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Endocrine: the kidneys are involved in the synthesis of renin (which generates angiotensin I from angiotensinogen hiv infection of t cells purchase prograf on line, and thus has a role in blood pressure and sodium balance) natural factors antiviral echinamide buy 1 mg prograf overnight delivery, erythropoietin (which controls erythrocyte production) and prostaglandins (involved in regulation of renal function) 4. The kidney is a major site for the catabolism of low-molecular-weight proteins including several hormones such as insulin, parathyroid hormone and calcitonin. The urinary tract epithelium is impermeable to water and solutes unlike the nephrons in the kidney, so the 1 Organization of the kidneys. Within the kidney, the ureter continues as the renal pelvis, which lies in a deep fissure called the hilum. The outer border of the renal pelvis divides into two or three major divisions (calyces). These subdivide into a number of minor calyces and are each indented by a papilla of renal tissue called the renal pyramid. Along with the renal pelvis, the renal artery, vein, nerve and lymphatics all enter the medial border of the kidney at the hilum. There are two types of nephron, depending on the length of the loop of Henle: Cortical nephrons: these have renal corpuscles in the outer part of the cortex, with a correspondingly short loop of Henle. In the human kidney, 85% of the nephrons are cortical nephrons and the remaining 15% are juxtamedullary nephrons. There is an abrupt transition between the thin and thick ascending segments and the level of this depends on the length of the loop. The thick ascending segment is 12 mm in length and consists of a single layer of columnar cells. The luminal membrane is invaginated to form many projections, although there is no brush border and there are few infoldings of the basal membrane. The function of the glomerulus is to produce a protein-free filtrate from the blood in the glomerular capillaries. The capillaries are supplied by the afferent arterioles and drained by the efferent arterioles. The filtration membrane of the renal corpuscle is made up of three layers and is fundamental to kidney function. Distal tubule the distal convoluted tubule is the continuation of the loop of Henle into the cortex, ending in the collecting ducts. The cells have very few microvilli, no brush border and basal infoldings surrounding mitochondria that gradually decrease towards the collecting ducts. Its wall is composed of a single layer of cuboidal cells, which interdigitate extensively and are connected by tight junctions at their luminal surfaces. The luminal edge of each cell is made up of millions of microvilli, forming a dense brush border that increases the surface area available for absorption of tubular filtrate. The extracellular space between the cells is known as the lateral intercellular space. The structure of the proximal tubule varies along its length: the first part is convoluted (pars convoluta) and cells have an increased density of microvilli and a greater number of mitochondria than cells in the second straight part. This suggests a role in transport of substances across the lumen and the filtrate the second straight part (pars recta) leads on to the first part of the loop of Henle (the thin descending limb). They are lined with cuboidal cells that have a few projections on the luminal surface. The ducts pass through the renal cortex and medulla and, at the apices of the renal pyramids, drain the urine into the renal pelvis. In the medulla the collecting ducts join together in pairs to form ducts of Bellini and from here drain into the renal calyx. Loop of Henle the loop of Henle consists of a single layer of flattened squamous cells, which form a thin-walled, hairpinshaped tube. The cells of the thin descending segment interdigitate sparingly and have few mitochondria and microvilli on the luminal surface. Its structure is similar to the preceding part of the tubule (the pars recta), except that the cells have extensive interdigitations. This might have a role in the Blood supply and vascular structure the kidneys receive 20­25% of the total cardiac output (1. They branch to form interlobar arteries, which further divide to form the arcuate arteries (located at the junction between the cortex and medulla). The interlobular arteries arise at 90 to the arcuate arteries through the cortex, dividing to form the afferent arterioles. The efferent arterioles drain blood from the glomerular capillaries and act as portal vessels. The vasa recta and the peritubular capillaries drain into the left and right renal veins. These lie anterior to the renal arteries and drain directly into the inferior vena cava. Clinical Note the intricate structure and complex nature of the renal blood supply make it very susceptible to damage. The glomerulus may be damaged by high blood pressure and high blood sugar levels in diabetes mellitus. Inflammatory conditions such as glomerulonephritis also lead to disruption of the glomerular capillary filter which results in the presence of blood and protein in the urine (haematuria and proteinuria, respectively). Although there is substantial blood flow, the arteriovenous oxygen difference is only about 15 mL/L, compared with 62 mL/L in the brain and 114 mL/L in the heart.

