Brief Report: Self-Injurious Behaviors in Preschool Children with Autism Spectrum Disorder Compared to Other Developmental Delays and Disorders.

We compared the prevalence of self-injurious behaviors (SIB) in preschoolers aged 30-68 months with autism spectrum disorder (ASD) (n = 691) versus other developmental delays and disorders (DD) (n = 977) accounting for sociodemographic, cognitive, and medical factors. SIB prevalence was higher in ASD versus all DD [adjusted odds-ratio (aOR) 2.13 (95% confidence interval (95% CI) 1.53, 2.97)]. In subgroup analyses, SIB prevalence was higher in ASD versus DD without ASD symptoms [aOR 4.42 (95% CI 2.66, 7.33)], but was similar between ASD and DD with ASD symptoms [aOR 1.09 (95% CI 0.68, 1.77)]. We confirmed higher prevalence of SIB in ASD versus DD, independent of confounders. In children with DD, SIB prevalence increased with more ASD symptoms. These findings are informative to clinicians, researchers, and policymakers.

Factors Associated with Self-Injurious Behaviors in Children with Autism Spectrum Disorder: Findings from Two Large National Samples.

In this study, we explored potential associations among self-injurious behaviors (SIB) and a diverse group of protective and risk factors in children with autism spectrum disorder from two databases: Autism and Developmental Disabilities Monitoring (ADDM) Network and the Autism Speaks-Autism Treatment Network (AS-ATN). The presence of SIB was determined from children's records in ADDM and a parent questionnaire in AS-ATN. We used multiple imputation to account for missing data and a non-linear mixed model with site as a random effect to test for associations. Despite differences between the two databases, similar associations were found; SIB were associated with developmental, behavioral, and somatic factors. Implications of these findings are discussed in relation to possible etiology, future longitudinal studies, and clinical practice.

p(1),p(4)-diadenosine 5'-tetraphosphate induces the uptake of arginine and citrulline by a pore on the plasma membrane of bovine aortic endothelial cells.

We have previously demonstrated that p(1),p(4)-diadenosine 5'-tetraphosphate (Ap(4)A) induces the release of nitric oxide (NO) and modulates the uptake of extracellular L-arginine (L-Arg) and L-citrulline (L-Cit) by bovine aortic endothelial cells (BAEC) [Hilderman, R.H. and Christensen, E.F. (1998) FEBS Lett. 427, 320-324 and Hilderman, R.H., Casey, T.E. and Pojoga, L.H. (2000) Arch. Biochem. Biophys. 375, 124-130]. In this communication we report that extracellular Ap(4)A enhances the uptake of L-Arg and L-Cit through a pore on the plasma membrane of BAEC that is selective for these two amino acids. We also demonstrate that Ap(2)A, which induces NO release, enhances L-Arg uptake while Ap(5)A, a vasoconstrictor, does not enhance the uptake of L-Arg. The potential physiological significance of the uptake of these two amino acids in relation to NO synthesis is discussed.

Potential angiotensin-converting enzyme inhibitor-epoetin alfa interaction in patients receiving chronic hemodialysis.

We compared epoetin alfa (EPO) dose requirements and hematocrit response in 17 patients receiving chronic hemodialysis at baseline and after 3 and 12 months of therapy with angiotensin-converting enzyme (ACE) inhibitors (12 enalapril, 5 captopril). No acute processes were present (infection, hemorrhage, inflammation) at time of starting ACE inhibitor therapy. Mean (+/- SD) intravenous EPO dosages at zero, 3, and 12 months were 6012 +/- 2575, 5800 +/- 2026, and 5660 +/- 2285 U 3 times/week (p=0.56), and mean differences were -212 U for 0-3 months (95% CI -1310 to 886) and -713 U for 0-12 months (95% CI -2142 to 716). Mean +/- SD hematocrits were 30.5 +/- 3.9%, 31.6 +/- 3.2%, and 34.2 +/- 3.1% (p=0.01, zero vs 12 mo), and mean differences were 1.7% for 0-3 months (95% CI -1.41 to 4.81) and 3.85% for zero-12 months (95% CI 0.71-7). Our results indicate that ACE inhibitors do not increase EPO dose requirements or reduce hematocrits in these patients.

