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PubMed2000

Molecular analysis of lineage-specific chimerism and minimal residual disease by RT-PCR of p210(BCR-ABL) and p190(BCR-ABL) after allogeneic bone marrow transplantation for chronic myeloid leukemia: increasing mixed myeloid chimerism and p190(BCR-ABL) detection precede cytogenetic relapse.

We studied lineage-specific chimerism and minimal residual disease (MRD) in sequential posttransplant samples from 55 patients who underwent unmanipulated (n = 44) or partially T-cell-depleted (n = 11) allogeneic bone marrow transplantation (BMT) for chronic myeloid leukemia (CML). Chimerism was assessed by polymerase chain reaction (VNTR [variable number of tandem repeats]-PCR) analysis in highly purified CD19+, CD3+, CD15+, and CD56+ cell fractions, whereas MRD was investigated in whole blood by reverse transcriptase-PCR (RT-PCR) of both p210(BCR-ABL) and p190(BCR-ABL) hybrid transcripts. Of 55 patients, 14 (including 6 T-cell-depleted patients) had cytogenetic relapse at 5-80 months and progressed to hematologic relapse, while 41 patients remained in prolonged cytogenetic remission 12-107 months post-BMT. Before leukemia recurrence, patients in the relapse group showed a consistent evolution pattern sequentially featured by persistent p210(BCR-ABL) positivity, increasing mixed chimerism (MC) in myeloid cells, p190(BCR-ABL) positivity, and, finally, cytogenetic relapse. Myeloid MC preceded cytogenetic relapse by 2-12 months, whereas p190(BCR/ABL) was detected 1-6 months prior to cytogenetic relapse in 11 patients and concomitant with cytogenetic relapse in 3 patients. In the remission group, all patients invariably tested negative for p190(BCR-ABL); 10 patients tested positive for p210(BCR-ABL) at variable time-points but showed persistent full donor chimerism (DC), whereas 31 patients tested p210(BCR-ABL) negative and displayed full DC or transient MC due to the persistence of recipient T cells. Two patients in the relapse group were successfully reinduced into molecular remission with donor lymphocyte infusion. Sequential molecular analysis after such treatment showed the inverse pattern to that observed prior to relapse, ie, progressive disappearance of p190(BCR-ABL) transcripts, conversion of myeloid chimerism to donor type, and, finally, p210(BCR-ABL) negativity. We conclude that lineage-specific chimerism and p190(BCR-ABL) messenger RNA (mRNA) analyses contribute a better characterization of CML evolution after BMT and enable early identification of patients at the highest risk of relapse. (Blood. 2000;95:2659-2665)

Adolescent↗

PubMed2002

A study on a possibility of predicting early relapse in leprosy using a ND-O-BSA based ELISA.

Serological methods have been used for detecting infection with Mycobacterium leprae. We have applied a serological test to explore the possibility it could detect a bacterial relapse among patients who have been cured with chemotherapy. More specifically we used an indirect enzyme-linked immunosorbant assay (ELISA) using the natural disaccharide (ND) of the phenolic glycolipid antigen of M. leprae linked to bovine serum albumin as antigen. Antibody levels were measured in sera from normal controls, active leprosy cases, cured leprosy patients, and relapsing leprosy patients. We correlated antibody levels with the type of leprosy, the bacterial index, and with relapse among cured leprosy patients. In our hands, the ND-ELISA, when applied to screening for infection with M. leprae, had excellent sensitivity, specificity, positive and negative predictive values, and both a low false positive rate and a low false negative rate. Antibody levels gradually increased among active patients from the tuberculoid to the lepromatous end of the leprosy spectrum. There was a year-by-year fall in antibody levels in patients responding to chemotherapy. Antibody levels and the bacterial index were correlated using the Spearman's rank correlation method. Serial antibody levels were measured in 666 leprosy patients after being cured with dapsone monotherapy. Over a three year follow up, 95 multibacillary patients became antibody positive and 12 of them had bacterial relapses of their disease. In contrast, among 335 cases that remained antibody negative, only one relapse was seen. Among 44 paucibacillary cured patients who became antibody positive, there was one relapse. There were 192 such patients who remained antibody negative and one relapsed. The risk of relapse is 6.7 times higher among cured multibacillary patients compared to cured paucibacillary patients. Overall, the cumulative relapse rate among antibody positive cases was 13.7%, compared to 0.4% among antibody negative patients. We conclude that the ND-ELISA is a useful tool both for screening for early infection with M. leprae and for predicting a relapse in cured patients, particularly in cured multibacillary patients.

