Proprotein convertase enzyme FURIN is upregulated in primary Sjögren's syndrome.

OBJECTIVES: The proprotein convertase enzyme FURIN is a critical regulator of the anti-inflammatory TGFß-1 cytokine and peripheral immune tolerance. In T cells, FURIN is co-regulated with IFN-γ and thus highly expressed in T helper 1 type cells. Previous studies have demonstrated that FURIN is upregulated in inflammatory conditions, including atherosclerosis, rheumatoid arthritis and systemic lupus erythematosus. Here, we evaluated the levels of FURIN in the plasma and peripheral blood mononuclear cells (PBMCs) of patients with primary Sjögren's syndrome (pSS) and in healthy controls. METHODS: FURIN plasma levels were determined by ELISA, and the mRNA expression in PBMCs was quantitated using qPCR. FURIN levels in the plasma were correlated with the clinical and demographic characteristics of the patients. RESULTS: FURIN was found to be significantly upregulated at both the protein and mRNA level in pSS patients compared to healthy controls. In pSS patients, high FURIN protein levels were significantly associated with elevated IFN-γ levels in the plasma as well as a longer duration of sicca symptoms in the eyes. pSS patients with high FURIN levels in their plasma showed a trend towards lower levels of serum beta-2 microglobulin, ESR and a lower systemic disease activity index ESSDAI. CONCLUSIONS: The proprotein convertase FURIN is significantly upregulated in pSS. Elevated FURIN levels associate with high levels of the Th1 type cytokine IFN-γ and long duration of dry eye symptoms. Patients with high FURIN levels show signs of lower disease activity suggesting that FURIN might have a protective role in pSS.

Serum retinol and xerophthalmia among a prison population in Papua New Guinea.

PURPOSE: To estimate the prevalence of vitamin A deficiency (VAD) and one of its clinical manifestations, xerophthalmia, and examine the predictive value of nyctalopia and ocular signs for serum retinol concentrations among a prison population in Papua New Guinea. METHODS: A cross-sectional study of 148 prisoners and 9 guards; all males aged ≥18 years. Interview-based questionnaire; ocular examination; serum retinol concentration determination. RESULTS: Two guards had marginal (retinol <1.05-≥0.70 µmol/L) VAD. For prisoners: mean retinol was 0.84 ± 0.49 µmol/L; 43.9% (95% CI 35.9, 52.2) had VAD (retinol <0.70 µmol/L); 9.6% (95% CI 5.1, 17.0) self-reported nyctalopia prior to, and 36.1% (95% CI 27.7, 45.5) after incarceration; 10.9% (95% CI 6.7, 17.0) exhibited at least one sign of xerophthalmia (2 had fundus changes; all 4 with more than conjunctival xerosis alone had severe [<0.35 µmol/L] retinol deficiency). Prisoners with ocular signs were more likely than those without to have VAD (OR 10.4; 95% CI 2.5, 70.3; P < 0.001) and severe retinol deficiency (OR 19.1; 95% CI 5.5, 77.2; P < 0.001). Positive (PPV) and Negative (NPV) Predictive Values: of nyctalopia for any (PPV 62.9%; NPV 32.8%) and severe (PPV 25.7%; NPV 85.9%) retinol deficiency; of ocular signs for any (PPV 93.3%; NPV 38.2%) and severe (PPV 73.1%; NPV 87.8%) retinol deficiency, and VAD (PPV 86.5%, NPV 38.2%). CONCLUSIONS: VAD and xerophthalmia were present in this prison population. There may be VAD in the wider community. The former needs remedy and the latter deserves investigation. Self-reported nyctalopia was not a useful indicator of retinol deficiency. Absence of ocular signs was unhelpful for ruling out VAD.

Incidence of low vitamin A levels and ocular symptoms after Roux-en-Y gastric bypass.

BACKGROUND: Previous reports have demonstrated a significant incidence of fat-soluble vitamin deficiency after bariatric surgery. The purpose of the present study was to determine the incidence of vitamin A deficiency after Roux-en-Y gastric bypass and to correlate the laboratory findings with ocular symptoms potentially related to vitamin A deficiency. METHODS: All patients who had undergone Roux-en-Y gastric bypass were invited to participate in a nutritional screening. The patients completed a detailed survey concerning ocular symptoms and had their vitamin A level evaluated. RESULTS: A low vitamin A level was identified in 7 (11%) of 64 RYBG patients. Ocular xerosis was present in 18 patients (27%), with night vision changes reported in 45 (68%). Visual disturbances were present in 7 patients (11%) found to have low vitamin A levels, with hypovitaminosis A present in 22% of patients with xerosis (P <.05). CONCLUSION: Low vitamin A levels and frequent ocular complaints that might be associated with decreased vitamin A are common findings in the post-RYBG patient population. Additional study is needed to assess the role of routine vitamin A screening and replacement in the postbariatric surgery patient.