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Smear microscopy how long does hiv infection symptoms last 5mg prograf order otc, despite optimisation acute hiv infection timeline prograf 0.5mg discount, remains widely used even though its sensitivity is poor. Fortunately, thanks to renewed global awareness, financial investment and international collaboration, several new diagnostic options have been developed. In particular, diagnostic test performance characteristics and optimal settings for use will be discussed, finally emphasising research ``gaps' and the ongoing unmet diagnostic needs. However, despite this modest diagnostic accuracy, another study in hospitalised patients suggested that the strict use of these clinical guidelines could reduce 8week mortality and hospital length of stay [24]. Unfortunately, optimal chest radiology utility requires interpretation by trained, skilled observers, which are not always available. Interobserver variability of chest radiology has been shown to be poor, irrespective of reader skill [27, 38, 39]. Description of test Bacteriophage viruses infect and detect the presence of viable M. Furthermore, automated computer systems to interpret and report digital chest radiograms are currently in development [40]. Attaining adequate samples can, however, be challenging and a major obstacle to diagnosis. Of these techniques, sputum induction is emerging as the optimal technique given its safety, efficacy and feasibility even in resource-limited settings. The challenge lies in successfully integrating sputum induction into busy, routine clinical practice settings with limited resources. Additionally, smear microscopy relies on well-trained microscopists, and sensitivities between field and reference laboratories can vary by as much as 28% [14]. In addition, several innovative approaches to further improve smear microscopy are under development, including improved concentration techniques using nanobeads, fluorescence in situ hybridisation, automated and computer-assisted smear reading technologies, and use of mobile phones for microscopy [64, 65]. Traditional solid culture methods are tedious, time-consuming and have limited clinical impact. Automated liquid culture systems, with approximately 10% higher yields and a decreased time to diagnosis [66], have largely replaced solid culture. However, automated liquid cultures are expensive, prone to contamination, and require considerable laboratory infrastructure and expertise. Lack of standardisation and local variations in methodology remain programmatic concerns and have thus far limited scale-up. Compared with smears and culture, these assays are expensive, requiring specialised laboratory infrastructure and expertise, while, being open systems, they are at risk for crosscontamination in settings with suboptimal laboratory quality. These factors have limited their widespread uptake in high-burden, resourcelimited settings. Wide variation and heterogeneity predominantly accounted for by differences in included study populations. Performance outcomes for novel diagnostics applied to acquired pulmonary samples are not included. For both adults and children, sputum induction using ultrasonic nebulisation is equivalent or superior to the more invasive techniques of gastric washing and bronchoscopy. For the detection of rifampicin resistance, the meta-analysis data show a sensitivity and specificity of 94. Despite the development of updated versions of both the GeneXpert1 cartridge and software to further improve assay specificity, this remains an important concern. Updated meta-analyses show current serological assays are of no clinical value, with high variability in both sensitivity and specificity [10], and poor cost-effectiveness [91]. Despite the demonstrated lack of either accuracy or cost-efficacy, these tests continue to be sold in 17 out of 22 high-burden settings [90]. These assays have been extensively studied and systematically reviewed in a number of settings [94, 100­102]. However, this survey suggests that most current guidelines do not use objective, transparent methods to grade evidence and recommendations, and do not disclose conflicts of interest [105]. Novel, highly predictive biomarkers, or combinations of biomarkers and risk factors. In addition, both platforms seem to be evolving toward simultaneous detection and diagnosis of different infectious disease. No single test has yet met, or perhaps will ever meet, all diagnostic requirements across resource, healthcare and clinical settings. Ongoing basic and clinical research, as well as increased operational research, will be required to address these gaps. Grey arrows: stages in the evaluation pathway; coloured boxes: policy decisions at the global level (red) and the country level (blue). In the stages before scale-up and during and after scale-up, evaluation data would be collected on diagnostic algorithms incorporating the new test. Unmet needs and research priorities rates and/or default rates, and hospital length of stay [132], are required to best develop and guide policy. Pai is supported by the Canadian Insti´ ´ tutes of Health Research, Grand Challenges Canada and Fonds de recherche du Quebec ­ Sante. Evaluation of light emitting diode-based fluorescence microscopy for the detection of mycobacteria in a tuberculosis-endemic region. A systematic review of rapid diagnostic tests for the detection of tuberculosis infection.