Antibodies, Bacterial↗

PubMed2002

Risk factors of relapse within eight weeks after an acute asthma exacerbation in Thai children.

BACKGROUND: Acute asthma relapse following treatment and discharge from hospital remains a substantial problem. Various potential risk factors for relapse have been reported including age, sex, frequency of hospitalization and emergency medications. All these factors, however, may not be generalized for all patients because of difference in prevalence, trigger factors, types of allergens, medical accessibility and psychosocial problems. OBJECTIVE: To identify factors associated with relapse following treatment for acute asthma within the next 8 weeks in Thai children. MATERIAL AND METHOD: The authors prospectively followed 91 children discharged from Ramathibodi Hospital after treatment of an asthma attack from June 1999 to December 2000. Parents were surveyed concerning their child's medical history, trigger factors, psychosocial and economic variables. Data on severity of the attack, asthma scores, emergency treatment, and response to treatment were recorded. Investigations included eosinophil count, total IgE, serum eosinophil cationic protein (ECP), skin test, methacholine bronchial challenge test, and IQ test were performed and recorded. RESULTS: Within the first week, only 6.6 per cent had relapsed and increased to 29.7 per cent by 8 weeks. Patients who suffered relapse were more likely associated with age at asthma diagnosis (OR, 2.90; 95% CI, 1.1-7.5) and 6 years of age or under (OR 4.49, CI 1.22-16.54). From the investigation results including eosinophil count, total IgE, serum ECP, skin test, methacholine bronchial challenge test, and IQ test, there was no significant difference in the factors between patients who suffered relapse and those who did not. From the psychosocial evaluation, 18 out 39 (46.2%) studied cases had significant psychosocial disorders. They were 4 cases with delayed development and mental retardation, 9 cases with parent-child relation problems, and 2 cases with serious intrafamilial disorders. Most of these patients were non-relapse cases. However, the relationship between asthma relapse and psychosocial disorders could not be ascertained since psychosocial evaluation was only performed in one-third of the study population. CONCLUSION: Among patients following acute asthma therapy, 29.7 per cent will have a relapse. The authors identified the age at onset of asthma before the age of 6 years as an important risk factor. This may help to decrease the relapse rate by more intensive and comprehensive management among patients at high risk.

Acute Disease↗

PubMed1992

Relapses in multibacillary leprosy patients after stopping treatment with rifampin-containing combined regimens. Marchoux Chemotherapy Study Group.

During the decade between the mid 1970s and the mid-1980s, 12 rifampin (RMP)-containing combined regimens were tested among lepromatous leprosy patients in the Institut Marchoux. The 384 patients who were seen at least once during the period beginning 12 months after completion of treatment were considered eligible for analysis of the relapse rate. By the end of May 1991, relapse, manifested by a significant increase of the bacterial index (BI) and the appearance of new lesions with a BI greater than that of preexisting lesions, had been observed in 68 (17.7%) of these patients. Relapse was confirmed by the presence of viable Mycobacterium leprae in skin biopsy specimens obtained from 54 of the first 61 cases; virtually all of the isolated strains remained susceptible to RMP. The relapses occurred late, about 5 +/- 2 years after stopping treatment; the shorter the duration of RMP administration, the earlier the appearance of the relapse. The variations of the relapse rate among regimens were considerable: total relapse rate ranged from 2.9% to 27.8%, and the relapse rate per 100 patient-years of observation ranged from 0.8 to 6.9. Among the 12 regimens, only the WHO/MDT yielded an acceptable relapse rate (defined as a rate lower than 1.0 per 100 patient-years). However, because the mean duration of follow up was shortest among the patients treated with WHO/MDT, the relative low relapse rate among these patients must be interpreted with great caution.

