By L. Ramon. Carlow College.
Other potentially chemotactic substances include secre- tory products of lymphocytes buy voltaren 50 mg with mastercard arthritis pain without inflammation, products of infected and damaged cells or the N-formyl peptides (fMet-Phe and fMet-Leu-Phe) buy voltaren 50 mg with visa arthritis in your neck symptoms. Particles adhering to the membrane are engulfed, in- gested and deposited in a membrane-bound vacuole, the so-called phago- some, which then fuses with lysosomes to form the phagolysosome. The bac- teria are killed by a combination of lysosomal factors: — Mechanisms that require no oxygen. Low pH; acid hydrolases, lysozyme; proteases; defensins (small cationic peptides). The Fc and C3b ligands bind to their specific receptors on the pha- gocyte surface. Humoral immunity is based on antitoxins, op- sonins, microbicidal antibodies, neutralizing antibodies, etc. Cellular immu- nity is based on cytotoxic T lymphocytes (T killer cells) and T helper cells. Congenital defects in the complement-dependent pha- gocytosis system are rare, as are B and T lymphocyte defects. One result of progress in modern medicine is that increasing numbers of pa- tients with secondary immune defects are now receiving hospital treatment. Such “problem patients” are frequently infected by opportunistic bacteria that would not present a serious threat to normal immune defenses. Often, the pathogens involved (“problem bacteria”) have developed a resistance to numerous antibiotics, resulting in difficult courses of antibiotic treatment in this patient category. They proliferate in varied profusion on the mucosa and most particularly in the gastrointestinal tract, where over 400 different species have been counted to date. The count of bacteria per gram of intestinal content is 101–105 in the duodenum, 103–107 in the small intestine, and 1010–1012 in the colon. Over 99% of the normal mucosal flora are obligate anaerobes, dominated by the Gram-neg. One way they do so is when organisms of the normal flora manage to penetrate into the host through microtraumas, resulting in a continuous stimulation of the immune system. Commensals also compete for living space with overtly pathogenic species, a function known as colo- Kayser, Medical Microbiology © 2005 Thieme All rights reserved. On the other hand, a potentially harmful effect of the normal flora is that they can also cause infections in immunocompromised individuals. General Epidemiology & Within the context of medical microbiology, epidemiology is the study of the occurrence, causality, and prevention of infectious diseases in the popu- lace. Infectious diseases occur either sporadically, in epidemics or pandemics, Kayser, Medical Microbiology © 2005 Thieme All rights reserved. The term mortality is used to describe how many deaths are caused by a given disease in a given population. Pathogens are transmitted from these sources to susceptible persons either directly (person-to-person) or indirectly via in- ert objects or biological vectors. Control of infectious diseases within a pop- ulace must be supported by effective legislation that regulates mandatory reporting where required. Further measures must be implemented to pre- vent exposure, for example isolation, quarantine, disinfection, sterilization, use of insecticides, and dispositional prophylaxis (active and passive immu- nization, chemoprophylaxis). The field covered by this discipline can thus be defined as medical problems involving large collectives. The rule of thumb on infectious diseases is that their characteristic spread depends on the virulence of the pathogen involved, the susceptibility of the threatened host species population, and environmental factors. Transmission, Sources of Infection Transmission Pathogens can be transmitted from a source of infection by direct contact or indirectly. Cattle, pig, goat, Contact with tissues or sheep, (dog) secretions from diseased animals; milk and dairy products Lyme disease Borrelia Wild rodents; Ticks burgdorferi red deer, roe deer Plague Yersinia pestis Rodents Contact with diseased animals; bite of rat flea Q fever Coxiella burnetii Sheep, goat, Dust; possibly milk or cattle dairy products Enteric Salmonella Pig, cattle, Meat, milk, eggs salmonellosis enterica (enteric poultry serovars) Kayser, Medical Microbiology © 2005 Thieme All rights reserved. Bacterial zoonoses Ehrlichiosis; erysipeloid; campylobacteriosis; cat scratch disease; leptospirosis; anthrax; ornithosis; rat-bite fever; rickettsioses (variety of types); tularemia; gastroenteritis caused by Vibrio parahaemolyticus; gastroenteritis caused by Yersinia enterocolitica. Protozoan zoonoses African trypanosomosis (sleeping sickness); American trypanosomosis (Chagas disease); babesiosis; balanti- dosis; cryptosporidosis; giardiosis; leishmaniosis; micro- sporidosis; sarcocystosis; toxoplasmosis. Zoonoses caused Flea infestation; larva migrans externa; mite infestation; by arthropods sand flea infestation. The primary source of infection is defined as the location at which the pathogen is present and reproduces.
