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PubMed2003

Relapses of hyperthyroidism in patients treated with radioiodine for nodular toxic goiter: relation to thyroid autoimmunity.

Relapses of hyperthyroidism after treatment with radioiodine for uni- or multi-nodular goiter may be accompanied by the appearance of TSAb. However, this phenomenon has only emerged from one retrospective study on Northern European patients, in which it was not possible to determine whether TSAb also appeared in treated patients who did not relapse. The present study aimed to assess the appearance, immunogenic nature and clinical characteristics of hyperthyroidism relapse after treatment with 131I for nodular toxic goiter in patients from the Mediterranean area. A retrospective study was performed on 76 consecutive patients, born and resident in Sicily and aged 56-80 yr at diagnosis, who were treated with radioiodine. Serum aliquots obtained from the patients before 131I treatment and during a follow-up of 36-144 months were assayed for TSAb and TPOAb. The clinical charts of the patients were also re-examined. Twenty-six out of 76 patients (36.8%) had a hyperthyroidism relapse after a first treatment with 131I. Eight of the 26 (30.7%) also relapsed after the second treatment. Three out of 26 (11.5%) relapsed after a third treatment. The 50 patients who required only one treatment and the 18 who relapsed only once were all TSAb-negative at baseline, while 3/8 (37.5%) who relapsed also after the second treatment were already TSAb-positive at baseline. TSAb became positive in 3/18 patients (16.7%) who relapsed once, and in 4/8 (50.0%) of those who relapsed after a second treatment. One of these 7 TSAb-positive relapsers was also already TPOAb-positive at baseline and another became TPOAb-positive after treatment. The presence of circulating TSAb in 3/76 (3.9%) patients before treatment for toxic goiter more probably points to a diagnosis of Marine-Lenhart's syndrome. In contrast, the de novo appearance of TSAb in the presence of hyperthyroidism relapse in 4/76 (5.3%) patients suggests the development of a Graves'-like disease after radioiodine treatment. This occurrence does not seem to have precise ethnic grounds, since the incidence we observed in Mediterranean patients was similar to that previously reported in Northern European patients.

Aged↗

PubMed1979

Orthodontic relapse in subjects with varying degrees of anteroposterior and vertical dysplasia.

Fifty seemingly well-treated orthodontic cases were studied by means of pretreatment, posttreatment, and postretention dental casts, lateral cephalograms, and other orthodontic records. The sample was restricted to cases exhibiting anteroposterior and/or vertical dysplasia as revealed by pretreatment dental casts. The sample was divided into a stable group and a relapse group. Each group contained twenty-five cases. A double-blind design was used. The raw data were analyzed by the stepwise discriminant analysis and by the multivariate analysis of variance. On the basis of the results obtained from this study, the following conclusions can be drawn: 1. In seemingly well-treated orthodontic cases, relapse or stability can neither be predicted nor judged from one set of records alone. 2. Relapse or stability of an orthodontic case can be predicted by comparing the posttreatment variables with the pretreatment variables. 3. Relapse or stability of an orthodontic case can be judged by comparing the postretention variables to the posttreatment variables. 4. The PP-GoGn angle and the mandibular intercanine width are the two most important variables associated with orthodontic relapse. 5. Changing the PP-GoGn angle, either by treatment or by growth, was associated with relapse. In other words, changes in the PP-GoGn angle tended to be unstable. This suggests that decreasing the PP-GoGn angle should be avoided. 6. In both the stable and the relapse groups, the mandibular intercanine width decreased postretention. This decrease was associated more with the relapse group than with the stable group. 7. The mandibular intercanine width tended to relapse toward its original pretreatment value. This suggests that, at the end of active treatment, the mandibular intercanine width should be maintained as originally presented. 8. There was no significant interaction between orthodontic relapse (or stability) and Angle Class I and II cases. 9. There was no significant interaction between relapse (or stability), of an orthodontic case, and the sex of the patient. 10. There was no significant interaction between orthodontic relapse (or stability) and whether or not extraction was included as a part of the mechanotherapy. Thus, the pretreatment deep overbite is not necessarily a contraindication to extraction.

