Pharmacogenetics: a laboratory tool for optimizing therapeutic efficiency

Pharmacogenetics is the study of the linkage between an individual's genotype and that individual's ability to metabolize a foreign compound. Differences in metabolism of therapeutics can lead to severe toxicity or therapeutic failure by altering the relation between dose and blood concentration of the pharmacologically active drug. Phenotypes exhibiting poor and ultraextensive metabolism result from genetic variance (polymorphism) of enzymes involved in metabolism. Thus, in pharmacogenetic studies one applies genotyping of polymorphic alleles encoding drug-metabolizing enzymes to the identification of an individual's drug metabolism phenotype. This knowledge, when applied to dosing or drug selection, can avoid adverse reactions or therapeutic failure and thus enhance therapeutic efficiency. More than 25 commonly prescribed medicines are metabolized by the cytochrome P-4502D6 (CYP2D6) isoenzyme, and polymorphism of the CYP2D6 gene affects the therapeutic management of up to 17% of individuals in some ethnic groups. In this review, we summarize and update information concerning drug-metabolizing genotypes with emphasis on CYP2D6 genotyping techniques that can be applied by the clinical laboratory for linking human genetics to therapeutic management.     

The art of nursing: the client-nurse relationship as a therapeutic tool

The C-N relationship is the cornerstone and essence of mental health/psychiatric nursing. However, that process has the same potential for nursing in general. The C-N relationship is an interpersonal, interactive, and ongoing relationship set up to assist clients in the continuous evolution toward quality health and well-being. Although this article focuses primarily on the mental health population, the value of a positive working C-N relationship is paramount in addressing all health care issues. The C-N relationship is, indeed, a therapeutic tool that can generate positive side effects, enhance treatment approaches, and greatly influence favorable health care outcomes. It is easy to apply, is flexible, and, when used effectively, can generate the power within health care situations to determine desired health care outcomes.     

Multidimensional reaction to therapeutic touch in a hospital setting.

Studied the effects of interpersonal touch over a relatively long time frame, for a broad range of response dimensions, and in a nonreactive setting characterized by dependency. On an applied level, the research studied the value of touch as a concomitant of nurse–patient interactions; Ss were 48 patients who had entered the hospital for elective surgery. Specifically, a 2 (touch vs no touch) by 2 (male vs female) between-Ss design assessed the effects of nurses touching Ss during preoperative teaching on Ss' affective, evaluative, behavioral, and physiological responses. Female Ss in the touch condition experienced more favorable affective, behavioral, and physiological reactions than a no-touch control group. In contrast, males in the touch condition reacted more negatively than control Ss on these dimensions. (29 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Comparison of cefoxitin and ceftizoxime in a hospital therapeutic interchange program

OBJECTIVE: To determine whether (a) ceftizoxime can replace cefoxitin in the prevention and treatment of various infections in a major teaching hospital, (b) a previously applied two-stage intervention program is an effective method of instituting a therapeutic interchange of ceftizoxime for cefoxitin and (c) the replacement of cefoxitin with ceftizoxime results in a more cost-effective therapy. DESIGN: Two-phase, open, sequential study. SETTING: Tertiary care teaching hospital. PATIENTS: One hundred patients who received cefoxitin during the 6 months immediately before the start of the interchange program (phase 1) and 100 who received ceftizoxime during the 6 months immediately after the start of the program (phase 2) were randomly selected. RESULTS: The demographic characteristics of the two patient groups were similar except for sex (p < 0.05). The cefoxitin doses were usually given every 6 hours (in 33% of the cases) or every 8 hours (in 61%), whereas the ceftizoxime doses were usually given every 12 hours (in 98%). Prescriber distribution was stable throughout the study period, the Department of General Surgery being responsible for about 70% of the orders. Prophylactic indications accounted for over 60% of the treatment courses. The proportion of prophylactic treatment courses that resulted in a successful clinical outcome did not differ between the two groups (cefoxitin 92% and ceftizoxime 91%). Of the empiric or directed treatment courses clinical success or improvement was observed in 89% of the cefoxitin and 91% of the ceftizoxime recipients. Microbiologic eradication was seen in 65% of the cefoxitin and 90% of the ceftizoxime directed treatment courses. Pathogens isolated during therapy were similar in the two treatment groups. Diarrhea was the most common adverse effect, occurring in 8% of the cefoxitin and 10% of the ceftizoxime recipients; no Clostridium difficile or C.-difficile-producing toxin was identified in these patients. The ceftizoxime therapy was 36% less expensive than the cefoxitin therapy on average, and the annual savings was estimated to be $83,123. An estimated 5615 drug doses were avoided annually, for an additional savings of $24,875 in drug administration. Therefore, the total estimated annual cost savings resulting from this two-stage interchange program was $107,998. Given the cost of $4856 to implement and maintain the program, the estimated net savings for the first year was $103,142. CONCLUSION: Ceftizoxime can replace cefoxitin in the prevention and treatment of various infections. The form of evaluation described herein is valuable when any formulary modification is being considered in a hospital.     

