CHAPTER 25 INDEXING PRINCIPLES FOR CATEGORY D (CHEMICALS AND DRUGS) 25.1 Category D is an array of chemicals and drugs grouped by chemical structure and by pharmacological or physiological activity. It is the largest of the MeSH categories. Terms in Category D tend to be IM concepts when the point of the article. 25.2 MeSH contains all the elements, all the major inorganic and organic structural groups, all major action or function groups in pharmacology, all major endogenous substances of the body, all major enzyme groups and all major chemicals of environmental and industrial significance. 25.2.1 The Tree Structure given below shows the specific coverage of chemicals in Category D. D1 INORGANIC CHEMICALS D2 ORGANIC CHEMICALS D3 HETEROCYCLIC COMPOUNDS D4 POLYCYCLIC HYDROCARBONS D5 ENVIRONMENTAL POLLUTANTS, NOXAE, AND PESTICIDES D6 HORMONES, SUBSTITUTES, ANTAGONISTS D7 REPRODUCTIVE CONTROL AGENTS D8 ENZYMES, COENZYMES, ENZYME INHIBITORS D9 CARBOHYDRATES AND HYPOGLYCEMIC AGENTS D10 LIPIDS AND ANTILIPEMIC AGENTS D11 GROWTH SUBSTANCES, PIGMENTS, VITAMINS D12 AMINO ACIDS, PEPTIDES AND PROTEINS D13 NUCLEIC ACIDS, NUCLEOSIDES AND NUCLEOTIDES D14 NEUROTRANSMITTERS AND NEUROTRANSMITTER AGENTS D15 CENTRAL NERVOUS SYSTEM AGENTS D16 PERIPHERAL NERVOUS SYSTEM AGENTS D17 ANTI-INFLAMMATORY AGENTS, ANTIRHEUMATIC AGENTS, AND INFLAMMATION MEDIATORS D18 CARDIOVASCULAR AGENTS D19 HEMATOLOGIC, GASTRIC, RENAL AGENTS D20 ANTI-INFECTIVE AGENTS D21 ANTI-ALLERGIC AND RESPIRATORY SYSTEM AGENTS D22 ANTINEOPLASTICS, IMMUNOSUPPRESSIVES D23 DERMATOLOGIC AGENTS D24 IMMUNOLOGIC AND BIOLOGIC FACTORS D25 BIOMEDICAL AND DENTAL MATERIALS D26 MISCELLANEOUS DRUGS AND AGENTS 25.3 The subheadings available for use with Category D terms are assigned based on whether the term is an exogenous "chemical" or an endogenous compound. The subheadings listed below are AQs for various groups of Category D terms: /administration and dosage /genetics /adverse effects /history /agonists /immunology /analogs & derivatives /isolation & purification /analysis /metabolism /antagonists & inhibitors /pharmacokinetics /biosynthesis /pharmacology /blood /physiology /cerebrospinal fluid /poisoning /chemical synthesis /radiation effects /chemistry /secretion /classification /standards /contraindications /supply & distribution /deficiency /therapeutic use /diagnostic use /toxicity /drug effects /ultrastructure /economics /urine 25.3.1 Although each of the subheadings listed above is assigned to at least one group of Category D terms, very few compounds have all of them as AQs. The front of the Annotated MeSH contains tables of Allowed Qualifiers which indicate in general which qualifiers are allowed with general groups of chemicals, but the indexer must always check the AQ field for each specific heading indexed. 25.4 MeSH contains two basic forms of chemical headings, singular and plural. The singular forms refer to specific compounds, while the plural forms apply to groups of chemicals sharing a common property such as structure or pharmacological activity. A plural MeSH chemical (structure) term must never be used to index a specific compound, only a group of compounds sharing a common structure. In the examples given below, note the different types of singular MeSH terms and the corresponding plural terms available. Singular Plural Inorganic compounds BORON BORATES CHLORINE CHLORIDES CYANOGEN BROMIDE BROMIDES Organic compounds CORTICOSTERONE PREGNENEDIONES HEPTACHLOR HYDROCARBONS, CHLORINATED TRETINOIN RETINOIDS Drugs ANISOMYCIN ANTIBIOTICS ACETAZOLAMIDE DIURETICS NONOXYMOL SPERMATOCIDAL AGENTS Physiological compounds CORTICOSTERONE ADRENAL CORTEX HORMONES INSULINASE PEPTIDE HYDROLASES BAND 3 PROTEIN BLOOD PROTEINS 25.5 Although MeSH contains thousands of chemical headings, indexers often need to index other compounds which are not available in MeSH. To enhance our coverage of chemicals, a separate file containing additional chemical records is available. Officially known as the Supplementary Chemical Records, it is called the Chemical Tool by indexers. A printed subset of the Chemical Tool is available for indexers working offline; online indexers have the entire file available to them. 25.5.1 A typical record in the Chemical Tool looks like this: 25.5.2 Although the records in the Chemical Tool look different than records for MeSH chemicals, the indexing process is similar for chemicals from either publication. 184.108.40.206 When indexing a chemical which is a MeSH heading, the indexer should check where it is treed; if the treeing adequately covers the chemical as discussed by the author, only the single MeSH heading needs to be indexed. Complete amino acid sequence of the Salmonella typhi heat shock protein groEL. GROEL PROTEIN / * chem SALMONELLA TYPHI / * chem AMINO ACID SEQUENCE MOLECULAR SEQUENCE DATA Not: BACTERIAL PROTEINS / * chem Not: HEAT-SHOCK PROTEINS / * chem because GROEL PROTEIN is treed under BACTERIAL PROTEINS and HEAT-SHOCK PROTEINS. 220.127.116.11.1 For MeSH chemicals which are being used as drugs, a MeSH heading for the Pharmacologic Activity (PA) must be indexed as well as the chemical entity, since individual chemicals are not treed under PA terms. The MeSH record for each chemical shows the PA term(s) most likely to be applicable to that compound. The PA term is added as a coordination; i.e., it should be IM if the chemical is IM (or NIM if the chemical is NIM), and the same subheading(s) should be used on both terms if AQ(s) for both. Phenobarbital in the treatment of focal epilepsy. PHENOBARBITAL / * ther use ANTICONVULSANTS / * ther use EPILEPSY, FOCAL / * drug ther 18.104.22.168.2 Prior to 1996, chemicals were treed under PA terms as well as under structure. The only time an indexer needed to index a PA term in coordination with an individual MeSH chemical was in the rare case when the drug was not treed under the appropriate PA. Thus fewer headings were required in indexing, but there were different indexing policies to learn for MeSH drugs versus drugs in the Chemical Tool (see 22.214.171.124.1), which have always required the addition of a PA. In addition, the fact that a drug could be treed in numerous PA trees (DIAZEPAM was treed in 13 pharmacology trees) led to difficulties for searchers who wanted articles on only one pharmacologic activity of a given drug. Each search on a drug name retrieved all citations on the drug and it was very difficult to eliminate unwanted retrieval. Searching and indexing are now simplified. Indexers use the same policy for all drugs, and searchers can easily retrieve a specific pharmacologic activity of a given drug by searching for the drug plus the specific PA term for the activity desired. However, since all specific chemicals have been removed from the PA trees beginning in 1996, it could be very difficult for searchers to retrieve citations indexed in prior years (since indexers did not formerly add PA terms for MeSH chemicals). If a searcher wanted articles on all drugs sharing a certain PA activity, a simple "Explode" command would no longer retrieve citations on specific drugs. The MEDLARS Management Section is developing a new command for searchers to use, which will perform the same function as "Explode" for drug articles indexed prior to 1996. 126.96.36.199 When indexing a chemical from the Chemical Tool, the indexer should check its HM ("Heading Mapped to"); this is the MeSH heading which will automatically be added to the indexing when the chemical is indexed. If the HM adequately covers the chemical as discussed by the author, only the single chemical term needs to be indexed. Complete amino acid sequence of Bacillus thuringiensis CryIA(b) protein. CryIA(b) protein / * chem BACILLUS THURINGIENSIS / * chem AMINO ACID SEQUENCE MOLECULAR SEQUENCE DATA Not: BACTERIAL PROTEINS / * chem because one of the HMs for CryIA(b) protein is BACTERIAL PROTEINS. 