Allergic contact dermatitis by ophthalmological medications in Brazil: experience of a dermatology department.

SUMMARY: Topical treatments in ophthalmologic therapy are significant for the development of allergic contact dermatitis (ACD) in the periorbital region. Preservatives, antibiotics, glucocorticoids, and beta-blocker eye drops are defined as drugs with the highest sensitizing potential. The unavailability of patch test batteries containing substances of ophthalmological use makes it difficult for this diagnosis. In the present report, we describe six patients who developed ACD induced by different agents presenting in eye drops, confirmed with the cutaneous patch tests. The ACD diagnosis due to ophthalmic medications can be challenging, since many different agents can cause it, and the sensitivity of these cutaneous tests is low. Thus, early diagnosis is essential to avoid the complications of ACD on the skin and ocular disorders related to chronic periorbital eczema.

Presenteeism among workers: health-related factors, work-related factors and health literacy.

BACKGROUND: Presenteeism is an important factor in workers' health. However, few studies have examined how variables such as socio-economic status, health status, workplace status and health literacy correlate with and affect presenteeism. AIMS: To assess the correlates of presenteeism with a focus on health-related factors, work-related factors and health literacy. METHODS: We conducted a cross-sectional study of 2914 Japanese workers from one company. We used a self-administered questionnaire to assess socio-demographic characteristics, health status, work environment, presenteeism and health literacy. RESULTS: Forty-one per cent of participants were under 40 years of age and 70% were male. We found that 59% of the participants were at high risk of presenteeism. Presenteeism was associated with sex, age, household income, marital status, health-related factors (i.e. self-rated health status, dietary choices, exercise habits), work-related factors (i.e. workplace support, job demands, job control) and health literacy. Logistic regression analyses indicated that presenteeism was associated with self-rated health status, overtime hours, workplace support, job demands, job control and health literacy after adjusting for sex, age and income. CONCLUSIONS: Health-related factors, work-related factors and health literacy are all associated with presenteeism. Improving the workplace environment, especially factors such as overtime working hours, workplace support, job demands and job control, and increasing health literacy may reduce presenteeism among general office workers.

Evaluation of anthropometric measurements at birth in predicting birthweight less than 2000 g in African and Asian newborns: a meta-analysis.

BACKGROUND: Particularly in developing countries, lower birthweight may be associated with higher neonatal mortality, and deliveries frequently take place at home where scales are not always available. Therefore, surrogate measurements for birthweight are necessary as a primary screening measure. The aim of this study was to determine whether newborn chest and arm circumferences can predict birthweight less than 2000 g. METHODS: The selection criteria were studies published in English that could provide all the true- and false-positive and true- and false-negative results with regard to the prediction of birthweight less than 2000 g by other anthropometric measurements among apparently healthy neonates. Ten bibliographic databases (e.g., PubMed) were searched and a bivariate meta-analysis was conducted with hierarchical summary receiver operating characteristic (ROC) curves. A total of 36,987 participants in 24 studies for chest circumference and 16,164 participants in 15 studies for arm circumference were included. The study regions were limited to Africa and Asia. RESULTS: For chest and arm circumferences (24 and 15 studies, respectively), pooled sensitivity (0.94 and 0.89, respectively) and specificity (0.94 and 0.96, respectively), and diagnostic odds ratios (263 and 174, respectively) were sufficiently high to allow good predictions. The diagnostic odds ratio for chest circumference was significantly higher than for arm circumference (P<0.001). The generalizability of the findings is to some extent guaranteed. CONCLUSION: Newborn chest and arm circumferences may be useful predictors of birthweight less than 2000 g, with chest circumference possibly better.

Hearing loss in diffuse cutaneous systemic scleroderma.