Drug Therapy, Combination↗

PubMed1992

Relapses in leprosy patients after release from dapsone monotherapy; experience in the leprosy control program of the all Africa Leprosy and Rehabilitation Training Center (ALERT) in Ethiopia.

Before implementation of multidrug therapy (MDT), leprosy patients who were clinically inactive, skin-smear negative and had been treated with dapsone monotherapy for at least 5 years (paucibacillary patients) or for at least 10 years (multibacillary patients) were released from treatment. An analysis was made of self-reporting relapses in 1081 paucibacillary (PB) patients and 1123 multibacillary (MB) patients who had been released in Addis Ababa and two rural districts of the leprosy control program of the All Africa Leprosy and Rehabilitation Training Center (ALERT). During an average period of 6.6 years after stopping dapsone, 44 relapses were diagnosed among the PB patients and 148 relapses among the MB patients. The overall relapse rate was 4.1% or 7.2 per 1000 patient-years after release from treatment for PB patients and 13.2% and 24.8, respectively, for MB patients. The annual relapse rate in PB patients did not differ significantly from year to year. However the relapse rate for MB patients was significantly lower during the fifth to seventh years after stopping treatment compared with the first 4 years. Based on clinical findings there was a strong suspicion of relapse with dapsone-resistant bacilli in 40.4% of MB relapses. It is concluded that the relapse rate for PB patients is acceptable. However, the relapse rate for MB patients is considered too high. It is strongly recommended to administer to all MB patients, including those who have been on long-term treatment with dapsone and have become clinically and bacteriologically inactive, a 2-year course of MDT.

Adolescent↗

PubMed2005

Anti-leukemic effect of graft-versus-host disease on bone marrow and extramedullary relapses in acute leukemia.

BACKGROUND AND OBJECTIVES: Several reports have suggested that the graft-versus-leukemia effect at extramedullary (EM) sites might be less prominent than that in the bone marrow (BM). We analyzed the effect of graft-versus-host disease (GVHD) on BM and EM relapses in 194 consecutive patients with acute leukemia who underwent allogeneic hematopoietic cell transplantation at a single institute. DESIGN AND METHODS: We compared relapse-free survival (RFS), BM RFS, and EM RFS after allografting according to the occurrence of GVHD. We also investigated the clinical outcome of patients who relapsed after their allogeneic transplantation. RESULTS: Relapse occurred in 65 patients; in 41 (63%) relapse occurred in the BM only, in 9 (14%) it occurred in both BM and EM sites, and 15 (23%) in EM sites only. Patients who developed acute GVHD after transplantation had significantly higher relapse-free survival (69.2% vs. 52.4%; p=0.042) and BM RFS (80.7% vs. 59.1%; p=0.030) compared to those who did not. However, EM RFS was similar between patients with and without acute GVHD (76.7% vs. 78.2%; p=0.744). Among the 65 patients who relapsed, 32 patients attained complete remission with salvage treatments and 22 experienced a second relapse, which occurred in the BM (n=9), BM and EM sites (n=1), or EM sites (n=12). INTERPRETATION AND CONCLUSIONS: Our study confirms that GVHD after allogeneic hematopoietic cell transplantation has an anti-leukemic effect, thus preventing relapse; however, it may be less effective in preventing EM relapse.

Adolescent↗

PubMed2006

Validation by RQ-PCR and flow cytometry of alpha-defensin1-3 (DEFA1-3) overexpression in relapsed and refractory acute lymphoblastic leukemia.

