Search PubMed⌕ Search

Biomedical subjects

J Verdaguer

Publications and source records attributed to J Verdaguer.

At least 19 recordsLinked to original sources
PubMed2006

Reg (regenerating) gene overexpression in islets from non-obese diabetic mice with accelerated diabetes: role of IFNbeta.

AIMS/HYPOTHESIS: The expression of IFNbeta in beta cells results in accelerated type 1 diabetes. The REG family of beta cell proliferation factors have been described as autoantigens in autoimmune diabetes. The aim of this study was to determine the effect of IFNbeta on Reg expression, and the implications of this in terms of autoimmunity. METHODS: Reg gene expression was determined in islets from non-obese diabetic (NOD) RIP-HuIFNbeta mice by cDNA microarray, quantitative real-time PCR and immunohistochemistry. The effect of IFNbeta on Reg1 and Reg2 expression was assessed in the NOD insulinoma cell line NIT-1. IL-6, known to induce Reg expression, was measured in the insulitis microenvironment. Morphological studies were carried out to determine islet enlargement in this model. RESULTS: Reg2 was upregulated in islets from the NOD RIP-HuIFNbeta mice at the onset of the autoimmune attack. IFNbeta upregulates Reg1 and Reg2 genes in NIT-1 cells. The expression of Il6 was increased in islets from transgenic mice and in NIT-1 cells exposed to HuIFNbeta. Moreover, islets from transgenic mice were enlarged compared with those from wild-type mice. CONCLUSIONS/INTERPRETATION: Reg overexpression correlates well with the acceleration of diabetes in this model. The upregulation of Reg suggests that islets try to improve hyperglycaemia by regenerating the cells lost in the autoimmune attack. Reg expression is regulated by several factors such as inflammation. Therefore, the overexpression of an IFNbeta-induced autoantigen (REG) in the islets during inflammation might contribute to the premature onset of diabetes.

Animals↗
PubMed2005

Reactogenicity and immunogenicity profile of a two-dose combined hepatitis A and B vaccine in 1-11-year-old children.

This study was conducted to compare the reactogenicity, immunogenicity and safety of a combined two-dose (0, 6 months) hepatitis A and B vaccine (720ELU HAV, 20 mcg HBsAg) with the established three-dose (0, 1 and 6 months) hepatitis A and B vaccine (360ELU HAV, 10 mcg HBsAg). A total of 511 children aged 1-11 years who had not previously received a hepatitis A or B vaccine were enrolled in the study. Both vaccines were well tolerated, and were shown to be safe and immunogenic. The analysis, stratified according to two age groups (1-5 year and 6-11-year-old children) demonstrated that the reactogenicity profile of the two-dose schedule was at least as good as that of the established schedule. Both vaccines and schedules provided at least 98% seroprotection against hepatitis B and 100% seroconversion against hepatitis A, 1 month after the end of the vaccination course (Month 7).

Child↗
PubMed2003

Comparison of the reactogenicity and immunogenicity of a combined diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated polio (DTPa-HBV-IPV) vaccine, mixed with the Haemophilus influenzae type b (Hib) conjugate vaccine and administered as a single injection, with the DTPa-IPV/Hib and hepatitis B vaccines administered in two simultaneous injections to infants at 2, 4 and 6 months of age.

An open, randomised, multicentre trial was performed to compare the reactogenicity and safety profile of the administration of a hexavalent diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated polio (DTPa-HBV-IPV) vaccine administered in one injection mixed with Haemophilus influenzae type b (Hib) conjugate vaccine (Group 1) with that of a pentavalent DTPa-IPV vaccine mixed with a Hib vaccine (DTPa-IPV/Hib), simultaneously administered with HBV (Group 2) in two injections in opposite thighs, as a primary vaccination course, to healthy infants at 2, 4 and 6 months of age. A total of 235 completed the study, 120 from Group 1 and 115 from Group 2. Blood samples (pre-vaccination and 1 month after the third dose) were obtained from a subset of infants (Group 1: 40; Group 2: 31) to assess the immune response to vaccination. Local and general solicited symptoms were recorded by parents on diary cards. Seven hundred and five diary cards (Group 1: 360; Group 2: 345) were collected. The clinically relevant and most commonly reported local reaction was pain (infant cried when the limb was moved) in 2.5% (Group 1) and 1.2% (Group 2) of diary cards. Fever was more frequently reported in Group 1 (21% of diary cards) than in Group 2 (12% of diary cards). However only 3 and 2% of doses in Groups 1 and 2, respectively, were responsible for a rectal temperature between 38.6 and 39.5 degrees C and only one case (Group 2) had > or =39.5 degrees C. Other clinically relevant general symptoms were rarely recorded: irritability (2-2.8%), loss of appetite (0.3-0.6%) and drowsiness (0.3-0.3%). All subjects included in the immunogenicity analysis had seroprotective titres to diphtheria, tetanus, polio virus types 1 and 3, Hib. Almost all subjects were seroprotected for anti-polio type 2 and hepatitis B (with the exception of 1 subject in Group 1 for each antigen). The vaccines response rates to pertussis antigens were over 97 and 90% in Groups 1 and 2, respectively. This study shows that, from a clinical perspective, the DTPa-HBV-IPV/Hib vaccine given in a single injection has a similar reactogenicity and safety profile to that of two licensed vaccines (DTPa-IPV/Hib, HBV) given in two simultaneous injections to infants at 2, 4 and 6 months of age. This is a valuable advantage, since in some countries, such as Spain and the UK, an additional injection (for the administration of meningococcal C conjugate vaccine) has been recently included in the infants' vaccination calendars.

