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PubMed2000

Stability of sirolimus (rapamycin) in whole blood.

The effects of storage time (0-8 days), temperature (4 degrees C and 30 degrees C in dark and light), and freeze-thaw cycles on the stability of sirolimus in blood were examined. Sirolimus quantification was undertaken using HPLC-electrospray-tandem mass spectrometry. Whole blood samples supplemented with sirolimus (5.0, 15.0, and 30.0 microg/L) and pooled renal and heart transplant samples were found to be stable during the 8 days under all conditions (<10% decrease in concentration). No significant difference was observed in sirolimus concentration between freshly collected patient samples and sirolimus-supplemented samples (5.0, 15.0, and 30.0 microg/L) after three freeze-thaw cycles (p > 0.198). In conclusion, blood samples can be transported with or without cooling for up to 8 days without sirolimus results being compromised. The reanalysis of sirolimus samples, which may entail freeze-thaw cycles, can be undertaken if the number of cycles is three or less.

Drug Stability↗
PubMed2004

Multicomponent screening for drugs of abuse: direct analysis of urine by LC-MS-MS.

By allowing for direct injection of urine, liquid chromatography-tandem mass spectrometry (LC-MS-MS) with atmospheric-pressure chemical ionization has proven to be useful for analysis of drugs of abuse in human urine. The purpose of this study was to evaluate this technique by direct screening for 23 different substances (phenylethylamines, hypnotics, and N-benzylpiperazine) in urine samples. It was possible to achieve lower detection limits compared with commercial immunochemical methods. There was a linear response for all analytes with an intraday coefficient of variation of about 16%, and the gradient elution gave a variability in relative retention time of about 1%. Positive results were confirmed by reanalysis including sample preparation by solid-phase extraction. Among the 529 authentic urine samples analyzed, 35 samples were screened positive for phenylethylamines, and 20 for hypnotics. Of these, 23 (66%) samples were confirmed to be positive for phenylethylamines, and 11 (55%) for hypnotics. This study demonstrates that LC-MS-MS is a valuable complement to immunochemical screening analysis, especially for substances for which immunochemical methods are not yet available or when an increased sensitivity is needed.

Chromatography, Liquid↗
PubMed1994

Molecular diagnosis of the Philadelphia chromosome translocation. A comparison of isotopic and chemiluminescent Southern blotting.

Southern blotting using radiolabeled probes is a well established technique for the detection of the Philadelphia translocation in the diagnosis of chronic myelogenous leukemia (CML). However, the use of radioisotopes in the clinical setting is often problematic. Because of this we investigated the use of a digoxigenin-labeled probe and chemiluminography in the detection of the Philadelphia translocation. In this study DNA was extracted from 19 bone marrow or blood samples from patients with CML or other malignancies and subjected to Southern blotting with a probe specific for the Philadelphia translocation, Phl/bcr3. The probe was labeled with either 32P or digoxigenin to determine the relative sensitivity and specificity of autoradiography and chemiluminography in the molecular diagnosis of the BCR/abl fusion gene. All 19 samples were tested by both methods. All blots were performed and interpreted by individuals blind to the initial patient diagnosis. In addition, 12 samples (6 positive for CML, 6 negative for CML as determined by Southern blotting with 32P-labeled probe) were subjected to triplicate Southern-blot analyses, with three separate lots of digoxigenin-labeled probe to assay batch to batch variability in the efficacy of the probe. Radiolabeled and digoxigenin-labeled probes resulted in identical diagnoses in all cases. All results obtained by molecular analysis correlated perfectly with the clinical diagnoses of the patients from whom the samples had been obtained. Reanalysis of patient samples with different batches of digoxigenin-labeled probe gave highly reproducible results. With digoxigenin-labeled probe, diagnostic results were obtained after exposure times of less than 1 h at room temperature.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoradiography↗
PubMed2006

Clinically significant change in pain intensity ratings in persons with spinal cord injury or amputation.

