Characteristics of depressive disorders in patients with rheumatoid arthritis and some related factors.

OBJECTIVE: Rheumatoid arthritis (RA), a type of chronic arthritis, is common in Vietnam. It has severe consequences for patients, both physically and psychologically, including depressive disorders. Therefore, early detection of depressive disorders is of high importance to help provide comprehensive treatment and improve RA patients' quality of life. This cross-sectional study explored the prevalence of depressive disorders and their salient characteristics and related factors in RA patients in Vietnam. PATIENTS AND METHODS: We enrolled 156 patients diagnosed with RA using the ACR-1987 criteria. The Patient Health Questionnaire-9 (PHQ-9) was used to screen for depressive disorders. Patients' demographic characteristics and clinical and laboratory investigation results, such as the visual analog score, complete blood count, erythrocyte sedimentation rate, Disease Activity Score 28 for RA with C-reactive protein (DAS28-CRP), and quality-of-life score (based on the SF-36 test) were analyzed. Depressive disorders assessed on the first day of admission were reevaluated by a psychiatrist if the PHQ-9 score was ≥ 5. RESULTS: According to the PHQ-9 results, depression prevalence among RA patients was 76.3%. The majority of patients (49.4%) had moderate-to-severe depression and 91% experienced sleep disorder symptoms. Negative thoughts -- suicidal ideation or self-injury - were reported by 21.8% of patients. Depression severity had a moderately positive relationship with disease activity level and a moderately negative relationship with quality of life. CONCLUSIONS: Depression prevalence was high among RA patients. Depression severity increased with disease activity and decreased quality of life.

Increasing sample diversity in psychiatric genetics - Introducing a new cohort of patients with schizophrenia and controls from Vietnam - Results from a pilot study.

OBJECTIVES: Genome-Wide Association Studies (GWAS) of Schizophrenia (SCZ) have provided new biological insights; however, most cohorts are of European ancestry. As a result, derived polygenic risk scores (PRS) show decreased predictive power when applied to populations of different ancestries. We aimed to assess the feasibility of a large-scale data collection in Hanoi, Vietnam, contribute to international efforts to diversify ancestry in SCZ genetic research and examine the transferability of SCZ-PRS to individuals of Vietnamese Kinh ancestry. METHODS: In a pilot study, 368 individuals (including 190 SCZ cases) were recruited at the Hanoi Medical University's associated psychiatric hospitals and outpatient facilities. Data collection included sociodemographic data, baseline clinical data, clinical interviews assessing symptom severity and genome-wide SNP genotyping. SCZ-PRS were generated using different training data sets: (i) European, (ii) East-Asian and (iii) trans-ancestry GWAS summary statistics from the latest SCZ GWAS meta-analysis. RESULTS: SCZ-PRS significantly predicted case status in Vietnamese individuals using mixed-ancestry (R2 liability = 4.9%, p = 6.83 × 10-8), East-Asian (R2 liability = 4.5%, p = 2.73 × 10-7) and European (R2 liability = 3.8%, p = 1.79 × 10-6) discovery samples. DISCUSSION: Our results corroborate previous findings of reduced PRS predictive power across populations, highlighting the importance of ancestral diversity in GWA studies.

Effects of glucose, Trolox-C, and glutathione disulphide on lipid peroxidation and cell death induced by oxidant stress in rat heart.

OBJECTIVE: The aim was to find effective protection of myocytes against peroxide induced damage in terms of preservation of contractile activity, protection against lipid peroxidation, and protection against cell death. METHODS: The components of the glutathione redox cycle, the production of malondialdehyde, cell contractions, and enzyme release from myocytes were measured in cultured neonatal rat heart cells before and after administration of cumene hydroperoxide, 80 mumol.litre-1. The protective action was tested of (1) glucose (10 mmol.litre-1) which stimulates the production of NADPH; (2) Trolox-C (0.16 mmol.litre-1) which is a water soluble analogue of alpha tocopherol and a scavenger of free radicals; and (3) GSSG (0.6 mmol.litre-1) which increases the intracellular concentrations of GSH and GSSG. RESULTS: Although the three substances tested were equally effective in reducing the formation of malondialdehyde, exogenous GSSG afforded only slight protection against cumene hydroperoxide induced cell death, whereas glucose and Trolox-C were highly effective protectors. The depressant effect of cumene hydroperoxide on beating frequency was not influenced by preincubation with GSSG, nor by coadministration of glucose, but Trolox-C was able to diminish the negative chronotropic action of cumene hydroperoxide. CONCLUSIONS: Effective protection against cumene hydroperoxide induced lipid peroxidation is not associated per se with effective protection against cumene hydroperoxide induced loss of beating frequency and cell death.

