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Biomedical subjects

J Mitchell

Publications and source records attributed to J Mitchell.

At least 37 records · Page 2Linked to original sources

Risks for suicidality in major depressive disorder.

This investigation developed a hierarchical multiple regression model to assess the potential risk factors for suicidality in youths 7 to 17 years old. Variables were assessed in three domains: self-perceptions, demography and diagnosis, and home/environment. The model controlled for major depressive disorder (MDD), which has confounded previous investigations, by evaluating potential risks in a diagnostically heterogenous sample, and then evaluating these risks in a subsample with MDD. Conduct problems and depressive thinking emerged as the most powerful predictors in both samples. Hopelessness, life stress, and maternal psychopathology predicted suicidality only in the total sample. Separation anxiety protected MDD youths. These results suggest that suicidal MDD youths may comprise a distinct subgroup of depressed youths.

Adolescent

Pediatric cardiovascular effects of imipramine and desipramine.

Electrocardiograms were evaluated in 39 children and adolescents before and after the clinical use of imipramine and desipramine. The average increase in PR interval was 0.01 seconds. The PR interval increased by 0.02 seconds in 11 subjects, and a new first-degree atrioventricular block developed in two subjects. These changes were not related to the choice between imipramine and desipramine, the dose, or the method of administration. An increase in PR interval by 0.02 seconds or more did correlate with having an abnormality disclosed on a pretreatment electrocardiogram. The average increase in PR interval was 0.007 seconds for subjects with normal baseline electrocardiograms and 0.019 seconds for subjects with conduction and nonconduction abnormalities disclosed in baseline tracings. None of the electrocardiogram changes resulted in adverse clinical consequences.

Adolescent

Chronic fatigue in adolescents.

Nine female and 6 male adolescents (mean age 14.5 +/- 1.7 [SD] years) were evaluated for chronic fatigue associated with at least three additional symptoms present for 18.4 +/- 8.4 months. Eleven subjects experienced the onset of symptoms with an acute illness (seven Monospot-positive). Medical history, physical examination, and laboratory testing yielded little helpful information. Serologic testing for Coxsackie B viruses 1 through 6, cytomegalovirus, Epstein-Barr virus, human herpesvirus 6, and Toxoplasma gondii in subjects and healthy controls provided little evidence for an infectious cause of persistent fatigue. Children's Depression Inventory scores and psychiatric interviews with the Schedule for Affective Disorders and Schizophrenia-Children's Version (K-SADS) identified five subjects with major depression. On the K-SADS, the 10 fatigued subjects without major depression endorsed many secondary symptoms of depression but were less likely than depressed psychiatric clinic patients to endorse primary symptoms such as depressed mood, guilt, and suicidality. At telephone follow-up 13 to 32 months after intake, 4 subjects were completely well, 4 markedly improved, and 7 unimproved or worse. Further research is necessary to determine whether chronic fatigue in adolescents is prodromal depression, a discrete psychosomatic condition, or an infectious or immunologic disorder that mimics depression.

Adolescent

A professional visit to Pakistan and Azad Kashmir.

Watford health visitor June Mitchell visited north east Pakistan and Azad Kashmir last year. Many health visitors have clients with close ties to Azad Kashmir. She describes three health initiatives she observed there.

Community Health Nursing

Risk of malaria in British residents returning from malarious areas.

OBJECTIVES: To identify which British residents travelling abroad are at greatest risk of malaria infection, and to determine the efficacy of malaria chemoprophylaxis for preventing P falciparum infections in tropical Africa. DESIGN: Prospective cohort study (case-base linkage) with routine national surveillance systems. Denominators (base population) were obtained from monitoring a random sample of returning British travellers with the international passenger survey. Numerators (cases) were obtained from reports of malaria infections in British residents, through the Malaria Reference Laboratory network. SETTING: International passenger survey conducted at passport control of international airports in Britain. Malaria reports received nationally were collated centrally in London. SUBJECTS: 2948 British residents (0.2%) returning to Britain in 1987 randomly selected and questioned and 1052 British residents with microscopically confirmed malaria infections in 1987, whose case reports were reviewed and on whom additional data were collected by postal survey. MAIN OUTCOME MEASURES: Annual incidence subdivided by categories of risk. Chemoprophylactic efficacy for east and west Africa by principal regimens and compliance. RESULTS: Annual rates of reported infection per 100,000 travellers to Oceania were 4100; to west and east Africa were 375 and 172 respectively; to Latin America, the Far East, and the Middle East were 12, 2, and 1 respectively. Immigrants visiting friends and relatives in Ghana and Nigeria were at greatest risk (1303 and 952 per 100,000 respectively) in west Africa. Business travellers to Kenya experienced the highest attack rates in east Africa (465 per 100,000). Age-sex specific attack rates varied by region. No prophylaxis was reported to have been used by 23% of British visitors to west Africa, 17% to east Africa, 46% to central or southern Africa, and 58% visiting south Asia. The efficacy of chloroquine plus proguanil against P falciparum infection was 73% and 54% in west and east Africa respectively. Lower values were obtained for chloroquine alone and proguanil alone. The efficacy of Maloprim (pyrimethamine-dapsone) was 61% in west Africa, but only 9% in east Africa. Visitors to west Africa who did not comply with their chemoprophylactic regimen were at a 2.5-fold higher risk of infection than fully compliant users. Non-compliant visitors to east Africa had similar rates of infection as non-drug users. CONCLUSIONS: In 1987 chloroquine plus proguanil was the preferred chemoprophylactic regimen for P falciparum infection in Africa; antimalarial drugs must be taken regularly to be effective.