OBJECTIVE: To examine the clinical significance of changes in chronic pain in 2 disability groups: spinal cord injury and lower limb amputation. METHODS: A reanalysis of 2 controlled clinical trials for pain in persons with disabilities. Eighty-two persons with spinal cord injuries and 34 persons with amputations provided pretreatment and posttreatment ratings of pain intensity on 0 to 10 numerical rating scales. After treatment, participants also rated the meaningfulness of any changes in pain they experienced. RESULTS: An average decrease of 1.80 points on the 0 to 10 numerical rating scales and percent decreases of about 36% corresponded to reports of a meaningful change in pain. There was no significant difference between samples, and also no differences due to gender or treatment condition. Age and pretreatment pain, however, were associated with the amount of pain decrease rated as meaningful. The change in pain intensity rated as meaningful was greater for older participants and participants with higher levels of pretreatment pain. Consistent with previous research, percent change scores were less biased by pretreatment pain than were absolute change scores. DISCUSSION: These findings are generally consistent with similar findings in other pain populations, and, in light of previous research, support an approximate 33% decrease in pain as a reasonable standard for meaningful change across chronic pain conditions. Percent change scores may be more useful for comparing the effects of pain treatments across samples or conditions because they are less biased by pretreatment pain level.

Adult↗
PubMed2006

The exploration of the establishment of cutpoints to categorize the severity of acute postoperative pain.

OBJECTIVES: Although several studies have established different cutpoints (CPs) for mild, moderate, and severe pain for a variety of chronic pain conditions, only one study by Mendoza and colleagues reported on CPs for acute postoperative pain that were derived using ratings of worst pain. The purpose of this study was to explore the establishment of the optimal CPs for mild, moderate, and severe postoperative pain using ratings of average and worst pain and to determine if these CPs distinguished among the pain severity groups on several outcomes. METHODS: The study is a reanalysis of data from patients who underwent hip and knee replacement surgery. Using the methodology described by Serlin et al, a series of CP derivations were performed based on both single item scores for pain intensity and mean scores for pain intensity. One-way analyses of variance, chi analyses, or Kruskal-Wallis tests were conducted to determine if the optimal CPs for pain severity distinguished among the 3 pain severity groups on several outcomes. RESULTS: CPs 3,5 were found using a mean score based on patients' ratings of average and worst pain on the third postoperative day. Findings suggest that mean pain scores of >3 have a significant effect on general activity, mood, walking ability, and sleep. DISCUSSION: Possible explanations for the differences in the CPs found in this study compared with the results by Mendoza and colleagues are discussed. The findings warrant replication in other samples of postoperative patients.

Acute Disease↗
PubMed2006

Model-based RSA of a femoral hip stem using surface and geometrical shape models.

Roentgen stereophotogrammetry (RSA) is a highly accurate three-dimensional measuring technique for assessing micromotion of orthopaedic implants. A drawback is that markers have to be attached to the implant. Model-based techniques have been developed to prevent using special marked implants. We compared two model-based RSA methods with standard marker-based RSA techniques. The first model-based RSA method used surface models, and the second method used elementary geometrical shape (EGS) models. We used a commercially available stem to perform experiments with a phantom as well as reanalysis of patient RSA radiographs. The data from the phantom experiment indicated the accuracy and precision of the elementary geometrical shape model-based RSA method is equal to marker-based RSA. For model-based RSA using surface models, the accuracy is equal to the accuracy of marker-based RSA, but its precision is worse. We found no difference in accuracy and precision between the two model-based RSA techniques in clinical data. For this particular hip stem, EGS model-based RSA is a good alternative for marker-based RSA.

Arthroplasty, Replacement, Hip↗
PubMed2003

Methodologic quality and genotyping reproducibility in studies of tumor necrosis factor -308 G-->A single nucleotide polymorphism and bacterial sepsis: implications for studies of complex traits.

OBJECTIVE: Studies of genetic associations with common diseases, such as between cytokine gene polymorphisms and severe bacterial sepsis, have reached conflicting conclusions. Failure to follow methodologic standards may have contributed to discordant findings. The -308 G-->A transition in the tumor necrosis factor-alpha promoter has been genotyped by a variety of methods. Based on our observation of genotyping inaccuracies, we sought to determine whether published studies followed a series of acceptable methodologic standards and whether failure to follow the standard of genotyping reproducibility could lead to erroneous conclusions about gene-disease associations. DESIGN: Systematic review and reanalysis of banked genetic material. We applied a published series of seven methodologic standards to five reports of the association between this variant and bacterial sepsis. We then studied the accuracy of restriction fragment length polymorphism for the -308 site using DNA from a cohort of injury victims. SETTING: Surgery research laboratory. MEASUREMENTS AND MAIN RESULTS: We observed that methodologic quality was not uniform and that reproducibility of genotyping was infrequently met. In our subjects, we found that 4 of 46 heterozygotes analyzed by restriction fragment length polymorphism were actually GG-homozygotes (9% misclassified) according to alternative genotyping methods. CONCLUSIONS: Failure to confirm genotype may have led to conclusions that this polymorphism is not associated with sepsis or outcome. Our observations have implications for the conduct and evaluation of studies of complex genetic disease.

