Patterns of coronoid fractures and their treatment.
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Elbow Joint↗
Biomedical subjects
R Fernandes
Publications and source records attributed to R Fernandes.
Thyroid hormone distribution in the mouse brain: the role of transthyretin.
Transthyretin is the major thyroxine-binding protein in the plasma of rodents, and the main thyroxine-binding protein in the cerebrospinal fluid of both rodents and humans. The choroid plexus synthesizes transthyretin and secretes it to the cerebrospinal fluid. Although it was suggested that transthyretin might play an important role in mediating thyroxine transfer from the blood into the brain across the choroid plexus-cerebrospinal fluid barrier, newer findings question this hypothesis. Because thyroid hormone passage across brain barriers is a precondition for its action in the CNS, and because brain is an important target of thyroid hormone action, we investigated the role of transthyretin in mediating thyroid hormone access to and distribution within the brain in a transthyretin-null mouse model system. In this report we describe the results derived from use of film autoradiography, a technique that yields definitive morphological results. Film autoradiograms were prepared at 3 and 19 h after intravenous injection of either high specific activity [(125)I]thyroxine or [(125)I]triiodothyronine. Image analyses were designed to demonstrate regional changes in hormone distribution, and to highlight alterations in iodothyronine delivery from ventricles to brain parenchyma. We find no qualitative or quantitative differences in these parameters between the transthyretin-null and the wild-type mouse brain after either [(125)I]thyroxine or [(125)I]triiodothyronine administration. The data presented here now provide definitive evidence that, under standard laboratory conditions, transthyretin is not required for thyroid hormone access to or distribution within the mouse brain. This study also provides the first map of iodothyronine distribution in the brain of the mouse.
Animals↗
Auditory evoked response during propofol anaesthesia after pre-induction with midazolam.
BACKGROUND: In clinical use, midazolam reduces the dose requirement for propofol. We studied the effect of midazolam given before anaesthesia on the amount of propofol needed and the time taken, to achieve loss of consciousness (LOC) in 20 patients. METHODS: We compared the auditory evoked responses (AER) in these patients with those in a group of 20 patients who were not given midazolam. RESULTS: LOC, as defined by a loss of response to verbal command and eyelash reflex, occurred after 113 (95% CI, 99-131) s in the control group and 75 (56-101) s in the midazolam group (P < 0.05). In the control group 2.3 (2.0-2.6) mg kg-1 propofol caused LOC compared with 1.3 (1.1-1.5) mg kg-1 in the group pretreated with midazolam (P < 0.001). Pa amplitude decreased by 60% in the control group and by 54% in the midazolam group while Nb latency increased by 24% in the control group and by 32% in the midazolam group following LOC. These differences were not significant. CONCLUSIONS: We confirmed that coinduction of anaesthesia with midazolam and propofol reduces the requirement of propofol. We also demonstrated that the AER reflects anaesthetic depth rather than plasma concentrations of anaesthetic drugs.
Adult↗
Familial amyloid polyneuropathy: receptor for advanced glycation end products-dependent triggering of neuronal inflammatory and apoptotic pathways.
Familial amyloid polyneuropathy (FAP) is a neurodegenerative disorder associated with extracellular deposition of mutant transthyretin (TTR) amyloid fibrils, particularly in the peripheral nervous system. We have hypothesized that binding of TTR fibrils to the receptor for advanced glycation end products (RAGE) on critical cellular targets is associated with a destructive stress response underlying peripheral nerve dysfunction. Analysis of nerve biopsy samples from patients with FAP (n = 16) at different stages of disease (0-3), compared with age-matched controls (n = 4), by semiquantitative immunohistology and in situ hybridization showed increased levels of RAGE, beginning at the earliest stages of the disease (FAP 0; p < 0.02) and especially localized in axons. Upregulation of proinflammatory cytokines (tumor necrosis factor-alpha and interleukin-1beta) (approximately threefold; p < 0.02) and the inducible form of nitric oxide synthase (iNOS) ( approximately 2.5-fold; p < 0.04) was also observed in a distribution overlapping RAGE expression. Tyrosine nitration and increased activated caspase-3 in axons from FAP patients (p < 0.03) were apparent. Although these data suggest the presence of ongoing neuronal stress, there was no upregulation of neurotrophins (nerve growth factor and neurotrophin-3) in FAP nerves. Studies on cultured neuronal-like, Schwann, and endothelial cells incubated with TTR fibrils displayed RAGE-dependent expression of cytokines and iNOS at early times (6 and 12 hr, respectively), followed by later (24 hr) activation of caspase-3 and DNA fragmentation. We propose that the interaction of TTR fibrils with RAGE may contribute to cellular stress and toxicity in FAP. Furthermore, there is an apparent lack of responsiveness of Schwann cells in FAP nerve to provide neurotrophic factors.
