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PubMed1982

Pure-tone and speech intelligibility disturbances in patients with ototoxic disorders.

The prevalence and severity of hearing impairment caused by ototoxic drugs are surprisingly high. This emphasizes the importance of the questions arising from the treatment. In 33.7% of the cases, the hearing impairment caused by ototoxic antibiotics was of severe degree and in 25.4%, it was extremely severe. Parenteral, topical or oral administration of aminioglycoside antibiotics is dangerous. Because of the very poor speech intelligibility, most probably not only the spiral organ but the vestibulocochlear nerve and the higher auditory pathways are also affected by these antibiotics. In some cases, the severe distortion in sound perception cannot be compensated even by a hearing aid of the best quality, and lip-reading which was advised occasionally was without any result. To prevent these toxic effects, these drugs should be administered very parsimoniously and then under very strict conditions and close control.

Aminoglycosides↗
PubMed2004

Management of insulin therapy in urban diabetes patients is facilitated by use of an intelligent dosing system.

The Intelligent Dosing System (IDS, Dimensional Dosing Systems, Inc., Wexford, PA) is a software suite that incorporates patient-specific, dose-response data in a mathematical model, and then calculates the new dose of agent needed to achieve the next desired therapeutic goal. We evaluated use of the IDS for titrating insulin therapy. The IDS was placed on handheld platforms and provided to practitioners to use in adjusting total daily insulin dose. Fasting glucose, random glucose, and hemoglobin A1c were used as markers against which insulin could be adjusted. Values of markers expected at the next follow-up visit, as predicted by the model, were compared with levels actually observed. For 264 patients, 334 paired visits were analyzed. Average age was 54 years, diabetes' duration was 10 years, and body mass index was 33.2 kg/m(2); 57% were female, 88% were African American, and 92% had type 2 diabetes. The correlation between IDS suggested and actual prescribed total daily dose was high (r = 0.99), suggesting good acceptability of the IDS by practitioners. Significant decreases in fasting glucose, random glucose, and hemoglobin A1c levels were seen (all P < 0.0001). No significant difference between average expected and observed follow-up fasting glucose values was found (145 vs. 149 mg/dL, P = 0.42), and correlation was high (r = 0.79). Mean observed random glucose value at follow-up was comparable to the IDS predicted level (167 vs. 168 mg/dL, P = 0.97), and correlation was high (r = 0.73). Observed follow-up hemoglobin A1c was higher than the value expected (7.9% vs. 7.4%, P < 0.0055), but correlation was good (r = 0.70). These analyses suggest the IDS is a useful adjunct for decisions regarding insulin therapy even when using a variety of markers of glucose control, and can be used by practitioners to assist in attainment of glycemic goals.

Artificial Intelligence↗
PubMed1991

Intellectual function in long-term survivors of childhood acute lymphoblastic leukemia: protective effect of pre-irradiation methotrexate? A Childrens Cancer Study Group study.

Having demonstrated in a laboratory model that the neurotoxicity of CNS irradiation can be ameliorated with pre-irradiation methotrexate, we retrospectively compared two methods of CNS prophylaxis in childhood acute lymphoblastic leukemia which differed only in the timing of intrathecal methotrexate and radiotherapy. The results of standard IQ tests conducted 2-11 years after 24 Gy of cranial radiotherapy were obtained in 72 patients, of whom 27 had pre-irradiation methotrexate and 45 did not (control group). The two groups were otherwise comparable. In girls, the full-, performance-, and verbal-scale IQ scores were consistently higher in the pre-irradiation methotrexate group than in the corresponding control group (P less than 0.025). Among girls less than 5 years of age when irradiated, the mean IQ scores were 25-29 points higher after pre-irradiation methotrexate than after the control treatment (P less than 0.0007). These results suggest that pre-irradiation methotrexate may help prevent CNS radiotoxicity in children, and that the benefit is dependent on patient age and gender.

Asparaginase↗
PubMed1999

Self-learning fuzzy control with temporal knowledge for atracurium-induced neuromuscular block during surgery.

