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C. Dennis, M.S., Ph.D.

Co-Director, University of Connecticut School of Medicine

Patients are usually young women of reproductive age who present with oligomenorrhea or secondary amenorrhea, hirsutism, infertility, or obesity. Gross examination is notable for bilaterally enlarged ovaries with multiple cysts; microscopic examination shows multiple cystic follicles. Previously, epithelial tumors were characterized by histology into the categories cystadenoma (benign), borderline, and cystadenocarcinoma. Now, serous tumors are classified as low grade and high grade for prognostic significance. Note · the Pap test has reduced the incidence of cervical cancer in the United States. Psammoma Bodies (Concentric Calcifications) in a Serous Tumor Ovarian Germ Cell Tumors · Teratoma (dermoid cyst) ° Vast majority (>95%) of ovarian (but not testicular) teratomas are benign; commonly occurs in early reproductive years ° Include elements from all 3 germ cell layers: ectoderm (skin, hair, adnexa, neural tissue), mesoderm (bone, cartilage), and endoderm (thyroid, bronchial tissue) ° Complications include torsion, rupture, and malignant transformation ° Can contain hair, teeth, and sebaceous material 204 Chapter 22 · Female Genital Pathology ° the term struma ovarii is used when there is a preponderance of thyroid tissue ° Immature teratoma is characterized by histologically immature tissue · Dysgerminoma ° Malignant; commonly occurs in children and young adults ° Risk factors include Turner syndrome and disorders of sexual development ° Gross and microscopic features are similar to seminomas ° Are radiosensitive; prognosis is good Ovarian Sex Cord­Stromal Tumors · Ovarian fibroma ° Most common stromal tumor; forms a firm, white mass ° Meigs syndrome refers to the combination of fibroma, ascites, and pleural effusion. Primary sites for metastatic tumor to the ovary include breast cancer, colon cancer, endometrial cancer, and gastric "signet-ring cell" cancer (Krukenberg tumor). Incidence in the United States is 1 per 1,000 pregnancies, with an even higher incidence in Asia. Choriocarcinoma is a malignant germ cell tumor derived from the trophoblast that forms a necrotic and hemorrhagic mass. Placental site trophoblastic tumor is a tumor of intermediate trophoblast which usually presents <2 years after pregnancy with bleeding and an enlarged uterus. In ectopic pregnancy, the fetus implants outside the normal location, most often in the fallopian tube, and less often in the ovaries or abdominal cavity. Enlarged placenta is common with maternal diabetes mellitus, Rh hemolytic disease, and congenital syphilis. Succenturiate lobes are accessory lobes of the placenta which may cause hemor- rhage if torn away from the main part of the placenta during delivery. Placental abruption is partial premature separation of the placenta away from the endometrium, with resulting hemorrhage and clot formation. Risk factors include hypertension, cigarette use, cocaine, and older maternal age. Vaginal delivery can cause the placenta to tear, with potentially fatal maternal or fetal hemorrhage. In placenta accreta, the placenta implants directly in the myometrium rather than in endometrium. Twin placentation · Fraternal twins always have 2 amnions and 2 chorions; placental discs are usually separate, but can grow together to appear to be a single placental disc. Acute mastitis causes an area of erythema and firmness in the breast, commonly during lactation. The breast is often biopsied to differentiate the condition from inflammatory carcinoma, another painful breast condition. Microscopically there is acute and chronic inflammation with abscess formation in some cases. Fat necrosis is often related to trauma or prior surgery, and it may produce a palpable mass or a discrete lesion with calcifications on mammography. Microscopic changes include fat necrosis, chronic inflammation, hemosiderin deposits and fibrosis with calcification. Because they carry varying degrees of risk for breast cancer, it is important to identify each type histologically. The changes most often involve the upper outer quadrant and may produce a palpable mass or nodularity. Nonproliferative Versus Proliferative Fibrocystic Changes Nonproliferative Fibrosis Cysts (blue-domed) Apocrine metaplasia Microcalcifications Proliferative Changes Ductal hyperplasia ± atypia Sclerosing adenosis Atypical lobular hyperplasia Table 23-2. Relative Risk of Developing Breast Cancer with Fibrocystic Change Relative Risk No increase 1. It causes a palpable, round, movable, rubbery mass, which on cross-section shows small, cleft-like spaces.

