Sustained supplementation and monitored response with differing carotenoid formulations in early age-related macular degeneration.

PURPOSE: To compare the impact of sustained supplementation using different macular carotenoid formulations on macular pigment (MP) and visual function in early age-related macular degeneration (AMD). PATIENTS AND METHODS: Sixty-seven subjects with early AMD were randomly assigned to: Group 1 (20 mg per day lutein (L), 0.86 mg per day zeaxanthin (Z); Ultra Lutein), Group 2 (10 mg per day meso-zeaxanthin (MZ), 10 mg per day L, 2 mg per day Z; Macushield; Macuhealth), Group 3 (17 mg per day MZ, 3 mg per day L, 2 mg per day Z). MP was measured using customised heterochromatic flicker photometry and visual function was assessed by measuring contrast sensitivity (CS) and best-corrected visual acuity (BCVA). AMD was graded using the Wisconsin Age-Related Maculopathy Grading System (AREDS 11-step severity scale). RESULTS: At 3 years, a significant increase in MP from baseline was observed in all groups at each eccentricity (P<0.05), except at 1.75° in Group 1 (P=0.160). Between 24 and 36 months, significant increases in MP at each eccentricity were seen in Group 3 (P<0.05 for all), and at 0.50° in Group 2 (P<0.05), whereas no significant increases were seen in Group 1 (P>0.05 for all). At 36 months, compared with baseline, the following significant improvements (P<0.05) in CS were observed: Group 2-1.2, 6, and 9.6 cycles per degree (c.p.d.); Group 1-15.15 c.p.d.; and Group 3-6, 9.6, and 15.15 c.p.d. No significant changes in BCVA, or progression to advanced AMD, were observed. CONCLUSION: In early AMD, MP can be augmented with a variety of supplements, although the inclusion of MZ may confer benefits in terms of panprofile augmentation and in terms of CS enhancement.

[Differential indications for psychotherapies in borderline personality disorder]. / Indication différentielle des psychothérapies adaptées au trouble de la personnalité limite.

BACKGROUND: Borderline personality disorder (BPD) accounts for 10% of outpatient psychiatric practice. The risk of suicide attempts is high and the psychosocial impairment significant. Different theoretical streams have suggested psychotherapeutical approaches for BPD. OBJECTIVE: to examine the efficacy of psychotherapy for BPD patients on affective symptoms, behavioural outcomes, interpersonal and social functioning, as well as BPD criteria. METHODS: We reviewed the medical literature from 1990 to 2008 on Medline by combining the following keywords "borderline personality disorder" and "psychotherapy" (inclusion criteria). We restricted the analysis to "randomised control trial" or "meta analysis". RESULTS: Of the 39 abstracts that came out from the search, we selected 17 (44%) after applying the exclusion criteria. According to our review, different types of psychotherapies have shown some efficacy on reducing affective symptoms and BPD criteria, as well as improving behavioural outcomes and psychosocial functioning. Dialectical behavioural therapy presents the best-documented efficacy, notably on reducing self-mutilating and suicidal behaviours (five randomized controlled trials [RCT]). Mentalization based treatment seems to be efficient on the four types of outcomes, but has been the object of only one RCT. Finally, some evidence suggests that Manual Assisted Cognitive Treatment and Systems Training for Emotional Predictability and Problem Solving are the most cost-effective and easiest to be implemented. CONCLUSION: According to our review, some evidence supports an efficiency of psychotherapies in the management of several features of BPD. It is likely that, depending on the target symptoms, one type of therapy might be more efficient than another. The acceptability of these long-term treatments is however unknown.

Mapping and characterization of Rf 5: a new gene conditioning pollen fertility restoration in A1 and A2 cytoplasm in sorghum (Sorghum bicolor (L.) Moench).