Tick-borne relapsing fever in children.

Three cases of tick-borne fever diagnosed during the summer of 1979 are reported and the ecoepidemiology, clinical manifestations, and treatment of this infection are reviewed. Although challenging, the diagnosis can be made easily if specific historical clues are sought and the patient's blood smear is carefully examined. The diagnosis of this condition early in its course can save clinicians and patients the anxiety and cost of the work-up of a "fever of unknown origin." Since vacationing in the national parks and forests has become increasingly popular among many American families, tick-borne relapsing fever should be considered in any patient with an acute or recurrent fever of unknown origin who exhibits nonspecific symptoms of an undifferentiated "viral illness," and who gives a history of sleeping overnight in log cabins in the coniferous forests of the Western mountains of the United States.

Epidemiology of otitis media onset by six months of age.

OBJECTIVE: Although early otitis media (OM) onset predicts later recurrent and chronic OM, little research has been directed at illuminating the role of prenatal exposures in early OM. This prospective study examined prenatal, innate, and early environmental exposures associated with acute otitis media (AOM) onset and recurrent OM (ROM) by age 6 months. DESIGN AND METHODS: Prospective study of 596 infants from a health maintenance organization followed from birth to 6 months. Mothers completed monthly forms on prenatal exposures (diet, medications, and illnesses) and infant risk factors (eg, smoke exposure and child care) during pregnancy and until infants were 6 months old. Urine samples were collected when infants were 2 months of age and analyzed for cotinine and creatinine. Physicians and nurse practitioners examined infants at each clinic visit and completed standard ear examination forms. RESULTS: Thirty-nine percent had an episode of AOM and 20% had ROM by age 6 months. Using Cox's regression models to control for confounding, respiratory tract infection (relative risk [RR] 7.5), day care (RR 1. 7), >1 sibling (RR 1.4), maternal, paternal, and sibling OM history (RR 1.6, 1.5, and 1.7, respectively) were significantly related to early OM onset. ROM was related to respiratory tract infection (RR 9. 5), day care (RR 1.9), conjunctivitis (RR 2.0), maternal OM history (RR 1.9), and birth in the fall (RR 2.6). Among prenatal exposures, only high prenatal dietary vitamin C intake was significantly inversely related to early AOM with univariate but not multivariate analysis. CONCLUSION: Prenatal factors were not linked to early AOM onset with multivariate analysis, but environmental and innate factors play an important role in early AOM onset. Strategies to reduce exposure to environmental variables could reduce rates of early AOM, which could potentially result in declining rates of ROM and chronic OME.

Evaluation of ventilating tubes and myringotomy in the treatment of recurrent or persistent otitis media.

In a prospective controlled study of the efficacy and sequelae of ventilating tubes, 44 children with bilateral recurrent acute otitis media (greater than 6 episodes/year) and 13 children with bilateral persistent middle ear effusion (greater than 3 months) received unilateral ventilating tube insertion in a randomly selected ear. The contralateral ears were randomized to receive either myringotomy alone or no surgery. Clinical, otoscopic, tympanometric and audiologic examinations were performed before the study and 2 to 4 weeks later, then at 3-month intervals for up to 2 years and at 36 months after surgical randomization. Medical therapy and antibiotic prophylaxis were used whenever indicated. While the ventilating tubes remained functional (mean duration, 10 months) the ears with a tube had significantly fewer episodes of otitis media than their contralateral ear (P less than 0.001; 95% confidence intervals -0.7, -1.7) and had more hearing improvement (P = 0.005; 95% confidence intervals, -5.9, -1.2). After tube extrusion there was a tendency for surgically treated ears to have more otitis and worse hearing, but not at a significant level. Tympanosclerosis, retraction and atrophy were more common in ears that received tubes. The majority of ears treated medically also improved. There is need for a more cautious and selective use of ventilating tubes.

