[Efficacy of a bendamustine and rituximab combination in first-line therapy for chronic lymphocytic leukemia: Results of the BEN-001 study]. / Éffektivnost' kombinatsii bendamustina i rituksimaba v pervoi linii terapii KhLL: rezul'taty issledovaniia BEN-001.

AIM: To evaluate the efficacy and safety of the BR regimen containing bendamustine in patients with chronic lymphocytic leukemia (CLL) who have not previously received specific therapy. SUBJECTS AND METHODS: The results of the Russian prospective observational multicenter study BEN-001 (2012-2015) covering 196 CLL patients from 34 centers of the Russian Federation were analyzed. The diagnosis was confirmed by the results of peripheral blood lymphocyte immunophenotyping. A centralized approach was employed to make IGHV gene mutational status analysis, FISH examination, and minimal residual disease according to standardized methods. Quality-of-life (QOL) indicators were estimated using the EQ-5D and FACT-Leu questionnaires. Survival rates were calculated applying by the Kaplan-Meier method. RESULTS: The patients' median age was 61 years. 41% of patients had a decline in estimated creatinine clearance less than 70 ml/min/1.73 m2. The combination of bendamustine and rituximab could achieve a common response in 83.2% of the patients, including complete remission in 59.7%. Eradication of minimal residual disease was achieved in 23 (27.4%) of 84 patients. Two-year progression-free survival rates were 85.9%. The QOL indicators were noted to be improved during the treatment. CONCLUSION: The investigation shows the good tolerability of bendamustine when it is used in clinical practice. Due to the high cost of new drugs (ibrutinib, obinutuzumab, ofatumumab, etc.) and toxicity of the FCR regimen, the combination including bendamustine can be the best first-line therapy option for all CLL patients, regardless of their age and comorbidity.

MARKERS OF THE PROSTATE BASAL LAYER CELLS ARE EFFECTIVE INDICATORS OF ITS MALIGNANT TRANSFORMATION.

Development of local or general forms of prostate cancer (PC) depends on formation of metastasis the biological nature of which is based on epithelial mesenchymal transition (EMT). ÅÌÒ presents highly conservative reversible program that is maintained by specific transcription factors which suppress E-cadherin expression and support production of mesenchymal polarity factors. The goal of this work was to study the functionally distinct markers in malignant prostate tissue of patients with prostate cancer using the histological evaluation, reverse polymerase chain reaction and immunobloting. Our results showed that mostly evident alterations in prostate tissue of patients with prostate cancer were associated with the cells of basal layer. Expression levels of the markers of this layer: Å-cadherin and ÑK5, were decreased, while that of AMACR ­ increased. These results support an idea that the basal cells are primarily targeted during transformation and acquired the luminal phenotype in the course of the following differentiation. The functional analysis of these results may be performed in future using selected prostate cancer stem cells.

[INCIDENCE, PREDISPOSING RISK FACTORS FOR THE DEVELOPMENT AND SPREADING OF ACUTE INTESTINAL INFECTIONS IN THE NORTH-EASTERN REGION OF UKRAINE].

Using data of the branch statistical reporting of the State Sanitary and Epidemiological Service in Sumy region and Sumy Regional State Laboratory of Veterinary Medicine, the incidence rate, modern risk factors for the development and spreading of acute infectious diarrheas were determined in the North-Eastern region of Ukraine. Under the current conditions incidence rate indices of acute intestinal infections and food toxicoinfections are within the range of 159.8-193.6 per 100 thousands. pop. Seasonal and epidemical rises are associated with a species of the agent. In the etiological structure of acute diarrheal infections there are dominated viruses, of food toxicoinfections--Klebsiellae pneumoniae, Staphylococcus aureus and Enterobacter cloacae (p < 0.05). Predictors of the complication of epidemiological situation of Shigella infections are the gain in the detection of bacterially contaminated samples of milk and dairy products (r = 0.75), for food toxicoinfections caused by Klebsiellae pneumoniae and Enterobacter cloacae--pastry with cream and cooking meat products (r = 0.64; r = 0.75). Epizootic situation in the region affects on the salmonellosis incidence rate of the population (r = 0.89). There were revealed correlations between the selection of E. coli bacteria from swabs taken from the enterprises of catering, in child care centers and the levels of incidence rates of salmonellosis, acute intestinal infections of unknown etiology (r = 0.59; r = 0.60). Timely detection and sanitation of Shigella carriers are a powerful instrument to reduce the incidence rate of shigellosis (r = 0.83).