In spite of high cure rates and improved overall survival, 25% of pediatric patients with acute lymphoblastic leukemia (ALL) relapse after obtaining complete remission. Additionally a small proportion of patients are refractory and do not attain remission. Microarray expression analysis of matched diagnosis-relapse B-lineage ALL sample pairs identified DEFA1-3 as a potential marker of relapse. Here, validation of DEFA1-3 as a marker for therapy resistance is explored. DEFA1-3 expression was analysed by RQ-PCR in patient paired samples at diagnosis and relapse of 6 early-relapse (within 18 months) and 8 late-relapse (beyond 18 months) B-lineage ALL. Diagnostic samples of 19 patients with ALL who are in continuous complete remission (median time from diagnosis 47 month) and diagnostic samples of 5 refractory patients who had not achieved remission at day 35 of therapy were also analyzed. In addition, overexpression of alpha-defensin1-3 proteins in blast cells at relapse was analysed by flow cytometry. DEFA1-3 was overexpressed at relapse as compared to diagnosis in 12 of 14 samples. At diagnosis, the expression of DEFA1-3 was significantly higher in samples from refractory patients as compared to those of patients who are in CR and to those of patients who experienced late relapse. At diagnosis, patients who relapsed early after diagnosis could not be distinguished from refractory patients based on DEFA1-3 expression levels. Results suggest that high levels of DEFA1-3 mRNA and alpha-defensin1-3 protein expression are correlated with disease progression and failure of adequate response to conventional chemotherapy.

Adolescent↗

PubMed2006

Estimating the relapse risk of Plasmodium vivax in Iran under national chemotherapy scheme using a novel method.

OBJECTIVES: This study aimed to estimate the relapse risk of Plasmodium vivax under national chemotherapy scheme using a novel method, and assessed its pattern in Kahnooj, a malaria endemic area in Iran. METHODS: The authors traced repeated episodes of malaria attack between 1994 and 2001 and then, estimated the risks of secondary attack of P. vivax, classified by the species in their primary attack. It is suggested that the difference between the secondary attack rate in those who were infected by P falciparum and P. vivax in their primary attack may estimate the P. vivax relapse rate indirectly. RESULTS: This method showed that the relapse risk of P. vivax with in one and two years after the primary attack were 16.8 and 24.5% respectively. The risks of relapse before three or after 18 months were very low. INTERPRETATION & CONCLUSION: The relapse pattern of P. vivax was compatible with the dominant pattern in most of the temperate areas. In addition, the relapse risk was very close to the estimated relapse risks in clinical trials on anti-relapse drugs. Therefore, we concluded that the anti-relapse therapy in the study area was effective; also, this method may estimate the relapse risk of P. vivax accurately.

Animals↗

PubMed1989

The hypnozoite and malarial relapse.

As described above, perhaps the most compelling arguments against the cyclic schizogony (Shortt-Garnham) hypothesis of malarial relapse have been (1) its inability to explain the disparate relapse patterns of P. vivax strains as they occur in nature, and (2) the dearth of concrete evidence for its support. The hypnozoite theory, in contrast, both provides an explanation for the variety of observed relapse patterns, and has direct morphologic and time-related, quantitative evidence for its support. Moreover, it provides a potential, unifying framework for the development of relapsing malaria from the time of introduction of sporozoites onward, taking as controlling factors, both the survival of the parasite and ecological interactions within its natural environment. It also suggests the possibility of an improved taxonomic classification, one based on whether or not the hypnozoite stage exists in a given species. Finally, Figure 6 presents a composite of relapse data pertinent to a number of strain groups of P. vivax, in comparison with a generalized, nonrelapsing species, schematically depicted within the framework of the hypnozoite theory. Thus, no hypnozoites are shown to result from sporozoites of the nonrelapsing species at one extreme, whereas no sporozoites undergoing immediate schizogony (i.e. without dormancy) are found at the other, the "lost" P. vivax strain of Nicolaiev. In between, varying proportions of sporozoites are depicted as producing hypnozoites, which exhibit varying periods of dormancy, ranging from less than 1 month (within the wide complement of the "tropical" strains) to approximately 21 months or more for the "northern" strains, before activation to schizogony and resultant relapse at the observed intervals. Although the actual proportions of each sporozoite/hypnozoite type within the strains depicted are unknown, a single, successful sporozoite can yield a parasitemic relapse--their distribution among the major strain groupings appears reasonably distinct, and, to some extent, defines each grouping. The sequences of sporozoite to pre-erythrocytic schizont, to merozoite release, to erythrocyte, as seen in nonrelapsing malarias and early primary parasitemias, versus sporozoite to hypnozoite, to pre-erythrocytic schizont, to erythrocyte, as seen in relapses, are easily inferred from this summary of observed relapses. It is difficult to see how these observed phenomena can be satisfactorily explained by a cyclic schizogony mechanism. It must be emphasized, nevertheless, that additional work with other relapsing and nonrelapsing species is necessary in order to establish the concept fully, and to determine the molecular mechanisms for dormancy and activation of hypnozoites.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1988