Analysis of Variance↗

PubMed1989

Cytogenetic studies of 103 patients with acute myelogenous leukemia in relapse.

In order to investigate the cytogenetic patterns in relapsed acute myelogenous leukemia (AML), a clinical and cytogenetic follow-up of patients newly diagnosed for the Fourth International Workshop on Chromosomes in Leukemia (4IWCL) was evaluated at the 6IWCL. Information was received on 103 patients in relapse who were then classified into seven groups according to the diagnostic karyotype. These groups were: normal, t(8;21), t(15;17), +8, a single specific abnormality either numerical or structural other than those already listed, a single nonrandom or miscellaneous abnormality again either numerical or structural, and complex abnormalities. The patient's age, diagnostic FAB type, the number of relapses, the total survival time, and the karyotype in relapse were considered in each of these cytogenetic groups. The remission and survival rates were comparable in all groups except the +8 group, where patients relapsed earlier and had a shorter survival time. Multiple relapses occurred most frequently in the t(8;21) group, whereas none of the patients with t(15;17) relapsed more than once, although the total survival time was similar to the two groups. Thirty-nine percent of the patients relapsed with the same karyotype as at diagnosis. A more complex karyotype showing evolution was found in 53%, and 8% showed either a less-complicated karyotype or appeared to have reverted to normal. Numerical abnormalities in relapse frequently involved trisomy of chromosomes 8 and/or 21. There was a nonrandom development of 9q- with relapse in patients with t(8;21). A pericentric inversion of chromosome 4, and abnormality infrequently reported at diagnosis, was found in relapse in association with t(15;17), t(8;21), and +8 karyotypes. Changes considered to be typically secondary in nature involving 5q, 7q, and 12p were seen in only seven cases. Twenty-one patients who had an apparently normal karyotype at diagnosis remained normal in relapse, indicating that absence of clonal chromosome abnormality is a real observation in AML rather than a failure of detection.

Adolescent↗

PubMedDate not supplied

An investigation of potential time effects in retrospective reports of cocaine relapses.

Retrospective reports are widely used in social science research, such as studies of the relapse process. There is evidence, however, that such reports can be affected by a number of factors, including the passage of time. The goal of this study was to determine whether retrospective reports of cocaine relapses were influenced by the amount of time that had elapsed between the onset of the relapse and when the relapse interview was administered. A structured cocaine relapse interview was used to gather information on experiences prior to relapse and attributions for relapse. Evidence of linear and/or nonlinear time effects was found in two of the six subscales assessing experiences prior to relapse (Social Pressure to Use Drugs and Sensation Seeking), and there was evidence of logarithmic time effects in four of the six subscales that assessed attributions for relapses. These findings indicate that the amount of time between the onset of a relapse and when the subject is interviewed can influence reports of experiences prior to relapse and attributions for relapse. However, the magnitude of the time effects was generally small.

Adult↗

PubMed1989

The predictors of distant relapse following conservative surgery and radiotherapy for early breast cancer are similar to those following mastectomy.