Such procedures would permit a more accurate determination of the fate of antibiotics in the animal after ingestion or injection and also allow for the monitoring of larger numbers of meat samples in a consumer protection not only the parent products program. Hides and Leather Analytical methods are needed to account quantitatively for sulfur-containing all of the compounds is it in the lime-sulfide unhairing of hides. Sulfide is used up by the excess cystine in the hair, but may be regenerated as sulfide or polysulfide by a second reaction which yields lanthionine. Whether these reactions are if directly involved in the hair- loosening or hair-dissolving step has never been established. Efficiency in the use of sulfide might be increased more were known of the actual hair-loosening reaction. If the rate the present analytical methods are not sufficient to clearly establish all of the competing and serial reactions involved. Since the same problem affects tanners throughout the world this is a problem of in- ternational significance. The introduction of pickled cattlehides as a marketable commodity has been hindered by a lack of adequate means of quality control and enforceable specification parameters. Ashing is unsatisfactory since some of the components will be volatilized or partially altered. The determination of pH values on a 1 0-fold water extract after 1 2 or 24 hours has little reliability as a measure of acidity. This method of analysis is adequate for research purposes where the tanned hide substance may be analyzed bedoes produce ultraviolet absorbing species (maximum fore the finishing operations necessary to produce the finished leathers. Many materials used in finishing also absorb in this region so that this for detecting method trol ble to finished leathers. This and estimating bound glutaraldehyde is not applicais a disadvantage from the standpoint of concommercial tanning process and of specification of this new of a new to establish the nature of the ultraviolet absorb- leather. Fundamental research ing species can be expected to contribute to the solution of this analytical problem. Because the tanning industry is lacking in research facilities and technical staff, sophisticated and expensive techniques are to be avoided. Sensory Characteristics of Foods Nearly all food research investigations require taste-panel evaluation of food products or intermediates as a primary criterion of the efficacy of raw material or processing variations. Flavor and odor evaluations by taste panel require a large enough group of tasters so that reliable statistical evaluation of results can be made because of the variability of sensory evaluations. However, it appears that flavor compounds frequently are present in amounts far below the detection limits of present-day instrumental sensors, since the most potent flavor and off-flavor compounds are often detected by odor or taste, not instrumentally. Present knowledge of the essential components of cooked aromas, as well as the methods of estimation, are inadequate to provide processing consuming and expensive and not adaptable to a continuous plant monitoring of the total production. Solution of this general problem will first require well coordinated chemical, analytical, and sensory evaluation of the commercially important cooked food aromas. Subjective odor panels are time cal proportions are established, then relatively simple plant control methods can be sought which will permit monitoring optimum flavor development in the further processing of meat, poultry, and other heatprocessed foods. Another important sensory characteristic of foods is "eye appeal," which is still measured largely by subjective techniques. Apparently, the wealth of spectrophotometric equipment in the modern laboratory can tell the scientist little about the spectrum of light reaching the eye from the surface of a peach, chocolate fudge, or a beef roast. Certainly the con- sumer easily notes color differences and reacts decisively to changes in the visible region that the photometers cannot detect or describe. In a typical instance, research on fortifying milk with iron to overcome fairly widespread incipient anemias in certain population groups has been hindered by the fact that the added iron causes color changes in some foods in which milk is traditionally used, such as cocoa. The eye easily detects off-colored cocoa, but the finest reflective spectrophotometers are blind to these changes. Obviously, spent in the study of light reflected from complex surfaces of multiphasic systems much more effort could be which have a measurable degree of translucence. Presently available and used methods of estimating total viable bacteria almost always involve culturing and counting, which are laborious and time-consuming operations. As a result, products are either unduly delayed, or they move through channels of processing and distribution without a current record of their bacterial load. Attempts so far to provide alternative chemical methods, such as dye reduction methods, have fallen short of their goals. A workable method should be general enough to react to and measure all viable microorganisms, and yet be specific enough to exclude all dead cells and foreign organic matter.

Trademarks or brand names may be established by usage in the market place but more commonly nowadays are registered with the relevant registry or trademarks office. Since the legal right to usage is limited by the jurisdiction of the registering authority it is possible for a single brand name to be used in several nations to represent products which may or may not be similar. For this reason the International Release should not contain any concepts that refer to a brand name whether as part of the moiety name or as the dose form. While it is preferable to provide a level of granularity that allows maximal decision support to function, the overhead cost of maintenance needs to be considered. It is also important that combinatorial explosion is avoided where clinically appropriate. For most decision support in relation to dosage and indications, route of administration is required. Route of administration is often not easy to determine at a terminology level as the licensed route of administration may vary by legal right, and usage is limited by the jurisdiction of the licensing authority. Additionally in some settings the clinicians may choose to use a non licensed route of administration. It is often more appropriate to use dose form in decision support, in particular to identify suitable dosing increments, and may also have some bearing on suitable routes for administration or dosage. Pack size may impact on decision support such as compliance however its use is limited and the overhead in maintaining all the internationally available pack sizes may be large. A basic level of decision support is based on contraindications, potential side effects and drug-drug interactions. However more sophisticated decision support requires knowledge of route of administration in order to provide guidance around dosage and in some cases contraindications and side effects. A greater level of decision support relating the previous or current medication history could be achieved by providing a concept that gave indication drug, strength and route. Populating this runs the risk of terminological explosion as all potential combinations of drug + dose + route would need to be populated. Although the Relationship between form and route is not an absolute many-to-one match, for most drug forms the route is implicit. The provision of a concept of drug + dose + form would provide a pragmatic solution since only those known to be available internationally would need to be populated. However this would also have the benefit of allowing sufficient granularity for effective decision support. If this is actioned then in order for a concept to be used for decision support it would be necessary to utilize a concept history mechanism that contains all the required data elements. The additional issue of the need to identify concept history resulting from correction as opposed to history resulting from cessation of availability of a product would also need to be addressed. Therefore it is proposed that concepts describing medicines that are no longer current therapeutics should not be retired routinely provided they are, or were, valid concepts. This method of population is unlikely to be sufficiently responsive for the population of this part of the hierarchy. It is proposed that when a medicinal product is licensed within one of the member nations it can be proposed for inclusion within the International Release. Unlicensed medications and other edge cases would be included as defined in the paper describing the scope of products to be included in the hierarchy. Below is more information provided to further describe the boundaries to be applied to concepts for inclusion in the International Release in relation to product types. The medicines to be included as the highest priority are those that could be added to a patient medication profile if they have been prescribed, dispensed and/or administered. Anesthetics ­ these and other supporting medications given during surgery are often recorded in specialist systems and not (yet) "shared" with medication profile applications. Note that medications administered during day case surgery would also fall into this category. X-ray contrast media and other diagnostic agents ­ these often highly allergenic products are often used in isolation and again recorded in specialist systems (which may still be paper-based) and the information does not find its way to a medication profile. Orphan drug products: these are licensed products intended for use in conditions where the patient population is likely to be very small, such as for rare diseases, resulting in lack of commercial development of the drug product due to limited revenue potential for the manufacturer. In some realms, the licensing process is modified to make it easier to gain marketing approval for drugs with "orphan" status.