Vitamin A deficiency in a Kenyan prison.

OBJECTIVE: To estimate the prevalence and causes of vitamin A deficiency disorders (VADD) in adult male prisoners in Nakuru, Kenya. METHODS: A total of 1048 male prisoners aged > or =16 years in Nakuru Government of Kenya prison in Nakuru, Kenya were examined by an ophthalmologist for signs of xerophthalmia. Two hundred and forty-one cases with xerophthalmia and 448 controls randomly selected from the remaining prison population were interviewed about risk factors for xerophthalmia and blood samples were taken to measure serum retinol and haemoglobin. RESULTS: 23.6% (95% CI = 21.1-26.3%) of examined inmates showed at least one sign of xerophthalmia, mostly night blindness (98.8% of cases). In the case-control study, the age-adjusted analyses showed that xerophthalmia was associated with age, length of imprisonment and previous imprisonment. Men with xerophthalmia were significantly more likely be in poor health characterised by significant illness, recent hospital admission, persistent cough, diarrhoea, fever or chronic illness. After multivariate adjustment, duration of imprisonment remained strongly associated with xerophthalmia (OR comparing >4 years with <6 months = 20.1, 95% CI = 8.3-48.8). Previous imprisonment, fever, diarrhoea, hospital admission and chronic illness were also significant predictors. Serum retinol levels were significantly lower in cases than controls, while there was no difference in haemoglobin levels. CONCLUSION: Vitamin A deficiency was a significant public health problem among these Kenyan male prisoners, indicating that it may be important in vulnerable groups other than young children and pregnant or lactating women.

The night vision threshold test is a better predictor of low serum vitamin A concentration than self-reported night blindness in pregnant urban Nepalese women.

This study was conducted to validate the night vision threshold test (NVTT) as an indicator of night blindness. A total of 1401 pregnant women from the National Maternity Hospital participated in this study. Women were queried about night blindness and took the NVTT using standardized procedures after 10 min of dark adaptation. Sixteen percent failed the NVTT, but only 6.4% reported having night blindness. Blood samples from women who failed the NVTT (cases) and matched controls indicated the serum vitamin A (SVA) concentration was lower (P < 0.05) in cases (1.19 +/- 0.03 micromol/L) than in controls (1.29 +/- 0.03 micromol/L). The SVA concentrations did not differ between women who reported and did not report night blindness. The SVA concentration was correlated (r = 0.22, P < 0.001) with the NVTT scores. Twenty-five percent of women with an SVA < 0.35 micromol/L reported night blindness while 100% failed the NVTT. Nineteen percent of women with an SVA < 0.70 micromol/L reported night blindness while 73% failed the NVTT. A receiver operating characteristics analysis indicated that the NVTT had greater sensitivity (0.73 vs. 0.19) and less specificity (0.51 vs. 0.87) compared with reported night blindness for women with SVA < 0.70 micromol/L and greater sensitivity (100.0 vs. 0.73) and similar specificity (0.51 vs. 0.50) for women with SVA < 0.35 micromol/L. The NVTT identified women with low SVA and self-reported night blindness was misleading. We provide a preliminary algorithm to predict the population of women with low SVA concentrations.

Vitamin A deficiency and xerophthalmia among school-aged children in Southeastern Asia.

OBJECTIVE: To determine provisional estimates of the extent of vitamin A (VA) deficiency and xerophthalmia among school-aged children. DESIGN: Literature search of published, unpublished and website-based population survey and study reports, with country-specific imputation of prevalence rates and numbers of children affected by: (1) VA deficiency based on measured or imputed distributions of serum retinol concentration < 0.70 micromol/l (equivalent to < 20 microg/dl) and (2) xerophthalmia, by country. SETTING: Countries within the WHO South-East Asian Region. SUBJECTS: The target group for estimation was children 5-15 y of age. INTERVENTIONS: None. RESULTS: The estimated prevalence of VA deficiency is 23.4%, suggesting that there are approximately 83 million VA-deficient school-aged children in the region, of whom 10.9% (9 million, at an overall prevalence of 2.6%) have mild xerophthalmia (night blindness or Bitot's spot). Potentially blinding corneal xerophthalmia appears to be negligible at this age. CONCLUSIONS: VA deficiency, including mild xerophthalmia, appears to affect large numbers of school-aged children in South-East Asia. However, nationally representative data on the prevalence, risk factors and health consequences of VA deficiency among school-aged children are lacking within the region and globally, representing a future public health research priority.