Although previous studies have indicated that the predictors of local recurrence following conservative surgery (CS) and radiotherapy (RT) are not the same as those following mastectomy, it remains unclear whether the predictors of distant relapse differ by local treatment modality. Clinical and pathologic features predictive of distant relapse for patients treated with mastectomy have been well established and include lymph node involvement, histologic grade, and peritumoral lymphatic vessel invasion (LVI). To study the influence of these and other factors on the rate of distant relapse in patients treated with CS and RT, we have identified a group of 438 patients treated between 1968 and 1981 who met the following criteria: primary tumor size less than or equal to 5 cm, excision of the primary tumor, infiltrating ductal carcinoma as the most aggressive histologic subtype, histology evaluable for the presence of an extensive intraductal component, and a dose to the primary site greater than or equal to 60 Gy. Estrogen receptor status was available in 58% of cases, 76% had an axillary dissection, and 23% were treated with adjuvant chemotherapy. With a median follow-up of 89 months, 107 patients (24%) developed a distant relapse. The 5-year actuarial freedom from distant relapse (FDR) was 80%. Stepdown Cox proportional hazards regression analysis identified several factors associated with a significantly (p less than 0.01) increased risk for distant relapse: positive lymph nodes, histologic grade, necrosis, and lymphatic vessel invasion. The magnitude of each effect was then examined with a lifetable calculation. Five-year freedom from distant relapse was 86% for the node-negative subgroup, 78% for patients with one to three positive nodes, and 45% for patients with four or more positive nodes. For histologic grades I, II, and III, 5-year freedom from distant relapse was 96%, 97%, and 75%, respectively. For necrosis scored as absent, scant, moderate, or marked, 5-year freedom from distant relapse was 90%, 78%, 77%, and 66%, respectively. For lymphatic vessel invasion scored as absent or present, 5-year freedom from distant relapse was 85% and 63%, respectively. We conclude that the clinico-pathologic predictors for distant relapse following conservative surgery and radiotherapy appear to be the same as those following mastectomy. This observation is consistent with the notion that distant relapse is caused by the presence of micrometastases at the time of initial patient sentation and is not greatly influenced by selection of local treatment.

Breast Neoplasms↗

PubMed1993

Local recurrence versus new primary: clinical analysis of 82 breast relapses and potential applications for genetic fingerprinting.

PURPOSE: The purpose of this study was to perform a detailed clinical pathological analysis of breast relapses in patients treated with conservative surgery and radiation therapy in an effort to classify those relapses as true local recurrences or second primary tumors, and to assess the prognostic and therapeutic implications of such a classification system. METHODS AND MATERIALS: Of 990 patients treated with conservative surgery and radiation therapy at our facilities prior to December 1987, 82 patients have experienced a relapse in the conservatively treated breast as the primary site of failure. Patients were classified as having new primary tumors if they fulfilled any one of the following criteria: a) breast relapse occurring at a site distinctly removed from the original tumor; b) histology of the breast relapse compared with the original tumor consistent with a new primary; or c) DNA flow cytometry converting from an aneuploid primary to a diploid relapse. RESULTS: As of 2/92, with a median follow-up of 5.4 years from the time of breast relapse, the overall 5-year survival rate following breast relapse was 55%. Forty-seven patients were classified as true recurrences and 33 patients were classified as new primaries. Patients classified as true recurrences had a shorter median time to breast relapse than patients classified as new primaries (3.16 years vs. 5.42 years, p < .05) and an inferior post breast recurrence survival rate compared to patients classified as new primaries (36% vs. 89%, p < .05). Residual disease outside of the recurrent tumor bed was also noted to be more frequent in patients classified as true recurrences compared to patients classified as new primaries (48% vs. 16%, p < .05). CONCLUSION: Based on the clinical and pathological criteria outlined, it appears that a significant portion of patients experiencing a relapse in the conservatively treated breast may have new primary tumors as opposed to true local relapses. Distinction between a true recurrence and a new primary tumor may have significant prognostic implications. Uncertainties associated with the clinical and pathological criteria are presented and further investigations with genetic fingerprinting techniques to establish the clonality of breast relapses are presented and discussed.

Adult↗

PubMed1995

Pelvic relapse following subtotal lymphoid irradiation in early stage Hodgkin's disease--an analysis of risk, management, and outcome.