Perpendicular planes of FtsZ arcs in spheroidal Escherichia coli cells.

Division planes in Escherichia coli, usually restricted to one dimension of the rod-shaped cell, were induced at all possible planes by transforming the cells to spheroids with mecillinam (inactivating PbpA). Such cells displayed many nucleoids and arcs of FtsZ, genetically tagged to green fluorescent protein, that developed to rings at constriction sites all around their surface. These observations are consistent with the view (Woldringh et al., J. Bacteriol. 176 (1994) 6030-6038) that nucleoids, forced during replication to segregate in the length axis of the cell by the rigid bacillary envelope, induce assembly of FtsZ to division rings in between them.

Visualizing multiple constrictions in spheroidal Escherichia coli cells.

An Escherichia coli cell grows by elongation and divides in a perpendicular plane. Alternating planes of successive divisions in three dimensions can only be ascertained when multiple constrictions exist simultaneously in large, spheroidal cells (with extended constriction process), if the division signals are enhanced. Large, spheroidal cells are obtained by a brief mecillinam treatment, and more frequent divisions are achieved by manipulating the rate of chromosome replication without affecting cell mass growth rate. Such a procedure has recently been performed by thymine-limitation of E. coli K12 strain CR34 (Zaritsky et al., Microbiology 145 (1999), 1052-1022). Enhancing the replication rate in cells with multi-forked replicating chromosomes (by addition of deoxyguanosine) shortens the intervals between successive terminations and thus triggers divisions more frequently. Monoclonal antibodies against FtsZ were used to visualize the rings of secondary constrictions, but apparent shortage of FtsZ to complete rings over wide cells allowed assembly of arcs only. The arcs observed were not parallel nor perpendicular; the tilted constriction planes are consistent with our 3-D 'nucleoid segregation'model for division under conditions which relieve the cylindrical constraint for nucleoid segregation by the bacillari peptidoglycan sacculus (Woldringh et al. , J. Bacteriol. 176 (1994) 6030-6038). The shortage in FtsZ may explain the longer time required to complete the division process in wide cells with long circumferences, observed during thymine step-up. Overexpression of fusion protein FtsZ-GFP on a multi-copy plasmid should circumvent the shortage.

Rapid loading of critically ill patients with carbamazepine suspension.

To determine the rate and factors that affect carbamazepine absorption, six patients being treated in the pediatric intensive care unit for frequent seizures received loading doses (7.4 to 10.4 mg/kg) of carbamazepine suspension by either nasogastric or nasoduodenal tube. Carbamazepine serum concentrations were determined 15, 30, 60, 120, and 480 minutes after administration by fluorescence polarization immunoassay. One patient who had an ileus did not attain therapeutic concentrations (greater than 4.0 mg/L). The other five patients with normal gastrointestinal function achieved mean serum concentrations at 1 hour and 2 hours of 4.3 mg/L and 7.3 mg/L, respectively. Delayed gastric emptying and concurrent enteral feedings appear to slow the absorption of carbamazepine. No adverse effects were observed. Rapid loading with carbamazepine suspension appears to be a useful alternative for the management of critically ill pediatric patients who are experienced frequent seizures.

Recommended guidelines for uniform reporting of pediatric advanced life support: the pediatric Utstein style. A statement for healthcare professionals from a task force of the American Academy of Pediatrics, the American Heart Association, and the European Resuscitation Council.

This consensus document is an attempt to provide an organized method of reporting pediatric ALS data in out-of-hospital, emergency department, and in-hospital settings. For this methodology to gain wide acceptance, the task force encourages development of a common data set for both adult and pediatric ALS interventions. In addition, every effort should be made to ensure that consistent definitions are used in all age groups. As health care changes, we will all be challenged to document the effectiveness of what we currently do and show how new interventions or methods of treatment improve outcome and/or reduce cost. Only through collaborative research will we obtain the necessary data. For these reasons, and to improve the quality of care and patient outcomes, it is the hope of the task force that clinical researchers will follow the recommendations in this document. It is recognized that further refinements of this statement will be needed; these recommendations will improve only when researchers, clinicians, and EMS personnel use them, work with them, and modify them. Suggestions, emendations, and other comments aimed at improving the reporting of pediatric resuscitation should be sent to Arno Zaritsky, MD, Eastern Virginia Medical School, Children's Hospital of The King's Daughter, Division of Critical Care Medicine, 601 Children's Lane, Norfolk, VA 23507.