Antibodies, Bacterial↗
PubMed2001

Sliding osteotomies in mandibular reconstruction.

The aim of this article is to describe a few simple and atraumatic methods for mandibular reconstruction following the ablation of tumors or traumas. These reconstruction techniques are indicated for rebuilding short mandibular defects (less than 4 cm) or for patients in poor general condition with larger defects that cannot be remedied using longer and more complicated procedures. Five types of osteotomies were used: "C," single, double, bilateral sliding, and sagittal sliding. Osteotomies were performed on 14 patients, 13 with malignant tumors and one with a gunshot wound. Good results were obtained in 10 patients, total failure occurred in two, and complications without failure of the reconstruction arose in the other two.

Adult↗
PubMed2000

Progression of autoimmune diabetes driven by avidity maturation of a T-cell population.

For unknown reasons, autoimmune diseases such as type 1 diabetes develop after prolonged periods of inflammation of mononuclear cells in target tissues. Here we show that progression of pancreatic islet inflammation to overt diabetes in nonobese diabetic (NOD) mice is driven by the 'avidity maturation' of a prevailing, pancreatic beta-cell-specific T-lymphocyte population carrying the CD8 antigen. This T-lymphocyte population recognizes two related peptides (NRP and NRP-A7) in the context of H-2Kd class I molecules of the major histocompatibility complex (MHC). As pre-diabetic NOD mice age, their islet-associated CD8+ T lymphocytes contain increasing numbers of NRP-A7-reactive cells, and these cells bind NRP-A7/H-2Kd tetramers with increased specificity, increased avidity and longer half-lives. Repeated treatment of pre-diabetic NOD mice with soluble NRP-A7 peptide blunts the avidity maturation of the NRP-A7-reactive CD8+ T-cell population by selectively deleting those clonotypes expressing T-cell receptors with the highest affinity and lowest dissociation rates for peptide-MHC binding. This inhibits the local production of T cells that are cytotoxic to beta cells, and halts the progression from severe insulitis to diabetes. We conclude that avidity maturation of pathogenic T-cell populations may be the key event in the progression of benign inflammation to overt disease in autoimmunity.

Animals↗
PubMed2000

IL-1alpha, IL-1beta, and IFN-gamma mark beta cells for Fas-dependent destruction by diabetogenic CD4(+) T lymphocytes.

Cytokines such as IL-1alpha, IL-1beta, and IFN-gamma have long been implicated in the pathogenesis of autoimmune diabetes, but the mechanisms through which they promote diabetogenesis remain unclear. Here we show that CD4(+) T lymphocytes propagated from transgenic nonobese diabetic (NOD) mice expressing the highly diabetogenic, beta cell-specific 4.1-T-cell receptor (4.1-TCR) can kill IL-1alpha-, IL-1beta-, and IFN-gamma-treated beta cells from NOD mice. Untreated NOD beta cells and cytokine-treated beta cells from Fas-deficient NOD.lpr mice are not targeted by these T cells. Killing of islet cells in vitro was associated with cytokine-induced upregulation of Fas on islet cells and was independent of MHC class II expression. Abrogation of Fas expression in 4.1-TCR-transgenic NOD mice afforded nearly complete protection from diabetes and did not interfere with the development of the transgenic CD4(+) T cells or with their ability to cause insulitis. In contrast, abrogation of perforin expression did not affect beta cell-specific cytotoxicity or the diabetogenic potential of these T cells. These data demonstrate a novel mechanism of action of IL-1alpha, IL-1beta, and IFN-gamma in autoimmune diabetes, whereby these cytokines mark beta cells for Fas-dependent lysis by autoreactive CD4(+) T cells.

