Micro winter lecture final

Chloramphenicol works against everything but unfortunately it causes aplastic anemia in 1 out of about every 24,000 to 40,000 patients. It's still good enough for government work though -- in third world countries (it helps that it can be given orally). In the US, chloramphenicol is only first line for meningitis when there are known severe allergies to penicillins AND cephalosporins; and for Rickettsial diseases (think Rocky Mountain Spotted Fever) in children or pregnant women.

Imipenem also works against everything, with the notable exception of MRSA. It is degraded renally by dihydropeptidase I (co-administer cilastatin) and excreted renally (reduce dose in renal failure). Meropenem is an improved version that is resistant to dihydropeptidase. Unfortunately, the carbepenems are limited in their use by CNS toxicity: they can cause seizures, though meropenem is better in this respect. They are also cross-allergenic with penicillin. They are first-line therapy for Enterobacter. Ertapenem, a newer carbepenem that only requires once daily I.V. administration, is the drug of choice for severe, polymicrobic diabetic foot infections.

Vancomycin works against all gram positive organisms, with the notable exception of VRE (resistance when D-ala D-ala becomes D-ala D-lac). The main indications for use are endocarditis, line sepsis, and meningitis -- think severe, nosocomial infections where MRSA coverage is crucial. Vancomycin is generally well tolerated (some nephrotoxicity, ototoxicity, thrombophlebitis, IgE-mediated "red man syndrome" if administered by I.V. too fast) but these side effects pale in comparison to the severe situations that actually warrant its use. Vancomycin could be used more broadly, but it's generally held in reserve as an ace card to prevent development of more widespread resistance.

Aztreonam, a monobactam, works against all gram negative organisms, with the notable exception of gram-negative anaerobes. Like other beta lactam antibiotics, they are synergistic with aminoglycosides. However, they are less nephrotoxic than aminoglycosides and can be used as a solo alternative in severe gram negative rod infections. They can also be used if the patient is allergic to penicillins, as unlike cephalosporins and carbepenems, monobactams are not cross-allergenic with penicillin. Monobactams are generally well-tolerated: the only main side effect is occasional GI upset.

Penicillin is first line for beta-hemolytic strep (long-acting IM benzathine penicillin for strep pharyngitis) and syphilis; less high yield -- Actinomyces israelii, and Leptospira interrogans. Penicillin may also be useful against alpha-hemolytic strep like Viridans strep and pneumococcus (latter now displays intermediate-level resistance to penicillin).

Penicillinase-resistant penicillins. Methicillin is no longer used due to interstial nephritis. Use nafcillin for MSSA; use "naf" for staph. Use dicloxacillin (can be given orally) for outpatient empiric treatment of infected skin wound.

Aminopenicillins are penicillinase-sensitive and therefore administered with clavulanic acid. Amoxicillin (oral) is used for outpatient treatment of bronchitis, otitis media, and sinusitis. Ampicillin combined with gentamicin is a combo used for broad empiric coverage (surgery, serious urinary tract infections). Amp-gent also treats enterococcal infections, which are resistant to most penicillin and cephalosporins. Ampicillin also covers Listeria, and is added empirically in meningitis for neonates, the elderly, and the immunocompromised.

Anti-pseudomonals: ticarcillin, carbenecillin, piperacillin.

Actinomyces is resistant to metronidazole; use penicillin. Use TMP-SMX for Nocardia.

First line therapy for meningitis is ceftriaxone and Vancomycin.

Normal flora: Candida; Viridans, Enteroccoci, GBS in women; S. epidermidis; Acinetobacter (only gram negative skin flora), Bacteroides, Fusobacterium, Actinomyces, Pseudomonas, a lot of other Enterobactericiae

Psychiatry final notes

The unique therapeutic actions of clozapine are attributed to 5HT2 receptors. This is also true of the other atypical antipsychotics: olanzapine, quetiapine, risperidone, aripiprazole, ziprasidone.

Risperidone, unlike most antipsychotics, actually increases salivation.

Schizophrenia has a high genetic component. Psychotic symptoms are influenced by life stresses. Intrauterine and perinatal insult is associated with higher risk for schizophrenia. There is no gender or racial difference in schizophrenia incidence. Abuse of hallucinogenic drugs, does NOT lead to schizophrenia. Negative symptoms are least likely to respond to drug therapy; paranoid type schizophrenia (no thought disorder, disorganized behavior, or affective flattening) has best prognosis. Schizotypal is the personality disorder most associated with schizophrenia.

Unipolar disease is more common than bipolar in both sexes. Bipolar disease has more genetic components. Bipolar patients tend to have shorter episodes of untreated illness than unipolar patients. Postpartum disorders are more common in bipolar than unipolar disorder.

