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Neurotological evaluation of Harada's disease.

We have had 30 patients with Harada's disease at our clinic from 1980 to 1993 and their neurotological findings were retrospectively reviewed. There were 12 males and 18 females, whose ages ranged from 15-years to 67-years. Preceding symptoms such as headache or common cold were observed in 50% of the patients. Pleocytosis of the cerebrospinal fluid was found in 89% of the patients. Subjective cochlear and/or vestibular symptoms were noted in 60% of the patients. In 43 of the 50 ears, sensorineural hearing loss (< 40 dB) was observed. In 77% of the patients, vestibular function tests gave abnormal results. On the basis of our findings, it was suggested that Harada's disease with vertiginous and cochlear symptoms could be classified as follows: cochlear type, peripheral vestibular type, cochleovestibular type, central type, and 'unclassified', based on the neurotological results.

Adolescent↗

Vestibular function in patients with a large vestibular aqueduct.

Four patients (7 ears) with a large vestibular aqueduct (VA) were examined for history of vertigo and vestibular function. Vertigo was observed in all the 4 patients. The caloric responses were significantly poorer in ears with a large VA than in the controls. On a patient with a large VA who had several attacks of sudden hearing loss and vertigo following minor head trauma, long-time exposure to sunshine, common cold, and exercise, vestibular function tests were performed several times; the caloric responses were found to fluctuate and direction changing apogeotropic positional nystagmus was observed. These findings suggest that in patients with a large VA, not only hearing but also the vestibular function are generally impaired. We believe than direct transmission of intracranial pressure changes to the inner ear or subsequent inner ear fluid movement through the large endolymphatic sac and duct have an influence on the cochlea and vestibule.

Adolescent↗

Significance of isolation of Moraxella catarrhalis in routine cultures from the respiratory tract in adults: antibody response studied in a whole cell EIA.

The significance of the isolation of Moraxella catarrhalis from sputum or nasopharynx was studied in patients treated at an infectious disease clinic. A whole-cell enzyme immunoassay was used to detect a specific antibody response to M. catarrhalis during infection. In all, 27 patients with respiratory tract infections and 4 with other infections were studied. Titre rises were recorded in 11/23 patients with lower respiratory tract infections, whereas patients with common cold or infections elsewhere all had negative serology. In patients with acute bronchitis, 7/10 patients responded with a significant titre rise. Patients with a low titre in their acute serum sample were those who responded with a titre increase during infection. The findings indicate that isolation of M. catarrhalis from sputa and nasopharyngeal samples in adults is of value for the etiological diagnosis of acute bronchitis and other lower respiratory tract infections, and is therefore important for the choice of drug for treatment, as many isolates are resistant to beta-lactam antibiotics.

Adolescent↗

Viral proteases: an emerging therapeutic target.

Only a few viral diseases are presently treatable because of our limited knowledge of specific viral target molecules. An attractive class of viral molecules toward which chemotherapeutic agents could be aimed are proteases coded by some virus groups such as retro- or picornaviruses (poliomyelitis, common cold virus). The picornavirus enzymes were discovered first, and they have now been characterized by a combination of molecular-genetic and biochemical approaches. Several laboratories have expressed the picornaviral enzymes in heterologous systems and have reported proteolytic activity, as well as the high cleavage fidelity diagnostic of the viral proteases. After dealing with several technical difficulties often encountered in standard genetic engineering approaches, one viral protease is now available to us in quantity and is amendable to mutagenic procedures. The initial outcome of the mutagenesis studies has been the confirmation of our earlier work with inhibitors, which suggested a cysteine active-site class. There is a clustering of active-site residues which may be unique to these viruses. The requirement for an active-site cysteine-histidine pair in combination with detailed information on the viral cleavage sites has permitted design of selective inhibitors with attractive antiviral properties. Future goals include investigation of the structural basis for selective processing and application of the cleavage specificity to general problems in genetic engineering.

Humans↗

Human coronavirus OC43 interacts with major histocompatibility complex class I molecules at the cell surface to establish infection.