Drug therapy of cardiopulmonary resuscitation in children.

In contrast to adults, cardiopulmonary arrest in infants and children is rarely an acute, primary cardiac event. Instead, it is often the terminal event in a progressive deterioration of respiratory or circulatory function. Successful resuscitation from cardiac arrest therefore is unusual in the paediatric patient and most survivors have persistent neurological impairment. Rapid vascular access and recall of drug dosages are major obstacles in treating paediatric emergencies. This paper reviews vascular access and alternative drug delivery methods. The endotracheal and intraosseous routes provide alternative sites for drug delivery, but the optimal doses and methods of drug administration via these routes are unknown. Indeed, although great progress in cardiopulmonary resuscitation (CPR) research has been made over the past 10 years, there are only limited data on paediatric arrest mechanisms and drug treatment. In this paper, recommended dosages and mechanisms of action of drugs useful during cardiopulmonary resuscitation are reviewed, highlighting recent data which suggest that changes in current drug recommendations may be needed. To avoid delays in management, precalculated tables of drugs should be readily available in emergency departments and other care areas where paediatric cases are likely to be seen. Adrenaline (epinephrine) remains the drug of choice in a cardiac arrest, but the most effective dose may be higher than currently used. Treatment of acidosis during the arrest concentrates on restoration of ventilation and blood flow and not on bicarbonate administration. In the post-arrest setting increasing data suggest bicarbonate may not be beneficial and may actually be detrimental. Calcium and atropine also have relatively minor roles in resuscitation pharmacology. Calcium is only indicated to treat hypocalcaemia, counteract the effects of hyperkalaemia or hypermagnesaemia, or reverse calcium channel blocker toxicity. Finally, the role of isoprenaline (isoproterenol), dopamine, dobutamine and adrenaline infusions to restore or maintain cardiovascular stability post-arrest is reviewed.

A statewide evaluation of pediatric prehospital and hospital emergency services.

OBJECTIVE: To evaluate the extent of pediatric emergency training and the availability of pediatric equipment and patient care protocols in the prehospital and hospital settings. DESIGN: Statewide surveys developed by the North Carolina Provisional Committee on Pediatric Emergency Medical Services and by the Office of Emergency Medical Services. SETTING AND PARTICIPANTS: Surveys were mailed to all 572 prehospital Emergency Medical Service (EMS) agencies and separately to all 125 acute-care hospitals in North Carolina. INTERVENTIONS: None. MEASUREMENTS/MAIN RESULTS: Surveys were returned by 335 (58.6%) of the prehospital providers, including all 45 paramedic and 14 advanced-intermediate provider agencies. One hundred (80%) of the acute-care hospitals returned surveys. Only 10.8% of the prehospital EMS agencies provided more than 10 hours of basic training in pediatric emergency care; 18% provided more than 5 hours of continuing education in pediatric emergencies over a 3-year period. Pediatric-specific equipment was available in many prehospital vehicles, although some deficiencies were noted. Written pediatric management, bypass, and helicopter transport protocols were absent in most prehospital programs. Paramedic programs generally were much better in all areas, although deficiencies were present. Only 14% of the responding hospitals had more than 20 pediatric beds; 13% reported seeing more than 100 patients per day in the emergency department. Deficiencies were identified in pediatric patient care protocols, triage and transport agreements, pediatric training of nurses and physicians, and equipment. Equipment deficiencies were more marked in the intensive care units than in the emergency departments. CONCLUSIONS: These survey data are inexpensive to obtain and demonstrate EMS system deficiencies. The survey information provides a baseline measurement that can lead to measurable, targeted changes in the state's EMS system for children.

Cardiopulmonary resuscitation in children.

The management of the pulseless, nonbreathing pediatric patient continues to be a frustrating experience because mortality and morbidity are high. Improvement in outcome awaits a better understanding of the pathophysiology of organ ischemia and reperfusion injury. In the interim, early recognition and therapy of respiratory and circulatory failure are the only effective means to affect outcome. The approach to the pediatric cardiac arrest victim differs from the adult, because dysrhythmias rarely are the etiology of pediatric arrest. Instead, attention to securing the airway and provision of adequate ventilation are keys. Epinephrine is the most effective drug in this setting, and may be administered through an endotracheal tube as well as intravenously or intraosseously. The latter route provides a useful means of rapid vascular access in the pediatric victim less than 3 years of age. Sodium bicarbonate use has been discouraged and there are few indications for calcium, greatly simplifying the pharmacologic approach to the pediatric cardiac arrest patient. In those patients in whom a rhythm and pulse are restored, support of the circulation often is required. Dopamine or epinephrine are the catecholamines of choice in this setting. Ventricular arrhythmias are treated with defibrillation or cardioversion as appropriate. Infrequently, lidocaine or bretylium may be needed. Once the patient has been stabilized, further care is best delivered at a tertiary care center with a pediatric intensive care unit.