Validation of night blindness reports among children and women in a vitamin A deficient population in rural Tanzania.

OBJECTIVE: This study validates different definitions of reported night blindness (XN) in a vitamin A deficient African population with no local term for XN. DESIGN: Case-control study with follow-up after treatment. SETTING: Eight primary schools and health centres in rural Tanzania. SUBJECTS: A total of 1214 participants were screened for reported XN and other eye signs of xerophthalmia: 461 children aged 24-71 months, 562 primary school-age children and 191 pregnant or breast-feeding women. All 152 cases of reported XN were selected for the validation study and group matched with 321 controls who did not complain of XN. XN reports were validated against serum retinol concentrations and pupillary dark adaptation measurements in cases and controls. INTERVENTION: All children and women who reported XN or had other signs of active xerophthalmia were treated with vitamin A and followed up 3-4 weeks later. Half of the untreated control group who had their serum retinol examined in the baseline examination were also followed up. RESULTS: The overall prevalence of reported XN was 12.5%. At baseline, mean pupillary threshold (-1.52 vs -1.55 log cd/m(2), P=0.501) and median serum retinol concentrations (0.95 vs 0.93 micromol/l, P=0.734) were not significantly different in cases and controls either overall or in each population group. More restricted case definitions reduced the prevalence of reported XN to 5.5% (P<0.001), but there was still no significant difference between cases and controls although the results were in the expected direction. After treatment, the median serum retinol concentration improved significantly only in the most deficient group, the young children. Dark adaptation improved in all the subgroups but the difference was only significant for young children and primary school-age children when the restricted case definitions were used. CONCLUSIONS: XN reports are a poor indicator of vitamin A deficiency in this population. SPONSORSHIP: Task Force Sight and Life, Basel, Switzerland.

Hyporetinolemia and acute phase proteins in children with and without xerophthalmia.

BACKGROUND: The relations among hyporetinolemia, acute phase proteins, and vitamin A status in children are unclear. OBJECTIVE: The objective was to examine the relations between acute phase proteins and plasma retinol concentrations in children with and without clinical vitamin A deficiency (Bitot spots and night blindness). DESIGN: The study was a nonconcurrent analysis of acute phase protein concentrations and other data from a previous clinical trial. Preschool children, 3-6 y of age, with (n = 118) and without (n = 118) xerophthalmia were assigned to receive oral vitamin A (60 mg retinol equivalent) or placebo and were seen at 5 wk. All children received oral vitamin A (60 mg retinol equivalent) at 5 wk. RESULTS: At baseline, alpha(1)-acid glycoprotein (AGP) was elevated in 42.9% and 23.5% (P < 0.003) and C-reactive protein (CRP) was elevated in 17.7% and 13.7% (NS) of children with and without xerophthalmia, respectively. Hyporetinolemia (retinol < 0.7 micromol/L) occurred in 61.0% and 47.4% (P < 0.04) of children with and without xerophthalmia, respectively. A history of fever, a history of cough, and nasal discharge noted on examination were each associated with elevated acute phase proteins. Vitamin A supplementation increased plasma retinol at 5 wk but had no significant effect on concentrations of acute phase proteins. CONCLUSIONS: Elevated acute phase protein concentrations and infectious disease morbidity are closely associated during vitamin A deficiency.

Hypovitaminosis A in metropolitan Adelaide.

Hypovitaminosis A is a well-recognized condition in many developing countries. However, in the developed world the diagnosis is frequently missed or delayed because of its rarity. A 67-year-old man from metropolitan Adelaide presented to us with gradual but severe bilateral visual loss. He had marked punctate epithelial keratopathy in both eyes. Hypovitaminosis was suspected because of his bizarre dietary habit, and this was confirmed by a combination of impression cytology of the ocular surface and biochemical testing of his venous blood. His vision responded dramatically to vitamin A supplementation. Hypovitaminosis A should be suspected in severe cases of 'dry-eye', especially in those patients with unusual dietary habit or malabsorption.

Malnutrition and xerophthalmia in rural communities of Ethiopia.