Animals↗
PubMed2000

[Clinical features and response to systemic treatment of primary and secondary episcleritis and scleritis resistant to local treatment].

BACKGROUND: Scleritis and episcleritis may extend to adjacent ocular tissues with blinding consequences and may be associated with potentially lethal systemic disorders. AIM: To evaluate the ocular complications and systemic disease associations of the different types of scleritis and episcleritis. PATIENTS AND METHODS: Forty six patients with refractory scleritis and episcleritis were studied and treated during the period 1991 to 1998. RESULTS: Necrotizing type was the most common and severe category in the scleritis group of patients. A decrease in vision occurred in 58.3% of patients with scleritis v/s a 23.5% of patients with epiescleritis (p < 0.05). Uveitis was present in 35.4% of patients with scleritis and scleromalacia was present in 33.3% (p < 0.05). A specific disease association was uncovered in 51% of scleritis and in 38% of episcleritis patients. Rheumatoid arthritis, primary systemic vasculitic disease and Sjögren syndrome with vasculitis were the most common associated systemic diseases. Three patients with scleritis had tuberculosis. CONCLUSIONS: Scleritis is more severe than episcleritis, and necrotizing scleritis is the most severe type of scleritis. Classification of scleritis and episcleritis provides valuable prognostic information. A meticulous approach for the detection of a specific associated disease must be undertaken. Scleritis associated with vasculitis has a worse ocular prognosis than other non infectious diseases. Cyclophosphamide is the most effective immunosuppressive treatment to control severe ocular involvement.

Adolescent↗
PubMed1999

Prevalent CD8(+) T cell response against one peptide/MHC complex in autoimmune diabetes.

Spontaneous autoimmune diabetes in nonobese diabetic (NOD) mice is the result of a CD4(+) and CD8(+) T cell-dependent autoimmune process directed against the pancreatic beta cells. CD8(+) T cells play a critical role in the initiation and progression of diabetes, but the specificity and diversity of their antigenic repertoire remain unknown. Here, we define the structure of a peptide mimotope that elicits the proliferation, cytokine secretion, differentiation, and cytotoxicity of a diabetogenic H-2K(d)-restricted CD8(+) T cell specificity (NY8.3) that uses a T cell receptor alpha (TCRalpha) rearrangement frequently expressed by CD8(+) T cells propagated from the earliest insulitic lesions of NOD mice (Valpha17-Jalpha42 elements, often joined by the N-region sequence M-R-D/E). Stimulation of splenic CD8(+) T cells from single-chain 8. 3-TCRbeta-transgenic NOD mice with this mimotope leads to preferential expansion of T cells bearing an endogenously derived TCRalpha chain identical to the one used by their islet-associated CD8(+) T cells, which is also identical to the 8.3-TCRalpha sequence. Cytotoxicity assays using islet-derived CD8(+) T cell clones from nontransgenic NOD mice as effectors and peptide-pulsed H-2K(d)-transfected RMA-S cells as targets indicate that nearly half of the CD8(+) T cells recruited to islets in NOD mice specifically recognize the same peptide/H-2K(d) complex. This work demonstrates that beta cell-reactive CD8(+) T cells mount a prevalent response against a single peptide/MHC complex and provides one peptide ligand for CD8(+) T cells in autoimmune diabetes.

Amino Acid Sequence↗
PubMed1999

Two mechanisms for the non-MHC-linked resistance to spontaneous autoimmunity.

Genetic susceptibility and resistance to most autoimmune disorders are associated with highly polymorphic genes of the MHC and with non-MHC-linked polygenic modifiers. It is known that non-MHC-linked polymorphisms can override or enhance the susceptibility to an autoimmune disease provided by pathogenic MHC genes, but the mechanisms remain elusive. In this study, we have followed the fate of two highly diabetogenic beta cell-specific T cell receptors (Kd and I-Ag7 restricted, respectively) in NOR/Lt mice, which are resistant to autoimmune diabetes despite expressing two copies of the diabetogenic MHC haplotype H-2g7. We show that at least two mechanisms of non-MHC-linked control of pathogenic T cells operate in these mice. One segregates as a recessive trait and is associated with a reduction in the peripheral frequency of diabetogenic CD8+ (but not CD4+) T cells. The other segregates as a dominant trait and is mediated by IL-4- and TGF-beta1-independent immune suppressive functions provided by lymphocytes that target diabetogenic CD4+ and CD8+ T cells, without causing their deletion, anergy, immune deviation, or ignorance. These results provide explanations as to how non-MHC-linked polymorphisms can override the susceptibility to an autoimmune disease provided by pathogenic MHC haplotypes, and demonstrate that protective non-MHC-linked genes may selectively target specific lymphoid cell types in cellularly complex autoimmune responses.

