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Certain point at which no further statistically significant crops cheap xenical 120 mg line, depending on the climatic conditions during increase in growth is observed would be considered to the growing season and at harvest (peanuts xenical 120 mg mastercard, hay purchase 120 mg xenical, be the requirement of that particular nutrient in that corn purchase 60mg xenical overnight delivery, wheat), may be considered the most common particular diet, under those specific experimental sources of aflatoxin. If this result is consistently reproducible, Mycotoxin contamination usually occurs when fun- it can be considered valid. This method is relatively gus is able to penetrate a seed hull or protective accurate, and a single study can be performed rather coating and reach the kernel. There is a severe need to set dietary guidelines to Because growth is the period in which most nutrients serve as a reference point that can be used as a are required at their highest levels, this type of study standard for testing. Safe guidelines are needed to can establish the upper end of the suggested nutrient help aviculturists and companion bird owners who range. The use of these levels for adults would cer- choose to feed a widely varied diet, to guide the tainly provide a level far greater than the true meta- commercial food manufacturers in producing diets bolic need but, in most cases, these would still be that can assure longevity and good health, and to within the safe range. The determination of the re- help veterinarians assess a patient’s diet and educate quirements for adults is very difficult, complex and the client in proper feeding methods. Additionally, the differing extreme difficulty in accurately determining the re- requirements for each separate strain within a spe- quirement of all nutrients, even for a single species, cies is often different. Because of this, the accepted documented studies and specific requirements will practice in humans has been to establish a minimum not be available for decades, if ever. It is therefore daily allowance, which is designed to meet or exceed necessary to derive these nutrient recommendations the estimated requirement of 97. Ex- population, or approximately two standard devia- trapolation from known species, if done wisely, can tions above the mean. This approach compensates for provide a reasonable starting point from which to the great degree of biological variability within the base diets and efficacy studies. With subsequent entire species, as well as bioavailability in foods, evaluation of this derived nutrient profile and long- variability of absorption efficiency, health status, en- term monitoring to assess overall nutrient status, vironmental conditions and genetic background. This meth- Evaluating Nutrient Status odology does not look at “minimums” but rather at The nutrient status of an individual is most easily nutrient levels that would attempt to optimize all accessed by carefully evaluating the adequacy of the experimental parameters by providing more gener- diet provided. The only prac- Nutrient Needs During Different Life Stages tical method for further testing is through serum or plasma samples. These samples are ideally taken Embryonic after a fast to reduce the presence of nutrients that An egg produced by a hen fed a nutrient-adequate were recently absorbed from a meal. Additionally, the diet is normally a rich source of the essential amino circulating levels of many nutrients are tightly con- acids, energy, linoleic acid and all of the required trolled, and, therefore, only show levels outside the vitamins and minerals for normal cell division, normal range when body stores are severely depleted growth and maturation. The matter is further complicated by the deficient diet that will allow production, embryo de- lack of reliable normal ranges (or in some cases, no velopment may progress, but will be abnormally af- information at all) and the high cost of certain nutri- fected. Many laboratories, however, are onic death, usually with the formation of a blood ring equipped to run plasma retinal or carotene levels (for after approximately three days of development (vita- vitamin A), plasma alkaline phosphatase (an indica- min A deficiency), losses immediately prior to hatch tor of vitamin D status), prothrombin time or clotting due to an embryo with insufficient strength to com- time (indicator of vitamin K status), serum calcium, plete the hatching process (riboflavin, biotin, folic phosphorous, electrolytes, trace minerals (although acid and vitamin B deficiencies) or embryonic mal- 12 they may inaccurately reflect status) and parameters formation (zinc and manganese deficiencies). Species differences do occur, but have not At hatch, the absorbed yolk sac serves as a temporary been listed due to insufficient research. The anticipated minimum requirement (as extrapolated from other species) is included for comparison. This may be adequate to supply the do not compensate for nutrient bioavailability, genetic variability and other conditions. As the chick’s digestive Anticipated