Orange Mullein (Mullein). Prograf.

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Source: http://www.rxlist.com/script/main/art.asp?articlekey=96569

Bacteria in this group are either located intracellularly within phagolysosomes of macrophages or extracellularly in the inflammatory zones of cavitary walls antiviral research center ucsd cheap prograf 0.5mg buy on line. The limited oxygenation of the environment contributes to the inhibition of bacterial growth symptoms of hiv infection immunology including aids generic prograf 1 mg with amex. Due to their altered metabolic activity, these bacteria are unlikely to be eliminated by the administered drugs. The capacity of drugs to eliminate this bacillary population (and the bacilli in sporadic multiplication phase; see later) is referred to as ``sterilising activity'. The sterilising activity can be quantified as the frequency of relapses that follow treatment completion. Bacilli in a sporadic multiplication phase Bacilli in a sporadic multiplication phase also constitute a limited population (103­105 bacilli), preferentially located in the solid caseum, where the pH is nearly neutral. These bacilli undergo long dormant periods with occasional and brief replication periods lasting hours. As a result, the administered medication is only able to destroy these bacteria during these periods of active metabolism, and such periods may not occur at any time in the course of therapy. However, the scant and occasional activity of these bacteria prevents them from developing resistance. The drug of choice for eliminating this population is R, fundamentally due to the rapid onset of its sterilising action (15­20 minutes versus 24 hours in the case of H) and the excellent tissue penetration [3, 5]. The drugs with the strongest sterilising action are R and Z (only capable of acting on the bacillary population described here), while H and E have a lower sterilising capacity. The greater the sterilising activity of drugs included in a treatment regimen, the more its duration can be shortened [3, 5]. If R, the best drug currently available, can be included in the regimen, treatment duration may be reduced to 9 months, even to 6 months if Z can also be used in the initial phase of the treatment. However, whenever R cannot be used (due to adverse events or drug resistance) treatment regimens should not be less than 18 months, and could be even longer if H cannot be used either [3]. The excellent sterilising capacity of Z has allowed reduction of the duration of treatment to 6 months. If Z is not included in the initial treatment phase, treatment must be extended to at least 9 months to give R the ability to kill slowly replicating mycobacteria [3, 5]. Only in the case of known drug susceptibility to H plus R could three drugs (H plus R plus Z) be enough. Although some prefer to use culture conversion as a proxy of bactericidal activity, most experts agree that sputum smear conversion is an appropriate proxy for bactericidal activity. The remaining drugs, with the possible exception of thionamides, play practically no role as core drugs. This treatment regimen offers potent bactericidal and sterilising action, curing more than 95­98% of the patients, with few relapses (less than 1­2%) and few adverse events (less than 5%). Z should only be administered for 2 months, since after this period, the great majority of infected phagolysosomes and extracellular compartments with acid pH conditions have disappeared. The sterilising action of Z may already be very scarce or nil after the second month of treatment if R is included in the regimen. In addition, as E is given to protect against the possibility that the patient has been infected by bacilli resistant to H, E should not be stopped until the M. In fact, this would probably relate to a bacillary load that is so low that R alone would be able cure the patient, even in the event of initial resistance to H [7]. However, missing drug doses are important risk factors for treatment failure in intermittent therapy. Therefore, the possible growth of the bacilli that are naturally resistant to each of these drugs is different [11]. The only requirement is to adjust the corresponding dose and to ensure close follow-up. In the 159 case of malabsorption or if the patient is unable to take medication orally, the same regimens are provided, but via enteric feeding or the parenteral route [3]. In advanced liver disease, the possibility of using R in the regimen as the only hepatotoxic drug should be considered. Drugs with potential nephrotoxic effects, such as E and the injectable agents, should be avoided. If these drugs are used, blood drug levels should be monitored to ensure dose adjustment [3, 14]. Furthermore, resistance to this drug is relatively simple to detect using rapid molecular methods. H should be included in the combination therapy but should preferably not be counted among the four drugs that must form the core of the treatment. Designing a multidrug-resistant 160 tuberculosis regimen during a consilium in Minsk, Belarus. However, it is recommended that at least four drugs are used in the combination because there is a risk that some of the strains transmitted in the community already carry some drug resistance. From each of group 2 (later-generation fluoroquinolones) and 3 (second-line injectable drugs), only one drug can be selected [20, 27]. However, the level of evidence for this conditional recommendation is very low [28, 29]. For this reason, the length of administration of the injectable drug should be decided in the context of the potency of other drugs in the regimen, the bacteriological status of the patient and upon the occurance of the adverse events. If a regimen provides three effective drugs from groups 1, 2 and 4 (table 2) in addition to the injectable, the latter drug could probably be safely withdrawn when the smear and/or culture becomes negative. However, when there are less than three effective drugs in the regimen, or if any of them belong to group 5, a longer administration of the injectable agent should be considered. The regimen for these patients might include one group 2 drug (high-dose Lfx or moxifloxacin (Mfx)), one group 3 drug, ethionamide/prothionamide plus one other group 4 drug (preferably Cs). Surgical procedures may also be indicated to obtain biological specimens for microbiological and histopathological investigations.