Adolescent

13C and 15N nuclear magnetic resonance evidence of the ionization state of substrates bound to bovine dihydrofolate reductase.

The state of protonation of substrates bound to mammalian dihydrofolate reductase (DHFR) has significance for the mechanism of catalysis. To investigate this, dihydrofolate and dihydropteroyl-pentaglutamate have been synthesized with 15N enrichment at N-2. 15N NMR studies have been performed on the binary complexes formed by bovine DHFR with these compounds and with [5-15N]dihydrobiopterin. The results indicate that there is no protonation at N-5 in the binary complexes, and this was confirmed by 13C NMR studies with folate and dihydrofolate synthesized with 13C enrichment at C-6. The chemical shift displacements produced by complex formation are in the same direction as those which result from deprotonation of the N-3/C-4-O "amide" group and are consistent with at least partial loss of the proton from N-3. This would be possible if, as crystallographic data indicate, there is interaction of N-3 and the 2-amino group of the bound ligands with the carboxylate of the active site glutamate residue (Glu30).

Animals

Characterization of the major parathyroid hormone target cell in the endosteal metaphysis of rat long bones.

The majority of in vivo competitive binding of parathyroid hormone (PTH) in the endosteal metaphysis of rat long bones was recently shown to be localized in the intertrabecular tissue to a cell that is distinct from a differentiated osteoblast. In the present report we have further characterized this cell, termed a parathyroid hormone target (PT) cell, by light and electron microscopy using radioautography and histochemical techniques. These studies demonstrate that the PT cell is a mononuclear cell with a large cell body located at times between clusters of differentiated osteoblasts, as well as in other regions of the intertrabecular tissue. Its long cytoplasmic processes extend from the bone matrix through the intertrabecular region toward vascular structures, interdigitating with various cells of the endosteum. A distinctive tubular structure originating in the Golgi system and often associated with long mitochondria and glycogen particles extends throughout the cytoplasmic processes of the PT cell. Based on its capacity to incorporate [3H]thymidine, the PT cell appears to divide rather slowly. The identification of occasional hybrid cells with ultrastructural features of both the PT cell and the differentiated osteoblast and the presence of histochemical evidence for alkaline phosphatase activity suggest that the PT cell is of the osteoblast lineage. These studies therefore morphologically define a major osseous target cell for PTH that, although of the osteoblast lineage, is not a differentiated osteoblast and provide in vivo evidence that characteristics of the "osteoblast phenotype" are not restricted to a sole osseous cell type.

Animals

Optimizing blood vessel contrast in fast three-dimensional MRI.

Magnetic resonance angiography has matured to the point where clinically useful images can be acquired in half an hour or less. In this paper, the role of 3D imaging techniques is primarily considered. Specifically, the optimal imaging parameters, sequences, and reconstruction techniques are evaluated for moving spins. A variant of FISP known as ROAST with low flip angles, short repeat times, and a thick slab has been found to yield the best 3D survey scan of the cranial vessels with roughly 1 X 1 X 1-mm3 resolution in each of the processed images (slices). For the faster flowing carotids, a sagittal scout with as short a TE as possible is required to avoid spin dephasing. Localization is accomplished in both cases by acquiring thin slab 3D, thin partition, larger flip angle, longer repeat time FLASH sequences. Different choices of dephase/rephase sequences and directions are also reviewed. These choices are discussed from a practical and theoretical perspective. In particular, improvements in contrast and resolution are evaluated using half-Fourier, 512 acquisition, small fields of view and constrained reconstruction for both rephased gradient echo sequences and dephased thin slice long TR spin-echo sequences. A resolution of 0.5-0.75 mm is recommended to obtain sufficient image quality for consistent clinical interpretation of stenoses and vessel abnormalities.

