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U. Lukjan, M.B. B.CH. B.A.O., M.B.B.Ch., Ph.D.

Medical Instructor, Charles R. Drew University of Medicine and Science

Experimental evidence An animal study found that pretreatment with cannabidiol significantly increased the levels of phencyclidine in the brain and blood of mice. Behavioural tests indicated that the increase in brain levels led to an increase in intoxication caused by phencyclidine. When the study was repeated using 9-tetrahydrocannabinol in doses of 120 mg/kg, the brain levels of phencyclidine were increased twofold. Cannabis Importance and management this preclinical study provides some evidence that cannabis might increase the abuse potential of phencyclidine. Cannabis + Phenytoin There is one in vitro study suggesting that 9-tetrahydrocannabinol, a major constituent of cannabis, might induce phenytoin metabolism. Experimental evidence In an in vitro study in which human liver microsomes were incubated with phenytoin alone, or phenytoin and 9-tetrahydrocannabinol, a major constituent of cannabis, the rate of metabolism of phenytoin was slightly increased in a dose-dependent manner. The rate of metabolism of 9-tetrahydrocannabinol to its 11-hydroxy metabolite was not altered by phenytoin. In one study, the antiepileptic effect of phenytoin was increased when combined with cannabidiol. Note also that there are no reports in the literature of cannabis use affecting phenytoin levels. Note that oral dronabinol (9-tetrahydrocannabinol) has caused seizures in clinical use, and the manufacturer recommends caution in those with a seizure disorder. C Cannabis + Sildenafil Myocardial infarction occurred in a man who had smoked cannabis and taken a tablet of sildenafil. Clinical evidence A 41-year old man with no history of cardiac disease experienced a myocardial infarction after smoking cannabis and recreationally taking a tablet of sildenafil (strength not specified). These included Cannabis + Irinotecan, page 111, and Cannabis + Docetaxel, page 110. Importance and management the vasodilatory effects of sildenafil necessitate caution in its use in patients with cardiovascular disease; myocardial infarction has rarely been associated with its use. The contribution of an interaction to this case is unclear, but bear the possibility in mind in the event of adverse effects on concurrent use. Myocardial infarction following the combined recreational use of Viagra and cannabis. Evidence, mechanism, importance and management One study found that tobacco or cannabis smoking similarly caused higher total clearances of theophylline (given as oral aminophylline) than in non-smokers (about 74 mL/kg per hour compared with 114 Cannabis C 52 mL/kg per hour), and that clearance was even higher (93 mL/kg per hour) in those who smoked both. Little is known about the effects of smoking cannabis on theophylline levels, but be alert for the need to increase the theophylline dosage in regular users. Factors affecting theophylline clearances: age, tobacco, marijuana, cirrhosis, congestive heart failure, obesity, oral contraceptives, benzodiazepines, barbiturates, and ethanol. Cannabis + Tricyclic antidepressants Tachycardia has been described when patients taking tricyclic antidepressants smoked cannabis. Evidence, mechanism, importance and management A 21-year-old woman taking nortriptyline 30 mg daily experienced marked tachycardia (an increase from 90 to 160 bpm) after smoking a cannabis cigarette. Direct information is limited but it has been suggested that concurrent use should be avoided. Marked sinus tachycardia resulting from the synergistic effects of marijuana and nortriptyline. Case study: adverse effects of smoking marijuana while receiving tricyclic antidepressants. Capsicum Capsicum species (Solanaceae) Synonym(s) and related species Caspic, Cayenne, Cayenne pepper, Chili pepper, Chilli pepper, Hot pepper, Paprika, Red pepper, Tabasco pepper. A further in vitro study has shown that the acute use of capsaicin inhibits P-glycoprotein whereas longterm exposure induces P-glycoprotein, see digoxin, page 116. Constituents the pungent principles of capsicum are the capsaicinoids (to which it may be standardised), present in concentrations up to 1. The major components are capsaicin, 6,7-dihydrocapsaicin, nordihydrocapsaicin, homodihydrocapsaicin and homocapsaicin.

