Overlap between functional abdominal pain disorders and organic diseases in children. / Sobreposición entre los trastornos funcionales de dolor abdominal y enfermedades orgánicas en niños.

Functional abdominal pain disorders are highly prevalent in children. These disorders can be present in isolation or combined with organic diseases, such as celiac disease and inflammatory bowel diseases. Intestinal inflammation (infectious and non-infectious) predisposes children to the development of visceral hypersensitivity that can manifest as functional abdominal pain disorders, including irritable bowel syndrome. The new onset of irritable bowel syndrome symptoms in a patient with an underlying organic disease, such as inflammatory bowel disease, is clinically challenging, given that the same symptomatology may represent a flare-up of the inflammatory bowel disease or an overlapping functional abdominal pain disorder. Similarly, irritable bowel syndrome symptoms in a child previously diagnosed with celiac disease may occur due to poorly controlled celiac disease or the overlap with a functional abdominal pain disorder. There is little research on the overlap of functional abdominal disorders with organic diseases in children. Studies suggest that the overlap between functional abdominal pain disorders and inflammatory bowel disease is more common in adults than in children. The causes for these differences in prevalence are unknown. Only a handful of studies have been published on the overlap between celiac disease and functional abdominal pain disorders in children. The present article provides a review of the literature on the overlap between celiac disease, inflammatory bowel disease, and functional abdominal pain disorders in children and establish comparisons with studies conducted on adults.

The efficacy and safety of ezetimibe/simvastatin combination compared with intensified lipid-lowering treatment strategies in diabetic subjects with and without metabolic syndrome.

AIMS: The objective was to assess the consistency of effect of switching to ezetimibe/simvastatin 10/20 mg versus doubling the baseline statin dose (to simvastatin 40 mg or atorvastatin 20 mg) or switching to rosuvastatin 10 mg across subgroups of subjects with (n = 617) and without (n = 191) metabolic syndrome (MetS). METHODS: This was a post hoc analysis of a randomized, double-blind, 6-week study of adults 18-79 years with cardiovascular disease and diabetes mellitus with low-density lipoprotein cholesterol (LDL-C) ≥70 and ≤160 mg/dl. The percent change in LDL-C and other lipids was estimated within each subgroup separately. Safety and tolerability were assessed. RESULTS: In subjects with MetS, percent changes in LDL-C and other lipids were greater with ezetimibe/simvastatin versus doubling baseline statin or numerically greater versus switching to rosuvastatin, except high-density lipoprotein cholesterol and apolipoprotein (Apo) AI (mean percent changes in LDL-C were: -22.49% ezetimibe/simvastatin, -9.64% doubled baseline statin and -19.20% rosuvastatin). In subjects without MetS, percent changes in LDL-C, total cholesterol and Apo B were greater with ezetimibe/simvastatin versus doubling baseline statin or numerically greater versus switching to rosuvastatin (mean percent changes in LDL-C were: -25.14% ezetimibe/simvastatin, -4.75% doubled baseline statin and -19.75% rosuvastatin). Safety profiles were generally similar. CONCLUSION: These results showed that switching to ezetimibe/simvastatin 10/20 mg was more effective at reducing LDL-C, total cholesterol and Apo B versus doubling the baseline statin dose to simvastatin 40 mg or atorvastatin 20 mg or switching to rosuvastatin 10 mg regardless of MetS status. These results were generally similar to those of the full cohort.

The brain decade in debate: III. Neurobiology of emotion.

This article is a transcription of an electronic symposium in which active researchers were invited by the Brazilian Society of Neuroscience and Behavior (SBNeC) to discuss the advances of the last decade in the neurobiology of emotion. Four basic questions were debated: 1) What are the most critical issues/questions in the neurobiology of emotion? 2) What do we know for certain about brain processes involved in emotion and what is controversial? 3) What kinds of research are needed to resolve these controversial issues? 4) What is the relationship between learning, memory and emotion? The focus was on the existence of different neural systems for different emotions and the nature of the neural coding for the emotional states. Is emotion the result of the interaction of different brain regions such as the amygdala, the nucleus accumbens, or the periaqueductal gray matter or is it an emergent property of the whole brain neural network? The relationship between unlearned and learned emotions was also discussed. Are the circuits of the former the underpinnings of the latter? It was pointed out that much of what we know about emotions refers to aversively motivated behaviors, like fear and anxiety. Appetitive emotions should attract much interest in the future. The learning and memory relationship with emotions was also discussed in terms of conditioned and unconditioned stimuli, innate and learned fear, contextual cues inducing emotional states, implicit memory and the property of using this term for animal memories. In a general way it could be said that learning modifies the neural circuits through which emotional responses are expressed.