With an aim to further characterize the cytoplasmic male sterility-fertility restoration system in sorghum, a major fertility restoration gene was mapped along with a second locus capable of partial restoration of pollen fertility. The major fertility restoration gene, Rf(5), was located on sorghum chromosome SBI-05, and was capable of restoring pollen fertility in both A(1) and A(2) male sterile cytoplasms. Depending on the restorer parent, mapping populations exhibited fertility restoration phenotypes that ranged from nearly bimodal distribution due to the action of Rf(5), to a more normalized distribution reflecting the action of Rf(5) and additional modifier/partial restoration genes. A second fertility restoration locus capable of partially restoring pollen fertility in A(1) cytoplasm was localized to chromosome SBI-04. Unlike Rf(5), this modifier/partial restorer gene acting alone resulted in less than 10% seed set in both A(1) and A(2) cytoplasms, and modified the extent of restoration conditioned by the major restorer Rf(5) in A(1) cytoplasm. In examining the genomic regions spanning the Rf(5) locus, a cluster of pentatricopeptide gene family members with high homology to rice Rf (1) and sorghum Rf (2) were identified as potential candidates encoding Rf(5).

[Autoimmune hepatitis: two case reports with different clinical courses - case 3/2011]. / Autoimmunhepatitis: Zwei Fallberichte mit unterschiedlichen Verläufen - Fall 3/2011.

HISTORY AND CLINICAL FINDINGS: Case 1: A 46-year old female patient presented with a recently occurred icterus of unknown origin as well as dark urine and decolored stool. No diseases were found in the patient's medical history. Clinical examination showed no other findings exept from the icterus. Case 2: A 48-year old female patient was admitted to hospital with epigastric pain and icterus. Similar symptoms reoccurred regularly since several years. The patient already underwent cholecystectomy and an ERCP (endoscopic retrograde cholangiopancreaticography) that showed no pathological findings. She reported chronic pain in her finger joints and appearance of haematomas without adequate trauma. CLINICAL INVESTIGATIONS: Case 1: We found highly elevated liver enzymes and bilirubin. Ultrasound examination was unremarkable.The laboratory examination showed a negative serology for hepatitis A, B and C, marked immunoglobulin G (IgG) elevation and hypergammaglobulinaemia. Liver biopsy and analysis of autoimmune antibodies were performed showing high titers of antinuclear antibodies (ANA) and smooth muscle antibodies (SMA). Case 2: We found a considerably reduced liver function with low albumin and prothrombin time, as well as a moderate elevation of liver enzymes and a high bilirubin. Ultrasound examination revealed hepatic parenchymal changes, splenomegaly, and ascites. Oesophagogastroduodenoscopy showed oesophageal varices I°. Serology for hepatitis A, B, and C was negative. Also in this case, a marked IgG elevation and hypergammaglobulinaemia were found. Liver biopsy was performed. Autoimmune antibodies (ANA and SMA) were detectable with high titers. DIAGNOSIS, TREATMENT AND COURSE: In both cases, we diagnosed an autoimmune hepatitis by means of laboratory values, histological findings and detection of typical autoantibodies. Immediate therapy with high-dose prednisolone therapy was initiated (case 1: 60 mg/day; case 2: 100 mg/day), resulting in improvement of patients' condition, clinical findings and laboratory values in both cases. Case 1: The patient showed fast recovery under prednisolone and the further course was without any complications. Continuous therapy with 15 mg /day and clinical monitoring through day hospital was recommended. Case 2: We saw a slower recovery and prolonged reduced liver function with the necessity to substitute coagulation factors. Furthermore, the therapy of subsequent complications, such as surgical drainage of a haematoma, oedema, wound healing disorder and infections under prednisolone was necessary. Liver transplantation is planned if the disease progresses further. CONCLUSION: Elevated liver enzymes should always be further investigated. Autoimmune hepatitis is a rare disease. Rapid response to immunosuppressive therapy, such as prednisolone, is characteristic. Early diagnosis and therapy are essential for the patients prognosis. Liver transplantation is indicated in advanced disease.

Molecular mapping and candidate gene identification of the Rf2 gene for pollen fertility restoration in sorghum [Sorghum bicolor (L.) Moench].

