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The inferior colliculus is the inferior pair of these enlargements and is part of the auditory brain stem pathway 120 mg cardizem amex. Neurons of the inferior colliculus project to the thalamus order cardizem cheap, which then sends auditory information to the cerebrum for the conscious perception of sound buy cardizem visa. The superior colliculus is the superior pair and combines sensory information about visual space buy generic cardizem from india, auditory space, and somatosensory space. If you are walking along the sidewalk on campus and you hear chirping, the superior colliculus coordinates that information with your awareness of the visual location of the tree right above you. If you suddenly feel something wet fall on your head, your superior colliculus integrates that with the auditory and visual maps and you know that the chirping bird just relieved itself on you. Throughout the midbrain, pons, and medulla, the tegmentum contains the nuclei that receive and send information through the cranial nerves, as well as regions that regulate important functions such as those of the cardiovascular and respiratory systems. It is visible on the anterior surface of the brain stem as the thick bundle of white matter attached to the cerebellum. The bridge-like white matter is only the anterior surface of the pons; the gray matter beneath that is a continuation of the tegmentum from the midbrain. Gray matter in the tegmentum region of the pons contains neurons receiving descending input from the forebrain that is sent to the cerebellum. The initial portion of the name, “myel,” refers to the significant white matter found in this region—especially on its exterior, which is continuous with the white matter of the spinal cord. The tegmentum of the midbrain and pons continues into the medulla because this gray matter is This OpenStax book is available for free at http://cnx. A diffuse region of gray matter throughout the brain stem, known as the reticular formation, is related to sleep and wakefulness, such as general brain activity and attention. The cerebellum is largely responsible for comparing information from the cerebrum with sensory feedback from the periphery through the spinal cord. Those neurons project into the cerebellum, providing a copy of motor commands sent to the spinal cord. Sensory information from the periphery, which enters through spinal or cranial nerves, is copied to a nucleus in the medulla known as the inferior olive. Fibers from this nucleus enter the cerebellum and are compared with the descending commands from the cerebrum. If the primary motor cortex of the frontal lobe sends a command down to the spinal cord to initiate walking, a copy of that instruction is sent to the cerebellum. Sensory feedback from the muscles and joints, proprioceptive information about the movements of walking, and sensations of balance are sent to the cerebellum through the inferior olive and the cerebellum compares them. If walking is not coordinated, perhaps because the ground is uneven or a strong wind is blowing, then the cerebellum sends out a corrective command to compensate for the difference between the original cortical command and the sensory feedback. The 566 Chapter 13 | Anatomy of the Nervous System output of the cerebellum is into the midbrain, which then sends a descending input to the spinal cord to correct the messages going to skeletal muscles. Whereas the brain develops out of expansions of the neural tube into primary and then secondary vesicles, the spinal cord maintains the tube structure and is only specialized into certain regions. The anterior midline is marked by the anterior median fissure, and the posterior midline is marked by the posterior median sulcus. Axons enter the posterior side through the dorsal (posterior) nerve root, which marks the posterolateral sulcus on either side. Note that it is common to see the terms dorsal (dorsal = “back”) and ventral (ventral = “belly”) used interchangeably with posterior and anterior, particularly in reference to nerves and the structures of the spinal cord. On the whole, the posterior regions are responsible for sensory functions and the anterior regions are associated with motor functions. This comes from the initial development of the spinal cord, which is divided into the basal plate and the alar plate. The basal plate is closest to the ventral midline of the neural tube, which will become the anterior face of the spinal cord and gives rise to motor neurons. The alar plate is on the dorsal side of the neural tube and gives rise to neurons that will receive sensory input from the periphery. The length of the spinal cord is divided into regions that correspond to the regions of the vertebral column. The name of a spinal cord region corresponds to the level at which spinal nerves pass through the intervertebral foramina. Immediately adjacent