Self-learning fuzzy logic control has the important property of accommodating uncertain, nonlinear, and time-varying process characteristics. This intelligent control scheme starts with no fuzzy control rules and learns how to control each process presented to it in real time without the need for detailed process modeling. In this study we utilize temporal knowledge of generated rules to improve control performance. A suitable medical application to investigate this control strategy is atracurium-induced neuromuscular block of patients in the operating theater where the patient response exhibits high nonlinearity and individual patient dose requirements may vary fivefold during an operating procedure. We developed a computer control system utilizing Relaxograph (Datex) measurements to assess the clinical performance of a self-learning fuzzy controller in this application. Using a T1 setpoint of 10% of baseline in 10 patients undergoing general surgery, we found a mean T1 error of 0.28% (SD = 0.39%) while accommodating a 0.25 to 0.38 mg/kg/h range in the mean atracurium infusion rate. This result compares favorably with more complex and computationally intensive model-based control strategies for atracurium infusion.

Algorithms↗
PubMed1984

Long-term follow-up of children whose mothers used oral contraceptives prior to conception.

Anthropometric, psychometric and hematologic measurements were made at intervals in the first 3 years of life in a cohort of 732 infants, including 177 (24.2%) whose mothers used oral contraceptives (OC) prior to conception. Analysis of the data focused on weight and height measurements at 3, 9, 12, 24 and 36 months of age; hemoglobin and hematocrit at 9 months; development quotient (DQ) at 2 years and its components, posture, coordination, language and social; and intelligence quotient (IQ) at 3 years and its verbal and nonverbal components. Analyses were made for both sexes combined and males and females separately, by examining crude means, and means adjusted through linear multiple regression for birthweight, age of child at the time of examination, height of mother, mother's weight-for-height centile, birth-order, maternal and paternal education, and maternal smoking. No significant differences were found between the children whose mothers did or did not use oral contraceptives.

Adult↗
PubMed1994

Depression in late life: the use of clinical characteristics to focus screening efforts.

BACKGROUND: The objective of the study was to identify clinical characteristics associated with depressive symptoms in late life so that screening could focus on elderly patients most likely to benefit from further evaluation. METHODS: We used cross-sectional screening for significant symptoms of depression using the Center for Epidemiologic Studies Depression scale and identification of patients' clinical characteristics from patient interviews and a computerized medical record. The setting was an academic primary care group practice at an urban ambulatory care center. Participants were 1,633 consecutively consenting patients aged 60 and older who visited the center between January and August 1991. Mean age was 70 years; 72% were women, 32% were White, 47% had less than 8 years of education, and 7% had no health insurance. RESULTS: There were 251 (15%) patients with significant symptoms of depression. Antidepressants were prescribed to 1 in 7 patients with such symptoms, with amitriptyline being the most commonly prescribed. Bivariate analyses indicated that patients with significant symptoms of depression were more likely to be White, female, without health insurance, and were more likely to have probable alcoholism, mild cognitive loss, and to receive narcotics, histamine H2 antagonists, and/or benzodiazepines. Depressive symptoms were not significantly correlated with age, education, income, or chronic medical conditions. CONCLUSIONS: Significant symptoms of depression were common and correlated with several readily available clinical variables. However, these variables lack sufficient discriminatory power to allow for the selective screening of elderly patients most likely to suffer from symptoms of depression. Thus, formal screening for depression among all elderly patients in primary care may be necessary to improve the recognition of this morbid illness.

Adrenergic beta-Antagonists↗
PubMed2005

Thyroid disease in pregnancy and childhood.

