Results of Watson-Jones ankle reconstruction for instability. The influence of articular damage

We reviewed 32 ankles in 30 patients at an average of five years after a Watson-Jones tenodesis. All but one patient had had ankle pain before operation and 19 had had clicking, catching, or locking of the ankle. Eleven of these had an ankle arthrotomy at the time of ligament reconstruction for intraarticular pathology. At review seven of 23 ankles had a significant decrease in ankle motion, and five in subtalar motion, but only two were unstable on examination. Twenty-one ankles, however, caused some pain on activity and nine were tender on palpation. These findings indicate intra-articular degeneration or injury rather than simple instability. Radiographs of 16 ankles showed good varus and anterior-drawer stability. Seven had talocrural osteoarthritis, but only four showed grade-1 subtalar osteoarthritis. We found no correlation between follow-up time and long-term results. The Watson-Jones tenodesis provides good rotational and lateral ankle instability and does not appear to lead to subtalar degeneration.     

Absolute metabolite quantification by in vivo NMR spectroscopy: II. A multicentre trial of protocols for in vivo localised proton studies of human brain

We have performed a multicentre trial to assess the performance of three techniques for absolute quantification of cerebral metabolites using in vivo proton nuclear magnetic resonance (NMR). The techniques included were 1) an internal water standard method, 2) an external standard method based on phantom replacement, and 3) a more sophisticated method incorporating elements of both the internal and external standard approaches, together with compartmental analysis of brain water. Only the internal water standard technique could be readily implemented at all participating sites and gave acceptable precision and interlaboratory reproducibility. This method was insensitive to many of the experimental factors affecting the performance of the alternative techniques, including effects related to loading, standing waves and B1 inhomogeneities; and practical issues of phantom positioning, user expertise and examination duration. However, the internal water standard method assumes a value for the concentration of NMR-visible water within the spectroscopic volume of interest. In general, it is necessary to modify this assumed concentration on the basis of the grey matter, white matter and cerebrospinal fluid (CSF) content of the volume, and the NMR-visible water content of the grey and white matter fractions. Combining data from 11 sites, the concentrations of the principal NMR-visible metabolites in the brains of healthy subjects (age range 20-35 years) determined using the internal water standard method were (mean+/-SD): [NAA]=10.0+/-3.4 mM (n=53), [tCho]=1.9+/-1.0 mM (n=51), [Cr + PCr]=6.5+/-3.7 mM (n=51). Evidence of system instability and other sources of error at some participating sites reinforces the need for rigorous quality assurance in quantitative spectroscopy.     

Amitriptyline metabolism in elderly depressed patients and normal controls in relation to hypothalamic-pituitary-adrenal system function

The pharmacokinetics of amitriptyline (AMI) have been extensively studied, and a large interindividual variability between oral dose and concentration of the drug in plasma has been documented. The aim of this study was twofold: first, to compare AMI kinetics in depressed patients with those of healthy controls and, second, to describe the relationship between AMI levels in plasma and hypothalamic-pituitary-adrenal (HPA) system changes during depression. Thirty-eight patients with a DSM-III-R diagnosis of major depression and 13 healthy control persons received 75 mg of AMI daily for 6 weeks. Levels of AMI and nortriptyline in plasma were determined, and neuroendocrine testing with the combined dexamethasone-suppression/CRH-stimulation test (DST) was done before AMI administration and after weeks 1, 3, and 6 of medication. AMI levels in plasma were significantly higher in the patient group compared with controls during the entire treatment period, whereas nortriptyline levels did not differ between the two groups. Drug levels correlated significantly with age, but gender had no effect on the concentration of the drug in plasma. Twenty-two patients remitted after treatment. There was no difference in drug levels between responders and nonresponders. Fifteen patients were DST nonsuppressors before treatment; 23 patients and all controls suppressed cortisol after dexamethasone. DST suppressors had significantly higher AMI levels in plasma at weeks 3, 5, and 6 compared with DST nonsuppressors. In comparison to patients with high AMI levels in plasma, those with low drug concentration had higher postdexamethasone cortisol and adrenocorticotropic hormone levels and an increased hormone release after additional CRH.(ABSTRACT TRUNCATED AT 250 WORDS)     