to the brain stem is the cervical region, followed by the thoracic, then the lumbar, and finally the sacral region. The spinal cord is not the full length of the vertebral column because the spinal cord does not grow significantly longer after the first or second year, but the skeleton continues to grow. The nerves that emerge from the spinal cord pass through the intervertebral formina at the respective levels. As the vertebral column grows, these nerves grow with it and result in a long bundle of nerves that resembles a horse’s tail and is named the cauda equina. Gray Horns In cross-section, the gray matter of the spinal cord has the appearance of an ink-blot test, with the spread of the gray matter on one side replicated on the other—a shape reminiscent of a bulbous capital “H. The lateral horn, which is only found in the thoracic, upper lumbar, and sacral regions, is the central component of the sympathetic division of the autonomic nervous system. The motor neuron that causes contraction of the big toe, for example, is located in the sacral spinal cord. The neuronal cell body that maintains that long fiber must be quite large, possibly several hundred micrometers in diameter, making it one of the largest cells in the body. Ascending tracts of nervous system fibers in these columns carry sensory information up to the brain, whereas descending tracts carry motor commands from the brain. Looking at the spinal cord longitudinally, the columns extend along its length as continuous bands of white matter. Between the two anterior horns, and bounded by the axons of motor neurons emerging from that gray matter area, are the anterior columns. The white matter on either side of the spinal cord, between the posterior horn and the axons of the anterior horn neurons, are the lateral columns. The anterior and lateral columns are composed of many different groups of axons of both ascending and descending tracts—the latter carrying motor commands down from the brain to the spinal cord to control output to the periphery. Basal Nuclei Parkinson’s disease is a disorder of the basal nuclei, specifically of the substantia nigra, that demonstrates the effects of the direct and indirect pathways. Without that modulatory influence, the basal nuclei are stuck in the indirect pathway, without the direct pathway being activated. The increased activity of the indirect pathway results in the hypokinetic disorder of Parkinson’s disease. Parkinson’s disease is neurodegenerative, meaning that neurons die that cannot be replaced, so there is no cure for the disorder. With levels of the precursor elevated, the remaining cells of the substantia nigra pars compacta can make more neurotransmitter and have a greater effect. According to one hypothesis about the expansion of brain size, what tissue might have been sacrificed so energy was available to grow our larger brain? Based on what you know about that tissue and nervous tissue, why would there be a trade-off between them in terms of energy use? To protect this region from the toxins and pathogens that may be traveling through the blood stream, there is strict control over what can move out of the general systems and into the brain and spinal cord. The next branches give rise to the common carotid arteries, which further branch into the internal carotid arteries. The bases of the common carotids contain stretch receptors that immediately respond to the drop in blood pressure upon standing. The orthostatic reflex is a reaction to this change in body position, so that blood pressure is maintained against the increasing effect of gravity (orthostatic means “standing up”). Heart rate increases—a reflex of the sympathetic division of the autonomic nervous system—and this raises blood pressure. Branches off the left and right vertebral arteries merge into the anterior spinal artery supplying the anterior aspect of the spinal cord, found along the anterior median fissure. The two vertebral arteries then merge into the basilar artery, which gives rise to branches to the brain stem and cerebellum. The left and right internal carotid arteries and branches of the basilar artery all become the circle of Willis, a confluence of arteries that can maintain perfusion of the brain even if narrowing or a blockage limits flow through one part (Figure 13. The circle of Willis is a specialized arrangement of arteries that ensure constant perfusion of the cerebrum even in the event of a blockage of one of the arteries in the circle. The animation shows the normal direction of flow through the circle of Willis to the middle cerebral artery. Where would the blood come from if there were a blockage just posterior to the middle cerebral artery on the left? The superior sagittal sinus drains to the confluence of sinuses, along with the occipital sinuses and straight sinus, to then drain into the transverse sinuses.