Amino Acid Sequence↗
PubMed1999

Autoantigen-independent deletion of diabetogenic CD4+ thymocytes by protective MHC class II molecules.

Some MHC class II genes provide dominant resistance to certain autoimmune diseases via mechanisms that remain unclear. We have shown that thymocytes bearing a highly diabetogenic, I-Ag7-restricted beta-cell-reactive TCR (4.1-TCR) undergo negative selection in diabetes-resistant H-2g7/x mice by engaging several different antidiabetogenic MHC class II molecules on thymic (but not peripheral) hemopoietic cells, independently of endogenous superantigens. Here we have investigated 1) whether this TCR can also engage protective MHC class II molecules (I-Ab) on cortical thymic epithelial cells in the absence of diabetogenic (I-Ag7) molecules, and 2) whether deletion of 4.1-CD4+ thymocytes in I-Ab-expressing mice might result from the ability of I-Ab molecules to present the target beta-cell autoantigen of the 4.1-TCR. We show that, unlike I-Ag7 molecules, I-Ab molecules can restrict neither the positive selection of 4.1-CD4+ thymocytes in the thymic cortex nor the presentation of their target autoantigen in the periphery. Deletion of 4.1-CD4+ thymocytes by I-Ab molecules in the thymic medulla, however, is a peptide-specific process, since it can be triggered by hemopoietic cells expressing heterogeneous peptide/I-Ab complexes, but not by hemopoietic cells expressing single peptide/I-Ab complexes. Thus, unlike MHC-autoreactive or alloreactive TCRs, which can engage deleting MHC molecules in the thymic cortex, thymic medulla, and peripheral APCs, the 4.1-TCR can only engage deleting MHC molecules (I-Ab) in the thymic medulla. We therefore conclude that this form of MHC-induced protection from diabetes is based on the presentation of an anatomically restricted, nonautoantigenic peptide to highly diabetogenic thymocytes.

Animals↗
PubMed1999

Perforin-independent beta-cell destruction by diabetogenic CD8(+) T lymphocytes in transgenic nonobese diabetic mice.

Autoimmune diabetes in nonobese diabetic (NOD) mice results from destruction of pancreatic beta cells by T lymphocytes. It is believed that CD8(+) cytotoxic T lymphocytes (CTLs) effect the initial beta-cell insult in diabetes, but the mechanisms remain unclear. Studies of NOD.lpr mice have suggested that disease initiation is a Fas-dependent process, yet perforin-deficient NOD mice rarely develop diabetes despite expressing Fas. Here, we have investigated the role of perforin and Fas in the ability of beta cell-reactive CD8(+) T cells bearing a T-cell receptor (8.3-TCR) that is representative of TCRs used by CD8(+) CTLs propagated from the earliest insulitic lesions of NOD mice, and that targets an immunodominant peptide/H-2Kd complex on beta cells, to effect beta-cell damage in vitro and in vivo. In vitro, 8.3-CTLs killed antigenic peptide-pulsed non-beta-cell targets via both perforin and Fas, but they killed NOD beta cells via Fas exclusively. Perforin-deficient 8.3-TCR-transgenic NOD mice expressing an oligoclonal or monoclonal T-cell repertoire developed diabetes even more frequently than their perforin-competent littermates. These results demonstrate that diabetogenic CD8(+) CTLs representative of CTLs putatively involved in the initiation of autoimmune diabetes kill beta cells in a Fas-dependent and perforin-independent manner.

Animals↗
PubMed1999

[Treatment of non infectious ocular inflammatory disease with low doses of cyclosporin A].