Dietary intake and biochemical, hematologic, and immune status of vegans compared with nonvegetarians. Influence of leucine on arterial concentrations and regional exchange of amino acids in healthy subjects. Serum amino acid patterns and toxicity symptoms following the absorption of irrigant containing glycine in transurethral prostatic surgery. Hara S, Shibuya T, Nakakawaji K, Kyu M, Nakamura Y, Hoshikawa H, Takeuchi T, Iwao T, Ino H. Observations of pharmacological actions and toxicity of sodium glutamate, with comparisons between natural and synthetic products. Clinical trials of vitamin B6 and proline supplementation for gyrate atrophy of the choroid and retina. Rate and amount of weight gain during adolescent pregnancy: Associations with maternal weight-for-height and birth weight. Cerebellar dysfunction, mental changes, anorexia, and taste and smell dysfunction. L-Tryptophan-associated eosinophilic fasciitis prior to the 1989 eosinophilia-myalgia syndrome outbreak. The effect of a histidineexcess diet on cholesterol synthesis and degradation in rats. Dimethylglycine and chemically related amines tested for mutagenicity under potential nitrosation conditions. L-Glutamine supplementation in home total parenteral nutrition patients: Stability, safety, and effects on intestinal absorption. Sweat losses by and nitrogen balance of preadolescent girls consuming three levels of dietary protein. Protein requirements of normal infants at the age of 1 year: Maintenance nitrogen requirement and obligatory nitrogen losses. Blood and tissue branched-chain amino and -keto acid concentrations: Effect of diet, starvation, and disease. Long-term toxicity/carcinogenicity study of L-histidine monohydrochloride in F344 rats. Studies on protein requirements of young men fed egg protein and rice protein with excess and maintenance energy intakes. ProteinEnergy Requirement Studies in Developing Countries: Results of International Research. Protein requirements of Filipino children 20 to 29 months old consuming local diets. Hormonal and dietary regulation of lysosomal cysteine proteinases in liver under gluconeogenesis conditions. Effects of dietary protein content and glucagon administration on tyrosine metabolism and tyrosine toxicity in the rat. A study of growth hormone release in man after oral administration of amino acids. An evaluation of the nutritional value of a soy protein concentrate in young adult men using the shortterm N-balance method. Behavioural studies in rats treated with monosodium L-glutamate during the early stages of life. Indices of protein metabolism in term infants fed either human milk or formulas with reduced protein concentration and various whey/casein ratios. The impact of alanyl-glutamine on clinical safety, nitrogen balance, intestinal permeability, and clinical outcome in postoperative patients: A randomized, double-blind, controlled study in 120 patients. Quantitative analysis of amino acid oxidation and related gluconeogenesis in humans. Relation between transamination of branched-chain amino acid and urea synthesis: Evidence from human pregnancy. A morphological study of the acute toxicity of L-cysteine on the retina of young rats.

Know that Cushing syndrome may be produced by systemic or topical (inhaled and dermal) glucocorticoid administration 2. Understand the clinical and laboratory evaluation needed to determine the etiology of hypercortisolism f. Understand effects of glucocorticoid and androgen excess on growth in patients with Cushing syndrome h. Know the disturbance in pattern and significance of serum urine, and salivary concentrations in Cushing syndrome o. Know diagnostic tools available to detect pituitary tumors in Cushing syndrome and the indications p. Know indications and contraindications for removal of pituitary microadenomata in Cushing syndrome r. Know indications for pituitary radiation therapy, either alone or in combination with other therapeutic modalities s. Understand methods of reducing or discontinuing hydrocortisone therapy after surgical treatment of Cushing syndrome u. Understand that radiation therapy is not immediately effective in controlling cortisol secretion, and that other modalities must be used in the interim c. Know that 3-beta-hydroxysteroid dehydrogenase activity is normally decreased in infancy 2. Know that prematurity is associated with higher levels of Delta 5 steroid hormones than observed in full-term infants 3. Know the maturational pattern of synthesis and secretion of the adrenal gland (androgens) in the fetus, infant, prepubertal and pubertal child b. Understand the importance of aromatase in sex hormone metabolism in the fetus and older individuals c. Understand that the adrenal androgens are largely bound to albumin and to a small extent to sex hormone- binding globulin 2. Understand the relative abundance of various androgens and their biologic sources. Understand that adrenal androgens exert their effect through peripheral conversion to more potent androgens 2. Understand the role of the adrenal androgens at adrenarche in the development of pubic and axillary hair 2. Know that adrenal androgen deficiency or resistance may contribute to paucity of pubic and axillary hair b. Know that androgen replacement can be used to treat adrenal androgen deficiency b. Know that elevated adrenal adrogens can suppress pitutiary secretion of gonadotropins 2. Know the clinical features, differential diagnosis, and laboratory diagnosis of premature adrenarche c. Understand the long-term outcome of classic and nonclassic congenital adrenal hyperplasia in terms of growth and reproductive function. Know the long-term outcome of premature adrenarche in that it may be associated with later ovarian hyperandrogenism and/or insulin resistance f. Know that androgen excess may be found in girls with insulin resistance syndrome b. Understand the therapeutic options for androgen excess of adrenal and ovarian derivation C. Know that the adrenal cortex synthesizes and secretes minimal amounts of estrone and estradiol 2. Know that most adrenal estrogens are derived indirectly from peripheral conversion of adrenal androgens 3. Know the clinical and laboratory findings in patients with feminizing adrenal tumors b. Know the pathways by which cholesterol is transformed to aldosterone; understand how this is different from cortisol synthesis 2. Know the enzymes and the genes encoding these enzymes necessary for the synthesis of aldosterone from cholesterol c.