OBJECTIVES: Patients with diffuse cutaneous systemic sclerosis (dcSSc) have distinct clinical manifestations, usually with more aggressive organ involvement and highermortality than limited cutaneous systemic sclerosis (lcSSC). Hearing loss had not yet been evaluated in this subtype, so our aim was to assess the auditory system of dcSSc patients in a controlled study. METHODS: Twenty-six patients with dcSSc, according to American College of Rheumatology (ACR) criteria, were evaluated. For each dcSSc patient included in the study, two healthy controls were matched for sex and age (± 2 years). All patients responded to a structured questionnaire regarding otological symptoms and risk factors with regard to hearing loss. A complete ear/nose/throat physical examination was performed followed by speech/pure tone audiometry and impedance measurements. RESULTS: The mean age of the dcSSc patients was 47.0 ± 11.9 years; the mean disease duration was 9.4 ± 9.1 years, and there was a clear female predominance (83%). The questionnaire revealed auditory complaints in 54% of the dcSSc patients (25% hearing loss, 21% aural fullness, 21% tinnitus, and 21% dizziness) and normal otoscopy. Nearly half (46%) of the dcSSc patients were diagnosed as having hearing loss on audiogram compared to only 19% in the control group (p = 0.01). All dcSSc with hearing loss had a sensorineural component, eight (73%) with excellent discrimination on the Percentage Index of Speech Recognition (PISR). Descending configuration and Metz recruitment were observed in 54% of these patients, suggesting cochlear involvement. CONCLUSION: Patients with dcSSc have a high prevalence of sensorineural audiometric hearing impairment and otological complaints, suggesting that the cochlea is an additional target organ in this disease.

Influence of anti-HBc seropositivity on the risk of hepatocellular carcinoma in HCV-infected patients after adjusting for confounding factors.

It is controversial whether past hepatitis B virus infection constitutes an additional risk of hepatocellular carcinoma (HCC) among patients with hepatitis C virus (HCV). The incidence of HCC between 1994 and 2004 was analysed among 1262 patients who were only positive for HCV. The cumulative incidence of HCC was assessed by Kaplan-Meier analysis and the difference between two groups was assessed by the log-rank test. The effect of anti-HBc positivity on the risk of HCC was assessed with multivariate Cox proportional analysis. Anti-HBc was positive in 522 (41.4%) patients. The proportion of male patients (56.7 vs 46.8%, P < 0.001) and mean age (60.8 vs 56.9 years, P < 0.001) were significantly higher in the anti-HBc positive group. HCC developed in 339 patients (mean follow-up 7.0 years), with cumulative incidence rates at 3, 5 and 10 years of 12.7, 24.5 and 41.9% in the anti-HBc positive group and 10.6, 17.7 and 33.4% in the negative group, respectively (P = 0.005). However, anti-HBc seropositivity did not reach statistical significance in multivariate analysis including age and gender (hazard ratio, 1.06; 95% CI, 0.85-1.31; P = 0.63). Anti-HBc positivity and HCC incidence were confounded by male gender and older age.

Visceral fat accumulation is an independent risk factor for hepatocellular carcinoma recurrence after curative treatment in patients with suspected NASH.

BACKGROUND AND AIMS: Visceral fat accumulation reportedly increases the risk of hepatocellular carcinoma (HCC) development in patients with chronic liver disease. However, it has not been fully elucidated whether visceral fat accumulation increases the risk of HCC recurrence after curative treatment in patients with suspected non-alcoholic steatohepatitis (NASH). Therefore this was investigated in the current study. METHODS: 62 patients with naive HCC with suspected NASH were enrolled. All were curatively treated with percutaneous radiofrequency ablation between 1999 and 2006. The visceral fat area (VFA) was determined in each patient from CT images, taken at the time of HCC diagnosis. Patients were divided into two groups based on VFA: the high VFA group (>130 cm(2) in males, >90 cm(2) in females, n = 27) and the others (n = 35). The effects of VFA on HCC recurrence were analysed together with other factors including patients' background, tumour-related factors and liver function-related factors. RESULTS: The cumulative recurrence rates differed significantly between the two groups; 15.9, 56.5 and 75.1% at 1, 2 and 3 years, respectively, in the high VFA group, and 9.7, 31.1 and 43.1%, respectively, in the controls (p = 0.018). Multivariate analysis indicated visceral fat accumulation (risk ratio 1.08, per 10 cm(2), p = 0.046) and older age (risk ratio 1.06 per 1 year, p = 0.04) as independent risk factors of HCC recurrence. CONCLUSIONS: Visceral fat accumulation is an independent risk factor of HCC recurrence after curative treatment in patients with suspected NASH.

Human bronchial intraepithelial T cells produce interferon-gamma and stimulate epithelial cells.