Vancomycin-binding characteristics in patients with serious infections.

STUDY OBJECTIVE: To examine the extent, variability, and factors affecting vancomycin protein binding. DESIGN: Prospective, open-label, cohort study. SETTING: A general hospital. PATIENTS: Forty-four adults [mean (+/- SD) age 50.9 +/- 17.1 yrs, range 16.8-92.0 yrs] with serious infections. INTERVENTIONS: Unbound (Vu) and total (Vtot) vancomycin concentrations were determined by fluorescence polarization immunoassay. A statistical analysis model used the maximum likelihood method to evaluate the association between several important variables and log Vu while controlling for log Vtot effects. MEASUREMENTS AND MAIN RESULTS: The mean fraction percentage of unbound vancomycin was 79.5 +/- 6.0% (range 53.0-96.3%). While controlling for Vtot the total variability of Vu was 8.3%, suggesting that vancomycin binding is relatively constant in sick adults. We were able to demonstrate a significant statistical interaction effect between gender and globulin protein concentration on Vu (p = 0.022). Globulin protein concentration in men was negatively associated with Vu (p = 0.0009), but there was no association in women (p = 0.645). Age, race, peak-trough association, serum creatinine, serum albumin, serum prealbumin, and hemodialysis were not significantly associated with log Vu in the statistical model. CONCLUSION: Compared with earlier studies in healthy adults, vancomycin binding appears to be decreased during acute illness, and intrapatient and interpatient variability are relatively small. Unbound vancomycin concentration appears to be gender dependent.

Recommended guidelines for uniform reporting of pediatric advanced life support: the Pediatric Utstein Style. A statement for healthcare professionals from a task force of the American Academy of Pediatrics, the American Heart Association, and the European Resuscitation Council.

This consensus document is an attempt to provide an organized method of reporting pediatric ALS data in out-of-hospital, emergency department, and in-hospital settings. For this methodology to gain wide acceptance, the task force encourages development of a common data set for both adult and pediatric ALS interventions. In addition, every effort should be made to ensure that consistent definitions are used in all age groups. As health care changes, we will all be challenged to document the effectiveness of what we currently do and show how new interventions or methods of treatment improve outcome and/or reduce cost. Only through collaborative research will we obtain the necessary data. For these reasons, and to improve the quality of care and patient outcomes, it is the hope of the task force that clinical researchers will follow the recommendations in this document. It is recognized that further refinements of this statement will be needed; these recommendations will improve only when researchers, clinicians, and EMS personnel use them, work with them, and modify them. Suggestions, recommendations, and other comments aimed at improving the reporting of pediatric resuscitation should be sent to Arno Zaritsky, MD, Eastern Virginia Medical School, Children's Hospital of The King's Daughter, Division of Critical Care Medicine, 601 Children's Lane, Norfolk, VA 23507.

Paediatric life support. An advisory statement by the Paediatric Life Support Working Group of the International Liaison Committee on Resuscitation.

This document reflects the deliberations of ILCOR. The epidemiology and outcome of paediatric cardiopulmonary arrest and the priorities, techniques and sequence of paediatric resuscitation assessments and interventions differ from those of adults. The working group identified areas of conflict and controversy in current paediatric basic and advanced life support guidelines, outlined solutions considered and made recommendations by consensus. The working group was surprised by the degree of conformity already existing in current guidelines advocated by the American Heart Association (AHA), the Heart and Stroke Foundation of Canada (HSFC), the European Resuscitation Council (ERC), the Australian Resuscitation Council (ARC), and the Resuscitation Council of Southern Africa (RCSA). Differences are currently based upon local and regional preferences, training networks and customs, rather than scientific controversy. Unresolved issues with potential for future universal application are highlighted. This document does not include a complete list of guidelines for which there is no perceived controversy and the algorithm/decision tree figures presented attempt to follow a common flow of assessments and interventions, in coordination with their adult counterparts. Survival following paediatric prehospital cardiopulmonary arrest occurs in only approximately 3-17% and survivors are often neurologically devastated. Most paediatric resuscitation reports have been retrospective in design and plagued with inconsistent resuscitation definitions and patient inclusion criteria. Careful and thoughtful application of uniform guidelines for reporting outcomes of advanced life support interventions using large, randomized, multicenter and multinational clinical trials are clearly needed. Paediatric advisory statements from ILCOR will, by necessity, be vibrant and evolving guidelines fostered by national and international organizations intent on improving the outcome of resuscitation for infants and children worldwide.

