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PubMed2003

ACE and alpha-adducin polymorphism as markers of individual response to diuretic therapy.

Renin-angiotensin system reactivity and the constitutive capacity of the renal tubule to reabsorb sodium play a role in the individual response to diuretic therapy; therefore we evaluated the blood pressure (BP) response to hydrochlorothiazide in 87 never-treated individuals with mild essential hypertension, according to ACE gene I/D and alpha-adducin Gly460Trp polymorphism. These genotypes where chosen because previous data showed their interaction in determining the BP response to salt probably was the result of their involvement in the activation of the renin-angiotensin system (ACE) and in the constitutive capacity of the kidney to reabsorb sodium (alpha-adducin) (treatment for 2 months). BP was measured after 3 run-in visits and after the first and second months of treatment by means of a standardized procedure. Data were analyzed by ANOVA, t test, and multivariate ANOVA for repeated measures (covarying for gender, age, and body mass index). Although basal mean BP (MBP) was similar in the different ACE and alpha-adducin genotypes, patients carrying at least one I allele of ACE and one 460Trp allele of alpha-adducin had the largest MBP decrease with treatment (12.7+/-1.9 mm Hg), the effect of the combination of genotypes being additive but not epistatic. These patients had an odds ratio of 15.75 of being a responder to hydrochlorothiazide compared with patients with Gly460Gly+DD, with the least MBP decrease (3.4+/-1.7 mm Hg). Alpha-adducin and ACE I/D polymorphism may be useful to predict the interindividual degree of response to hydrochlorothiazide; the analysis of the combination of the 2 genotypes increases the accuracy of the prediction of response to the drug.

Antihypertensive Agents↗

PubMed1988

Individual responses to converting enzyme inhibitors and calcium antagonists.

This study was designed to assess whether the acute blood pressure response of an individual hypertensive patient to a calcium antagonist or an angiotensin converting enzyme (ACE) inhibitor is a good predictor of the long-term efficacy of these drug classes in this particular patient. The concept that good responses to ACE inhibitors and calcium antagonists may be mutually exclusive was also tested. Sixteen patients were included in a randomized crossover trial of enalapril, 20 mg daily, and diltiazem, 120 mg daily, for 6 weeks each. Blood pressure was measured by ambulatory blood pressure recording. During the washout phase, the acute effect of nifedipine, 10 mg p.o., and enalaprilat, 5 mg i.v., was evaluated. Nifedipine and enalaprilat reduced blood pressure equally well. The long-term blood pressure reduction induced by enalapril and diltiazem was similar. The acute blood pressure response to a given drug was not a good predictor of the result obtained with long-term therapy. No age dependency of the antihypertensive effect of either drug class was apparent. There was no evidence that a good response to one drug excluded a similarly good response to the other.

Adult↗

PubMed1988

Dosage effects and individual responsivity to methylphenidate in attention deficit disorder.

Effects of three dosages of methylphenidate (0.15, 0.30 and 0.60 mg/kg) were assessed in 19 ADD-H children on a variety of cognitive, academic and behavioral measures in the laboratory and the classroom. A predominant linear pattern of improvement was found across almost all measures. A slight decrease between 0.3 and 0.6 mg/kg on one cognitive task leaves open the possibility that higher dosages reduce stimulant effectiveness or cause decrements on some kinds of "high-level/high load" tasks. Response patterns of individual children varied considerably across measures. All children improved on at least several measures. Results were interpreted as evidence for stimulant activation of self-regulatory processes.

Attention↗

PubMed1976

Predicting individual responses to drug treatment in schizophrenia: a test dose model.

The literature and the findings from the Camarillo Schizophrenia Research Project reported in this paper indicate that a satisfactory method for predicting the response of an individual schizophrenic patient to antipsychotic drugs has yet to be devised. A test dose procedure is described which offers promise of a practical approach to selecting the most appropriate drug and dosage for a particular patient and tailoring blood concentrations to the needs of the individual case. Preliminary findings indicate that the test dose procedure is feasible; that detectable changes occur after a single test dose; and that measurements made during the test dose period may be predictive of eventual outcome. These findings are, of course, only a report of a preliminary pilot experiment, subject to important caveats about small number of cases, interpretation of large numbers of correlation coefficients, and need for cross-validation. Nevertheless, they are encouraging and suggest that the test dose approach has considerable potential for further research.

