[Ocular Cicatricial Pemphigoid - a Retrospective Study]. / Ocní jizevnatý pemfigoid - retrospektivní studie.

INTRODUCTION: Ocular cicatricial pemphigoid (OCP) is rare, severe, sight threatening autoimmune disease of the conjunctiva, which affects elderly patients, more often women. AIM: To evaluate the success rate of stabilisation of ocular findings in patients with OCP. METHODS: Retrospective study of patients from Centre of Conjunctival and Corneal Diseases at Department of Ophthalmology, General University Hospital and 1st Medical Faculty of Charles University in Prague in 1992-2013 was performed. Frequency of OCP clinical stages, visual acuity (VA), disease activity and ocular complications of referred patients were monitored. Moreover, type of immunosuppressive (IS) therapy, the number of relapses of the disease and progress of OCP clinical stages were evaluated. Especially, we evaluated effects and side effects of mycophenolate mofetil (MM) therapy. In addition to that, type and frequency of ocular surgery that was carried out to the patients before and after the referral were recorded. Furthermore, we evaluated percentage of patients with mucous membranous pemphigoid (MMP). Also, the positive yield of diagnostic methods was assessed. RESULTS: The OCP was diagnosed and monitored in 51 patients (21 men and 30 women) during 21 years, the average age on the day of diagnosis was 68,4 years, the average period of observation was 57 months. 55 % of eyes were referred to our department at clinical stage 3, 27 % at stage 4. VA was maintained in 76 % of eyes, improved in 5 % of eyes and in 19 % of eyes deteriorated. Activity of OCP was detected during the first examination in 96 % of patients, the most common complications at that time was corneal ulcer or perforation. Patients were treated by immunosuppressive therapy, most often in combination: corticosteroids (47 patients), azathioprine (28 patients), cyclophosphamide (25 patients), MM (16 patients), sulphasalazine (5 patients), dapsone (5 patients). We ascertained relapses in 40 % of patients. The progression to the next stage of OCP were found in 7 eyes (6,9 %) and 95 eyes (93,1 %) remained stable. Activity of disease was well controlled in 11 patients out of 16 (69 %) by MM, IS therapy of remain 5 patients (31 %) had to be changed. Side effects of MM such as lymphopenia were present in 1 patient. Before OCP was diagnosed, patients underwent cataract surgery with the intraocular lens implantation, cryoepilation of eyelashes and eyelid plastic surgery, especially entropion. The most common indicated surgery in our clinic was amniotic membrane transplantation and retro position of muscular cutaneous leaf. 31 % of patients were diagnosed with MMP. Positive results of conjunctival biopsy were detected in 48 % from 42 examined samples and 22 % from 32 examined samples had positive results of indirect immunofluorescence (anti-desmosoms). CONCLUSION: OCP diagnosis is established on the basis of patient´s ophthalmic history and clinical findings. Positive results of direct and indirect immunofluorescence support the diagnosis. Activity of the disease and progression of OCP is effectively suppressed by systemic immunosuppressive therapy (for example MM), mainly if started at early stage of the disease. KEY WORDS: ocular cicatricial pemphigoid, immunosuppressive therapy, direct and indirect immunofluorescence, mycophenolate mofetil.

Expulsión espontánea de litiasis de gran tamaño / Spontaneous expulsion of large ureteral lithiasis

No disponible

Macular corneal dystrophy and associated corneal thinning.

PURPOSE: To identify the molecular genetic cause of macular corneal dystrophy (MCD) in four probands, and characterize phenotypic similarities between MCD and keratoconus. METHODS: We performed ophthalmological examination, Scheimpflug imaging (Pentacam, Oculus Inc.), histopathological examination of excised corneal buttons, and direct sequencing of the CHST6 coding region. RESULTS: Pentacam measurements were taken in six eyes of three probands. All showed diffuse corneal thinning with paracentral steepening of the anterior corneal surface that was graded as keratoconus by the integrated software, but without associated ectasia of the posterior corneal surface or regional thinning. Homozygous or compound heterozygous CHST6 mutations were identified in all cases, including two novel mutations, c.13C>T; p.(Arg5Cys) and c.289C>T; p.(Arg97Cys). DISCUSSION: Localized elevation of the anterior corneal curvature can occur in MCD in the absence of other features of keratoconus. The identification of a further two Czech probands with the compound allele c.[484C>G; 599T>G] supports the enrichment of this allele in the study population.