Intraepithelial lymphocytes (IELs) can be identified among epithelial cells in systemic mucosal tissues. Although intestinal IELs play a crucial role in mucosal immunity, their bronchial counterparts have not been well studied. The purpose of this study was to determine the immunological functions of human bronchial IELs, which interact directly with epithelial cells, unlike lamina propria lymphocytes (LPLs). We isolated successfully bronchial IELs and LPLs using a magnetic cell separation system from the T cell suspensions extracted from bronchial specimens far from the tumours of resected lungs. Human bronchial IELs showed an apparent type 1 cytokine profile and proliferated more actively in response to CD2 signalling than did bronchial LPLs. CD8(+) IELs were identified as the most significant sources of interferon (IFN)-gamma. Human bronchial epithelial cells constitutively produced the T cell growth factors interleukin (IL)-7 and IL-15, and levels of those factors increased when cells were stimulated by IFN-gamma. Bronchial epithelial cells expressed cell surface proteins CD58 and E-cadherin, possibly enabling adhesion to IELs. In summary, human bronchial IELs have immunological functions distinct from bronchial LPLs and may interact with epithelial cells to maintain mucosal homeostasis.

Kinin B1 receptors facilitate the development of temporal lobe epilepsy in mice.

Kinins may play a relevant role in epilepsy. In the present study, we evaluated the hippocampal expression of the remaining kinin receptor in B1 (B1KO) and B2 (B2KO) knockout mice strains during the development of pilocarpine epilepsy model. After pilocarpine injection, animals had their behavior parameters monitored to determine different phases of temporal lobe epilepsy (TLE) progression. Hippocampal mRNA expression was evaluated using specific primers for kinin receptors by Real Time-PCR. B1KO hippocampus from acute, silent and chronic phases showed no differences in B2 receptor mRNA expression when compared to control. An increased B1 receptor mRNA expression in treated B2KO hippocampus (0.97+/-0.12, acute; 0.86+/-0.09, silent; and 0.94+/-0.11, chronic phase; p<0,001) when compared to control (0.12+/-0.03) was observed. Behavioral and neurochemistry parameters suggest that kinin B1 receptor is fundamental to development of epilepsy on pilocarpine-induced model.

Lecithin-bound superoxide dismutase in the prevention of neutrophil-induced damage of corneal tissue.

PURPOSE: To evaluate the effects of a lipophilic analog of superoxide dismutase (SOD) in the prevention of polymorphonuclear leukocyte (PMN)-induced damage to corneal epithelial cells in vitro and in bacterial corneal ulcers in vivo. METHODS: Immortalized human corneal epithelial cells (T-HCEC) were cocultured with human PMNs activated with N-formyl-methionyl-leucyl-phenylalanine for 18 hours, after which lactate dehydrogenase (LDH) activity of the supernatant was measured as a marker of cellular damage. The inhibitory effects of lecithin-bound SOD (PC-SOD) and unmodified SOD, as well as PMNs pretreated with anti-CD 18 monoclonal antibody, were compared with untreated control. The retention of each drug on the ocular surface of healthy volunteers was measured by flow cytometry using brush cytology samples. The protective effects of a 0.1% solution of PC-SOD on Pseudomonas aeruginosa corneal infection in guinea pigs were assessed by inflammatory grading scores and histology. RESULTS: Both PC-SOD and SOD effectively suppressed PMN-induced LDH release in T-HCEC in a dose-dependent manner. LDH release was also attenuated when PMNs were pretreated with anti-CD 18 antibodies, suggesting that adhesion molecules were involved in the process. Brush cytology of conjunctival samples showed that PC-SOD was retained longer on the ocular surface compared with unmodified SOD. PC-SOD significantly prevented excessive tissue damage by infiltrating PMNs in P. aeruginosa corneal infection, whereas in control eyes, perforation of the cornea occurred by 6 days. CONCLUSIONS: PC-SOD was effective in attenuating PMN-related tissue damage to corneal tissue both in vitro and in P. aeruginosa infection in guinea pigs.

Thymidine phosphorylase expression results in a decrease in apoptosis and increase in intratumoral microvessel density in human gastric carcinomas.