Recommended system becomes fully functional, the period of rapid Nutrient Minimum Allowance for 1 growth begins. Due to the high metabolic rate and Requirement Maintenance the rapid division and growth of cells, the amino acid, Protein, % 10. As the chick advances through the growth period, at some point the once Potassium, % 0. The recommended allowances will support normal maintenance of companion birds and have been demonstrated to be adequate during long-term feeding. Similarly, the need for vitamins and minerals is to These levels, however, may not be sufficient for optimized health under varying replace those that were lost through metabolic proc- conditions and will not be adequate for breeding and growth, which may require higher levels of certain nutrients. This will allow for ably lower than for the growth period (or any other adequate chick growth and satisfactory levels of all stage of production) due to the lower rate of cell nutrients for egg production. Any increase in repleted without the risk of over-supplementing by activity level, ambient temperature outside of the providing an “egg production” diet during the breed- thermoneutral zone, molting and the exposure to any ing season. Feeding for optimal chick growth not only type of stress will alter the minimum nutrient levels decreases the duration in the nest of parent-raised required for maintenance. The increased requirements by the hen for breeding can be divided into two general categories: those Geriatric Nutrition required for egg production and those required for To date, there has been no research on the nutritional maximum hatchability of the embryo. This is due largely ter basis, the egg (without the shell) consists of ap- to the relative scarcity of geriatric birds in aviculture proximately 45% fat and 50% protein. Because of the historically the shell, which comprises approximately 10% of the poor diets offered to these birds and their subsequent total egg weight, is approximately 94% calcium car- shortened life-span, the mean population age of com- bonate (38% calcium). As resent the largest increase in nutrient needs in order the husbandry and veterinary care of these species for the hen to produce eggs. Because birds generally continue to improve, proper geriatric nutrition will eat to meet their energy demands, increasing the become a concern. Based primarily on geriatric re- energy content of the diet is not generally necessary. Calcium levels in the diet weight while providing slightly reduced levels of pro- should be increased to minimize the decalcification of teins, phosphorous and sodium, and levels of other the bone and to prevent the formation of soft egg vitamins and minerals similar to those received ear- shells. Slight increases in vitamins A, E, B12, (in poultry) when present at levels higher than the thiamine, pyridoxine, zinc, linoleic acid and lysine minimum maintenance requirement are vitamins A, may be helpful to overcome some of the metabolic and B12, riboflavin and zinc. Stresses are both psychological and physi- copper and manganese are required over what is cal. The caretaker is often Much of the reason for dramatically increasing the viewed as a threat, and the natural social interac- nutritional plane of a breeding bird’s diet is to pro- tions (flocking, mate selection) are inhibited. Crowd- vide adequate dietary components for the chick to be ing, handling, exposure to unusual pathogens, un- fed. Psittacine and passerine birds are relatively low sanitary conditions and malnutrition may all be egg producers and their increased demand for nutri- considered stress factors. With lative, and a single stress often has very little clinical adequate body stores through proper daily feeding, a effect on the bird. However, when one or more addi- diet designed specifically for egg production is not tional stress is applied, the bird may be weakened to necessary (such as a diet that will meet the immedi- the point of clinical illness or death. The synthesize enough vitamin C, especially in the case changes in metabolism also affect the normal meta- of hepatic damage. Increased vitamin C in other species exposed to a number of different types of bolism or levels of vitamin A, C, calcium, zinc, iron, stresses has shown to improve production and health copper and magnesium. Instead, adequate diets should be zymes required to produce the metabolically active provided to ensure the normal presence of sufficient form of vitamin D3 will be impaired. In these situations, body stores, which will also allow for satisfactory or in the case of a marginally deficient animal, it may 44 be beneficial to provide vitamin D3 therapy. Vitamin K For animals that have undergone extensive antibiotic Disease therapy and are being maintained on an unsupple- mented or marginally supplemented diet, it may be There has been very little research done on the spe- necessary to provide vitamin K because of its de- cific effects of diseases on the requirement and meta- creased synthesis by normal intestinal flora. The protein and energy metabolism; therefore, these vita- most critical nutrient for the body to maintain