The A1 cytoplasmic-nuclear male sterility system in sorghum is used almost exclusively for the production of commercial hybrid seed and thus, the dominant genes that restore male fertility in F(1) hybrids are of critical importance to commercial seed production. The genetics of fertility restoration in sorghum can appear complex, being controlled by at least two major genes with additional modifiers and additional gene-environment interaction. To elucidate the molecular processes controlling fertility restoration and to develop a marker screening system for this important trait, two sorghum recombinant inbred line populations were created by crossing a restorer and a non-restoring inbred line, with fertility phenotypes evaluated in hybrid combination with three unique cytoplasmic male sterile lines. In both populations, a single major gene segregated for restoration which was localized to chromosome SBI-02 at approximately 0.5 cM from microsatellite marker, Xtxp304. In the two populations we observed that approximately 85 and 87% of the phenotypic variation in seed set was associated with the major Rf gene on SBI-02. Some evidence for modifier genes was also observed since a continuum of partial restored fertility was exhibited by lines in both RIL populations. With the prior report (Klein et al. in Theor Appl Genet 111:994-1012, 2005) of the cloning of the major fertility restoration gene Rf1 in sorghum, the major fertility restorer locus identified in this study was designated Rf2. A fine-mapping population was used to resolve the Rf2 locus to a 236,219-bp region of chromosome SBI-02, which spanned ~31 predicted open reading frames including a pentatricopeptide repeat (PPR) gene family member. The PPR gene displayed high homology with rice Rf1. Progress towards the development of a marker-assisted screen for fertility restoration is discussed.

Does eating particular diets alter the risk of age-related macular degeneration in users of the Age-Related Eye Disease Study supplements?

BACKGROUND: Recent information suggests that the Age-Related Eye Disease Study (AREDS) supplement, enhanced intake of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), and reducing dietary glycaemic index (dGI) are protective against advanced age-related macular degeneration (AMD). METHODS: Dietary information was collected at baseline, and fundus photograph grades were obtained during the 8-year trial period from 2924 eligible AREDS AMD trial participants. Using the eye as the unit of analysis and multifailure Cox proportional-hazards regression, the risk of AMD progression was related to dietary intake in the four arms of the trial. RESULTS: Independent of AREDS supplementation, higher intakes of DHA (> or =64.0 vs <26.0 mg/day) (hazard ratio (HR) = 0.73, 95% confidence interval (CI), 0.57 to 0.94), EPA (> or =42.3 vs <12.7 mg/day) (HR = 0.74, 95% CI 0.59 to 0.94), and lower dGI (dGI, <75.2 vs > or =81.5) (HR = 0.76, 95% CI 0.60 to 0.96) were associated with a lower risk for progression to advanced AMD. Participants consuming a lower dGI and higher DHA or EPA had the lowest risk (p value for synergistic interaction <0.001). Only participants in the "placebo" (p value for antagonistic interaction = 0.006) benefited from a higher DHA intake against early AMD progression (HR = 0.58, 95% CI 0.37 to 0.92; P(trend) = 0.01). CONCLUSIONS: The findings show an association of consuming a diet rich in DHA with a lower progression of early AMD. In addition to the AREDS supplement, a lower dGI with higher intakes of DHA and EPA was associated with a reduced progression to advanced AMD. TRIAL REGISTRATION NUMBER: NCT00000145.

Diagnostic relevance of the determination of lymphocyte subpopulations in environmental medicine.

Earlier hopes that determination of lymphocyte subpopulations might become a strong diagnostic tool in environmental medicine have not been fulfilled in recent years. Analysis of the scientific literature rather shows that there are only few examples for environmental exposures causing reproducible shifts of lymphocyte subpopulations. Moreover, current knowledge suggests that "environmental diseases" are not associated with characteristic changes of subpopulation patterns. If lymphocyte subpopulations are analyzed, each diagnostic step, including indication, sample handling, analytic procedure and data-interpretation, should adhere to good quality criteria. Taking all together, the determination of lymphocyte subpopulations in the context of environmental medicine comes under category IV of the criteria of the Commission for Methods and Quality Assurance in Environmental Medicine of the German federal health authority (Robert Koch-Institute; RKI): "A procedure cannot be recommended because there is not sufficient information to justify it" (here: no solid trends in epidemiological examinations), "and because theoretical considerations speak against an application" (here: high physiological variability and missing exposure or substance specificity).