Resolution of otitis media with effusion with the use of a stepped treatment regimen of trimethoprim-sulfamethoxazole and prednisone.

This double blind, placebo-controlled trial was designed to determine whether intervention with a stepped regimen of trimethoprim-sulfamethoxazole (TMP-SMX) and prednisone would prevent high risk children from developing chronic otitis media with effusion (OME) and recurrent acute otitis media. Forty-two children were enrolled, assigned to treatment with active drug or placebo and then examined at 2-week intervals. They received TMP-SMX (or placebo) during the first 2 weeks, TMP-SMX and prednisone (or placebo) during Weeks 3 and 4 for persistent OME and TMP-SMX (or placebo) for Weeks 5 and 6 if OME was still unresolved. After treatment 48% of active drug and 14% of placebo subjects resolved OME bilaterally (P less than 0.05). Active drug subjects also had fewer acute otitis media episodes than placebo subjects while receiving study treatment (P less than 0.01). Although this treatment regimen produced short term OME resolution, long term benefits were not demonstrated.

Determining risk for chronic otitis media with effusion.

Chronic otitis media with effusion (OME) has been observed in 10 to 20% of children following acute, symptomatic otitis media. To determine factors that place children at increased risk of chronic OME, we conducted a 6-week prospective study of 386 children who had 3 or more recent episodes of otitis media and who had middle ear effusion present for at least 2 weeks. Of these children 23% developed chronic OME (i.e. effusion lasting 8 continuous weeks or more), and 26% developed chronic OME complicated by acute, symptomatic otitis media. Predictors for chronic OME were (1) bilateral OME, (2) duration of effusion for greater than 2 weeks at enrollment and (3) day care attendance. Children with these 3 factors had twice the risk of developing chronic OME as children lacking all 3 factors. These risk factors can be used to target children for early, aggressive OME therapy.

A controlled trial comparing three treatments for chronic otitis media with effusion.

A randomized, controlled clinical trial was conducted in 76 children to evaluate the efficacy of trimethoprim-sulfamethoxazole for 4 weeks, prednisone for 2 weeks and aluminum ibuprofen suspension for 2 weeks in resolving chronic otitis media with effusion which had persisted for more than 8 weeks. After 2 weeks of treatment resolution rates of chronic otitis media with effusion in the prednisone and trimethoprim-sulfamethoxazole groups were significantly greater than those in the control (no treatment) and ibuprofen groups. After 4 weeks the differences in resolution rates between the control, trimethoprim-sulfamethoxazole and prednisone groups became smaller. After 12 months of follow-up, differences in hearing sensitivity among study groups were not statistically significant, although 83% of patients had a 15-dB or greater hearing loss. Therefore short term antimicrobial and antiinflammatory treatment did not appear to have a long lasting effect on chronic middle ear inflammation.

Randomized trial of the efficacy of trimethoprim-sulfamethoxazole and prednisone in preventing post-tympanostomy tube morbidity.

This study was designed to determine whether treatment with prednisone and trimethoprim-sulfamethoxazole would reduce first year post-operative morbidity in children with chronic otitis media with effusion undergoing tympanostomy tube insertion (intubation). Eighty children ages 6 months to 8 years were enrolled at intubation and randomized from age strata to receive active drugs or placebos for 14 days after surgery. They were examined with pneumatic otoscopy and tympanometry preoperatively and at 3 weeks and 3, 6, 9 and 12 months after surgery. Active drug treatment significantly reduced tube obstruction or extrusion in the first 3 postoperative months compared with placebos (4% vs. 17%, P = .01). However, rates of repeat intubation, otorrhea and recurrence of otitis media did not differ significantly in the two groups. Children with chronic otitis media with effusion treated with intubation may benefit from a 2-week course of prednisone and trimethoprim-sulfamethoxazole at the time of surgery. However, there is no apparent long term benefit of this treatment.

