Increased expression of Filaggrin and Claudin-1 in the ocular surface of patients with atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is an itchy, chronic and inflammatory skin condition, with dysfunctional immune response and skin barrier defects. Reduction of filaggrin (FLG) and tight junctions (TJ) proteins, such as claudin-1 (CLDN-1), expression in cutaneous epithelial barrier is remarkable in AD pathogenesis. Ocular involvement occurs in approximately 40% of AD patients leading to changes in the structure of the conjunctiva. OBJECTIVES: We aimed to evaluate the expression of FLG and CLDN-1 in the ocular surface of adults with AD, analysing bulbar conjunctival cells collected by a novel non-invasive cellular imprint. METHODS: Bulbar conjunctival epithelial cells were collected by cellular imprint technique, and FLG and CLDN-1 expression were assessed by immunofluorescence (IF) and real-time polymerase chain reaction (RT-PCR). RESULTS: We detected increased expression of FLG and CLDN-1, as well as their transcript levels in AD patients compared with healthy controls (HC). There was a positive correlation between tear film break-up time (TBUT) and FLG expression. Fluorescein staining was inversely associated with FLG expression. CONCLUSIONS: Our results may reflect a reactive response of the ocular surface to AD-related ocular inflammation and associated dry eye disease. Further investigations focusing on the role of FLG and TJ expression in the ocular surface of AD patients may increment the understanding of the pathophysiology of extracutaneous AD and developing future targeted therapies.

Evaluation of the 'putative' role of intraoperative intact parathyroid hormone assay during parathyroidectomy for secondary hyperparathyroidism. A retrospective study on 35 consecutive patients: intraoperative iPTH assay during parathyroidectomy.

In the surgical treatment of secondary hyperparathyroidism (2HPT) of chronic kidney disease (CKD), a parathyroidectomy (PTx) of 4 glands can only be presumed as 'total', and indications for autoimplantation are complex. Intraoperative rapid parathyroid hormone assay could be useful to predict a radical resection. We evaluated iPTH levels 20 min and 24 h after a 4-gland PTx in 35 patients to determine the predictive value of intraoperative iPTH assay. We analysed retrospectively 35 patients affected by 2HPT of CKD, 13 undergoing total parathyroidectomy (TP) and 22 TP + autoimplantation (TPai), after removing 4 glands in 33 cases and 5 glands in 2. Intact PTH assays were acquired after 40 min before induction of anaesthesia, after removing both ipselateral glands, at 20 min after surgery and on postoperative day 1. 20 min after 4-gland PTx, a decrease of iPTH levels >80 % of the preoperative value was observed in 27 of 35 cases (77.1 %) and <80 % in 8 of 35 cases (22.8 %). In 6 of these 8 patients, iPTH levels were within the normal range 24 h after surgery. Although the intraoperative iPTH assays are of interest in the treatment of 2HPT, the predictive value of this method is not entirely satisfactory. In fact, a 4-gland PTx ensures euparathyroidism in most cases, even when intraoperative iPTH assays are not trustworthy; however, intraoperative iPTH assay, although not a perfect 'tool', is a proved aid for the surgeon in making his decision.

Sleep disorders in kidney disease.

Sleep disorders are common in patients with end stage renal disease receiving hemodialysis or peritoneal dialysis. However also a well functioning renal graft does not cure the poor sleep pattern which now emerges as a problem even in early chronic kidney disease (CKD). When patients are made aware for the first time of a disease such as CKD, which may brink to dialysis or at the best to a renal transplant patients begin to experience a disordered sleep. Sleeping disorders include insomnia (I), sleep apnoea (SAS), restless legs syndrome (RLS), periodic limb movement disorder (PLMD), excessive daily sleeping (EDS), sleepwalking, nightmares, and narcolepsy. Disordered sleep did not meet the clinical and scientific interest it deserves, in addition and we do not have a well defined solution for sleeping complaints. However, awareness that a poor sleep is associated with poor quality of life and carries an increase in mortality risk has recently stimulated interest in the field. There are many putative causes for a disordered sleep in chronic kidney disease and in end-stage renal disease. For a unifying hypothesis demographic factors, lifestyles, disease related factors, psychological factors, treatment related factors, and social factor must be taken into consideration.

[Survival is not enough: improving quality of life]. / Sopravvivere non basta--migliorare la qualità della vita.

We need a new health care system that is based on patients' needs. The present cadre of health managers who acquired power by cutting expenditures must be removed from office. We need to educate a new cadre of health managers who are 1) convinced that safeguarding health does not use up the resources of the next generations; 2) capable of switching the system from curative to preventive medicine; and 3) able to reinforce clinical research. Such principles have been recently adopted by the French President Sarkozy in devising the national health care program.