The metabolic effects of oxytocin are mediated by a uterine type of receptor and are inhibited by oxytocin antagonist and by arginine vasopressin in the dog.

Infusion of oxytocin (OT) into normal dogs, in doses which produced plasma levels of OT in the physiological range, has been shown to increase plasma levels of glucose, insulin and glucagon and increase rates of glucose production and uptake. This study sought to determine whether there was a correlation between these metabolic effects and the oxytocic potency of four less potent oxytocic analogues when infused into normal dogs. The rank order of oxytocic potency of all 4 correlated well with the rise in plasma glucose levels, and in 3 of the 4 with the rise in plasma insulin levels. An antagonist of the oxytocic effect of OT suppressed the usual OT-induced rise in plasma glucose, insulin and glucagon as well as the increased glucose production and uptake. Arginine vasopressin (AVP) infusion, which by itself did not produce any metabolic effects, blocked completely the effects of OT infusion to raise plasma glucose and insulin levels and increase glucose production and uptake. The data suggest that the metabolic effects of OT in the dog are mediated by OT receptors that are similar to those producing the oxytocic effects. Whether the inhibition by AVP of the metabolic and hormonal effects of OT occurs at the receptor or post receptor level or via other mechanisms remains to be determined.

On the stability of salivary progesterone under various conditions of storage.

The concentrations of progesterone in saliva of women exhibited significant decreases when the fluid was stored in plastic vials for 3 days at room temperature or 37 C. The addition of antibiotics or a variety of metabolic poisons to the saliva prior to storage did not prevent the progesterone decrement. However, the addition of albumin (2 g/dl) was protective, suggesting that the protein impeded adsorption of salivary progesterone by the plastic container. Saliva could be maintained at 37 C for 3 days in glass vials or at -20 C in plastic containers for indefinite periods without loss of progesterone titers. These data indicate that a patient under luteal function assessment may collect saliva samples in glass vials at regular intervals during the latter half of her cycle and store them in the freezer compartment of the refrigerator until shipment by mail to the laboratory for progesterone assay. With special care, plastic vials charged with albumin may also be used.

Effectiveness of selective use of intravenous pyelography in patients presenting to the emergency department with ureteral colic.

OBJECTIVE: To determine whether i.v. pyelography (IVP) is required routinely for all patients presenting to the ED with ureteral colic. METHODS: A randomized prospective study was conducted with 2 patient group-a routine IVP group, in which all patients underwent IVP, and a selective IVP group, in which patients were treated, observed, and released without undergoing IVP unless they experienced continued symptoms. The study was performed in a large university-affiliated, community hospital ED. Participants were patients aged 18-65 years with signs and symptoms consistent with ureteral colic. RESULTS: Among the 40 patients enrolled in the routine IVP group, 26 had positive studies, 8 of which necessitated hospitalization. Among the 41 patients randomized to the selective IVP group, there were only 19 IVPs performed, of which 6 were positive and 4 necessitated hospitalization. Compared with the routine IVP group, there were 54% fewer IVPs performed and a 51% lower admission rate in the selective IVP group. Despite the fact that fewer IVPs were performed in the selective IVP group, clinical outcomes in the 2 groups were similar, without significant complication in either group. CONCLUSIONS: IVPs do not need to be routinely performed for all patients presenting to the ED with ureteral colic. The decision to perform an IVP may be dictated by symptoms that persist after initial evaluation and treatment.

The effects of regionalization on clinical outcomes for a high risk surgical procedure: a study of the Whipple procedure in New York State.