Antipsychotic Agents↗

PubMed1989

Social phobia: individual response patterns and the effects of behavioral and cognitive interventions.

In the present study, the role of individual response patterns in the treatment of social phobic patients was investigated. Seventy-four patients were diagnosed as social phobics. On the basis of extreme scores on a behavioral test (the Simulated Social Interaction Test) and on a cognitive measure (the Rational Behavior Inventory), the response patterns of 39 patients were analyzed, and the patients themselves were classified as either 'behavioral reactors' or 'cognitive reactors'. Half of the patients with each response pattern received a behavioral focused treatment, i.e. social skills training (SST), while the other half received a cognitive oriented treatment, i.e. rational emotive therapy (RET). Patients received group therapy in eight weekly sessions. Within-group differences showed a considerable improvement in all treatment groups. Between-group differences failed to lend support to the hypothesis that treatment that fits a response pattern (i.e. SST for behavioral reactors and RET for cognitive reactors) will result in a greater improvement than one that does not.

Adolescent↗

PubMed1993

Variability in individual responses of 532 patients with rheumatoid arthritis to first-line and second-line drugs.

Variability in individual responses to drugs used to treat rheumatoid arthritis was studied in 532 patients under care in seven U.S. rheumatology private practices. Among 15 nonsteroidal anti-inflammatory drugs (NSAIDs), estimated continuation of 1,775 courses was 48% at 12 months and 20% at 60 months. Acetylated salicylates, other than plain aspirin, were continued significantly longer than other NSAIDs. Among second-line drugs, estimated continuation of 50% of courses was 10 months for oral gold, 20 months for hydroxychloroquine, 21 months for penicillamine, 25 months for parenteral gold, 27 months for azathioprine, and more than 60 months for methotrexate and prednisone, the only drugs continued by more than 50% of patients 60 months after initiation.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1975

Individual responses to methylphenidate and caffeine in children with minimal brain dysfunction.

Eight children with minimal brain dysfunction were studied for their individual responses to two stimulant medications--methylphenidate hydrochloride and caffeine citrate. Four types of behavioural responses were observed in the double-blind crossover experiment: four children responded favourably to both psychostimulants, one responded to methylphenidate alone and two responded to the placebo. The behaviour of one child deteriorated while he was taking methylphenidate and caffeine. In general, methylphenidate was superior to caffeine in diminishing hyperactive and aggressive behaviour. It is apparent that such stimulant medication exerts its therapeutic effects in these two areas primarily and would therefore be useful as one aspect of a complete treatment program for children with this syndrome.

Attention Deficit Disorder with Hyperactivity↗

PubMed1988

Diagnosis ex juvantibus. Individual response patterns to drugs reveal hypertension mechanisms and simplify treatment.

Heterogeneity of response to antihypertensive therapy is a well-recognized clinical phenomenon. An agent that is antihypertensive in one patient may increase blood pressure in another or have no effect in a third. We believe that this variety of individual response to drug treatment can provide a new framework for the study of hypertensive subjects. Different patterns of response elicited by sequential trials of individual drugs with different mechanisms of action (diuretics, calcium channel blockers, alpha-blockers, beta-blockers, and converting enzyme inhibitors) should provide another means to classify hypertensive patients into biologically relevant groups. The documentation and analysis of this therapeutic heterogeneity in relation to renin profiling and to other physiological and demographic parameters may add a new dimension to the investigation of the pathophysiology of hypertension; it may serve as a basis for more appropriate stratification of participants in clinical trials and may ultimately contribute to a more rational approach to patient management.

Animals↗

PubMed1999

The effects of treatment and the individual responsiveness to growth hormone (GH) replacement therapy in 665 GH-deficient adults. KIMS Study Group and the KIMS International Board.

