mortality rate. RESULTS: Nine patients were withdrawn from the study before randomization, and 10 failed to complete both study periods. Thus, 48 patients completed both phases of the study. The mean distance walked in six minutes was 22 percent greater with active pacing (399+/-100 m vs. 326+/-134 m, P<0.001), the quality-of-life score improved by 32 percent (P<0.001), peak oxygen uptake increased by 8 percent (P<0.03), hospitalizations were decreased by two thirds (P<0.05), and active pacing was preferred by 85 percent of the patients (P<0.001). CONCLUSIONS: Although it is technically complex, atriobiventricular pacing significantly improves exercise tolerance and quality of life in patients with chronic heart failure and intraventricular conduction delay.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1999

Effect of technical and functional quality on patient perceptions of pharmaceutical service quality.

PURPOSE: To evaluate the relative importance of functional quality (how services were provided) and technical quality (what was received for those services) on patient perceptions of pharmaceutical service quality. METHODS: A scenario-based experimental design was chosen to manipulate functional (FQ) and technical quality (TQ). Subjects were asked to read one of four scenarios describing a pharmacy service experience and imagine that he or she were in the situation described. High and low TQ were manipulated by describing the presence or absence of a prescription medication dispensing error made by the pharmacist in the scenario. Each subject completed a survey about their evaluations of the service provided in the scenario. An ANOVA using a 2 x 2 completely randomized factorial design was conducted to compare the effects of TQ, FQ, and their interaction on perceptions of service quality and behavioral intention. Effect sizes were measured with the calculation of omega-square. RESULTS: FQ had the greatest impact on patient perceptions of service quality and behavioral intentions. FQ explained 44% of the variance in service quality and 39% in intention to return. TQ and the interaction accounted for a significant but much lesser effect. The interaction showed that the effect of FQ was greatest under conditions of high TQ. There were no significant associations between any demographic characteristics and responses to service quality. CONCLUSIONS: The results suggest that FQ has the greatest impact on consumer perceptions of pharmaceutical service quality even under conditions of an obvious example of low TQ which respondents perceive as serious and possibly harmful. This study underscores the limitations of relying on patient perceptions in evaluating pharmaceutical services. Although patient evaluations are important, they can be inadequate for assessing the professional quality of services.

Adult↗

PubMed1990

[The significance of incorrect spray technic on the consumption of terbutaline in patients with chronic obstructive lung disease].

A total of 140 patients with chronic obstructive pulmonary disease was included in this multicentre parallel group investigation with the object of assessing whether poor inhalation technique results in increased consumption of beta 2-agonist. On the basis of measurements of pulmonary function, the patients were stratified into two groups with good and poor inhalation techniques, respectively, and these were subdivided at random to inhalation of terbutaline via either a freon spray (aerosol) or Turbohaler (powder). During a period of four weeks the daily terbutaline consumption, the symptoms and pulmonary function were noted. Patients with poor inhalation technique did not have significantly increased terbutaline consumption. The consumption of terbutaline was independent of the method of administration. The Turbohaler was just as effective as the spray and the patients preferred this method, (p less than 0.05).

Adult↗

PubMed1998

Secular trends in blood pressure levels in Denmark 1964-1991.

BACKGROUND: Hypertension is an essential risk factor for development of cardiovascular diseases. Prospective studies show a reduction in risk of myocardial infarction with reduction of blood pressure. In Denmark there was a decrease in ischaemic heart disease mortality during the period (1968-1992) with around 34% in 30-65 year old men and 30% in women. OBJECTIVE: To assess the changes in casual blood pressure between 1964 and 1991 in seven cross-sectional population studies. SETTING: Centre of Preventive Medicine, University of Copenhagen, DK-2600 Glostrup. POPULATION: 10359 subjects, equal numbers of men and women, age exactly 30, 40, 50 and 60 years drawn as random samples from a background population of 300000 inhabitants and surveyed in 1964-1974 and five cross-sectional studies 1976, 1978, 1982-1984, 1986-1987 and 1991. METHODS: Blood pressure was measured according to WHO criteria by one technician in each survey. Alcohol consumption and physical activity were measured by a self-administered questionnaire. The weight and height were measured by standardized methods. Data on mortality from ischaemic heart disease were obtained from death certificates recorded by the National Board of Health. RESULTS: Blood pressure increased with increasing age in both genders and was significantly higher in men than in women. Median blood pressure in 50 year old men in 1964 was 135/85 mmHg and in 1991 it was 123/79, whereas in women in 1964 it was 140/85, against 119/74 in 1991. The prevalence of hypertensives among 30 and 40 year olds declined throughout the period. The performance of blood pressure measurements, technical variation, examination programme, seasonal variation and inter-observer variation were potential bias sources and influenced blood pressure levels, but cannot be shown to be responsible for the declining trend in blood pressure and hypertension. Women became a little more physical active in leisure time and men less active. Women consumed less alcohol than men, but the amounts slightly increased by the end of the period. Body mass index >25 was seen less frequently in women than in men and this increased in men over the period. Sale of antihypertensive drugs increased in Denmark over the 1964-1991 period. There seems to be good agreement between the changes in blood pressure in the population and the decline in mortality from stroke and coronary heart disease in Denmark, which is influenced by other risk factors as well. CONCLUSION: Blood pressure distributions have shifted towards lower values in 1964-1991. Prevalence of hypertension declined up to 1983. Risk factor changes as well as treatment for hypertension contribute to this.