Thymidine phosphorylase (dThdPase)/platelet-derived endothelial cell growth factor (PD-ECGF) is expressed at higher levels in a variety of human carcinomas than in adjacent normal tissue. The higher expression is associated with an increase in intratumoral microvessel density (IMVD) and an unfavorable patient prognosis. This study examined the role of dThdPase in apoptosis, IMVD and p53 expression in human gastric carcinomas, dThdPase expression was noted in 12 (35.3%) of 34 early carcinomas, and in 20 (55.6%) of 36 advanced carcinomas. At least 10 areas consisting of carcinoma cells with diffuse dThdPase expression from the 32 dThdPase-positive tumors (category I), and 10 areas without dThdPase expression from the 38 negative tumors (category II) were selected from each case. For early gastric carcinoma, the mean IMVD was 88.8+/-19.4 in category I and 61.4+/-17.3 in category II carcinomas, while for advanced gastric carcinoma, the mean IMVD was 98.8+/-21.0 in category I and 76.0+/-27.1 in category II carcinomas. The mean IMVD was significantly higher in category I than in category II tumors (P<0.05). The mean apoptotic index (AI: percentage of apoptotic cells) was 1.95+/-1.30 in category I, and 3.76+/-1.49 in category II carcinomas for early gastric carcinoma, and 1.51+/-0.98 in category I and 2.14+/-0.66 in category II carcinomas for advanced gastric carcinoma, the value of the mean AI being significantly (P<0.05) higher in dThdPase-negative tumors (category II) than in the positive tumors (category I), regardless of tumor stage or histological type. There was a significant inverse correlation (P<0.001) between AI and IMVD. These results indicate that dThdPase expression is associated with both an increase in intratumoral microvessels and a decrease in apoptosis in human gastric carcinomas.

Possible involvement of central C-type natriuretic polypeptide receptor on water intake in spontaneously hypertensive rats, but not in normotensive Wistar-Kyoto rats.

The present study was designed to examine the possible role of brain C-type natriuretic polypeptide receptor (GC-B) in spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto rats (WKY). The level of GC-B mRNA in various regions of the brain in both SHR and WKY was examined in the present study. The GC-B mRNA was unevenly distributed in rat brain, the transcript being expressed predominantly in the hypothalamus and cerebellum but comparatively at low level in the striatum and septum. However, the level in the septum was 3-fold higher in SHR than than in age-matched WKY, while no differences were observed in other regions of the brain. Intracerebroventricular administration of antisense oligonucleotide to GC-B mRNA inhibits the night-time water intake in SHR, but not in WKY. However, the daily food intake was not significantly altered by the injection of antisense oligonucleotide in both strains. These results demonstrate that the brain GC-B mRNA, particularly in septum, is increased in SHR and this increase may be closely related to the regulation of water-drinking behaviour in SHR.

Viscosity-dependent fluid dynamics of eyedrops on the ocular surface.

PURPOSE: To determine whether the viscosity of eyedrops affects the distribution of the precorneal tear film. METHODS: Using a differential pachymetry map, we obtained tear film thickness in healthy volunteers before and after the instillation of nonviscous, aqueous artificial tears and a 0.3% sodium hyaluronate solution. RESULTS: The instillation of aqueous artificial tears disclosed a significant (P < .05) thickening of the superior corneal tear film compared with the inferior corneal tear film. The increase in thickness by 0.3% sodium hyaluronate solution was uniform, with no differences between the superior and inferior cornea. CONCLUSIONS: Aqueous artificial tears caused an uneven thickening of the precorneal tear film, with most of the thickening observed at the superior cornea. Lower sections of the cornea may benefit less from the instillation of nonviscous solutions.

The maximum and minimum water content and cell volume of human erythrocytes in vitro.

The maximum and minimum water contents of human erythrocytes were measured after exposure to various osmotic pressures. Within a range of osmolarities, at which no haemolysis occurred, the water content reached its maximum, 78.1%, at 180 mosM and its minimum, 54.8%, at 800 mosM. Simultaneously, the mean cell volume increased to 98.5 microns 3 at 180 mosM and decreased to 77.2 microns 3 at 800 mosM.

New treatment of dry eye: the effect of calcium ointment through eyelid skin delivery.