The purpose of this study was to analyze the effects on clinical outcomes of regionalization for a high risk surgical procedure, pancreaticoduodenectomy (the Whipple procedure). Claims data were examined for all Medicare patients undergoing the procedure in New York State for the 4-year period 1991-1994. Outcomes were analyzed for two regional hospitals and for 115 other hospitals that performed the procedure. In-hospital mortality and length of stay were significantly less at the two high volume regional hospitals when compared with the remaining low volume hospitals. In-hospital mortality rates at all hospitals generally decreased as the number of procedures increased. The results of this study demonstrate that there is significant value in regionalization for even relatively lower volume high risk surgical procedures.

An analysis of the reliability of self reported work histories from a cohort of workers exposed to polychlorinated biphenyls.

An investigation was conducted to examine the reliability (reproducibility) of self reported occupational histories obtained from a cohort of 326 capacitor manufacturing workers who had participated in an epidemiological study relating health abnormalities to exposure to polychlorinated biphenyls (PCBs). For a subsample of the cohort (n = 164) in which occupational histories were obtained twice (in 1976 and 1979), reliability of cumulative exposure to PCBs ranged from 93.6% for the early PCB period (1947-70) to 95.7% for the late PCB period (1971-6). These respective reliabilities were lower, however, for workers who changed jobs often. Workers above the median value of a weighted job change index had early and late reliabilities of 89.9% and 83.6% respectively. Reliability is a relevant factor when calculating power or sample size during the planning stage of epidemiological studies, for interpretation or adjustment of estimates in the analysis stage, or for determination of study feasibility.

Cross-dependence to opioid and alpha 2-adrenergic receptor agonists in NG108-15 cells.

Clonidine, a partial alpha 2-agonist, has been used empirically to alleviate opiate withdrawal symptoms, but the mechanism of its effects is not completely understood. We studied the interactions of opioid and adrenergic receptor agonists in the NG108-15 cells, which are a model of opiate dependence. We determined that in these cells the adenylate cyclase (AC) [EC 4.6.1.1; ATP pyrophosphate-lyase (cyclizing) overshoot response to opioid or alpha 2-agonist withdrawal can be significantly attenuated or suppressed by the other agonist. Subsequently, the AC overshoot response can be triggered with the antagonist to the second agonist to which the cells were not dependent. These results demonstrate that convergent dependence to morphine and alpha 2 agonists can occur in a homogeneous cell population without neuronal loops. Therefore, the basic mechanisms that can account for convergent dependence in this model take place at the level of intracellular regulatory pathways that do not require neuronal networks.

Height and mortality after myocardial infarction.

A case-control analysis was conducted to determine the relationship between height and mortality among patients enrolled in the already completed Beta Blocker Heart Attack Trial (BHAT). In a basic model including height (continuous) and relevant covariates the relative risk (RR) per 4-inch reduction in height (approximately 1 standard deviation) was 1.18 (95% confidence interval, 0.92 to 1.51). When sex was considered, the effect of short stature on mortality was found to be restricted to male subjects. The male RR per 4-inch reduction in height was 1.26 (0.96 to 1.63) whereas for women it was 0.89 (0.49 to 1.59). In males not randomized to propranolol (untreated) the effect was further modified with a RR per 4-inch reduction in height of 1.41 (1.00 to 1.99). It is hypothesized that short stature could be a marker for factors operating as far back as childhood that predispose males to mortality from coronary heart disease in later life.

The effect of relaxin on calcium fluxes in the rat uterus.

Relaxin is a polypeptide hormone that inhibits rat uterine contractions. To test the hypothesis that the mechanism of action of this effect may involve shifts in calcium ions, the biologic action of relaxin on isolated rat uterine horns was directly correlated with measurements of 45Ca2+ efflux from and uptake into the tissues. Kinetic analysis demonstrated that the efflux of 45Ca2+ from rat uterine horns was significantly faster when tissue was incubated with 25 ng/ml relaxin as compared with control tissues incubated with no relaxin. In addition, at the end of the efflux experiments, control uteri contained 3.9% of the starting 45Ca2+, whereas the relaxin-treated uteri contained only 2.55%, indicating greater total Ca2+ efflux from the relaxin-treated horns (p less than 0.05). The effect of relaxin on 45Ca2+ uptake by uterine tissue was also studied. Analysis of uptake curves by linear regression demonstrated that relaxin treatment leads to less total uptake of 45Ca2+ in the uterine tissue, although the differences are not statistically significant. These experiments demonstrate that relaxin inhibition of rat uterine contractions in vitro is associated with a decrease in intracellular free Ca2+, caused, at least in part, by the promotion of Ca2+ efflux. These results represent the first step in defining the mechanism of action of this hormone.