Relapse after allogeneic bone marrow transplantation for Philadelphia chromosome positive chronic myeloid leukemia: cytogenetic analysis of 24 patients.

One hundred patients with chronic myeloid leukemia (CML) submitted to bone marrow transplantation (BMT) were included in a cooperative cytogenetic study. Relapse (defined on the basis of hematological and cytogenetic findings) occurred in 24 (24%) patients at different intervals after BMT. In 18 of these patients (studied on average 3.3 times between BMT and relapse) no Ph-positive metaphases were detected before relapse. Sixteen (75%) of the patients relapsed with the same chromosomal pattern as that seen before BMT; eight patients, of whom five relapsed in blast crisis, showed additional chromosomal abnormalities resembling those seen in non-transplanted patients. One of these patients relapsed in cells of donor origin. After recognition of relapse, various hematological and cytogenetic patterns were observed. Four patients showed spontaneous reversion to normal (donor-type) chromosomes and hematology. Two other patients were followed for prolonged periods with hypercellular marrows with more than 50% Ph-positive cells but with normal peripheral blood values. The majority of patients proceeded to clinical relapse and required treatment with chemotherapy. We conclude that the isolated finding of a minority of Ph-positive metaphases after BMT should not be classified as relapse; for patients who do relapse, the sequence of cytogenetic and hematological events thereafter is variable.

Adolescent↗

PubMed1993

Relapse in melioidosis: incidence and risk factors.

From 1986 to 1991, 602 patients with melioidosis were seen in Sappasitprasong Hospital, Ubon Ratchatani, Thailand. The in-hospital mortality was 42%. Of 118 adult patients followed long-term, 27 (23%) had culture-proven relapses of melioidosis (3 relapsed twice), a relapse rate of 15% (95% confidence interval [CI], 11-22) per year. The median time from discharge to relapse was 21 weeks (range, 1-290). In 44% of patients, relapses included septicemia, and 27% died. Patients with severe disease (multiple foci of infection or septicemia) relapsed 4.7 times (95% CI, 1.6-14.1) more frequently than patients with localized melioidosis. Underlying disease was not a risk factor, but initial parenteral treatment with ceftazidime reduced the risk of relapse 2-fold (95% CI, 1.1-3.4). Relapses were 3.3 (95% CI, 1.4-9.0) times more frequent following short-course (< or = 8 weeks) oral coamoxiclav than after the oral combination regimen of chloramphenicol, doxycycline, and cotrimoxazole. Longer oral treatment with either reduced relapse 1.6-fold (95% CI, 1.2-1.9). The optimum choice and duration of antibiotic treatment to prevent relapse in melioidosis remain to be determined.

Adolescent↗

PubMed1996

Molecular analysis of transient cytogenetic relapse after allogeneic bone marrow transplantation for chronic myeloid leukaemia.

Serial quantification of residual disease in CML patients after allogeneic BMT is useful for early detection of relapse. However, the fact that some cytogenetic relapses appear to be transient may complicate protocols for early therapeutic intervention based on molecular analysis and could result in the unnecessary treatment of some patients. To determine the frequency and significance of transient cytogenetic relapse, we have studied serial samples from 98 CML patients after allogeneic BMT by conventional cytogenetics and competitive RT-PCR for BCR-ABL mRNA. During the period of study, 26 patients had cytogenetic or haematologic evidence or relapse. In four cases (15% of those who relapsed; 4% of all patients) relapse appeared to be transient; i.e., subsequent marrow samples were completely Ph chromosome-negative despite the fact that there had been no change in treatment, including the level of immunosuppression. BCR-ABL mRNA levels broadly paralleled the cytogenetic findings. Of these four patients, two subsequently progressed to frank haematologic relapse and two remained strongly positive for BCR-ABL transcripts and are therefore presumably still at risk of relapse. Analysis of B cell-enriched, T cell-enriched and lymphoid-depleted fractions for three patients demonstrated that transient relapse was not due to the proliferations of BCR-ABL-positive lymphoid cells. In contrast, BCR-ABL-positive myeloid precursor cells were detected in two of three patients tested. We conclude that transient cytogenetic relapse followed by sustained remission is a relatively infrequent occurrence after current allogeneic transplant regimens.