during mins have increased importance in the disease state. Zinc In a nutritionally compromised animal, zinc will im- prove healing and is an important component in pro- Secondly, the necessary energy supplies to the body tein synthesis; therefore, zinc is necessary for the must be maintained. Because of the increased meta- maintenance of the immune system and phagocytic bolic rate during illness, there is a higher energy activity. In humans, it has been found that the basal energy requirement will be exceeded by 50-120%, depending on the severity of the stress response. There is a lack of consistent studies in the literature Although much of this energy demand still falls indicating increased vitamin or mineral require- within the normal maintenance requirement, it is ments in the debilitated animal. Supplying nutrients critical to maintain or exceed the typical energy in- at recommended levels is probably sufficient in most take, which can be provided via carbohydrates, fats cases; an increase in certain vitamins and minerals or protein. Dietary protein is the third most critical component to be provided to the debilitated patient. With the increased metabolic rate, there is a subsequent in- crease in body protein turnover, much of which is Current recycled by the body and not lost. Because this deg- radation and resynthesis is not completely efficient, Nutritional Knowledge an increase in metabolic rate results in an increased amino acid requirement. There is also increased de- mand for amino acids because of the need for addi- tional immune components and tissue repair. With- Protein Needs out adequate amino acid intake, labile protein stores There have been few scientific studies conducted to (plasma, liver, muscle) are degraded for the process investigate the nutritional needs of companion and of gluconeogenesis. Most of the beliefs on nutrition stem efficiency in the utilization of proteins, thereby fur- from observations in clinical and avicultural settings. The exceptions to increasing the have been published investigated the total protein protein in the diet are during the acute phase of liver requirement and lysine requirement of the growing or renal disease.

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Effects of exercise on glycemic control and body mass in type 2 diabetes mellitus: a meta-analysis of controlled clinical trials buy 120mg xenical. Effects of a multivitamin and mineral supplement on infection and quality of life generic 120 mg xenical. Chromium treatment has no effect in patients with type 2 diabetes in a Western population: a randomized order xenical 120mg without prescription, double-blind buy discount xenical 120 mg on-line, placebo-controlled trial. Chromium picolinate and biotin combination improves glucose metabolism in treated, uncontrolled overweight to obese patients with type 2 diabetes. Chromium picolinate and biotin combination reduces atherogenic index of plasma in patients with type 2 diabetes mellitus: a placebo-controlled, double-blinded, randomized clinical trial. The glucose/insulin system and vitamin C: implications in insulin-dependent diabetes mellitus. Antioxidant supplementation effects on low-density lipoprotein oxidation for individuals with type 2 diabetes mellitus. Vitamin E supplementation improves endothelial function in type 1 diabetes mellitus: a randomized, placebo-controlled study. Effect of oral vitamin E (alpha-tocopherol) supplementation on vascular endothelial function in type 2 diabetes mellitus. Chronic vitamin E administration improves brachial reactivity and increases intracellular magnesium concentration in type 2 diabetic patients. Alpha tocopherol supplementation decreases serum C-reactive protein and monocyte interleukin-6 levels in normal volunteers and type 2 diabetic patients. Reversal of defective nerve conduction with vitamin E supplementation in type 2 diabetes: a preliminary study. High-dose vitamin E supplementation normalizes retinal blood flow and creatinine clearance in patients with type 1 diabetes. Vitamin E supplementation reduces cardiovascular events in a subgroup of middle-aged individuals with both type 2 diabetes mellitus and the haptoglobin 2-2 genotype: a prospective double-blinded clinical trial. The effect of vitamin E on blood pressure in individuals with type 2 diabetes: a randomized, double-blind, placebo-controlled trial. Nicotinamide improves insulin secretion and metabolic control in lean type 2 diabetic patients with secondary failure to sulphonylureas. Erythrocyte O2 transport and metabolism and effects of vitamin B6 therapy in type 2 diabetes mellitus. The effect of magnesium supplementation in increasing doses on the control of type 2 diabetes. Zinc and diabetes mellitus: is there a need of zinc supplementation in diabetes mellitus patients? Therapeutic evaluation of the effect of biotin on hyperglycemia in patients with non-insulin dependent diabetes mellitus. Effects of purified eicosapentaenoic and docosahexaenoic acids on glycemic control, blood pressure, and serum lipids in type 2 diabetic patients with treated hypertension. Konjac-mannan (glucomannan) improves glycemia