PASAT performance and the pattern of uptake of 99mTc-exametazime in brain estimated with single photon emission tomography

The effect of the paced auditory serial addition test (PASAT) on the regional uptake of 99mTc-exametazime was determined by single photon emission computed tomography. Twenty insulin-treated diabetic outpatients were scanned at rest and during the performance of the PASAT task using split-dose injection of tracer. When resting and activation scans were compared there were significant decreases in tracer uptake in the right anterior cingulate and left posterior cingulate areas during PASAT activation. The findings are compared with previous studies which had implicated the anterior cingulate area in the mechanisms of attention in humans and other animals. The potentially confounding role of anxiety during attentional tasks is discussed.     

Oligonucleotide (GTG)5 as a marker for Mycobacterium tuberculosis strain identification

Culture of Mycobacterium tuberculosis provides no information on the identity of a strain or the distribution of such a strain in the community. Strain identification of M. tuberculosis can help to address important epidemiological questions, e.g., the origin of an infection in a patient's household or community, whether reactivation of infection is endogenous or exogenous in origin, and the spread and early detection of organisms with acquired antibiotic resistance. To research this problem, strain identification must be reliable and accurate. Although genetic identification techniques already exist, it is valuable to have genetic identification techniques based on a number of genetic markers to improve the accurate identification of M. tuberculosis strains. We show that oligonucleotide (GTG)5 can be successfully applied to the identification of M. tuberculosis strains. This technique may be particularly useful in cases in which M. tuberculosis strains have few or no insertion elements (e.g., IS6110) or in identifying other strains of mycobacteria when informative probes are lacking.     

Characterization of a mouse monoclonal IgG3 antibody to the tumor-associated globo H structure produced by immunization with a synthetic glycoconjugate

OBJECTIVE: The objective of this study was to assess the degree of BP Tracking from childhood to adulthood and to evaluate whether high BP levels persist over time and progress to adult hypertension. PATIENTS AND METHODS: Two hundred and twenty-two healthy schoolchildren living in the North of Portugal were assessed at 17 year intervals, starting in 1979 (cohort 1) aged 5 to 18 years, and again in 1996 (cohort 2). Tracking indices (Ti) were calculated as follows: Ti = (2x + y-z) /N/0.89, where x, y and z refer to the total number in the same, adjacent and remote trisections, respectively, and N = x + y + z. If Ti > 1 there is positive tracking. RESULTS AND CONCLUSIONS: For systolic and diastolic blood pressure, all Ti were greater than 1.0. All individuals that remained in the 3rd tertil, 17 years later, weigh more and are more obese than those of the 1st tertil. 56.6% of the individuals that belong to the 3rd tertil are now hypertensive, which means that a significant percentage of the children with high blood pressure in the first survey will be hypertensive in the future.     

Metastatic brain involvement in Ewing family of tumors in children

OBJECTIVE: To evaluate the incidence and clinical characteristics of CNS involvement in Ewing family of tumors (EF) in children. METHODS: Chart reviews of children with EF treated in our center from 1972 to 1997. Clinical and imaging data regarding possible CNS involvement were collected. RESULTS: During this 25-year period, 80 children with EF were treated. Intracranial involvement was found in eight (10%) children: the brain was involved in seven children (8.8%) and a retro-orbital metastasis without parenchymal brain involvement was noted in one child. Metastases were localized intrahemispherically, or in the cerebellum or the basal ganglia. Intracranial spread was hematogenous in five children and by contiguous spread from the skull in three children. Intracranial involvement was diagnosed 1.3 to 11 years from initial presentation. Seizures and hemiparesis were the main neurologic complications. CONCLUSIONS: The rate of parenchymal brain involvement in our patients with EF was 8.8%. Spread was mainly hematogenous. Substantial morbidity was associated with CNS disease, which appeared in most patients late in the course of disease.     