Syndromes

• Poisoning by aspirin, ethylene glycol (found in antifreeze), or methanol
• Yellow skin or eyes
• Cognitive behavioral therapy
• Disorders of the adrenal gland (such as pheochromocytoma or Cushing syndrome)
• Aspirin or NSAID use
• Trees
• Clotting with treatment
• Urinalysis
• Patent ductus arteriosus (PDA)
• Thyroid disease

Novel drugs with potential activity in asthma are currently being trialled in adults with asthma and some of these may eventually find their way into paediatric use hiv infection early symptoms rash cheap prograf online mastercard. However hiv infection brain order prograf 0.5mg online, the most exciting advances in childhood asthma are likely to come from trials designed to prevent asthma. While several potential strategies can be identified from epidemiological studies, well conducted randomised clinical trials will be required to determine whether they are effective. While the appropriate use of currently available drugs does reduce the mortality and morbidity associated with asthma, these drugs do not ``cure' asthma or effectively alter the natural course of the disease [1]. Many children who are recommended to take regular medication do not receive it regularly, and those who do not take regular medication have poorer asthma control [4]. However, even with good treatment adherence, asthma control with current medications is far from perfect [4­6]. Mainstream therapy will not be considered, as it is not new and is covered elsewhere in this Monograph. Recent publications of novel treatment approaches will be reviewed, together with highlights from clinical trial registries to present what is forthcoming. Finally, comments will be made concerning the hopes for future treatment strategies, including approaches to preventing asthma. The study used a crossover design with two 4-week treatment periods, separated by a 2-week washout period. Treatment failure, defined as an asthma-related unscheduled visit, hospitalisation or additional systemic steroids within 8 days of the initial discharge, occurred in 7. Omalizumab While omalizumab has been in use in adults with asthma for some time, studies are only now defining its role in treating asthmatic children. Omalizumab is a humanised immunoglobulin (Ig)G1 antibody constructed from the constant region of the IgG1k human framework with a variable sequence of mouse antibody; the commercial product is greater than 95% human and less than 5% mouse antibody. The results of two clinical trials adding omalizumab to standard asthma management have recently been published [10, 11]. In the second phase of the trial, where adjustment of inhaled steroid does was allowed, omalizumab was associated with a 63% reduction in exacerbations (p,0. In this study, omalizumab reduced the number of days with asthma symptoms (reduction of 0. Omalizumab was generally well tolerated, with the most significant side-effect noted as being anaphylaxis. Injection immunotherapy A 2010 update of the Cochrane review on injection immunotherapy for asthma reviewed 88 trials, including 13 new trials [13]. Overall, the authors reported a significant reduction in asthma symptoms scores (standardised mean difference -0. From a safety viewpoint, if 16 patients were treated with injection immunotherapy, one would be expected to develop a local adverse reaction, with one in every nine patients that had been treated developing a systemic reaction (of any severity) [13]. While the review includes studies in both adults and children, there was no attempt to report results in the two age groups separately. When compared with non-asthmatic control children (n513), children with asthma had indications of oxidative stress, i. In addition, the combined therapy was associated with statistically and clinically significant improvements in lung function. Whether these results can be replicated in other populations, and in larger studies, remains to be determined; however, they do support the use of structured physical exercise programmes as an aid to asthma management in children. A systematic review of chiropractic spinal manipulation failed to show any evidence that this therapy was effective in improving asthma [16]. Evidence that acupuncture-like transcutaneous electric nerve stimulation improves childhood asthma is sparse, with one small open-label trial claiming improvements in the ``activity limitation' domain of the paediatric asthma quality of life (QoL) questionnaire, but not in other domains [17]. The traditional method of assessing new asthma drugs is for the initial trials to be performed on adults, with subsequent paediatric trials on drugs that ``show sufficient promise'. The problem with this paradigm is that the nature of childhood and adult asthma is different, i. A number of ``designer drugs' with immunomodulatory activity, targeted against specific components of inflammatory pathways, thought to be important in asthma, continue to be trialled in adult asthma. However, whether any of these agents are trialled in children and eventually join the therapeutic armamentarium available to paediatricians remains to be seen. Searching the various clinical trial sites reveals a large amount of clinical trial activity in paediatric asthma. While some trials specifically seek to recruit children, many others overlap into the paediatric age range, setting target recruitment ages at 16­65 years or 12­65 years. However, seeing a trial registered on a clinical trial site does not guarantee that the trial is underway or will actually occur. While the registration of clinical trials is a laudable advance, more attention needs to be paid to keeping trial listings up to date. The registered clinical trials fall into a number of areas, these include: drug therapy; exercise, nutrition and weight loss; therapeutic devices; education, management support or behavioural modification; anti-allergy strategies; and a variety of miscellaneous strategies. Trials of drug therapy While there is a large number of drug therapy trials on childhood asthma currently registered, very few new developments are on offer. New trials with other marketed drugs include: montelukast (eight trials); macrolides (four trials), anticholinergics (five 227 P. Few trials have been registered to treat acute asthma; there are four trials using oral steroids and one using magnesium sulphate. Trials using exercise, nutritional strategies or weight loss Weight loss, using low-calorie diets with the support from professional dieticians, is the focus of two registered trial. While combined physical exercise, nutritional and behavioural intervention forms the basis of another trial.