Human coronaviruses have been associated with common colds, diarrhea and enterocolitis, and have been implicated in multiple sclerosis. HLA class I molecules may play a critical role as receptor for OC43 because monoclonal antibody (mAb)W6/32 to HLA-A, -B and -C specificities completely blocks infectivity in human rhabdomyosarcoma (RD) cells. The role of HLA class 1 antigen as the virus receptor was examined using HLA-A3.1 stably transfected human plasma cells and untransfected HMY.C1R cells which do not express HLA-A and -B molecules. When the cells (5 x 10(6)) were infected at a multiplicity of one, the HLA.A3 transfected cells produced 10(8) PFU of virus whereas no replication occurred in the HMY.C1R cells mAb W6/32 reduced the virus yield by 99.9%. Cell membranes from HMY.C1R, HMY.A3 cells and chicken erythrocytes were biotinylated as live cells. Immunoprecipitation with polyclonal antiviral antibody to detect binding of biotinylated cell membranes to virus revealed that biotinylated HMY.A3 membranes coprecipitated with virus-antibody complexes when the immunoprecipitates were electrophoresed on SDS-PAGE gel, electroblotted and stained with Avidin-horseradish peroxidase. The results provide direct evidence that OC43 virus can recognize HLA class I as receptor on the cell surface.

Coronavirus↗

Review: clinical opportunities provided by the nasal administration of peptides.

Peptides are rapidly being developed as potential new therapeutic agents and the nasal route is being evaluated as a means of achieving systemic absorption. Current research in man is being directed at a number of polypeptides, including calcitonin, growth hormone releasing hormones (GHRH), insulin, gonadotropin hormone releasing hormones (GnRH) and vasopressin analogues. The underlying protective functions of the nose provide anatomical, temporal and enzymatic barriers to absorption of peptides. The nasal route is relatively unsuccessful when used for high molecular weight polypeptides. Penetration enhancers improve bioavailability but are poorly tolerated. Reproducibility of effect is highly variable, major contributing factors including the site of deposition and type of delivery system as well as changes in the mucous secretion and mucociliary clearance, compounded by the presence of allergy, hay fever and the common cold in treated subjects. The future potential for this route lies in development of effective and well tolerated formulations in highly accurate delivery systems for the chronic administration of peptides, enabling the replacement of impractical and invasive intravenous injections in patients on lifelong substitution treatment for various deficiency states.

Administration, Intranasal↗

Zinc gluconate: acute ingestion.

CASE REPORT: Despite the popularity of zinc gluconate for use in attenuation of common cold symptoms, there is little information on the effects of acute overdose. A 17-year-old male ingested approximately 85 tablets or 4 g zinc gluconate (570 mg elemental zinc). He experienced severe nausea and vomiting within 30 minutes of the ingestion but had no further sequelae such as diarrhea, gastric erosions, esophageal burns, shock, neurologic dysfunction, symptoms of anemia, or hepatic inflammation. Serum zinc level was 4.97 mg/dL at approximately 5 hours postingestion.

Administration, Oral↗

Antibiotics for upper respiratory tract infections in ambulatory practice in the United States, 1997-1999: does physician specialty matter?

BACKGROUND: The dangers of overuse of antibiotics for upper respiratory infections (URIs) has been widely recognized, but the rate of change in prescribing patterns in recent years is unknown. METHODS: Data on the use of antibiotics for URIs was extracted from the 1997 to 1999 National Ambulatory Medical Care Survey (a national multistage probability sample survey of patients' office visits to office-based physicians). Adult patients (>/=18 years) with a primary diagnosis of URI (bronchitis, common colds, and other acute upper respiratory infections) were included. The decision to prescribe antibiotics was modeled as a function of patient, physician, and practice characteristics using logistic regression. RESULTS: The rate of antibiotic prescription for URIs decreased from 52.1% in 1997 to 41.5% in 1999. In a multivariate logistic regression model, treatment by general internal medicine physicians [odds ratio (OR), 0.37; 95% confidence interval (CI), 0.18 to 0.76] was associated with lower prescription rates. Of patients visiting general internal medicine physicians for URIs, 36.2% received antibiotics compared with 42.9% of those seeing a general/family medicine physician. Patients treated by their primary care physicians had a higher risk of receiving antibiotics (OR, 1.70; 95% CI, 1.08 to 2.68). CONCLUSIONS: Despite a downward trend in antibiotic prescribing over the years, overprescription of antibiotics for upper respiratory infections persists. General internal medicine physicians are less likely than general/family physicians to prescribe antibiotics, but this gap seems to be narrowing. Specific interventions must be designed to address these disparities.