Early postnatal dexamethasone treatment and increased incidence of cerebral palsy.

OBJECTIVE: To study the long term neurodevelopmental outcome of children who participated in a randomised, double blind, placebo controlled study of early postnatal dexamethasone treatment for prevention of chronic lung disease. METHODS: The original study compared a three day course of dexamethasone (n = 132) with a saline placebo (n = 116) administered from before 12 hours of age in preterm infants, who were ventilated for respiratory distress syndrome and had received surfactant treatment. Dexamethasone treatment was associated with an increased incidence of hypertension, hyperglycaemia, and gastrointestinal haemorrhage and no reduction in either the incidence or severity of chronic lung disease or mortality. A total of 195 infants survived to discharge and five died later. Follow up data were obtained on 159 of 190 survivors at a mean (SD) age of 53 (18) months. RESULTS: No differences were found between the groups in terms of perinatal or neonatal course, antenatal steroid administration, severity of initial disease, or major neonatal morbidity. Dexamethasone treated children had a significantly higher incidence of cerebral palsy than those receiving placebo (39/80 (49%) v. 12/79 (15%) respectively; odds ratio (OR) 4.62, 95% confidence interval (95% CI) 2.38 to 8.98). The most common form of cerebral palsy was spastic diplegia (incidence 22/80 (28%) v. 5/79 (6%) in dexamethasone and placebo treated infants respectively; OR 4.45, 95% CI 1.95 to 10.15). Developmental delay was significantly more common in the dexamethasone treated group (44/80 (55%)) than in the placebo treated group (23/79 (29%); OR 2. 87, 95% CI 1.53 to 5.38). Dexamethasone treated infants had more periventricular leucomalacia and less intraventricular haemorrhage in the neonatal period than those in the placebo group, although these differences were not statistically significant. Eleven children with cerebral palsy had normal ultrasound scans in the neonatal period; all 11 had received dexamethasone. Logistic regression analysis showed both periventricular leucomalacia and drug assignment to dexamethasone to be highly significant predictors of abnormal neurological outcome. CONCLUSIONS: A three day course of dexamethasone administered shortly after birth in preterm infants with respiratory distress syndrome is associated with a significantly increased incidence of cerebral palsy and developmental delay.

Neonatologists are using much less dexamethasone.

Two historical cohorts (1993-1994 and 2001) of preterm infants ventilated for respiratory distress syndrome were compared. Dexamethasone administration fell from 22% to 6%. Chronic lung disease in survivors rose slightly from 13% to 17%, and mortality fell from 21% to 15% (other causes). The effect of restriction of dexamethasone use on chronic lung disease and mortality remains to be seen.

Selected concepts and controversies in pediatric cardiopulmonary resuscitation.

Although more than 80 years of research in cardiac resuscitation produced many important findings and greatly enhanced our understanding of the arrest state, outcome following pediatric cardiac arrest remains poor. Resuscitation guidelines have recently been published, but they may not reflect optimal therapy. Closed-chest compression-induced cardiac output may be higher in pediatric patients, particularly infants, than that previously reported in adults. To achieve higher cardiac outputs, direct cardiac compression is important; the recommended compression location has therefore been changed based on recent data. The optimal rate of compression, however, is uncertain, so further research is needed. Alternative vascular access sites, such as the endotracheal and intraosseous route for drug administration may permit more rapid drug delivery, but data suggest that a larger epinephrine dose than currently recommended should be used. It may also be helpful to dilute the drug in normal saline before endotracheal administration. Although experimental data suggest that a pure alpha-adrenergic agonist may be beneficial in a cardiac arrest, recent data show that epinephrine remains the drug of choice. Finally, the role of sodium bicarbonate in both the arrest and postarrest setting has become controversial. Recent data suggest that bicarbonate may be detrimental and that therapy of acidosis is best directed at improving perfusion, oxygenation, and ventilation. Alternative forms of therapy for acidosis, such as THAM and dichloroacetate may prove beneficial in the postarrest setting.