Negative results were found by Riggio with longer times to stop heparin treatment in patients experiencing heparin induced thrombocytopenia following implementation of an alert for 100 patients purchase voltaren 50 mg online arthritis pain chart. Time from alert to laboratory test and start of direct thrombin inhibitor treatment did not vary before and after the implementation cheap 50mg voltaren arthritis pain doterra. We considered positive studies to have at least 50 percent of the outcomes as being significantly impacted by the technology. Under this measure, four of the studies did not show significant impact of the technologies on patient 425,555,685,702 701 outcomes though they tended towards being positive. Balcezak and colleagues found better prescribing of heparin when a computerized nomogram was used by prescribers, but the nomogram was only used for 10 percent of prescriptions written. The highest quality 507 618 612 evidence comes from Raebel, White, and Feldstein and their colleagues who all showed positive, significant impacts of the technologies on narrow therapeutic index drug management. The observational study 564 by Smith and colleagues in 15 primary care clinics to reduce prescribing on nonpreferred drugs in elderly patients showed a significant decrease in exposure of elderly patients to nonpreferred drugs, but no change in nonelderly patients, and a nonsignificant positive trend of preferred drugs in elderly patients. Peterson and colleagues found no change in length of stay or rate of altered status, but a significant reduction in falls (p = 0. Wrona and colleagues found improved respiratory rate in patients on morphine and hydromorphone with order sets outlining monitoring and documentation requirements. Unintended consequences can be minor or major and they can be viewed as being helpful to the installation or detrimental. Because we report only those outcomes that the authors reported as the primary or main findings of the study, this listing of articles on unintended consequences is likely not comprehensive. As in previous sections of this 508 report most of the studies evaluated prescribing. The order communication phase was evaluated in two studies, one 69 15 732 15 observational and one qualitative study. No studies of unintended consequences evaluated the monitoring phase or education and reconciliation. Most of the studies were done at an institution level rather than a patient or 508 provider level. Nurses were evaluated in two studies, and the rest of the studies included a range of clinicians. Raebel and colleagues studied drugs with potential for harm to the fetus in pregnant women (category D and X medications). These unintended consequences were categorized into direct compared with indirect, desirable compared with undesirable, and anticipated compared with unanticipated occurrences. Ash and colleagues contend that most unintended consequences center on errors, security concerns, and issues related to alerts, workflow, ergonomics, interpersonal relations, and reimplementation (e. Because of the seriousness of the implications of this study, many people reviewed this article. New and different types of errors were identified as unintended consequences in three 450,457,503 studies. One study felt that problems with communication 775 would probably lead to errors in medication management, and another study postulated the 734 same increase in errors based on challenges to existing and changing roles. The study of use of inappropriate medications during pregnancy was stopped early because the system was not 70 accurate enough, causing the system to “miss” notification of drugs that should have been alerted 508 and to give alerts that were not needed. Ash and colleagues list 47 types of unintended consequences and Kopppel and 752 colleagues list 22. Ash and colleagues go on to verify that the types of unintended consequences they found were common in institutions outside those that she and her colleagues 777 734,743,752,776,781 775,779 studied. Unintended consequences were related to roles, communication, 752,759,779 workflow alterations or automation of poor existing workflows, inflexibility of the new 743,752,759 752,759,776 480,776,779 system, poor content or poor display of content, alert fatigue, and 779 overdependence on the system. Rather than fix the system, most often workarounds were 732,743 instituted by clinical staff. Discuss gaps in research, including specific areas that should be addressed and suggest possible public and private organizational types to perform the research and/or analysis. Where an issue is more strongly associated with a phase we mention the phase or other aspect (e.