Mistletoe treatment induces GM-CSF- and IL-5 production by PBMC and increases blood granulocyte- and eosinophil counts: a placebo controlled randomized study in healthy subjects.

OBJECTIVE: Various immunological effects have been reported during application of mistletoe preparations. Because these data are heterogeneous, we performed a placebo controlled study to investigate (1) effects on peripheral granulocyte and eosinophil counts, (2) related cytokine levels and (3) whether effects are related to mistletoe lectin (ML). METHODS: 43 volunteers were randomized to receive the mistletoe plant extract Iscador Quercus spezial (IQ), purified ML, IQ which was depleted from ML, or placebo subcutaneously twice per week for 8 weeks. Weekly, differential blood count and every four weeks spontaneous and IQ- and ML-induced cytokine production by peripheral blood mononuclear cells (PBMC) were analyzed. RESULTS: Leukocyte-, granulocyte-, and eosinophil counts were significantly higher during treatment in the IQ- and ML-groups than in the placebo group. Furthermore, a significant increase of antigen-induced production of GM-CSF, IL-5 and IFNgamma by PBMC was observed in the IQ- and ML-group but not in the groups receiving ML-depleted IQ or placebo. Severe side effects did not occur in any of the subjects. CONCLUSIONS: Treatment with IQ or ML stimulates the production of GM-CSF, IL-5 and IFNgamma by PBMC, and this is accompanied by an increase of eosinophil- and granulocyte-counts. These observations may, therefore, open rational therapeutic indications for mistletoe extracts.

In vitro study on the immunological effect of bromelain and trypsin on mononuclear cells from humans.

BACKGROUND: Proteolytic enzymes such as bromelain and trypsin are used as an adjuvant therapeutic approach in the treatment of chronic inflammatory, malignant and autoimmune diseases. In vitro studies have shown that proteolytic enzymes modulate surface adhesion molecules on T-cells. In this study we analysed the influence of bromelain and trypsin on the cytokine production and proliferation of peripheral blood mononuclear cells (PBMC) from patients with a classical cellular mediated autoimmune disorder, namely encephalomyelitis disseminata (ED) as well as from healthy controls. - METHODS: PBMC from patients with ED (n=12) and healthy controls (n=12) were cultured for seven days at 37 degrees C under three different conditions: without antigen, with bromelain and with trypsin (final concentrations 10-1000 microg/ml). Proliferation was determined by superset3H-thymidine incorporation. Secretion of cytokines into the supernatant was measured by a double sandwich ELISA. Intracellular cytokines were determined by flow cytometric analysis. - RESULTS: PBMC from patients with ED and healthy controls showed a significantly increased proliferative response to bromelain (ED: 14053+/- 7585 cpm with bromelain vs. spontaneous proliferation of 430+/- 255 cpm; healthy controls: 10689+/- 4607 cpm vs. 327+/-193) but not to trypsin. Bromelain induced in all 24 individuals a significant increase of the macro-phage/monocyte associated cytokines interleukin (IL)-6, granulocyte-macrophage-colony stimulating factor (GM-CSF), tumour necrosis factor alpha (TNFa) (p<0.01) as well as of the type 1 cytokine gamma-interferon (IFNgamma). In contrast, the type 2 cytokines IL-4 and IL-5 were not induced. Flow cytometric analysis revealed a significant increase of IFNgamma-producing CD4+ T-cells. There were no differences in cytokine production between ED patients and healthy controls. - CONCLUSION: These results indicate that bromelain - but not trypsin - activates macrophages/monocytes and type 1 cells independently from the underlying disease and may stimulate, therefore, the innate as well as the adaptive immune system.