Blood Flow Velocity

Improved contrast at 1.5 tesla using half-Fourier imaging: application to spin-echo and angiographic imaging.

Half-Fourier imaging is useful for reducing imaging time by requiring less than the usual number of phase-encoding steps. This increase in speed can be traded off for longer repeat times, TR, for improved contrast-to-noise in the same imaging time or to collect short asymmetric echoes. Consequently, it is shown to be especially useful for long TR spin-echo imaging where at 1.5 T a repeat time of 4 sec is recommended for a double-echo TE = 30/90 sequence or 3 sec for a double-echo TE = 15/90 sequence. Short TR FLASH imaging also benefits from a longer TR since there is more time to spoil the signal. In both cases, there is the advantage when a multislice acquisition mode is used that more slices (and hence, a larger volume) can be taken. Another application is to apply half-Fourier imaging in the read direction to avoid spin dephasing and motion artifacts. This is particularly useful in angiographic imaging where smaller pixel sizes and shorter echo times both reduce pixel dephasing. Again, even though taking less than the usual number of data points leads to a reduction in S/N, the improved signal and resolution for blood vessels can more than compensate this loss.

Adult

A model preclinical, clinical, and graduate educational curriculum in emergency medicine for medical students and rotating residents.

The Society for Academic Emergency Medicine model curriculum for medical students and rotating residents was developed over a two-year period. The document was created as a complementary work to the undergraduate Core Content to provide appropriate emphasis, structure, and suggestions on the teaching of emergency medicine core curriculum topics at all levels. Consensus on the curriculum contents was reached from a national sample of emergency medicine educators. An educational matrix format was used to enhance flexibility based on the educational level of the learner and the instructional strengths of the teacher, and allowing for incorporation of a problem-based learning format. An outline of document contents and representative samples from each section are included; the entire document is available from SAEM.

Curriculum

Correlation of electroencephalogram, respiration and movement in the Rett syndrome.

Day time video records of 14 girls with the Rett syndrome (RS) (6-17, mean 7 years) were analysed to correlate episodic abnormalities in respiration, movement and electroencephalograms (EEG). Records were compared with those of 12 healthy girls (6-18, median 14 years) who hyperventilated voluntarily. Three RS girls (6-7 years) had minimal respiratory dysrhythmia and showed no correlation between EEG respiration and movement. The other 11 RS girls (6-17 years) had severe awake respiratory dysrhythmia; 10 showing hyperventilation (with hypocapnia) which alternated with active expiratory apnoeic pauses and one with the latter only. All had periods of awake regular breathing with normal respiratory gases. In these girls EEG showed non-epileptic generalised slow activity some of which was paroxysmal. In the six youngest (6-10 years) of these 11 RS girls, non-epileptic paroxysms of EEG slow activity at 1 1/2-4 Hz occurred and were associated with periods of normal breathing and normal pCO2 levels whether girls were alert, drowsy or asleep, but were uncommon during episodes of hyperventilation (and hypocapnia). In four of these girls the EEG paroxysms occupied less than or equal to 1-3% of the time during periods of respiratory dysrhythmia (81 minutes) and 8-100% of the time during alert periods with normal breathing (29 minutes), p less than or equal to 0.001 for this difference. Short bursts of EEG slowing occasionally followed prolonged apnoeic pauses. In two cases brief partial complex seizures occurred. In five of these girls stereotypic movements exacerbated during episodes of respiratory dysrhythmia and reduced during normal breathing.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Isolation and restraint in juvenile correctional facilities.

Although mental health and correctional programs for juveniles house similar populations, their approaches to behavioral management can be quite different. This difference is evident in the use of isolation and restraint. Both of these interventions are effective behavioral management tools but are subject to abuse if not closely monitored. The authors, drawing from their experiences as mental health consultants to juvenile correctional programs and as expert witnesses in litigation, review the wide range of isolation and restraint practices in correctional programs and make recommendations for supervision and standardization.

Adolescent

Validation of malaria surveillance case reports: implications for studies of malaria risk.