Congenital buy generic cardizem 120mg line, as well as acquired order cardizem 120 mg with visa, valvular disease of non- rheumatic origin has to be excluded buy cardizem uk. Echocardiography may assist physicians to decide the timing of surgical intervention for diseased valves (29) cheap cardizem online master card. These ﬁndings are easily and accurately detected and displayed by echocardiography. Echocardiographic images reveal: (i) a regurgitant jet >1cm in length; (ii) a regurgitant jet in at least two planes; (iii) a mosaic colour jet with a peak velocity >2. Based on the presence of very mild “silent but signiﬁcant” valvular regurgitation, a new category of “subclinical carditis”, “echocarditis” or “asymptomatic carditis” has been proposed in patients with chorea and polyarthritis (30–35, 37, 41, 42). In such cases of subclinical rheu- matic carditis, annular dilatation, leaﬂet prolapse, and elongation of the anterior mitral chordae were observed, indicating that the valve might have been sensitized or damaged (30, 33). Patients with sub- clinical valvular regurgitation may develop an audible murmur in two weeks (31), may continue without audible murmur for 18 months to ﬁve years (35–37), or may progress to irreversible sequelae, such as mitral stenosis (35). Although other studies do not support these ﬁndings (10, 43, 44), 2D echo-Doppler echocardiography detected trivial-to-mild mitral valvular regurgitation in 38–45% of normal/ healthy children (7, 9, 10), and in even higher proportions of febrile patients (10). These results conﬁrm the usefulness of 2D echo-Doppler and colour ﬂow Doppler echocardiography for diagnosing subclinical rheumatic carditis. However, the use of echocardiography to detect left-side valvular regurgitation and conﬁrm a diagnosis of subclinical rheu- matic carditis remains controversial. As such, until the results of long- term encompassing prospective studies are available to substantiate the therapeutic and prognostic importance of subclinical rheumatic carditis, the addition of this criterion to the Jones criteria cannot be justiﬁed (10, 43–47). However, the acute management of such patients and the duration of secondary prophylaxis would not change signiﬁcantly, even if a diagnosis of subclinical carditis were made (10, 43, 44). It is also important to recognize that technical expertise with colour ﬂow Doppler echocardiography is necessary to make an accurate diagnosis of subclinical carditis and to avoid overdiagnosis. As a 44 result, the impact of erroneous diagnoses of rheumatic carditis based on subclinical echocardiographic ﬁndings should not be underesti- mated, nor should the potentially adverse consequences to patients and health systems in such settings (10, 44). Conclusions: the advantages and disadvantages of Doppler echocardiography There are signiﬁcant advantages in using echocardiography to detect valvulitis. Foremost, is its superior sensitivity in detecting rheumatic carditis, which should prevent patients with carditis from being misclassiﬁed as noncarditic and placed on abbreviated secondary pro- phylaxis, in line with the more benign prognosis. It is reasonable to accept that valvular regurgitation may not always be detected by routine clinical auscultation. This suggests that carditis was missed by clinical examination, even in the golden era of clinical auscultation. A second advantage of echocardiography is that it should allow the valve structure to be detected, as well as nonrheumatic causes of valvular dysfunction (e. This could be ascribed either to the high sensitivity of Doppler echocardiography for diagnosing valvular regurgitation, or to the overdiagnosis of physiological valvular regurgitation as an organic dysfunction, or to both. But in many developing countries, it is unreasonable to expect that previous echocardiograms or records will be available for comparison. Transesophageal echocardiography: technique, anatomic correlations, implementation, and clinical applications. Role of echocardiography in the diagnosis and follow-up evaluation of rheumatic carditis. Directions for the use of intracardiac high-frequency ultrasound scanning for monitoring pediatric interventional catheterization procedures. Three-dimensional and four-dimensional transesophageal echocardiographic imaging of the heart and aorta in humans using a computed tomographic imaging probe. Prevalence of rheumatic fever and rheumatic heart disease in school children of Kathmandu city. The prevalence of valvular regurgitation in children with structurally normal hearts: a colour Doppler echocardiographic study. Is continuous wave Doppler too sensitive in diagnosing pathologic valvular regurgitation? Evidence against a myocardial factor as the cause of left ventricular dilation in active rheumatic carditis. Echocardiographic evaluation of patients with acute rheumatic fever and rheumatic carditis. Inﬂammatory valvular prolapse produced by acute rheumatic carditis: echocardiographic analysis of 66 cases of acute rheumatic carditis. Quantitative assessment of mitral regurgitation by Doppler colour ﬂow imaging: angiographic and hemodynamic correlations. Semiquantitative assessment of mitral regurgitation by Doppler colour ﬂow imaging in patients aged <20 years. Noninvasive estimation of left ventricular end-diastolic pressure using transthoracic Doppler-determined pulmonary venous atrial ﬂow reversal. American Heart Association guidelines for the diagnosis of rheumatic fever: Jones criteria, 1992 update. Long-term outcome of patients with rheumatic fever receiving benzathine penicillin G prophylaxis every three weeks versus every four weeks. Three-versus four-week administration of benzathine penicillin G: effects on incidence of streptococcal infections and recurrences of rheumatic fever. Role of echocardiography in the timing of surgical intervention for chronic mitral and aortic regurgitation. Doppler echocardiographic ﬁndings of mitral and aortic valvular regurgitation in children manifesting only rheumatic arthritis. Echocardiographic diagnosis of subclinical carditis in acute rheumatic fever (editorial). Usefulness of echocardiography in detection of subclinical carditis in acute rheumatic polyarthritis and rheumatic chorea. Advocacy for echocardiography in Jones criteria for the diagnosis of rheumatic fever. Manila, Philippine Foundation for the Prevention and Control of Rheumatic Fever and Rheumatic Heart Disease, 2001:27–33. Prospective comparison of clinical and echocardiographic diagnosis of rheumatic carditis: long term follow up of patients with subclinical disease. Intravenous immunoglobulin in acute rheumatic fever: a randomized controlled trial. Occurrence of valvular heart disease in acute rheumatic fever without evident carditis: colour ﬂow Doppler identiﬁcation. A common colour ﬂow Doppler ﬁnding in the mitral regurgitation of acute rheumatic fever. Doppler echocardiography distinguishes between physiologic and pathologic “silent” mitral regurgitation in patients with rheumatic fever. Persistence of acute rheumatic fever in the intermountain area of the United States. The value of echocardiography in the diagnosis and follow up of rheumatic carditis in children and adolescents: a 2 years prospective study. Echocardiographic evaluation of patients with acute rheumatic fever and rheumatic carditis. American Heart Association guidelines for the diagnosis of rheumatic fever: Jones criteria, updated 1992. A long-term epidemiologic study of subsequent prophylaxis, streptococcal infections, and clinical sequelae. Relation of the rheumatic fever recurrence rate per streptococcal infection to preexisting clinical features of the patients. A long- term epidemiologic study of subsequent prophylaxis, streptococcal infections, and clinical sequelae. The teaching and practice of cardiac auscultation during internal medicine and cardiology training. The microbiol- ogy laboratory plays an important role in ensuring that the documen- tation of group A streptococcal infections is accurate. It does so by using scientiﬁc methods both to determine whether group A strepto- cocci (Streptococcus pyogenes) are present on swabs from suspected streptococcal throat infections, and to measure streptococcal serum antibody titres for documenting previous infection. The conventional methods and procedures for serologically identifying group A strep- tococcal infections are described elsewhere (3).
These granules appear bluish purple or bluish black when observed microscopically on a stained blood smear buy cheapest cardizem and cardizem. Basophilic stippling Erythrocyte inclusions composed of precipitated ribonucleoprotein and mitochondrial remnant buy cheap cardizem 180mg. Observed on Romanowsky stained blood smears as diffuse or punctate bluish black granules in toxic states such as drug (lead) exposure cardizem 120 mg online. Bilineage leukemia A leukemia that has two separate populations of leukemic cells order cardizem with visa, one of which phenotypes as lymphoid and the other as myeloid. Biphenotypic leukemia An acute leukemia that has myeloid and lymphoid markers on the same population of neoplastic cells. Birefringent Characteristic of a substance to change the direction of light rays that are directed at the substance; can be used to identify crystals. As the H+ concentration in tissues increases, the affinity of hemoglobin for oxygen is decreased, permitting unloading of oxygen. Bone marrow trephine Removal of a small piece of the bone marrow biopsy core that contains marrow, fat, and trabeula. Examination of the trephine biopsy is useful in observing the bone marrow architecture and cellularity and allows interpretation of the spatial relationships of bone, fat, and marrow cellularity. Cabot ring Reddish-violet erythrocyte inclusion resembling the figure 8 on Romanowsky stained blood smears that can be found in some cases of severe