The subject of thyroid disease in pregnancy is receiving increasing attention from many scientific disciplines. Thyroid function in pregnancy is characterised by a T4 surge at 12 weeks declining thereafter. Serum thyroid hormone concentrations fall in the second half of pregnancy but there are few data on normal reference ranges. Fetal brain development depends on T4 transport into the fetus which in turn depends on sufficient maternal iodine supply. There is current concern that adequate iodisation is not present in large parts of Europe. There is increasing evidence that thyroid autoimmunity is associated with fetal loss but the mechanism is unclear and therapy requires carefully conducted studies. While hyperthyroidism in pregnancy is uncommon, effects on both mother and child are critical if untreated. The use of propylthiouracil is recommended together with measurement of TSH receptor antibodies at 36 weeks gestation. Women receiving thyroxine therapy for hypothyroidism or as suppressive therapy should have their dose increased by up to 50% during pregnancy. There are now substantial data to show deleterious effects on child IQ resulting from low maternal T4 (or high TSH) during gestation. Major advances in molecular biology have contributed to elucidation of many genetic causes of congenital hypothyroidism. However, the aetiology of the majority of cases is still unclear and further research is required. The presence of TPO antibodies in about 10% of pregnant women in early gestation is a predictor of an increased incidence of subclinical hypothyroidism during pregnancy and also of postpartum thyroid dysfunction. The latter condition occurs in 5-9% of women and 25-30% progress to permanent hypothyroidism. This review suggests that screening for thyroid function in early pregnancy and levothyroxine intervention therapy for maternal subclinical hypothyroidism should be considered but evidence is awaited. Screening for both thyroid dysfunction and thyroid antibodies ideally at a preconception clinic but certainly in early gestation is recommended.

Antithyroid Agents↗
PubMed1988

The persistent threat of lead: medical and sociological issues.

Lead exposure is an ancient malady. Its history serves as a useful paradigm through which to understand many other pollutants that our technological society has inserted into the human environment and may guide preventive steps for other agents. Lead poisoning was first recognized in workers exposed to high doses. The discovery of childhood toxicity occurred a century ago in Australia, when children with striking symptoms of paralysis, ophthalmoplegia, or meningitis were found to be highly lead exposed. Encephalopathy generally occurs at blood lead levels of 80 micrograms/dL or more, but unequivocal brain damage has been demonstrated at doses well below this level. At lower doses, the neurocognitive effects of lead are expressed as diminished psychometric intelligence, attention deficits, conduct problems, alterations in the electroencephalogram, school failure, and increased referral rates for special needs. Careful epidemiologic studies, which have controlled for the important confounders, have set the effect level at 10-15 micrograms/dL. Elegant animal studies in which confounding is not an issue have confirmed these findings. Although blood lead levels in the population have dropped over time for a number of reasons, there are some 3-4 million American children with blood lead levels of more than 15 micrograms/dL. Biochemical and functional changes have been demonstrated in the heme biosynthetic pathway and in the renal, cardiovascular, endocrine, immune, and nervous systems. The threshold for effect depends on the sensitivity of the methods used. A no-effect level has not been found. Further, this is not a disease of the poor alone. But the poor are exposed to much more lead than are the more economically favored. Deficiencies in body calcium, zinc, iron, and protein stores are associated with increased uptake. Optimizing nutrition enhances the resistance to lead. All children should be screened for lead at regular intervals, especially those with anemia, growth failure, and developmental or behavioral problems. Treatment protocols are well worked out, but chelation is only part of the therapy. Controlling the environment, strengthening the family's supports, enhancing nutrition, and offering remedial education are essential to a successful therapeutic outcome. Lead control has involved a continuing struggle between vested economic interests and regulatory agencies. In one area, the control of airbone lead, science, and public health have prevailed. In the past decade, the amount of alkyl lead consumed in gasoline additives has been reduced by 99%. Body lead burdens have dropped in close correspondence.(ABSTRACT TRUNCATED AT 400 WORDS)

Chelating Agents↗
PubMed2007

Risperidone and cognitive function in children with disruptive behavior disorders.