A single exclusion can result from germ line suﬃciently polymorphic that the mother’s sample is mutation within one locus being tested not necessary to determine paternity cheap voltaren 100 mg with visa essential oils for arthritis in dogs. Te biological father may be a blood relative to based on the premise that the biological father must the alleged father have at least one allele in common with the child at D order voltaren 100 mg with amex arthritis of feet. D Hereditary hemochromatosis is an autosomal Molecular/Apply knowledge of special procedures/ recessive disease with a frequency as high as 0. Hereditary hemochromatosis is the result of which base that results in tyrosine substituting for cysteine type of mutation? The remaining cases Molecular/Correlate clinical and laboratory data/Point are caused by a single-point mutation at position mutations/2 63 on the protein (H63D), which produces a milder 27. N-Myc which activate transcription by up-regulating the Molecular/Apply knowledge of fundamental biological signal transduction pathway of the cell. Talassemia/2 β-Thalassemia may be caused by single base substitutions, deletions, or mutations in the ﬂanking 29. A In ﬂow cytometry, cells can be divided into of cells of interest subpopulations based upon their light-scattering C. Cells to be interrogated by the laser(s) are single antibody selected by identifying the area in which they appear D. B The gated population is selected by evaluating the procedures/Flow cytometry/1 scatterplot of forward light scattering (x axis) and right angular or side scatter (y axis). Which of the following parameters are used to gate within the speciﬁed limits are counted. Font surface ﬂuorescence versus incident laser because the former have greater forward scatter and intensity less side scatter. A Forward scatter of light from a laser directed through wavelengths the aperture of the cytometer is directly related to cell D. Right angular scatter (side scatter) is dependent conductance upon the number of granules inside the cytoplasm. Molecular diagnostics/Apply principles of special For example, small lymphocytes that are agranular procedures/Flow cytometry/1 have the lowest forward and side scatter and are easily identiﬁed as the cluster of cells closest to the 32. In general, which statement best characterizes the bottom and left of the scatterplot. Forward scatter is related to cell size and side speciﬁc antibodies that bind to surface antigens scatter to granularity that characterize their lineage and maturation B. The antibodies are conjugated to ﬂuorescent side scatter to size dyes that are excited by the laser. Forward scatter is inversely related to size and characteristic wavelength emitted by the ﬂuorescent side scatter is directly related to size label is detected, then the cell bound the labeled D. Forward scatter is related to shape and side antibody and is positive for the respective antigen. Since Molecular diagnostics/Apply principles of special they emit green and red light, respectively, they procedures/Flow cytometry/2 can be diﬀerentiated in the same sample, allowing 33. Fluorescent dyes most commonly conjugated to two antibodies to be tested simultaneously. Fluorescein isothiocyanate and Texas red simultaneous measurement of more markers. Calcoﬂuor white and Texas red example, diﬀerent ﬂuorescent dyes can be attached C. Phycoerythrin and ﬂuorescein isothiocyanate to latex beads in diﬀerent proportions so that up to D. Acridine orange and rhodamine 100 combinations can be discriminated by the optics. Molecular diagnostics/Apply principles of special This allows 100 diﬀerent markers to be measured in procedures/Flow cytometry/1 the same sample simultaneously. Flow cytometry is used to measure speciﬁc plasma proteins and antibodies using ﬂuorescent antibody–coated beads. Tyroid cancer of the gene is involved, giving rise to a 210 dalton Molecular/Apply principles of special laboratory chimeric protein. The absorbance ratio 260:280 was essential thrombocythemia that occurs at disease 1.