PURPOSE: To evaluate the time of onset, method of identification, management, and outcome of pelvic relapse following subtotal lymphoid irradiation (STLI) alone (mantle and paraaortic/spleen or splenic pedicle fields, excluding the pelvis) in supradiaphragmatic Stage I-II Hodgkin's disease. METHODS AND MATERIALS: A retrospective analysis was performed of the initial, relapse, and regular follow-up evaluations of patients with pelvic relapse following STLI alone from 1968 to the present for supradiaphragmatic Stage I-II Hodgkin's disease after pathologic staging (PS-laparotomy staging) and clinical staging (CS-no laparotomy staging). RESULTS: Following staging, which included bipedal lymphangiography, 482 patients (408 PS and 74 CS), were treated with STLI alone for supradiaphragmatic Stage I-II Hodgkin's disease. The actuarial freedom from relapse at 20 years was 75% in PS patients and 81% in CS patients. The actuarial pelvic failure at 20 years was 7% for PS patients and 3% for CS patients. Of the 29 patients with pelvic relapse, 97% (28 of 29) occurred within 5 years of treatment, including 1 patient who progressed during initial treatment. Pelvic relapse was most commonly initially identified by abnormalities involving patient symptoms (62%), physical examination (55%), erythrocyte sedimentation rate (48%), and bipedal lymphangiogram and/or abdominal radiograph (38%). Relapse was limited to previously unirradiated sites in 17 patients (58%). In addition to pelvic lymph node disease, 3 patients (10%) had involvement of bone, and 4 patients (14%) had bone marrow involvement. Following relapse, all patients were treated with chemotherapy (MOP[P], MOP[P]/ABV[D], ABVD, or PAVe) and 19 of 29 patients received involved field consolidative irradiation. Twenty-one of 29 (72%) remained relapse free at the time of last follow-up evaluation, including 15 of 19 (79%) treated with combined therapy. Eight patients experienced a second relapse despite salvage therapy, and all eight expired with recurrent Hodgkin's disease. Two patients died of complications related to prior treatment. Therefore, the actuarial risk of death at 20 years associated with pelvic failure in the entire cohort of 482 patients was 2%. CONCLUSION: Pelvic relapse occurred in 7% of patients following STLI alone and was effectively diagnosed by regular follow-up, which included a combination of patient history, physical examination, and radiographic laboratory evaluation. Seventy-two percent of patients remained relapse free following salvage treatment, which included chemotherapy, resulting in an overall survival rate associated with pelvic control of 98%. This approach, therefore, spared the majority of patients the long-term risks associated with pelvic irradiation and/or chemotherapy, such as infertility, but maintained an excellent prognosis.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2006

Alcohol relapse repetition, gender, and predictive validity.

Earlier exploratory work on a scoring algorithm for the Reasons for Drinking Questionnaire. Exploratory findings from the Reasons for Drinking Questionnaire presented a number of interesting findings, but were limited by a fairly low consistency in type of relapse between the first relapse and the second relapse (63%). This scoring algorithm objectively classifies alcohol relapses into one of three types (negative affect, social pressure, or craving/cued). While examining gender differences in the type of first relapse, evidence indicating that relapses were more consistent for men (81%) than for women (44%) was uncovered. For initial posttreatment relapses, women were more likely to have negative affect relapses, and men were more likely to have social pressure relapses. For men, negative affect relapses were predicted by the Beck Depression Inventory score. For women, negative affect relapses were predicted by the Alcohol Dependence Scale score, and craving/cued relapses were predicted by situational craving.

Alcoholism↗

PubMed2026

Genomic and transcriptomic features of relapsed small cell lung cancer.

