By L. Gorn. Loyola University, New Orleans.
World Health Organization (2007) International statistical classification of diseases and related health problems discount 150mg epivir-hbv fast delivery, 10th revision (2e) order epivir-hbv 100mg mastercard. American Psychiatric Association (1994) Diagnostic and statistical manual of mental disorders (4e) epivir-hbv 150 mg online. Goldman D purchase 150 mg epivir-hbv amex, Oroszi G & Ducci F (2005) The genetics of addictions: uncovering the genes. House of Commons Science and Technology Select Committee Drug classification: making a hash of it: fifth report of session 2005-2006. European Monitoring Centre for Drugs and Drug Addiction (2011) Annual report on the state of the drugs problem in Europe. Hoare J & Moon D (eds) (2010) Drug misuse declared: findings from the 2009/10 British Crime Survey. Home Office (2012) Drug misuse declared: findings from the 2011/2012 British Crime Survey. The Scottish Government (2012) 2010-11 Scottish crime and justice survey: drug use. Department of Justice (2010) Experience of drug misuse: findings from the 2008/09 Northern Ireland Crime Survey. Hay G, Gannon M, Casey J et al (2011) Estimates of the prevalence of opiate use and/or crack cocaine use, 2009/10: Sweep 6 report. Fuller E (2012) Smoking, drinking and drug use amongst young people in England 2011. Measham F, Moore K, Newcombe R et al (2010) Tweaking, bombing, dabbing and stockpiling: the emergence of mephedrone and the perversity of prohibition. Newcombe R (2004) Attitudes to drug policy and drug laws: a review of the international evidence. Royal Society for the encouragement of Arts, Manufactures and Commerce (2007) Drugs – facing facts. Bailey R, Fuller E & Ormston R (2010) Smoking, drinking and drugs: reaction to reform. Scottish Government (2010) Scottisocial attitudes survey 2009: public attitudes to drugs and drug use in Scotland. Roques B (1999) La dangerosité de drogues: rapport au Secrétariat d’Etat à la Santé. Best D, Gross S, Vingoe L et al (2003) Dangerousness of drugs: a guide to the risks and harms associated witubstance use. Rolles S & Measham F (2011) Questioning the method and utility of ranking drug harms in drug policy. Nutt D (2011) Let not the best be the enemy of the good: a reply to Caulkins et al. Room R (2011) Scales and blinkers, motes and beams: whose view is obstructed on drug scheduling? Darke S & Hall W (2003) Heroin overdose: research and evidence-based intervention. Darke S, Degenhardt L & Mattik R (2007) Mortality amongst illicit drug users: epidemiology, causes and intervention. O’Driscoll P, McGough J, Hogan H et al (2001) Predictors of accidental fatal drug overdose among a cohort of injection drug users. Warner-Smith M, Darke S, Lynskey M et al (2001) Heroin overdose: causes and consequences. Favrod-Coune T & Broers B (2010) The health effect of psychostimulants: a literature review. Singleton J, Degenhardt L, Hall W et al (2009) Mortality among amphetamine users: a systematic review of cohort studies. Srisurapanont M, Ali R, Marsden J et al (2003) Psychotic symptoms in methamphetamine psychotic in- patients. Aldington S, Harwood M, Cox B et al (2008) Cannabis use and risk of lung cancer: a case-control study. Hall W (2009) The adverse health effects of cannabis use: what are they, and what are their implications for policy? Kuepper R, Van Os J, Lieb R et al (2011) Continued cannabis use and risk of incidence and persistence of psychotic symptoms: 10 year follow-up cohort study. Advisory Council on the Misuse of Drugs (2008) Cannabis: classification and public health. Arseneault L, Cannon M, Witton J et al (2004) Causal association between cannabis and psychosis: examination of the evidence. Rubino T, Zamberletti E & Parolaro D (2012) Adolescent exposure to cannabis as a risk factor for psychiatric disorders. Macleod J, Oakes R, Copello A et al (2004) Psychological and social sequelae of cannabis and other illicit drug use by young people: a systematic review of longitudinal, general population studies. A scientific statement from the American Heart Association Acute Cardiac Care Committee of the Council on Clinical Cardiology. Darke S, Kaye S & Duflou J (2006) Comparative cardiac pathology among deaths due to cocaine toxicity, opioid toxicity and non-drug-related causes. Kaye S & Darke S (2004) Non-fatal cocaine overdose among injecting and non-injecting cocaine users in Sydney, Australia. Alaraj A, Wallace A, Mander N et al (2010) Effect of acute cocaine use on vasospasm and outcome in aneurysmal subarachnoid hemorrhage. Kaye S & Darke S (2004) Injecting and non-injecting cocaine use in Sydney, Australia: physical and psychological morbidity. European Monitoring Centre for Drugs and Drug Addiction (2007) Cocaine and crack cocaine: a growing public health issue. Darke S, Kaye S & Duflou J (2005) Cocaine related fatalities in New South Wales, Australia 1993-2002. Rogers G, Elston J, Garside R et al (2009) The harmful health effects of recreational ecstasy: a systematic review of observational evidence. Miotto K, Darakjian J, Basch J et al (2001) Gamma-hydroxybutyric acid: patterns of use, effects and withdrawal. Hickman M, Carnwath Z, Madden P et al (2003) Drug-related mortality and fatal overdose risk: pilot cohort study of heroin users recruited from specialist drug treatment sites in London. Smyth B, Hoffman V, Fan J et al (2007) Years of potential life lost among heroin addicts 33 years after treatment. Shahani R, Streutker C, Dickson B et al (2007) Ketamine-associated ulcerative cystitis: a new clinical entity. European Monitoring Centre for Drugs and Drug Addiction (2009) Polydrug use: patterns and responses. Cruts G, Buster M, Vicente J et al (2008) Estimating the total mortality among problem drug users. British Medical Association (2007) Fetal alcohol spectrum disorders – a guide for healthcare professionals.