Nakonieczna discount 50 mg voltaren visa gouty arthritis in the knee, and chronic cumulative toxicities due to long-term adminis- “Innovative strategies to overcome bioflm resistance buy 50 mg voltaren amex arthritis muscle pain relief,” BioMed tration is needed prior to clinical application of these drugs. Bou, “Antimicrobial resistance Conflict of Interests and virulence: a successful or deleterious association in the bacterial world? Kouznetsov, “Recent devel- “Characterization of the -Acetylglucosaminyltransferase opments on antimicrobial quinoline chemistry,” in Microbial activity involved in the biosynthesis of the Staphylococcus Pathogens and Strategies for Combating Tem: Science, Technol- epidermidis polysaccharide intercellular adhesin,” Te Journal ogy and Education,A. Jabbouri, “Neither the cultureplates:aquantitativemodelfortheadherenceofstaphy- presence of ica locus, nor in vitro-bioflm formation ability is a lococci to medical devices,” Journal of Clinical Microbiology,vol. Gotz, “Characteriza-¨  Clinical and Laboratory Standards Institute, “Performance tion of the importance of Staphylococcus epidermidis autolysin standards for antimicrobial disk and dilution susceptibility and polysaccharide intercellular adhesin in the pathogenesis of test: M2-A9. Performance standards for antimicrobial sus- intravascular catheter-associated infection in a rat model,” Te ceptibility testing,” Tech. Greenberg, “Te involvement of cell-to-cell Complementary and Alternative Medicine,vol. Gotz,¨ “Activity of gallidermin on Staphylococcus “Resistance of bacterial bioflms to disinfectants: a review,” aureus and Staphylococcus epidermidis bioflms,” Antimicrobial Biofouling,vol. Stewart, “Reduced glucopyranose on bioflm formation by Staphylococcus aureus,” susceptibility of thin Pseudomonas aeruginosa bioflms to Antimicrobial Agents and Chemotherapy,vol. Gilbert, “Changes Shindo, “Antimicrobial susceptibility of Staphylococcus aureus in the biocide susceptibility of Staphylococcus epidermidis and and Staphylococcus epidermidis bioflms isolated from infected Escherichia coli cells associated with rapid attachment to plastic total hip arthroplasty cases,” Journal of Orthopaedic Science,vol. Antimicrobial activity of novel 1-methyl-3- rapid determination of antibiotic susceptibilities of bacterial thio-4-aminoquinolinium salts,” Folia Microbiologica,vol. Deighton, “Antibiotic susceptibility of coagulase-negative 4-aminoquinolinium chlorides,” Acta Poloniae Pharmaceutica: staphylococci isolated from very low birth weight babies: com- Drug Research,vol. Woodmansee, “Activities of daptomycin and vancomycin alone and in combination with rifampin and gentamicin against bioflm-forming methicillin-resistant Staphylococcus aureus isolates in an experimental model of endocarditis,” Antimicrobial Agents and Chemotherapy,vol. Shanks, “AzaSite inhibits Staphylococcus aureus and coagulase-negative Staphylococcus bioflm forma- tion in vitro,” Journal of Ocular Pharmacology and Terapeutics, vol. AboZahra, “In vitro activities of three kinds of antibiotics against Staphylococcal bioflm and planktonic cultures,” African Journal of Microbiology Research,vol. Tis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Tose results showed that the diferent test systems and the mixed infection with particular genotypes of M. Twenty- positive isolates were included in this study which were isolated in fve microliter of 0. In this study of all the total 1412 culture positive incubated for an additional 2 days. Results for determining drug susceptibility in the L-J agar proportion from our genotyping analysis showed that 10 paired isolates method in this study (Table 4). Te isolates ahpC further confrmed one patient (number 18) with mixed with particular genotypes, such as Spoligotype International infection by the heterogeneous genotypes (Table 4). Cangelosi, “Drug susceptibility testing of Mycobacterium tuberculosis: a neglected problem at the turn of the century,” International Journal of Tuberculosis and Lung Authors’ Contribution Disease,vol. Scarparo, Zaoxian Mei and Zhaogang Sun contributed equally to this “Current perspectives on drug susceptibility testing ofMycobac- work. Acknowledgments  Chinese Anti-Tuberculosis Association, Protocols for Tubercu- Te authors thank the Beijing Bio-Bank of Clinical Resources losis Diagnosis in Laboratory, Chinese Educational and Cultural on Tuberculosis and the Outpatient Department of Tian- Publisher, Beijing, China, 1st edition, 2006. References Shinnick, “Association of specifc mutations in katG, rpoB, rpsL and rrsgeneswithspoligotypesofmultidrug-resistantMycobac-  J. Gumbo, “Meta-analysis terium tuberculosis isolates in Russia,” Clinical Microbiology and of clinical studies supports the pharmacokinetic variability Infection, vol. Locht, “Variable human minisatellite-like regions in the and cause disease,” Journal of Clinical Microbiology,vol. Kim, “Drug-susceptibility testing in tuberculosis: methods and reliability of results,” European Respiratory Journal,vol. Tis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