Hyperechogenicity of the thalamus and basal ganglia in very preterm infants: radiological findings and short-term neurological outcome.

Cerebral ultrasound of preterm infants may show diffuse, bilateral, hyperechogenic "haze" over the thalami and basal ganglia (hyperechogenicity BGT). We explored whether this could be a pathological phenomenon. All cerebral ultrasound examinations performed in 2001 on infants < 35 weeks of age were reviewed. This resulted in a hyperechogenicity and non-hyperechogenicity group. The character of the hyperechogenicity BGT and the presence of concomitant brain lesions were noted. Detailed clinical and follow-up data from a selected group of infants < 32 weeks were reviewed and compared between the 2 groups. The incidence of hyperechogenicity BGT was 11 % (39/359) in infants < 35 weeks and 26 % (37/143) in infants < 32 weeks. Birth weight and gestational age were significantly lower and clinical course was more complicated in the hyperechogenicity group. Concomitant brain lesions were always present. In 12/39 infants with hyperechogenicity BGT, MRI (always performed for other reasons) was available, showing signal intensity changes in thalamic region in 5 infants. The neurological outcome at term was less favorable in the hyperechogenicity group, but similar at 1 year. Thus hyperechogenicity BGT mainly occurred in very small, sick infants and was always associated with cerebral pathology. MRI did not consistently show abnormalities in the thalamic region. It was not associated with a poorer outcome at 1 year.

Demonstration of antibodies to the chitin-binding mistletoe lectin (cbML) in tumor patients before and during therapy with an aqueous mistletoe extract.

Mistletoe extracts exert immunomodulatory properties in vivo and in vitro, and these effects have been related mainly to mistletoe lectin 1 (ML-1). Recently, a new chitin-binding mistletoe lectin (cbML) has been isolated and structurally characterized in these extracts. Aim of the present study was, therefore, to evaluate whether this cbML also affects immunocompetent cells and can for instance activate B-cells to produce anti-cbML-specific antibodies. Sera from patients with different tumors who were treated with the mistletoe extract ABNOBAviscum Mali (AM) 4 for at least 18 weeks were analysed before therapy and after 3, 6, 9, 12, 18, and 24 weeks. Sera were tested by ELISA against ML-1, -3, and cbML, isolated from a single mistletoe plant collected from an apple tree (Malus domestica). Eight of the 26 patients (31%) had IgG anti-cbML antibodies already before therapy, while only four had anti-ML-1 and -3 antibodies. Of the 18 anti-cbML negative patients before therapy 54% developed these antibodies during therapy, and there was a significant increase in anti-cbML antibody titers. In contrast, anti-ML-1 or -3-antibodies developed in almost 100% of the 25 patients being negative before therapy. These data indicate that cbML can induce immunological responses in patients treated with mistletoe extracts, although it seems to have lower antigenicity. Interestingly, anti-cbML antibodies can be observed in a low incidence also in individuals, not having yet received mistletoe therapy.

The novel differentiation of human blood mononuclear cells into CD1a-negative dendritic cells is stimulated in the absence of exogenous cytokines by an extract prepared from pinecones.

The production of dendritic cells, both in-vivo and in-vitro, has become the intense focus of research activities. Common to many of these production protocols is the use of cytokines, typically granulocyte-monocyte colony stimulating factor and either interleukin 4 or tumor necrosis factor alpha or a combination of all three. Herein, we report our findings that a proprietary pinecone extract is capable of in a dose-dependent manner, and in the absence of exogenous cytokines, the rapid differentiation from peripheral blood mononuclear cells of mature CD1a-negative dendritic cells.

Induction of uncoupling protein 1 by central interleukin-6 gene delivery is dependent on sympathetic innervation of brown adipose tissue and underlies one mechanism of body weight reduction in rats.