Regulation of distinct steps of angiogenesis by different angiogenic molecules

This study was designed to determine the relative activity of basic fibroblast growth factor (bFGF), vascular endothelial growth factor/vascular permeability factor (VEGF/VPF), platelet-derived growth factor (PDGF), platelet-derived endothelial cell growth factor (PD-ECGF), hepatocyte growth factor (HGF), and interleukin-8 (IL-8) in regulating endothelial cell division, migration, degradation of the extracellular matrix (ECM), morphogenesis, and survival. Human umbilical vein endothelial cells (HUVEC) were treated with different concentrations of the six cytokines. bFGF was the most potent mitogen followed by VEGF/VPF and PD-ECGF. VEGF/VPF and bFGF also enhanced the survival of the endothelial cells in serum-free medium. Interstitial collagenase (MMP-1) and urokinase plasminogen activator (uPA) were significantly upregulated only by bFGF. HGF, bFGF, and VEGF/VPF induced chemotactic migration of the endothelial cells, but only HGF (scatter factor) enhanced nondirectional motility. The organization of endothelial cells to form tubes on Matrigel was induced by bFGF and, to a lesser extent, by VEGF/VPF and IL-8. Permeability across endothelial cell monolayers was induced only by VEGF/VPF. These data demonstrate that different angiogenic molecules differentially regulate distinct steps in the process of angiogenesis, suggesting that any given molecule may be necessary but in itself insufficient for establishment of a viable vasculature.     

Human thyroid adenyl cyclase-stimulating activity in immunoglobulin G of patients with Graves' disease

We have studied the characteristics of the stimulation of adenyl cyclase (AC) activity in human thyroid plasma membranes by thyroid-stimulating hormone (TSH) and by immunoglobulin G (IgG) from the sera of patients with Graves' disease. AC activity was measured as adenosine 3',5'-cyclic monophosphate (cAMP) generated by membranes in a 10 minute incubation. IgG from two patients with Graves' disease possessed particularly potent human thyroid AC-stimulating activity; the dose-response curves with these IgGs were essentially parallel to those obtained with TSH. As little as 30 mug of the IgG of one patient with Graves' disease or 8 muU of TSH caused significant AC stimulation. A Lineweaver-Burk plot of the data suggested similarity in the site of action of both TSH and human thyroid adenyl cyclase stimulator (HTACS) in Graves' IgG. Submaximal doses of HTACS and TSH had additive effects on AC stimulation, but a large dose of a Graves' IgG with potent AC stimulating activity did not enhance AC stimulation by a maximal dose of TSH. The effect of HTACS on AC was slower in onset and longer in duration than an equipotent dose of TSH. HTACS was detectable in IgGs of 9 of 15 untreated hyperthyroid Graves' disease patients; its concentration, however, did not correlate significantly with tests of thyroid function, nor with long-acting thyroid stimulator (LATS) activity. In another 11 treated patients with Graves' disease, selected for the presence of LATS, HTACS and LATS were significantly correlated. We observed no inhibition of LATS activity in a Graves' IgG chosen for such testing because of its high titer of HTACS and no detectable LATS. However, an inhibitor of HTACS was detected in 2 of 4 IgGs; one of these two IgGs also inhibited AC stimulation by TSH. Conclusions: 1) Some Graves' disease IgGs contain a human thyroid AC stimulator (HTACS), probably different from LATS. 2) HTACS may act via a common pathway with TSH; it differs from TSH, however, in having a slower onset and a greater effect during more prolonged incubation with plasma membranes. 3) There is also an inhibitor of HTACS activity in some Graves' disease IgGs.