and other associated risk factors for coronary heart disease in type 2 diabetes. Viscous and nonviscous fibres, nonabsorbable and low glycaemic index carbohydrates, blood lipids and coronary heart disease. Position of the American Dietetic Association: health implications of dietary fiber. An analytical ultracentrifuge study on ternary mixtures of konjac glucomannan supplemented with sodium alginate and xanthan gum. Studies on macromolecular interactions in ternary mixtures of konjac glucomannan, xanthan gum and sodium alginate. Beneficial effects of viscous dietary fiber from konjac-mannan in subjects with the insulin resistance syndrome: results of a controlled metabolic trial. Presented at the 64th Annual Meeting of the American Diabetes Association, Orlando, Fla. Fermented soybean-derived water-soluble touchi extract inhibits alpha-glucosidase and is antiglycemic in rats and humans after single oral treatments. Efficacy and safety of touchi extract, an alpha-glucosidase inhibitor derived from fermented soybeans, in non-insulin-dependent diabetic mellitus. Long-term ingestion of a fermented soybean-derived touchi-extract with alpha-glucosidase inhibitory activity is safe and effective in humans with borderline and mild type-2 diabetes. Hypoglycemic activity and mechanisms of extracts from mulberry leaves (folium mori) and cortex mori radicis in streptozotocin-induced diabetic mice. An overview on the advances of Gymnema sylvestre: chemistry, pharmacology and patents. Use of Gymnema sylvestre leaf extract in the control of blood glucose in insulin-dependent diabetes mellitus. Antidiabetic effect of a leaf extract from Gymnema sylvestre in non- insulin dependent diabetes mellitus patients. Antidiabetic and adaptogenic properties of Momordica charantia extract: an experimental and clinical evaluation. Effect of Momordica charantia on the glucose tolerance in maturity onset diabetes. American ginseng ( Panax quinquefolius) reduces postproandial glycemia in nondiabetic subjects with type 2 diabetes mellitus. Similar postprandial glycemic reductions with escalation of dose and administration time of American ginseng in Type 2 diabetes. American ginseng ( Panax quinquefolius) attenuates postprandial glycemia in a time dependent but not dose dependent manner in healthy individuals. American ginseng improves glycemia in individuals with normal glucose tolerance: effect of dose and time escalation. Variable effects of American ginseng: a batch of American ginseng ( Panax quinquefolius) with a depressed ginsenoside profile does not affect postprandial glycemia. Evidence-based nutrition principles and recommendations for the treatment and prevention of diabetes and related complications. Effect of Trigonella foenum-graecum (fenugreek) seeds on glycaemic control and insulin resistance in type 2 diabetes mellitus: a double blind placebo controlled study. Antihyperglycemic effect of onion: effect on fasting blood sugar and induced hyperglycemia in man. The effect of flavonoid treatment on the glycation and antioxidant status in type 1 diabetic patients. Effect of low-dose niacin on glucose control in patients with non-insulin-dependent diabetes mellitus and hyperlipidemia. Efficacy, safety, and tolerability of once-daily niacin for the treatment of dyslipidemia associated with type 2 diabetes: results of the assessment of diabetes control and evaluation of the efficacy of niaspan trial. The role of nicotinic acid and inositol hexaniacinate as anticholesterolemic and antilipemic agents. Benfotiamine prevents macro- and microvascular endothelial dysfunction and oxidative stress following a meal rich in advanced glycation end products in individuals with type 2 diabetes. A double-blind, randomized, placebo-controlled clinical trial on benfotiamine treatment in patients with diabetic nephropathy. Oral benfotiamine plus alpha-lipoic acid normalises complication-causing pathways in type 1 diabetes. The influence of local capsaicin treatment on small nerve fibre function and neurovascular control in symptomatic diabetic neuropathy. Topical capsaicin: a review of its pharmacological properties and therapeutic potential in post-herpetic neuralgia, diabetic neuropathy and osteoarthritis. Acupuncture for the treatment of chronic painful peripheral diabetic neuropathy: a long-term study. Role of fermentable carbohydrate supplements with a low-protein diet in the course of chronic renal failure: experimental bases. Double-blind, randomised study of the effect of combined treatment with vitamin C and E on albuminuria in type 2 diabetic patients. J Pediatr Gastroenterol Nutr = Journal of Pediatric Gastroenterology and Nutrition 1989; 8: 480–485. Efficacy of tolerability of insoluble carob fraction in the treatment of travellers’ diarrhea. Prophylaxis against ampicillin-associated diarrhea with a lactobacillus preparation. Antibiotic associated diarrhoea: a controlled study comparing plain antibiotic with those containing protected lactobacilli.