BACKGROUND: Effects of risperidone on cognitive function in children with disruptive behavior disorders (DBDs) and subaverage intelligence quotient (IQ) were assessed. METHODS: Data from two 6-week, double-blind, placebo-controlled studies (n = 228) were combined, as were three 1-year, open-label studies (n = 688). Patients with DBDs and subaverage IQ, 5 to14 years, received placebo or risperidone .02 to .06 mg/kg/day. Cognitive measures included the Continuous Performance Task (CPT) and Verbal Learning Test for Children (VLT-C). Efficacy was assessed using the Nisonger Child Behavior Rating Form (NCBRF). Adverse events were collected via spontaneous report; sedation was assessed using visual analog scale. RESULTS: Improvements on the NCBRF Conduct Problem subscale were significantly greater for risperidone- versus placebo-treated patients (-15.8 vs. -6.4, p < .0001) in short-term studies; significant reductions were observed in long-term studies (-16.3, p < .0001). No overall decline and some significant improvement in attention (CPT) and memory (VLT-C) were noted regardless of treatment in short-term studies. VLT-C improved significantly (p < .0001) for both groups, with no difference between treatment groups. Improvements in memory (VLT-C) and attention (CPT) were noted in long-term studies. Somnolence/sedation did not affect cognitive function. CONCLUSIONS: Cognitive function was not altered by risperidone in short-term studies and was maintained or improved with one year of treatment in children with DBDs and subaverage IQ, potentially representing age-appropriate gains.

Adolescent↗
PubMedDate not supplied

Chemoinformatics-based classification of prohibited substances employed for doping in sport.

Representative molecules from 10 classes of prohibited substances were taken from the World Anti-Doping Agency (WADA) list, augmented by molecules from corresponding activity classes found in the MDDR database. Together with some explicitly allowed compounds, these formed a set of 5245 molecules. Five types of fingerprints were calculated for these substances. The random forest classification method was used to predict membership of each prohibited class on the basis of each type of fingerprint, using 5-fold cross-validation. We also used a k-nearest neighbors (kNN) approach, which worked well for the smallest values of k. The most successful classifiers are based on Unity 2D fingerprints and give very similar Matthews correlation coefficients of 0.836 (kNN) and 0.829 (random forest). The kNN classifiers tend to give a higher recall of positives at the expense of lower precision. A naïve Bayesian classifier, however, lies much further toward the extreme of high recall and low precision. Our results suggest that it will be possible to produce a reliable and quantitative assignment of membership or otherwise of each class of prohibited substances. This should aid the fight against the use of bioactive novel compounds as doping agents, while also protecting athletes against unjust disqualification.

Algorithms↗
PubMed2005

Risperidone in children with disruptive behavior disorders and subaverage intelligence: a 1-year, open-label study of 504 patients.

OBJECTIVE: To determine the long-term safety and effectiveness of risperidone for severe disruptive behaviors in children. METHOD: A multisite, 1-year, open-label study of patients aged 5 to 14 years with disruptive behaviors and subaverage intelligence was conducted. RESULTS: Seventy-three percent of the 504 patients enrolled completed the study. The mean +/- SE dose of risperidone was 1.6 +/- 0.0 mg/day. The most common adverse events were somnolence (30%), rhinitis (27%), and headache (22%). The incidence of movement disorders was low, and mean Extrapyramidal Symptom Rating Scale scores decreased during risperidone treatment. No clinically significant changes in mean laboratory values were noted, except for a transient increase in serum prolactin levels. Scores on the Nisonger Child Behavior Rating Form Conduct Problem Scale improved significantly as early as week 1, and improvement was maintained throughout the trial (p < .001 at each time point). Significant improvements were noted on positive social behavior and other Nisonger Child Behavior Rating Form subscales, Aberrant Behavior Checklist, Clinical Global Impressions scale, and tests of patients' cognitive function (each p < .001). CONCLUSIONS: Risperidone was well tolerated and effective in the long-term treatment of disruptive behavior disorders in children with subaverage intelligence.

Adolescent↗
PubMed2004

Analysis of dyes in illicit pills (amphetamine and derivatives).

The determination of dyes present in illicit pills is shown to be useful and easy-to-get information in strategic and tactical drug intelligence. An analytical strategy including solid-phase extraction (SPE) thin-layer chromatography (TLC) and capillary zone electrophoresis equipped with a diode array detector (CZE-DAD) was developed to identify and quantify 14 hydrosoluble, acidic, synthetic food dyes allowed in the European Community. Indeed, these may be the most susceptible dyes to be found in illicit pills through their availability and easiness of use. The results show (1) that this analytical method is well adapted to small samples such as illicit pills, (2) that most dyes actually found belong to hydrosoluble, acidic, synthetic food dyes allowed in the European Community, and (3) that this evidence turns out to be important in drug intelligence and may be assessed into a Bayesian framework.