188.8.131.52.1 As with MeSH headings, a PA term may be needed as a coordinate for a term from the Chemical Tool, if the author discusses an aspect of the compound which is not covered by the HM. Again, the relevant PA should be indexed IM if the compound is IM (or NIM if the compound is NIM), and the same subheading(s) should be used on both terms if AQ(s) for both. Oxaliplatin activity against metastatic colorectal adenocarcinoma. oxaliplatin / * ther use ANTINEOPLASTIC AGENTS / * ther use COLORECTAL NEOPLASMS / * drug ther ADENOCARCINOMA / * drug ther / second 184.108.40.206.2 Terms in the Chemical Tool may have an additional field labeled II ("Indexing Instructions"). IIs are similar to PAs and should be indexed instead of or in addition to a PA if relevant, but in most cases they are not pharmacologic actions. Thus, the subheading used with the chemical may not apply to its II. If an indexable II can logically take the same subheading(s) as the chemical for which it is a coordinate, and if the AQs are the same for both terms, the subheading(s) used on both terms should be the same. Localization of pleiotrophin in the postnatal developing cerebellum. pleiotrophin / * anal NERVE TISSUE PROTEINS / * anal CEREBELLUM / * chem / * growth (NERVE TISSUE PROTEINS is the II for pleiotrophin) Solubility of the opiate receptor agonist tifluadom. tifluadom / * chem SOLUBILITY RECEPTORS, OPIOID / * agon Not: RECEPTORS, OPIOID / * chem since the article is not about the chemistry of the receptors but the compound that acts on them. (RECEPTORS, OPIOID is the II for tifluadom) Biosynthesis of E. coli heat-labile toxin. E coli heat-labile toxin / * biosyn ESCHERICHIA COLI / * metab (ESCHERICHIA COLI is the II for E coli heat-labile toxin) 220.127.116.11 Listed below are instructions for using PA terms with chemicals, whether MeSH headings or compounds from the Chemical Tool. 18.104.22.168.1 Occasionally a PA may have different AQs than the chemical it is being coordinated with. If the subheading used on the chemical is not an AQ for its PA, consult the Subheading Trees (Figure 19.5) and use the subheading treed above the one used on the chemical. The same logic should also be used if the subheading desired is not an AQ for the chemical but is allowed on the PA. Blood levels of the sunscreen lawsone after dermal administration. lawsone / * blood / admin SUNSCREENING AGENTS / * metab / admin DRUG ADMINISTRATION, DERMAL 22.214.171.124.2 Each chemical may have more than one PA. The indexer should index those applicable to the article as discussed by the author (in most cases probably just one) no matter how many show in the record. Use of diazepam in the treatment of anxiety. DIAZEPAM / * ther use ANTI-ANXIETY AGENTS, BENZODIAZEPINE / * ther use ANXIETY / * drug ther Not: Any of the other PAs from the DIAZEPAM record 126.96.36.199.3 Conversely, an author may discuss a new activity of a drug which does not appear in its PA field. The indexer should index a MeSH heading which covers the PA as described by the author, even if it is not in the record for the term. (If an appropriate PA is not known, the Tree in the correct category should be consulted; see section 25.2.1.) Then the new PA should be flagged so that it can be added to the record for the chemical. The green Chemical Flag (see section 188.8.131.52) is used to flag new PAs, whether for MeSH headings or terms in the Chemical Tool. This is the only exception to the rule that green Chemical Flags are not used for MeSH chemicals (see section 184.108.40.206). Effects of the muscarinic agonist nebracetam on heart rate. nebracetam / * pharmacol MUSCARINIC AGONISTS / * pharmacol HEART RATE / * drug eff (Flag the new PA) 220.127.116.11.4 If the author indicates the pharmacology of a drug in either the title or statement of purpose for the article, index that PA even if the drug's pharmacology is not directly relevant to the study. Pharmacokinetics of the antidepressant adinazolam. adinazolam / * pharmacokin ANTIDEPRESSIVE AGENTS / * pharmacokin 18.104.22.168.5 When three or more related drugs need to be grouped for the IM, make the group PA the IM concept, and index the specific chemicals NIM. Similarly, if more than three related drugs are discussed but are not the main point of the article, use just their group PA and do not pick up the individual compounds at all. Use of the cholinesterase inhibitors eptastigmine, tacrine, and velnacrine in Alzheimer's disease. CHOLINESTERASE INHIBITORS / * ther use eptastigmine / ther use TACRINE / ther use velnacrine / ther use ALZHEIMER'S DISEASE / * drug ther New drug treatments for Alzheimers' disease: a review. (There is a lengthy section on the use of four cholinesterase inhibitors.) ALZHEIMER'S DISEASE / * drug ther CHOLINESTERASE INHIBITORS / ther use Not: Any of the specific drugs 22.214.171.124.6 Although the policy is to use the PA as described by the author, frequently authors use a general activity term such as "antineoplastic agent", while the record for the chemical shows a more specific PA such as ANTINEOPLASTIC AGENTS, PHYTOGENIC. In such cases, use the more specific PA. The article will still be available to searchers who explode the general term, but will be more precisely indexed according to MeSH policy. Adverse effects of the antidepressant fluoxetine in the elderly. FLUOXETINE / * adv eff ANTIDEPRESSIVE AGENTS, SECOND-GENERATION / * adv eff AGED (check tag) HUMAN (check tag) 126.96.36.199.7 Another discrepancy between author nomenclature and the use of PAs occurs when an author uses a structural term like "macrolide" in a clinical context where the pharmacologic activity is an obvious implication. Frequently compounds sharing a certain chemical structure also share a pharmacologic activity, and clinicians know that the activity is implied when only the structural term is used. Indexers should always note the treeing of any MeSH heading so that if pharmacologic activity seems to be implied but is not conveyed by purely chemical treeing, a PA term can be added. In many cases, the annotation for such a term will give the existence of the related PA term available. (The annotation for MACROLIDES states "in ther of dis is likely to be ANTIBIOTICS, MACROLIDE".) When indexing a group concept, use only the PA term, not the structural term. Use of macrolides in atypical mycobacterial infections. MYCOBACTERIUM INFECTIONS, ATYPICAL / * drug ther ANTIBIOTICS, MACROLIDES / * ther use Not: MACROLIDES / * ther use When indexing a specific compound given such a structural designation by the author, check the record for the compound and note that, while the compound may be treed under or have an HM of the structural term, the PA field has an entry of the related PA term which combines both structure and function. This PA term must also be added to the indexing. Use of the butyrophenone haloperidol in schizophrenia. HALOPERIDOL / * ther use ANTIPSYCHOTIC AGENTS, BUTYROPHENONE / * ther use SCHIZOPHRENIA / * drug ther (HALOPERIDOL is treed under the structural term BUTYROPHENONES) 188.8.131.52.8 When indexing an enzyme inhibitor for which there is no MeSH pre- coordinated (ENZYME) INHIBITOR term, the PA listed will be ENZYME INHIBITORS or another somewhat more specific but still relatively general term like SERINE PROTEINASE INHIBITORS. The indexer should add the listed PA (IM if the chemical is IM) but also index the specific enzyme with the subheading /antag (IM if the chemical and its PA are IM). This violates the general indexing policy as stated in section 19.7+ of not indexing both a specific subheading and its main heading equivalent, but searchers need PAs for all drugs. Effects of the HMC CoA reductase inhibitor lovastatin on erythrocyte membrane lipid levels. LOVASTATIN / * pharmacol ENZYME INHIBITORS / * pharmacol HMG COA REDUCTASES / * antag ERYTHROCYTE MEMBRANE / * drug eff / metab MEMBRANE LIPIDS / * blood Compounds in the Chemical Tool will have an II of the specific enzyme/antag if the term for the enzyme is a MeSH heading; if the enzyme is itself an entry in the Chemical Tool, its name will appear in the NO field and that is the term which should be used by the indexer. The N-terminal sequence of the bacterial ribonuclease inhibitor, barstar. barstar / * chem ENZYME INHIBITORS / * chem RIBONUCLEASES / * antag AMINO ACID SEQUENCE MOLECULAR SEQUENCE DATA Effects of the endothelin-converting enzyme inhibitor phosphoramidon on endothelin metabolism. phosphoramidon / * pharmacol PROTEINASE INHIBITORS / * pharmacol endothelin converting enzyme / * antag ENDOTHELINS / * metab Occasionally, the Chemical Tool enzyme is mapped (HM) to CYSTEINE PROTEINASES or SERINE PROTEINASES, which have pre-coordinated inhibition terms of CYSTEINE PROTEINASE INHIBITORS and SERINE PROTEINASE INHIBITORS, respectively. In such cases, CYSTEINE (SERINE) PROTEINASE INHIBITORS is listed as the PA for the drug which inhibits the enzyme, but /antag cannot be used on the enzyme as it is not an AQ for the HM. Rather than following the policy of moving up the Subheading Trees as stated in section 184.108.40.206.1, use the subheading /drug eff on the enzyme term. Antagonism of prolyl endopeptidase by Z-Pro-prolinal. Z-Pro-prolinal / * pharmacol SERINE PROTEINASE INHIBITORS / * pharmacol prolyl endopeptidase / * drug eff 220.127.116.11.9 Compounds which act on specific receptors are indexed the same way as compounds which inhibit specific enzymes. Index the listed PA which is general (IM if the compound is), but also add the specific receptor with /agon or /antag as appropriate (IM if the compound and its PA are). Effects of bromocriptine, a D2 receptor agonist, on self stimulation in rats. BROMOCRIPTINE / * pharmacol DOPAMINE AGONISTS / * pharmacol DOPAMINE D2 RECEPTORS / * agon SELF STIMULATION / * drug eff RATS (check tag) ANIMAL (check tag) 18.104.22.168.10 When indexing multidrug cancer chemotherapy, (see sections 22.214.171.124.1 and 126.96.36.199), index the specific drugs or the protocol as given in the Chemical Tool but do not index the specific PAs (ANTIMETABOLITES, ANTINEOPLASTIC, etc.) for the components. The only PA will be ANTINEOPLASTIC AGENTS, COMBINED. Inhibition of prostate cancer growth by vinblastine and tamoxifen. ANTINEOPLASTIC AGENTS, COMBINED / * ther use VINBLASTINE / admin TAMOXIFEN / admin PROSTATIC NEOPLASMS / * drug ther HUMAN (check tag) MALE (check tag) Not: ANTINEOPLASTIC AGENTS, HORMONAL / admin Not: ANTINEOPLASTIC AGENTS, PHYTOGENIC / admin even though these are the listed PAs for the two drugs. Treatment of Hodgkin's disease with the MOPP protocol. MOPP protocol / admin ANTINEOPLASTIC AGENTS, COMBINED / * ther use HODGKIN'S DISEASE / * drug ther Not: ANTINEOPLASTIC AGENTS, PHYTOGENIC even though that is the PA for VINCRISTINE, one of the components of the protocol, etc. 188.8.131.52 Many PA terms will be related to other PA terms; for example, a particular mechanism at a given receptor may result in a pharmacologic effect. The record for the PA will have an FX to the other related PA. Indexers should always look for FXs in records as well as PAs. For example, the record for SEROTONIN UPTAKE INHIBITORS has an FX of ANTIDEPRESSIVE AGENTS, SECOND- GENERATION because many serotonin uptake inhibitors act as antidepressants. 25.5.3 The instructions listed below summarize the indexing of cjemicals from MeSH or the Chemical Tool. When indexing a chemical, the steps to be taken are as follows: 1. Look it up in MeSH, and use it if there. 2. If the chemical is in MeSH and is discussed in the article as having pharmacological activity, add the appropriate PA term as discussed in the article (whether or not the record in MeSH lists that particular PA). The PA should be made IM if the chemical is, and the same subheading(s) should be used on both if AQs for both. 3. If the chemical is not in MeSH, look in the Chemical Tool. 4. If the chemical is in the Chemical Tool, add any appropriate PA or II term as discussed in the article (whether or not the record in the Chemical Tool lists that particular PA or II). The PA or II should be made IM if the chemical is an IM concept, and the same subheading(s) should be used on both the chemical and its PA if AQs for both. The same subheading should be used on the II if logical and if an AQ. 5. For chemicals in the Chemical Tool, SYs may be typed instead of NMs (just as X-references may be typed instead of MHs for MeSH headings). However, unlike MeSH headings and X-references, NMs or SYs may not be used if more than 36 characters; use a shorter NM or SY instead. If the record does not contain a short NM or SY, flag for the chemists to add one. 6. RNs may not be used instead of NMs or SYs for chemicals in the Chemical Tool. The "sort" (how entries are put in order alphabetically, etc.) is different for the Chemical Tool than for MeSH, so indexers need to know two sets of rules in order to be able to find chemicals in both places. In sections 184.108.40.206 to 220.127.116.11, the differences in the "sort" are compared. 18.104.22.168 In MeSH, alphabetization is by the shortest word first; in the Chemical Tool, alphabetization is letter-by-letter. MeSH Chemical Tool METHYL VIOLOGEN methylmethacrylate METHYLADENINE RECEPTORS methyl methanesulfothioate 22.214.171.124 In MeSH, hyphenated words are alphabetized as if they are all one word; in the Chemical Tool, hyphenated words are alphabetized letter-by-letter. (In other words, the publications treat hyphenated words the same way.) MeSH Chemical Tool ISOBUTYLCYANOACRYLATE 4-aminophenyl-beta-galactoside 3-ISOBUTYL-1-METHYLXANTHINE aminophenylboronic acid 126.96.36.199 In both publications, number prefixes are ignored. See examples above. 188.8.131.52 In both publications, most single-letter prefixes are ignored, but if the complete word is spelled out, it is alphabetized at the word. MeSH Chemical Tool BROMCRESOL PURPLE acetamide amidohydrolase P-BROMDYLAMINE p-acetamidobenzoic acid BROMELAINS acetanilide hydroxylase PAPUA NEW GUINEA PAPS sulfotransferase PARA-AMINOAZOBENZENE para-acetamidobenzoic acid 184.108.40.206 In both publications, single letters may be read under some circumstances. If a term containing a single letter cannot be found when the letter is ignored, look for it as if the letter were read and vice versa. MeSH Chemical Tool (letter ignored) (letter ignored) LYMPHOCYTES hemoglobin Bart's B-LYMPHOCYTES hemoglobin M Boston T-LYMPHOCYTES hemoglobin A, carbamylated LYMPHOCYTIC CHORIOMENINGITIS MeSH Chemical Tool (letter read) (letter read) SZONDI TEST tazobactam T-CELLS t-butanol TABES DORSALIS TCAOB 220.127.116.11 In MeSH, combinations of letters and numbers precede longer words beginning with the same letters; in the Chemical Tool, such combinations follow longer words beginning with the same letters. MeSH Chemical Tool A-23187 gyromitrin ABATE G 130 Ha antigen RO 20-1724 335 squaric acid dibutyl ester ROBENIDINE SQ-10996 SR gene product 18.104.22.168 In MeSH, numbers are in numerical order; in the Chemical Tool, numbers are in numerical order digit-by-digit, not by the whole number. MeSH Chemical Tool RO 7-0207 MK 196 RO 7-0582 MK-2 RO 10-9359 MK 302 MK 571 MK 7 25.5.4 When an indexer determines that a chemical needs to be indexed, but it cannot be found in either MeSH or the Chemical Tool, it must be flagged to the attention of the Chemical Specialists so that a record can be created for it in the Supplementary Chemical Records file and the compound can be added to the article. 22.214.171.124 Fill out the Chemical Flag as follows (see Figure 25.5.4): a. Indexer: Supply indexer number on all flags. b. Chemical: Supply enough information for the Chemical Specialists to know exactly which compound is to be indexed. (1). If the chemical is the only compound in the title of the article, "Title cpd" is sufficient. If more than one chemical is in the title, or when flagging a compound not in the title, use the rules in (2) or (3). (2). If the chemical has a short name, write the complete name. (3). If the chemical has a long name, write as much as needed to identify it and to differentiate it from any other chemicals on the same page (for example, "5-phenyl..." if no other chemical on the same page begins that way, "5-phenyl-6-hydroxy..." if another chemical begins "5-phenyl-3-hydroxy", etc.) c. Page: This is the page where the most complete description of the chemical is located (not necessarily the first page of the article or the page on which the name of the chemical first appears). Pencil a small asterisk or arrow where the description is found, and paperclip the flag on the facing page. d. Needed as IM with / *: If the chemical is an IM concept, indicate the subheading needed IM here. The 2-letter subheading abbreviations may be used, but write them distinctly; the Chemical Specialists often have trouble determining if the subheading needed is "bi" or "bl", "ch" or "cl", "ae" or "ai", etc. If the chemical is an IM concept but no subheading is to be used IM (very rare), put a zero or write "none" in this section. e. NIM with /: If the chemical is an NIM concept, or is an IM concept but needs additional NIM subheadings, indicate any NIM subheadings here. Again, be sure to write distinctly if using a 2-letter abbreviation. If the chemical is an NIM concept but no subheading is to be used with it (as, for example, a reagent), put a zero or write "none" in this section. f, g. Pharmacological Action (PA): or Indexing Instruction (II): If the chemical is being used as a drug or has a physiological action in the article, index the appropriate PA or II term, using the subheadings indicated for the chemical itself, if applicable (see 126.96.36.199.1 and 188.8.131.52.2). Then indicate the PA or II used on these lines. Also indicate any other possible PAs or IIs listed by the author but not indexed as not being relevant to the article. h, i, j. New data available: If the chemical is already in the Chemical Tool but new information about it is given in the article, or if the chemical is a MeSH heading but the PA needed for the article is not listed in its record, index the chemical and any applicable PA (or II if it is a Chemical Tool Term). Then fill out a chemical flag briefly so that the new information in this article can be added