Adolescent↗
Deposition of transthyretin in early stages of familial amyloidotic polyneuropathy: evidence for toxicity of nonfibrillar aggregates.
Familial amyloidotic polyneuropathy (FAP) is a neurodegenerative disorder characterized by extracellular deposition of transthyretin (TTR) amyloid fibrils, particularly in the peripheral nervous system. No systematic immunohistochemical data exists relating TTR deposition with FAP progression. We assessed nerves from FAP patients in different stages of disease progression (FAP 0 to FAP 3) for TTR deposition by immunohistochemistry, and for the presence of amyloid fibrils by Congo Red staining. The nature of the deposited material was further studied by electron microscopy. We observed that early in FAP (FAP 0), TTR is already deposited in an aggregated nonfibrillar form, negative by Congo Red staining. This suggested that in vivo, preamyloidogenic forms of TTR exist in the nerve, in a stage before fibril formation. Cytotoxicity of nonfibrillar TTR was assessed in nerves of different FAP stages by immunohistochemistry for macrophage colony-stimulating factor. FAP 0 patients already presented increased axonal expression of macrophage colony-stimulating factor that was maintained in all other stages, in sites related to TTR deposition. Toxicity of synthetic TTR fibrils formed in vitro at physiological pH was studied on a Schwannoma cell line by caspase-3 activation assays and showed that early aggregates but not mature fibrils are toxic to cells. Taken together, these results show that nonfibrillar cytotoxic deposits occur in early stages of FAP.
Adolescent↗
Choroid plexus tumours: a surgically treated series.
Choroid plexus tumours-carcinomas and papillomas are rare, especially in adults, and they pose some problems in their diagnosis and management. We have reviewed a series of nine cases from our institution surgically treated during the last 18 years. Their clinical charts, neuroradiological examinations, surgical technique, neuropathology and follow-up were analysed. In only one case total removal proved to be impossible, but even in cases of total removal recurrence appeared in two cases (one carcinoma and one papilloma). Morbility is especially associated with posterior fossa tumours. These rare tumours are managed surgically. They are usually associated with hydrocephalus, and it is difficult to forecast whether or not permanent CSF drainage will be required. A long-term follow-up is needed in patients with this type of tumour.
Adolescent↗
Cystic intraventricular schwannoma: case report and review of the literature.
Intraventricular schwannoma is an exceedingly rare tumour with only 6 cases described in the literature. One case of a cystic intraventricular schwannoma operated on at our Institution is analyzed and the other cases reported in the literature are reviewed. Complete removal was achieved and no recurrence was noted after a follow-up period of 10 years. Intraventricular schwannomas are rare tumours that are amenable to complete surgical removal, having a good prognosis without the need of adjuvant therapy.
Adolescent↗
Another problem with reusable tubes.
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Acute Disease↗
Temporary stabilization of the mandible with an external fixation device.
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Bone Wires↗
Review of systemic lupus erythematosus.
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Humans↗
Aggressive osteoblastoma of the mandible closely simulating calcifying epithelial odontogenic tumor. Report of two cases with unusual histopathologic findings.