A modified rapid method of nucleic acid isolation from suspension of matured virus: applied in restriction analysis of DNA from an adenovirus prototype strain and a patient isolate.

This report describes a method for the isolation of nucleic acid from a suspension of matured virus. Nucleic acid (DNA) was isolated from a prototype strain of adenovirus type 7 and a clinical isolate of adenovirus type 7. Instead of the usual method of ultracentifugation, a filtration method was applied to concentrate the virus rapidly and nucleic acid was then isolated by a standard phenol/chloroform/isoamyl-alcohol extraction procedure. The DNA was found to be sufficiently purified to generate a reproducible restriction endonuclease digestion pattern. The clinical isolate of adenovirus type 7 revealed loss of restriction site for the endonuclease HindIII when compared with the prototype strain.

Evaluation of the feasibility of and results of measuring health-status changes in patients undergoing surgical treatment for skeletal metastases.

The goal of treating patients with skeletal metastases is to decrease pain and improve or maintain physical function. Assessment of the effectiveness of treatment should therefore include evaluation of patient-rated measures of quality of life. The primary objective of the study was to determine the feasibility of studying the effect of surgical treatment of skeletal metastases on quality of life. The secondary objective was to provide data that begin to characterize this effect. The characteristics of patients with skeletal metastases are heterogeneous, patient enrollment in the study may be low, high attrition occurs secondary to death, and well accepted health-status measures (such as the Short Form-36) may be ineffective at detecting changes in health status; therefore, it is difficult to study these patients. High attrition and adjuvant treatment with radiation or chemotherapy made it impractical to draw firm conclusions about the effect of surgical treatment, but a trend toward improvement in selected health-status measures for both physical and mental health was noted. Analysis of patient-rated health-status scores as predictors of survival indicates that improvement in these scores 6 weeks after surgery is associated with an increase in the length of survival following surgery.

Bronchodilation from intravenous theophylline in patients with cystic fibrosis: results of a blinded placebo-controlled crossover clinical trial.

Most patients with cystic fibrosis (CF) eventually develop chronic obstructive pulmonary disease and theoretically could benefit from theophylline therapy. The purpose of this study was to investigate the pharmacologic response to intravenous theophylline by pulmonary function tests (PFT) and the theophylline pharmacokinetics in patients with CF. A randomized, double-blind, placebo-controlled, crossover trial was conducted in 10 ambulant patients with CF (5 females, 5 males), aged 11 to 21 years. Each patient received an intravenous dose of theophylline and normal saline over 1/2 hour on consecutive days. Spirometry and whole-body plethysmography were performed at baseline, 1, 3, 5, and 7 h after the theophylline dose, and 10 blood samples were collected over 9 h on both study days. The percent change of PFT from the baseline was recorded. Analysis of variance for balanced two-period crossover design was used to evaluate the effectiveness of theophylline therapy. The serum concentration (Conc.) vs. time data were fitted using nonlinear least-squares regression analysis. The theophylline dose administered was 7.9 +/- 0.4 (mean +/- SD) mg/kg, which produced a maximal Conc. (Cmax) of 14.6 +/- 2.7 microgram/ml. The half-life (T1/2), volume of distribution (Vd), and total body clearance (TBC) were 4.9 +/- 1.9 h, 537 +/- 124 mL/kg, and 80 +/- 16 ml/h/kg, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Residual mesenchyme in temporal bones of children.

The role of mesenchyme in the temporal bone is still poorly understood. A microscopic study of residual mesenchyme was undertaken in temporal bones of children from birth to 5 years of age. Residual mesenchyme was found to be located in the mastoid antrum and epitympanum more often than in the mesotympanum. The amount of mesenchymal tissue remaining in the temporal bones decreased with increasing age. Persistence of mesenchyme in the temporal bone was related to congenital morphologic ear anomalies and syndromes. There was also an association evident with pulmonary disease, but not with congenital heart defects. Persistent mesenchyme was also found to be significantly associated with chronic middle ear inflammation, and in cases of unilateral otitis media the ear with otitis media had more residual mesenchyme than the non-otitis media ear.

Prediction of serous versus purulent otitis media by otoscopy and tympanometry in an animal model.