to the record for the chemical. Put the name of the chemical on line (b) so the Chemical Specialists know which chemical is being flagged, then check the appropriate box for the new data and write enough information on the flag so that the Specialists will know exactly what new information is to be added to the record. k. Comment: This field is rarely needed, but sometimes it is helpful to write a comment to the Chemical Specialists, (for example, alerting them to another compound with a similar name). When indexing a foreign-language journal, use this field to give the Chemical Specialists any information which would help them if they cannot read the language (for example, "Structure given on p. 13", or "See ref 14", etc.). Figure 25.5.4 184.108.40.206 After flagging the chemical, the indexer must index any relevant PA or II, making it IM if the compound is and using all subheadings desired with the flagged compound if the subheadings are AQs and if the subheadings apply (see 220.127.116.11.1 and 18.104.22.168.2). The indexer must not attempt to index the chemical structure of the flagged compound; that is the job of the Chemical Specialist who processes the flag. If the indexer adds a chemical structure term to the article in an attempt to index the flagged compound, the Chemical Specialist does not know whether the term has been added for some other reason, and will not remove it, even if the compound ends up being mapped to a different chemical. Blood levels of a new antineoplastic ammonium compound, XYZ-123, when used in the treatment of experimental mammary neoplasms in mice. (XYZ-123 is not in MeSH or the Chemical Tool and is flagged to be added to the article with a PA of ANTINEOPLASTIC AGENTS and the subheadings / * blood and / ther use) ANTINEOPLASTIC AGENTS / * blood / ther use MAMMARY NEOPLASMS, EXPERIMENTAL / * drug ther MICE (check tag) ANIMAL (check tag) FEMALE (check tag) (Not: AMMONIUM COMPOUNDS/ * blood/ ther use) (The Chemical Specialist will index the chemical aspect) 22.214.171.124 Only one compound may be entered on each Chemical Flag. If two related compounds (for example, two antibiotics with the same group name, but A and B) need to be flagged, both may be entered on one flag if they are both IM or NIM and if they are to be indexed with the same subheading(s), but a blank flag should be inserted behind the single flag so that there are two flags for the two compounds. When a flaggable compound appears in a series of articles, a separate flag should be used for each article, because it is highly unlikely that the compound will need the same subheadings in all the articles; however, the indexer need not repeat information on subsequent flags (for example, the PA) if the chemists do not need the information to process the article. 126.96.36.199 Do not use the green Chemical Flag to request a new MeSH heading for a group of chemicals (either a structural grouping or an action group). These flags are to be used only for individual chemicals which need to be indexed in an article but are not available in MeSH or the Chemical Tool; terms created by the Chemical Specialists in response to the green flags appear only in the Supplementary Chemical Records file, not in MeSH. If an indexer would like MeSH to create a new term to cover a group of chemicals, the correct form to be used is the REQUEST FOR NEW MeSH TERM form. 188.8.131.52 The green Chemical Flag may be used to request a new PA for an existing MeSH heading. This is the only time the Chemical Flag may be used for MeSH heading. Use the REQUEST FOR CHANGE TO EXISTING MeSH TERM form to let MeSH know of any change needed in a chemical term (singular or plural, structural or activity term) which already exists in MeSH (for example, that the term should be treed differently). The green Chemical Flag is not to be used for this purpose either. 25.5.5 Occasionally, an indexer finds a term in MeSH which looks similar to the compound to be indexed, but if it is not identical the indexer may wonder whether to use that MeSH term or to check the Chemical Tool and/or flag the compound. Sections 184.108.40.206 to 220.127.116.11 list the situations in which the MeSH term may be used. 18.104.22.168 The initial letters d,l, dl, R or S and the symbols + or - may be ignored. d-propranolol = PROPRANOLOL The letters listed above refer to stereoisomers (molecules which have the same molecular structure but a different spatial arrangement). If the article especially discusses the stereoisomers, the term STEREOISOMERS may be added (NIM with no subheading). Effects of (S)- and (R)- isomers of the antiarrhythmic propafenone on the activity of cytochrome P-450. PROPAFENONE / * pharmacol ANTI-ARRHYTHMIA AGENTS / * pharmacol CYTOCHROME P-450 / * drug eff STEREOISOMERS 22.214.171.124 The salts sodium (Na), potassium (K), hydrochloride (HCl) and sulfate (SO4) may be ignored for organic compounds, but esters must be considered as separate compounds. Ampicillin sodium = AMPICILLIN Fluphenazine decanoate must not be indexed as FLUPHENAZINE; look it up in the Chemical Tool. 126.96.36.199 The singular suffix -IC ACID may be used interchangeably with-ATE (and -IC ACIDS may be interchanged with -ATES, but a plural term must never be used for a singular concept and vice versa. "Iodohippurate" may be indexed as IODOHIPPURIC ACID. "Hydroxybutyric acids" may be indexed as HYDROXYBUTYRATES. "Acetate" or "acetic acid" must not be indexed as ACETATES; look it up in the Chemical Tool. 25.5.6 Specific instructions are given below on when to flag various other types of compounds encountered in the biomedical literature. 188.8.131.52 A peptide, protein, gene product, or biological "factor", even when given a specific name in the article, should usually be flagged only if its full amino acid sequence is given. If the sequence is not given but something in the article indicates that it has been determined previously, mark this information with an arrow in the text and flag the compound. Be careful to distinguish between a gene and the protein or gene product it encodes; the protein or gene product should be flagged, but if the article is merely about the gene, no chemical flag should be submitted. If an article discusses a protein but does not state that its sequence has been determined, index only the group term(s) for the protein (GLYCOPROTEINS, BACTERIAL PROTEINS, etc.). Immunology of rotavirus outer coat proteins VP3 and VP9. (No sequence information given or discussed) rotavirus VP3 protein / * immunol ROTAVIRUS / * immunol VIRAL COAT PROTEINS / * immunol (Rotavirus VP3 protein is in the Chemical Tool, so it can be indexed. Rotavirus VP9 protein is not in the Chemical Tool; since no sequence information is given, it should not be flagged but merely indexed as VIRAL COAT PROTEINS.) There are two exceptions to the rule stated above: 1. Flag a disease-related protein, gene product, peptide, or other biological "factor" such as a tumor marker if a molecular weight is given for it, even though no indication of amino acid sequence is given. (It must be related to a disease, not just a disease-causing organism.) 2. Flag any HIV- or HIV-infection-related protein, gene product, peptide, or biological "factor" even if it has not been isolated or purified and no molecular weight or amino acid sequence information is given for it. 184.108.40.206 An antigen should be flagged under the same conditions as those given for proteins in 220.127.116.11. Most antigens are proteins, but many are carbohydrates; for carbohydrates a complete carbohydrate sequence must have been determined. Unless the antigen has been sequenced, it should be indexed only with the appropriate group term in MeSH (ANTIGENS, VIRAL, etc.).The same exceptions apply for disease-related and HIV-related antigens as apply for proteins and other biological "factors". Do not flag blood group antigens. 18.104.22.168 No proof of isolation or amino acid sequence is necessary to flag a receptor. Any article in which the author discusses a receptor for a particular compound should be flagged if the term for the receptor is not already available in MeSH or the Chemical Tool. However, the author must indicate that there is a specific cell surface molecule which is acting as the receptor; do not flag a "binding site" if it is not clear from the article that a specific molecule is involved (merely index BINDING SITES), and do not flag an article on the binding process irrespective of a specific site. 22.214.171.124 An enzyme should be flagged if it has been isolated and a defined reaction is catalyzed; no proof of amino acid sequence or molecular weight determination is needed, even though enzymes are proteins. 