Adult↗

PubMed2006

Can evidence-based prevention programs be sustained in community practice settings? The Early Risers' Advanced-Stage Effectiveness Trial.

This study evaluated institutional sustainability of the Early Risers "Skills for Success" conduct problems prevention program. In a previous early-stage effectiveness trial Early Risers had been successfully implemented by a nonprofit community agency with guidance, supervision, technical assistance and fiscal support/oversight provided by program developers. The current advanced-stage effectiveness trial applied a randomized, control group design to determine whether this community agency could replicate earlier positive findings with a new cohort of participants, but with less direct involvement of program developers. An intent-to-intervene strategy was used to compare children randomly assigned to Early Risers or a no-intervention comparison group. Compared to results obtained in an early-stage effectiveness trial, program attendance rates were much lower and only one positive outcome was replicated. Failure to replicate program effects was not attributed to poor program implementation, because data collected pertaining to exposure, adherence and quality of delivery were acceptable, and a participation analysis showed that families who attended at higher levels did benefit. It was difficulties that the community agency experienced in engaging families in program components at recommended levels that primarily accounted for the results. Possible organizational barriers that impeded sustainability included unreliable transportation, poor collaboration between the agency and the local public school system, high staff turnover, agency downsizing, and fiduciary responsibility and accountability. It was concluded that both program developers and program providers need to be proactive in planning for sustainability.

Child↗

PubMed1993

Diode laser photocoagulation for threshold retinopathy of prematurity. A randomized study.

BACKGROUND: Although peripheral cryotherapy decreases the incidence of unfavorable anatomic outcomes in threshold retinopathy of prematurity (ROP), apnea, bradycardia, and lid edema can occur. Argon laser indirect ophthalmoscope photocoagulation has been used as an alternative to cryotherapy, with fewer adverse effects. Retinal lesions placed with diode lasers are deeper than similar argon laser lesions, and it is not known whether this difference could influence the response to ablative therapy. METHODS: Patients were enrolled under a prospective, randomized protocol. One eye of each patient with symmetric, threshold ROP was treated with an 814/815 nm diode laser, while the other eye was treated with cryotherapy. Patients with asymmetric diseases also were randomized for treatment in the threshold eye. RESULTS: Nineteen infants (33 eyes) were treated, ranging from 485 to 863 g birth weight (23 to 27 weeks gestational age); 18 patients (32 eyes) were followed for 3 months or longer. Four patients (8 eyes) had bilateral zone 1 disease. Postconceptional age was 36 to 45 weeks at the time of treatment. The diode laser treatment was better tolerated than cryotherapy, and the treatment apparatus was more easily transported. Apneic episodes requiring intubation resulted from two cryotherapy sessions but no diode laser sessions. Five cryotherapy-treated eyes required retreatment because of persistent disease with adjacent skip areas. In the group followed for 3 to 15 months, 1 cryotherapy-treated eye and 1 diode laser-treated eye progressed to stage 5 retinal detachment. CONCLUSION: Compared with cryotherapy, the diode laser was more convenient, technically easier to administer, and better tolerated by the patient. Although the number of patients was too small for meaningful statistical analysis of outcome, diode laser peripheral retinal ablation appeared to be as effective as cryotherapy for the treatment of threshold ROP.

Cryosurgery↗

PubMed2005

Transjugular intrahepatic portosystemic shunt.

The transjugular intrahepatic portosystemic shunt (TIPS) is an interventional treatment resulting in decompression of the portal system by creation of a side-to-side portosystemic anastomosis. Since its introduction 16 years ago, more than 1,000 publications have appeared demonstrating broad acceptance and increasing clinical use. This review summarizes our present knowledge about technical aspects and complications, follow-up of patients and indications. A technical success rate near 100% and a low occurrence of complications clearly depend on the skills of the operator. The follow-up of the TIPS patient has to assess shunt patency, liver function, hepatic encephalopathy and the possible development of hepatocellular carcinoma. Shunt patency can best be monitored by duplex sonography and can avoid routine radiological revision. Short-term patency may be improved by anticoagulation, while such a treatment does not influence long-term patency. Stent grafts covered with expanded polytetrafluoroethylene show promising long-term patency comparable with that of surgical shunts. With respect to the indications of TIPS, much is known about treatment of variceal bleeding and refractory ascites. The thirteen randomized studies that are available to date show that survival is comparable in patients receiving TIPS or endoscopic treatment for acute or recurrent variceal bleeding. Another group comprises patients with refractory ascites and related complications, such as hepatorenal syndrome and hepatic hydrothorax. It has been demonstrated that TIPS improves these complications. Five randomized studies comparing TIPS with paracentesis and one study comparing TIPS with the peritoneo-venous shunt showed good response of ascites but controversial results on survival. In addition, TIPS has been successfully applied to patients with Budd-Chiari syndrome, portal vein thrombosis, before liver transplantation, and for the treatment of ectopic variceal bleeding.

Ascites↗