Diabetes mellitus presenting as paroxysmal kinesigenic dystonic choreoathetosis.
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Biomedical subjects
Publications and source records attributed to J D Clark.
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Early diagnosis of osteomyelitis continues to be a clinical problem. Multiple imaging modalities are being used for the diagnosis of osteomyelitis, but none of them is ideal for all cases. The choice of modality depends on several factors based on an understanding of the pathophysiologic aspects of different forms of osteomyelitis. After a brief introduction outlining some basic principles regarding the diagnosis of osteomyelitis, pathophysiologic aspects are reviewed. Advantages and disadvantages of each imaging modality and their applications in different forms of osteomyelitis are discussed. The use of different imaging modalities in the diagnosis of special forms of osteomyelitis, including chronic, diabetic foot, and vertebral osteomyelitis, and osteomyelitis associated with orthopedic appliances and sickle cell disease is reviewed. Taking into account the site of suspected osteomyelitis and the presence or absence of underlying pathologic changes and their nature, an algorithm summarizing the use of various imaging modalities in the diagnosis of osteomyelitis is presented.
To summarize the regulation of cPLA2, we have proposed a model for the activation of cPLA2 based both on our previous studies (Clark et al., 1991; Lin et al., 1993) and the work of many others (Fig. 5). In this model, cPLA2 is tightly regulated by multiple pathways, including those that control Ca2+ concentration, phosphorylation states and cPLA2 protein levels, to exert both rapid and prolonged effects on cellular processes, such as inflammation. cPLA2 is rapidly activated by increased intracellular Ca2+ concentration and phosphorylation by MAP kinase. When cells are stimulated with a ligand for a receptor, such as ATP or PDGF, PLC is activated via either a G protein-dependent or -independent process, leading to the production of diacylglycerol (DAG) and inositol triphosphate (IP3). The rise in these intracellular messengers cause the activation of PKC and mobilization of intracellular Ca2+. Alternatively, the increase in intracellular Ca2+ can result from a Ca2+ influx. Increased Ca2+ acts through the CaLB domain to cause translocation of cPLA2 from the cytosol to the membrane where its substrate, phospholipid, is localized. This step is essential for the activation of cPLA2 and may account for the partial activation of cPLA2 in the absence of phosphorylation. MAP kinase activation can occur through both PKC-dependent and -independent mechanisms (Cobb et al., 1991; Posada and Cooper, 1992; Qiu and Leslie, 1994). In many cases, this pathway is also G protein-dependent. Activated MAP kinase phosphorylates cPLA2 at Ser-505, causing increased enzymatic activity of cPLA2, which is realized only upon translocation of cPLA2 to the membrane. Therefore, full activation of cPLA2 requires both increased cytosolic Ca2+ and cPLA2 phosphorylation at Ser-505. In a more delayed response, cPLA2 activity in the cells can be controlled by changes in its expression levels, such as in response to inflammatory cytokines and certain growth factors. Thus the expression level of cPLA2 is regulated by both transcriptional and post-transcriptional mechanisms.
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UNLABELLED: The purpose of this retrospective study was to evaluate the utility of 131I as therapy for hyperthyroidism in children and to evaluate its short-term side effects. METHODS: The results of 131I therapy of hyperthyroidism were evaluated in a group of 35 pediatric patients. RESULTS: In 29 patients propylthiouracil or methimazole therapy was abandoned due to noncompliance (13), relapse or failure to control hyperthyroidism (13), vasculitis (1), neutropenia (1) or a lupus-like syndrome (1). Average treatment activity was 7.7 +/- 2.9 (s.d.) mCi, corresponding to 0.16 +/- 0.03 mCi/g. Thirty patients (86%) received a single radioiodine treatment and five (14%) were retreated. In patients who became hypothyroid after a single dose, hypothyroidism was noted within 100 days of treatment. Clinical management problems included vomiting in four patients and enuresis in four patients. Mild radiation thyroiditis occurred in one patient and nodularity was noted after therapy in two patients. CONCLUSION: Iodine-131 is effective for both initial treatment of hyperthyroidism and the treatment of medical treatment failures in pediatric patients. Awareness of vomiting and enuresis as potential management problems is crucial when using 131I in this age group. Therefore, special treatment precautions may be required.