W henever possible buy 100mg voltaren with mastercard arthritis upper arm, pain care offices for insisting on proper pain con- management should be discussed with care trol discount 100mg voltaren visa arthritis relief naturally. Effort should be made to find physicians providers before surgery or dental procedures. Patients ple, 50 percent of the usual dose can be given with arthritis or disc disease might have chronic before surgery and 50 percent after. Patients who complain of chronic pain first ï Patientsí levels of pain should be monitored need a thorough examination to determine and and, if increases are evident, pain should treat the cause of the pain. Doses of short-acting need referral to specialists for testing and treat- opioids might have to be administered in ment. Several options should be tried before a addition to maintenance treatment, which is patient receives opioids for pain. A other pharmacotherapies and physical therapy patientís previous drug of abuse should not or surgery. Patient- approaches to managing chronic, nonmalignant controlled analgesia can be successful to treat pain. Unfortunately, many pain centers that postoperative pain in patients who are opioid provide these treatments hesitate to accept addicted, although the increments used patients taking opioid treatment medications. A pain Patients should be seen at shorter intervals management expert and an addiction specialist for refills, and prescriptions should specify a should coordinate treatment of patients in fixed schedule rather than ìas needed. Drug testing can be ìrescueî doses) of opioid analgesics to manage useful in evaluating the degree to which such breakthrough pain may be indicated as part of patients are complying with treatment regimens a comprehensive approach. If so, the amount although it is not foolproof; urine drug tests, of rescue medication should be calculated for example, identify only the presence or prospectively based on a patientís history absence of substances, not the amount taken (Savage 1999). A primary care physician or a pain spe- Adjustm ent of M ethadone cialist can prescribe rescue medication. If a Schedule patient needs frequent rescue medication, then his or her substance abuse treatment medica- The methadone-dosing schedule to treat pain is tion probably should be increased in lieu of three or four times daily or every 6 to 8 hours. For example, a patient on dialysis lead to a sharp reduction in serum methadone might require repeated shunt revisions, a levels. The hospital team modify their lifestyles, and participate in the should be informed of the patientís methadone medical followup needed to manage common dosage, the date on which methadone was chronic illnesses. In general, their medical care last administered, and the patientís medical, co- for other conditions should be identical to that occurring, or social problems. In some that adequate pain relief might require the cases, medications for these medical conditions patient to receive a normal methadone dose might need adjustment because of interactions (or its equivalent) plus additional medication, with opioid addiction treatment medications as described earlier in this chapter. Age- and risk- advised to institute appropriate controls to pre- appropriate medical screening, such as mam- vent a patient from obtaining and using illicit mograms, sigmoidoscopy, prostate checks, or substances or abusing prescription drugs while exercise stress tests, should be discussed with in the hospital. Such controls include limiting material or videotapes to present this informa- visitors, preventing a patientís wandering tion. Some programs have developed health- through the hospital, and conducting regular related educational videotapes that are played drug tests. Patterns of use range from occasional low doses to regular high doses that meet dependence criteria. Treatment providers should treat patients for their concurrent substance abuse aggressively or refer them appropriately. Providers should try to understand and address the underlying causes of concurrent substance use. In Although not shown in Exhibit 11-1, rates of 2001, 93,064 nonfatal admissions mentioned cigarette smoking in this population reportedly heroin use. Patients with 90 percent of heroin-related deaths may co-occurring disorders had higher rates of sub- involve concurrent use of other substances stance co-dependence than patients without (Substance Abuse and Mental Health Services co-occurring disorders. Another common regimens that vary throughout the day, for reason is the need to self-medicate withdrawal example, using stimulants in the morning, anxi- symptoms or uncomfortable affects (e. Patientsí initial sub- Effects of Other stance use experiences and continued attrac- Substance Use tion to drugs may indicate enhancementñ avoidance reactions. Overdose or adolescentsí substance use before sex to deaths can occur when alcohol is used alone in avoid accepting responsibility for their high doses or in lower doses with opioid treat- actions). Exhibit 11-3 Drug Com binations and Com m on Reasons for Use Combination Reasons Heroin plus alcohol Enhance a high; create euphoria or sedation Heroin followed by alcohol Medicate opioid withdrawal; medicate cocaine overstimulation (e.