Usage: q.2h.

The clinical presentation of myxomas is often part of the triad of intracardiac obstruction acute hiv infection timeline buy prograf in united states online, embolization statistics hiv infection rates nsw purchase prograf 1mg mastercard, and constitutional symptoms. Nearly 70% of patients with left atrial myxomas have cardiac symptoms, typically related to obstructive heart failure and syncope. Embolic events occur in approximately 30% of patients, with left atrial myxomas causing strokes and transient ischemic attacks and with right atrial myxomas leading to pulmonary emboli. Myxomas may secrete interleukin-6, an inflammatory cytokine associated with systemic symptoms such as fever, malaise, and weight loss. Surgical resection of myxomas is warranted to relieve systemic or intracardiac obstructive symptoms and to prevent embolic complications. In 1985, successful balloon valvuloplasty using a transseptal approach was first reported in young adult patients with rheumatic mitral stenosis, and this technique is now the mainstay of interventional therapy for this condition. Mitral valvuloplasty is especially useful in patients without mitral valvular calcification 239 or thickening. One minor complication without significant hemodynamic consequence is that approximately 5% of patients show evidence of a persistent, left-to-right shunt at the site of atrial septal puncture, owing to the necessary transseptal left-sided heart catheterization. Although the initial relief of critical stenosis can be achieved in most patients, the rates of serious complications and restenosis are very high. Percutaneous prosthetic aortic valve implantation is undergoing active clinical investigation as an alternative to surgical valve replacement in suitable patients whose comorbidities place them are at excessive risk of standard surgical replacement. Lipomas and papillary fibroelastomas are the next most common benign primary tumors. The most frequent malignant primary tumor of the heart in adults is angiosarcoma, accounting for 30% to 37% of cases. Butany J, Nair V, Naseemuddin A, et al: Cardiac tumours: Diagnosis and management. Characteristic symptoms include failure to thrive, progressive hypotonia, lethargy, and a weak cry. The chest radiograph frequently shows cardiomegaly with pulmonary vascular redistribution. The diagnosis is confirmed by demonstrating the enzymatic deficiency in lymphocytes, skeletal muscle, or liver. Cardiac glycogenosis may be confused with other entities that cause cardiac failure, particularly in association with cardiomegaly in the early months of life. Furthermore, in endocardial fibroelastosis, mitral regurgitation and abnormalities of the cardiac valves, especially mitral and aortic, are frequent. Coarctation of the aorta, another common cause of congestive heart failure in infants, can readily be distinguished by the presence of pulse and blood pressure discrepancies between the upper and lower extremities. Myocarditis, yet another cause of congestive heart failure, is usually of abrupt onset and is not associated with hypotonia. Anomalous pulmonary origin of the left coronary artery can cause cardiomegaly but usually has a distinctive electrocardiographic pattern of anterolateral myocardial infarction. Shone syndrome is a developmental complex that consists of four obstructive anomalies: (1) a supravalvular ring of the left atrium; (2) a parachute mitral valve; (3) subaortic stenosis; and (4) coarctation of the aorta. It typically manifests with findings of mitral stenosis, because flow from the left atrium must pass through the abnormal intrachordal spaces of the mitral valve, which poses functional obstruction. Pulmonary venous hypertension is a common finding in this condition because