Interleukin-6 (IL-6) is a multifunctional cytokine that may have a role in energy regulation. Using a recombinant adeno-associated viral vector expressing murine interleukin-6 (rAAV-IL-6), we examined the chronic effects of centrally expressed IL-6 on food intake, body weight and adiposity in male Sprague-Dawley rats, and investigated the underlying mechanisms. Direct delivery of rAAV-IL-6 into rat hypothalamus suppressed weight gain and visceral adiposity without affecting food intake over a 5-week period. rAAV-IL-6 enhanced uncoupling protein 1 (UCP1) protein levels in interscapular brown adipose tissue (BAT). To investigate if the induction of UCP1 and the reduction in body weight are dependent on sympathetic innervation of BAT, we administered rAAV-IL-6 or a control vector into the hypothalamus of rats in which the interscapular BAT was unilaterally denervated. Over 21 days, there was no difference in food consumption or body weight between rAAV-IL-6- and control vector-treated rats. rAAV-IL-6 delivery increased UCP1 mRNA and protein levels in innervated BAT pads but not denervated BAT pads. Hypothalamic IL-6 signal transduction, indicated by phosphorylated signal transducer and activator of transcription 3 (P-STAT3) levels, was elevated by 2.6-fold at day 21, but returned to control levels by day 35. However, the suppressor of cytokine signaling-3 mRNA level was significantly elevated both at day 21 and day 35. These data demonstrate that chronic elevation of IL-6 in the CNS reduces body weight gain and visceral adiposity without affecting food intake. The mechanism involves sympathetic induction of UCP1 in BAT and, presumably, enhanced thermogenesis in BAT. Furthermore, chronic central IL-6 stimulation desensitizes IL-6 signal transduction characterized by reversal of elevated P-STAT3 levels.

In vivo-induction of antibodies to mistletoe lectin-1 and viscotoxin by exposure to aqueous mistletoe extracts: a randomised double-blinded placebo controlled phase I study in healthy individuals.

BACKGROUND: Several studies have been performed in tumour patients to analyse the immunological response to mistletoe extracts. Considering the fact that these extracts are given subcutaneously in most instances, the kind of application resembles a typical immunization schedule. We therefore wanted to see how those extracts act on immunocompetent cells of healthy individuals hoping that this kind of provocation test may give new informations about a more specific application of these extracts in certain diseases. SUBJECTS/METHODS: 47 healthy individuals were exposed for twelve weeks either to Iscador Quercus special (IQ) known to be rich in mistletoe lectin (ML)-1 (n = 16), to Iscador Pini (IP) being poor in ML-1 but enriched in viscotoxins (n = 15), or to placebo (physiological saline) (n = 16) in a randomised, double-blinded placebo-controlled study. Humoral immunoreactivity was analysed by measuring antibodies towards the two compounds ML-1 and viscotoxin VA2 (VA2). Sera were collected in intervals of four weeks up to week 12 and again three months after last exposure. RESULTS: None of the subjects had antibodies to ML-1 or VA2 before exposure. In week 12, anti-ML-1 antibodies of the IgG-type were found in all 16 IQ-treated individuals but only 6 of the 15 probands exposed to IP. In contrast, anti-VA2 IgG-antibodies could be detected in all individuals of both groups. The antibodies were preferentially of the IgG1 and IgG3 type while antibodies of the IgA and IgM type were produced only in a few probands. Antibodies of the IgE-type occurred only in the IQ-exposed individuals and were directed against ML-1 but not VA2. None of the probands receiving placebo developed antibodies to ML-1 or VA2. Severe side effects were not observed in any of the probands. CONCLUSIONS: These data obtained in healthy individuals clearly indicate that IQ and IP-extracts can induce antigen-specific humoral responses. They may, therefore, provide, a solid basic for the evaluation of the humoral immune response in disease states.

Oral administration of Lactobacillus induces cardioprotection.