Haloperidol in schizophrenic children: early findings from a study in progress.

This report presents preliminary findings in an ongoing double-blind, placebo-controlled study of the safety and efficacy of haloperidol in hospitalized schizophrenic children. The subjects are diagnosed schizophrenic by DSM-III-R criteria and admitted to the Bellevue Hospital Children's Inpatient Psychiatric Unit. The study is 10 weeks in duration and employs a crossover design. After a 2-week placebo baseline period, the subjects enter double-blind treatment for 8 weeks, by random assignment receiving either haloperidol for 4 weeks followed by placebo for 4 weeks, or alternatively, placebo for 4 weeks followed by haloperidol for 4 weeks. Dosage, regulated individually, ranges from 0.5 to 10.0 mg/day. To date, of an anticipated 20 subjects, 12 have completed the study. These children, 9 boys and 3 girls, were ages 5.5 to 11.75 years upon study entry. Haloperidol was superior to placebo for reduction of target symptoms with optimal haloperidol dose of 0.5 to 3.5 mg/day (0.02-0.12 mg/kg/day).

An analysis of the validity of self reported occupational histories using a cohort of workers exposed to PCBs.

An investigation was conducted to examine the validity of self reported work histories obtained from a sample of 326 capacitor manufacturing workers who had participated in an epidemiological study relating health abnormalities to exposure to polychlorinated biphenyls. Based on objective personnel records obtained for 288 members of the sample group, validity scores ranged from 20% to 100% with most falling between 70% and 75%. This validity range corresponded to misclassification proportions ranging from 13% to 29%. Exposure misclassification tended to be random for men but non-random for women (overestimation of exposure). By means of multiple regression analysis, the diversity of the job categorical pattern was found to be a significant independent predictor of validity. The factors sex, duration, and time lapse were also significant validity predictors but only interactively with job diversity. There were also indications that interviewer skill could be an important factor. Knowledge of the magnitude of these factor effects could be critical in planning retrospective epidemiological studies.

Laser-assisted venous anastomosis: a comparison study.

A low-powered carbon dioxide laser was used to perform 25 vein grafts (50 anastomoses) on the femoral veins of Sprague-Dawley rats. The patency rate, clamp time, and bleeding time were compared with 50 conventional microvascular vein grafts (100 anastomoses). The patency of the laser-assisted anastomoses (LAVA) was 84 percent, while the conventional vein grafts yielded a 94 percent patency rate. The average clamp time and bleeding time for the LAVA were 47.2 min and 4.88 sec, respectively, while the conventional anastomoses required 57.6 min and had an average bleeding time of 9.44 sec. Histologically, both specimens healed at the same rate, but the laser-assisted anastomoses produced less inflammation and granulation tissue. These results suggest that the laser has potential as a tool for clinical application in microsurgery. In addition, the 94 percent patency rate achieved with the vein interposition graft would suggest that a decrease in the tension across the anastomosis can improve patency.

Role of insulin and glucagon in oxytocin effects on glucose metabolism.