anemia. Carboxyhemoglobin Compound formed when hemoglobin is exposed to carbon monoxide; it is incapable of oxygen transport. It is produced by the choroid plexus cells, absorbed by the arachnoid pia and circulates in the subarachnoid space. In the chronic phase, there are less than 30% blasts in the bone marrow or peripheral blood, whereas in the blast crisis phase there are more than 30% blasts. An absolute monocytosis (>1 X 109/L) is present and immature erythrocytes and granulocytes may also be present. The bone marrow is hypercellular with proliferation of abnormal myelocytes, promonocytes, and monoblasts, and there are <20% blasts. Chylous A body effusion that has a milky, opaque appearance due to the presence of lymph fluid and chylomicrons. Circulating leukocyte The population of neutrophils actively circulating pool within the peripheral blood stream. Can be detected by the identification of only one of the immunoglobulin light chains (kappa or lambda) on B cells or the presence of a population of cells with a common phenotype. Clot Extravascular coagulation, whether occurring in vitro or in blood shed into the tissues or body cavities. Retraction of the clot occurs over a period of time and results in the expression of serum and a firm mass of cells and fibrin. Cold agglutinin disease Condition associated with the presence of cold- reacting autoantibodies (IgM) directed against erythrocyte surface antigens. Colony forming unit A visible aggregation (seen in vitro) of cells that developed from a single stem cell. Colony stimulating factorCytokine that stimulates the growth of immature leukocytes in the bone marrow. The common pathway includes three rate-limiting steps: (1) activation of factor X by the intrinsic and extrinsic pathways, (2) conversion of prothrombin to thrombin by activated factor X, and (3) cleavage of fibrinogen to fibrin. Compensated hemolytic A disorder in which the erythrocyte life span is disease decreased but the bone marrow is able to increase erythropoiesis enough to compensate for the decreased erythrocyte life span; anemia does not develop. Complement Any of the eleven serum proteins that when sequentially activated causes lysis of the cell membrane. Congenital Heinz body Inherited disorder characterized by anemia due hemolytic anemia to decreased erythrocyte lifespan. Erythrocyte hemolysis results from the precipitation of hemoglobin in the form of heinz bodies, which damages the cell membrane and causes cell rigidity. Contact group A group of coagulation factors in the intrinsic pathway that is involved with the initial activation of the coagulation system and requires contact with a negatively charged surface for activity. Continuous flow analysisAn automated method of analyzing blood cells that allows measurement of cellular characteristics as the individual cells flow singly through a laser beam. Contour gating Subclassification of cell populations based on two characteristics such as size (x-axis) and nuclear density (y-axis) and the frequency (z- axis) of that characterized cell type. Coverglass smear Blood smear prepared by placing a drop of blood in the center of one coverglass, then placing a second coverglass on top of the blood at a 45° angle to the first coverglass. Cyanosis Develops as a result of excess deoxygenated hemoglobin in the blood, resulting in a bluish color of the skin and mucous membranes. Cytochemistry Chemical staining procedures used to identify various constituents (enzymes and proteins) within white blood cells. Useful in differentiating blasts in acute leukemia, especially when morphologic differentiation on romanowsky stained smears is impossible. Cytokine Protein produced by many cell types that modulates the function of other cell types; cytokines include interleukins, colony stimulating factors, and interferons. This occurs because the primary hemostatic plug is not adequately stabilized by the formation of fibrin. Döhle bodies An oval aggregate of rough endoplasmic reticulum that stains light gray blue (with Romanowsky stain) found within the cytoplasm of neutophils and eosinophils. It is associated with severe bacterial infection, pregnancy, burns, cancer, aplastic anemia, and toxic states. The antibody reacts with erythrocytes in capillaries at temperatures below 15°C and fixes complement to the cell membrane. Upon warming, the terminal complement components on erythrocytes are activated, causing cell hemolysis. Dysfibrinogenemia A hereditary condition in which there is a structural alteration in the fibrinogen molecule. Dyspoiesis Abnormal development of blood cells frequently characterized by asynchrony in nuclear to cytoplasmic maturation and/or abnormal granule development. Echinocyte A spiculated erythrocyte with short, equally spaced projections over the entire outer surface of the cell. Effector lymphocytes Antigen stimulated lymphocytes that mediate the efferent arm of the