Group B Streptococcal septicaemia/meningitis in neonates in a Singapore teaching hospital

Several studies have indicated that frequent allelic losses in some specific chromosomal regions occur during colorectal cancer (CRC) progression. To clarify the correlation between such allelic losses and metastatic potential, the allelotype of lymph node-positive early CRCs, which are small but extremely malignant cancers consisting of metastatically competent cells, were investigated. Nineteen paraffin-embedded specimens of early CRC (pT1 tumors according to TNM classification) with positive lymph nodes were collected. The tumor tissues were examined for loss of heterozygosity (LOH), using microsatellite markers on chromosomes 1p34-36, 8p21-22, 14q32, 18q21 and 22q12-13. The relationship between p53 protein expression and the metastatic status was also investigated by immunohistochemical staining. A group of 20 early CRCs with negative lymph nodes having a similar distribution of macroscopic appearance were used as controls. Among the 19 node-positive tumors, LOH at 8p21-22 and 18q21 was detected in 11 cases (57.9%) and 17 cases (89.4%), respectively. Allelic losses within these 2 regions in node-positive tumors were significantly more frequent than that in node-negative ones (p < 0.01). No significant correlation was found between LOH at 1p34-36, 14q32 or 22q12-13 and lymph node metastasis. p53 protein expression was not significantly associated with lymph node metastasis. Our results suggest that putative tumor suppressor genes, which may be involved in the metastatic process of CRC, are located on chromosomes 8p21-22 and 18q21. Allelic losses in these regions are possible risk factors for lymph node metastasis of early CRC.     

Carotid sinus massage as a diagnostic and therapeutic tool for atrial flutter-fibrillation

Alterations in vagal tone can influence the atrial fibrillatory process by changing the atrial refractory period. We observed in a patient with paroxysmal atrial fibrillation (AF) that carotid sinus massage (CSM) changed a "coarse" type of fibrillation into a "fine" type, followed by termination of the arrhythmia. Although coincidental conversion of AF into sinus rhythm could not be excluded, we concluded that it is worth while to try CSM in every patient presenting with AF prior to other interventions to restore sinus rhythm.     

HIV and other sexually transmitted diseases at a rural hospital in Zimbabwe

OBJECTIVE: To define the epidemiological characteristics of STD patients attending an outpatient clinic in rural Zimbabwe, to examine the aetiologic agents causing infection and to determine their relationship with HIV infection. SUBJECTS: 319 men and 146 women, making a sample of about 7% all patients attending an STD clinic during the 3 month study period. Microbiological data were collected from 104 men and 72 women selected randomly from these. Pregnant women were excluded and patients who had received antibiotics within the previous 14 days were excluded from the microbiology sub-sample. SETTING: An outpatient STD clinic at a District Hospital on a major truck route about 300 km north of the capital, Harare. METHODS: All new patients attending the clinic during a 3 month period were enrolled for clinical and epidemiological investigations using a standard procedure. Specimens for microbiological investigation were taken from every second patient seen on the first three days of each week. RESULTS: The typical patient was male (m:f ratio 2.2) aged 20-29 years (68% patients), not married (56% men) and in paid employment (66% men vs. 27% for the district). In men the most common presenting feature was genital ulceration, while in women, discharges were more common. Genital warts were noted frequently in both sexes. In the sub-sample examined microbiologically, H ducreyi was isolated from 46% ulcers clinically diagnosed as chancroid, and motile spirochaetes were detected in 25% painless ulcers. Neither of these were detected in ulcers in women, but HSV antigen was found as frequently in ulcers from men (19%) as from women (17%). In patients with genital discharges, gonococcal infection occurred in 64% men and 17% women, while T vaginalis was isolated from 39% women and only 8% men. Over 60% gonococcal isolates were PPNG, and 18% showed in vitro resistance to tetracycline. Yeasts, mainly C albicans were isolated from 42% women with a discharge and 25% women with ulcers. In men the presence of yeasts was associated with superficial ulceration and itchiness of the glans. Positive HIV-1 serology was found in 64% patients. There was no statistical association with current genital ulcers, though there was an association with previous STD episodes and particularly with serological evidence of syphilis. Apart from yeasts, there was no association between positive HIV-1 serology and the presence of pathogens in the genital tract. CONCLUSIONS: The high prevalence of HIV-1 antibodies in STD patients in Karoi suggests integration of STD and AIDS control programmes to be a necessity. Since paid employment was a common feature of both STD clinic attendance and HIV-1 seropositivity, these programmes may be effectively directed through the work place.     