Adult↗

[An elderly case of chronic inflammatory demyelinating polyneuropathy with acute onset in the course of diabetes mellitus].

A 77-year-old man was admitted because of muscle weakness in both upper and lower extremities. Diabetes mellitus was diagnosed in 1988 and he had been treated by oral hypoglycemic agents. He had a common cold at the end of January, 1997. Muscle weakness appeared in the upper extremities, followed by the lower extremities at the end of February. No sensory disturbance or dysuria was recognized. Nerve conduction study revealed distally dominant demyelinating polyneuropathy. Guillain-Barré's syndrome was diagnosed and he recovered completely following immunological absorption therapy (IAT). However, he had quadriplegia again at the end of April. He was treated by IAT combined with corticosteroid and has shown no relapse. In June, 1997, gastric cancer was detected by upper gastrointestinal fiberscopy and subtotal gastrectomy was performed. Judging from this clinical course, this case seems to be chronic inflammatory demyelinating polyneuropathy (CIDP) with acute onset. Many kinds of causes often contribute to the pathogenesis of neuropathy in the elderly. So in cases of progression or worsening, we should consider such possibilities and it is necessary not to exclude treatable causes of neuropathy.

Aged↗

Composite type of split cord malformation: two different types at three different levels: case report.

The authors report on a child with a composite type of split cord malformation (SCM). The patient presented with symptoms of a common cold. The diagnosis of SCM was made based on computerized tomography and magnetic resonance (MR) imaging of whole spinal axis. The SCM was Type I at T-4 and T-5 and Type II at T-12, according to the classification developed by Pang. The child underwent resection of the splitting lesions and terminal filum release. No case of composite-type SCM reported to date contains documentation of such a malformation. Because of the possible neurological and urological problems, the authors recommend MR imaging of the whole spine be performed during/an evaluation for SCM.

Female↗

Vascular hamartoma of the orbit.

The aim of this presentation is to report a combined form of vascular malformation of the orbit. A 2-year-old girl had a four-month history of severe proptosis in the right eye. The patient had intermittent proptosis in association with a common cold. The globe was displaced downward and extraocular motility was markedly limited. Multiple intraconal and some extraconal cysts were removed with transcutaneous transseptal anterior orbitotomy. Histological examination showed several characteristics of vascular anomaly. There were malformatively dilated veins intermingled with dilated lymphatic channels, focal cavernous and capillary hemangiomatous features. This combined form of vascular anomaly can be presented as a venous lymphatic malformation associated with hemangiomatous features.

Child, Preschool↗

Allergic rhinitis. Recognizing signs, symptoms, and triggering allergens.

Runny noses, sneezing, nasal congestion, and other nuisance symptoms are part and parcel of primary care practice. But how can you quickly discern which symptoms are related to common colds and which stem from allergic rhinitis? Careful history taking usually provides clues, but allergy testing may be needed when triggers are not clear. In this first of two articles on allergic rhinitis, Dr Ferguson explains what to look for, what questions to ask, when to test for allergies, and how to modify a patient's environment to minimize problems. The second article, beginning on page 117, discusses pharmacologic treatment and immunotherapy for allergic rhinitis.

Allergens↗

What role for antibiotics in otitis media and sinusitis?