126.96.36.199 A recombinant protein should not be flagged, but merely indexed as the specific protein (IM), coordinated with RECOMBINANT PROTEINS (NIM, with the same subheading(s) if allowable). Recombinant interleukin-1 induces heat-shock proteins. INTERLEUKIN-1 / * pharmacol RECOMBINANT PROTEINS / pharmacol HEAT-SHOCK PROTEINS / * drug eff / biosyn If the article gives a new generic or trade name for the recombinant protein, flag it for the Chemical Specialists but index in the same manner as above even though flagged; indicate on the flag that the protein has been indexed. The Chemical Specialists and MeSH will use the information from flags to determine when a new term should be created for an especially important recombinant protein (such as INTERFERON-GAMMA, RECOMBINANT). 188.8.131.52 A monoclonal antibody, even if given a name, should in general be indexed only as ANTIBODIES, MONOCLONAL. Flag a monoclonal antibody only if the article states that it is available commercially or undergoing clinical trials, and that it is being used diagnostically or therapeutically, and that it has been given a generic or trade name. 184.108.40.206 An alloy should be flagged if it contains three or fewer metals. If an alloy contains more than 3 metals, flag it only if it has been given a specific name and is used for anything other than a dental alloy (such as a surgical implant, biocompatible material, etc.). If an alloy has not been given a name and contains more than 3 metals, index it only with the appropriate alloy term available in MeSH, such as NICKEL-CHROMIUM ALLOYS, DENTAL ALLOYS, etc. 220.127.116.11 Antineoplastic agents are often administered in combination with other anticancer drugs which have a different mechanism of action, producing a better response than if a single drug were given. Such combinations of antineoplastic drugs are called "protocols"; the drugs do not have to be administered at the same time to constitute a protocol. Protocols are usually named by acronyms composed of the first letters of the drugs used, but the derivation may not be readily apparent because the researchers may use the first letter of the trade name in the protocol name, and call the drug by its generic name in the article. (For example, a drug commonly used in cancer protocols is DOXORUBICIN, but the letter in most protocols is A, for Adriamycin, its trade name.) Anticancer protocols are available in the Chemical Tool. When an article discusses such a protocol, index the term ANTINEOPLASTIC AGENTS, COMBINED / ther use (IM or NIM, depending on whether or not the protocol is the main point of the article). Then check the Chemical Tool for the name of the protocol, and index it with the subheading /administration & dosage (always NIM) if available. If it is not in the Chemical Tool, index ANTINEOPLASTIC AGENTS, COMBINED / ther use (IM or NIM) and flag the protocol for the Chemical Specialists, indicating its subheading to be /admin (NIM), and its PA to be ANTINEOPLASTIC AGENTS, COMBINED. (NOTE! These rules on subheadings apply to the most common studies we index, where the main point is the therapeutic use of the protocol. It is always acceptable to use other subheadings when indexing a study on a different aspect of a protocol such as its pharmakokinetics.) Because protocol names are usually comprised of the first letters of the drugs included in them, it is possible for two different protocols to be given the same name by different researchers. Be sure to verify the drugs included in any protocol found in the Chemical Tool; flag any new protocol given the same name but composed of different drugs. Treatment of ovarian neoplasms with CAP (cyclophosphamide, doxorubicin and cisplatin). OVARIAN NEOPLASMS / * drug ther ANTINEOPLASTIC AGENTS, COMBINED / * ther use CAP-regimen 1 / admin HUMAN (check tag) FEMALE (check tag) (Not: CAP combination or CAP protocol 1, both of which are also in the Chemical Tool but are composed of different drugs) 18.104.22.168 Occasionally, drug manufacturers combine two or more drugs into one dosage form. If the combination has a trade name, the Chemical Specialists will enter it into the Supplementary Chemical Records file, so look in the Chemical Tool for all such trade-named combinations and flag if not available. 25.5.7 When an article is about a group of structurally-related chemicals, the indexer should merely index the best MeSH group term available, because group terms are not added to the Chemical Tool. If, however, the indexer is unsure of the indexing, the group concept may be flagged with the green Chemical Flag as long as the indexer states that the Chemical Specialists merely need to supply the correct MeSH term to cover the group concept. A statement in the Comment field such as "Unsure of best MeSH term" is sufficient. 22.214.171.124 Before flagging a group concept, however, the indexer should try to determine a MeSH term from clues in the article. For example, the indexer might not know what heading to use for an article entitled "Synthesis of indanediones". However, the introduction states that the compounds methindione and chlorophacinone have been studied and the authors are synthesizing 20 similar compounds. By looking at the records for methindione and chlorophacinone in the Chemical Tool, the indexer can determine that both are INDANS (the HM for both) and that this is thus the correct MeSH heading to use to cover the group concept. 126.96.36.199 In addition, before flagging a group concept the indexer should be sure that a group term is actually needed; it may well be that the article really is about only two or three specific compounds. The Chemical Specialists will add up to three specific related terms to the Chemical Tool per article. Since the indexing "Rule of Three" permits the indexing of up to three related terms (if there is not too much depth and all three are discussed), two or three specific compounds should be flagged individually, even if a group concept appears in the title. (Of course, it is still possible that a general MeSH heading may be needed to group these individual compounds for the IM.) 25.5.8 The subheading /analogs & derivatives is available in MeSH but has a very restricted use by indexers--only for articles on groups of analogues, since any specific analogue must be flagged if not available in MeSH or the Chemical Tool. The Chemical Specialists, however, use /analogs & derivatives frequently because the HM for any term in the Chemical Tool is either a plural MeSH term (such as PYRIDINES) or a singular MeSH term with the subheading /analogs & derivatives. 188.8.131.52 The subheading /analogs & derivatives is not permitted with any term from the Chemical Tool, because each is mapped to a plural term or as an analogue already. Thus, any article on a group of structural analogues of a term from the Chemical Tool may be indexed using just the term. Synthesis of analogs of efaroxan. efaroxan / * chem syn (The HMs for efaroxan are BENZOFURANS and IMIDAZOLES, so this article will print in Index Medicus at BENZOFURANS / chem syn and IMIDAZOLES / chem syn) 25.6 The PA terms in MeSH (usually referred to as the Pharmacologic Activity terms although also used for physiologic activity concepts), group compounds which share the same activity. MeSH contains all the major action groups in pharmacology and physiology. Examples of PA terms include ANTIHYPERTENSIVE AGENTS, ANTIBIOTICS, ANTINEOPLASTIC AGENTS, BACTERIAL PROTEINS, ENZYMES, etc. The following are some general observations about indexing policy regarding PA terms. 25.6.1 Do not index a PA term with /analogs & derivatives. This subheading cannot be used with group concepts. In addition, "analogues" are structurally related compounds, while PA terms refer to activity. 