Phenotyping patients

Eap CB, Bender S, Gastpar M, et al. Steady-state plasma levels of the enantiomers of trimipramine and of its metabolites in CYP2D6-, CYP2C19-, and CYP3A4/5-phenotyped patients. Ther Drug Monit 2000 22 209-214. 

Vandel S, Bertschy G, Baumann P, Bouquet S, Bonin B, Francois T, Sechter D, Bizouard P. Fluvoxamine and fluoxetine Interaction studies widi amitriptyline, clomipramine and neuroleptics in phenotyped patients. PharmacolRes (1995) 31,347-53. 

About 30% of the patients on chronic procainamide dosing develop a systemic lupusfike syndrome consisting of arthralgia, myalgia, skin rash, and fever. Patients who are slow acetylator phenotypes may be prone to this condition. Some may exhibit pleuropneumonic involvement and hepatomegaly... 

Czeizel AE. 1994. Phenotypic and cytogenetic studies in self-poisoned patients. Mutat Res 313 175-181. 

It can be expected that the requirement to accumulate multiple mutations to generate a resistant phenotype may translate into a relatively slow development of clinical HCMV resistance, hi addition, a mechanism that is distinct from those of the marketed drugs will offer the possibility of treating patients who have acquired resistance to these agents. 

The situation is somewhat more complex for virus sample amphfied or isolated directly from patient plasma, as these samples comprise a heterologous mix of related yet genetically distinct quasi-species. Often these samples contain mixtures of CCR5-tropic (R5), CXCR4-tropic (X4), and/or dual-tropic viruses these samples are classified in phenotypic ttopism assays as dual/mixed tropic (D/M) (Whitcomb etal. 2007). 

Sarrazin C, Kieffer TL, Bartels D, Hanzelka B, Muh U, Welker M, Wincheringer D, Zhou Y, Chu HM, Lin C, WeeginkCJ, ReesinkHW, Zeuzem S, Kwong AD (2007) Dynamic HCV genotypic and phenotypic changes in patients treated with the protease inhibitor telaprevir (VX-950). Gastroenterology 132 1767-1777... 

Hertogs K, de Bethune MP, Miller V, Ivens T, Schel P, Van Cauwenberge A, Van Den Eynde C, Van Gerwen V, Azijn H, Van Houtte M, Peelers F, Staszewski S, Conant M, Bloor S, Kemp S, Larder B, Pauwels R (1998) A rapid method for simultaneous detection of phenotypic resistance to inhibitors of protease and reverse transcriptase in recombinant human immunodeficiency virus type 1 isolates from patients treated with antiretroviral drugs. Antimicrob Agents Chemother 42 269-276... 

Mammano F, Petit C, Clavel F (1998) Resistance-associated loss of viral fitness in human immunodeficiency vims type 1 phenotypic analysis of protease and gag coevolution in protease inhibitor-treated patients. J Virol 72 7632-7637... 

Rosacea is a chronic disorder affecting the central parts of the face, characterized by flushing, persistent erythema and teleangectasia. Inflammatory papules and pustules can develop within the areas of erythema. Rosacea typically occurs in adults with fair skin and light eye and hair color. In contrast to acne, rosacea is not typically follicular in nature and comedones and seborrhea are usually absent. Pyoderma fa-dale is deemed to be an explosive form of rosacea, often occurring in young women with a phenotype typical of rosacea patients, often in the context of stress (Fig. 11.16). 

Certain mutant hemoglobins are common in many populations, and a patient may inherit more than one type. Hemoglobin disorders thus present a complex pattern of clinical phenotypes. The use of DNA probes for their diagnosis is considered in Chapter 40. 

The phenotype and clinical presentation of antiretroviral toxic neuropathy (ATN) are similar to those of HIV-associated DSP. However, ATN is more likely to be painful, and has an abrupt onset and rapid progression. The main diagnostic clue is the temporal relationship of peripheral neuropathy to the start of NRTI therapy and stabilization, or at least the partial resolution when therapy is interrupted (Moyle and Sadler 1998). ATN most often develops after a mean of 16 to 20 weeks of treatment, unless there are other conditions that lower the threshold. Symptomatic improvement over weeks to months has been reported in two thirds of patients after discontinuation of the offending drug, but may be preceded by an initial period of worsening symptoms, also known as coasting (Berger et al. 1993). Despite the improvement, most patients do not return to a completely asymptomatic state (Hoke and Comblath 2004). 

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