Reports Of Relapse Research Articles

Rituximab as a Therapeutic Strategy in Hemophagocytic Lymphohistiocytosis: Efficacy, Outcomes, and Survival-Insights From a Systematic Review.

Hemophagocytic lymphohistiocytosis (HLH) is a severe immunologic disorder that can be fatal if left untreated. The condition is characterized by excessive immune system activation and is often triggered by infections such as Epstein-Barr virus (EBV). Rituximab, an anti-CD20 monoclonal antibody, has been suggested as a treatment, particularly for EBV-associated HLH. A systematic review was conducted using PRISMA guidelines, with a literature search spanning PubMed, Scopus, Web of Science, and the Cochrane Library. The inclusion criteria focused on studies that assessed rituximab's efficacy in treating HLH. Quality assessment was performed using the Joanna Briggs Institute Critical Appraisal Checklist for Case Reports. Of 783 identified records, 24 studies were included in the final analysis. Rituximab was typically administered at 375mg/m2, with varying doses and treatment frequency. Clinical response, often seen within 1 month, was assessed by improvements in clinical symptoms and laboratory findings. Survival rates posttreatment displayed a wide range, with instances of complete remission and disease-free periods, as well as reports of relapse and mortality. Rituximab demonstrates the potential for significant clinical benefit in treating HLH, particularly when associated with EBV, showing promise in reducing disease activity and contributing to remission. These findings encourage further research and clinical trials to refine the therapeutic protocols and better understand the long-term effects of rituximab in HLH management.

Assessing the Efficacy and Safety of Liposomal Amphotericin B and Miltefosine in Combination for Treatment of Post Kala-Azar Dermal Leishmaniasis.

No satisfactory canonical treatment is available for post-kala-azar dermal leishmaniasis (PKDL), clinical sequela of visceral leishmaniasis. Confined treatment options and substantial increase in relapse rate after miltefosine (MIL) treatment warrant the need to adapt resilient combination therapies. In this study, we assessed the safety and efficacy of combination therapy using liposomal amphotericin B (LAmB) and MIL for treating PKDL. Thirty-two PKDL patients, confirmed by microscopy or quantitative polymerase chain reaction (qPCR), were included in the study. An equal number of cases (n = 16) were put on MIL monotherapy (100 mg/day for 90 days) or MIL and LAmB combination for 45 days (3 injections of LAmB, 5 mg/kg body weight, and 100 mg/day MIL). Parasite load in slit aspirate was monitored using qPCR. Patients treated with combination therapy demonstrated a rapid decline in parasite load and achieved 100% cure, with no reports of relapse. Those treated with MIL monotherapy attained clinical cure with a gradual decrease in parasite load; however, 25% relapsed within 18 months of follow-up. Liposomal amphotericin B and MIL combination for treating PKDL is efficacious and safe, with high tolerability. Furthermore, this study established the utility of minimally invasive slit aspirate method for monitoring of parasite load and assessment of cure in PKDL.

A cluster of the first reported Plasmodium ovale spp. infections in Peru occuring among returning UN peace-keepers, a review of epidemiology, prevention and diagnostic challenges in nonendemic regions

BackgroundPlasmodium ovale curtisi and Plasmodium ovale wallikeri are regarded as less virulent forms of malaria with a geographic distribution including Southeast Asia, Central and West Africa, and is increasingly reported as an infection in returning travellers. A species of malaria that may have delayed or relapsing presentations similar to Plasmodium vivax, the clinical presentation of P. ovale spp. has been described to have prepatent periods of 2 weeks or slightly longer with reports of relapse following primary infection out to 8–9 months. This presentation may be obscured further in the setting of anti-malarial exposure, with report of delayed primary infection out to 4 years. Presented is a cluster of 4 imported P. ovale spp. cases in returning Peruvian military personnel assigned to United Nations peace-keeping operations in the Central African Republic.Case presentationFrom January to December 2016, Peruvian peace-keepers were deployed in support of United Nations (UN) operations in the Central African Republic (CAR). While serving abroad, Navy, Army, and Air Force members experienced 223 episodes of Plasmodium falciparum malaria following interruption of prophylaxis with mefloquine. Diagnosis was made using rapid diagnostics tests (RDTs) and/or smear with no coinfections identified. Cases of malaria were treated with locally-procured artemether-lumefantrine. Returning to Peru in January 2017, 200 peace-keepers were screened via thick and thin smear while on weekly mefloquine prophylaxis with only 1 showing nucleic acid within red blood cells consistent with Plasmodium spp. and 11 reporting syndromes of ill-defined somatic complaints. Between a period of 5 days to 11 months post return, 4 cases of P. ovale spp. were diagnosed using smear and polymerase chain reaction (PCR) following febrile complaints. All cases were subsequently treated with chloroquine and primaquine, with cure of clinical disease and documented clearance of parasitaemia.ConclusionThese patients represent the first imported cases in Peru of this species of malaria as well as highlight the challenges in implementing population level prophylaxis in a deployed environment, and the steps for timely diagnosis and management in a non-endemic region where risk of introduction for local transmission exists.