Cytosolic phospholipase A2 (cPLA2) associates with natural membranes in response to physiological increases in Ca2+, resulting in the selective hydrolysis of arachidonyl phospholipids. The isolation and sequence analysis of cPLA2 cDNA clones from four different species revealed several highly conserved regions. The NH2-terminal conserved region is homologous to several other Ca(2+)-dependent lipid-binding proteins. Here we report that the first 178 residues of cPLA2, containing the homologous Ca(2+)-dependent lipid-binding (CaLB) motif, and another recombinant protein containing the cPLA2(1-178) fragment placed at the COOH terminus of the maltose-binding protein (MBP-CaLB) associate with membranes in a Ca(2+)-dependent manner. cPLA2 and MBP-CaLB also bind to synthetic liposomes at physiological Ca2+ concentrations, demonstrating that accessory proteins are not required. In contrast, delta C2, a truncated cPLA2 lacking the CaLB domain, fails to associate with membranes and fails to hydrolyze liposomal substrates. However, both delta C2 and cPLA2 hydrolyze monomeric 1-palmitoyl-2-lysophosphatidylcholine at identical rates in a Ca(2+)-independent fashion. These results delineate two functionally distinct domains of cPLA2, the Ca(2+)-independent catalytic domain, and the regulatory CaLB domain that presents the catalytic domain to the membrane in response to elevated Ca2+.
Fossils and artifacts recovered from the middle Awash Valley of Ethiopia's Afar depression sample the Middle Pleistocene transition from Homo erectus to Homo sapiens. Ar/Ar ages, biostratigraphy, and tephrachronology from this area indicate that the Pleistocene Bodo hominid cranium and newer specimens are approximately 0.6 million years old. Only Oldowan chopper and flake assemblages are present in the lower stratigraphic units, but Acheulean bifacial artifacts are consistently prevalent and widespread in directly overlying deposits. This technological transition is related to a shift in sedimentary regime, supporting the hypothesis that Middle Pleistocene Oldowan assemblages represent a behavioral facies of the Acheulean industrial complex.
Production of leukotriene B4 (LTB4) by human neutrophils (PMN) in response to different stimuli is increased after pretreatment with lipopolysaccharides (LPS). We have analyzed the steps in arachidonic acid (AA) metabolism affected by LPS by examining release of AA and its metabolites from [3H]AA prelabeled PMN. Pretreatment of PMN for 60 min with up to 1 microgram/ml of LPS alone had no effect, but release of [3H]AA was stimulated up to fivefold during subsequent stimulation with a second agent. In the absence of LPS-binding protein (LBP), priming was maximal after pretreatment of PMN with 10 ng of LPS/ml for 60 min; in the presence of LBP maximal priming occurred within 45 min at 0.1 ng of LPS/ml and within 15 min at 100 ng of LPS/ml. Treatment of PMN with 10 ng of LPS/ml also increased uptake of opsonized zymosan by up to 60%. Phospholipids are the source of released [3H]AA. No release was observed from [14C]oleic acid (OA)-labeled PMN suggesting that phospholipolysis may be specific for [3H]AA-labeled phospholipid pools. Cytosol from PMN primed with LPS contains two to three times the phospholipase A2 (PLA2) activity of control PMN, against 1-palmitoyl-[2-14C]arachidonoyl-phosphatidylcholine. This activity is Ca2+ dependent and dithiothreitol resistant. LPS priming is accompanied by reduced migration during SDS-PAGE of an 85-kD protein, identified as a cytosolic PLA2. The extent and kinetics of this effect of LPS on cPLA2 parallel the priming of [3H]AA release, both depending on LPS concentration either with or without LBP. These findings suggest that priming by LPS of AA metabolism by PMN includes phosphorylation of an AA-phospholipid-selective cytosolic PLA2 that is dissociated from activation until a second stimulus is applied.
The taxonomy of Australopithecus afarensis, the oldest known hominid species, has been a matter of debate since its description in 1978 (ref. 1). Some authorities regard all specimens assigned to A. afarensis as belonging to a single taxon whereas others regard the Tanzanian and Ethiopian specimens as each representing a different species. Further controversy surrounds the issues of sexual dimorphism and locomotion among these hominids. Resolution of these problems would shed light on hominid phylogeny in general and on the ancestry of later Australopithecus and Homo. Fossils discovered in the Afar of Ethiopia in 1990 constitute the first major addition to the 3-4 million year (Myr) hominid record since the 1970s. We report here the discovery of new fossils from Maka, dated to 3.4 Myr ago, which provide powerful support for the interpretation of A. afarensis as a single, ecologically diverse, sexually dimorphic, bipedal Pliocene primate species whose known range encompassed Ethiopia and Tanzania.