Assuming the samples are Standard collected and stored in the same way and the analysis Instrument Mean Deviation is done by a technologist who is familiar with the Osmometer A 280 mOsm/kg 3 order voltaren 100 mg otc treating arthritis of the hands. The F test is calculated by dividing the variance (s )2 If the critical value for F = 2 purchase 50 mg voltaren free shipping symptoms of arthritis in horses neck. Precision cannot be evaluated statistically when the two instruments) is accepted. D The bias is defined as the difference between the Chemistry/Evaluate laboratory data to assess the means of the two methods and is calculated using validity/Accuracy of procedures/Statistics/3 the formula: bias = y – ×. The student’s t test is used to determine by running 40 paired patient samples in duplicate if bias is statistically significant. Te following results are is the ratio of bias to the standard error of the obtained: mean difference. B Proportional error (slope or percent error) results Method x (reference 235 mg/dL 3. For example, if both level 1 and Assuming the samples are collected and stored level 2 controls for laboratory A average 5 mg/dL in the same way and the analysis done by a below the cumulative mean reported by all technologist who is familiar with both methods, other laboratories using the same method, then what is the bias of method y? When the magnitude of error increases with increasing sample concentration, it is called: A. Bias Chemistry/Evaluate laboratory data to assess validity/ Accuracy of procedures/Statistics/2 5. D A bias plot compares the bias (candidate method minus reference method) to the result of the 5 reference method. When the majority of points is below the zero line, 0 the candidate method is negatively biased (lower than the reference). A The linear regression analysis is the most useful statistic to compare paired patient results because -15 it estimates the magnitude of specific errors. Two methods that measure the same margin analyte will have a high correlation coefficient, C. Te new method is lower than the reference provided the concentrations are measured over a method by 5 mg/dL wide range, and this statistic should not be used D. Te new method is lower than the reference and to judge the acceptability of the new method. Each sample was assayed by both methods within 30 minutes of collection by a technologist familiar with both methods. Linear regression analysis was performed by the least-squares method, and results are as follows: Linear Correlation Standard Error of Regression Coefficient (r) Estimate (sy/x) ŷ=2. Tere is no disagreement between the methods because the correlation coeﬃcient approaches 1. Tere is no systematic error, but the random error of the new method is unacceptable Chemistry/Evaluate laboratory data to assess the validity/Accuracy of procedures/Statistics/2 234 Chapter 5 | Clinical Chemistry 44. False positives Chemistry/Calculation/Speciﬁcity/2 80 Answers to Questions 44–46 60 44. B The scatterplot shows that each sample produces a coordinate (x corresponds to the reference result 40 and y to the candidate method result) that is very close to the regression line. This means that the variance of regression is low and there is a high 20 degree of certainty that the predicted value of y will be close to its measured value. Te methods agree very well but show a high equation for this scatterplot is y = –0. Tere will be a signiﬁcant degree of uncertainty which is equal to (ŷ – xc) where xc is the expected in the regression equation concentration, and ŷ is the value predicted by the D. The probability of false positives is calculated from the speciﬁcity as: % speciﬁcity 1–( ) 100 5. A new tumor marker for ovarian cancer is Answers to Questions 47–50 evaluated for sensitivity by testing serum samples from patients who have been diagnosed by staging 47. C Sensitivity is deﬁned as the percentage of persons biopsy as having malignant or benign lesions. A new test for prostate cancer is found to have a 100, then dividing by the sum of true positives and sensitivity of 80. B Since the concentration of an analyte may not be by the regional population of adults age 18 and normally distributed in a population, the reference older. Te analyte concentration is known to be range should not be determined from the standard independent of race and gender. A minimum of 120 samples is the analyte from 40 healthy adults and calculate needed for statistical significance.