Non-invasive methods for distinguishing different types of otitis media would have clinical value in predicting otologic morbidity. Two such methods, otoscopy and tympanometry, were used in two experimental models of otitis media to determine whether there are unique otoscopic and tympanometric characteristics of serous and purulent otitis media. A flat (type B or B+) tympanogram and yellow tympanic membrane each had a high likelihood of predicting middle ear effusion in these models, and the best prediction was obtained using both parameters simultaneously. A yellow tympanic membrane color predicted purulent otitis media in one model but did not distinguish purulent from serous ears in the other model. In one model, serous otitis media was frequently associated with a type C (negative pressure) tympanogram. Tympanometry provided a valuable adjunct to otoscopy in detecting effusion and in distinguishing serous and purulent disease. These observations may apply to otitis media in humans, although the variable etiologies of otitis media in humans may confound the ability of otoscopy and tympanometry to distinguish middle ear effusion types.

Expression of glycoconjugates in human eustachian tubes with otitis media.

OBJECTIVES: To characterize glycoconjugate expression in normal human eustachian tubes and study the alterations in glycoconjugate expression found in eustachian tubes with otitis media. STUDY DESIGN: Using lectin histochemistry, alterations in glycoconjugates were studied in three normal temporal bones, in four temporal bones with mucoid otitis media (MOM), and in five with serous otitis media (SOM). METHODS: Sections of previously processed temporal bones were decelloidinized, and then incubated with seven biotinylated lectins--WGA, SNA, MAA, BPA, PNA, UEA-1, and LcH--that reflect seven carbohydrate residues of glycoconjugates, respectively: GlcNAc/NeuNAc, NeuNAc alpha(2-6)GalNAc, NeuNAc alpha(2-3)GalNAc, Gal beta(1-3) GalNAc, L-fucose, and alpha-mannose residues. Control sections were incubated with inhibitory carbohydrates or without biotinylated lectins. RESULTS: In the normal temporal bones, five carbohydrate residues in goblet cells and cilia of the eustachian tube demonstrated moderate to strong activity--NeuNAc alpha(2-6)GalNAc, NeuNAc alpha(2-3)GalNAc, GalNAc, Gal beta(1-3)GalNAc, and L-fucose. Two residues demonstrated weak activity--GlcNAc/NeuNAc and alpha-mannose. Temporal bones with MOM revealed increases in sialic acid and alpha-mannose, and a decrease in L-fucose. Residues of carbohydrates in the cilia of bones with SOM were notably decreased, especially for GalNAc, Gal beta(1-3)GalNAc, and NeuNAc alpha(2-6)GalNAc. CONCLUSIONS: Glycoconjugates in the normal human eustachian tube are rich in GalNAc, Gal beta(1-3)GalNAc, L-fucose, and NeuNAc alpha(2-3/2-6) GalNAc, but low in alpha-mannose and sialic acid. Eustachian tubes from cases with SOM or MOM demonstrated alterations in glycoconjugate expression in cilia and goblet cells, which may reflect disorder of the carbohydrate metabolism during otitis media, especially in SOM.

Tympanic membrane/middle ear pathologic correlates in chronic otitis media.

OBJECTIVE: To correlate pathologic findings of the tympanic membrane with pathologic changes in the middle ear cleft in chronic otitis media. STUDY DESIGN: Retrospective. MATERIAL AND METHODS: One hundred-fifty temporal bones from 97 subjects with chronic otitis media (defined as middle ear pathologic changes including granulation tissue, fluid, cholesteatoma, cholesterol granuloma, tympanosclerosis, and ossicular changes) were selected to correlate the presence of these middle ear pathologies with histopathologic changes of the tympanic membrane. The tympanic membrane pathologies included perforation, myringosclerosis, retraction, hemorrhage, fluid-filled cystic spaces, or dilated vessels. Temporal bones were also assessed for atelectasis. Fifty-six normal temporal bones were taken as controls for measurements. RESULTS: Significant correlations between tympanic membrane and middle ear pathology included myringosclerosis and granulation tissue, myringosclerosis and ossicular pathology, retraction and cholesterol granuloma, retraction and cholesteatoma, retraction and ossicular pathology, perforation and ossicular pathology, and hemorrhage and granulation tissue. Additive effects of some pathologies were also observed. Almost half the bones with middle ear pathology had no associated tympanic membrane pathology, whereas multiple pathologic changes in the tympanic membrane generally showed underlying multiple pathologic changes in the middle ear. CONCLUSION: When tympanic membrane pathology is detected otoscopically, its presence, alone or in combination, can be a strong indicator of underlying middle ear pathology. However, a normal-appearing tympanic membrane does not exclude the possibility of middle ear pathology. These findings suggest the need for other diagnostic tools such as multifrequency tympanometry and otoacoustic emissions to complement otoscopy for diagnosis of middle ear pathology, especially in a tympanic membrane that appears "normal."

