Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0010200 (cough)
 23,843 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Imiglucerase, the recombinantly produced enzyme, is gradually replacing the human placental derived alglucerase in the treatment of gaucher patients. We describe the first case, to the best of our knowledge, of an anaphylactoid reaction to imiglucerase in a patient who tolerated alglucerase. The patient was diagnosed at the age of 2 4/12 years with anemia and hepatosplenomegaly. Over the years he had suffered from marked splenomegaly, thrombocytopenia and recurrent bleeding episodes. At the age of 24 he started treatment with imiglucerase. After 3 months of treatment, immediately after starting an infusion, he experienced flushing, cough, tachycardia, palpitation, chest pain and excessive sweating, which reoccurred on a consecutive administration. Substitution with alglucerase was tolerated well, with only mild rash when he was premedicated with benadryl. Immediate skin tests to alglucerase, imiglucerase and gelatin were negative. IgG against alglucerase was undetectable. The in vitro mast cell degranulation test was positive for alglucerase, imiglucerase heamaccel (a gelatin based plasma substitute, which is a component of imiglucerase). This sensitivity to imiglucerase but not to alglucerase, raises the question of future treatment for this patient, since the production of alglucerase may cease, once imiglucerase production will cover the need for replacement enzyme.
Blood Cells Mol Dis 1999 Apr
PMID:Anaphylactoid reaction to imiglucerase, but not to alglucerase, in a type I Gaucher patient. 1038 90

Sierra Leone ranks at the bottom of the global World Bank Development Index based on multiple health and economic indices and lacks the resources to purchase HIV diagnostic kits. Our study has defined some common clinical features presenting HIV infection that could form clinical algorithms for the diagnosis and recognition of HIV infection by health workers in Sierra Leone. In a private clinic in Freetown, Sierra Leone, West Africa, 106 out of a total of 124 patients presenting with various symptoms and strong clinical suspicion of HIV infection within a two-year period (1999 and 2000), were deemed positive by two different ELISA tests. The prevalence of HIV infection seen in this private clinic in Freetown in 2000 was 14.89% as compared to 9.25% in 1999. The positive predictive value of our clinical diagnosis of HIV/AIDS infection was 85.5%. The male:female ratio of the patients in our series was 1:1.9, with a mean age of 39 years for males and 28 years for females. HIV infection was found in a cross-section of the population that we examined. Heterosexual contact appeared to be the major mode of transmission amongst our patients and there seemed to be a significant epidemiological risk of HIV infection amongst those who traveled to other countries in the West African sub region. Common clinical features in decreasing frequency were fever (92.5%), weight loss (84.1%), lymphadenopathy (78.3%), cough (48.1%), diarrhea (37.7%), candidiasis (32.1%) and body aches (30.1%).
Cell Mol Biol (Noisy-le-grand) 2001 Nov
PMID:The usefulness of defined clinical features in the diagnosis of HIV/AIDS infection in Sierra Leone. 1183 63

Ambroxol has a long history for the treatment of airway diseases because of its beneficial effects on surfactant synthesis and mucus-modifying properties. Some findings, however, point to an additional effect on neuronal signal transduction: ambroxol can suppress reflexes such as the cough or the corneal reflex. The airways and the cornea are innervated by C-fibers, which express voltage-gated Na(+) channels with and without sensitivity to tetrodotoxin (TTX). In this study, we performed voltage-clamp experiments to investigate whether ambroxol affects these channel types. In rat dorsal root ganglia, TTX-resistant Na(+) currents were suppressed in a concentration-dependent manner with IC(50) values of 35.2 and 22.5 microM for tonic and phasic block, respectively. Depolarizing prepulses increased the potency of ambroxol, and steady-state inhibition curves were shifted to more negative values. The inhibition was not frequency-dependent. TTX-sensitive currents were inhibited with lower potency (approximately 50% inhibition with 100 microM). Recombinant rat brain IIA channels in Chinese hamster ovary cells were blocked with IC(50) values of 111.5 and 57.6 microM for tonic and phasic block, respectively; in contrast to TTX-resistant channels the block was frequency-dependent. Thus, ambroxol indeed blocks neuronal voltage-gated Na(+) channels, and TTX-resistant channels in sensory neurons were more sensitive than TTX-sensitive. Compared with known local anesthetics (e.g., lidocaine or benzocaine), the potency for Na(+) channel block was relatively high. A recent clinical trial has further confirmed that ambroxol relieved pain and was beneficial in patients who suffered from sore throat.
Mol Pharmacol 2002 Sep
PMID:Inhibition of tetrodotoxin (TTX)-resistant and TTX-sensitive neuronal Na(+) channels by the secretolytic ambroxol. 1218 17