Genetic Techniques↗
PubMed2004

Incidence and regional distribution of lung overinflation during mechanical ventilation with positive end-expiratory pressure.

OBJECTIVE: In patients with acute lung injury, alveolar recruitment resulting from positive end-expiratory pressure (PEEP) may be associated with overinflation of previously aerated lung regions. The aim of this study was to assess the incidence and regional distribution of lung overinflation resulting from mechanical ventilation with PEEP. DESIGN: Reanalysis with a specific software including a color-coding system of quantitative lung computed tomography data obtained in four previous prospective studies. SETTING: A 20-bed surgical intensive care unit of a Parisian university hospital. PATIENTS: Thirty-two patients with acute lung injury in whom computed tomography of the whole lung was obtained at zero end-expiratory pressure (ZEEP) and PEEP 15 cm H2O. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Total lung recruitment was measured as the reaeration of poorly aerated (computed tomography attenuations ranging between -500 and -100 Hounsfield units) and nonaerated (computed tomography attenuations > or = -100 Hounsfield units) lung areas, and overinflation was measured as the lung volume characterized by computed tomography attenuations < or = -900 Hounsfield units. PEEP was associated with a significant alveolar recruitment (423 +/- 178 mL). Concomitantly, a lung overinflation of 123 +/- 138 mL was found in 14 patients (44%). In eight patients without chronic obstructive pulmonary disease, lung overinflation was predominantly found in nondependent lung regions located beneath the dome of diaphragm. In six patients with a past history of chronic obstructive pulmonary disease, PEEP increased the volume of emphysematous areas present in apical lung regions and produced an overinflation of nondependent lung regions located beneath the dome of diaphragm. CONCLUSION: Lung overinflation resulting from mechanical ventilation with PEEP is observed in more than one third of patients with acute lung injury lying supine and predominates in caudal and nondependent lung regions. Furthermore, in patients with a history of chronic obstructive pulmonary disease, PEEP markedly increases the volume of emphysematous lung regions.

Female↗
PubMed2006

High-dose antithrombin III in the treatment of severe sepsis in patients with a high risk of death: efficacy and safety.

OBJECTIVE: To explore if patients with severe sepsis and with a predicted high risk of death (according to the Simplified Acute Physiology Score II) might have a treatment benefit from high-dose antithrombin III. DESIGN: Subgroup analysis of a randomized, placebo-controlled, double-blind, prospective phase III study. SETTING: Unifactorial and multifactorial reanalysis of prospectively defined populations from the KyberSept trial. PATIENTS: We studied 1,008 patients (43.6% of the overall intention-to-treat population, n = 2,314) with a predicted mortality rate of 30-60% at study entry as defined by the Simplified Acute Physiology Score II. INTERVENTIONS: Patients were randomized in a 1:1 fashion to receive either high-dose antithrombin III (30,000 IU intravenously over the period of 4 days) or placebo. MEASUREMENTS AND MAIN RESULTS: In a Kaplan-Meier analysis of patients with a predicted mortality of 30-60%, the survival time when followed up for 90 days after admission was increased in the high-dose antithrombin III group compared with placebo (p = .04). If heparin was avoided during the 4-day treatment phase with high-dose antithrombin III (n = 140) or placebo (n = 162), the treatment effect appeared to be even more pronounced: 28-day mortality rate, 35.7% vs. 44.4% (risk ratio, 0.804; 95% confidence interval, 0.607-1.064); 56-day mortality rate, 39.9% vs. 52.2% (risk ratio, 0.764; 95% confidence interval, 0.593-0.984); 90-day mortality rate, 42.8% vs. 55.1% (risk ratio, 0.776; 95% confidence interval, 0.614-0.986). Like in the overall population, the percentage with any bleeding was increased in patients receiving high-dose antithrombin III compared with placebo. Survival rates were in favor of high-dose antithrombin III in patients both with and without bleeding complications. CONCLUSIONS: Treatment with high-dose antithrombin III may increase survival time up to 90 days in patients with severe sepsis and high risk of death. This benefit may even be stronger when concomitant heparin is avoided.