[Survival is not enough: taking care of the patient as a whole]. / Sopravvivere non basta--prendersi cura del malato nella sua totalità.

The ill deserve holistic care including assistance for the anxiety and fear generated by his illness. Illness may be viewed as a call for help, as the nocturnal side of life, or as a product of culture. All moments of the illness are precious, and its last instants may even reveal the infinite. The Western world is afraid of death--even now that our lives get longer--and abates the fear by removing the idea of death, even if poets have emphasized the richness it carries within.

Sleep disorders in hemodialyzed patients--the role of comorbidities.

BACKGROUND: Sleep disorders are very frequent in hemodialyzed patients, but the relationship between these disorders and water withdrawal, urea removal and comorbidities has not been sufficiently clarified. METHODS: The study comprised a group of 88 patients in good nutritional condition, with target hemoglobin concentration, good control of blood pressure and optimal dry weight. After answering a questionnaire (SDQ) based on the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) patients were assigned to one of 3 groups: those with no disturbances (no.20), those with subclinical disorders (n.35) and insomniacs (n.33). Yearly fluid and urea withdrawal by dialysis and the Charlson Comorbity Index were measured. RESULTS: Sleep disorders were observed in 77.27% of the patients. There was no difference in body fluid and urea withdrawal between groups. In the group of patients with no sleeping disturbances, the Charlson Comorbidity Index was significantly lower (p<0.001) than in patients with subclinical disorders or insomnia and emerged as a strongly associated with sleep disturbances. The study also attributes a predictive role to age, dialytic age, dialysis shift, antihypertensive drugs. The data indicate that, in evaluating sleeping disorders in patients on maintenance hemodialysis, comorbidities should be assessed.

The heart in uremia: role of hypertension, hypotension, and sleep apnea.

Cardiovascular disease is the leading cause of morbidity and mortality in end-stage renal disease. Causes include those usually found in the general population, those related to the uremic status, and those related to dialytic treatment. Hypertension, hypotension, anemia, hypoalbuminemia, malnutrition, dyslipidemia, reactive C protein, calcium-phosphate product, dialysis modalities, and hyperhomocysteinemia are discussed extensively. Special emphasis is put on hyperparathyroidism as a traditional toxin. The emergent role of sleep apnea has been confirmed in animal models as well as in humans studied using polysomnography. There are difficulties in diagnosing coronary disease, because angiography is not risk-free, is expensive, and should be reserved for patients having symptoms of heart failure and/or patients having diabetes mellitus, and/or patients entering a transplantation list. This allows patients with coronary disease to undergo coronary artery bypass (preferably) or percutaneous transluminal angioplasty. Patients for whom surgery is not appropriate should be treated using more traditional medical procedures.

Erectile dysfunction in uremic dialysis patients: diagnostic evaluation in the sildenafil era.

The two words that mean sexual dysfunction, impotence and erectile dysfunction (ED), express two different concepts. Impotence is a general male sexual dysfunction that includes libidinal, orgasmic, and ejaculatory dysfunction. ED is the inability to achieve or maintain an erection sufficient to allow satisfactory sexual intercourse and is part of the general male sexual dysfunction termed impotence that includes libidinal, orgasmic, and ejaculatory dysfunction. Uremic men of different ages report a variety of sexual problems, including sexual hormonal pattern alterations, reduction in or loss of libido, infertility, and impotence, conditioning their well-being status. In evaluating and treating sexual dysfunction, a nephrologist must consider factors involved in its pathogenesis, such as hypothalamic-pituitary-gonadal axis alterations, psychological problems related to chronic disease, secondary hyperparathyroidism, anemia, autonomic neuropathy, derangements in arterial supply or venous outflow, and the normal structure of cavernous body smooth muscle cells. The introduction of sildenafil to treat impotent patients has completely changed the approach to evaluating these subjects because this drug is considered an effective well-tolerated treatment for men with ED. In the past, we proposed an algorithm that gave the opportunity to explore the previously mentioned factors using such instrumental interventions as the nocturnal penile tumescence test, penile echo color Doppler, nervous conduction velocity, and cavernous body biopsy, addressed to prescribe needed surgical or medical interventions. The complexity of the proposed algorithm requires many diagnostic procedures and much time and economic resources to localize the pathological lesions responsible for ED. Because of the new oral drug sildenafil, we propose a new algorithm to test the possibility of obtaining an erection and classify patients as responders or nonresponders to the sildenafil test.

Insomnia is associated with systolic hypertension in uremic patients on hemodialysis.