Data from 665 adults with GH deficiency (GHD; 332 women; 169 childhood-onset GHD; mean age, 44 yr) were analyzed to determine the efficacy of and individual responsiveness to GH replacement therapy. GH replacement was started at enrolment into KIMS (Pharmacia & Upjohn, Inc. International Metabolic Database). Mean maintenance doses of GH after 6 and 12 months were 0.43 and 0.53 mg/day (1.3 and 1.6 IU/day) for men and women, respectively. Serum insulin-like growth factor I (IGF-I) SD score increased from -2.2 and -4.2 in men and women, respectively, to 1.8 and -0.9 at 6 months and 0.8 and -0.7 at 12 months. The waist/hip ratio decreased after 6 and 12 months, with the changes more pronounced in men. The waist/hip ratio was not influenced by age of onset of GHD, severity of hypopituitarism, or gonadal status. Total cholesterol decreased significantly in men, and high density lipoprotein cholesterol increased in women. Systolic blood pressure was unchanged during GH therapy, but diastolic blood pressure decreased in women. Quality of life, determined by a specific questionnaire for assessment of GHD in adults, improved after 6 and 12 months of GH therapy; this was more pronounced in adult-onset than in childhood-onset GHD, but was not influenced by gender, severity of hypopituitarism, or gonadal status. In 80% of patients, the starting dose of GH was 0.27 mg/day or less. This and the absence of a correlation between body weight and change in IGF-I were consistent with a dose-titration approach, which would tend to obscure individual variations in responses (determined by IGF-I levels). Nonetheless, the increase in IGF-I was significantly higher in men than in women on similar mean GH doses. Weak correlations were observed between the maintenance dose of GH and the change in IGF-I in men and women receiving sex steroid replacement, but not in patients with untreated hypogonadism or an intact gonadotropin reserve. Similarly, the increment in IGF-I was not related to the severity of GHD, as determined by the number of additional pituitary hormone deficiencies. Differences in IGF-I generation may partly explain the gender differences in reduction of central adiposity. These data highlight the value of large longitudinal surveillance databases in defining the optimum dose regimen for GH replacement and indicate that women may need a higher replacement dose of GH than men.

Adult↗

PubMedDate not supplied

Non-deterministic individual responses to receptor-selective opioid agonists.

To assess within a single rat strain individual variability of analgesic responses to sub-ED50 doses of receptor-selective opioids, we measured: 1) tail flick latency (TFL) responses after intrathecal (ith) injection of delta, mu, and kappa agonists administered serially; 2) TFL and tail pinch latencies (TPch) after intravenous (iv) mu and kappa agonists; and 3) TFL and TPch after iv agonists of mu or combined mu + delta selectivity. Mean values in each study confirmed an analgesic response, but individual TFL and TPch responses were chaotic and, within each study, rank order correlations between TFL and TPch values within or between drugs were insignificant. Our results suggest a hypothesis that such responses are intrinsically nondeterministic because--resembling other complex dynamic systems--they are generated by stochastic receptor-transmitter interactions that in turn evoke a series of nonlinearly coupled cellular and neural events.

Amino Acid Sequence↗

PubMed1990

Prediction of individual response to controlled ovarian hyperstimulation by means of a clomiphene citrate challenge test.

A clomiphene citrate (CC) challenge test was carried out in 114 patients to evaluate the capacity of this test to predict the patient's individual response to controlled ovarian hyperstimulation (COH) performed with a gonadotropin-releasing hormone agonist and human menopausal gonadotrophins (hMG) for in vitro fertilization. The sum of follicle-stimulating hormone measured before and after CC intake, is the parameter that correlated best with subsequent response to COH. The upper limit of the reference value for this parameter, established by considering the CC challenge test performed on 26 patients who became pregnant, was 26.03 mIU/mL. Twenty patients who presented a CC challenge test result above the reference value were compared with patients with a normal test result. For these 20 patients, COH required more hMG and was cancelled in 25% of the cases (instead of 1% in the control group). The number of follicles aspirated, oocytes retrieved, and embryos obtained were on average six times lower than in patients with a CC challenge test result within the reference value, and no pregnancy was obtained. We concluded that CC challenge test provides a reliable individual prognosis for the ovarian response to COH.

Clomiphene↗

PubMed1980

[Metabolic response of leukocytes as an index of the individual response of an animal to stress and traumatic shock].