Endocrine manifestations of critical illness in the child.

The stress response in humans commonly includes elevations in plasma concentrations of glucocorticoids, catecholamines, glucagon, growth hormone, aldosterone, and renin, resulting in alterations in the metabolism of glucose and other energy substrates, and in increased sodium and water retention. In severe illness, triiodothyronine and sometimes thyroxine are decreased without evidence of clinical hypothyroidism. Antidiuretic hormone may be elevated in bacterial meningitis and other central nervous system disorders, as well as in acute asthma, chronic ventilator therapy, pneumothorax, atelectasis, and postoperatively. Increased ADH concentration can lead to significant hypoosmolality and hyponatremia with adverse effects on the patient. In the setting of severe intracerebral insults, ADH may be inappropriately low, resulting in diabetes insipidus. Insulin concentrations may be inappropriately low for serum glucose concentration, or insulin may have diminished receptor responsiveness in seriously stressed patients. Either situation leads to hyperglycemia. Disturbances in calcium, phosphorus, and magnesium homeostasis may occur relatively frequently in the critically ill patient in response to therapeutic interventions, or illness-induced altered metabolism. It is not always clear when an altered metabolic or hormonal state is an appropriate response to a stress, or represents decompensation of the body's mechanisms for coping with that stress. It is important, however to recognize the common responses of the organism to severe illness, and to monitor for treatable abnormalities which occur.

Neural computing in discovering RNA interactions.

High-order RNA structures are involved in regulating many biological processes; various algorithms have been designed to predict them. Experimental methods to probe such structures and to decipher the results are tedious. Artificial intelligence and the neural network approach can support the process of discovering RNA structures. Secondary structures of RNA molecules are probed by autoradiographing gels, separating end-labeled fragments generated by base-specific RNases. This process is performed in both conditions, denaturing (for sequencing purposes) and native. The resultant autoradiograms are scanned using line-detection techniques to identify the fragments by comparing the lines with those obtained by 'alkaline ladders'. The identified paired bases are treated by either one of two methods to find the foldings which are consistent with the RNases' 'cutting' rules. One exploits the maximum independent set algorithm; the other, the planarization algorithm. They require, respectively, n and n2 processing elements, where n is the number of base pairs. The state of the system usually converges to the near-optimum solution within about 500 iteration steps, where each processing element implements the McCulloch-Pitts binary neuron. Our simulator, based on the proposed algorithm, discovered a new structure in a sequence of 38 bases, which is more stable than that formerly proposed.

Successful treatment of Candida-infected caval thrombosis in critically ill infants by low-dose streptokinase infusion.

Chronic central venous catheters are an important component in the management of chronically ill infants and children. Sepsis and thrombosis are common complications of these catheters. When the combination of Candida sepsis and caval thrombosis occurs, the prognosis is very poor. Lysis of the thrombus is critical to effective therapy and allows preservation of vascular access. We report the successful treatment of four critically ill infants with Candida-infected caval thrombosis treated with low-dose infusion of streptokinase combined with standard antimicrobial therapy. All four infants survived, and in all cases thrombolysis was complete and Candida sepsis resolved. Each of the infants required continued central venous access, which was made possible by resolution of the caval thrombosis. There were no hemorrhagic or other complications of the therapy.

Raising activity of Bacillus thuringiensis var. israelensis against Anopheles stephensi larvae by encapsulation in Tetrahymena pyriformis (Hymenostomatida:Tetrahymenidae).

Toxicity of Bacillus thuringiensis var israelensis (B.t.i.) against surface-feeding mosquito larvae of Anopheles stephensi was enhanced by encapsulation in the protozoan Tetrahymena pyriformis. In the laboratory, larvae died about 8 times faster when exposed to protozoan cells filled with B.t.i. than when exposed to the same concentrations of B.t.i. alone. Best larvicidal activities were achieved with ratios of 1:200-1:500 T. pyriformis cells to B.t.i. spores. The concentration of B.t.i. needed to kill 50% of exposed populations was 4-fold lower with T. pyriformis than with B.t.i. alone in 100 ml-test cups. Toxicity enhancement is very likely a consequence of concentrating B.t.i. insecticidal crystal proteins in T. pyriformis cells and floating them to the water surface in the larval feeding zone. Reduction in the exposure time of B.t.i. to unfavorable field conditions, as a result of the decrease in larval mortality time, might improve the persistence of this biological control agent in nature.