The brain decade in debate: III. Neurobiology of emotion

This article is a transcription of an electronic symposium in which active researchers were invited by the Brazilian Society of Neuroscience and Behavior (SBNeC) to discuss the advances of the last decade in the neurobiology of emotion. Four basic questions were debated: 1) What are the most critical issues/questions in the neurobiology of emotion? 2) What do we know for certain about brain processes involved in emotion and what is controversial? 3) What kinds of research are needed to resolve these controversial issues? 4) What is the relationship between learning, memory and emotion? The focus was on the existence of different neural systems for different emotions and the nature of the neural coding for the emotional states. Is emotion the result of the interaction of different brain regions such as the amygdala, the nucleus accumbens, or the periaqueductal gray matter or is it an emergent property of the whole brain neural network? The relationship between unlearned and learned emotions was also discussed. Are the circuits of the former the underpinnings of the latter? It was pointed out that much of what we know about emotions refers to aversively motivated behaviors, like fear and anxiety. Appetitive emotions should attract much interest in the future. The learning and memory relationship with emotions was also discussed in terms of conditioned and unconditioned stimuli, innate and learned fear, contextual cues inducing emotional states, implicit memory and the property of using this term for animal memories. In a general way it could be said that learning modifies the neural circuits through which emotional responses are expressed

Reliability of NINDS-AIREN clinical criteria for the diagnosis of vascular dementia.

We evaluated the reliability of clinical diagnoses using the recently standardized criteria for the diagnosis of vascular dementia (VaD) developed by the National Institute of Neurological Disorders and Stroke (NINDS) and the Association Internationale pour la Recherche et l'Enseignement en Neurosciences (AIREN). Two neurologists and two psychiatrists independently reviewed clinical data abstracted from those of 42 demented subjects participating in a longitudinal study of dementia at the University of Pittsburgh. For each patient we abstracted the clinical data on a standardized form. Each physician diagnosed each case according to the NINDS-AIREN criteria, using both clinical information and MRIs. We calculated the interrater agreement for all two-way combinations of clinicians with kappa statistics, which ranged from 0.46 (moderate agreement) to 0.72 (substantial agreement). The moderate reliability observed in this study may be attributable to patient-, clinician-, or criteria-centered sources of variance.

Effects of a history of heavy alcohol consumption on Alzheimer's disease.

Neuropsychological and psychiatric evaluations were made of 39 subjects with possible Alzheimer's disease and a history of excessive alcohol consumption (AD + ETOH), who had been abstinent or had drunk minimally for at least three months before evaluation, and 225 patients with probable Alzheimer's disease (PAD) of comparable age, years of education, and baseline global impairment. At baseline, there were no significant differences between the groups in terms of age of onset of dementia, neuropsychological test scores, or current behavioural or psychiatric symptoms. One year later, no differences in rates of decline between 20 abstinent AD + ETOH patients and 88 PAD subjects could be shown. Thus, past heavy alcohol consumption does not appear to modify the presentation of dementia of the Alzheimer's type, nor does it modify progression over a one-year interval.

Impact of psychiatric hospitalization on behavioral complications of Alzheimer's disease.