of left ventricular inflow and outflow obstruction. Shone syndrome manifests more often in early childhood than in infancy and lacks the skeletal muscle changes of Pompe disease. Friedreich ataxia is a hereditary autosomal recessive disease that manifests during late childhood with progressive ataxia. About 50% of patients with Friedreich ataxia have cardiac involvement, typically hypertrophic cardiomyopathy. At that point, the transpericardial pressure distending the cardiac chambers declines to zero, and tamponade physiology occurs. Cardiac output in this setting may initially be maintained by reflex tachycardia and the blood pressure maintained by increased vascular tone. However, as pericardial fluid continues to accumulate, compensatory mechanisms are no longer able to maintain cardiac output and blood pressure falls. Whereas tachycardia is the usual response to falling stroke volume, bradycardia can be seen in severe cases. Both the cardiac depressor branches of the vagus nerve and sinoatrial node ischemia are believed to contribute to this phenomenon. Sagristà-Sauleda J, Angel J, Sambola A, et al: Low-pressure cardiac tamponade: Clinical and hemodynamic profile. By history, the course of her illness is relatively rapid and includes systemic symptoms of fatigue, weight loss, and episodes of rapid heartbeat, flushing, and diarrhea. Carcinoid is a slowly growing tumor that leads to focal or diffuse deposits of fibrous tissue in the endocardium of the valvular cusps and cardiac chambers. The white fibrous carcinoid plaques are most extensive on the right side of the heart because vasoactive substances are released from hepatic metastases and drain through the inferior vena cava into the right atrium. Other less common causes include endomyocardial fibroelastosis, trauma, cardiac tumors (particularly right atrial myxomas), transvenous pacemaker leads, repeated endomyocardial biopsies in a transplanted heart, or exposure to certain drugs, such as methysergide or the appetite suppressant dexfenfluramine. Pulmonary findings are frequent in those with right-sided endocarditis, with 65% to 75% displaying evidence of septic pulmonary emboli on chest radiograph. Other pulmonary complications include pulmonary infarction, abscess formation, and empyema. Serious cardiac complications include destruction of the tricuspid valve apparatus, with consequent severe regurgitation and right-sided heart failure. The most common causes of blunt chest trauma in the United States are motor vehicle accidents, usually involving impact against the steering wheel. Other causes include blows to the chest from a kick, a fall, or a projectile object.

References

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• Montalescot G, Borentain M, Payot L, et al. Early vs late administration of glycoprotein IIb/IIIa inhibitors in primary percutaneous coronary intervention of acute ST-segment elevation myocardial infarction: a meta-analysis. JAMA 2004;292:362-366.
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• Hashimoto K, Mayahara H, Takashima A, et al. Palliative radiation therapy for hemorrhage of unresectable gastric cancer: a single institute experience. J Cancer Res Clin Oncol 2009;135(8):1117-1123.
• Schuffler MD, Baird HW, Fleming CR, et al. Intestinal pseudoobstruction as the presenting manifestation of small cell carcinoma of the lung: a paraneoplastic neuropathy of the gastrointestinal tract. Arch Intern Med 1983;98:129.
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• Cussen LJ: Dimensions of the normal ureter in infancy and childhood, Invest Urol 5(2):164n178, 1967.
• Thompson KD, Welkyj S, Massa MC: Antibacterial activity of lidocaine in combination with a bicarbonate buffer. J Dermatol Surg Oncol 19: 216-220, 1993.