BACKGROUND: Relapsed small cell lung cancer is characterized by treatment resistance and poor outcomes. Genomic and transcriptomic alterations in relapsed SCLC have not been characterized well. We comprehensively profiled relapsed SCLC samples along with patient-matched treatment-naive samples, when available, using whole-exome (WES), whole-genome (WGS), and RNA-sequencing (RNA-seq) to describe the molecular landscape of relapsed SCLC. Our goal is to identify potential novel pathways for additional functional validation and eventually novel therapeutic options. METHODS: We analyzed 54 relapsed and 27 treatment-naive SCLC samples using WES (with 26 patient-matched paired samples). A subset of the samples was also analyzed by WGS (n=28) and RNA-seq (n=31). Differences in mutational signatures, gene expression, structural variants, splicing, and neoantigen profiles at diagnosis and relapse were investigated. RESULTS: Relapsed SCLC samples demonstrated mutation signatures characteristic of platinum and APOBEC mutagenesis. Furthermore, these samples were characterized by MYC, MYCL and MYCN amplifications. Both treatment-naive and relapsed SCLC samples showed high prevalence of mutation-associated neoantigens (median= 86 in treatment-naive and 90 in relapsed SCLC; p=0.8) and TP53 was the most frequently altered gene to result in a neoantigen (48% of analyzed samples). Potential mechanisms of immune evasion, including amplification of CD24, overexpression of IDO1, increased M2 macrophage presence, and upregulation of HLA-E were also observed in relapse samples. Differences in alternative splicing patterns were observed between treatment-naive and relapsed small cell samples. Retained intron events were significantly enriched in treatment-naive samples and affected genes involved in DNA repair, metabolism, and WNT and MYC pathways. CONCLUSIONS: This study highlights the genomic and transcriptomic features of relapsed SCLC. These samples were characterized by genomic instability, WNT and MYC dysregulation, and splicing aberrations. Additional studies targeting the splicing machinery, WNT signaling, and immune evasion pathways could identify novel therapeutic vulnerabilities in SCLC.

Journal Article↗

PubMed2000

Extramedullary relapse after allogeneic bone marrow transplantation for haematological malignancy.

We describe the risk factors for and the natural history and response to treatment of extramedullary (EM) relapse in 183 patients who underwent allogeneic bone marrow transplantation (alloBMT) for a variety of haematological malignancies at our institution over a 7 1/2 year period. Fifty-one patients relapsed; 15 had EM relapse either alone or in association with marrow involvement. A retrospective analysis found that the presence of chronic GVHD and a longer interval between transplant and relapse were independently associated with an increased risk of EM compared to marrow-only relapse. EM relapse was also associated with a longer post-relapse survival. Patients with EM relapse appeared to respond to cytotoxic therapy but not to DLI. EM relapse after alloBMT may be more common than previously thought and have a better prognosis than marrow-only relapse. While patients developing chronic GVHD after alloBMT have a lower overall relapse risk than those who do not, they may be more prone to delayed relapse at EM sites.

Adolescent↗

PubMed1996

Development of the cocaine relapse interview: an initial report.

Although fine-grained analyses of circumstances surrounding relapses have been conducted with alcoholics, smokers and opiate users, there is comparatively little information about the relapse process in cocaine abusers. The Cocaine Relapse Interview (CRI) is a structured interview that gathers information on the onset, course and termination of cocaine relapse episodes. This article describes the development of the CRI and presents initial data on its reliability and validity. Sections of the CRI assess experiences on the day of the relapse, experiences during the week prior to the relapse, attributions for the relapse, experiences following initial use of cocaine and factors in terminating the relapse. Most of the subscales in each section of the CRI had adequate internal consistency and test-retest reliabilities. Validity studies indicated that most of the subscales that assess experiences prior to relapse differentiated relapsers from two control groups of non-relapsers, and that several subscales and individual items from the sections that assess experiences following initial use and factors in termination differentiated "lapsers" from "relapsers". Limitations of the CRI and recommendations for its use were also discussed.

Adult↗

PubMed2004

Mechanisms of relapse prevention in schizophrenia.