Oxytocin (OT) infusion in normal dogs increases plasma insulin and glucagon levels and increases rates of glucose production and uptake. The purpose of this study was to determine whether the effects of OT on glucose metabolism were direct or indirect. The studies were carried out in normal, unanesthetized dogs in which OT infusion was superimposed on infusion of either somatostatin, which suppresses insulin and glucagon secretion, or clonidine, which suppresses insulin secretion only. Infusion of 0.2 microgram/kg/min of somatostatin suppressed basal levels of plasma insulin and glucagon and inhibited the OT-induced rise of these hormones by about 60-80% of that seen with OT alone. The rates of glucose production and uptake by tissues, measured with [6-3H] glucose, were significantly lower than those seen with OT alone, and the rise in glucose clearance was completely inhibited. Clonidine (30 micrograms/kg, sc), given along with an insulin infusion to replace basal levels of insulin, completely prevented the OT-induced rise in plasma insulin and markedly reduced the glucose uptake seen with OT alone, but did not reduce the usual increase in plasma glucose and glucagon levels or glucose production. To determine whether the OT-induced rise in plasma insulin was in response to the concomitant increase in plasma glucose, similar plasma glucose levels were established in normal dogs by a continuous infusion of glucose and an OT infusion was superimposed. OT did not raise plasma glucose levels further, but plasma insulin levels were increased, indicating that OT can stimulate insulin secretion independently of the plasma glucose changes. Studies by others have shown that the addition of OT to pancreatic islets or intact pancreas can stimulate insulin and glucagon secretion, indicating a direct effect. Our studies agree with that and suggest that in vivo, OT raises plasma insulin levels, at least in part, through a direct action on the pancreas. These studies also show that OT increases glucose production by increasing glucagon secretion and, in addition, a direct effect of OT on glucose production is likely. The OT-induced increase in glucose uptake is mediated largely by increased insulin secretion.

p53 gene mutation in B-cell chronic lymphocytic leukemia is associated with drug resistance and is independent of MDR1/MDR3 gene expression.

We studied 53 patients with B-cell chronic lymphocytic leukemia (B-CLL) and found mutations of the p53 gene in 15%. Patients with p53 gene mutations were found to have an aggressive form of B-CLL disease characterized by advanced Rai stage, rapid lymphocyte doubling time (LDT), and resistance to chemotherapy. While 27 of 29 treated patients (93%) without p53 mutations achieved a partial remission, only one of seven treated patients (14%) with p53 mutations achieved a partial remission (P = .00009). Adjusting for prognostic factors (age, sex, race, and Rai stage), patients with p53 gene mutations had a 13-fold greater risk of death than patients without p53 mutations (P = .013). In addition to examining the clinical relevance of p53 gene mutations in B-CLL, we investigated the possible role of p53 gene regulation in the expression of the multidrug resistance genes MDR1 and MDR3. We quantitated MDR1 and MDR3 mRNA expression by reverse transcription-polymerase chain reaction (RT-PCR). Expression of both the MDR1 and MDR3 genes was independent of p53 gene mutation or prior drug treatment, and did not predict for clinical response. Our findings indicate that p53 gene mutations in B-CLL are associated with a poor clinical outcome and may be a prognostic indicator for drug resistance.

Premenopausal estradiol levels and the risk of breast cancer: a new method of controlling for day of the menstrual cycle.

Levels of total estradiol in premenopausal women vary widely over the course of the menstrual cycle with a spike at the time of ovulation and dissimilar patterns pre- and post-ovulation. Evaluating the association between breast cancer and premenopausal measurements of total estradiol when the measurements cannot be taken on a uniform day of the cycle is therefore a difficult methodological challenge. In a matched case-control study of breast cancer nested within a prospective study, premenopausal serum samples obtained up to 7 years before breast cancer diagnosis were available for total estradiol assay. By fitting a three-piece spline model that regressed the logarithm of total estradiol (ln estradiol) on day of menstrual cycle, the authors were able to adjust the measurements for day of the cycle on which they were collected by expressing them in terms of the number of standard deviations above or below the fitted ln estradiol value for that day. Applying the adjusted measurements to the nested case-control study, they found evidence of a 1.5 to 2-fold risk for women in the upper two tertiles of ln estradiol relative to women in the lowest tertile. Conditional logistic regression analysis for day-of-cycle-adjusted ln estradiol treated as a continuous variable resulted in a relative risk estimate of 1.19 (95% confidence interval 0.91-1.55) per standard-deviation increase in adjusted ln estradiol.