In patients with otitis media or sinusitis, antibiotics must be used judiciously. First-line treatment for both uncomplicated acute otitis media and acute sinusitis is amoxicillin. Erythromycin ethylsuccinate and sulfisoxazole or TMP-SMZ may be used in patients who are allergic to penicillin. Beta-lactamase-stable agents should be given when no response occurs within 48 to 72 hours. In cases in which penicillin-resistant pneumococcus is suspected, high-dose amoxicillin, with or without clavulanate, or clindamycin should be considered. Antibiotics are not indicated for initial treatment of otitis media with effusion but may be considered for effusions lasting longer than 3 months. Prophylactic antibiotics should be considered only for recurrent acute infections occurring three or more times within 6 months or four or more times within a year. The common cold should not be treated with antibiotics, and antimicrobial therapy should be initiated only when there is reasonable clinical certainty about the presence of acute sinusitis.

Acute Disease↗

[Study on difference in olfactory response in dysosmia patients].

Using 1952 dysosmia patients, we studied the difference in olfactory response to 5 types of odorous substances used in the standard olfactory acuity test in Japan--beta-phenyl ethyl alcohol, methyl cyclopentenolone, isovaleric acid, gamma-undecalactone, and scatol. Olfactory dysfunctions included 887 patients with chronic paranasal sinusitis, 255 with allergic rhinitis, 326 with common cold sequela, 77 with complications from head injuries, 28 with drug-induced dysosmia, 39 with congenital dysosmia, 257 with dysosmia of unknown etiology, and 83 miscellaneous. The standard olfactory acuity test before treatment indicated that 82 patients detected only one odor within the detection threshold and 157 within the recognition threshold; 40 responded only to isovaleric acid at the detection threshold and 101 at the recognition threshold. Both figures were significantly greater than those who responded to other odors (p < 0.01). No specific trends were noted in etiologies of dysosmia that allowed smelling of isovaleric acid only either at the detection or recognition threshold. Among those whose olfactory thresholds were judged to be scaled out against all 5 odorous substances, 552 were rated as scaled out at the detection threshold and 630 at the recognition threshold. During post treatment, 33 scaled out at the detection threshold and 32 scaled out at the recognition threshold improved enough to smell 1 type of odor. Of these, 15 scaled out at the detection threshold and 13 scaled out at the recognition threshold became able to smell only isovaleric acid. Those becoming able to smell only isovaleric acid either at the detection or recognition threshold, significantly outnumbered those becoming able to smell other odors (p < 0.01). No outstanding cause of dysosmia was seen in those able to smell isovaleric acid. This data indicates that olfactory function for detecting isovaleric acid is relatively resistant to disease and is most likely to be restored. The difference in olfactory response of patients with olfactory dysfunction such as those above may be due to variations in the number of olfactory receptor proteins for specific odors within olfactory cells or different responses to the type of molecules of odor-emitting substances.

Adolescent↗

[The activity of superoxide dismutase in patients with taste and smell dysfunction].

It was revealed that Zinc deficiency might cause taste and smell dysfunction. Superoxide dismutase (SOD), which scavenges superoxide, is a type of zinc enzyme. It was also demonstrated that the overproduction of superoxide damages normal tissue. We therefore measured the activity of SOD in serum and saliva of patients with taste or smell dysfunction by the cytochrome C reduction method using a xanthine-xanthine oxidase system. As a result, in the patients with taste dysfunction, the activities of SOD in both serum and saliva were normal, but mean level of serum Zinc was near to the lower normal limit. On the other hand, in the patients with smell dysfunction caused by chronic sinusitis or common cold, the activity of SOD in serum was significantly lower than that of healthy volunteers, and that in saliva was normal. These results suggest that Zinc enzymes, except serum and salivary SOD, are involved in the sense of taste, and that further investigation is necessary to clarify the relation between serum SOD deficiency and olfactory dysfunction.

Adult↗

IL-12-activated NK cells reduce lung eosinophilia to the attachment protein of respiratory syncytial virus but do not enhance the severity of illness in CD8 T cell-immunodeficient conditions.

