Smoking and Parkinson''s disease: a dose-response relationship

BACKGROUND: Previous studies questioned the link between early childhood anemia and detrimental child development. OBJECTIVE: A population-based study was conducted to examine the association between early childhood anemia and mild or moderate metal retardation at 10 y of age. DESIGN: The present study linked early childhood nutrition data collected by the Special Supplemental Program for Women, Infants, and Children (WIC) and school records. Hemoglobin values were used to determine the relation between anemia in early life and children's placement in special education classes for mild or moderate mental retardation. Subjects were all participants in the WIC program. A computer program was used to link data from birth, WIC, and school records. RESULTS: Logistic regression showed an increased likelihood of mild or moderate mental retardation associated with anemia, independent of birth weight, maternal education, sex, race-ethnicity, the mother's age, or the child's age at entry into the WIC program. CONCLUSION: These findings support the proposition that efforts to prevent mild and moderate mental retardation should include providing children with adequate nutrition during early childhood.     

In search of a dose-response relationship with radiotherapy in the management of recurrent rectal carcinoma in the pelvis: a systematic review

BACKGROUND: Research on the subject of insight has been hampered by difficulties in definition and reliable measurement. METHODS: We compared several rating scales to measure insight on a group of 33 psychotic patients as well as assessing patients' psychopathology, clinical characteristics and cognitive functioning. RESULTS: Most currently used scales showed a high degree of inter-correlation. Measures of insight related strongly to the presence of delusions; grandiosity (inversely), and depression (positively). Higher insight scores correlated with indices of treatment compliance and inversely with substance abuse. Measures of pre-morbid IQ and impaired executive functioning, including the Wisconsin Card Sorting Test were not associated with poor insight. CONCLUSIONS: The study highlights aspects of psychopathology and clinical variables particularly related to insight and supports the continued use of standardized scales in further research in this area.     

Lack of dose-response with Pancrease MT for the treatment of exocrine pancreatic insufficiency in adults

BACKGROUND: Choosing the optimum pancreatic enzyme replacement therapy for patients with exocrine insufficiency remains a problem. An enteric coated enzyme microsphere pancreatic enzyme preparation (Pancrease) has been marketed with several levels of lipase activity, implying that there is a dose-response relationship between dose and effectiveness such that the high potency form appears to be the most cost effective. METHODS: In a randomized, single-blind, cross-over study, we evaluated the effectiveness of a commercial enzyme preparation with different amounts of lipase per dosage unit in adults with exocrine pancreatic insufficiency. Patients received a diet comprising 100 g fat each day for 6 days. With each meal (three per day) they received two capsules of either Pancrease MT4 (8000 unit lipase), Pancrease MT10 (20,000 units lipase), Pancrease MT16 (32,000 units lipase) or placebo. A 72-h quantitative faecal collection was carried out for the last 3 days of the 6-day period. RESULTS: There was a reduction in faecal fat excretion with each of the preparations compared to placebo. The difference failed to reach significance with the 8000 units lipase preparation (P > 0.05) but was significant (P = 0.02) with the 20,000 units lipase and the 32,000 units lipase preparations (faecal fat excretion: placebo = 42.1 +/- 29 g, lipase 8000 = 22.1 +/- 7.3 g, lipase 20,000 = 10.2 +/- 4.5 g and lipase 32,000 = 15.8 +/- 12.5 g, P < for 20,000 units and 32,000 units lipase compared to placebo). CONCLUSION: A dose-response relationship between the amount of lipase administered with each meal and a reduction in faecal fat was not evident. The most potent preparation did not provide additional benefits compared to the less expensive lower potency dosage form.     

Propranolol in hypertension: a dose-response study

The effect of propranolol was studied in a double-blind crossover trial in 24 carefully selected hypertensive outpatients. Each patient received propranolol 60 mg/day, 120 mg/day, 240 mg/day, and placebo for four weeks each according to a randomised sequence. Propranolol 60 mg/day was no better than placebo in reducing blood pressure. The effects of propranolol 120 mg/day and 240 mg/day were not significantly different. Both doses reduced lying blood pressure by about 20/10 mm Hg from an initial level of 173/104 mm Hg. No difference was detected between the effects of the different doses of propranolol and placebo on weight or on the occurrence of adverse reactions.     

The degree and type of relationship between psychosocial variables and smoking status for students in grade 8: is there a dose-response relationship?