A newly developed questionnaire was administered to 140 hemodialyzed patients (82 M and 58 F) who have achieved adequate anemia correction according to the best guidelines with the aim: to evaluate the prevalence of clinical/subclinical dyssomnias in these patients; to study the influence of the dialytic shift (morning versus afternoon schedules) on sleep duration and disturbancies; and to evaluate the relationship between clinical sleep disorders and blood pressure values in uremic patients. Results indicated that 85% of uremic patients undergoing hemodialysis complain of clinical insomnia (frequent, persistent and associated with daytime consequences) or sub-clinical sleep disorders; patients dialyzing in the morning sleep significantly less during the night preceding the treatment, than those dialyzing in the afternoon; older patients complaining of clinical insomnia have a higher risk of failure to achieve target-optimal values in systolic blood pressure.

Berengario da Carpi.

Berengario da Carpi was magister of anatomy and surgery at the University of Bologna from 1502 to 1527. Eustachio and Falloppia defined him as 'the restaurator of anatomy'. He was a great surgeon, anatomist and physician of illustrious patients including Lorenzo II dei Medici, Giovanni dalle Bande Nere, Galeazzo Pallavicini, Cardinal Colonna, and Alessandro Soderini. He had strong links to the intellectuals of his time (Forni, Bonamici, Manuzio, Pomponazzi) as well as with the Medici family. He was respected by the Popes Julius II, Leo X and Clement VII. His main contributions are the Isogogae Breves, De Fractura calvae sive cranei, and the illustrated Commentaria on the Anatomy of Mondino de Liucci, a textbook utilized for more than 200 years, which Berengario aimed to restore to its initial text. The Commentaria constitutes the material for the last part of this paper which concludes with a personal translation of some passages on 'The kidney', where the author gives poignant examples of experimental ingenuity.

Corneal topography in asymptomatic family members of a patient with pellucid marginal degeneration.

PURPOSE: To report corneal topographic patterns in asymptomatic family members of a patient with pellucid marginal degeneration. METHODS: Computer-assisted corneal topography was used to study the corneas of five family members of a patient with pellucid marginal degeneration. RESULTS: In all five asymptomatic family members, corneal biomicroscopy was normal. Corneal topography, however, showed various abnormalities in different members of this family, particularly a topographic pattern suggesting keratoconus in one family member and a topographic pattern suggesting pellucid marginal degeneration in another family member. CONCLUSION: This study reinforces the hypothesis that corneal ectatic disorders may represent different manifestations of a clinical spectrum.

Salt: a sacred substance.

Salt is the last relic of the ocean where life was born. Its presence has influenced the whole gamut of history and its name is linked to hundred of geographical locations. Its importance for nutrition is supported by the discovery of Aeneolithic salt cellars. Salt cellars and pyramids of salt have been included in paintings and other works of art. In Japan where salt was and still is obtained from the sea, a salt culture has developed that can be traced in the rituals of everyday life, including meal preparation, sports, and Shinto ceremonies.

The symbolism of salt in paintings.

Many artists have used the symbol of salt in both religious and profane works, yet very few studies have explored the symbolism of salt as used in works of art. In this study, Panofsky's method has been adopted to evaluate works of art through an organic process articulated into three stages: (1) pre-iconographic, (2) iconographic and (3) iconological. The method was used for (a) religious paintings of the Old and New Testaments and (b) mythological and profane themes. Various salt-cellars were also studied. In particular, the paper examines the following themes: Isaac blessing Jacob, the return of Esau, Samuel consecrating David, the Last Supper, the suppers at Emmaus and at the house of Simon, the birth of St. John the Baptist, the Baptism of Constantine, the prodigal son, Bacchus-Apollo, the nuptial banquet of Love and Psyche, the death of the Cavalier of Celano, the king drinks, the landlord's visit, 'Phitopolis faisant servir des mets en or au roi Pithès', certain still life paintings and various salt-cellars including those of Cellini and Giulio Romano. The paper discusses the works of many artists including Raphael, Leonardo and his school (Boltraffio, Giampietrino, d'Oggiono, Solario), Hendricksz, Corenzio, Jean-Baptiste and Philippe de Champaigne, Damaskinos, Tintoretto, Titian, Romanino, Rubens, Bellini, Bloemaert, Veronese, Sustris, Just of Ghent, Jan Van Hemessen, Poussin, Loir, Giotto, Jordaens, Brueghel and Mimmo Paladino with his enchanted mountain. From the data examined it emerged that salt is a primary iconological presence in various works of art.

Clinical and histopathologic features of corneal dystrophies in Japan.