APACHE↗
PubMed2005

Analysis of mortality data from cancer screening studies: looking in the right window.

BACKGROUND: Appropriate statistical analysis is required to measure the impact of early detection and treatment of cancer. The current practice of using cumulative mortality ignores both (1) the delay between early treatment and the time that any averted deaths would have otherwise occurred, and (2) cessation of these delayed benefits some time after screening is discontinued. METHODS: We use time-specific mortality density ratios to estimate the mortality ratio in the "window of influence." We then use time-specific incidence density ratios to assess the extent to which the removal of polyps and other possibly precancerous lesions detected by fecal occult blood screening reduces the incidence of colorectal cancer. RESULTS: Applied to a theoretical example, the current practice of using cumulative mortality substantially underestimates the reduction in mortality achievable by early treatment. If there is sufficient time for the full impact to emerge, time-specific mortality patterns provide a more accurate measure. In a previous analysis of the screening study, the reduction in cumulative incidence in the screened groups was just under 20%. In our reanalysis, yearly incidence density ratios indicate that had screening not been interrupted, there might have been a 40% reduction in incidence. CONCLUSIONS: Time-specific mortality ratios provide a more sensitive measure of the effects of early detection and treatment. Measures based on cumulative mortality are diluted by inclusion of deaths that occur soon after the initiation of screening as well as deaths that occur too long after the cessation of screening.

Colorectal Neoplasms↗
PubMed2005

Hydroxyzine and metabolites as a source of interference in carbamazepine particle-enhanced turbidimetric inhibition immunoassay (PETINIA).

A 32-year-old epileptic patient with a lengthy history of multiple-drug abuse and psychotic disorders was found to have an elevated serum carbamazepine concentration of 40.5 mg/L (therapeutic range 4-12 mg/L) using particle-enhanced turbidimetric inhibition immunoassay (PETINIA). Serum reanalysis by LC-DAD revealed only high hydroxyzine (HDZ) concentration (HDZ = 0.55 mg/L; therapeutic range <0.1 mg/L), suggesting cross-reactivity between HDZ and PETINIA. To confirm this hypothesis, the authors tested 2 commercially available carbamazepine immunoassays, PETINIA and EMIT 2000, for in vitro cross-reactivity with HDZ and 2 HDZ metabolites (cetirizine and norchlorcyclizine). To determine the frequency of this interaction in a clinical setting, 40 sera of 39 patients taking HDZ without carbamazepine were tested by both immunoassays. For some samples, LC-ESI-MS analysis of HDZ metabolites was performed. Additionally, cross-reactivities produced by other benzhydrylpiperazine drugs were evaluated. in vitro, 5 mg of HDZ, cetirizine, and norchlorcyclizine cross-reacted with PETINIA at 85%, 125%, and 66%, respectively. Conversely, EMIT 2000 showed no cross-reactivity. For PETINIA, erroneous carbamazepine concentrations were detected in 35 out of 40 sera of patients taking HDZ. The magnitude of interference correlated moderately with serum HDZ concentrations (Spearman rho coefficient 0.58, P < 0.001), suggesting a major role for the multiple HDZ metabolites (4 serum metabolites were detected by LC-ESI-MS). Furthermore, other benzhydrylpiperazine drugs (eg, oxatomide) showed in vitro cross-reactivity with PETINIA. In conclusion, HDZ and its metabolites cross-react with carbamazepine PETINIA immunoassay, which could significantly affect the correct interpretation of serum carbamazepine concentrations in patients treated with HDZ.

Adult↗
PubMed2006

The relationship between P-glycoprotein (PGP) polymorphisms and response to olanzapine treatment in schizophrenia.