OBJECTIVE: The authors conducted a prospective study of the clinical utility of the four DSM-III-R subtypes of primary degenerative dementia of the Alzheimer type (with delirium, with delusions, with depression, or uncomplicated) and acute psychiatric hospitalization for treatment of these subtypes. METHOD: The subjects were 120 consecutive inpatients with Alzheimer's disease, most of whom had behavioral abnormalities. Each subject received detailed physical, neurological, psychiatric, and mental status examinations. The presence or absence of specific behavioral problems was also documented. Patients were treated with medication, psychotherapy, and behavioral techniques. RESULTS: While all patients could be assigned to one of the four DSM-III-R behavioral subtypes, the uncomplicated subtype did not accurately reflect the burden of behavioral symptoms in the patients who did not have delirium, delusions, or depression. Each behavioral subtype responded in a characteristic way to inpatient treatment, as reflected by changes in scores on four psychometric scales used to assess cognitive impairment, psychiatric symptoms severity, and level of functioning at admission and at discharge, as well as by changes in residential setting following hospitalization. Half of all patients admitted from their homes and two-thirds of those with depression were able to go home following discharge. CONCLUSIONS: Behavioral syndromes in Alzheimer's disease should not be overlooked, because they have both clinical and prognostic significance. Short-term psychiatric hospitalization is effective and efficient for achieving the goal of returning patients to their homes and for safely implementing specific treatments in this frail population, and it may reduce the need for institutionalization.

Lithium-induced delirium with therapeutic serum lithium levels: a case report.

Lithium-induced delirium occurring in geriatric patients with serum lithium levels that are within the "therapeutic" range (less than 1.5 mEq/L) has been described in the literature. We present a case that illustrates three major issues regarding this syndrome: (1) differentiating lithium-induced delirium from a recurrence of a chronic psychiatric disorder; (2) the use of the electroencephalogram in supporting this diagnosis; and (3) factors that may increase a patient's vulnerability to delirium while on lithium. A brief review of the most relevant literature is then presented. We conclude that lithium-induced neurotoxicity should be suspected in any patient receiving lithium who develops delirium, regardless of the serum level, and that immediate discontinuation of the medication be considered.

Need for the lead mobilization test in children with lead poisoning.

We evaluated the recommendation of the Centers for Disease Control, that children with moderate lead poisoning undergo the lead mobilization test (LMT) to determine the need for a full course of chelation treatment. Current criteria for selection for this test include a blood Pb concentration (bPb) between 25 and 55 micrograms/dl and an erythrocyte protoporphyrin level greater than 35 micrograms/dl. To determine whether the eligibility criteria could be refined to a smaller group of patients, we compared bPb determinations obtained on the day of the LMT in 198 children with moderate Pb poisoning to the results of the LMT. We found that children with bPb less than 25 micrograms/dl were unlikely to respond to the test dose of calcium disodium ethylenediamine tetraacetate with a Pb diuresis (24/25 patients had low urinary Pb excretion on the LMT). In contrast, 88% of children with bPb greater than or equal to 40 micrograms/dl were likely to excrete sufficient Pb to indicate the need for a full course of chelation. We conclude that the LMT is indicated for children with bPbs between 25 and 40 micrograms/dl. Children with bPb between 40 and 55 micrograms/dl may receive chelation therapy without having an LMT, if the performance of the LMT is not practical. Patients with levels less than 25 micrograms/dl should be followed clinically and removed from further Pb exposure.

Neuropathologic and neurochemical correlates of psychosis in primary dementia.

Neuropathologic and neurochemical correlates of psychosis were determined using brain tissue from 27 autopsy-confirmed cases of Alzheimer's disease. The densities of senile plaques and neurofibrillary tangles were determined in the middle frontal and superior temporal cortex, the prosubiculum, and the entorhinal cortex of the hippocampus. The concentrations of norepinephrine, dopamine, and serotonin, the metabolites of these biogenic amines, and the specific activity of choline acetyltransferase were also determined in these four cortical regions as well as in the substantia nigra, thalamus, amygdala, and caudate nucleus. Psychosis was associated with significantly increased densities of senile plaques and neurofibrillary tangles in the prosubiculum and middle frontal cortex, respectively, with trends toward increased densities of these lesions in the other areas examined. This finding is consistent with the increased rate of cognitive decline that accompanies this behavioral disorder. Psychosis was also associated with the relative preservation of norepinephrine in the substantia nigra, with trends in this direction for five of the remaining seven brain regions examined, and a significant reduction of serotonin in the prosubiculum that was accompanied by trends toward reduced levels of serotonin and 5 hydroxyindoleacetic acid in the remaining regions. The profile of neuropathologic and neurochemical changes associated with psychosis is distinct from that previously reported for major depression in the context of primary dementia.