INTRODUCTION: A relapse can be expected in 70 % of patients after the first schizophrenic episode; in parallel 70 % of patients show an incomplete remission of the disorder after the first episode. This includes a cognitive decline and persistence of schizophrenic negative symptoms, often associated with social disabilities, social decline and a worsened quality of life. The risk for a relapse after a schizophrenic episode remains increased throughout the patient's lifetime. Moreover, the risk for chronic disorder increases with every relapse of the patient. Therefore relapse prevention is a primary focus in the treatment of schizophrenia. METHODS: Studies point out that atypical antipsychotics have advantages in relapse prevention of schizophrenia compared to the "classical" antipsychotics, although comparative studies are still lacking. RESULTS: The main risk factor for a relapse is the withdrawal of antipsychotic medication. Nonbiological factors such as high-expressed emotions, adverse life events and stress contribute to an increased risk of schizophrenic relapse. Studies of relapse after withdrawal of antipsychotic medication revealed that noradrenergic, serotonergic, and dopaminergic neurotransmission are involved, low serotonergic and high dopaminergic neurotransmission are associated with a relapse, and possibly high noradrenergic neurotransmission plays a role in short-term relapses. Inflammation and the activation of certain cytokines, which have rarely been studied to date, seem to have an even higher impact on schizophrenic relapse. Methodological aspects of these studies are discussed. CONCLUSION: Biological mechanisms of relapse may not become fully elucidated before the mechanisms of the schizophrenic pathophysiology are clarified.

Biomarkers↗

PubMed2005

Systemic and local cytokine production in quiescent ulcerative colitis and its relationship to future relapse: a prospective pilot study.

BACKGROUND: The main aim of this prospective study was to examine whether systemic (plasma) and local (mucosal) cytokine production is a predictor of future relapse in patients with quiescent ulcerative colitis (UC). The impact of other clinical and laboratory parameters on relapse was also studied. METHODS: Fifty consecutive patients with quiescent UC were included. At enrollment, blood and mucosal (rectal biopsies) samples were collected. All patients were followed up regularly for 1 year after enrollment. Plasma and mucosal cytokine levels were measured by enzyme-linked immunosorbent assay. To identify independent significant predictive factors for relapse, time-dependent analyses using the Kaplan-Meier method and the Cox proportional hazard model were performed. RESULTS: Thirty-four patients remained in remission, and 16 patients relapsed during the 1-year follow-up. Higher interleukin (IL)-8 levels in the rectal mucosa were significantly associated with relapse. In contrast, IL-1beta, IL-6, and tumor necrosis factor-alpha levels in the rectal mucosa were not associated with relapse. Conventional blood markers and plasma cytokines (IL-1beta, IL-6, IL-8, and tumor necrosis factor-alpha) did not correlate with relapse. Among clinical factors, age and number of prior relapses were significantly associated with relapse. In multivariate analysis, a higher rectal mucosal IL-8 level (> or = 160 pg/mg of tissue; hazard ratio, 4.7), younger age (<30 yr; hazard ratio, 7.3), and a greater number of prior relapses (> or = 5; hazard ratio, 4.3) were independent significant risk factors for future relapse. CONCLUSIONS: Rectal mucosal IL-8 measurement might be an additional objective diagnostic tool that can predict relapse in patients with quiescent UC.

Adult↗

PubMed1991

Acute myeloid leukaemia relapsing following interleukin-2 treatment expresses the alpha chain of the interleukin-2 receptor.

Immunotherapy with recombinant human Interleukin-2 (rhIL-2) was given to nine patients in first complete remission from acute myeloid leukaemia (AML). Five patients relapsed. The median time to relapse after commencing rhIL-2 was 26 weeks (range 2-44). Four patients were studied at relapse. The morphological and cytochemical features at relapse and presentation were similar. Cytogenetic analysis at relapse in patients 1 and 3 showed a normal karyotype. At relapse, patient 4 had the abnormality 46,XY, t(2;3). Patient 2 had the chromosomal abnormality t(8;21) at presentation and relapse. Patients 3 and 4 with M5 AML relapsed rapidly at 2 and 9 weeks after starting rhIL-2 treatment. Relapse leukaemia cells had features normally associated with lymphoid development. Patient 3 was TdT positive, with rearranged immunoglobulin genes, and a proportion of cells expressing the CD7 antigen; patient 4 also expressed the CD7 antigen. Relapse leukaemic cells from three of four patients expressed the alpha chain of the IL-2 receptor as assessed by flow cytometry. After overnight incubation and removal of T-lymphocytes the proportion of cells from these patients expressing the alpha chain increased from 15% to 61% (P less than 0.01). Using tritiated thymidine uptake to assess cell proliferation, two of three patients who expressed the IL-2 receptor alpha chain proliferated in response to 1000 u/ml of rhIL-2 in vitro, with a stimulation index greater than 1.95 (P less than 0.05). Following rhIL-2 immunotherapy for AML, relapse cells may express an inducible form of the alpha chain of the IL-2 receptor, which can mediate a proliferative response. It is possible that rhIL-2 when administered to AML patients in remission, may induce relapse. This may be a particular risk in patients with the M5 subtype.