P-glycoprotein (PGP) is a polymorphic efflux transporter located on the blood brain barrier that potentially affects the penetration of atypical antipsychotics into the central nervous system. Increased antipsychotic penetration to the primary site of activity may result in greater symptom improvement or the occurrence of side effects. This investigation examined the relationship between three common PGP polymorphisms (C1236T, G2677TA, and C3435T) and response to 6 weeks of open-label olanzapine treatment in patients with schizophrenia. Individuals with a PGP T allele at any of these polymorphisms would be expected to have greater antipsychotic penetration through the blood brain barrier, due to lower PGP activity. Forty-one patients were included in this reanalysis. For subjects in the 3435T allele carrier group, the plasma olanzapine level alone was positively associated with percent change in Brief Psychiatric Rating Scale score (p = 0.02). This relationship was not seen for the 3435CC group (p = 0.583). A similar trend was observed for negative symptom reduction, olanzapine plasma concentration, and the 3435T allele (p = 0.06), but this relationship did not meet statistical significance. There was no relationship between the PGP genotypes and changes in weight over the course of this 6 week study. The analysis using C1236T or G2677AT genotypes gave similar results, due to linkage of these polymorphisms.PGP polymorphisms may affect the penetration of olanzapine into the central nervous system as seen by a relationship between the 3435T allele, olanzapine plasma levels, and reduction in the positive symptoms of schizophrenia. This may stem from greater olanzapine central nervous system latency due to the presence of the 3435T allele and reduced PGP activity. The PGP C3435T genotype may help to determine positive symptom reduction from olanzapine clinically, but these findings should be replicated in a larger sample of subjects.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMedDate not supplied

Does QTc interval predict the response to beta-blockers and calcium channel blockers in hypertensives?

The QT interval corrected for heart rate (QTc) is believed to reflect sympathovagal balance. It has also been established that beta-blockers and dihydropyridine-type calcium channel blockers (DHPCCB) influence the autonomic nervous system. This study tested the hypothesis that QTc interval length is a predictor of the blood pressure reduction induced by beta1-selective beta-blockers or DHPCCB. The predictive values of pretreatment heart rate and of the heart rate change with therapy were also evaluated. The authors conducted an historical reanalysis of 5 clinical trials that looked at the antihypertensive effects of beta-blockers (nebivolol) or DHPCCB (amlodipine, felodipine, isradipine, nifedipine). Correlation and quintile analyses were performed to measure the association between QTc interval, heart rate, or heart rate change and therapeutic blood pressure response. Separate analyses were undertaken for beta-blockers and DHPCCB. Seventy-three and 98 hypertensive subjects respectively were included in the beta-blocker and DHPCCB analyses. QTc interval, pretreatment heart rate, and heart rate change with therapy were not associated with therapeutic blood pressure response. In this study, QTc interval length, pretreatment heart rate, and heart rate change with therapy were not good predictors of the blood pressure response to beta1-selective beta-blockers or DHPCCB in hypertensive subjects.

Adrenergic beta-Antagonists↗
PubMed2004

Residential radon exposure and lung cancer risk: commentary on Cohen's county-based study.

The large United States county-based study () in which an inverse relationship has been suggested between residential low-dose radon levels and lung cancer mortality has been reviewed. While this study has been used to evaluate the validity of the linear nonthreshold theory, the grouped nature of its data limits the usefulness of this application. Our assessment of the study's approach, including a reanalysis of its data, also indicates that the likelihood of strong, undetected confounding effects by cigarette smoking, coupled with approximations of data values and uncertainties in accuracy of data sources regarding levels of radon exposure and intensity of smoking, compromises the study's analytic power. The most clear data for estimating lung cancer risk from low levels of radon exposure continue to rest with higher-dose studies of miner populations in which projections to zero dose are consistent with estimates arising from most case-control studies regarding residential exposure.

Female↗
PubMed2003

Truncating the dose range for methacholine challenge tests: three occupational studies.

The methacholine challenge test protocol was assessed in the reanalysis of three occupational studies. We evaluated the impact of truncating the range of methacholine on responsiveness, as defined by slope and PC(20). In original analysis, reactivity was similar for apprentices and auto body shop workers, whereas boilermakers were more responsive. Truncating high concentrations did not change the classification of subjects with PC(20) <8 or 16 in any population. However, when responsiveness was measured by slope, the mean responsiveness increased, from -7.9 to -15.3 for apprentices and -7.2 to -10.0 for auto-body shop workers. Results support the American Thoracic Society's recommended maximum of 16 mg/ml and provide evidence that extending the dose range beyond that does not increase sensitivity, whereas stopping before 16 may exaggerate response. Furthermore, to ensure validity, neither slope nor PC(20) should be extrapolated beyond data.