OBJECTIVES: Our goal was to investigate the potential of oral administration of Lactobacillus to induce cardioprotection against ischemia-reperfusion injury in rat hearts, and to determine whether this protection is associated with myocardial catalase activation and heat shock protein 70 expression. DESIGN: Lactobacillus was administered orally to rats on a daily basis, from 1 to 21 days before global ischemia. Global ischemia was produced by full-stop flow in isolated Langendorff-perfused rat hearts for 20 minutes and was followed by reperfusion. Similarly, saline was administered to control animals. RESULTS: Lactobacillus significantly reduced reperfusion tachyarrhythmia and improved functional recovery of the ischemic rat hearts. These cardioprotective effects were associated with reduction of norepinephrine release at the first minute of reperfusion, activation of myocardial catalase, and overexpression of 70 kd heat stress protein at ischemia and reperfusion (p < 0.05). CONCLUSIONS: Oral administration of Lactobacillus produces marked cardioprotection against ischemia-reperfusion injury. This effect is attributed to activation of the cellular defense system, manifested by activation of the antioxidant pathway, and by expression of protective proteins. Norepinephrine is involved in this process. The results of this study suggest that Lactobacillus, which is generally considered safe, could serve as a basis for the development of a new agent for preventive therapy of various ischemic heart syndromes.

The relation of coffee and caffeine to the 5-year incidence of early age-related maculopathy: the Beaver Dam Eye Study.

PURPOSE: To examine the relationship between coffee and caffeine consumption and the 5-year incidence of early age-related maculopathy and its component lesions, soft indistinct drusen or pigmentary abnormalities. DESIGN: A prospective cohort study conducted from 1988 to 1995 with an average follow-up of 4.8 years. METHODS: Data from baseline and 5-year follow-up examinations were analyzed for Beaver Dam Eye Study participants (n = 3435). The Wisconsin Age-Related Maculopathy Grading System was used to assess the presence and severity of early age-related maculopathy. RESULTS: Men were more likely to be coffee and caffeine drinkers than were women. For both men and women, coffee and caffeine intake decreased with age. Coffee and caffeine consumption were not associated with the 5-year incidence of early age-related maculopathy, soft indistinct drusen, or pigmentary abnormalities. CONCLUSION: Neither a history of coffee nor caffeine consumption is associated with incident early age-related maculopathy.

The relation of socioeconomic factors to the incidence of early age-related maculopathy: the Beaver Dam eye study.

PURPOSE: To investigate the relationship between socioeconomic factors and the 5-year incidence of age-related maculopathy. METHODS: The Beaver Dam Eye Study, a population-based cohort study, examined 3681 adults (range, 43-86 years of age at baseline) living in Beaver Dam, Wisconsin, at baseline and 5 years later. Standardized protocols for physical examination, including administration of a questionnaire that included questions regarding income, education level, and status and type of employment, and fundus photography to determine age-related maculopathy, were performed. RESULTS: While controlling for age and sex, less education, and being in a service-related occupation compared with a white collar professional occupation, was associated (P <.05) with the incidence of early age-related maculopathy. CONCLUSION: These data show an association of education and occupation but not income with the incidence of early age-related maculopathy that appears independent of smoking or vitamin supplement use status.

Neutral endopeptidase terminates substance P-induced inflammation in allergic contact dermatitis.

Sensory nerve-derived neuropeptides such as substance P demonstrate a number of proinflammatory bioactivities, but less is known about their role in inflammatory skin disease. The cell surface metalloprotease neutral endopeptidase (NEP) is the principal proteolytic substance P-degrading enzyme. This study tests the hypothesis that the absence of NEP results in dysregulated inflammatory skin responses. The effector phase of allergic contact dermatitis (ACD) responses was examined in NEP(-/-) knockout and NEP(+/+) wild-type mice and compared with the irritant contact dermatitis response in these animals. NEP was found to be normally immunolocalized in epidermal keratinocytes and dermal blood vessels. The ACD ear swelling response was 2.5-fold higher in animals lacking NEP and was accompanied by a significant increase in plasma extravasation and infiltration of inflammatory leukocytes. The augmented ACD response in NEP(-/-) animals was abrogated by either administration of a neurokinin receptor 1 antagonist or by repeated pretreatment with topical capsaicin. Similar to NEP(-/-) mice, the acute inhibition of NEP in NEP(+/+) animals resulted in an augmented ACD response. In contrast to the ACD responses, little differences were observed in the irritant contact dermatitis response of NEP(-/-) compared with NEP(+/+) animals after epicutaneous application of the skin irritants croton oil or SDS. Thus, these results indicate that NEP and cutaneous neuropeptides have a significant role in the pathogenesis of ACD.