STUDY OBJECTIVE: The aim of the study was to investigate the quality of national malaria surveillance reports in the United Kingdom. DESIGN: Persons with malaria reported to the Malaria Reference Laboratory (MRL) in 1987 were contacted by post to verify existing records with respect to key variables. The MRL data set was then analysed for inaccuracies. SETTING: The study was confined to UK residents. PARTICIPANTS: 602 persons with malaria in 1987 responded (53%). MEASUREMENTS AND MAIN RESULTS: Review of case reports showed few missing data except for duration of residence in the UK, detailed chemoprophylactic regimens, and compliance. There were more missing surveillance data in reports of ethnic minority groups, principally in dates of travel (p = 0.008) and chemoprophylaxis use (p less than 0.0001). Patient recall in the survey was at variance with the surveillance reports in dates of travel and onset of infection, chemoprophylaxis use, and in compliance. Surveillance reports overestimated the number of days between leaving a malarious area and onset of symptoms (by 9 d for P falciparum and by 24 d for P vivax), and underestimated the delay between onset and diagnosis of P falciparum by 3 d. Over 50% of patients who had recalled the use of chloroquine, proguanil, pyrimethamine/dapsone, and pyrimethamine had not been recorded as having taken these drugs on the surveillance reports. Reported compliance also differed between the two data sets. CONCLUSIONS: It is recommended that research units test the quality of their surveillance data before embarking on analytical studies used to generate health policy guidelines.

Adult

Organic diseases mimicking atypical eating disorders.

The authors present three case studies of patients referred to Children's Hospital and Medical Center, Seattle, Washington, for evaluation of possible eating disorders. The atypical manifestations of the cases warranted further investigation, which revealed an organic basis for their weight loss. The authors summarize the typical findings of bulimia and anorexia nervosa and discuss the clues from the case studies that mandated further evaluation.

Adolescent

Biochemical and morphological characterization of parathyroid hormone receptor binding to the rat osteosarcoma cell line UMR-106.

We have used both biochemical and morphological techniques to characterize PTH receptors on the clonal osteosarcoma cell line UMR-106, a widely used model of the osteoblast phenotype. 125I-labeled rat (r) PTH-(1-34) bound to a single class of specific saturable receptors on both whole cells and membranes prepared from UMR-106 cells in a time- and temperature-dependent manner. A decrease in PTH receptor affinity seen in the presence of guanine nucleotides demonstrated that PTH receptors on the UMR-106 cells are coupled to guanyl nucleotide-binding proteins. Although PTH is a potent stimulator of adenylate cyclase in the UMR-106 cells, comparison of PTH-stimulated adenylate cyclase and PTH binding curves indicated the presence of receptors that are not linked to the adenylate cyclase system. Our studies also demonstrated that 125I-labeled rPTH-(1-34) bound to UMR-106 cells is rapidly internalized at 22 C, whereas PTH bound at 4 C remains intact and on the cell surface. Internalization of 125I-labeled rPTH-(1-34) was associated with degradation and release of the hormone at 22 C. Three morphologically distinct cell types were identified in subconfluent cultures of UMR-106 cells. Autoradiographic analysis of 125I-labeled rPTH-(1-34) binding demonstrated differential PTH receptor expression in these cell types. The most abundant PTH binding was observed over a cell type with long cytoplasmic extensions. This cell was reminiscent of the predominant PTH target cell previously identified in the rat metaphysis in vivo, suggesting that the UMR-106 cell line may represent neoplastic transformation of the PTH target cell.

Adenylyl Cyclases

Mechanisms of homologous and heterologous regulation of parathyroid hormone receptors in the rat osteosarcoma cell line UMR-106.

We have examined the mechanisms of homologous and heterologous regulation of PTH receptor binding and receptor-mediated adenylate cyclase activity in the osteosarcoma cell line UMR-106. Pretreatment with PTH resulted in a time- and dose-dependent decrease in PTH-stimulated adenylate cyclase which was maximal after 2 h and at a concentration of 10(-8) M rat (r)PTH-(1-34). PTH pretreatment over the same dose range also diminished receptor binding of 125I-labeled rPTH-(1-34); however, maximal loss of binding required 14 h and was greater than the loss of maximal adenylate cyclase activity. After 24 h pretreatment with rPTH-(1-34), cell surface receptors were decreased from 21,000 sites per cell to 2,700 sites per cell, and these down-regulated PTH receptors could not be detected in either vesicular or cytosolic subcellular fractions. Recovery from such homologous down-regulation appeared to require new receptor synthesis. Heterologous down-regulation of PTH receptors was demonstrated when UMR-106 cells were preincubated with prostaglandin E2 or (Bu)2cAMP. Heterologous desensitization was shown to be the result of a reversible modification of the PTH receptor which decreased binding affinity and decreased PTH-stimulated adenylate cyclase. Postreceptor components were also examined, and PTH but not prostaglandin E2 pretreatment was shown to decrease guanyl nucleotide binding (G) protein-mediated adenylate cyclase stimulation. This decrease in G protein function was associated with a loss of cholera toxin-catalyzed ADP ribosylation and was also detected by immunoblotting. These results indicate that PTH responses in osteoblastic cells are modulated by diverse mechanisms involving modifications both to the receptor and to postreceptor components of adenylate cyclase.

Adenosine Diphosphate Ribose