25.6.2 Index a PA term with /pharmacology when an article is about the pharmacology of the group of compounds sharing that activity. Effects of cholinesterase inhibitors on heart rate. CHOLINESTERASE INHIBITORS / * pharmacol HEART RATE / * drug eff 25.6.3 In addition, index a PA term with /pharmacology when an article is about the pharmacology of a MeSH compound with that PA activity but not treed under it, or the pharmacology of a Chemical Tool term having that PA activity. In these cases, the PA term is used as a coordinate and is always indexed IM if the compound is, using the same subheading(s) on the PA as on the compound, if possible (see 184.108.40.206.1 and 220.127.116.11.1). Effects of the MAO inhibitor pargyline on heart rate. PARGYLINE / * pharmacol MONOAMINE OXIDASE INHIBITORS / * pharmacol HEART RATE / * drug eff Is OK-432 a biological response modifier? OK-432 / * pharmacol BIOLOGICAL RESPONSE MODIFIERS / * pharmacol Effects of the antidepressant drug adinazolam on liver function. adinazolam / * pharmacol ANTIDEPRESSIVE AGENTS / * pharmacol LIVER / * drug eff 25.7 For many PA terms in MeSH, there is a corresponding process or disease term available also; examples include ANESTHETICS and ANESTHESIA, ANTIDEPRESSIVE AGENTS and DEPRESSION, IMMUNOSUPPRESSIVE AGENTS and IMMUNOSUPPRESSION or IMMUNOSUPPRESSION (PHYSIOLOGY), etc. The choice of heading depends upon the slant of the article; the author may discuss only the drug group, only the process or disease, or both the drug group and the process or disease. Therapeutic use of antihypertensive agents. ANTIHYPERTENSIVE AGENTS / * ther use Drug therapy of hypertension. HYPERTENSION / * drug ther Use of the most common antihypertensive agents in hypertension. ANTIHYPERTENSIVE AGENTS / * ther use HYPERTENSION / * drug ther 25.8 When indexing a drug or chemical with the subheading /pharmacology, the usual coordination is an organ, organism, physiological or psychological process with the subheading /drug effects. The effect of non-steroidal anti-inflammatory agents on the liver. ANTI-INFLAMMATORY AGENTS, NON-STEROIDAL / * pharmacol LIVER / * drug eff The effect of the stimulant methylphenidate on short-term memory. METHYLPHENIDATE / * pharmacol CENTRAL NERVOUS SYSTEM STIMULANTS / * pharmacol MEMORY, SHORT-TERM / * drug eff 25.8.1 If the drug affects a specific aspect of an organ or organism, that aspect should be indexed also, but will probably be an NIM concept in articles where the pharmacology is the main point. The effect of NSAIDs on liver cytology. NSAID / * pharmacol LIVER / * drug eff / cytol The effect of erythromycin on metabolism in Streptococcus pyogenes. ERYTHROMYCIN / * pharmacol ANTIBIOTICS, MACROLIDE / * pharmacol STREPTOCOCCUS PYOGENES / * drug eff / metab In the examples given above, if the cytology of the liver or metabolism in Streptococcus pyogenes were as important as the effects of the drug, both subheadings could be made IM, following the rules given in section 19.6.1. 25.8.2 When an article is about the effects of an exogenous drug on some physiological function which can be expressed as a subheading, it must be remembered that the subheading on the drug is /pharmacology, not that physiologic subheading. In the following examples, note the use of /pharmacology versus the correct use of the physiologic subheading on the drug. Effects of the gout suppressant allopurinol on liver metabolism. ALLOPURINOL / * pharmacol GOUT SUPPRESSANTS / * pharmacol LIVER / * drug eff / metab (Not: ALLOPURINOL / * metab) Metabolism of the gout suppressant allopurinol in the liver. ALLOPURINOL / * metab GOUT SUPPRESSANTS / * metab LIVER / * metab Immunopharmacology of the immunosuppressant azathioprine. (Author studies the effects of azathioprine on cellular immunity) AZATHIOPRINE / * pharmacol IMMUNOSUPPRESSIVE AGENTS / * pharmacol IMMUNITY, CELLULAR / * drug eff (Not: AZATHIOPRINE / * immunol) Production of an anti-azathioprine antibody. AZATHIOPRINE / * immunol * ANTIBODY FORMATION (Here the drug is acting as an antigen) 25.9 Many compounds in MeSH are endogenous substances for which the subheading /physiology is an AQ; however, they may also be given as exogenous drugs. It can be difficult to determine whether a given article is about the physiologic role or pharmacology of such a compound, but the indexer must make the distinction depending upon the slant of the article. Effects of epinephrine on blood pressure. (Author discusses the use of epinephrine as a vasoconstrictor agent used in with anesthesia, and how it can affect blood pressure during surgery) EPINEPHRINE / * pharmacol VASOCONSTRICTOR AGENTS / * pharmacol BLOOD PRESSURE / * drug eff The physiological role of epinephrine in maintaining blood pressure. EPINEPHRINE / * physiol BLOOD PRESSURE / * physiol 25.9.1 As stated in 19.8.55 and 25.8.2, an article about the effects of an exogenous drug on a physiological process is indexed as the /pharmacology of the drug, not /physiology even if /physiology is an AQ for the drug. The subheading /physiology is to be used only for an article on the role of an endogenous compound. 25.10 Although /pharmacology is usually the correct subheading to cover "effects of" an exogenous drug, /therapeutic use is better when the main point of the article is merely to determine if the drug has therapeutic effects. The effect of rifampin on tuberculosis in rats. RIFAMPIN / * ther use ANTIBIOTICS, ANTITUBERCULAR / * ther use TUBERCULOSIS / * drug ther RATS (check tag) ANIMAL (check tag) 25.10.1 It is possible, however, for an article to be about the effect of a drug on a specific aspect of a disease and not about the treatment of the disease with the drug; in these cases, the correct subheading to use on the drug is /pharmacology, not /therapeutic use. Effects of immunosuppressive agents on T-lymphocytes in patients with chronic kidney failure being prepared for transplantation. IMMUNOSUPPRESSIVE AGENTS / * pharmacol T-LYMPHOCYTES / * drug eff KIDNEY FAILURE, CHRONIC / * immunol / surg (Not: IMMUNOSUPPRESSIVE AGENTS / * ther use) (Not: KIDNEY FAILURE, CHRONIC / * drug ther) Effects of the beta-blocker propranolol on heart rate in obese patients. PROPRANOLOL / * pharmacol ADRENERGIC BETA-ANTAGONISTS / * pharmacol HEART RATE / * drug eff OBESITY / * physiopathol (Not: PROPRANOLOL / * ther use) (Not: OBESITY / * drug ther) 25.11 The injurious effects of a chemical are indexed as /adverse effects, /toxicity, or /poisoning; see section 19.9 for a comparison of these subheadings. 25.11.1 When a drug or chemical causes a harmful effect, the subheading used on the disease produced is /chemically induced. NSAID-induced gastric ulcer in the elderly. NSAID / * adv eff STOMACH ULCER / * chem ind 25.11.2 In research, a chemical known to have harmful effects on an organ may be used to induce a disease of that organ in order to study some aspect of the disease; the chemical and the induction of the disease are not the main points of the article but merely the research technique. In such a case, index the experimental disease with the subheading appropriate to the study as the IM concept. Index the disease NIM with the subheading /chemically induced, and add the chemical NIM but do not use a subheading on it (since the study is not about the drug's adverse effects, nor poisoning by it, nor a study to see if it is toxic). Lung transplantation as an effective treatment of methylcholanthrene induced lung cancers in rats. * LUNG TRANSPLANTATION LUNG NEOPLASMS / * surg / chem ind METHYLCHOLANTHRENE CARCINOGENS RATS (check tag) ANIMAL (check tag) In many instances, the induction of the disease by the chemical is merely the research tool and quite incidental to the material of the article. In these cases, the chemical is third-tier and need not be indexed at all, nor does /chemically induced have to be added to the disease concept. 25.11.3 Do not confuse experimental studies where a chemical is used deliberately to induce a disease in order to study some aspect of the disease with those in which the toxicity of the drug itself is the point. Does methylcholanthrene induce LUNG cancers in rats? METHYLCHOLANTHRENE / * tox CARCINOGENS / * tox LUNG NEOPLASMS / * chem ind RATS (check tag) ANIMAL (check tag) 25.11.4 Many articles on poisoning by a drug or chemical discuss some aspect of the poisoning; in these articles, the subheading needed may be used with the MeSH heading POISONING, but it must be made NIM in reference to poisoning by a specific drug (see section 19.7.4). Treatment of barbiturate poisoning. BARBITURATES / * pois POISONING / ther 25.12 Indexers sometimes have difficulty deciding whether to use /therapeutic use or /administration & dosage with a drug. Usually the point of the article is whether the drug is an effective treatment, so /therapeutic use is more likely to be the correct subheading. The subheading /administration & dosage should be saved for articles in which how to administer the drug is the main point (how much to give, how often to give it, by what route, etc.). Vancomycin administration for staphylococcal endocarditis. VANCOMYCIN / * ther use ANTIBIOTICS, GLYCOPEPTIDE / * ther use ENDOCARDITIS, BACTERIAL / * drug ther / microbiol STAPHYLOCOCCAL INFECTIONS / * drug ther Short-term vancomycin administration versus the standard 28-day schedule. VANCOMYCIN / * admin ANTIBIOTICS, GLYCOPEPTIDE / * admin DRUG ADMINISTRATION SCHEDULE 25.12.1 Since /administration & dosage is treed under /therapeutic use in the Subheading Trees (see Figure 19.5), administration routes and/or dosage forms may be added as NIM coordinations for drugs which have been indexed with /therapeutic use; it is not necessary to use /administration & dosage also. Use of albuterol in the treatment of asthma. (A section contains a discussion on oral versus inhalation administration) ALBUTEROL / * ther use BRONCHODILATOR AGENTS / * ther use ASTHMA / * drug ther ADMINSTRATION, ORAL ADMINISTRATION, INHALATION 25.12.2 When the route of administration or dosage form is indexed for a drug, avoid using subheadings with the dosage form or route, because the subheading in question usually applies to the drug itself. Adverse effects of intramuscular penicillin G. PENICILLIN G / * adv eff / admin PENICILLINS / * adv eff / admin INJECTIONS, INTRAMUSCULAR (Not: INJECTIONS, INTRAMUSCULAR / adv eff) Poisoning with aspirin tablets. ASPIRIN / * pois / admin TABLETS (Not: TABLETS / pois) But: Pain associated with intravenous injections of vinblastine. (Article discusses how intravenous injections of various types of drugs can be painful) VINBLASTINE / * adv eff / admin ANTINEOPLASTIC AGENTS, PHYTOGENIC / * adv eff / admin INJECTIONS, INTRAVENOUS / * adv eff PAIN / * etiol 25.13 Indexers must frequently distinguish between the /analysis, /chemistry, /isolation & purification, /metabolism, and /pharmacokinetics of chemical compounds. For a comparison of these subheadings, see section 19.10. 