[Frequency of the common cold in healthy subjects during exposure to a lectin-rich and a lectin-poor mistletoe preparation in a randomized, double-blind, placebo-controlled study]. / Häufigkeit grippaler Infekte bei Gesunden unter Gabe eines lektinreichen und eines lektinarmen Mistelpräparats im Rahmen einer randomisierten, doppelblinden, placebokontrollierten Studie.

BACKGROUND/OBJECTIVE: Mistletoe preparations have immunomodulatory properties in vitro and in vivo. We wanted to investigate whether or not these properties have an effect on the frequency of the common cold in healthy subjects. PROBANDS AND METHODS: During a randomized, placebo-controlled, double-blind study 16 volunteers received the mistletoe lectin(ML)-poor preparation Iscador Pini(R) (IP), 16 the ML-rich preparation Iscador Quercus spezial(R) (IQ), and 16 placebo (physiological saline solution) twice a week subcutaneously for 12 weeks. Weekly during weeks 1-12 and finally at week 26, a careful history of common cold symptoms was taken. Because the frequency of the common cold was not the main outcome criterion in this study, the number of cases needed to treat was not adjusted to this criterion. RESULTS: The mean frequency of the common cold during the 12 weeks of injection was 1.5 in the placebo, 1.4 in the IP and 1.1 in the IQ group. During this period in 2.3 (placebo), 1.9 (IP) and 1.4 (IQ) weeks symptoms of common cold were present. The difference in favor to IQ lasted until the end of the observation period in week 26. It was, however, not significant. Leukocyte and granulocyte count as well as C-reactive protein were not different between the groups. CONCLUSIONS: The study showed a trend (p = 0.4, exact Kruskal- Wallis test) to reduced frequency and duration of the common cold in subjects who were exposed to IQ.

Vitamin supplement use and incident cataracts in a population-based study.

OBJECTIVE: To determine the relationship between vitamin supplement use and the 5-year incidence of nuclear, cortical, and posterior subcapsular cataract in the Beaver Dam Eye Study cohort. DESIGN: The 5-year incidence of cataract, determined from slitlamp (nuclear cataract) and retroillumination (cortical and posterior subcapsular cataract) photographs, was assessed in a population-based cohort of persons participating in baseline (1988-1990) and follow-up (1993-1995) examinations. Detailed data regarding the type, dosage, and duration of supplement use were obtained by in-person interviews at follow-up. PARTICIPANTS: Residents of Beaver Dam, Wis, aged 43 to 86 years, were identified by private census. Of the 3684 participants in both baseline and follow-up examinations, 3089 were eligible for incident cataract analysis in the present study. RESULTS: Compared with nonusers, the 5-year risk for any cataract was 60% lower among persons who, at follow-up, reported the use of multivitamins or any supplement containing vitamin C or E for more than 10 years. Taking multivitamins for this duration lowered the risk for nuclear and cortical cataracts but not for posterior subcapsular cataracts (odds ratios [95% confidence intervals] = 0.6 [0.4-0.9], 0.4 [0.2-0.8], and 0.9 [0.5-1.9], respectively). Use of supplements for shorter periods was not associated with reduced risk for cataract. Measured differences in lifestyle between supplement users and nonusers did not influence these associations, nor did variations in diet as measured in a random subsample. CONCLUSIONS: These data add to a body of evidence suggesting lower risk for cataract among users of vitamin supplements and stronger associations with long-term use. However, the specific nutrients that are responsible cannot be ascertained at this time, and unmeasured lifestyle differences between supplement users and nonusers may explain these results. Arch Ophthalmol. 2000;118:1556-1563