AIM: To demonstrate the efficacy of a petrolatum based calcium ointment applied to the lower lid skin in the management of dry eye. METHODS: In a controlled double masked study, the effects of water free petrolatum ointment containing calcium carbonate (10% w/w) on tear functional factors and ocular surface vital staining in dry eye patients were observed. Petrolatum without calcium carbonate served as control. Patients were instructed to place ointment to the lower lid skin twice a day. Evaluation of subjective complaints, fluorescein and rose bengal staining patterns, blink rate, tear evaporation and tear break up time (BUT) were performed before and 3 months after treatment. In order to demonstrate the movement of petrolatum from the skin to the tear film, petrolatum containing 1% sodium fluorescein was placed on the lower lid of four healthy volunteers, and the concentration of fluorescein in the tear film was followed up to 6 hours using an anterior fluorometer. RESULTS: Subjective symptoms significantly improved in both the calcium group (p=0.001) and control (p=0.012), while only the calcium group demonstrated a significant improvement in fluorescein (p=0.043), rose bengal (p=0.021) scores, and blink rate (p=0.004). Tear evaporation also significantly decreased in both the calcium group (p=0.0004) and control (0.043). BUT did not improve in either group. CONCLUSION: Petrolatum based calcium ointment significantly improved symptoms, tear dynamics, and ocular surface staining in dry eye patients. However, some of the therapeutic effects may be due to lipids in the petrolatum vehicle. Petrolatum applied to the lower lid skin is an effective drug delivery system for slowly releasing drugs to the ocular surface.

Albumin as a tear supplement in the treatment of severe dry eye.

AIM: To determine the efficacy of using albumin tear supplements in the treatment of ocular surface disorders as a substitute for serum eye drops. METHODS: The effects of albumin on the viability of serum deprived conjunctival cell were observed in vitro. The ability for albumin to compensate for serum was demonstrated by measuring the activity of the apoptosis related enzyme, caspase-3. In an animal study, corneal erosions were inflicted in 40 Japanese white rabbits. Rabbits were treated with 5% or 10% solutions of human albumin, and the decrease in epithelial defect size was compared with saline control and 0.3% sodium hyaluronate. A clinical case series trial of 5% albumin drops was conducted in nine patients with Sjögren's syndrome with severe dry eye. RESULTS: The addition of albumin to serum deprived conjunctival cells inhibited caspase activity and increased cell viability, showing that albumin can compensate for some of the physiological properties of serum. Corneal erosions in rabbits healed significantly faster (p<0.05) in eyes treated with 10% albumin compared with control and sodium hyaluronate. Patients with Sjögren's syndrome used albumin drops showed statistically significant improvement in fluorescein and rose bengal scores, but not in tear break up time and subjective symptoms. No adverse effects of albumin were observed during the study. CONCLUSIONS: The use of albumin as a protein supplement in artificial tear solutions is a viable approach in the treatment of ocular surface disorders associated with tear deficiency.

Efficacy of core vitrectomy preceding triple corneal procedure.

AIMS: To evaluate the effectiveness of core vitrectomy preceding triple corneal procedure (penetrating keratoplasty, extracapsular cataract extraction, and intraocular lens (IOL) implantation). METHODS: Thirty one consecutive eyes of 31 patients with indication for triple corneal procedure were randomly assigned to either triple procedure with core vitrectomy (vitrectomy group) or without vitrectomy (control group). The success rate of IOL implantation, IOL positioning, intraoperative and postoperative complications, endothelial cell loss, and best corrected visual acuity (BCVA) were compared. Follow up period was six months. Factors that may contribute to vitreous pressure elevation were also investigated in each case. RESULTS: There was no statistically significant difference in each clinical parameter examined except a tendency of facilitating IOL implantation (p = 0.11). There were two cases of vitreous loss in the control group. Retinal detachment was not seen in any of the cases. The body mass index and age were related to higher vitreous pressure (p<0.05). CONCLUSION: Core vitrectomy preceding triple corneal procedure is not necessary for all cases.

Treatment of dry eye by autologous serum application in Sjögren's syndrome.