Alzheimer's disease with delusions and hallucinations: neuropsychological and electroencephalographic correlates.

We longitudinally evaluated the neuropsychological functions, rate of progression, and waking EEG findings in 17 patients with probable Alzheimer's disease (AD) with delusions and hallucinations, and compared them with those of matched AD patients without delusions and hallucinations. AD patients with delusions and hallucinations had a more rapid rate of decline, as measured by the Mini-Mental State Examination, a specific defect in receptive language, and a greater frequency of aggression and hostility. Visual EEG analysis showed that these patients had a significantly greater proportion of moderately abnormal EEGs, and spectral analysis confirmed the increased amount of delta and theta activity. These data demonstrate that AD patients with delusions and hallucinations have a greater degree of cerebral dysfunction and a relatively focal neuropsychological defect, which may indicate a localized pathologic abnormality.

Monoclonal antibodies to conserved regions of the major core protein (gag24) of HIV-1 and HIV-2.

Five mouse monoclonal antibodies were raised against a recombinant protein comprising the complete sequence of gag24 protein from HTLV-IIIB. All monoclonal antibodies recognized the native protein in enzyme-linked immunosorbant assay (ELISA) and Western blots. All monoclonal antibodies also cross-reacted with an human immunodeficiency virus type 2 (HIV-2) strain in western blots, whereas only one antibody detected HIV-2 p25 in ELISA. By using synthetic peptides, cross-reacting epitopes were mapped and three regions were defined. The conserved immunogenic sites were located in the carboxyterminal region of the protein. Inhibition experiments with human sera showed that this region is also immunogenic in humans.

The impact of service delivery frequency on family planning program output and efficiency.

Operations research is the study of factors that can be controlled by program administrators. Among such factors is the frequency of performing program activities. The present experiment, conducted in Lima, Peru during 1985-86, tested the impact of holding family planning post sessions once per month, twice per month, and weekly. Frequency was shown to have a major impact on program outputs, costs, and cost-effectiveness. Depending on the indicator, sessions held twice per month produced between 1.5 and 2.1 times the output of those conducted once per month. Weekly sessions produced between 1.3 and 1.6 times the output of those held twice per month. At an output level of nearly 11,200 visits per year, twice-per-month sessions were estimated to be 7-38 percent more cost-effective, depending on the indicator, than once-per-month sessions, and 6-28 percent more cost-effective than weekly sessions.

PIP: Operations research is the study of factors that can be controlled by program administrators. One of these factors is the frequency of performing program activities. The operational variable is the frequency of having clinical sessions in medical back-up posts in a community-based distribution (CBD) program in Lima, Peru. The study covered 42 posts in urban marginal areas of Lima. 3 performing frequencies were compared: 1) once a month; 2) twice a month; and 3) weekly. A randomized block design was used. The study lasted 12 months--from August, 1985-July, 1986. 3 output indicators were chosen: 1) effectiveness; 2) efficiency; and 3) cost-effectiveness. Outputs include program acceptors, total visits, IUD insertions, sessions and family planning (FP) visits. The once-per-month posts finished 98% of scheduled sessions while the twice-a-month and weekly sessions finished 97% and 96%, respectively. Mean duration of the clinic sessions held by the monthly and twice-monthly posts was 2.9 hours (s.d.=.84 and .73, respectively). Mean duration for the weekly group was 2.8 hours (s.d.=.67). About 73% of the FP talks scheduled for the monthly post were really accomplished compared to 66% for the twice-monthly and weekly groups. The 42 posts held 1136 clinic sessions during the year and had 11,196 visits, including 5371 FP visits. 1705 women accepted a FP method at the posts. 77% were IUD takers; 15% chose pills; and 8% accepted barrier methods. There were 4768 IUD visits. There were 414 pill visits and 18% barrier method visits. About 89% of all FP visits were IUD-related. 87% of all IUD insertions were referred by CBD workers and 5% by supervisors. There were 2954 total visits in monthly posts; 3501 in twice-monthly; and 5641 in weekly posts. Output went up linearly with session frequency, but in lesser proportion than the rise in the number of sessions held. Differences are statistically significant for all outputs. Twice-a-month posts had 1.5-2.1 times the output of once-a-month posts; weekly posts had about 1.3-1.6 times the output as twice-a-month posts, depending on the variable chosen. With output level of nearly 11,200 visits per year, twice-a-month sessions were estimated to be 7-38% more cost-effective than once-a-month sessions; 6-28% more cost-effective than weekly sessions.