We investigated the behavioral response of rat pups to intraplantar injection of varying formalin concentrations using a time-sampling method. At 3 days of age, the response was monophasic and persisted for the whole hour, even at low formalin concentrations. Flexion, shaking and licking the injected limb and hind-limb kicking correlated strongly with log formalin concentration (r = 0.82); behavioral state was altered only at the highest concentration. The response on day 15 was also monophasic, but it waned in 30 min, even at the highest formalin concentration tested. Flexion, shaking and licking of the injected limb were strong pain measures (r = 0.83). The response at 25 days was biphasic, and the adult measures, paw lifting and licking, produced a good formalin concentration-effect relationship (r = 0.80). The log concentration-effect relationships for formalin at the three developmental stages and for adult rats were parallel, but between 3 days and 15 days of age, the relationship shifted to the right by 2.5-fold, and by a further 4-fold between 15 and 25 days, when the sensitivity to formalin-induced pain was similar to that in adults. The data describe efficient, quantitative measures of formalin-induced pain for developing rats, show that the pain response is log-linearly related to formalin concentration throughout development, and demonstrate that the sensitivity to formalin-induced pain is about 10-fold higher in neonatal rats than in weanlings. the data imply that there are major qualitative changes in pain processing as the nervous system develops.     

Severity of perinatal cerebral injury and developmental outcome: A dose-response relationship.

The purpose of this study was to establish a dose–response relationship between extent of perinatal cerebral injury and quality of developmental outcome in childhood. To attain this goal, 54 school and preschool-age children who had incurred perinatal intracranial hemorrhage were recruited. The main index of hemorrhage severity—the degree of acute ventriculomegaly observed on the cranial ultrasonogram during the neonatal period—was significantly associated with outcome in all measured domains. These included verbal and nonverbal intelligence, motor skills, and behavioral problems associated with the externalizing and internalizing syndromal groupings. The putative neurobiological mechanisms underlying the observed dose–response relationship between perinatal lesion severity and developmental outcome are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Ultraviolet-B irradiation of leukapheresis. Products: dose-response relationship with the mixed lymphocyte reaction

Our aim was to study the influence of infection with the respiratory syncytial virus (RSV) in non-hospitalized infants on sensitization to aeroallergens and the early manifestation of atopy. Six hundred and nine infants from the prospective German Multicenter Cohort Study on Atopy were included, 38% of whom had an elevated atopic risk. RSV IgG and IgM antibodies were tested by ELISA with gradient purified RSV antigen. Specific IgE against mites, cat dandruff, birch and grass pollens and relevant nutritional antigens were tested with CAP-RAST-FEIA (Pharmacia, Sweden). Of the cord sera 99% were positive for RSV-IgG, 44.7% at one year and 64.2% (n = 265) at two years of age. The positivity rate after 12 months varied with the season of birth, the number of siblings and the degree of exposure to tobacco smoke; and correlated closely with attacks of wheezing during infancy. Twenty (2.8%) children were found to be sensitized against at least one aeroallergen at one year, and 28 (10.5%) at two years. By the first birthday, mite sensitization (n = 3) could only be seen in the RSV-infected children; grass pollen sensitization (n = 9) was associated with RSV seropositivity (logistic regression model including the confounders mentioned above: with RSV IgG < p = 0.048 > and IgM < p = 0.0006 >), as was birch sensitization (n = 5) with RSV IgM (p = 0.009). No such differences could be detected at two years. No correlation of RSV seropositivity to any allergic manifestation could be found. We conclude, that it is only in the first year of life, that RSV infection plays a significant role in promoting sensitization against aeroallergens, which do not at this time produce allergic symptoms.     

Platelet transfusion: a dose-response study

Early recommendations on prophylactic transfusion of thrombocytopenic patients involved a standard platelet dose of about 0.5 x 10(11)/10 kg body weight. Given the lack of data supporting this dose, we prospectively studied the dose response to platelet transfusions in adults and children with hematologic malignancies. Each patient received, in similar clinical conditions, a medium, high, and very high dose of fresh (< 24 hours old) ABO-compatible platelets, in the form of apheresis platelet concentrates (APC). For the adults, the medium dose was defined as APC containing between 4 and 6 x 10(11) platelets, the high dose between 6 and 8 x 10(11), and the very high dose > 8 x 10(11); for the children, the three doses corresponded to 2 to 4, 4 to 6, and > 6 x 10(11) platelets. The end points were the platelet increment, platelet recovery, and the transfusion interval, and the results were compared with a paired t-test. Sixty-nine adults and 13 children could be assessed. Recoveries in the adults were similar with the three doses (from 28% to 30%), but the high and very high doses led to a significantly better platelet increment (52 and 61 x 10(9)/L, respectively) than the medium dose (33 x 10(9)/L, P < .01). The main difference was in the transfusion interval, which increased with the dose of platelets transfused, from 2.6 days with the medium dose to 3.3 and 4.1 days with the high and very high doses, respectively (P < .01). The positive effect of the high dose was observed regardless of pretransfusional clinical status, but was more marked in patients with no clinical factors known to impair platelet recovery. In these patients, a platelet dose of 0.07 x 10(11) per kg of body weight led to a transfusion interval of more than 2 days in 95% of cases. In patients with clinical factors favoring platelet consumption, the proportion of transfusions yielding an optimal platelet increment and transfusion interval increased with the dose of platelets. The platelet dose-effect was also significant in the children, in whom the high and very high doses led to 1.5-fold to twofold higher posttransfusion platelet counts and transfusion intervals. We conclude that transfusion of high platelet doses can reduce the number of platelet concentrates required by thrombocytopenic patients and significantly reduce donor exposure.     