General study would be the same for a given factor or across For original applications buy 150 mg epivir-hbv otc, a matrixing design should different factors should be provided if available buy epivir-hbv 100mg overnight delivery. Data Evaluation months proven 150 mg epivir-hbv, that is buy epivir-hbv 100mg low price, at least three time points including the initial and 12-month time points. This approach is espe- The stability data obtained under a matrixing protocol cially important if the original application contains less should be subjected to the same type of statistical analysis than full long-term data at the time of submission. The same principle and procedure on attributes, different matrixing designs for different poolability (i. The only exception is that, if necessary, the drug product (two of which should be at least pilot it is acceptable to revert back to full stability testing during scale); reference is made to the drug substance and drug the study. Size of Matrixing Design batches should be made, this section provides recommen- The appropriate size of a matrix is generally related to the dations on site-speciﬁc stability data: the number and size number of combinations of factors and the amount of of drug substance and drug product stability batches made supportive data available. The size of a matrixing design at the intended manufacturing-scale production sites, and is expressed as a fraction of the total number of samples the length of stability data on these batches, for an original to be tested in the corresponding full stability protocol. Applicants are For a product available in three batches, three strengths, advised to consult with the respective chemistry review and three container or ﬁll sizes, the number of combina- team when questions arise. The larger the number of In principle, primary stability batches should be made at combinations of factors to be tested and the greater the the intended commercial site. If the primary stability amount of available supportive data, the smaller the size batches are not made at the intended commercial site, Stability Testing of Drug Substances and Drug Products 49 stability data from the drug substance product batches batches are made is located at the intended commercial manufactured at that site (i. If at the time ommendations are met (provided the processes and equip- of application submission there are 12 months of long- ment are the same) and no additional data will be needed. In addition, these site-speciﬁc batches may recommendations above would be applicable to each site. If the primary stability batch or batches are not primary stability data from another site, should be pro- made at the intended commercial site, stability data should vided at the time of application submission. Three site-speciﬁc batches are needed for a on the same campus as the intended commercial facility), complex dosage form to provide an independent and sta- the site-speciﬁc stability recommendations are met and no tistically meaningful stability proﬁle for the product made additional data will be needed. One site-speciﬁc batch may be sufﬁcient to made to place the ﬁrst three production batches and annual verify the stability proﬁle of a simple dosage form. Other factors, such as lack of experience at the new For complex dosage forms as described in the previous site in a particular dosage form or difference in the envi- section, a reduced number of site-speciﬁc batches may be ronmental conditions between the sites, can potentially justiﬁed if accelerated and long-term data are available at affect the quality or stability of a drug product. Therefore, the time of application submission on batches made at a one site-speciﬁc batch may not be sufﬁcient in these cases. General statistical analysis for the establishment of a retest period or expiration dating period. Q1B does not speciﬁcally cesses and equipment of the same design and operating address other photostability studies that may be needed to principles. If different processes or equipment are used, support, for example, the photostability of a product under more site-speciﬁc batches or longer duration of data are in-use conditions or the photostability of analytical sam- recommended. For example, if a product has been The extent of drug product testing should be established determined to photodegrade on direct exposure but is ade- by assessing whether acceptable change has occurred quately protected by packaging, an in-use study may be