Typical suicide genes include herpes simplex thymidine kinase and Escherichia coli cytosine deaminase generic 100 mg voltaren with mastercard arthritis treatment germany. Although any gene delivery vector may be employed to deliver the gene (see Section 14 trusted 50 mg voltaren arthritis in fingers and wrists. These chemical approaches to advanced drug targeting are embryonic and their future development will be dependent on the “fruits” of the genomic and proteomic revolutions. Even though it may ultimately be possible to develop site-specific chemical drug delivery systems for a wide range of therapeutic applications, there will still be a need to address the challenges of chronopharmacology in order to achieve better therapeutic control. Such control requires means of sensing and responding to changes in biological stimuli. This can be achieved by having either a separate biosensor which electronically controls drug release from a drug delivery device or a combination system in which the stimulus has a direct effect on the release of drug from the system. Such a system quantifies electronic signals arising from the interaction between a biosensor and an analyte of interest. Catalytic biosensors use enzymes, microorganisms, or whole cells to catalyze a reaction with the target analyte, while affinity biosensors utilize antibodies, receptors, or nucleic acids to bind with the target analyte. The integration of biosensors with drug delivery systems allows the controlled release of a drug substance in response to the levels of biological modulator. For example, the use of a glucose biosensor may be used to control the release of insulin from an implanted device or perhaps even an iontophoretic delivery device (see Chapter 8). Following physicians’ recommendation, patients have to frequently test glucose concentrations by collecting blood or urine samples. A closed-loop system, which automatically monitors the change in glucose levels and accordingly dispenses an accurate dose of insulin, would present an ideal insulin therapy for long-term routine patient care. Concerted research efforts to develop an implantable glucose monitor have been driven by the necessity for such an ideal insulin therapy. A presently available external potentiometric glucose sensor has glucose oxidase affixed on the top of a pH electrode. The enzymatic action on glucose leads to the formation of gluconic acid and hydrogen peroxide. An amperometric sensor also depends on the enzyme-catalyzed oxidation of glucose, but measures the change in current as a function of the concentration of hydrogen peroxide. Its implantable device consists of a titanium-encased battery and microprocessor, a silicone-sheathed platinum electrode and glucose oxidase immobilized in a semipermeable membrane. The implantable monitor is about the size of a pacemaker and is connected to an external telemetry device. The structure of the inner enzyme layer attenuates the amount of glucose that permeates through. When the immobilized enzyme is in contact with glucose, it produces gluconic acid and hydrogen peroxide at the expense of oxygen. The resultant change in the ratio of hydrogen peroxide to oxygen affects the current in the sensor, and its signal is transmitted to the receiver outside the body. An accurate blood glucose concentration can be inferred from the levels of glucose in tissue fluids. The implantable glucose monitor is expected to be a convenient, reliable alternative to daily finger sticks or pen-sized external glucose monitors frequently used to check glucose levels in diabetic patients. Although state-of-the-art biosensor technology allows rapid detection of low concentrations of biological molecules, the biofouling of implanted sensors still represents a major challenges. The biosensing mechanism is based on the glucose oxidase-catalyzed oxidation of glucose drawn from tissue fluids. After the enzymatic metabolism, the ratio of hydrogen peroxide to oxygen is detected and expressed by a change in electric current. This signal is transmitted to the receiver outside the body biosensors with serum proteins following implantation reduces the sensitivity and longevity of such devices. Such foreign bodies also elicit an acute inflammatory response which may ultimately result in encapsulation of the implant in a fibrous matrix (see Section 4. Various approaches are presently being investigated to reduce the biofouling and bioincompatibility of such devices including the use of biocompatible coatings. These coatings include systems such as the biomimetic phosphorylcholine-based technologies developed to improve the biocompatibility of medical implants and the poly(ethylene oxide) technologies described in Chapter 5 as means of increasing the circulation times of liposomes.