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The absences at seminars should be made up for with another group cheap xenical 60 mg visa, at another time discount 60 mg xenical overnight delivery. Requirements for the final exam: The final exam (at the end of the second semester) consists of a written part and an oral exam (practical exam) quality 120 mg xenical. The oral exam will cover the topics of all laboratory practices and seminars of the full academic year purchase 60 mg xenical with amex. The final mark of the practical exam is the average of the mark given for the interpretation of public health databases (week 9) and the mark obtained for the oral exam. The written exam will be accomplished by computer based test that covers the topics of all Lectures and group seminars of the full academic year. It is composed of three parts: environmental health, epidemiology and health policy (the three parts will be evaluated separately). The mark of the final exam will be calculated on the basis of the average of the mark given for the practical exam and for the written exam. The final exam will be failed if either the practical or any part of the written exam is graded unsatisfactory. The mark of the final exam will be calculated on the basis of the average of the repeated part and the previous parts of the exam. Requirements The rules written in the statue of the Organization and Operation of Medical University of Debrecen will be applied. In case of absence the student must compensate on the same week with another student’s group or should ask the tutor. The Head of the Department may refuse to sign the Lecture Book if a student is absent more than twice from practices in a semester. The final examination will consist of a practical (X-ray examination) and an oral part, two questions from the topics. Year, Semester: 4th year/2nd semester Number of teaching hours: Lecture: 10 Practical: 30 1st week: therapy Lecture: Principles of radionuclide imaging Practical: Radiology: Traumatology Nuclear medicine: Practical: Radiology: Diseases of the pancreas Nuclear Oncology. Visit to the Nuclear Medicine department 6th week: 2nd week: Lecture: Examination of the breast. Contrast media Lecture: Thyroid and parathyroid imaging Practical: The diseases of the breast Practical: Radiology: Diseases of the gastrointestinal tract. Brain tumors Lung 9th week: 4th week: Lecture: The spine and the spinal cord Lecture: Radionuclide imaging of the kidney and the Practical: The diseases of the spine and the spinal cord gastrointestinal tract Practical: Radiology: The bone diseases Nuclear 10th week: medicine: Hepatobiliary scintigraphy. Kidney Lecture: The vascular and lymphatic system Practical: The vascular diseases 5th week: Lecture: Nuclear medicine in oncology. Year, Semester: 4th year/2nd semester Number of teaching hours: Lecture: 10 1st week: Lecture: Inflammatory Bowel Diseases 6th week: Lecture: Adrenal surgery. Proctology 8th week: Lecture: Vascular surgery (arterial and venous diseases) 4th week: Lecture: Acute abdomen. Mid-year practice block: Students complete two weeks of practice in the Institute under the supervision of an assigned tutor. Following the daily schedule of their tutor, students are encouraged to participate in the ward activities and also in the outpatient care. Practical: Introduction to urological clinical practice, 6th week: describing the place of urology among all fields of Lecture: Tumors of the kidney. Practical: Differential diagnosis of scrotal disorders: varicocele, hydrocele, retention of the testicle, tescticular 2nd week: atrophy, epididymitis, orchitis, trauma, torsion, testicular Lecture: Disorders of the testis, scrotum and spermatic cancer, inguinal hernia, oedema. Practical: Clinical investigation of genitourinary tract, urological laboratory and imaging examinations. Surgical and non surgical Lecture: Injuries to the genitourinary tract, emergency treatment. Defining differences between the two Requirements Exam: oral type, the student has to pull 2 topics (1 cancer and 1 general). Students have to answer 20 simple questions, 16 correct answer is necessary to get passed to the oral exam. The list of questions along with the correct answers is available at the website of the Department (www. It is recommended to know the following reading material Paragh/Hajnal: Tessék mondani, since during practice sudents have to have the ability to communicate with patients. History and elements of genetics, classification of congenital 7th week: disorders. Quality management in 4th week: genetic testing, risk assessment in monogenic diseases. Practice 5th week: in clinical genetics: case reports, interpretation of Lecture: Prenatal diagnostics. Evaluation: Students take the oral examination (two titles) during the examination period. Practical: Recognising and treatment of orthodontic Practical: Anatomy of teeth and identification of teeth in disorders. Requirements Students who are absent from the practice lessons will not have their lecture-books signed. Compensation of absence: The student has to attend the missed topic with the other group with the agreement of the chief educational officer. The number of compensated or uncompensated practical occasion can not exceed one (3 hours). Topic of exam: textbook + lectures + topic