at the end of the light exposure testing. Light Sources Under some circumstances, photostability studies should be repeated if certain postapproval or supplemental changes, The light sources described below may be used for pho- such as changes in formulation or packaging, are made to tostability testing. The applicant should either maintain an the product or if a new dosage form is proposed. Whether appropriate control of temperature to minimize the effect these studies should be repeated depends on the photosta- of localized temperature changes or include a dark control bility characteristics determined at the time of initial ﬁling in the same environment unless otherwise justiﬁed. For example, if initial studies both options 1 and 2, a pharmaceutical manufacturer or demonstrate that an active moiety in a simple solution applicant can rely on the spectral distribution speciﬁcation degrades on exposure to light and the tablet drug product is of the light-source manufacturer. Option 1 dosage form may warrant additional studies to characterize Option 1 is any light source that is designed to produce the photostability characteristics of the new dosage form. If deviations in packaging or labeling state- source emitting signiﬁcant radiation below 320 nm, an ments are made, additional studies may be recommended. Option 2 The intrinsic photostability characteristics of new drug For option 2 the same sample should be exposed to both substances and products should be evaluated to demon- the cool white ﬂuorescent and the near-ultraviolet lamp. An example of an actino- should be chosen to provide minimal interference with the metric procedure is provided in the Annex. For drug substances, photostability testing should consist Solid drug substances should be spread across the con- of two parts: forced degradation testing and conﬁrmatory tainer to give a thickness of typically not more than 3 mm. Drug substances that are liquids should be exposed in The purpose of forced degradation testing studies is chemically inert and transparent containers. This testing may involve the drug substance At the end of the exposure period, the samples should alone or in simple solutions or suspensions to validate the be examined for any changes in physical properties analytical procedures. In these assay and degradants by a method suitably validated for forced degradation studies, a variety of exposure condi- products likely to arise from photochemical degradation tions may be used, depending on the photosensitivity of processes. For development and validation purposes, sampling should ensure that a representative portion is it is appropriate to limit exposure and end the studies if used in individual tests. For photostable materi- ations, such as homogenization of the entire sample, als, studies may be terminated after an appropriate expo- apply to other materials that may not be homogeneous sure level has been used. The analysis of the exposed sample is left to the applicant’s discretion, although the exposure should be performed concomitantly with that of any levels used should be justiﬁed. Judgment of Results may be useful in developing and validating suitable ana- The forced degradation studies should be designed to pro- lytical methods. If, in practice, it has been demonstrated vide suitable information to develop and validate test they are not formed in the conﬁrmatory studies, these methods for the conﬁrmatory studies. If the results of the con- of the drug product and if light-resistant packaging is ﬁrmatory study are equivocal, testing of up to two additional needed. Samples should be selected ies to determine whether change caused by exposure to as described in the parent guidance. Some adjustment of testing conditions may have to be made when testing large-volume containers Normally, the studies on drug products should be carried (e. Analysis of Samples product in the immediate pack and then in the marketing At the end of the exposure period, the samples should be pack. Testing should progress until the results demonstrate examined for any changes in physical properties (e. For solid oral dosage–form products, testing should conﬁrmatory study are equivocal, testing of up to two be conducted on an appropriately sized composite of, for additional batches should be conducted. Similar sampling consid- For some products where it has been demonstrated that erations, such as homogenization or solubilization of the the immediate pack is completely impenetrable to light, entire sample, apply to other materials that may not be such as aluminum tubes or cans, testing should normally homogeneous after exposure (e. The analysis of the exposed sample should be It may be appropriate to test certain products, such as performed concomitantly with that of any protected sam- infusion liquids or dermal creams, to support their photo- ples used as dark controls if they are used in the test. Judgment of Results on and relate to the directions for use and is left to the applicant’s discretion. Depending on the extent of change, special labeling or The analytical procedures used should be suitably val- packaging may be needed to mitigate exposure to light.
Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic people generic epivir-hbv 150mg on line. It has been reported that sulfamethoxazole; trimethoprim may prolong the prothrombin time in patients who are receiving the anticoagulant warfarin buy epivir-hbv 100 mg on line. This interaction should be kept in mind when sulfamethoxazole; trimethoprim is given to patients already on anticoagulant therapy cheap epivir-hbv 150 mg without prescription, and the coagulation time should be reassessed order epivir-hbv 100 mg fast delivery. Allergic Reactions: Stevens-Johnson syndrome, toxic epidermal necrolysis, anaphylaxis, allergic myocarditis, erythema multiforme, exfoliative dermatitis, angioedema, drug fever, chills. Henoch-Schoenlein purpura, serum sickness-like syndrome, generalized allergic reactions, generalized skin eruptions, conjunctival and scleral injection, photosensitivity, pruritus, urticaria and rash. In addition, periarteritis nodosa and systemic lupus erythematosus have been reported. Gastrointestinal: Hepatitis (including cholestatic jaundice and hepatic necrosis), elevation of serum transaminase and bilirubin, pseudomembranous enterocolitis, pancreatitis, stomatitis, glossitis, nausea, emesis, abdominal pain, diarrhoea, anorexia. Neurologic: Aseptic meningitis, convulsions, peripheral neuritis, ataxia, vertigo, tinnitus, headache. Diuresis and hypoglycaemia have occurred rarely in patients receiving sulfonamides. Cyclizine may be mixed with morphine in a syringe immediately before use If cyclizine must be diluted in a syringe, either water for injection or 5% dextrose is recommended as the diluent rather than normal saline. In such patients, cyclizine may cause a fall in cardiac output associated with increases in heart rate, mean arterial pressure and pulmonary wedge pressure. Because of its anticholinergic activity cyclizine may enhance the side-effects of other anticholinergic drugs. Respiratory System: dryness of the mouth, nose and throat Cardiovascular System: tachycardia Gastrointestinal System: Cholestatic jaundice, constipation, hypersensitivity hepatitis Haematological System: agranulocytosis Urogenital System: Urinary retention, Skin: Urticaria, drug rash Cyclizine! Patients admitted to the intensive care unit may be on cyclosporin at the time of admission for the following indications: 1. Ensure concentrate is well mixed in diluent fluid to reduce risk of an initial bolus of heavier non-solubilised polyoxyethylated castor oil, which carries an increased risk of anaphylactoid reactions. Visually inspect infusion concentrated and infusion solution for particulate matter and / or discolouration. Laboratory Tests: Cyclosporin has a narrow therapeutic index and variable pharmacokinetics and so monitoring of therapy is mandatory in the critically ill. C0 sampling has been widely used although it appears that C0 is only a weak indicator of absorption of drug. Moreover, the results are assay-dependent as samples of this type contain a large proportion of metabolite that may interfere. Moreover, most of the measured drug found at this time is parent drug, making the measurement relatively free of interference from metabolites. A disadvantage of C2 is the need for samples to be taken close to the 2-hour time-point (+ or -15 minutes). Factors affecting the target ranges for treatment include time of sampling (C0 or C2), organ transplanted, time since transplantation, and other medications. More specific recommended target concentrations for transplant patients are as follows. They may vary in individual cases on the basis of age, gender, renal function, number of episodes of rejection, and concomitant immunosuppressive medication. Target trough (C0) ranges are as follows: Liver: Induction 225-300 ng/mL Maintenance 100-150 ng/mL Heart: Induction 250-325 ng/mL Maintenance 125-175 ng/mL Kidney: Induction 150-225 ng/mL Maintenance 100-180 ng/mL Bone Marrow: Induction 95-205 ng/mL