Plaque was assessed using the plaque index and gingival health by the gingival index. Results demonstrated that effective oral hygiene procedures at intervals of 48 hours are compatible with gingival health. However, if the intervals between complete removal of bacterial plaque exceeded 48 hours, gingivitis developed. Waerhaug (1981) reported on the effect of toothbrushing on subgingival plaque formation. Thirty-two (32) upper and lower molars in 4 healthy adult monkeys were used in a split-mouth design in which all teeth were cleaned initially, and then only one side was brushed using the Bass method 3 times a week for one year. Rotary Brushes Long and Killoy (1985) evaluated the effectiveness of the Interplak versus manual toothbrushing (modified Bass) in removing plaque in 14 orthodontic patients. The improvement in postbrushing scores after use of the Interplak instrument was significantly better than that of the manual toothbrush. Patients requiring extraction of teeth for periodontal or prosthetic reasons were chosen for study. There were no significant differences when the Surface Area Plaque Index was used. With the bristles between the teeth, gentle pressure is exerted during slight rotary movements, causing the sides of the bristles to come into contact with the gum margin, producing an ideal massage. After 3 to 4 movements, the brush is removed and replaced in the same area, making another 3 to 4 movements. The brush is then moved the distance of one embrasure, and the process repeated, holding the sides of the bristles firmly on the gum margin. When teeth are missing, patients must depend on the sense of touch to keep the proper pressure, with the sides of the bristles on the gum margin. When used in conjunction with a soft-tomedium brush, this technique can be recommended for temporary cleaning in areas of healing wounds following periodontal surgery (Charters, 1948). With the Bass method of toothbrushing, the head of a soft-to-medium toothbrush is placed parallel with the occlusal plane with the "tip" of the brush distal to the last molar. A gentle vibratory motion is then exerted in the long axis of the bristles and the bristles are forced into the gingival sulcus as well as into the interproximal embrasures. The brush is activated with a short back-and-forth motion without dislodging the tips of the bristles, completing 20 such strokes in the same position. For the palatal aspect of the maxillary anteriors and the lingual of the mandibular anteriors, the toothbrush is held in a vertical position. This technique may be used on the buccal, facial, palatal, and lingual surfaces of all teeth (Bass, 1948). Following the vibratory motion, the bristles are swept towards the occlusal surface of the tooth, cleaning the remaining facial or lingual surface. In the modified Stillman method of brushing, the bristle ends rest partly on the cervical position of the teeth and partly on the adjacent gingiva, directly apically at an oblique angle to the long axis of the teeth. Pressure is applied laterally against the gingival margin, producing a perceptible blanching. The brush is activated with 20 short back-and-forth strokes and is simultaneously moved in a coronal direction along the attached gingiva, the gingival margin, and the tooth surface. This process is repeated on all tooth surfaces, proceeding systematically around the mouth. With this technique, the sides rather than the ends of the bristles are used and penetration of the bristles into the gingival sulci is avoided. The modified Stillman method is recommended for cleaning in areas with progressing gingival recession and root exposure in order to prevent abrasive tissue destruction (Hirschfeld, 1953). According to the Stillman method, the bristles rest partly on the gingiva and partly on the cervical portion of the teeth. The bristles are placed obliquely to the long axis of the tooth, or at an angle to the plane of the gingival surface and directed apically. Sufficient pressure is applied by bending the bristles slightly, creating a perceptible gingival blanching. The brushing action is repeated several times, incorporating a slight rotary motion, but not enough to cause displacement of the bristles. The bristles may be bent in any of 3 directions, but the ends of the bristles should always remain as placed.