Effects of iron deficiency on lead excretion in children with moderate lead intoxication.

The effect of iron status on calcium disodium edetate (CaNa2EDTA)-induced lead diuresis was examined in 112 children with moderate lead intoxication. Patients whose blood lead levels were between 25 and 55 micrograms/dl and who had erythrocyte protoporphyrin concentrations greater than or equal to 35 micrograms/dl underwent provocative testing to determine the need for a full course of chelation therapy. A blood sample for lead, erythrocyte protoporphyrin, and serum ferritin determinations was obtained immediately before the intramuscular administration of CaNa2EDTA, 500 mg/m2. Determination of urinary lead level was based on an 8-hour urine collection. Blood lead and ferritin levels were significantly correlated with urinary lead excretion: r = 0.542 and 0.298, respectively, p less than 0.01 for both. Multiple regression models were tested to assess the independent effects of the variables. With blood lead level controlled, ferritin remained significantly associated with urinary lead excretion; for every 1 ng/ml increase in ferritin, urinary lead increased by 2.4 micrograms. This small effect of ferritin on urinary lead was illustrated in a discriminant analysis. Using blood lead level by itself as the independent variable resulted in a 76% correct assignment of provocative test outcomes. Knowing the ferritin level improved this assignment accuracy by only 3%. We conclude that the iron status, as measured by serum ferritin, of children with moderate lead intoxication, has a small but significant effect on CaNa2EDTA-induced lead diuresis. This effect may influence the interpretation of borderline provocative test outcomes. Although chelation therapy should not be withheld pending treatment of iron deficiency, lead stores should be reassessed after iron repletion.

Antipsychotics in the elderly.

Neuroleptics are commonly prescribed medications in the geriatric population and have a broader spectrum of indications than in younger patients. In spite of the frequent use of neuroleptics in elderly patients with organic brain syndromes, there are relatively few studies that use double-blind, placebo-controlled methodology. The results of these studies are conflicting; however, there is sufficient evidence that symptoms of agitation, behaviourial dyscontrol, and psychosis are often responsive to neuroleptic treatment. Elderly patients with schizophrenia or other psychotic disorders may also benefit from neuroleptic treatment. As there is a potential for overuse of these medications among the elderly, clear definition of checklist symptoms is imperative. Furthermore, periodic reduction of dose and possible discontinuation of the drug should be considered since many of the checklist symptoms in this age group are environmentally related and time-limited. There has so far been little evidence to support the use of one neuroleptic over another. Side-effect profiles suggest that low doses of the high potency agents are safer and better tolerated in the elderly. Both therapeutic effects and side effects should be assessed at regular intervals.

Assessment of lead stores in children: validation of an 8-hour CaNa2EDTA provocative test.

Twenty-four-hour CaNa2EDTA provocative tests for the assessment of lead stores were successfully performed in 36 asymptomatic children with mild to moderate undue lead absorption (blood lead concentration less than or equal to 69 micrograms/dl and erythrocyte protoporphyrin greater than or equal to 50 micrograms/dl). By comparing lead excretion during the first 8 hours with that excreted during the entire 24-hour test, new criteria have been developed to define positive outcomes. We suggest that the excretion of greater than or equal to 200 micrograms lead per 8 hours or a ratio of urinary lead (micrograms)/CaNa2EDTA administered (mg) greater than or equal to 0.70 after a single intramuscular injection of CaNa2EDTA (500 mg/m2) can identify those children who will respond to chelation treatment with lead diuresis.