Aggressive osteoblastoma is a rare bone-forming neoplasm composed of prominent epithelioid cells that demonstrate locally invasive growth with a high rate of recurrence but no metastatic potential. Clinical, radiographic and pathologic features of mandibular aggressive osteoblastoma in a 21-year-old African-American male and a 12-year-old Caucasian female are presented. Both tumors were resected with wide surgical margins and neither patient had adjuvant radiation or chemotherapy. The patients showed no evidence of local recurrence or distant spread either clinically or radiographically after two years of follow-up. These tumors were composed of solid sheets of pleomorphic epithelioid cells, eosinophilic amorphous osteoid with foci of calcification, which closely simulated amyloid. Differentiation of this tumor from histologically similar calcifying epithelial odontogenic tumor and low-grade osteosarcoma proved difficult. Immunohistochemical study with osteocalcin confirmed the osteoblastic nature of these epithelioid cells.
Adult↗
New transthyretin mutation V28M in a Portuguese kindred with amyloid polyneuropathy.
A 62-year-old Portuguese man, with no history of familial amyloid polyneuropathy (FAP), and a 2(1/2)-year history of tingling in the toes and sexual dysfunction was found neurophysiologically to have a sensory-motor axonal polyneuropathy. Autonomic tests showed slight sympathetic and marked parasympathetic involvement. Heart, kidney, and eyes were normal. Single strand conformation polymorphism (SSCP) mutation analysis for the transthyretin (TTR) gene was performed. The SSCP pattern suggested the presence of a mutation in exon 2, but was different from the pattern observed for a control representing the most common TTR mutation associated with FAP, i.e., TTR V30M. DNA sequencing analysis revealed an A-to-G transition in the first base of codon 28 normally encoding a valine, giving rise to a methionine residue. The presence of this extra methionine was confirmed by peptide mapping and mass spectrometry analysis. Biopsy of nerve and skin of the propositus showed amyloid deposits that were immunoreactive for TTR. This is a new variant TTR related to late-onset amyloid neuropathy with autonomic dysfunction. This case confirms that TTR mutation screening should be considered in patients with a clinical disorder consistent with amyloid neuropathy even in the absence of a family history.
Adult↗
Apolipoprotein AI and transthyretin as components of amyloid fibrils in a kindred with apoAI Leu178His amyloidosis.
We found a new C-terminal amyloidogenic variant of apolipoprotein AI (apoAI), Leu178His in a French kindred, associated with cardiac and larynx amyloidosis and skin lesions with onset during the fourth decade. This single-point mutation in exon 4 of the apoAI gene was detected by DNA sequencing of polymerase chain reaction amplified material and restriction fragment length polymorphism analysis in two siblings. Blood, larynx, and skin biopsies were available from one sibling. Anti-apoAI immunoblotting of isoelectric focusing of plasma showed a +1 alteration in the charge of the protein. Extraction of fibrils from the skin biopsy revealed both full-length and N-terminal fragments of apoAI and transthyretin (TTR). ApoAI and TTR co-localized in amyloid deposits as demonstrated by immunohistochemistry. The present report, together with the first recently described C-terminal amyloidogenic variant of apoAI, Arg173Pro, shows that amyloidogenicity of apoAI is not a feature exclusive to N-terminal variants. The most striking characteristic of amyloid fibrils in Leu178His is that wild-type TTR is co-localized with apoAI in the fibrils. We have previously determined that a fraction of plasma TTR circulates in plasma bound to high-density lipoprotein and that this interaction occurs through binding to apoAI. Therefore we hypothesize that nonmutated TTR might influence deposition of apoAI as amyloid.
Adult↗
4'-Iodo-4'-deoxydoxorubicin disrupts the fibrillar structure of transthyretin amyloid.