Maintenance 95-205 ng/mL Autoimmune indications: Induction 150-200 ng/mL Maintenance 100-150 ng/mL Target C2 ranges are as follows: Liver: 0-3 months post transplant 800-1200 ng/mL 3-6 months post transplant 640-960 ng/mL >6 months post transplant 480-720 ng/mL Renal: 1 months post transplant 1360-2040 ng/mL 2 months post transplant 1200-1800 ng/mL 3 months post transplant 1040-1560 ng/mL 4-6 months post transplant 880-1320 ng/mL 7-12 months post transplant 720-1080 ng/mL >12 months post transplant 640-960 ng/mL Lung: 0-2 days post transplant >800 1-7 days post transplant 1200 1-4 weeks post transplant 1200-1700 2 months post transplant 1000-1500 3 months post transplant 800-1200 4-6 months post transplant 700-1000 7-12 months post transplant 600-900 >12 months post transplant 600-800 Cyclosporin! Drugs That Alter Cyclosporin Concentrations Cyclosporin is extensively metabolized cytochrome P-450 3A. Substances that inhibit this enzyme could decrease metabolism and increase cyclosporin concentrations. Substances that are inducers of cytochrome P-450 activity could increase metabolism and decrease cyclosporin concentrations. Monitoring of circulating cyclosporin concentrations and appropriate dosage adjustment are essential when these drugs are used concomitantly. Drugs That Increase Cyclosporin Concentrations Calcium Channel Blockers: Diltiazem, nicardipine, verapamil. Other Drugs: Allopurinol, bromocriptine, danazol, metoclopramide, colchicine, amiodarone. Severe digitalis toxicity has been seen within days of starting cyclosporin in several patients taking digoxin. There are also reports on the potential of cyclosporin to enhance the toxic effects of colchicine such as myopathy and neuropathy, especially in patients with renal dysfunction. Cyclosporin should not be used with potassium-sparing diuretics because hyperkalaemia can occur. A large bore, vented needle (as found in the malignant hyperthermia box in theatre) will hasten the transfer of diluent and reconstituted solution. Reconstituted solution should be stored at room temperature and must be protected from direct light. The usual dose for chronic spasticity is between 25mg daily and 50mg four times a day. It is hypothesized that addition of dantrolene to the "triggered" malignant hyperthermic muscle cell! Inhibition of calcium release from the sarcoplasmic reticulum by dantrolene re-establishes the myoplasmic calcium equilibrium, increasing the percentage of bound calcium. These measures must be individualized, but it will usually be necessary to discontinue the suspect triggering agents, attend to increased oxygen requirements, manage the metabolic acidosis, institute cooling when necessary, monitor urinary output, and monitor for electrolyte imbalance. Fatal and non-fatal liver disorders of an idiosyncratic or hypersensitivity type may occur with dantrolene therapy. Administration of dantrolene may potentiate vecuronium-induced neuromuscular block. The following events have been reported in patients receiving oral dantrolene: Hepatitis, seizures, pericarditis, aplastic anaemia, leukopaenia, lymphocytic lymphoma, and heart failure. For doses of greater than 4mcg in adults or children weighing more than 10kg, dilute with 50ml of normal saline and infuse the first 5ml slowly over 5 minutes. For children weighing less than 10kg, dilute in 10ml of normal saline and infuse the first 1-2ml over 5 minutes. Particular attention should be paid to the possibility of the rare occurrence of an extreme decrease in plasma osmolality that may result in seizures which could lead to coma. The drug should be used with caution in patients with coronary artery insufficiency and/or hypertensive cardiovascular disease. There have been rare reports of thrombotic events following desmopressin acetate Severe allergic reactions have been reported rarely. Laboratory Tests: Laboratory tests for monitoring the patient include urine volume and osmolality.