Bronchiolitis caused by respiratory syncytial virus (RSV) infection is a major cause of hospitalization in children under 1 year of age. RSV causes common colds in older children and adults, but can cause serious disease in immunodeficient patients and the elderly. Development of effective vaccines and treatments for RSV infection is therefore a priority. Because bronchiolitis and vaccine-augmented disease are thought to be caused by exuberant T cell activation, attention has focused on the use of immunomodulators that affect T cell responses. In mice, IL-12 treatment down-regulates type 2 cytokine responses to the attachment protein G of RSV, reducing lung eosinophilia but further enhancing illness. We now show that CD8(+) T cells are responsible for enhanced weight loss, whereas IL-12-activated NK cells express high levels of IFN-gamma and inhibit lung eosinophilia without causing illness. Moreover, unlike immunocompetent mice, virus is detected in the mediastinal lymph nodes after elimination of both CD8(+) T cells and NK cells. These studies show that innate immune responses to viral infections direct the pattern of subsequent specific immunity and are critical to the development of nonpathogenic antiviral effects. We speculate that IL-12 treatment might be beneficial and safe in T cell-deficient patients with RSV pneumonitis.

Animals↗

Bioavailability and pharmacokinetics of Echinacea purpurea preparations and their interaction with the immune system.

Echinacea is a widely used herbal remedy for the prevention and treatment of the common cold. Recently, many new insights concerning the molecular mode of action of the main lipophilic constituents, the alkamides, have renewed interest in this plant. In order to compare the bioavailability of alkamides from liquid and tablet preparations of E. purpurea (Echinaforce) in humans and to study the effects on ex vivo stimulated blood cells, a randomized, single-dose, crossover study with 10 (8 test, 2 placebo) volunteers has been performed. They received either 4 ml of the standardized E. purpurea (Echinaforce) tincture or 12 E. purpurea (Echinaforce) tablets or placebo. Both doses contained the same amount (0.07 mg) of the major alkamides, dodeca-2E,4E,8Z, 10E/Z-tetraenoic acid isobutylamides. Liquid chromatography electrospray ionization ion-trap mass spectrometry was used to determine the content of alkamides in serum. It was found that the arithmetic mean C(max) of dodeca-2E,4E, 8Z,10E/Z-tetraenoic acid isobutylamides absorbed after oral application of the Echinaforce tincture appeared after 30 min (0.40 ng/ml serum). In comparison, the t(max) of tablets was 45 min with a C(max) of 0.12 ng/ml. An ex vivo stimulation of blood by LPS was carried out to measure the influence of E. purpurea on the innate and adaptive immune system. Both E. purpurea preparations led to the same effects on the immune system according to the concentration of pro-inflammatory cytokines TNF-alpha and IL-8. 23 hours after oral application a significant down-regulation of TNF-alpha and IL-8 in LPS pre-stimulated whole blood was found. However, no significant changes in the concentration of IL-6 were observed. Although a quarter of the dodeca-2E,4E,8Z, 10E/Z-tetraenoic acid isobutylamides was absorbed from the tablets, the study shows that the formulations trigger the same effects on the measured immune parameters.

Adult↗

Vitamin C supplementation and respiratory infections: a systematic review.

In this review, the vitamin C trials with military personnel and with other subjects living under conditions comparable to those of military recruits are analyzed to find out whether vitamin C supplementation affects respiratory infections. For this systematic review, we identified seven trials with military personnel, three trials with students in crowded lodgings, and two trials with marathon runners. Eight of these trials were double blind and placebo controlled and seven were randomized. Five small trials found a statistically significant 45 to 91% reduction in common cold incidence in the vitamin C group. These trials were short and the participants were under heavy exertion during the trial. Furthermore, three other trials found a statistically significant 80 to 100% reduction in the incidence of pneumonia in the vitamin C group. The large number of positive findings seems to warrant further consideration of the role of vitamin C in respiratory infections, particularly in military recruits.

Ascorbic Acid↗