25.13.1 One aspect of /anal encountered frequently is HISTOCYTOCHEMISTRY, which refers to the identification of chemical compounds present in tissue slices using stains or other methods which allow them to be seen in their location in the tissue, rather than being extracted. When indexing HISTOCYTOCHEMISTRY or its indentions, the subheading on the chemical is /anal, and the corresponding subheading on the organ is /chem; since /chem is not an AQ for diseases, the subheading on any disease studied should be /metab (except for neoplasm terms from Category C4, for which /chem is an AQ). Although histochemistry articles will almost always have pictures of the tissue showing the location of the chemicals, if the author is concerned only with chemical content rather than tissue structure, /anatomy & histology, /cytology, /pathology or /ultrastructure need not be added. Histochemical determination of serotonin in the liver in cirrhosis and liver neoplasms. SEROTONIN / * anal LIVER / * chem LIVER CIRRHOSIS / * metab LIVER NEOPLASMS / * chem HISTOCYTOCHEMISTRY 25.13.2 If an article discusses how a disease causes changes in the levels of the compounds studied, then /metab is the correct subheading to use on the compound and the organ as well as the disease, rather than /anal and /chem. (See sections 19.10.1 and 19.10.4.) 25.13.3 HISTOCYTOCHEMISTRY and its indentions can also be used by pathologists to characterize tissue, since many compounds are present only in certain types of tissues or cells. In such studies, /pathol may be the only subheading needed on the tissue and disease (although /anal will still, of course, be needed on the chemical.) 25.13.4 HISTOCYTOCHEMISTRY and its indentions can be used to demonstrate the presence of enzymes or genetic or immune compounds in tissue; if so, the more specific subheading /enzymology or /immunology should be used on the organ and any disease rather than /chem or /metab; /genetics is an AQ for diseases but not for organs or other anatomical terms except for some subcellular terms such as MITOCHONDRIA, so /chem or /metab should be used on the tissue in which the genetic compound is localized. Immunohistochemical demonstration of C3 levels in the kidney in IgA glomerulonephritis using an immunoperoxidase technique. COMPLEMENT 3 / * anal KIDNEY / * immunol GLOMERULONEPHRITIS, IGA / * immunol IMMUNOPEROXIDASE TECHNIQUES Immunoenzyme analysis of DNA in mitochondria of the facial muscles in familial Bell's palsy. FACIAL MUSCLES / * chem MITOCHONDRIA, MUSCLE / *genet DNA, MITOCHONDRIAL / * anal BELL'S PALSY / * genet IMMUNOENZYME TECHNIQUES 25.14 Three subheadings which are frequently used in indexing chemicals, and which can be thought of as either analytical or metabolic, are /blood, /cerebrospinal fluid, and /urine. The following examples will use /blood as representative of the other two subheadings. 25.14.1 Use the subheading /blood for a study of the analysis of a compound in the blood or blood cells, or its metabolism in blood or blood cells, even if the study is performed in vitro. Analysis of blood sodium. SODIUM / * blood Transport of sodium in isolated erythrocytes. SODIUM / * blood ERYTHROCYTES / * metab BIOLOGICAL TRANSPORT IN VITRO (check tag) 25.14.2 If a pre-coordinated MeSH heading exists for a substance in the blood, use it rather than indexing the substance with the subheading /blood. Analysis of blood proteins. BLOOD PROTEINS / * anal (Not: PROTEINS / * blood) 25.14.3 Do not use the term BLOOD CHEMICAL ANALYSIS routinely in addition to or instead of indexing a specific chemical with the subheading /blood. BLOOD CHEMICAL ANALYSIS should be reserved for general articles, such as articles on methods or instrumentation irrespective of any specific compound. If the methods or instrumentation are particularly discussed in an article on the analysis of a specific blood chemical, and if no MeSH term exists for the specific technique, BLOOD CHEMICAL ANALYSIS may be added to the article with the subheading desired, but it must be made NIM (see section 19.7.4). A new instrument for analyzing blood ferritin levels. FERRITIN / * blood BLOOD CHEMICAL ANALYSIS / instrum But: A newly designed radioimmunoassay instrument for analyzing blood ferritin levels. FERRITIN/ * blood RADIOIMMUNOASSAY / * instrum EQUIPMENT DESIGN (Not: BLOOD CHEMICAL ANALYSIS / instrum) 25.14.4 MeSH contains many Category C terms for diseases in which there is a deficiency or excess of a specific compound in the blood: examples include HYPOCALCEMIA and HYPERCALCEMIA, HYPOKALEMIA and HYPERKALEMIA, HYPOGLYCEMIA and HYPERGLYCEMIA. These terms should be reserved for articles on disease states. Frequently we see articles in which an author uses this type of-emia nomenclature but where there is no actual disease; in these cases, index the compound with the subheading /blood (or the pre-coordinated BLOOD term) instead of the disease term. The hypokalemic effect of thiazide diuretics. (Author is merely studying what the drugs do to levels of potassium in the blood) DIURETICS, THIAZIDE / * pharmacol POTASSIUM / * blood DEPRESSION, CHEMICAL But: Severe hypokalemia caused by an overdose of the diuretic hydrochlorothiazide. HYPOKALEMIA / * chem ind HYDROCHLOROTHIAZIDE / * pois DIURETICS, THIAZIDE / * pois OVERDOSE / compl 25.14.5 "Plasma" and "serum" are often used loosely by authors as synonymous with "blood" for articles on blood levels of various substances. Index any article on "plasma" levels of a compound as just the compound with the subheading /blood; do not add PLASMA unless the author makes a distinction between levels in plasma versus whole blood, serum, or specific blood cells. Plasma copper levels in Wilson's disease. COPPER / * blood WILSON'S DISEASE / * blood But: Elevated levels of hydrocortisone in the plasma and erythrocytes in patients with Addison's disease. HYDROCORTISONE / * blood ADDISON'S DISEASE / * blood PLASMA / * metab ERYTHROCYTES / * metab 25.15 Index a drug or chemical administered exogenously to study a physiologic process or to diagnose a disease with the subheading /diagnostic use. Whether the term with /diagnostic use is IM or NIM depends on the article; in many cases it is third-tier and should not even be indexed. Thyrotropin-releasing hormone stimulation of TSH release in the diagnosis of hyperthyroidism. THYROTROPIN-RELEASING HORMONE / * diag use TSH / * secret HYPERTHYROIDISM / * diag STIMULATION, CHEMICAL Can bromsulphalein be used to study liver function in pregnancy? BROMSULPHALEIN / * diag use LIVER FUNCTION TESTS / * methods PREGNANCY / * physiol Liver metabolic function in pregnancy. (A page of discussion devoted to the bromsulphalein test) LIVER / * metab PREGNANCY / * metab BROMSULPHALEIN / diag use LIVER FUNCTION TESTS / methods Liver metabolism in pregnancy. (Bromsulphalein mentioned in 1 sentence in Materials and Methods) LIVER / * metab PREGNANCY / * metab 25.15.1 The subheading for radioisotopes used in radionuclide imaging is /diagnostic use. Radioisotopes ("tracers") may also be used to label chemical compounds so that their pharmacokinetics can be studied by seeing where the radioactivity goes. The subheading to use on the radioisotope in a tracer study is also /diagnostic use (not /pharmacokinetics, because the /pharmacokinetics of the isotope itself are not being studied). As with other compounds used diagnostically, tracers are often very routine and are considered to be