immune response. The cell is an oval to elongated ellipsoid with a central area of pallor and hemoglobin at both ends; also known as ovalocyte, pencil cell, or cigar cell. Embolism The blockage of an artery by embolus, usually by a portion of blood clot but can be other foreign matter, resulting in obstruction of blood flow to the tissues. Embolus A piece of blood clot or other foreign matter that circulates in the blood stream and usually becomes lodged in a small vessel obstructing blood flow. Endothelial cells Flat cells that line the cavities of the blood and lymphatic vessels, heart, and other related body cavities. Granules contain acid phosphatase, glycuronidase cathepsins, ribonuclease, arylsulfatase, peroxidase, phospholipids, and basic proteins. Associated with parasitic infection, allergic conditions, hypersensitivity reactions, cancer, and chronic inflammatory states. Erythroblastic island A composite of erythroid cells in the bone marrow that surrounds a central macrophage. These groups of cells are usually disrupted when the bone marrow smears are made but may be found in erythroid hyperplasia. The least mature cells are closest to the center of the island and the more mature cells on the periphery. It is caused by an antigen— antibody reaction in the newborn when maternal antibodies traverse the placenta and attach to antigens on the fetal cells. It contains the respiratory pigment hemoglobin, which readily combines with oxygen to form oxyhemoglobin. The cell develops from the pluripotential stem cell in the bone marrow under the influence of the hematopoietic growth factor, erythropoietin, and is released to the peripheral blood as a reticulocyte. The average life span is about 120 days, after which the cell is removed by cells in the mononuclear-phagocyte system.
Test bias Another bias safe cardizem 120 mg, which is often not addressed in field studies purchase cardizem online now, is the difference between the true prevalence and the observed or “test” prevalence order cardizem 180mg fast delivery. That difference depends on the magnitude of the true prevalence in the population purchase cardizem cheap, and the performance of the test under study conditions (i. Therefore reported prevalence will either over- or underestimate the true prevalence in the population. Representativeness of rates Some settings reported a small number of resistant cases, and a few settings reported a small number of total cases examined. There were a number of possible reasons for these small denominators in various participating geographical settings, ranging from small absolute populations in some surveillance settings to feasibility problems in survey settings. The resulting reported prevalences thus lack stability and important variations are seen over time, though most of the variations are not statistically significant. Analysis of trends Although serious efforts have been made to obtain data that are as reliable as possible, some residual irregularities were detected in a number of settings. Such irregularities may be caused by diagnostic misclassification, changes in coverage, or reporting errors. Ecological fallacy Whenever data to be analysed consist of summaries at group level, as is the case here, there is risk of ecological fallacy,a where observed relationships at one level do not hold true at another level. With survey data, the estimation was based on the sample rates and new and re-treatment notifications. Upper and lower estimates were based on the assumption of reasonable representativeness of the sample and parent populations. Patterns The analysis included only the isolates examined at the most recent data point. The advantage of this approach is the avoidance of excessive weighting of crude results by those settings with several data points and a large sample size. A correlation between variables based on group (ecological) characteristics is not necessarily reproduced between variables based on individual characteristics. An association at one level may disappear or even be reversed by grouping the data. Two settings have not been included in the analysis: Mpumalanga Province, South Africa, and Chile. Six countries had results for 21 projects: eight in South Africa covering the entire country (the provinces of Eastern Cape, Free State, Gauteng, Kwazulu-Natal, Limpopo, North West, Mpumalanga, and Western Cape), four in China (the provinces of Henan, Hubei, and Liaoning, and Hong Kong Special Administrative Region), three in India (North Arcot District, Tamil Nadu State; Raichur District, Karnataka State; and Wardha District, Maharashtra State), two in the Russian Federation (Orel and Tomsk Oblasts), two in Spain (Barcelona and Galicia Provinces), and two in the United Kingdom (England, Wales, and Northern Ireland; and Scotland). Thus analyses were possible for: new cases (74 settings); previously treated cases (65 settings); and combined cases (69 