Remission of congenital epulide - case report

The lesion of congenital granular cells also known as Neumann Tumor or Congenital Epulide Tumor is a benign and rare congenital lesion with incidence in newborns with predilection by the female gender and occurs predominantly in the anterior alveolar ridge of the maxilla This lesion exhibits benign behavior and there are no reports of relapse in the literature This report aims to describe the observed case of a newborn seven days old melanoderma presenting lesion of congenital granular cells in the gingival mucosa of the maxilla with difficulties in breastfeeding The treatment consisted of observation and control since there was a natural rupture of the lesion without other complications and without recurrence culminating with the natural return of the newborn to breastfeeding

Transcriptome profiling identifies genes/pathways associated with experimental resistance to paromomycin in Leishmania donovani

Widespread resistance towards antimony and reports of relapses following miltefosine treatment has severely affected the management of visceral leishmaniasis (VL) in the Indian subcontinent. Paromomycin (PMM), an aminoglycoside antibiotic, has been licensed for VL treatment in India in 2007. Although its use is still restricted in the field, unraveling the molecular mechanism of resistance towards PMM is the key to preserve the drug. In this study, PMM resistant lines were selected up to 100 μM of PMM in three distinct field isolates of Leishmania donovani at promastigote stage. The resistance induced at promastigote level was also evident in amastigotes which showed 6 fold decreases in PMM susceptibility. Comparative transcriptome profiling of PMM resistant (PMM-R) and the corresponding PMM sensitive (PMM-S) parasites revealed modulated expression of 500 genes (1.5 fold cut off) in PMM-R parasites. Selected genes were validated for their modulated expression by quantitative real-time PCR. Functional classification and pathway analysis of modulated genes indicated probable adaptations in drug resistant lines which included a) reduced oxidative phosphorylation; b) increased glycosomal succinate fermentation and substrate level phosphorylation; c) dependency on lipids and amino acids for energy generation; d) reduced DNA synthesis and increased DNA damage repair and e) decreased protein synthesis and degradation. Interestingly, PMM-R parasites showed a marked increase in PMM susceptibility in presence of verapamil and amlodipine, antagonists of Ca2+ channel that are also modulators of ABC transporters. Moreover, infection of macrophages by PMM-R parasites led to modulated nitric oxide (NO) levels while reactive oxygen species (ROS) level remained unaltered. The present study highlights the putative mechanisms of PMM resistance in Leishmania.

Abstract 1793: POLE gene mutations confer good progression free survival in Asian women with FIGO grade 3 endometrioid endometrial carcinoma

Abstract Introduction: Endometrial carcinoma (EC) is the most common gynaecological cancer in developed countries. Mortality rates of patients with FIGO grade 3 endometrioid ECs are almost similar to that of uterine serous carcinoma and clear cell carcinoma. In 2013, the Cancer Tumour Genome Atlast (TGCA) identified POLE gene mutations in a subset of ECs, predominantly in the endometrioid subtype with high FIGO grade. While it has been suggested that POLE mutation confers good prognosis, the data remains conflicting. Our study aims to evaluate the association between the POLE gene mutations and progression free survival in Asian women with FIGO grade 3 endometrioid EC. Methods: Forty-five Asian patients diagnosed with FIGO Grade 3 endometrioid EC between 2009 and 2013 were included. Next generation sequencing (NGS) performed utilizing the Ion Torrent Personal Genome Machine (PGM) and custom designed AmpliSeq panel for formalin fixed embedded (FFPE) tissue was performed. Using the Ion Reporter, mutations with at least 10% allele frequency and present in the COSMIC database were deemed to be pathogenic. All other mutations, excluding silent mutations, were considered as variants of unknown significance (VUS). Survival curves for pathogenic somatic POLE mutated and wild-type tumors were estimated by Kaplan-Meier method and compared using logrank test. Results: All detected pathogenic and VUS POLE gene mutations were missense mutations. Our results provide further evidence to corroborate the mutation effect of POLE gene with 100% recurrence free survival in FIGO Grade 3 endometrioid EC patients with pathogenic POLE gene mutations, extends to South East Asian women as well (median follow-up POLE vs wild type; 52.5 vs 45; p = 0.2). Pathogenic somatic POLE gene mutations were present in 25.5% (12/45) patients with Grade 3 endometrioid EC. All were still alive at the time of censure with no reports of relapse following initial treatment. Three of these women harbored mutations outside exons 9 to 14 with one mutation listed as pathogenic in colorectal carcinomas. Among women without the pathogenic somatic POLE mutation, recurrence was seen in 24.2% (8/33) with 15.1% (5/33) subsequently dying of the disease. Conclusion: POLE gene mutations confer a good prognosis for FIGO grade 3 endometrioid EC and will be important in clinical decision making. POLE wild-type patients potentially show have closer follow-up and should be considered for newer targeted chemotherapeutic agents. Citation Format: Adele Wong, Chik Hong Kuick, Wai Loong Wong, Jill M. Tham, Sorsiah Mansor, Loh Eva, Sudhanshi Jain, Sock Hoai Chan, Sze Huey Tan, Shao Tzu Li, Nadkarni N. Vikas, Sung Hock Chew, Joanne Ngeow, Wanjin Hong. POLE gene mutations confer good progression free survival in Asian women with FIGO grade 3 endometrioid endometrial carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1793.