Transthyretin (TTR) is a tetrameric protein synthesized mainly by the liver and the choroid plexus, from where it is secreted into the plasma and the cerebrospinal fluid, respectively. Some forms of polyneuropathy, vitreopathy, and cardiomyopathy are caused by the deposition of normal and/or mutant TTR molecules in the form of amyloid fibrils. Familial amyloidotic polyneuropathy is the most common form of TTR amyloidosis related to the V30M variant. It is still unclear the process by which soluble proteins deposit as amyloid. The treatment of amyloid-related disorders might attempt the stabilization of the soluble protein precursor to retard or inhibit its deposition as amyloid; or aim at the resorption of the deposited amyloid. The anthracycline 4'-iodo-4'-deoxydoxorubicin (I-DOX) has been shown to reduce the amyloid load in immunoglobulin light-chain amyloidosis. We investigated 1) whether I-DOX has affinity for TTR amyloid in tissues, 2) determined the I-DOX binding constants to TTR synthetic fibrils, and 3) determined the nature of the effect of I-DOX on TTR fibrils. We report that 1) I-DOX co-localizes with amyloid deposits in tissue sections of patients with familial amyloidotic polyneuropathy; 2) I-DOX strongly interacts with TTR amyloid fibrils and presents two binding sites with k(d) of 1.5 x 10(-11) mol/L and 5.6 x 10(-10) mol/L, respectively; and 3) I-DOX disrupts the fibrillar structure of TTR amyloid into amorphous material, as assessed by electron microscopy but does not solubilize the fibrils as confirmed by filter assays. These data support the hypothesis that I-DOX and less toxic derivatives can prove efficient in the treatment of TTR-related amyloidosis.
Amyloid↗
Isolated azygos continuation of the inferior vena cava in the elderly.
A 70-year-old woman with the isolated anomaly of azygos continuation of the inferior vena cava is presented. The interest in this anomaly lies in its presentation as a mediastinal mass on the chest roentgenogram. This article reviews the embryogenesis and the diagnostic testing of this venous anomaly.
Aged↗
Transthyretin regulates thyroid hormone levels in the choroid plexus, but not in the brain parenchyma: study in a transthyretin-null mouse model.
Transthyretin (TTR) is the major T4-binding protein in rodents. Using a TTR-null mouse model we asked the following questions. 1) Do other T4 binding moieties replace TTR in the cerebrospinal fluid (CSF)? 2) Are the low whole brain total T4 levels found in this mouse model associated with hypothyroidism, e.g. increased 5'-deiodinase type 2 (D2) activity and RC3-neurogranin messenger RNA levels? 3) Which brain regions account for the decreased total whole brain T4 levels? 4) Are there changes in T3 levels in the brain? Our results show the following. 1) No other T4-binding protein replaces TTR in the CSF of the TTR-null mice. 2) D2 activity is normal in the cortex, cerebellum, and hippocampus, and total brain RC3-neurogranin messenger RNA levels are not altered. 3) T4 levels measured in the cortex, cerebellum, and hippocampus are normal. However T4 and T3 levels in the choroid plexus are only 14% and 48% of the normal values, respectively. 4) T3 levels are normal in the brain parenchyma. The data presented here suggest that TTR influences thyroid hormone levels in the choroid plexus, but not in the brain. Interference with the blood-choroid-plexus-CSF-TTR-mediated route of T4 entry into the brain caused by the absence of TTR does not produce measurable features of hypothyroidism. It thus appears that TTR is not required for T4 entry or for maintenance of the euthyroid state in the mouse brain.
Animals↗
Confocal imaging of gene expression during hamster submandibular gland biogenesis.
The data presented here provide evidence that the abundance of the ALG7 protein product, GPT, correlates with high proliferative activity during the postnatal development of the hamster SMG development, and that it becomes downregulated with differentiation. Based on our previous studies with yeast, changes in the level of ALG7 expression may be necessary for the events directing salivary cell polarization, migration, differentiation, and apoptosis at distinct developmental stages.
Animals↗
Poverty, psychological disorder and disability in primary care attenders in Goa, India.
BACKGROUND: This study examined the association of common mental disorders in primary health clinic attenders with indicators of poverty and disability in Goa, India. METHOD: Adult attenders (n = 303) in two primary health clinics were recruited. RESULTS: There were 141 (46.5%) cases of common mental disorder. The following were associated with common mental disorder: female gender; inability to buy food due to lack of money; and being in debt. Cases scored significantly higher on all measures of disability. Primary health clinic staff recognised a third of the morbidity but used multiple oral drugs, injectable vitamins and benzodiazepines to treat common mental disorders. CONCLUSIONS: Poverty is closely associated with common mental disorder which in turn is associated with deprivation and despair. Primary mental health care priorities in low-income countries need to shift from psychotic disorders which often need specialist care to common mental disorders. Health policy and development agencies need to acknowledge the intimate association of female gender and poverty with these disorders.
Adolescent↗