PURPOSE: To examine retrospectively the frequency of various corneal dystrophies among Japanese patients who underwent keratoplasty or keratectomy at the authors' institution over a 34-year period, and to compare the histopathologic features of these disorders in the Japanese population with those reported in the Western literature. METHODS: Corneal specimens obtained during keratectomy or keratoplasty (lamellar and penetrating) performed at the authors' institution from 1959 through 1992 were reviewed. Immunohistochemical studies were performed using monoclonal antibodies to keratan sulfate and gelsolin, as well as two lectins (concanavalin A and wheat germ agglutinin). RESULTS: Of 1259 corneal specimens, 159 (12.6%) specimens from a total of 80 patients showed corneal dystrophy. Virtually all were non-Fuchs dystrophies; only one case of primary Fuchs dystrophy was identified histologically. Granular dystrophy and gelatinous drop-like dystrophy were the most common dystrophies identified in the specimens, largely because of multiple specimens from individual patients with recurrent disease. These two disorders accounted for 86 of the 159 specimens. In terms of numbers of patients, lattice dystrophy was the most common (26 patients, 32.5%), followed by macular dystrophy (16 patients, 20%), gelatinous drop-like dystrophy (15 patients, 18.8%), granular dystrophy (14 patients, 17.5%), and Avellino dystrophy (3 patients, 3.75%). Dystrophies represented by only one or two patients included congenital hereditary endothelial dystrophy, primary spheroidal keratopathy, posterior polymorphous dystrophy, Schnyder crystalline dystrophy, and Fuchs dystrophy. CONCLUSIONS: This histopathologic study showed a very low incidence of Fuchs dystrophy in the authors' Japanese patient population, compared with the incidences seen in studies of populations in Western countries. Of the non-Fuchs dystrophies, lattice dystrophy was the most common among the patients, although there were large numbers of specimens with granular dystrophy and gelatinous drop-like dystrophy due to their recurrent character. The causes of clinical and histopathologic differences and similarities among the Japanese patients and the patients described in the Western literature are likely related to genetic factors, but a complete understanding of their specific mechanisms awaits future molecular biologic and genetic elucidation.

Spheroidal keratopathy associated with subepithelial corneal amyloidosis. A clinicopathologic case report and a proposed new classification for spheroidal keratopathy.

PURPOSE: An unusual case of primary spheroidal degeneration associated with subepithelial corneal amyloidosis is described clinically and histopathologically, and a new classification for spheroidal keratopathy is proposed. METHODS: The corneal button obtained by lamellar keratoplasty was examined by light and transmission electron microscopy. Amyloid deposits were evaluated further by means of the thioflavin T fluorescence technique, the potassium permanganate reaction, and immunohistochemical studies using antibodies against immunoglobulin light chains and proteins AA and AP. RESULTS: Spheroidal droplets were observed in basement membrane, Bowman's layer, and anterior stroma, and exhibited characteristic staining with Verhoeff's iron hematoxylin. Amyloid deposits were found beneath the epithelium, almost exclusively in the central area of the corneal button. The deposits showed no immunohistochemical staining with antibodies to amyloid proteins AA and AP or kappa and lambda light chains. CONCLUSIONS: The histochemical properties of the spheroidal droplets in this case were similar to those observed by other authors and suggested a sulfur-rich protein other than keratin. The combination of clinical and pathologic findings permitted the differential diagnosis of subepithelial amyloidosis and distinguished this condition from that of gelatinous drop-like dystrophy. To the authors' knowledge, this is the first description of primary spheroidal keratopathy associated with secondary subepithelial corneal amyloidosis in an eye that had not undergone previous keratoplasty.

Incidence of Paneth cells in minute tubular adenomas and adenocarcinomas of the large bowel.

This study attempted to demonstrate the incidence of Paneth cells within large bowel tubular adenoma and adenocarcinoma according to location and macroscopic appearance using minute tumors (up to 5 mm in size). We have shown that Paneth cells were sometimes seen in the early stage of the development of large bowel epithelial neoplasia. According to the macroscopic appearance (elevated or depressed type), in large bowel epithelial neoplasia, there was a statistical difference between the depressed type (32.5%, 14 of 40 cases) and the elevated type (16.6%, 24 of 145 cases) (Chi square analysis, p < 0.05) in the incidence of Paneth cells. Paneth cells were seen more frequently in adenocarcinoma (45.8%, 11 of 24 cases) than in tubular adenoma (16.8%, 27 of 161 cases), with a significant statistical difference (Chi square analysis, p < 0.01). According to location, in both tubular adenoma and adenocarcinoma, Paneth cells were more frequently observed in the proximal colon (tubular adenoma: p < 0.01, adenocarcinoma: p < 0.05, Chi square analysis).