settings). Puerto Rico reported only new cases in 2001, but new, previously treated and combined cases from 1997 until 2000. Of these, nine reported prevalences near 30%, and four reported substantially higher levels: Kazakhstan (57. The box represents the interquartile range, which contains 50% of the observations, and shows the median value and adjusted 25th and 75th percentiles. The whiskers are lines extending from the box to the highest and lowest values that are not outliers. Outliers and extreme values are so low or so high that they stand apart from the data batch. They merit attention as they present valuable information about epidemiological clues or data validity. Extreme values are more than 3 box lengths from the upper or lower edge of the box. The number of cases tested ranged from 1 (Malta and Iceland) to 668 (Poland) with a median of 100 cases per setting. Several settings reported a small number of cases tested (1–19 cases in 6 settings; 20–49 cases in 14 settings; 50–99 cases in 11 settings). There was no resistance reported in the Gambia, Iceland, Malta and Luxembourg, where the number of previously treated cases was very small. In contrast, Kazakhstan and Karakalpakstan, Uzbekistan, showed tremendously high prevalences of any resistance – 82. Twelve settings reported no resistance to three or four drugs (Belgrade, Finland, the Gambia, Iceland, Ireland, Luxembourg, Malta, New Zealand, Norway, Sweden, Switzerland, and Zambia). The highest prevalences of resistance to three or four drugs were reported in Orel Oblast, Russian Federation (52. Full details of drug resistance prevalence among combined cases for the period 1999–2002 are given in Annex 5 and Annex 6. Any resistance among combined cases The overall prevalence of drug resistance ranged from 0% (Andorra, Iceland and Malta) to 63. Figure 9 shows the ten countries/settings with combined prevalence of any resistance higher than 30%. Resistance to three or four drugs was less than 2% in almost two-thirds of the settings, with a median of 1. Any resistance among combined cases by individual drug Annex 6 shows the prevalence of any resistance to each of the four drugs among combined cases. The highest prevalence of resistance to all four drugs was observed in Kazakhstan. The distribution of the prevalence of resistance to each individual drug is illustrated in figure 11. Exceptionally high prevalences and outliers were found in many countries/ settings. However the range of resistance prevalence varied considerably within regions (Figure 12). The ranges in the Western Pacific Region and especially in the European region were much wider than for the other regions. The range of any resistance to each of the four drugs was by far the widest in the European region. The ranges of values for the African Region and the Americas were quite narrow, those of the Western Pacific Region wider, while the widest are observed in the European Region, reflecting the diversity of the resistance prevalence. The median prevalences of any resistance in the Regions of Africa, the Americas and Europe were around 20%, while the median prevalence in the Western Pacific Region reached 32. This was also true for the prevalence of resistance to 3 or 4 drugs, where Kazakhstan was an outlier (62. The Puerto Rico outlier (25%) is an artefact caused by the small sample size (n = 4). For most of the parameters the African Region had the lowest medians as well as the smallest ranges. We therefore explored stratification in three geographical subregions – Western, Central and Eastern Europe (Table 3). This was also true for the ranges of the parameters – narrow for Central Europe, somewhat wider for Western Europe, and widest for the Eastern European subregion. A high rate of immigration from areas with a higher prevalence of resistance, such as countries of the former Soviet Union, is one possible reason. The following analysis includes data from the three global reports, as well as data provided between the publication of reports. The present report examines time trends for resistance in new cases in 46 settings: 20 settings provided two data points and 26 three or more data points (Table 4). Twelve showed only slight variations in prevalence, while significant changes were observed in five settings: Poland, Peru, Argentina,b Henan Province (China),c and Thailand. In three of these settings (Argentina, Henan (China), and Thailand) the decrease was significant. Seven settings showed an increase over time, of which only Poland and Ivanovo Oblast were significant. New Zealand and Norway reported a doubling and Botswana a tripling of the prevalence. Figure 17 depicts the trend of prevalence of any resistance among new cases in Botswana. Tomsk Oblast (Russian Federation) showed a steady and significant increase, reaching a level of resistance 1. Tomsk Oblast, Russian Federation, and Slovakia both reported significant increases.