Adult↗

PubMed1997

Detection of prostate cancer relapse with prostate specific antigen monitoring at levels of 0.001 to 0.1 microG./L.

PURPOSE: The development of prostate specific antigen (PSA) assays with detection limits of approximately 0.001 microgram./l. is technically feasible. We examined if serum PSA changes of 0.001 to 0.1 microgram./l. for up to 3 years after radical prostatectomy have any clinical value. MATERIALS AND METHODS: We studied 148 patients with a postoperative PSA of less than 0.1 microgram./l. by a conventional PSA assay. At least 3 serial serum samples were collected per patient along with detailed clinicopathological features. Serial serum samples were analyzed for PSA with the ultrasensitive method. Associations between increase in serum PSA and clinicopathological features were analyzed with the unconditional logistic regression model. RESULTS: After establishing a set of interpretative criteria, we divided the patients into 51 with biochemical relapse, 93 who were free of relapse and 4 with equivocal status. Between the groups with and without relapse there was no difference in year of surgery, age at operation or length of followup. Compared to patients without relapse, those with biochemical relapse were likely to have positive surgical margins (p < 0.01), larger tumor volumes (p < 0.01), greater preoperative PSA (p = 0.03) and disease extending outside the prostate (p = 0.02). The relative risks for biochemical relapse estimated by a univariate logistic regression model were 3.1 (95% confidence interval 1.39 to 6.82, p < 0.01) for positive surgical margin, 3.4 (95% confidence interval 1.46 to 8.13, p < 0.01) for tumor volume, 2.3 (95% confidence interval 1.08 to 5.02, p = 0.03) for high preoperative PSA and 2.7 (95% confidence interval 1.12 to 6.26, p = 0.03) for extraprostatic tumor extension. At multivariate analysis with the same model the associations between positive surgical margins and biochemical relapse (relative risk 2.95, p = 0.04) and tumor volume (relative risk 3.36, p = 0.03) remained significant. These associations were still observed when we analyzed a subset of patients classified as having biochemical relapse based on PSA changes of 0.001 to 0.08 microgram./l. CONCLUSIONS: Increases in postoperative serum PSA at levels of 0.001 to 0.1 microgram./l. after radical prostatectomy are associated with clinicopathological features of poor prognosis. Monitoring postoperative cases with a highly sensitive PSA assay (detection limit 0.001 microgram./l.) could offer a simple and effective means of detecting clinically important biochemical relapse early after radical prostatectomy. These patients may be suitable for early intervention when effective treatments for relapse become available.

Follow-Up Studies↗

PubMed1997

Prognostic factors for relapse in stage I testicular seminoma treated with surveillance.