of practice lessons Exam-days will be announced 4 weeks before the exam-period. Guidelines of volume therapy Requirements Conditions of signing the Lecture book: The student is required to attend the practicals, two absences are allowed in a semester. Any further absences are accepted if the student attends the practical of another group and certifies his/her absence. In case of uncertainty, the examiner might ask other questions related to other topics in order to make sure his decision on the mark given. Primary and secondary lesions, dermatological test) status, moulages 10th week: 2nd week: Lecture: The skin and internal disease. A maximum of 2 practicals (4 practical hours) can be compensated during one semester. No signature will be given in lecture book with more than 1 uncompensated practice and 2 unattended compulsory lectures.. The written tests (prescription test, patient admission test) have to be completed, otherwise no signature will be given in lecture book. Requirements Requirements for signing the lecture book: The grade is calculated according to the result of the written exam and activity during the seminars. Year, Semester: 5th year/1 semesterst Number of teaching hours: Lecture: 10 Practical: 10 1st week: 4th week: Lecture: Introduction to Forensic Medicine. Infection and immunity; antimicrobial host Practical: Nosocomial infections in hematology/oncology defense mechanisms. Anaerob infections Practical: Catheter-related and invasive infections in Practical: Infectious diseases practice. Deparment of Internal Medicine Infectious and Pediatric Immunology) 8th week: 3rd week: Lecture: 10. Infections by herpesviruses and enteroviruses infections Practical: Infectious diseases practice. Differential diagnosis of exanthematous Requirements Attendance of seminars and practices are obligatory for students. In case of more than one absence the Lecture Book will not be signed except in case of documented disease or other reasonable cause. Neoplasms of the esophagus, stomach and Practical: Treatment of inflammatory bowel disease small intestine. Diabetes mellitus: patomechanism, types, 3rd week: clinical symptoms and complications 16. Practical: Gastrointestinal endoscopy Diverticulosis 9th week: 4th week: Lecture: 17. Diseases of the Practical: Functional gastrointestinal disorders biliary tract 10th week: 5th week: Lecture: 19. Alcoholic liver disease, Non-alcoholic fatty hyperlipoproteinemias: types, symptoms and treatment. Metabolic bone disorders 6th week: Practical: Treatment of diabetes mellitus Lecture: 11.

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For these groups the ranges of individual values are superimposable on the range from the control patients buy xenical 60 mg. These observations support the clinical impression of euthyroidism in these patients discount 60mg xenical with mastercard. It is easy to use and presents some advantages compared with other methods which rely on two separate measurements with subsequent calculation discount xenical 120mg without a prescription. Other particular conditions such as pregnancy purchase 120mg xenical mastercard, newborns, patients treated by drugs known to interfere in thyroid function tests, and patients with circulating autoantibodies to thyroid hormones, remain Jo be investigated before a complete validation of the method is obtained. Réévaluation of thyroxine binding and free thyroxine in human serum by pa­ per electrophoresis and equilibrium dialysis, and a new free thyroxine index, J. M,, et al,, Thyroid function evalu­ ation in patients with increased or decreased thyroxine-binding protein. Comparison of thyroid func­ tion in each trimester of pregnancy with the use of triiodothyronine uptake, thyroxine iodi­ ne, free thyroxine, and free thyroxine index. Use of direct thyroxine- binding globulin measurement in the evaluation of thyroid function, J. Measurement of free thyro­ id hormones in serum by column adsorption chro­ matography and radioimmunoassay, J. Free thyroid hormone con­ centrations in serum from patients on thyroxine replacement therapy, Nucl, Med. A simple, rapid radioimmunoassay for salivary oestriol has been developed based upon a radioiodinated tracer and a Sepharose-coupled antiserum with high specificity for oestriol and oestriol-3-coryugates. This assay, with a short incubation time (15 min) and a high tracer activity, has proved suitable for automation using a continuous-flow system based upon the ‘Southmead System’ described by Ismail and co-workers. Preliminary ether extraction is unnecessary since salivary oestriol is predominantly in the unconjugated form. Measurements of unconjugated oestriol in matched samples of plasma and saliva show an excellent correlation (r = 0. A preliminary study has been carried out to assess the feasibility of constructing individual daily salivary oestriol profiles throughout the third trimester. Data have now been collected on normal, diabetic and other high-risk patients, and these indicate that salivary oestriol measure­ ments provide a practical alternative to the determination of plasma unconjugated oestriol. B io c h e m ic a l a s s e