Systemic pseudohypoaldosteronism type I (PHAI) is an autosomal recessive disorder that arises from loss of function mutations of the alpha, beta, or gamma subunit of Epithelial Na(+) Channel (ENaC). In addition to a severe renal phenotype in the neonatal period, patients with PHAI develop a childhood pulmonary syndrome characterized by cough and frequent respiratory infections. We tested a patient, born to consanguineous parents, who presented with dehydration, metabolic acidosis, hyperkalemia, elevated renin and aldosterone levels at birth, and recurrent respiratory symptoms in his first year. He demonstrated defective epithelial Na(+) transport in multiple organs (raised sweat Cl(-), 120 mM; raised salivary Na(+) and Cl(-), 118 and 111 mM, respectively; and little nasal amiloride-sensitive potential difference). No deleterious mutation was identified in the coding region of the three ENaC subunits. Reverse transcriptase-polymerase chain reaction of nasal epithelial RNA showed reduced betaENaC expression, and inability to amplify promoter elements indicated the possibility of a deletion in the 5' region. Using a probe that corresponded to exon 1A of betaENaC, we confirmed a large deletion (> 1,300 bp). In summary, a homozygous mutation in the promoter region of betaENaC leads to PHAI, the first description of a mutation in the regulatory regions of an ENaC subunit leading to a clinical phenotype.
Am J Respir Cell Mol Biol 2002 Sep
PMID:Systemic pseudohypoaldosteronism from deletion of the promoter region of the human Beta epithelial na(+) channel subunit. 1220 93

Haemophilus influenzae is a human-specific pathogen and a major source of morbidity worldwide. Infection with this organism begins with colonization of the nasopharynx, a process that probably depends on adherence to respiratory epithelium. The Hia autotransporter protein is the major adhesin ex-pressed by a subset of non-typeable H. influenzae strains and promotes high-level adherence to a variety of human epithelial cell lines. In the current study, we discovered that the Hia passenger domain contains two distinct binding pockets, including one at the C-terminal end and a second at the N-terminal end. Competition assays revealed that the two binding pockets interact with the same host cell receptor structure, although with differing affinities. Additional experiments demonstrated that both binding domains are required for full-level bacterial adherence. These observations are reminiscent of eukaryotic cell adhesion molecules and highlight the first example of a bacterial adhesin with two domains that participate in a bivalent interaction with identical host cell receptors. Such an interaction increases avidity, thus stabilizing bacterial adherence to the epithelial surface, despite physical forces such as coughing, sneezing and mucociliary clearance.
Mol Microbiol 2002 Nov
PMID:The Haemophilus influenzae Hia autotransporter harbours two adhesive pockets that reside in the passenger domain and recognize the same host cell receptor. 1241 Aug 30

Rapidly adapting receptors (RARs) in the airway mucosa are found from the nasopharynx to the bronchi. They have thin (Adelta) vagal afferent fibres and lie in and under the epithelium, but their morphology has not been defined. They are very sensitive to mechanical stimuli, and have a rapidly adapting irregular discharge. However, with in vitro preparations they are rather insensitive to chemical stimuli, apart from acid and nonisosmolar solutions. Their pattern of response varies with site. RARs in the nasopharynx, larynx, and trachea usually respond only during the onset of stimuli, while those in the trachea often have an off-response as well. Those in the bronchi are less rapidly adapting and more chemosensitive. Their membranes have mechanosensitive and acid-sensitive ion channels, but no vanilloid receptors. In vivo RARs are sensitive to a wide range of chemical irritants and mediators, and presumably are excited secondarily to mechanical changes in the mucosa and airway smooth muscle. In the central nervous system (CNS) they interact with other vagal afferent pathways. The reflexes they cause vary with site (inspiratory efforts from the nasopharynx, cough or expiratory efforts from the larynx and trachea, and deep breaths or tachypnoea from the bronchi). Pathways from RARs and other vagal reflexes show plasticity at the peripheral, ganglionic, and CNS levels.
Anat Rec A Discov Mol Cell Evol Biol 2003 Jan
PMID:Functional morphology and physiology of pulmonary rapidly adapting receptors (RARs). 1249 84