BACKGROUND: Cyclosporin A has an adequate immunosuppressive capacity and can be useful in the treatment of non infectious ocular inflammatory diseases. AIM: To describe the clinical effect of cyclosporin A treatment in low doses, along with corticosteroids, in the treatment of refractory ocular inflammatory diseases. PATIENTS AND METHODS: Twenty patients (13 female), aged 17 to 74 years old with severe and refractory ocular inflammatory diseases were studied. All except one, received variable doses of prednisone (10 to 60 mg/kg/day) and all received cyclosporin in doses that started in 2.5 mg/day and were increased to 5 mg/kg/day, according to clinical response. Patients were followed from 8 to 24 months, with monthly assessments of ocular inflammation (using a four point score), visual acuity and adverse effects of treatment. RESULTS: A two points or more reduction in the ocular inflammation score was observed in 52% of patients. Visual acuity improved in 10 subjects, stabilized in 8 and worsened in 2. Prednisone doses were reduced in most patients. Observed adverse effects were hypertension in 2 patients, creatinine elevation in 2, gastrointestinal disturbances in 3 and hypertrichosis in 12. A reduction of cyclosporin dose was required in these cases, but it was discontinued only in one patient with a vascular purpura. CONCLUSIONS: Low cyclosporin doses, associated to prednisone, are useful to reduce inflammation and improve visual acuity in patients with non infectious ocular inflammatory diseases, refractory to other treatment methods.

Adolescent↗
PubMed1997

Spontaneous autoimmune diabetes in monoclonal T cell nonobese diabetic mice.

It has been established that insulin-dependent diabetes mellitus (IDDM) in nonobese diabetic (NOD) mice results from a CD4+ and CD8+ T cell-dependent autoimmune process directed against the pancreatic beta cells. The precise roles that beta cell-reactive CD8+ and CD4+ T cells play in the disease process, however, remain ill defined. Here we have investigated whether naive beta cell-specific CD8+ and CD4+ T cells can spontaneously accumulate in pancreatic islets, differentiate into effector cells, and destroy beta cells in the absence of other T cell specificities. This was done by introducing Kd- or I-Ag7-restricted beta cell-specific T cell receptor (TCR) transgenes that are highly diabetogenic in NOD mice (8.3- and 4.1-TCR, respectively), into recombination-activating gene (RAG)-2-deficient NOD mice, which cannot rearrange endogenous TCR genes and thus bear monoclonal TCR repertoires. We show that while RAG-2(-/-) 4.1-NOD mice, which only bear beta cell-specific CD4+ T cells, develop diabetes as early and as frequently as RAG-2+ 4.1-NOD mice, RAG-2(-/-) 8.3-NOD mice, which only bear beta cell-specific CD8+ T cells, develop diabetes less frequently and significantly later than RAG-2(+) 8.3-NOD mice. The monoclonal CD8+ T cells of RAG-2(-/-) 8.3-NOD mice mature properly, proliferate vigorously in response to antigenic stimulation in vitro, and can differentiate into beta cell-cytotoxic T cells in vivo, but do not efficiently accumulate in islets in the absence of a CD4+ T cell-derived signal, which can be provided by splenic CD4+ T cells from nontransgenic NOD mice. These results demonstrate that naive beta cell- specific CD8+ and CD4+ T cells can trigger diabetes in the absence of other T or B cell specificities, but suggest that efficient recruitment of naive diabetogenic beta cell-reactive CD8+ T cells to islets requires the assistance of beta cell-reactive CD4+ T cells.

Animals↗
PubMed1997

A mechanism for the major histocompatibility complex-linked resistance to autoimmunity.

Certain major histocompatibility complex (MHC) class II haplotypes encode elements providing either susceptibility or dominant resistance to the development of spontaneous autoimmune diseases via mechanisms that remain undefined. Here we show that a pancreatic beta cell-reactive, I-Ag7-restricted, transgenic TCR that is highly diabetogenic in nonobese diabetic mice (H-2(g7)) undergoes thymocyte negative selection in diabetes-resistant H-2(g7/b), H-2(g7/k), H-2(g7/q), and H-2(g7/nb1) NOD mice by engaging antidiabetogenic MHC class II molecules on thymic bone marrow-derived cells, independently of endogenous superantigens. Thymocyte deletion is complete in the presence of I-Ab, I-Ak + I-Ek or I-Anb1 + I-Enb1 molecules, partial in the presence of I-Aq or I-Ak molecules alone, and absent in the presence of I-As molecules. Mice that delete the transgenic TCR develop variable degrees of insulitis that correlate with the extent of thymocyte deletion, but are invariably resistant to diabetes development. These results provide an explanation as to how protective MHC class II genes carried on one haplotype can override the genetic susceptibility to an autoimmune disease provided by allelic MHC class II genes carried on a second haplotype.

Animals↗
PubMed1997

[Herpetic keratitis: clinical-virological correlation].