OBJECTIVE: To determine the level of malnutrition and xerophthalmia in pre-school children. DESIGNS: Non-randomised community based study. SETTINGS: Four different administrative regions: Harari, Tigray, Southern Nation Nationalities and people region (SNNPR) and Oromiya, with different eco-zones, were studied from May to June 1996. SUBJECTS: Fifteen thousand and eighty seven children, aged between six and 71 months, examined for clinical symptoms and signs of xerophthalmia. Anthropometry and blood samples were taken from every 20 children (n = 634) of same age, for serum retinol and nutritional determination. INTERVENTION MEASURES: Disease targeted approach of vitamin A supplementation was employed in the regions. RESULTS: The overall prevalence rates of night blindness and Bitot's spots exceeded WHO cut-off point for xerophthalmia as a public health problem, with higher prevalence rates in males (53%) than females (26%). The proportion of children with deficient serum retinol concentrations (SRC), and Bitot's spot were observed to be higher in Oromiya and Harari regions followed by Tigray, than SNNPR administrative regions. Most of the affected children were aged between 36 and 72 months. The greatest low SRC was also observed in the same age group of children in all regions. There was higher prevalence rate of stunting (60.1%) than wasting (12.2%) with an additional (8.8%) of children both stunted and wasted. The proportion of stunted children was high in Tigray followed by Oromiya, SNNPR and Harari regions. CONCLUSION: The high level of stunting and Bitot's spot, together with the low level of serum retinol concentrations found in these regions, indicates the need to strengthen this intervention strategy further with universal vitamin A capsule distribution, nutrition education and promotion of horticulture activities.

Association of xerophthalmia, flecked retina, and pseudotumor cerebri caused by hypovitaminosis A.

PURPOSE: To report an unusual case of hypovitaminosis A with bilateral papilledema and flecked retina that regressed after restoration of vitamin A deficiency. METHOD: Case report. A 27-year-old woman had undergone a biliopancreatic bypass for obesity in 1990. In 1995, she presented with bilateral xerophthalmia, bilateral papilledema, and bilateral flecked retina. RESULTS: Laboratory tests demonstrated low serum levels of vitamin A (0.8 micromol/l) and vitamin E (8.54 micromol/l). Xerophthalmia, papilledema, and flecked retina disappeared after restoration of normal vitamin A blood levels. CONCLUSION: Hypovitaminosis A after biliopancreatic bypass for obesity may be associated with xerophthalmia, pseudotumor cerebri, and flecked retina.

A population-based study of xerophthalmia in the extreme North Province of Cameroon, West Africa.

OBJECTIVE: To obtain cross-sectional data on clinical and nutritional vitamin A deficiency from which to design appropriate intervention strategies. DESIGN: A population-based survey using multistage, cluster sampling. SETTING: Extreme North Province of Cameroon, West Africa. PARTICIPANTS: Children aged 0 to 5 years. MAIN OUTCOME MEASURES: Clinical signs of active xerophthalmia and dietary vitamin A intake. RESULTS: Of 5352 children examined, signs of active xerophthalmia were noted in 0.62%. Bitot's spots, corneal xerosis, and corneal ulceration were noted in 0.47%, 0.06%, and 0.12% of the subjects, respectively. Children with xerophthalmia had lower vitamin A intake scores when compared with age-matched controls and with a 20% systematic subsample of children. CONCLUSION: Xerophthalmia is a major public health problem in this region.

Ocular findings in cystic fibrosis patients receiving vitamin A supplementation.

BACKGROUND: Vitamin A deficiency with eye symptoms has been reported in patients with cystic fibrosis who received the recommended daily intake of vitamin A. METHODS: We measured serum retinol, dark adaptation, contrast sensitivity, and dry eye status in 35 adult cystic fibrosis patients to ascertain whether they had ocular signs or symptoms. RESULTS: Median serum retinol concentration was 1.95 mumol/l, range 1.08-4.01 mumol/l, with no values indicating vitamin A deficiency. Retinal light sensitivity was normal. Nineteen patients had reduced contrast sensitivity. Conjunctival imprints all showed plenty of goblet cells, but were characteristic of dry eye in 42% of patients (n = 14). Decreased tear film stability was found in 49% (n = 17), tear production was low in 31% (n = 11), and 23% (n = 8) showed an increased amount of dying epithelial cells. Nine patients (26%) had keratoconjunctivitis sicca according to the Copenhagen criteria. CONCLUSION: Our patients had no biochemical or clinical signs of vitamin A deficiency. We speculate that the high incidence of dry eye could be a primary manifestation of cystic fibrosis.