B-1 cells and concomitant immunity in Ehrlich tumour progression.

Concomitant immunity is a phenomenon in which a tumour-bearing host is resistant to the growth of an implanted secondary tumour. Metastases are considered to be secondary tumours that develop spontaneously during primary tumour growth, suggesting the involvement of concomitant immunity in controlling the rise of metastases. It has been demonstrated that B-1 cells, a subset of B-lymphocytes found predominantly in pleural and peritoneal cavities, not only increase the metastatic development of murine melanoma B16F10, but also are capable of differentiating into mononuclear phagocytes, modulating inflammatory responses in wound healing, in oral tolerance and in Paracoccidiose brasiliensis infections. Here, we studied B-1 cells' participation in concomitant immunity during Ehrlich tumour progression. Our results show that B-1 cells obtained from BALB/c mice previously injected with Ehrlich tumour in the footpad were able to protect BALB/c and BALB/Xid mice against Ehrlich tumour challenge. In addition, it was demonstrated that BALB/Xid show faster tumour growth and have lost concomitant immunity, and that this state can be partially restored by reconstituting these animals with B-1 cells. However, further researches are required to establish the mechanism involving B-1 cells in Ehrlich tumour growth.

Different inflammatory stimuli in the footpad of mice influence the kinetics of resident peritoneal cells.

OBJECTIVES: Evidence from the literature that inflammation is a systemic biological phenomenon prompted us to investigate whether inoculation of different irritants to the footpad of mice might influence the kinetics of resident peritoneal cells. METHODS: Mice were inoculated in the footpad at different time intervals with Mycobacterium bovis bacillus Calmette-Guerin (BCG), Ehrlich ascitic tumor cells or lipopolysaccharide (LPS), and resident peritoneal cells were analyzed by flow cytometry. RESULTS: The results indicate that different stimuli induced different responses in resident peritoneal cells. FoxP3 positive regulatory T cells increased drastically in number after BCG inoculation. Conversely, tumor cell inoculation induced a decrease in FoxP3-positive T cells in the peritoneal cavity, although this effect was not statistically significant. Results also show that cells from the paw migrate to the popliteal lymph node and to the peritoneal cavity. Yet, there are cells in the peritoneal cavity that migrate to the popliteal lymph node. CONCLUSION: These data show that cells from the peritoneal cavity are influenced by pathologies in remote regions of the animal. How this novel phenomenon influences overall immune responses, courses of infection and tumor growth are open to further investigation.

N-Domain angiotensin I-converting enzyme expression in renal artery of Wistar, Wistar Kyoto, and spontaneously hypertensive rats.

One of the most intriguing features in kidney transplantation is the finding that kidneys from hypertensive rats can transfer arterial hypertension on transplantation into normotensive rats. Some evidence also suggest that, in humans undergoing renal transplantation, the genotype of the donor kidney determines the blood pressure in the recipient. The renin-angiotensin-aldosterone system is the major etiological candidate in hypertension because it plays an important role in the control of cardiovascular homeostasis. Angiotensin-converting enzyme (ACE) cleaves the C-terminal from angiotensin I as well as from bradykinin. Thus, by generating the potent vasoconstrictor angiotensin II and by degrading the vasodepressor bradykinin, ACE is considered to play a role in blood pressure regulation. We have previously described the presence of N-domain ACE in urine of Wistar (W), Wistar Kyoto (WKY), and spontaneously hypertensive rats (SHR), all of which can hydrolyze the vasodilator peptide Angiotensin 1-7 and also the N-Acetyl-Ser-Asp-Lys-Pro, two peptides described as specific for N-domain ACE. These findings suggest that the 90 kd ACE isoform found in urine and in tissues of SHR is a possible genetic marker of hypertension. Based on the fact that the renal artery has an important role in the control of renal blood flow, we evaluated the presence of N-domain ACE in the renal artery of hypertensive and normotensive rats. Using Western blotting techniques on the renal arteries of W and WKY rats, we detected the 190-kd ACE (similar to somatic ACE) and also the 65-kd ACE previously described in urine and renal tissue as N-domain ACE. The 65-kd and 90-kd isoforms of ACE were also detected in renal arteries in SHR rats. Further studies are required to understand the role of 90-kd enzyme described as a possible local marker of hypertension, its contribution in angiotensin catabolism, and whether this abnormal form of the enzyme has any link with the development and transfer of hypertension after transplantation.