BACKGROUND: Herpetic keratitis is the main infectious cause of corneal opacity. The existence of effective antiviral agents underscores the need of an early diagnosis. AIM: To correlate clinical features of herpetic keratitis with virological studies. PATIENTS AND METHODS: Forty one patients with a clinical diagnosis of herpetic keratitis were studied. Viral isolation, polymerase chain reaction (PCR) and typification were done in a sample taken by swabbing the ocular lesion. RESULTS: Twenty six patients (31% female) had epithelial keratitis, that was mild or moderate in 88% of cases and acute in 77% of them. In 20 patients (77%), viral isolation and PCR were positive (HSV-2 in one case). Fifteen patients (67% female) had stromal keratitis, 93% of cases were moderate or severe and 53% were acute. Viral isolation was negative in all cases and in 20% PCR was positive. CONCLUSIONS: Viral isolation and PCR were equally sensitive in epithelial keratitis, but in stromal keratitis only PCR could detect the virus. Moderate acute dendrite was the predominant clinical manifestation. The higher proportion of women with stromal keratitis supports its possibly autoimmune etiology. HSV-2 is seldomly isolated and possibly associated to vertical transmission.

Acute Disease↗
PubMed1996

Acceleration of spontaneous diabetes in TCR-beta-transgenic nonobese diabetic mice by beta-cell cytotoxic CD8+ T cells expressing identical endogenous TCR-alpha chains.

The role of target cell autoantigens and their repertoire vs those of foreign Ags, superantigens, or non-Ag-specific stimuli in the activation and recruitment of effector T cells in most spontaneous models of autoimmune diseases remains elusive. Here we report on the use of single TCR-beta transgenic mice to study the mechanisms that drive the accumulation of pathogenic T cells in the pancreatic islets of nonobese diabetic (NOD) mice, a model for insulin-dependent diabetes mellitus. Expression of the V(beta)8.1+ TCR-beta rearrangement of a diabetogenic H-2Kd-restricted beta cell cytotoxic CD8+ T cell (beta-CTL) clone in NOD mice caused a 10-fold increase in the peripheral precursor frequency of beta-CTL and a selective acceleration of the recruitment of CD8+ T cells to the pancreatic islets of prediabetic animals. This resulted in an earlier onset and a faster progression of beta cell depletion, and led to a dramatic acceleration of the onset of diabetes. Most islet-derived beta-CTL from diabetic transgenic NOD mice expressed an endogenously-derived TCR-alpha sequence identical to that of the clonotype donating the TCR-beta transgene, and a TCR-alpha-CDR3 sequence homologous to those expressed by most islet-derived beta-CTL from nontransgenic NOD mice. TCR-beta transgene expression did not change the peripheral frequency of beta cell-specific CD4+ T cells, the rate at which these cells accumulated in the pancreatic islets, or the incidence of diabetes. Taken together, our data indicate that retention of CD8+ and CD4+ T cells in the pancreatic islets of NOD mice is driven by beta cell autoantigens, rather than by local superantigens or non-Ag-specific stimuli, and that beta-CTL are major effectors of beta cell damage in spontaneous insulin-dependent diabetes mellitus.

Amino Acid Sequence↗
PubMed1995

[Treatment of ocular inflammatory disease with glucocorticoids and cyclophosphamide pulses].

UNLABELLED: The effectiveness, toxicity and prognostic factors influencing responses to cyclophosphamide (CP) iv pulses plus oral glucocorticosteroids (GC) in patients with GC-resistant ocular inflammatory diseases (OID) was evaluated in a cohort of 15 consecutive patients suffering from active, non-infectious OID refractory to oral GC. All patients underwent monthly evaluations with clinical, hematological, hepatic, renal and ophthalmologic tests. These included checking visual acuity and both anterior chamber and posterior segment inflammation. The overall effect evaluated by repeated measurements ANOVA demonstrated that after an average of 5 CP pulses 1-10, the group showed significant improvement regarding of visual acuity and inflammation (p < 0.000001). Amelioration was not sustained over time in patients with granulomatous uveitis. Patients with retinal vasculitis experienced rapid and sustained recovery. By the end of the follow-up period, 53% of the patients had improved, 20% remained stationary and 26% suffered visual acuity deterioration as compared with the baseline. No serious side effects were detected during treatment and follow-up. CONCLUSIONS: A combination of oral GC and iv CP pulses appears to be an effective way to treat patients suffering from noninfectious, non-granulomatous, GC-resistant OID.

Adult↗