Adult↗
PubMed2004

Depression in young adolescents: investigations using 2 and 3 factor versions of the Parental Bonding Instrument.

Associations between parenting style and depressive symptomatology in a community sample of young adolescents (N = 2596) were investigated using self-report measures including the Parental Bonding Instrument and the Center for Epidemiologic Studies Depression Scale. Specifically, the 25-item 2-factor and 3-factor models by Parker et al. (1979), Kendler's (1996) 16-item 3-factor model, and Parker's (1983) quadrant model for the Parental Bonding Instrument were compared. Data analysis included analysis of variance and logistic regression. Reanalysis of Parker's original scale indicates that overprotection is composed of separate factors: intrusiveness (at the individual level) and restrictiveness (in the social context). All models reveal significant independent contributions from paternal care, maternal care, and maternal overprotection (2-factor) or intrusiveness (3-factor) to moderate and serious depressive symptomatology, controlling for sex and family living arrangement. Additive rather than multiplicative interactions between care and overprotection were found. Regardless of the level of parental care and affection, clinicians should note that maternal intrusiveness is strongly associated with adverse psychosocial health in young adolescents.

Adolescent↗
PubMed2003

Group B streptococcus: prevention of early-onset neonatal sepsis.

UNLABELLED: Group B streptococcus (GBS) was recognized as a major pathogen of neonatal disease in the 1970s. With a case-fatality rate of 5% to 20%, prevention of GBS neonatal disease has been an ongoing concern. The Centers for Disease Control and Prevention (CDC), and American College of Obstetricians and Gynecologists (ACOG) published guidelines for preventive strategies in 1996. These strategies, either a risk-based or a culture-based program, have been responsible for reduced incidence of GBS-newborn disease from 1.7 to 0.4 per 1,000 live births in the years 1993 to 1999. However, there has been considerable variability in practice patterns. Reanalysis now shows that a culture-based prevention strategy provides greater reduction in early-onset neonatal disease than a risk-based protocol. The CDC replacement guidelines of August 2002 recommend culture-based GBS prevention; the risk-based strategy is no longer supported. Continued efforts to eradicate GBS-newborn disease require an understanding of the pathogen, colonization, and transmission, GBS sampling and detection methods, and maternal therapy. Until a reliable vaccination against GBS is developed, prevention of neonatal GBS disease will rely upon intrapartum treatment of maternal carriers. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians LEARNING OBJECTIVES: After completion of this article, the reader will be able to define the pathogen, describe the methods of transmission and detection, and outline the current recommendations for maternal group B streptococcus therapy.

Colony Count, Microbial↗
PubMedDate not supplied

Allelic variation in the serotonin transporter gene-linked polymorphic region (5-HTTLPR) and cardiovascular reactivity in young adult male and female twins of European-American descent.

OBJECTIVE: To examine the effect of length variation in the serotonin transporter gene-linked polymorphic region (5-HTTLPR) on individual differences in cardiovascular response to psychological challenge. METHODS: Heart rate (HR) and systolic and diastolic blood pressure (SBP, DBP) responses to computerized versions of two psychological challenges, the Stroop Color-Word Interference Test and mental arithmetic, were measured among 131 monozygotic (MZ) and 60 dizygotic (DZ) male or female (same-sex) European-American twin pairs. Among the 382 participants, 140 were homozygous for the "long" allele (l/l) at 5-HTTLPR, 61 were homozygous for the "short" allele (s/s), and 181 participants had one long and one short allele (l/s). Association and sib-pair analyses were performed to characterize genetic associations. RESULTS: In the full sample, 5-HTTLPR was associated with HR reactivity to psychological challenge, albeit in interaction with sex. Task-elicited HR responses of women homozygous for the short allele were significantly greater than among: a) men of the same genotype; and b) women having either one (l/s) or two (l/l) long alleles at 5-HTTLPR. SBP and DBP responsivity was unrelated to genotype. These results were corroborated on reanalysis in two genetically independent subsamples. Variability at 5-HTTLPR also predicted HR reactivity in sib-pair analyses among DZ twins. CONCLUSIONS: These results suggest that the commonly observed sex difference in HR reactivity may be, in part, genetically mediated and perhaps occur only among individuals homozygous for the short allele at 5-HTTLPR.

Adult↗