Buproprion: less risk of rebound mania.

Therapy of depression. After first major episode: 6-9 months of taking antidepressants. If repeated episodes: at least several years and then re-evaluation.

Cognitive behavioral therapy (CBT): corrects distortions in thinking about oneself and their life; negative triad -- towards oneself, the present world, the future

Interpersonal therapy (IPT): Concentrates on relationships, role transitions; suggests depression often occurs in the context of interpersonal conflict, anger turned inward, loss of a loved one.

Psychodynamic psychotherapy (psychoanalysis-lite): Concentrates on unconscious drives

Panic disorder and generalized anxiety disorder are often comorbid with depression.

Micro lab final notes

M. bovis (TB complex) and M. kansasii cause TB-like respiratory illness in humans -- they are also INH-sensitive. Remember that M. avium-intracellulare and most other nontuberculous mycobacterium are INH-resistant.

Photochromogens (yellow-orange pigment in light): M. kansasii and M. marinum (swimming pool granuloma). It's sunny in Kansas, and over the ocean.

Scotochromogens (pigment in dark and in light): M. scrofulaceum (scrofula, granulomatous cervical lymphadenitis). It's dark where your scrotum is.

Nonchromogens (no pigment): M. avium-intracellulare.

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Rapid death in stationary phase: Strep pneumo, Neisseria.

Klebsiella - butanediol; E. coli -- mixed acids (lactic, formic, acetic acids)

Both Mycoplasma and all fungi have sterols in their cell membranes.

Normal flora: Haemophilus influenza, Candida albicans,

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Isoniazid is activated by catalase and inhibits cell wall synthesis by binding to an enoyl-acyl carrier protein reductase involved in mycolic acid synthesis. Isoniazid resistance is mediated by mutations that knock out catalase or the reductase.

Clavulanic acid is not effective against all beta lactamases, including Class I chromosomally encoded ones (Pseudomonas, Enterobacter, Citrobacter, Serratia).

Metronidazole: intrinsic resistance in Actinomyces; must be reduced to active toxic metabolites in the cell -- these damage DNA.

Quinolones: Both stepwise chromosomal (altered gyrase, reduced uptake) and plasmid-mediated resistance.

Streptomycin binds to single site (S12 protein) on 30S ribosome and is susceptible to single base pair change mutation. Other aminoglycosides bind to multiple sites and are less susceptible. Main mechanism of resistance to aminoglycosides, however, is plasmid- or chromosomally-encoded enzyme inactivation.

Tetracycline: increase efflux of drug (plasmid encoded), or modify ribosome (plasmid encoded).

Path lab exam notes I

Basal cell carcinoma -- arises from basal cell layer of epidermis; multifocal nests of intensely basophilic cells, palisading at the borders; invasion into the dermis -- hence malignant. Like locations: upper lip, inner canthus of the eye.

Psoriasis -- red plaques with white scales; symmetric distribution, frequently on elbows and knees, scalp, genitalia, in general extensor surfaces (in contrast to eczema); acanthosis (thickening of the stratum spinosum), hyperkeratosis (thickening of stratum corneum), perikeratosis (retention of nuclei in stratum corneum); tall dermal papillae.

Herpes zoster -- intraepidermal blisters; at borders of blisters, can see eosinophilic intranuclear inclusions with clear border and then round rim of basophilic marginated chromatin; "dew drop on a rose petal" -- small blister on a red macule; Tzanck stain detects multinucleated epidermal giant cells.

Eczematous dermatitis -- spongiosus.

Melanoma -- brown melanin pigment

Squamous cell carcinoma -- Scaly to nodular lesions, often ulcerated; lower lip, dorsum of hand, or earlobe are common locations (contrast basal cell).

Acne -- hair follicle with keratin and sebum in dermis; foci of inflammation in adjacent wall.

Lupus -- lymphocytic infiltrates in dermis and dermal-epidermal junction; follicular plugging in epidermis; forehead, ear lesions, wolf rash

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Eosinophil -- bilobed nucleus, red granules (look like they have rods or long scrolls in them on EM).

Type II pneumocytes also have distinctive lamellar bodies.

Peritoneal inflammation -- opaque rather than glistening peritoneal surface, petechial hemorrhages,

Alveolar inflammation -- first pass is neutrophils, second pass is macrophages; foamy quality due to lipids in cell walls of phagocytosed bacteria. Macrophages are like a diagnosis of exclusion: not particularly distinctive -- renniform (kidney-shaped) nucleus (not lobulated like neutrophils), more cytoplasm and larger than neutrophils, not really any distinctive granules.

Plasma cell -- eccentric and clockface nucleus, perinuclear clear space; large cell like macrophage, but reddish purple (darker) cytoplasm due to large amount of RER.