Trough-to-peak ratio and circadian blood pressure profile after treatment with once-daily extended-release diltiazem, 240 mg, in patients with mild-to-moderate essential hypertension.

Once-daily diltiazem extended-release 240 mg (Lacerol-HTA Retard) was evaluated for safety, efficacy, and trough-to-peak ratio in a multicenter open study by using 24-h blood pressure (BP) monitoring in mild-to-moderate essential hypertension. After a 4-week washout period, 30 patients (17 men, 13 women) aged 25-76 years, showing a mean daytime diastolic BP (DBP) >90 mm Hg, were treated with diltiazem-ER, 240 mg, given once daily for 8 weeks. Ambulatory BP monitoring was obtained at the end of a 4-week placebo run-in period and during the last week of treatment. A significant reduction of the mean values of clinical BP [161.6 +/- 16.2 to 151.2 +/- 15.6 mm Hg; p < 0.01 for systolic BP (SBP); and 101.1 +/- 4.8 to 93.3 +/- 9.2 mm Hg; p < 0.001 for DBP] was observed at the end of treatment in the group of 30 patients, with no significant changes in heart rate (77.1 +/- 9.9 to 73.1 +/- 11.1 beats/min; p = NS). Likewise, mean values of 24-h SBP, DBP, SBP-load, and DBP-load were significantly reduced. In the group of 21 responders, the average reduction at peak was -18.6 +/- 12.9 mm Hg for SBP and -14.7 +/- 9.5 mm Hg for DBP. The residual effect at trough was -12.2 +/- 14.7 and -8.1 +/- 10 mm Hg, respectively. The trough-to-peak ratio was estimated as 0.66 for SBP and 0.55 for DBP. Long-term variability expressed as the mean standard deviation of BP for the 24-h period was reduced in responders (16.2 +/- 4.3 to 14.6 +/- 2.7 mm Hg for SBP; p = 0.0395; and 12.1 +/- 2.7 to 10.7 +/- 2.5 mm Hg for DBP; p = 0.0019), although no changes were observed in the variation coefficient (10.58-10.57% for SBP and 12.88-12.87% for DBP). We conclude that once-daily diltiazem-ER, 240 mg, was effective and well tolerated. Blood pressure was controlled over the entire period of 24 h, preserving the circadian profile and reducing long-term variability in responders. The significant reduction of both BP values and long-term variability may have implications involving protection from end-organ damage in essential hypertension.

Una nueva tienodiacepina, brotizolam, en el tratamiento del insomnio. / A new drug for the treatment of insomnia, a thienodiazepine, brotizolam

Estudio doble ciego,comparativo en 20 pacientes hospitalizados por distintas causas y con insomnio de origen no psiquiatrico. Los pacientes recibieron en forma cruzada 0,5 mg de brotizolam o 30 mg de flurazepam, por un periodo de 14 dias. Ambos farmacos mejoraron la induccion del sueno, su continuidad y aumentaron las horas de sueno. Estos parametros evolucionaron mas favorablemente con brotizolam

Spontaneous hepatic rupture in rheumatoid arthritis.

A fatal hepatic rupture developed, in a patient with rheumatoid arthritis, as a result of hepatic arteritis. The patient had hypotension, falling hematocrit level, hepatomegaly, and evidence of progressive hepatocellular dysfunction. Hepatic dysfunction is not uncommon in rheumatoid arthritis, but is usually asymptomatic. Hepatic arteritis is a rare manifestation of rheumatoid arthritis; however, recognition of this complication is important, since early intervention may be important in successful management.