A relationship has been established between varying metabolic response of leukocytes to immobilization stress and severity of the shock progress. Initiation of the shock is accompanied by different response of animal leukocytes that correlates with the severity of the subsequent process. Formation of the resistance to shock is associated with an active glucose involvement into energy and plastic metabolic reactions, activation of the substrate-enzymic systems of glycolysis, pentose shunt, terminal stage of the respiratory chain, decreased rate of succinte dehydrogenation.

Animals↗

PubMed1988

[Absence of polymorphism in individual response to the dihydropyridines nifedipine and (+/-)-nicardipine].

Nifedipine, the dihydropyridine calcium channel antagonist prototype, is characterized by wide variability of its hepatic first-pass metabolism and individual response. This could be due to a new genetic polymorphism of drug metabolism, and this hypothesis was investigated in a randomized and cross-over population study in normal volunteers (n = 80). The kinetics and effects of an oral dose of nifedipine (10 mg) and (+/-)-nicardipine (20 mg), a second generation derivative with presumed different biotransformation routes, were evaluated at 0, 1, 2 and 3 h. The two drugs displayed a similar pharmacodynamic profile in terms of heart rate and blood pressure. The observed frequency distributions showed no asymmetry or bimodality suggesting polymorphism. The frequency of headaches and flushes were 21/80 and 19/80 respectively for nifedipine and (+/-)-nicardipine. At the doses administered nifedipine and (+/-)-nicardipine show the same efficacy. This study does not confirm the presence of polymorphism in the response to these dihydropyridines.

Adult↗

PubMed2006

Prediction of individual response to platinum/paclitaxel combination using novel marker genes in ovarian cancers.

We attempted to identify potent marker genes using a new statistical analysis and developed a prediction system for individual response to platinum/paclitaxel combination chemotherapy in ovarian cancer patients based on the hypothesis that expression analysis of a set of the key drug sensitivity genes for platinum and paclitaxel could allow us to predict therapeutic response to the combination. From 10 human ovarian cancer cell lines, genes correlative in the expression levels with cytotoxicities of cisplatin (CDDP) and paclitaxel were chosen. We first selected five reliable prediction markers for the two drugs from 22 genes already known as sensitivity determinants and then identified another 8 novel genes through a two-dimensional mixed normal model using oligomicroarray expression data. Using expression data of genes quantified by real-time reverse transcription-PCR, we fixed the best linear model, which converted the quantified expression data into an IC(50) of each drug. Multiple regression analysis of the selected genes yielded three prediction formulae for in vitro activity of CDDP and paclitaxel. In the same way, using the same genes selected in vitro, we then attempted to develop prediction formulae for progression-free survival to the platinum/paclitaxel combination. We therefore constructed possible formulae using different sets of 13 selected marker genes (5 known and 8 novel genes): Utility confirmation analyses using another nine test samples seemed to show that the formulae using a set of 8 novel marker genes alone could accurately predict progression-free survival (r = 0.683; P = 0.042).

Antineoplastic Agents, Phytogenic↗

PubMed2005

Individual responsiveness to induction of micronuclei in human lymphocytes after exposure in vitro to 1800-MHz microwave radiation.

The widespread application of microwaves is of great concern in view of possible consequences for human health. Many in vitro studies have been carried out to detect possible effects on DNA and chromatin structure following exposure to microwave radiation. The aim of this study is to assess the capability of microwaves, at different power densities and exposure times, to induce genotoxic effects as evaluated by the in vitro micronucleus (MN) assay on peripheral blood lymphocytes from nine different healthy donors, and to investigate also the possible inter-individual response variability. Whole blood samples were exposed for 60, 120 and 180 min to continuous microwave radiation with a frequency of 1800 MHz and power densities of 5, 10 and 20 mW/cm(2). Reproducibility was tested by repeating the experiment 3 months later. Multivariate analysis showed that lymphocyte proliferation indices were significantly different among donors (p<0.004) and between experiments (p<0.01), whereas the applied power density and the exposure time did not have any effect on them. Both spontaneous and induced MN frequencies varied in a highly significant way among donors (p<0.009) and between experiments (p<0.002), and a statistically significant increase of MN, although rather low, was observed dependent on exposure time (p=0.0004) and applied power density (p=0.0166). A considerable decrease in spontaneous and induced MN frequencies was measured in the second experiment. The results show that microwaves are able to induce MN in short-time exposures to medium power density fields. Our data analysis highlights a wide inter-individual variability in the response, which was confirmed to be a characteristic reproducible trait by means of the second experiment.