In assessing different modes of regulation best epivir-hbv 150 mg, we fnd both authorities pursuing different aims generic epivir-hbv 100mg on line, using different tools and treating different objects buy epivir-hbv 150mg on-line. The deputation was clearly an institution in which scientifc values dovetailed with professional interests purchase epivir-hbv 150mg. But the Medical Department had frst and foremost to take political and especially economic interests into account. Searching for cheap alternatives, looking for home-grown plants such as poppy or rhubarb, and encouraging new methods of treatment for epidemic diseases were important considerations in the minds of ministerial authorities. But let us look frst at the professional way of regulation: The aims of physicians and scientists were clear. Their practical and technical assessment served primarily to prevent the sale of secret remedies (table 2). The technical assessment was especially demanding: of the one hundred examinations conducted in the frst half of the century, only six resulted in positive reports. Compared with the clinical trials, of which a ffth returned positive results, the theoretical assessment was considerably morearduous. The experts of the Scientifc Deputation found very different reasons for rejecting petitions. First, the experts challenged the remedy’s supposed worth und therapeutic applicability. Some applicants were advised that “this disease could just as easily be cured using known remedies”. Cunz’s coagulant remedy (report of Klug, Horn, Schmidt), 29 Volker Hess components if the “mixture was less powerful than the similar, popular one”. However, instead of targeting the substances, it was directed at applicants themselves. The central issue here was the popular belief in panaceas, from which academic medicine had only recently distanced itself. The reports often seem to express relief at not having to deal with such superstitious relics. Examining such treatment was rather absurd and [sic] could not be demanded of scientifc experts. He had “recklessly specifed the quantities and volumes – what else can one expect from a potion that did nothing more than enhance his self-delusion”. In the early 1850s, long before the new pathological anatomy came to be widely used in rejecting applications, a report noted that “A toothache is not a specifc disease. The members of the board represented the medical and scientifc elite of the Prussian capital. The physicians, pharmacists, and chemists didn’t hesitate to use the board to advance their own interests. They regarded themselves as gatekeepers to the medical market where they tried hard to 28 November 1846, 2121, Ibid. Die Entstehung der klinischen Methode zwischen 1750 und 1850 (= Abhandlungen zur Geschichte der Medizin und der Naturwissenschaften. Kluge about the therapeutic experiments with Schramm’s remedy against arterial rheumatism. They mobilized both the technical facilities for analyzing the chemistry of compositions and the social skills needed to fnd information in natural history networks. In doing so, they reduced the verbose applications to a formalized regime which also seemed to shift the evaluation away from the realm of a moral economy. The fourth, frequent, and decisive argument shows, however, that the examination of secret remedies was not governed by professional interests alone. This meant examining remedies to determine whether “their formulas were new, and their ingredients and mixture unused”. In principal, the deputation accepted that is was possible to mix the drugs listed in the pharmacopoeia to produce new and powerful remedies. Thus, the remedies had to involve more than a simple modifcation of the recipes found in the Materia Medica. Oftentimes, the applicants must have been aware that the carefully guarded formula was known and had been published long ago. Like patent offcers, the members of the Scientifc Deputation consulted long registers for the medication. In the case of Seewald’s gout balsam, the referee of the Medical Faculty was convinced that the remedy “represented a distinctly new kind of medicine due to the way in which the inventor had prepared it”. The Deputation decided to deny the submission without further investigation because the ingredients and mixture had already been published in Phoebus’s Arzneiverordnungslehre58. Comparing the arguments of producers and professionals reveals that the two rarely overlapped. Indeed, the clash between both reference systems indicates how regulation began to shift secret remedies into a new framework. While the applicants referred to the traditional regimes of poor relief and enlightened humanity, the deputation was mired in a web of competing interests, maxims and concepts. On the one hand, the members of Deputation were not able to ignore their professional background, on the other they tried to operationalize the criteria for an “invention”. Among other things59 they watched the markets for secret remedies in France or the Netherlands in search of new developments. Offcials poured over newspapers and magazines, carefully watching public debates in hopes of discovering new drugs, remedies, or therapeutic regimes for the Prussian state. Thus the ministry dealt with issues of public health as well as with the tasks 55 Ministry of Cultural Affairs to the Scientifc Deputation, 6 January 1846, 1 0 (Acta, betr. The offcers, physicians, and scientists were all well aware of the web of interests and maxims which arose from their conficting roles and functions. It may be that the Prussian reforms sensitized them to this organizational confict of interests. Defned as a “purely scientifc advisory board”, the Deputation was neither subordinated to nor integrated into regular administrative decision-making mechanisms. Consequently, the physicians and scientists seemed to distinguish carefully between their roles as state offcers and scientifc experts. The best example was Johann Nepomuk Rust, a key fgure in the reorganization of the Prussian bureaucracy. Rust was part of the medical establishment, holding positions at the Charité hospital, the Berlin University, and the academy of military medicine. He infuenced the medical landscape of the period as a medical attendant to the Prussian King, as president of the hospital committee, and as council to the ministry of culture. In the 1830s he published a critique of the relationship between politics and science. Concerning the reform era, Rust emphasized that modern bureaucracy depended upon and could not function without scientifc expertise.
8 of 10 - Review by L. Gorn
Votes: 346 votes
Total customer reviews: 346