Klinefelter's syndrome as a model for skin changes in venous insufficiency

Chronic venous insufficiency is a common disease with skin changes, varicosity and leg ulceration. Several theories have been proposed to explain all the changes that occur. We recently saw several patients with Klinefelter's syndrome complicated by leg ulceration and all the typical skin changes of venous insufficiency. The underlying disease was however lacking. They all showed disturbances in their fibrinolytic parameters. In this article we discuss (local) fibrinolytic disturbances as a possible factor in the pathogenesis of the skin changes in chronic venous insufficiency.     

Ribosomal RNA: a key to phylogeny

Subjects studied a list of words (e.g., cheetah) and received an implicit word fragment completion test (complete -h-t-h). On the test, the ratio of studied to nonstudied items (proportion overlap) was 0, 25, 50, 75, or 100%. Subjects were administered the identical test twice. Proportion overlap did not affect priming in word fragment completion, on either the first or second test. Also, the completion of studied and nonstudied fragments increased over repeated tests, but priming (the studied-nonstudied rate) remained unchanged. The proportion overlap of items between study and test does not affect performance on primed word fragment completion.     

A review of tests for detecting a monotone dose-response relationship with ordinal response data

This tutorial reviews methods for testing independence between discrete levels of a dose and an ordered categorical response variable. The tests are designed to be powerful for cases in which the response improves monotonically as dosage level increases. First, we show how to apply some standard tests for doubly-ordered contingency tables. Then, we show how to construct tests as part of a model-building strategy. Other topics discussed include generalizations to stratified data, small-sample methods, and sample size and power considerations.     

Cogan's syndrome with arthritis and aortic insufficiency

A young man with nonsyphilitic keratitis and vestibulo-auditory dysfunction (Cogan's syndrome) and a recurrent febrile illness has been observed over a 10 year period. The systemic manifestations have included a splenic abscess vasculitis, pericarditis, aortic valvulitis, and mono-articular inflammatory arthritis.     

Peptides and anxiety: a dose-response evaluation of pentagastrin in healthy volunteers

A large body of data suggest that brain cholecystokinin (CCK) systems are involved in the regulation of anxiety, and numerous studies have demonstrated that CCK-4, a CCKB agonist, reliably induces panic attacks in patients with panic disorder. Recently, pentagastrin, a commercially available CCKB agonist, has been reported to have similar anxiogenic properties. To further explore the utility of pentagastrin as a challenge agent and to determine whether its effects are dose-related, a dose-response study was conducted in ten healthy volunteers. Pentagastrin (0.2 microgram/kg, 0.6 microgram/kg and 1.0 microgram/kg) and inactive placebo were infused over one minute on four separate challenge days in a double-blind fashion. Subjects received pentagastrin while participating in a structured social interaction task. Repeated measures of anxiety, blood pressure, pulse, ACTH, and cortisol were taken at baseline and postinfusion. Pentagastrin administration led to increases in anxiety, pulse, ACTH, cortisol and physical symptoms of panic, in a dose-related manner. Participation in the social interaction task led to increases in measures of anxiety as well as increases in pulse and blood pressure. Few differences were found between the 0.2 microgram/kg dose of pentagastrin and placebo, or between the 0.6 microgram/kg and the 1.0 microgram/kg doses of pentagastrin. These findings support the notion that CCK systems are involved in the regulation of anxiety, and suggest that the 0.6 microgram/kg dose may be optimal for increasing symptoms of anxiety while minimizing unpleasant side effects. The powerful anxiogenic effects of the social interaction task underscore the importance of contextual variables in challenge studies.