Relationships between fructosamine and HbA1, and mean blood glucose over the previous 1-8 weeks, determined from self blood glucose monitoring with memory meters, were studied prospectively throughout 16 pregnancies in Type 1 diabetic women. Fructosamine correlated best (Spearman rank) with mean blood glucose over the previous 2 weeks in the first and second trimesters (0.5) and over the previous 1 week in the third trimester (0.39). HbA1 correlated best with mean blood glucose over the previous 8 weeks in the first and second trimesters (0.56), but over the previous 2 weeks in the third trimester (0.524) probably because of increased erythropoiesis in late pregnancy. From Deming regression models, 95% prediction intervals for mean blood glucose for fructosamine and HbA1 values were calculated, showing that fructosamine predicted levels of mean blood glucose more precisely than HbA1. These intervals can be used to estimate an individual pregnant diabetic woman's mean blood glucose from her fructosamine or HbA1 results and to verify self blood glucose monitoring data. In well-controlled diabetic pregnancy, both fructosamine and HbA1 reliably indicated trends in blood glucose but fructosamine estimated blood glucose levels more precisely.
A case of acute bacterial endocarditis associated with orthodontic treatment is described and the problems associated with orthodontic treatment for 'at risk' patients are discussed. The American Heart Association recommendations for orthodontic patients are summarized, and the general recommendations of the Endocarditis Working Party of the British Society for Antimicrobial Chemotherapy are appended.
The ways in which the cultural evidence - in its chronological context - can be used to imply behavioural patterning and to identify possible causes of change are discussed. Improved reliability in dating methods, suites of dates from different regional localities, and new, firmly dated fossil hominids from crucial regions such as northeast Africa, the Levant, India and China, are essential for clarification of the origin and spread of the modern genepool. Hominid ancestry in Africa is reviewed, as well as the claims for an independent origin in Asia. The cultural differences and changes within Africa, West and South Asia and the Far East in the later Middle and early Upper Pleistocene are examined and compared, and some behavioural implications are suggested, taking account of the evolutionary frameworks suggested by the 'multiregional evolution' and 'Noah's Ark' hypotheses of human evolution. A possible explanation is proposed for the cultural differences between Africa, West Asia and India on the one hand, and southeast Asia and the Far East on the other. The apparent hiatus between the appearance of the first anatomically modern humans, ca. 100 ka ago, and the appearance of the Upper Palaeolithic and other contemporaneous technological and behavioural changes around 40 ka ago, is discussed. It is suggested that the anatomical changes occurred first, and that neurological changes permitted the development of fully syntactic language some 50 ka later. The intellectual and behavioural revolution, best demonstrated by the 'Upper Palaeolithic' of Eurasia, seems to have been dependent on this linguistic development - within the modern genepool - and triggered the rapid migration of human populations throughout the Old World.
The effect of side-chain cyclization on accessible backbone conformations of tripeptides, X-Ala-Y (X and/or Y = Cys, Hcy (Hcy: homocysteine), cis 4-mercaptoproline (MPc), and trans 4-mercaptoproline (MPt)), was elucidated using two variants of systematic conformational search. In addition to cyclization through a disulfide bond, the thioether (-S-CH2-) and amide (-CO-NH-) side-chain analogues of Cys-Ala-Cys and Hcy-Ala-Hcy were evaluated. The number of valid backbone conformations and the allowed phi, psi space were evaluated for each compound, and the ability of the cyclic tripeptides to accommodate beta-turn conformations was examined in order to assess the value of cyclization in limiting conformational freedom. Based on the number of conformations, cyclization was highly effective in reducing the backbone degree of freedom: in order of decreasing number of conformations, Ala-Ala-Ala 1 >> Hcy-Ala-Hcy 2 >> Cys-Ala-Hcy 3 approximately equal to Hcy-Ala-Cys 4 >> MPc-Ala-Hcy 5, 7 > Cys-Ala-Cys 6 > MPc-Ala-Cys 8 > Hcy-Ala-MPt 9 > Cys-Ala-MPt 10 approximately equal to MPc-Ala-MPt 11. Although Hcy-Ala-Hcy 2 had the greatest number of conformations of the cyclic peptides studied, it was still greatly constrained relative to its linear analogue 1. The bicyclic ring system introduced by MP was even more effective in constraining the cycle, having greater impact at position 3 than at position 1. Under the conditions of the