Syndromes

• Keep the feeding as brief and low-key as possible. Do not entertain the baby.
• Deformity of the arm or hand
• Stool ova and parasites exam
• Chronic lymphocytic leukemia (CLL)
• Ulceration of bladder wall
• Suspected sexual assault
• Rest and avoid activities that aggravate your pain, especially weight bearing activities.
• Did it begin with an illness or injury?
• Falls or injury caused by fainting

This in- formation, together with the knowledge that in ammonium nitrogen exhaust gases and that amino and pyridinium fragments can found arise from is gasoline additives, implicates automotive emissions as the source of these particles. Urone - There are two areas where the analytical community can help tremendously. One of course is the research area, not only in responding to the everlasting demand for better, quicker, and more specific methods, but also for broadening the horizon in environmental areas by looking for new compounds, new mechanisms, and relationships investigating cause-and-effect between environmental pollution and the receivers, be they is in the development of man power. There is many areas - local agencies, universities, junior colleges, people, animals, plants, or materials. The analytical chemist should not only help instruct on methodology but emphasis should be given to the importance of careful analysis. As more people enter the field, the validity and meaning of their measurements increasingly important. Measurements of polluinterpreted by an increasing number of persons, other than analytical chemists. Unfortunately, many of these have vague or incomplete knowledge of the basic analytical principles involved. He stated that the carbon monoxide concentration in 1967 at seven Los Angeles stations was 1 1. The explanation is based on the improper use of the non-dispersive infrared method for the measurement. The 1969 measurements had not been properly corrected for interferences by a variable amount of water vapor. There is a very great need at present for analysts who can identify and measure the organic substances which are produced as primary or secondary products of photochemical and thermal reactions. Laboratory experiments tend to repeat the primary photochemical products but do not adequately and measure those substances which form aerosols or respiratory atmospheres. Air pollution analysis tricky stuff numbers that truly and reams of data taken by a black box are not necessarily meaningful just because used and masses of data fall out of the box. The high-volume sampler, while adequate for the determination of total mass of airborne material, is not especially well suited for the chemical analysis of particulates. The values for volatile materials such as selenium dioxide are completely erroneous. Also, the filter media themselves are often too contaminated to provide meaningful measurement because of a pollutant meter is some An example of a pitfall in high or variable blank. Arsenic, of certain materials in particulate matter is of special chromium, nickel, and asbestos are known to be carcinogenic. Elements which have been indicated as possible carcinogens include beryllium, cadmium, cobalt, lead, and selenium. A sequential tape sampler is excellent for collecting these materials and can provide the 20-30 micrograms needed by modern analytical methods. The ring oven provides a simple field method for identification and determination of the approximate levels of most of the above-mentioned elements. Essentially it is a solvent extraction separation technique in filter which the sample is dissolved at the center of a paper and carried by it a solvent front to the circumference of a heated circle where a thin but concentrated ring. Sectors of the filter collects as may be cut out and treated with suitable reagents to provide colored ring sections that are compared with standards for their quantitative estimation. Comparisons with other methods, especially atomic absorption spectroscopy, have been very favorable. Too little effort has been applied to the use of several techniques on the same sample to estimate the accuracy of methods. The lack of suitable Standard Reference Materials makes it impossible to compare results obtained by various investigators. The consensus is that errors should be no greater than ±20 percent at tolerance levels and results accurate to within a factor of two should be obtained at subliminal levels. The subject of pollution indices involving a combination of the levels of total particulates and specific pollutants was discussed. The interpretation of such indices is uncertain not only because of the paucity of data but the is known fact that what present is more important than the total amount of suspended material in the atmosphere.