Adult↗

PubMed1985

The choice of ulcer healing agent influences duodenal ulcer relapse rate and long-term clinical outcome.

The mode of pharmacological healing influences subsequent ulcer relapse. Duodenal ulcer relapse following healing and withdrawal of active therapy has been studied in 18 prospectively randomised comparative studies involving cimetidine and alternative healing agents. Most studies (eleven of the 18) showed comparative agents with a lower (greater than 10%) incidence of relapse than cimetidine while a minority (seven of the 18) showed equal (+/- 10%) relapse. The probability of this distribution occurring by chance is less than 1:1000 (p = 0.0005, sign test). In three of the 11 published comparative studies the relapse rate was significantly higher in those who had previously received cimetidine (p less than 0.05, two-sided significance test). This was despite the fact that most of the individual studies were small and required a substantial difference in results for the 5% significance level to be reached. Paired comparative incidences of relapse at six months were converted to relapse rates (percentage of healed population relapsing monthly), average rates for comparative agents were 8.05 +/- 2.7% while those for cimetidine were 16.9 +/- 4.4% (means +/- SEM, n = 5); cimetidine relapse rates derived from non-comparative trials were 17.0 +/- 1.9% (means +/- SEM, n = 7). Higher relapse rates translate into larger numbers of patients at risk and in need of active therapy. These results are of biological and clinical significance. Differences in relapse must reflect beneficial effects of one group of agents on the ulcer diathesis or adverse effects of the comparator, cimetidine. Each alternative reflects negatively on cimetidine as an antiulcer medication; however, confirmation of adverse effects would force radical review of most current therapy of ulcer disease. Research into ulcer therapeutics must emphasise both the relapse and the healing potential of pharmacologic agents.

Anti-Ulcer Agents↗

PubMed2003

Monitoring proteinase 3 antineutrophil cytoplasmic antibodies for detection of relapses in small vessel vasculitis.

The clinical usefulness of antineutrophil cytoplasmic antibodies (ANCAs) in the monitoring of patients treated for small vessel vasculitis is debated. A capture enzyme-linked immunosorbent assay (ELISA) based on anti-proteinase 3 (anti-PR3) monoclonal antibody 4A3 has previously been proven to be superior to indirect immunofluorescence (IIF) and standard ELISA for the diagnosis of vasculitis. The present study compared the effectiveness of the capture ELISA for the detection of disease relapse. Samples from patients with relapses and remissions (relapse and remission samples, respectively) were identified through the database of the Glomerular Disease Collaborate Network. Twenty-one relapse samples and 49 remission samples were analyzed by the capture PR3-ANCA ELISA from Wieslab AB, the standard PR3-ANCA ELISA from Inova, and IIF. A Medline search was performed to identify published data on ANCA status at relapse. The capture ELISA was positive for 21 instances of relapses in 14 patients, while the standard ELISA and IIF each failed to detect 2 relapses (P was not significant). By using a higher cutoff value, the capture ELISA correctly categorized 84% of the remission samples and 81% of the relapse samples. Similar degrees of discrimination could be achieved by IIF but not by the standard ELISA. In previously published series, the median proportions of patients positive at relapse were 100% by IIF (range, 75 to 100%) and 86% by standard ELISA (range, 38 to 100%). The corresponding values for a rise that accompanied or preceded a relapse were 75% (range, 20 to 100%) for IIF and 50% (range, 25 to 81%) for ELISA. The capture PR3-ANCA ELISA is a sensitive tool for the detection of relapses. Larger studies are needed to detect differences between methods. Negative results by tests for ANCAs are rare during relapses.