Identification of MUC5B mucin gene in human middle ear with chronic otitis media.

OBJECTIVES: To identify the mucin gene and its expressing cells in the middle ear mucosa with chronic otitis media (COM), and to study the correlation between infiltration of inflammatory cells in the submucosa and expression of the mucin gene in the mucosal epithelium with COM. STUDY DESIGN: Middle ear mucosal specimens removed from the inferior promontory area of 19 patients undergoing middle ear surgery for COM were studied. METHODS: Sections were stained with H&E, Alcian blue-periodic acid Schiff (AB-PAS), polyclonal MUC5B antibody, and specific MUC5B riboprobe for histological, histochemical, immunohistochemical, and mucin mRNA analyses. RESULTS: H&E staining revealed pseudostratified epithelia in 18 of the middle ear specimens with COM and cuboidal secretory epithelia in one. AB-PAS staining of epithelia revealed abundant secretory cells and their products (glycoconjugates). In situ hybridization and immunohistochemistry studies demonstrated that the secretory cells of the middle ear mucosa with COM expressed MUC5B mucin mRNA and its product MUC5B mucin. CONCLUSIONS: The MUC5B mucin gene and its product were identified in the middle ear secretory cells of patients with COM. Its expression was extensive in pseudostratified mucosal epithelia and related to infiltration of inflammatory cells in the submucosa of the middle ear cleft with COM, suggestive that inflammatory cell products are involved in the production of MUC5B.

Thickness of the human round window membrane in different forms of otitis media.

The thickness and morphologic characteristics of the round window membrane were evaluated in temporal bones from normal subjects as well as those with serous otitis media, purulent otitis media, and chronic otitis media. Temporal bones were studied in chronological order in six age ranges to determine the possibility of age-related differences. No significant difference in the mean thickness of the round window membrane was observed in terms of age groups in normal temporal bones or temporal bones from patients with otitis media; however, a significant difference in the mean thickness was observed in the various forms of otitis media compared with the normal round window membrane in all age groups. The membrane was thickest in patients with chronic otitis media when compared with that in normal subjects or those with serous or purulent otitis media. The epithelial layer (including the subepithelial space) and the fibrous layer were measured individually to determine in which layer the change in mean thickness occurred. These measurements showed an involvement of all layers of the round window membrane in those groups with otitis media, with maximal involvement of the combined epithelial layer and subepithelial space.

Significance of epidermoid formations in the middle ear in fetuses and children.

OBJECTIVE: To determine the incidence, size, and location of epidermoid formations (EFs), which have been suggested to be precursors of congenital cholesteatomas, in temporal bones from fetuses and children. DESIGN: We examined temporal bones from 226 fetuses and children up to the age of 10 years for the incidence, size, and location of EFs. RESULTS: Twenty-five EFs were identified in middle ears of 3 fetuses, 7 neonates, 9 infants, and 2 children aged 2 and 3 years. There was a male-female preponderance of 5:4. Generally, we saw EFs between the anterosuperior edge of the eardrum and the anterior limb of the tympanic ring, but 4 were below the level of the handle of the malleus. Their widths ranged from 25 to 300 microns. Keratinization was not observed in any EF. Contrary to previous reports, we found EFs not only in ears of fetuses, but also in ears of infants and children. CONCLUSION: Although EFs may persist in some ears, possibly developing into congenital cholesteatomas, our findings do not provide direct support for this concept.