A priming dose of oral vitamin A given to preschool children may extend protection conferred by a subsequent large dose of vitamin A.

A randomized trial tested whether a priming dose of vitamin A would extend the protection of a subsequent 60,000-micrograms retinol equivalent (RE) oral dose. Seventy-five xerophthalmic and 74 age- and neighborhood-matched non-xerophthalmic preschool children were randomized to one of three oral regimens of vitamin A, receiving peanut oil only (Group A), 7500 micrograms RE (Group B) or 60,000 micrograms RE (Group C), followed in all instances by 60,000 micrograms RE 1 wk later. Serum retinol was measured 2, 4, 6 and 12 mo following the second dose by technicians unaware of the children's treatment status. Among xerophthalmic children, mean values differed across treatment groups at 2 mo (C > A) and tended to be different at 12 mo (C > A and B > A). Among non-xerophthalmic children mean retinol concentrations differed across treatment groups at 6 mo, but not in a consistent way (A > C > B), and at 12 mo (C > A and B > A). Xerophthalmic children reverted to biochemical deficiency faster than non-xerophthalmic children. A small or large priming dose may extend the protection conferred by a 60,000-micrograms RE dose, supporting the use of repeated, spaced doses of vitamin A for treating xerophthalmia. Similar retinol concentrations in Groups B and C at 12 mo suggest the 60,000-micrograms RE prophylactic dose currently recommended by the World Health Organization need not be increased.

Abnormal T-cell subset proportions in vitamin-A-deficient children.

Although vitamin A deficiency in children seems to increase susceptibility to infection and community trials have shown that vitamin A supplementation can reduce childhood mortality from infectious diseases, the underlying biological mechanisms are largely unknown. We conducted a randomised, double-masked, placebo-controlled clinical trial among children in West Java, Indonesia, to determine whether vitamin A deficiency is associated with abnormalities in T-cell subsets and whether vitamin A supplementation affects T-cell subsets. We studied 55 children aged 3-6 years--30 with xerophthalmia and 25 without. Acutely malnourished children (< 80% of reference weight-for-height) were excluded. CD4/CD8 ratios and the proportions of circulating CD4 naive, CD4 memory, CD8, CD45RA, and CD8, CD45RO T-cell subsets were measured. Children with xerophthalmia had lower CD4/CD8 ratios (p < 0.08), lower proportions of CD4 naive T cells (p < 0.03), and higher proportions of CD8, CD45RO T cells (p < 0.04) than those without xerophthalmia. 26 children were given vitamin A supplementation (60 mg retinol equivalent) and 29 received placebo. 5 weeks later the vitamin A group had higher CD4/CD8 ratios (p < 0.001), higher proportions of CD4 naive T cells (p < 0.01), and lower proportions of CD8, CD45RO T cells (p < 0.05) than the placebo group. Vitamin-A-deficient children have underlying immune abnormalities in T-cell subsets and these abnormalities are reversible with vitamin A supplementation.

Impression Cytology with Transfer in xerophthalmia and conjunctival diseases.

During a countrywide survey, we assessed the prevalence of clinical signs of xerophthalmia and of major conjunctival diseases in a randomized sample of 2,445 subjects representative of the population of the Republic of Djibouti. On a part of this sample, conjunctival Impression Cytology with Transfer (ICT) test and a plasma retinol determination were performed. Xerophthalmia as a public health problem was displayed by clinical signs (Bitot's spots, corneal scars among preschool children), low plasma retinol levels and ICT test results: 9.3% with deficient cytology in the rural area and 12.3% in the urban one (age-standardized rates). Results of ICT were related to age (p < 0.00001). Vitamin A deficiency was prevalent not only in preschool children but also up to 15 years. Moreover, ICT results are influenced by conjunctival diseases: compared to age-matched controls, there were more abnormal cytologies among patients with trachomatous inflammation (p = 0.025), conjunctivitis (p = 0.024) or Limbal Vernal Keratoconjunctivitis (p = 0.015). Thus ICT shouldn't be performed among children with conjunctival diseases. In the region under study conjunctival diseases had high rates of prevalence: 16.4% of trachomatous scarrings in the urban area (standardized rate), 8% of conjunctivitis among rural preschool children, and 5% of Limbal Vernal Keratoconjunctivitis among children between 5 and 14 years in both areas.