AIM: To evaluate the efficacy of autologous serum application for the treatment of dry eye in Sjögren's syndrome. METHODS: The stability of essential components (EGF, vitamin A, and TGF-beta) in preserved serum were examined following preservation at 4 degrees C and -20 degrees C. In a primary clinical trial, 12 patients with Sjögren's syndrome were treated with autologous serum (diluted to 20% with sterile saline) for 4 weeks, and vital staining of the ocular surface was compared before and after treatment. The effects of serum on mucin (MUC-1) expression were observed in cultured conjunctival epithelial cells in vitro. RESULTS: EGF, vitamin A, and TGF-beta were well preserved for up to 1 month in the refrigerator at 4 degrees C and up to 3 months in the freezer at -20 degrees C. Rose bengal and fluorescein scores improved significantly from the initial scores of 5.3 and 5.6 to 1.7 and 2.5 after 4 weeks, respectively. The additive effect of human serum for cultured conjunctival epithelial cells showed significant MUC-1 upregulation on the cell surface. CONCLUSION: Autologous serum application is a safe and efficient way to provide essential components to the ocular surface in the treatment of dry eye associated with Sjögren's syndrome.

Treatment of non-inflamed obstructive meibomian gland dysfunction by an infrared warm compression device.

AIM: To test the short term efficacy and safety of an infrared warm compression device (IWCD, Eye Hot, Cept Co, Tokyo, Japan) as treatment for non-inflamed meibomian gland dysfunction (MGD). METHODS: 37 subjects with non-inflamed obstructive MGD, with and without aqueous tear deficiency (ATD) dry eye, participated in a prospective non-comparative interventional case series. Symptom scores, face scores, tear evaporation rates, fluorescein and rose bengal vital staining, tear break up time (BUT), Schirmer test, meibomian gland obstruction, and meibography were compared before and after 2 weeks of therapy. RESULTS: In a total of 37 cases, total subjective symptom scores and subjective face scores improved significantly, from 12.3 (SD 5.9) to 8.4 (6.1), and from 7.0 (1.7) to 5.3 (2.0) (both p <0.0001). The results for tear evaporation rates during forced blinking (p = 0.002), fluorescein staining (p = 0.03), rose bengal staining (p = 0.03), BUT (p <0.0001), and meibomian gland orifice obstruction score (p <0.0001) had also improved significantly at the end of the 2 week period of infrared thermotherapy. No complaints and/or complications of the IWCD were reported. CONCLUSION: The IWCD was effective and safe for the treatment of MGD. Improved tear stability associated with release of meibum is a possible mechanism of this treatment.

Tachykinin antagonist FK224 inhibits neurokinin A-, substance P- and capsaicin-induced human bronchial contraction.

To determine the roles of endogenously released tachykinins (substance P [SP] and neurokinin A [NKA]) in the human bronchial tissues, we studied the effects of tachykinin antagonist FK224 on bronchial smooth muscle contraction induced by SP, NKA and capsaicin in an organ bath. FK224 (10(-6) M and 10(-5) M, respectively) significantly inhibited NKA-induced contraction and 10(-5) M FK224 shifted the dose-response curve to more than one log unit higher concentration. Because SP- and capsaicin-induced contractions were small, we pretreated the tissues with the neutral endopeptidase inhibitor phosphoramidon (10(-5) M), which inhibits degradation of exogenous tachykinins in order to potentiate the contractions. FK224 (10(-5) M) significantly inhibited SP-induced contraction and it shifted the dose-response curves to about one log unit higher concentration. FK224 (10(-5) M) also significantly inhibited capsaicin-induced contraction and it shifted the dose-response curves to more than one log unit higher concentration. In contrast, FK224 (10(-5) M) did not affect on acetylcholine-, histamine-, and leukotriene D4-induced contraction. These results suggest that FK224 is a tachykinin receptor antagonist in the human bronchial smooth muscle, and that capsaicin-induced contraction is due to endogenously released tachykinin-like substances in the human bronchus.

Treatment of superior limbic keratoconjunctivitis by application of autologous serum.

PURPOSE: To determine the efficacy of autologous serum drops in the treatment of superior limbic keratoconjunctivitis (SLK). METHODS: Twenty-two eyes of 11 patients were diagnosed with SLK. All eyes were treated with 20% diluted autologous serum eyedrops 10 times a day in addition to ongoing treatment of dry eye. Fluorescein and rose bengal staining scores, as well as subjective symptom gradings, were performed before and after 4 weeks of therapy. RESULTS: Nine of the 11 patients responded well to treatment (82%). The average rose bengal and fluorescein score improved ( p < 0.05), and there was subjective improvement. CONCLUSION: Autologous serum application can be used as an alternative mode of therapy in SLK.