Amphetamines↗
PubMed1995

Cognitive sequelae of treatment in childhood acute lymphoblastic leukemia: cranial radiation requires an accomplice.

PURPOSE: We evaluated cognitive sequelae of treatment for childhood acute lymphoblastic leukemia (ALL). CNS therapy consisted of cranial irradiation (CRT) or no radiation. Children were also randomized to single intravenous high-dose methotrexate (HD-MTX) or conventional-dose methotrexate (CD-MTX) during induction, and all patients received intrathecal (IT) and systemic continuation chemotherapy. PATIENTS AND METHODS: Sixty-six patients treated for ALL on Dana-Farber Cancer Institute protocol 87-01 were evaluated by standardized cognitive and achievement tests. These children had been assigned at diagnosis to a standard-risk (SR) or high-risk (HR) group and received no CRT or 18 Gy CRT, respectively. All patients were randomized to receive MTX during remission induction, either as CD-MTX (40 mg/m2) or HD-MTX (4 g/m2) with leucovorin rescue. RESULTS: There was no difference in cognitive outcomes between radiated and unirradiated patients (P > .4). However, the HD-MTX/CRT combination was associated with decreased intelligence quotient (IQ estimate, 9.3 points) for girls only (P < .08). A specific deficit in verbal coding and memory was documented for all patients (P < .0001). CONCLUSION: We conclude the following: (1) 18 Gy CRT per se was not an independent toxic agent for cognitive outcome; (2) HD-MTX during induction was associated with IQ decline in girls, but only when it was followed by CRT; and (3) impairment of verbal memory and coding was a consistent finding that was independent of CRT, which implicates some component of chemotherapy, possibly prednisone, as a CNS toxin.

Analysis of Variance↗
PubMed2006

Questioning the social intelligence hypothesis.

The social intelligence hypothesis posits that complex cognition and enlarged "executive brains" evolved in response to challenges that are associated with social complexity. This hypothesis has been well supported, but some recent data are inconsistent with its predictions. It is becoming increasingly clear that multiple selective agents, and non-selective constraints, must have acted to shape cognitive abilities in humans and other animals. The task now is to develop a larger theoretical framework that takes into account both inter-specific differences and similarities in cognition. This new framework should facilitate consideration of how selection pressures that are associated with sociality interact with those that are imposed by non-social forms of environmental complexity, and how both types of functional demands interact with phylogenetic and developmental constraints.

Animals↗
PubMed2004

Late neurocognitive sequelae in survivors of brain tumours in childhood.

As survival among children treated for cancer continues to improve, more attention is being focussed on the late effects of cancer treatment. In children treated for brain tumours, chronic neurocognitive effects are especially challenging. Deficits in cognitive development have been described most thoroughly among children treated for posterior-fossa tumours, specifically medulloblastomas and ependymomas, which account for about 30% of all newly diagnosed cases of brain tumours in children. Most children who have survived brain tumours have required surgical resection and focal or craniospinal radiotherapy (irradiation of the entire subarachnoid volume of the brain and spine), with or without systemic chemotherapy. Historically, intelligence quotient (IQ) scores have provided a benchmark against which to measure changes in cognitive development after treatment. Observed declines in IQ are most likely a result of failure to learn at a rate that is appropriate for the age of the child, rather than from a loss of previously acquired knowledge. The rate of IQ decline is associated with a several risk factors, including younger age at time of treatment, longer time since treatment, female sex, as well as clinical variables such as hydrocephalus, use of radiotherapy and radiotherapy dose, and the volume of the brain that received treatment. Loss of cerebral white matter and failure to develop white matter at a rate appropriate to the developmental stage of the child could partly account for changes in IQ score. Technical advances in radiotherapy hold promise for lowering the frequency of neurocognitive sequelae. Further efforts to limit neurocognitive sequelae have included design of clinical trials to test the effectiveness of cognitive, behavioural, and pharmacological interventions.

Antineoplastic Agents↗