From a prospective study of chronic cough: diagnostic and therapeutic aspects in older adults

We examined cardiovascular complication of interferon (IFN) therapy in 23 patients with chronic hepatitis C who did not have cardiac disease prospectively. Twenty four-h Holter monitor recordings were performed before and during IFN therapy. Seven of these patients (30%) showed abnormalities on their 24-h Holter monitoring recordings. Premature ventricular contraction (PVC) occurred in two patients, intermittent WPW syndrome in one, and ST-T change in four. Only one patient with PVC complained of palpitation. These complications were not severe and immediately after IFN therapy was stopped. There was no correlation between Holter ECG abnormalities and sex, age, quantity of HCV, or 2-5 oligoadenylate synthetase activity. It was suggested that cardiovascular complications caused by IFN therapy occurred more frequently than expected. However, diagnosis of these complications is difficult because most patients have no subjective symptoms and there is scarcely any change in laboratory test results. Careful observation of patients may be required during IFN therapy regardless of cardiovascular symptoms.     

Splenic vein thrombosis and chronic pancreatitis: therapeutic approach

10% of chronic pancreatitis (CP) cases are complicated by splenic vein thrombosis (SVT) which is responsible for upper digestive haemorrhages. To improve our approach to treatment we reviewed 30 cases of SVT associated with CP treated in our centre from 1985 to 1995. 14 patients were treated conservatively. Six of them were refused for surgery due to extension of splenic vein thrombosis into the portal vein. Two patients without extrinsic compression of the vein were treated with anticoagulants. 16 patients were treated by surgery with low morbidity and without mortality. The standard treatment in fourteen cases was splenopancreatectomy. The average follow-up of seven years shows that these patients have preserved their body mass index (BMI). The results suggest that early surgical intervention is beneficial in preventing progression of SVT to the portomesenteric vein.     

Vanadium salts as insulin substitutes: mechanisms of action, a scientific and therapeutic tool in diabetes mellitus research

Vanadium and its compounds exhibit a wide variety of insulin-like effects. In this review, these effects are discussed with respect to the treatment of type I and type II diabetes in animal models, in vitro actions, antineoplastic role, treatment of IDDM and NIDDM patients, toxicity, and the possible mechanism(s) involved. Newly established CytPTK plays a major role in the bioresponses of vanadium. It has a molecular weight of approximately 53 kDa and is active in the presence of Co2+ rather than Mn2+. Among the protein-tyrosine kinase blockers, staurosporine is found to be a potent inhibitor of CytPTK but a poor inhibitor of InsRTK. Vanadium inhibits PTPase activity, and this in turn enhances the activity of protein tyrosine kinases. Our data show that inhibition of PTPase and protein tyrosine kinase activation has a major role in the therapeutic efficacy of vanadium in treating diabetes mellitus.     

Emergence of Western diseases in the tropical world: the experience with chronic cardiovascular diseases

We investigated the effects of intrinsic motivation to do research and perceived lack of rewards contingent on doing research on burnout or disenchantment from research. Findings, based on a survey of 328 faculty at a major university, indicate that these two variables account for 74% and 81% of the variance in scores on a scale relating to burnout among 260 tenured and 68 untenured professors, respectively. The effect of perceived lack of rewards contingent on doing research on burnout was moderated by the tenure status.