s s m e n t o f f o e t o - p l a c e n t a l w e l l ­ b e in g b y m e a su r e m e n t o f s a l i v a r y o e s t r o g e n s i s t h e r e ­ f o r e p o s s i b l e an d o f f e r s t h e a d v a n ta g e o f an e a s y , n o n - i n v a s i v e p r o c e d u r e f o r s p e c im e n c o l l e c t i o n w h ic h may b e c a r r i e d o u t on a d a i l y b a s i s b y t h e p a t i e n t h e r s e l f. F r e q u e n t c o l l e c t i o n o f s a l i v a s a m p le s m u s t, h o w e v e r , b e c o m p le m e n te d b y an a s s a y w h ic h a l l o w s a r a p id r e t u r n o f r e s u l t s on l a r g e n u m b ers o f s p e c im e n s. T h is p a p e r d e s c r i b e s a m a n u a l a s s a y w h ic h m e e ts t h e s e r e q u ir e m e n t s by u s e o f a r a d io ­ i o d i n a t e d t r a c e r , a s o l i d - p h a s e a n t is e r u m an d a s h o r t in c u b a t io n t im e (1 5 m i n u t e s ). A p r e lim in a r y s t u d y h a s b e e n c a r r i e d o u t i n o r d e r t o a s s e s s t h e f e a s i b i l i t y o f c o n s t r u c t i n g i n d i v i d u a l d a i l y s a l i v a r y o e s t r i o l p r o f i l e s th r o u g h o u t t h e t h i r d t r i m e s t e r. S p e c im e n s w e r e r e t u r n e d a t r o u t i n e v i s i t s t o t h e a n t e - n a t a l c l i n i c. The b o u n d f r a c t i o n i s r e t a i n e d b y t h e m em brane an d p a s s e s t o w a s t e. H ow ever t h e a s s a y s y s te m d o e s n o t d e p e n d f o r i t s s u c c e s s u p on a r i g o r o u s l y s e l e c t e d a n t is e r u m. A n tis e r u m w as c o u p le d t o c y a n o g e n b r o m id e - a c t iv a t e d S e p h a r o s e 4B (P h a r m a c ia ) w it h n o s i g n i f i c a n t l o s s o f s e n s i t i v i t y. S t o c k p r e p a r a t io n s o f s o l i d - p h a s e a n t is e r u m i n a s s a y b u f f e r a r e s t a b l e on s t o r a g e a t 4 o c f o r a t l e a s t o n e y e a r. T he p r o t o c o l f o r t h e m a n u a l a s s a y is o u t l i n e d in F ig u r e 1. A lth o u g h t h i s a s s a y h a s a s h o r t in c u b a t io n t im e (1 5 m in u te s ) i t a v o id s m any o f t h e p r o b le m s a s s o c i a t e d w it h t h e s e t t i n g up o f n o n - e q u ilib r iu m a s s a y s s i n c e e q u ilib r iu m i s a t t a i n e d v e r y s l o w l y u n l e s s t h e S e p h a r o s e b e a d s a r e m a in t a in e d i n s u s p e n s io n. Dose-response curves (*) and precision profiles (°) for (a) the manual radioimmuno­ assay, and (bj the automated radioimmunoassay. T he a d d i t i o n o f c e l l u l o s e s u s p e n s io n p r i o r t o c e n t r i f u g a t i o n e n s u r e s t h a t a s t a b l e p e l l e t i s fo r m e d. A h ig h t r a c e r a c t i v i t y ( 6 0 ,0 0 0 cpm n o m in a l/t u b e ) i s e m p lo y e d b e c a u s e o f t h e s h o r t e f f e c t i v e c o u n t in g t im e o f t h e a u to m a te d s y s t e m. T he s h e l f - l i f e o f t h e r a d i o l i g a n d i s t h e r e b y i n c r e a s e d , an d s u f f i c i e n t a c t i v i t y i s p r e s e n t f o u r m o n th s a f t e r t h e a c t i v i t y d a t e t o a llo w p r e p a r a t io n o f s t a n d a r d c u r v e s w h ic h a r e s u p e r im p o s a b le u p on t h o s e p r e p a r e d w it h f r e s h t r a c e r. L o g - l o g i t l i n e a r r e g r e s s i o n a n a l y s i s o f t h e s t a n d a r d c u r v e d a t a g i v e s a c o r r e l a t i o n c o e f f i c i e n t e x c e e d in g 0. P r e c i s i o n o f t h e s t a n d a r d c u r v e i s e x c e l l e n t a t a l l f i x e d p o i n t s , c o e f f i c i e n t s o f v a r i a t i o n f o r s i x r e p l i c a t e s n o t e x c e e d in g 3. S e n s i t i v i t y o f t h e s ta n d a r d c u r v e , d e f i n e d a c c o r d in g t o K a is e r an d S p e c k e r [8 ] a s t h e l e a s t am ount d i s t i n g u i s h a b l e fro m z e r o a t t h e 95% c o n f id e n c e l e v e l , i s 4 p g p e r a s s a y tu b e ( 0. Comparison of oestriol concentrations measured in saliva dilutions (a) with (o) and without (*) a preliminary ether extraction, (b) with (°) and without (*) a preliminary hydrolysis with ß-glucuronidase. E x t r a c t io n o f u n c o n ju g a te d o e s t r i o l w it h d i e t h y l e t h e r i s u n n e c e s s a r y , h o w e v e r , s i n c e t h e o e s t r i o l c o n j u g a t e s , w h ic h c o n s t i t u t e t h e m a jo r f r a c t i o n o f p la sm a t o t a l o e s t r i o l , a r e n o t p r e s e n t i n s a l i v a i n s i g n i f i c a n t c o n c e n t r a t i o n s. M e a su r e m e n ts o f u n c o n j u g a t e d o e s t r i o l i n d i e t h y l e t h e r e x t r a c t s o f a s e r i e s o f d i l u t i o n s o f p o o le d s a l i v a s a m p le s sh o w ed n o s i g n i f i c a n t d e c r e a s e s i n m e a su r e d o e s t r i o l c o n c e n t r a t i o n s w hen co m p a red w it h t h o s e o b t a in e d u s in g t h e d i r e c t a s s a y. C o l i , from S ig m a , L on d on ) p r o d u c e d n o i n c r e a s e i n m e a su r e d o e s t r i o l c o n c e n t r a t i o n s ( F ig. T h is s i m p l e , d i r e c t