study, cyclization of MP-containing analogues could be effected only with the cis isomer (MPc) at position 1 and/or the trans isomer (MPt) at position 3. Sterically allowed conformations of Ala2 for the cyclic tripeptides 2-4 were generally similar to those of the linear tripeptide 1, while those of Cys-Ala-Cys 6 and MPc-Ala-Hcy 7 were restricted to a smaller region of phi 2, psi 2 space: the right- and left-handed alpha-helical conformation and the beta-conformation. This trend was even more pronounced for Hcy-Ala-MPt 9, Cys-Ala-MPt 10, and MPc-Ala-MPt 11, in which Ala2 was severely restricted to a very small region of phi, psi space: the left-handed alpha-helical conformation for 9-11, plus the beta conformation for 9. This suggests that MP at the 3-position is incompatible with a right-handed alpha-helical conformation at position 2.(ABSTRACT TRUNCATED AT 400 WORDS)
OBJECTIVE: We aimed to investigate the mechanisms of hypogonadism which develops after head injury. DESIGN: Pulsatile secretion of LH was studied in subjects 6-10 days after major head injury. PATIENTS: We studied five male subjects admitted with major head injuries and six healthy age-matched control subjects. MEASUREMENTS: During the pulsatility study, LH was measured at 5-minute intervals for 4 hours and 15-minute intervals for a further 2 hours. In addition, testosterone and LH were measured on Days 1-5, 14 and after 3-6 months. RESULTS: The analysis of pulsatile secretion of LH demonstrated an LH pulse frequency similar to control subjects, but a significantly reduced LH pulse amplitude (P less than 0.001, fixed threshold method; P less than 0.02, Detect method). Both testosterone and LH levels were reduced after injury with the nadir occurring on Day 4. CONCLUSIONS: Hypogonadism after head injury is due to defective LH secretion, with normal pulse frequency but a reduced pulse amplitude.
A questionnaire survey of anaesthetists, based at the three main hospitals in Bristol, was undertaken to determine what methods are currently being used by anaesthetists to manage diabetes in patients for surgery. Replies were received from 56 of the 90 anaesthetists (62%). Surgical procedures were defined as minor, moderate, and major. Two areas were identified where considerable differences in management between anaesthetists occurred, namely insulin-treated patients requiring minor surgery, and non-insulin-treated patients requiring moderate surgery. In addition, no consensus view was apparent for the preferred intra-operative blood glucose range or for the threshold blood glucose level at which to postpone an operation. It was apparent that anaesthetists preferred to administer intravenous insulin by a syringe pump rather than by a drip bag containing insulin, potassium, and glucose, particularly if more severe metabolic upset was anticipated. No difference in management was apparent between different hospital grades or between the three hospitals.
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Relationships between maternal glycaemia and neonatal birth weight were studied prospectively in 14 tightly controlled pregnant women with pre-existing type 1 diabetes mellitus. Maternal glycaemia throughout pregnancy was determined from daily self blood glucose (BG) monitoring with memory meters and fortnightly fructosamine (Fr) and glycated haemoglobin (HbA1) measurements. Mean non-fasting BG and mean HbA1 throughout pregnancy correlated strongly (Spearman rank) with birth weight (0.64 and 0.73 respectively), as did mean second trimester non fasting BG (0.54), HbA1 (0.7) and Fr (0.64) and mean third trimester HbA1 (0.65), whereas mean fasting BG showed no significant correlations with birth weight at any age of pregnancy. The disparity between the strong correlation of non fasting BG with birth weight and the poor correlation of fasting BG suggests that postprandial as opposed to basal glycaemia significantly influences foetal growth and neonatal size.
An outbreak of salmonellosis in a gerbil colony was investigated. The clinical, bacteriologic, and pathologic findings are reported. Clinical signs included an occasional sudden death, depression, emaciation, dehydration, rough hair coat, and testicular enlargement. Not every sign was observed in every infected gerbil. At necropsy, 11 animals had lesions consistent with salmonellosis. Histopathologic lesions consisted of interstitial pneumonia, hepatic and splenic necrosis, meningitis, and suppurative orchitis. Splenic and intestinal amyloidosis were also noted. Salmonella, group D, was recovered from gerbil feces, a container in which adult mosquitos were reared, filarial inoculum, and a cockroach. An epizootiologic investigation led to salmonella-infected cockroaches as the possible source of animal contamination via mosquitos and the subsequent filarial inoculum.