Adult↗

PubMed2006

Risks of relapse in patients with acute anterior uveitis.

AIM: To quantify the rate of recurrence of acute anterior uveitis (AAU), and evaluate the influence of associated risk factors. METHODS: We retrospectively reviewed the case notes of 185 patients with acute anterior uveitis, from their time of presentation to August 2001. The time to the first three recurrences of AAU from the onset of the disease was recorded, as well as the site of recurrence. Information regarding risk factors (for example (HLA-B27) status, spondyloarthropathy (SpA), family history of AAU/SpA and history of non-specific joint pain) were also collected. RESULTS: Patients were followed up until their third relapse, or up to the censoring date (August 2001) if less than three relapses had occurred. The median length of follow-up was 35 months. One hundred and twenty-two patients (66%) developed at least one relapse and 67 (36%) had three or more relapses. Kaplan-Meier estimate of median interval between disease onset and the first relapse was 24 months 95% CI (16 to 34) and between the first and second relapse was 14 months 95% CI (9 to 22), and was 15 months 95% CI (10 to 25) months between the second and third relapse. Using Cox regression only the number of previous relapses was significantly associated with the risk of AAU recurrence. There was no significant association between other reported risk factors and the risk of relapse, and neither did any risk factor significantly modify the association between previous relapses and AAU recurrence (p>0.066 for all interactions). There was a borderline significant difference in survival according to the laterality pattern of recurrences (ipsilateral, alternate, or bilateral) with a slightly greater than expected number of events in those with bilateral recurrence (p = 0.048). CONCLUSION: Patients with previous relapse(s) of AAU have a greater risk of AAU recurrence compared to those at disease onset but the risk of recurrence appears not to increase in a dose-response manner with increasing number of previous relapses. Demographic and extraocular features do not appear to influence the rate, or risk of recurrence of AAU.

Acute Disease↗

PubMed2005

High relapse rate in patients with MALT lymphoma warrants lifelong follow-up.

BACKGROUND: B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT lymphoma) is thought to be an indolent disease, with a good prognosis following various forms of treatment. Little, however, is known about the rate and pattern of relapse following successful treatment. PATIENTS AND METHODS: We have analyzed time to and pattern of relapse in patients with MALT lymphoma, along with investigation of t(11;18)(q21;q21), t(1;14)(p22;q32), and t(14;18)(q32;q21) involving IGH/MALT1, trisomy 3, and trisomy 18. Eighty-six patients achieving complete remission (CR) after initial therapy with sufficient follow-up data were available. Primary site of disease was the stomach (n = 36), salivary gland (n = 19), ocular adnexa/orbit (n = 12), lung (n = 8), thyroid (n = 5), breast (n = 3), liver (n = 2), and skin (n = 1). RESULTS: Thirty-two patients (37%) relapsed between 14 and 307 months (median 47 months) after initial CR. Ten relapses were local, whereas the remaining patients relapsed in a distant organ. Eight of 36 gastric versus 24 of 50 nongastric MALT lymphomas (P = 0.02) relapsed. Five patients had a second recurrence 26 to 56 months after a second CR. Relapse rates were not related to forms of initial treatment. Chromosomal aberrations were detected in 14 of 28 (50%) relapsing patients, and chromosomal alterations were identical at diagnosis and relapse. No significant association of any of the genetic changes investigated with relapse was found. Interestingly, patients with t(11;18)(q21;q21) had a significantly longer median time to relapse (76 months) than patients without this translocation (29 months; P = 0.012). CONCLUSIONS: In view of the late relapses seen in our series, lifelong observation of all patients treated for MALT lymphoma seems to be required.

Adult↗