third- tier unless especially discussed. Thallium radioisotope imaging of the heart. THALLIUM RADIOISOTOPES / * diag use HEART / * radionuclide Pharmacokinetics of [76Br]bromospiperone. (Has a long section about the fact that bromine radioisotopes are used infrequently but were desirable for this study) 4-bromospiperone / * pharmacokin BROMINE RADIOISOTOPES / diag use Pharmacokinetics of [14C]salbutamol. (The radioisotope mentioned briefly in Materials and Methods) SALBUTAMOL / * pharmacokin 25.15.2 Indicators and reagents used in performing various laboratory tests as well as stains, monoclonal antibodies, etc. used merely to stain tissue ex vivo should be indexed with no subheading; save /diagnostic use for chemicals which are administered to diagnose a disease or to demonstrate a process occurring in the body. Immunohistochemical demonstration of acetylcholine in nerve fibers using monoclonal antibodies. ACETYLCHOLINE / * anal NERVE FIBERS / * chem IMMUNOHISTOCHEMISTRY / methods ANTIBODIES, MONOCLONAL Visualization of nerve degeneration by administration of monoclonal antibodies to nerve tissue proteins. * NERVE DEGENERATION ANTIBODIES, MONOCLONAL / * diag use NERVE TISSUE PROTEINS / * immunol Restriction mapping with the HaeIII endonuclease. RESTRICTION MAPPING / * methods * HAEIII ENDONUCLEASE 25.16 When indexing biochemistry articles, any article which contains genetic sequences must be flagged for the specialists inputting data into the GenInfo Backbone Database, using the red SEQUENCE DATA flag; at the same time, the term MOLECULAR SEQUENCE DATA must be indexed. See Chapter 28 for a discussion of biochemical genetics and the rules for flagging items for the GenInfo Backbone Database. 25.17 Gene Symbols often appear in articles on biochemical genetics. See Chapter 40 for instructions on indexing Gene Symbols. 25.18 MeSH has many terms to describe molecular characteristics or reactions studied in biochemistry; some examples are given below. These descriptive terms should be made NIM when a specific chemical or group of chemicals is made IM; the terms are IM concepts only for very general articles irrespective of any specific compound(s). BASE COMPOSITION OXIDATION-REDUCTION HYDROXYLATION PROTEIN DENATURATION CARBOHYDRATE SEQUENCE Sequence of myosin and its messenger RNA. MYOSIN / * chem / * genet RNA, MESSENGER / * chem AMINO ACID SEQUENCE BASE SEQUENCE MOLECULAR SEQUENCE DATA Inferring amino acid sequence from nucleic acid sequence. * AMINO ACID SEQUENCE * BASE SEQUENCE 25.19 Enzymes are studied in almost all fields of biomedicine. MeSH contains hundreds of enzymes and even more are available in the Chemical Tool. The authority for enzyme headings is the Enzyme Nomenclature published by the International Union of Biochemistry and Molecular Biology. The indexing of enzymes varies according to the context in which they are discussed. 25.19.1 The most common concept to be covered when indexing an enzyme is its "activity". Enzyme activity is indexed as the /metabolism of the enzyme, paired with /enzymology on any organ, organism, or disease in which the activity is studied. Glutamine synthetase activity in Escherichia coli. ESCHERICHIA COLI / * enzymol GLUTAMINE SYNTHETASE / * metab Brain hexokinase activity in diabetes mellitus. BRAIN / * enzymol DIABETES MELLITUS / * enzymol HEXOKINASE / * metab 25.19.2 If the activity of the enzyme is demonstrated in a specific body fluid, the more specific subheading is used rather than /metabolism. Activity of cerebrospinal fluid hexosaminidases. HEXOSAMINIDASES / * csf 25.19.3 If the enzyme activity is studied in a blood cell, use /blood on the enzyme and /enzymology on the blood cell. Esterase activity in erythrocytes. ESTERASES / * blood ERYTHROCYTES / * enzymol 25.19.4 Although enzyme activity in a disease is usually indexed as the /enzymology of the disease, enzyme levels may be a means of diagnosis and should then be indexed with the term ENZYME TESTS, coordinated with /diagnosis rather than /enzymology on the disease. Diagnosis of lead poisoning by demonstrating elevated levels of delta- aminolevulinic acid dehydratase in the blood. LEAD POISONING / * diag AMINOLEVULINIC ACID DEHYDRATASE / * blood * ENZYME TESTS But: Erythrocyte porphobilinogen deaminase in lead poisoning. (Levels are studied but not discussed as a diagnostic test) ERYTHROCYTES/ * enzymol PORPHOBILINOGEN DEAMINASE / * blood LEAD POISONING / * enzymol 25.20 There are many elements in MeSH in three forms: the element, the isotope of the element, and the radioisotope of the element. When a pre- coordinated term does not exist for the isotope or radioisotope form, index the element (IM) and coordinate with ISOTOPES (NIM) or RADIOISOTOPES (IM), respectively. The annotations indicate when to index the element, its isotope form or its radioisotope form. 25.20.1 ISOTOPES as an IM concept is reserved for general articles only. Whether used as an IM concept or NIM as a coordinate for a specific element, the term has no AQs. Similarly, a pre-coordinated (ELEMENT) ISOTOPES term is indexed with no qualifiers. 25.20.2 The term RADIOISOTOPES may be indexed IM for general articles on radioisotopes, but it may also be used IM as a coordinate for the radioisotope form of an element for which no pre-coordinated term exists; in these cases, use the same subheading on both the element term and RADIOISOTOPES. 25.20.3 If an element is naturally radioactive, a pre-coordinated RADIOISOTOPES term does not exist for it, nor should the term RADIOISOTOPES be added as a coordinate. Each of the naturally radioactive elements is treed under ELEMENTS, RADIOACTIVE in Category D1 and has been annotated "naturally radioactive". 25.20.4 An element is sometimes written with an "m" after the atomic weight (barium 137m, technetium-99m, 204mPb, etc.). The "m" stands for "metastable" and refers to an unstable state which can change to a more or less stable state. To index an element or isotope followed by the letter "m", use the appropriate radioisotope heading for the element (barium 137m = BARIUM RADIOISOTOPES even though barium 137 = BARIUM + ISOTOPES). In the case of an element which is naturally radioactive, merely index the term for the element itself (technetium99m = TECHNETIUM). 25.20.5 See section 25.15.1 for the use of /diagnostic use on radioisotopes used in imaging or as tracers. 25.20.6 The effect of a radioisotope or radioactive element is related to its radioactivity, not its chemical identity. Do not index the effects of a radioisotope or radioactive element with the subheading /pharmacology; index the isotope or element with no subheading, and use /radiation effects on the target of its effects. The effect of radiocobalt on liver metabolism. LIVER / * rad eff / metab * COBALT RADIOISOTOPES 25.20.7 Similarly, the subheading on a disease treated with a radioactive element or radioisotope is /radiotherapy, not /drug therapy. Radioiodine therapy of thyroid neoplasms. IODINE RADIOISOTOPES / * ther use THYROID NEOPLASMS / * radiother 25.20.8 Chemicals may be indexed with the subheading /radiation effects for articles about the effects of radiation on them; the subheading is not used with a radioisotope or radioactive element for its effects. Effects of uranium on blood proteins. * URANIUM BLOOD PROTEINS / * rad eff 25.21 Index anesthetics without subheadings for articles merely on their use as anesthetics; in most cases, an anesthesia term from Category E will also be required. Ketamine as an intravenous anesthetic for surgery in horses. * KETAMINE * ANESTHETICS, DISSOCIATIVE ANESTHESIA, INTRAVENOUS / * vet HORSES / * surg ANIMAL (check tag) 25.21.1 Most articles on anesthetics, however, discuss some aspect of the particular anesthetic being studied: its administration, adverse effects, pharmacokinetics, etc. In these cases it is perfectly acceptable to use the appropriate subheading with the anesthetic. Adverse effects of halothane inhalation anesthesia in relation to the amount administered. HALOTHANE / * adv eff / admin ANESTHETICS, INHALATION / * adv eff / admin ANESTHESIA, INHALATION / * adv eff DOSE-RESPONSE RELATIONSHIP, DRUG Effects of inhaled isoflurane on liver enzymes. ISOFLURANE / * pharmacol ANESTHETICS, INHALATION / * pharmacol LIVER / * drug eff / enzymol 25.22 When indexing a chemical compound from an animal (mouse monoclonal antibodies, rat prolactin, etc.), always check the tag ANIMAL. In addition, check the tag or index the MeSH heading for the animal species if the animal is the point of the article, or if the species appears in the title or statement of purpose for the article. It is not necessary to pick up the animal species if it is just mentioned in passing in the text of the article.