Vagus nerve stimulation (VNS) has gained recognition as a treatment for refractory epilepsies where surgical treatment is not possible. While it appears that this treatment is effective in some patients, the mechanism of action is not clearly understood. The purpose of this study was to clarify findings of other positron emission tomography and single-photon emission tomography (SPET) investigations by measuring the acute effect of VNS on patients who have normal cerebral anatomy on magnetic resonance imaging and who have not previously been exposed to VNS. We investigated six subjects (two males and four females, mean age 29.5 years, range 21-39 years) with intractable epilepsy. One patient had primary generalised epilepsy causing generalised tonic-clonic seizures; the remaining five patients had localisation-related epilepsy causing complex partial seizures. SPET imaging was performed using 250 MBq of (99m)Tc-HMPAO and a four-scan paradigm - two with and two without stimulation. The stimulation began at VNS current levels of 0.25 mA and was increased according to the limit of patients' tolerance, usually defined by coughing or discomfort. The stimulating waveform was of continuous square wave pulses of 500 micro s duration at 30 Hz. Image analysis was by SPM99. Reduced perfusion during stimulation was observed in the ipsilateral brain stem, cingulate, amygdala and hippocampus and contralateral thalamus and cingulate. The study provides further evidence of the involvement of the limbic system in the action of vagal nerve stimulation.
Eur J Nucl Med Mol Imaging 2003 Feb
PMID:Investigation into the mechanisms of vagus nerve stimulation for the treatment of intractable epilepsy, using 99mTc-HMPAO SPET brain images. 1255 50

We describe a reconstitution syndrome of immune responses to Pneumocystis carinii pneumonia (PCP) in 2 HIV-infected individuals who received highly active antiretroviral therapy (HAART). Patient 1, who had been successfully treated for PCP 3 years before the initiation of HAART, developed cough and pulmonary shadows 6 weeks after the start of HAART. Patient 2 was introduced HAART immediately after completing the responsive treatment of PCP, and then showed dyspnea and diffuse pulmonary infiltrates 7 months later. Histologic findings of lung-tissue samples showed granulomatous tissue (patient 1) and organizing pneumonia with thickening of alveolar septa (patient 2), and immunohistochemical findings revealed both CD4 and CD8 cell subsets represented in the lesions. The tissue and bronchoalveolar lavage (BAL) specimens showed no organisms, but PCR methods with the BAL samples were positive for P. carinii DNA. It is hypothesized that these second respiratory episodes may have arisen as immune reconstitution syndrome in response to residual P. carinii antigen in the lung.
Res Commun Mol Pathol Pharmacol 2002
PMID:Reconstitution of immune responses to Pneumocystis carinii pneumonia in patients with HIV infection who receive highly active antiretroviral therapy. 1508 Apr 97

A 28-year-old Caucasian female with no personal or family history of cystic fibrosis (CF) presented for preconception counseling and screening. Cystic fibrosis transmembrane conductance regulator (CFTR) mutation analysis using the Inno-LiPa CFTR assay revealed lack of hybridization for both the wild-type and mutant oligonucleotides for 3120+1G>A. This region was sequenced, and an apparent homozygous 3120G>A mutation was detected. Additional testing revealed an abnormal sweat chloride (77 mmol/L). Review of systems was essentially unremarkable with an absence of sinus symptoms, occasional nonproductive cough, and no features of malabsorption. Physical examination, chest X-ray, and pulmonary function tests were within normal limits. Only two other patients (siblings) with homozygous 3120G>A mutations have been reported (http://www.genet.sickkids.on.ca/cftr/). Both siblings had pancreatic insufficiency, mild pulmonary symptoms, and abnormal sweat chloride levels. Our findings suggest that a homozygous mutation of a G>A conversion at 3120 is associated with abnormal CFTR function and either a mild form of CF or no overt symptoms of disease, emphasizing the difficulties in assigning genotype/phenotype correlation.
J Mol Diagn 2006 Feb
PMID:Detection of an apparent homozygous 3120G>A cystic fibrosis mutation on a routine carrier screen. 1643 46

We have previously found that dextromethorphan (DM), over-the-counter cough suppressant, impairs memory retention in water maze task, when it is repeatedly administrated to adolescent female rats at high doses. In this study we examined first if ovariectomy ameliorates the DM-induced memory impairment in female rats, and then whether or not the DM effect is revived by estrogen replacement in ovariectomized female rats. Female rat pups received bilateral ovariectomy or sham operation on postnatal day (PND) 21, and then intraperitoneal DM (40 mg/kg) daily during PND 28-37. Rats were subjected to the Morris water maze task from PND 38, approximately 24 h after the last DM injection. In probe trial, goal quadrant dwell time was significantly reduced by DM in the sham operated group, however, the reduction by DM did not occur in the ovariectomy group. When 17beta-estradiol was supplied to ovariectomized females during DM treatment, the goal quadrant dwell time was significantly decreased, compared to the vehicle control group. Furthermore, a major effect of estrogen replacement was found in the escape latency during the last 3 days of initial learning trials. These results suggest that ovariectomy may ameliorate the adverse effect of DM treatment on memory retention in young female rats, and that estrogen replacement may revive it, i.e. estrogen may take a major role in DM-induced memory impairment in female rats.
J Cell Mol Med
PMID:Ovariectomy ameliorates dextromethorphan--induced memory impairment in young female rats. 1656 29


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