Adult↗

PubMed1992

[Health promotion and disease prevention: an individual responsibility or social responsibility].

This article is about some theoretical assumptions that have guided health promotion and disease prevention strategies. Some questions are raised in relation to the professional's interventions that consider health promotion as an individual responsibility. It is suggested that the focus should be on social changes through the professionals' consciousness in social, political, behavioral and economic aspects that exert influences over the population's health. These ideas ought to be incorporated to the nurse-client interaction.

Brazil↗

PubMed1996

The individual responsiveness to growth hormone (GH) treatment in GH-deficient adults is dependent on the level of GH-binding protein, body mass index, age, and gender.

The aim of the present trial was to study the individual responsiveness to GH treatment in terms of body composition and to search for possible predictors of the response in GH-deficient adults. Sixty-eight patients (44 men and 24 women) with a mean age of 44.3 (1.2) yr and verified GH deficiency participated in a 2-phase treatment trial with an initial randomized, double blind, placebo-controlled, 6-month period, followed by an open treatment period, thereby ensuring all patients 12 months of GH treatment. Recombinant human GH was administered sc daily at bedtime, with a target dose of 12 micrograms/kg x day. GHBP was measured by ligand-mediated immunofunctional assay, and serum insulin-like growth factor I (IGF-I) was determined by RIA after acid-ethanol extraction, using a truncated IGF-I analog as the radioligand. Lean body mass (LBM) and body fat (BF) were determined by dual energy x-ray absorptiometry, and total body water (TBW) was determined by bioelectrical impedance. During the placebo control period, serum IGF-I,LBM, and TBW increased (P < 0.001), whereas BF decreased (P < 0.001) and serum GHBP was unchanged in the group treated with GH compared with the patients treated with placebo. After 12 months of GH treatment, the individual changes in BF ranged from -12.5 to 4.3 kg and from -4.5 to 10.1 kg in LBM. Age (P < 0.05) and baseline GHBP level (P < 0.01) were inversely correlated with the increase in LBM. The GH-induced increment in IGF-I and TBW was greater in men than in women (P < 0.01), whereas the decreases in BF were similar in men and women. This trial demonstrates the variability in responsiveness to GH administration in GH-deficient adults. The best response to GH was obtained in younger patients with low GHBP levels. Furthermore, men responded better than women.

Absorptiometry, Photon↗

PubMed1990

Kinetic-dynamic relations and individual responses to enalapril.

Pharmacokinetic and pharmacodynamic variability largely account for interindividual differences in the response to antihypertensive drugs including angiotensin converting enzyme inhibitors. The factors determining the response to enalapril have been investigated in a placebo-controlled study in essential hypertension. The effects of placebo, the initial dose of enalapril, and long-term (1 and 6 weeks) treatment with enalapril were studied in 13 subjects. By using an integrated kinetic-dynamic model that incorporates a parameter for saturable protein binding, individual responses for blood pressure reduction and angiotensin converting enzyme inhibition were characterized in terms of the maximum effect (Emax) and the drug concentration required to produce 50% of Emax (Ce50). In individual subjects, plasma enalaprilat concentrations could be correlated with falls in blood pressure and changes in plasma angiotensin converting enzyme activity. For the group, Emax was -46.1 +/- 16.5 and -19.7 +/- 3.8 mm Hg for systolic and diastolic blood pressure, respectively, and the corresponding Ce50 values were 66.1 +/- 20.2 and 61.6 +/- 22.5 ng/ml. For angiotensin converting enzyme inhibition, Emax (%) and Ce50 (ng/ml) were, respectively, 102.4 +/- 5 and 19.8 +/- 13 after the first dose, 103 +/- 5 and 33.4 +/- 20.3 after 1 week, and 101.3 +/- 2.2 and 31.3 +/- 18.9 after 6 weeks. There was no relation between the responsiveness to enalapril (Emax or Ce50) and patient age or plasma renin activity, but there was a significant positive correlation between Emax and the pretreatment blood pressure. In individual subjects, Emax (first dose) was directly correlated with Emax after 1 and 6 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