PURPOSE: We sought to identify prognostic factors predictive of disease progression in patients with clinical stage I seminoma on surveillance following orchiectomy. MATERIALS AND METHODS: Between January 1981 and December 1993, 201 patients 20 to 86 years old (median age 34) with clinical stage I seminoma were placed on surveillance following orchiectomy. The potential prognostic factors studied included age, tumor size, mitotic count, S phase fraction, ploidy, presence of small vessel invasion, syncytiotrophoblasts and tumor infiltrating lymphocytes, expression of beta-human chorionic gonadotropin and low molecular weight keratin on immunohistochemistry. RESULTS: With a median followup of 6.1 years (range 1.3 to 12.3) 31 patients had relapse for an actuarial 5-year relapse-free rate of 84.9%. The 5-year actuarial survival rate was 97.1% and the cause specific survival rate was 99.5%. On univariate analysis factors predictive of relapse were tumor size (5-year relapse-free rate 88 and 67% for tumors 6 cm. or less and greater than 6 cm., respectively, p = 0.004), age (5-year relapse-free rate 79 and 91% for age 34 years or younger versus older than 34 years, respectively, p = 0.009) and presence of small vessel invasion (5-year relapse-free rate 86 versus 69%, p = 0.01). On multivariate analysis age and tumor size were predictive of relapse, while small vessel invasion approached statistical significance. The risk of relapse in 57 patients with none of the 3 adverse prognostic factors (age greater than 34 years, tumor 6 cm. or smaller and no small vessel invasion) was 6%. CONCLUSIONS: We identified age, size of the primary tumor and small vessel invasion as important prognostic factors for relapse in patients with stage I seminoma treated with surveillance. Further followup and assessment of biological factors are needed to optimize selection of patients at a high risk for relapse who should receive immediate postoperative therapy.

Actuarial Analysis↗

PubMed1996

Studies on Plasmodium vivax relapse pattern in Kheda district, Gujarat.

Relapse pattern in P. vivax malaria was studied in five villages of Nadiad taluka, Kheda district, Gujarat. P. vivax cases treated with 600 mg chloroquine and in combination with 50 mg pyrimethamine (adult dose) yielded 28.31 and 27.73% relapse rate respectively. While relapse rate of 5.78% was observed with five day course of 75 mg primaquine (15 mg/day) administered as radical treatment. Relapse rate in 5-10 yr of age group was comparatively more than other age groups. There was no noticeable difference in relapse rates among male and female. The short-term relapse with a lag period of 2-3 months was significantly higher in this area. The longest relapse with an interval of 17 months was found in one case treated with chloroquine along with pyrimethamine. However, primaquine regimen prevented consecutive relapses. Primaquine has been found adequate to prevent relapse in more than 90% vivax cases, while efficacy of chloroquine-pyrimethamine and chloroquine alone was almost comparable. A high proportion of relapse may be minimized, if 5-days radical treatment is given at appropriate time.

Adolescent↗

PubMed1997

The lived experience of relapsing multiple sclerosis: a phenomenological study.

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system that is well known but poorly understood by the medical and nursing community as well as the general public. The myriad neurological symptoms result from an autoimmune attack on the insulating myelin of the nerves which cause a disruption of nerve impulses in the brain and spinal cord. MS most often affects young adults and may be broadly categorized as either a relapsing or a chronic progressive disease course. Until recently, research has focused on the progressive form of MS though it accounts for less than half of the cases. People who are diagnosed with relapsing MS are cared for in the same way as those with the debilitating progressive form. Relapsing MS affects individuals periodically with exacerbations from which they often recover completely, whereas chronic MS results in a progressive functional deterioration. People with relapsing MS are not given a realistic prediction of what to expect in their future nor are they left with any hope for normalcy in their lives. The purpose of this study was to provide a description of the lived experience of people who have relapsing MS. To answer the question, "What is the lived experience of people with relapsing multiple sclerosis?" this study was conducted using hermeneutic phenomenology. A sample of 10 patients with relapsing MS was interviewed over a seven month period. Interviews began with the question, "What is it like for you living with multiple sclerosis?" The interviews were tape recorded and transcribed verbatim. Data were analyzed using the Colaizzi method of hermeneutic phenomenology. Themes that emerged from the data were combined and abstracted into twelve dimensions that described the lived experience of people with relapsing MS. Participants' social networks served as either positive or negative influences in their adjustment process and led to conflicts for some. Coping with recurrent symptoms and social situations related to the MS was facilitated by maintaining control and a sense of hope. Most expressed a sense of relief with diagnosis because they had secretly feared their symptoms were a result of a fatal illness or psychological instability. Uncertainty surfaced as a major theme due to the unpredictability of relapsing MS. Participants also experienced fear and loss. Getting to know MS was an integral part of the experience often made difficult by concealment of facts. Participants experienced acts of revealing and concealing throughout their illness process and often attempted to conceal their illness from a society that did not understand. Nurses should be aware of the relapsing MS experience when providing care and teaching to patients and families with MS. The nurse should also reflect on the importance of maintaining hope and open communication.