a s s a y h a s now b e e n i n r e g u la r u s e f o r s i x m o n th s an d sh o w s i n t e r - an d i n t r a - a s s a y c o e f f i c i e n t s o f v a r i a t i o n o f l e s s th a n 9% i n a p p r o ­ p r i a t e lo w , m edium an d h ig h q u a l i t y c o n t r o l s. R e a g e n t s , a t t h e sam e c o n c e n ­ t r a t i o n s an d i n t h e sam e p r o p o r t io n s a s t h e m a n u a l a s s a y , a r e a s p i r a t e d , m ix e d an d pum ped th r o u g h a t h i r t e e n m in u te in c u b a t io n c o i l. S e p a r a t io n o f t h e b o u n d an d f r e e f r a c t i o n s t a k e s p l a c e b y m ean s o f a p o ly c a r b o n a t e m em b ran e. A s p i r a t i o n o f s a l i v a sa m p le o r s t a n d a r d f o r 60 s e c o n d s i s f o llo w e d b y 6 0 s e c o n d s o f w a s h , an d t h i s g i v e s a th r o u g h p u t r a t e o f 30 s a m p le s p e r h o u r w it h an a c c e p t a b l e sa m p le c a r r y o v e r o f <2%. F ig u r e 2 i l l u s t r a t e s d o s e r e s p o n s e c u r v e s an d p r e c i s o n p r o f i l e s o b t a in e d u s in g t h e sam e r e a g e n t s f o r t h e m a n u a l a s s a y an d t h e a u to m a te d a s s a y. A s e r i e s o f s i x s t a n d a r d c u r v e s w as g e n e r a t e d u s in g t h e a u t o ­ m a te d s y s te m an d co m p a red w it h s i x c u r v e s p r o d u c e d u s in g t h e m a n u a l a s s a y. M eans w e r e p l o t t e d f o r t h e r e s p o n s e m e ta m e te r (B /B 0 ) a t e a c h f i x e d p o i n t in t h e s t a n d a r d c u r v e s an d t h e c o e f f i c i e n t s o f v a r i a t i o n w e r e c a l c u l a t e d. T he a u to m a te d a s s a y sh o w s a lo w e r p o t e n ­ t i a l s e n s i t i v i t y (1 2 p g / t u b e , 0. S im ila r p r e c i s i o n p r o f i l e s w e r e o b t a in e d f o r t h e a u to m a te d an d m a n u a l a s s a y s. D e t e r m in a t io n s o f s a l i v a r y o e s t r i o l u s in g t h e a u to m a te d an d m an u a l m e th o d s sh ow a v e r y g o o d c o r r e l a t i o n ( r = 0. A lth o u g h t h e a u to m a te d s y s t e m h a s an a d e q u a te p e r fo r m a n c e i n i t s p r e s e n t fo r m , i t i s l i m i t e d i n s e n s i t i v i t y b y t h e r e q u ir e m e n t f o r c o u n t in g t h e u n b ou n d r a d i o l i g a n d f r a c t i o n. I t w as c o n s id e r e d a p p r o p r ia t e t o e s t a b l i s h : ( i ) t h e r e l a t i o n s h i p b e tw e e n p la s m a an d s a l i v a r y u n c o n ju g a te d o e s t r i o l c o n c e n t r a t i o n s , ( i i ) t h e s h o r t te r m ( h o u r ly ) a n d d a i l y v a r i a t i o n s in s a l i v a r y o e s t r i o l c o n c e n t r a t i o n s , ( i i i ) a p r o v i s i o n a l n o rm a l r a n g e f o r s a l i v a r y o e s t r i o l c o n c e n t r a t i o n s. S a l i v a r y o e s t r i o l c o n c e n t r a t i o n s w e r e d e te r m in e d b y t h e d i r e c t , s o l i d - p h a s e m e th o d. P la sm a a l i q u o t s (2 0 0 pL) w e r e e x t r a c t e d w it h d i e t h y l e t h e r (5 mL). E v a p o r a te d e x t r a c t s w e r e r e d i s s o l v e d i n a s s a y b u f f e r (1 mL) an d a l i q u o t s (2 0 0 yL) w e r e a s s a y e d a s d e s c r ib e d f o r s a l i v a s a m p le s. T h e s e r e s u l t s a r e i n g o o d a g r e e m e n t w it h t h o s e r e p o r t e d b y o t h e r w o r k e r s [ 2 , 1 0 ]. T he m ean i n d i v i d u a l v a r i a t i o n o v e r t h i s p e r io d w as 1 4. D a ily v a r i a t i o n s i n s a l i v a r y o e s t r i o l c o n c e n t r a t i o n s w e r e e x p r e s s e d a s p e r c e n t a g e d e c r e a s e s o r i n c r e a s e s co m p a red w it h t h e m ean o f t h r e e p r e c e d in g d e t e r m in a t io n s. T he m ean d a i l y d e c r e a s e s and i n c r e a s e s i n s a l i v a r y o e s t r i o l c o n c e n t r a t i o n s , m e a su r e d i n e i g h t n o rm a l women c o l l e c t i n g d u r in g t h e l a s t t h r e e w e e k s o f p r e g n a n c y , w e r e 17. O f t h e s e 1 5 1 d a i l y d e t e r m in a t io n s t h e r e w e r e f o u r o c c a ­ s i o n s (2. T h e s e f i g u r e s co m p a re som ew h at u n f a v o u r a b ly w it h d a i l y v a r i a t i o n s i n p la sm a u n c o n ju g a te d o e s t r i o l c o n c e n t r a t i o n s r e p o r t e d b y o t h e r w o r k e r s [ 1 2 , 1 3 ]. Our o b s e r v a t i o n s s u g g e s t , h o w e v e r , t h a t i n d i v i d u a l p a t i e n t s sh ow g r e a t d i f f e r e n c e s i n t h e d e g r e e t o w h ic h t h e i r s a l i v a r y o e s t r i o l c o n c e n t r a t io n s v a r y from d ay t o d a y , and i t may b e im p o r ta n t t o a s s e s s t h e s i g n i f i ­ c a n c e o f a p a r t i c u l a r f a l l i n s a l i v a r y o e s t r i o l c o n c e n t r a t io n i n te r m s o f t h e d a i l y v a r i a t i o n show n b y t h a t p a t i e n t. F ig u r e 5 sh o w s t h e g e o ­ m e t r i c a l m ean c o n c e n t r a t io n s o f s a l i v a r y u n c o n j u g a t e d o e s t r i o l d u r in g t h e 3 0 th t o 4 0 th w e e k s o f g e s t a t i o n.