Activities of Daily Living↗

PubMed2005

Anti-IL-16 therapy reduces CD4+ T-cell infiltration and improves paralysis and histopathology of relapsing EAE.

Infiltration of the central nervous system (CNS) by CD4+ Th1 cells precedes onset and relapses of experimental autoimmune encephalomyelitis (EAE). We reported that (B6xSJL) F1 (H-2b/s) mice with severe relapsing-remitting disease had extensive infiltration by CD4+ T cells compared to that in C57BL/6 (B6) (H-2b) mice, which developed mild low-relapsing disease in response to myelin oligodendrocyte peptide 35-55 (MOG(35-55)). This observation led us to search for mechanisms that specifically regulate trafficking of CD4+ cells in relapsing H-2b/s mice. We show that the CD4+ cell chemoattractant cytokine interleukin (IL)-16 has an important role in regulation of relapsing EAE induced by MOG(35-55) in the (B6xSJL) F1 (H-2b/s) mice. We found production of IL-16 in the CNS of mice with EAE. IL-16 levels in the CNS correlated well with the extent of CD4+ T-cell and B-cell infiltration during acute and relapsing disease. Infiltrating CD4+ T cells, B cells, and to a lesser extent CD8+ T cells all contained IL-16 immunoreactivity. Treatment with neutralizing anti-IL-16 antibody successfully reversed paralysis and ameliorated relapsing disease. In treated mice, diminished infiltration by CD4+ T cells, less demyelination, and more sparing of axons was observed. Taken together, our results show an important role for IL-16 in regulation of relapsing EAE. We describe a novel therapeutic approach to specifically impede CD4+ T cell chemoattraction in EAE based on IL-16 neutralization. Our findings have high relevance for the development of new therapies for relapsing EAE and potentially MS.

Animals↗

PubMed2005

Post-marketing survey on clinical response to interferon beta in relapsing multiple sclerosis: the Roman experience.

Safety, tolerability and efficacy profiles of interferon beta (IFNbeta) therapy in relapsing multiple sclerosis (MS) has been widely verified both in trial settings and in daily clinical practice. However, for a variable percentage of treated patients, it remains only partially effective. In this study, we reported the post-marketing experience of the efficacy of IFNbeta therapy for a large cohort of MS patients regularly attending the MS Outpatient Clinic of "La Sapienza University" in Rome. In this cohort we also sought clinical and paraclinical variables responsible for the clinical course of MS during IFNbeta therapy. Patients that received treatment with one of the IFNbeta formulations for at least 1 year were included. Clinical outcomes (i. e., relapses and disability score) were monitored throughout the entire study period. Magnetic resonance imaging (MRI) scans were performed twice for each subject: at baseline and after 1 year of therapy. The occurrence of more than one relapse during the study period or a sustained disability progression in the Expanded Disability Status Scale (EDSS) score were considered as criteria for the definition of suboptimal clinical response to IFNbeta therapy. During IFNbeta therapy (number of patients 242, mean length of treatment 4.3+/-2.3 years) a reduction in the annualised relapse rate of 59% (p<0.001) was observed. Eighty-six patients (35%) fulfilled the criterion for defining "suboptimal responder" on the basis of relapses, and 69 (28.5%) did the same on the basis of EDSS sustained progression. Twenty-seven (11.1%) patients showed both an EDSS progression and two or more relapses. The presence of T1-enhancing lesions and new T2 hyperintense lesions on the scan performed after the first year of therapy were the best MRI features associated with both the occurrence of relapses during the treatment period (OR for enhancing lesions and relapses 3.6; OR for new T2 lesion and relapses 2.8). The present post-marketing experience confirms the efficacy of IFNbeta in modifying the natural course of MS and encourages the use of paraclinical variables measuring subclinical disease activity as surrogate markers to monitor the clinical course of MS during IFNbeta therapy.

Adjuvants, Immunologic↗