A Review of Inflammatory Bowel Disease in Patients with Human Immunodeficiency Virus Infection

The coexistence of inflammatory bowel disease and human immunodeficiency virus infection is rare but does occur. Since immune mechanisms have an important role in the pathophysiology of both diseases, we might expect HIV infection to significantly alter the course of IBD. The pathophysiologic relationship between HIV and IBD is complex and controversial. Although many studies suggest spontaneous improvement in IBD symptoms and stable remissions after HIV infection, there are reports of relapse and new onset IBD with the decline in CD4 counts. Many of the opportunistic infections in HIV can mimic IBD and can lead to misdiagnosis and treatment as IBD. The treatment of IBD in HIV is associated with an increased risk of infections and lymphoma, and careful follow-up is essential.

Lineage Switch As a Relapse Mechanism of Pre-B Acute Lymphoblastic Leukemia Following CD19 CAR

Resistance or relapse following adoptive immunotherapy can occur as a result of antigen loss. T cells armed with chimeric antigen receptors (CARs) targeting CD19 have shown remission rates of over 70% in early clinical trials, although reports of relapse in the presence of persistent CAR T cells are emerging. To further investigate potential resistance mechanisms to CAR T cell therapy, we used 2 syngeneic murine pre-B acute lymphoblastic leukemia (ALL) cell models driven by E2a:PBX1 and Eu-RET. Transplantable cell lines generated from both models have high expression of CD19, CD22, B220, CD43 and CD127, with absence of surface immunoglobulins consistent with a pre-B cell phenotype and result in lethality within 21 days. Treatment with CD19 CAR T cells induced long-term remission with persistence of CAR T cells beyond 100 days. However, mice bearing E2a:PBX1-driven leukemia experienced relapses occurring in the majority of CAR treated animals within 1 year, all with loss of CD19 expression. Relatively early post-CAR relapses retained a pre-B phenotype with isolated loss of CD19 extracellular expression by flow cytometry, loss in CD19 exon 1 and 2 mRNA but intact mRNA for all other CD19 exons. In contrast, late post-CAR relapses demonstrated complete loss of CD19 protein and mRNA expression with concomitant loss of the major B cell transcription factors PAX5 and EBF1 suggesting loss of the B-cell developmental program. Furthermore, late post CD19 CAR relapses typically gained myeloid, stem cell or T cell phenotypic markers, consistent with a lineage switch, which was confirmed at the genomic level by RNA-seq of multiple late relapse samples. We could not identify cells in leukemia culture lacking pre-B phenotype either by single cell cloning following depletion of CD19+ cells indicating that cells with the late relapse phenotype do not exist as a rare population. Finally, we could also demonstrate intermediate phenotypes of post-CD19 CAR relapse in vivo with co-expression of both myeloid (Gr1, CD11b) and B cell markers (B220, CD22) on the same cells, suggesting a differentiation rather than a selection process. We next undertook serial in vivo passaging experiments, and confirmed leukemic-initiating potential of all CD19-loss relapses irrespective of relapse phenotype. Interestingly, leukemic relapse with CD19 expression loss that retain a B-cell program rapidly regain CD19 upon in vivo passage in the absence of CD19 CAR pressure. However, relapses due to lineage reprogramming retained a stable myeloid phenotype upon serial passage without regain of CD19 or other B cell markers. Knock-out of CD19 from leukemic cells using the CRISPR/CAS system did not alter proliferative capability or phenotype during prolonged (30 day) culture and did not diminish engraftment capacity and lethality in vivo, confirming that loss of CD19 alone is insufficient to drive lineage switch. Overall, we demonstrate a novel mechanism of resistance to immunotherapy via lineage switch and demonstrate reprograming potential of ALL under lineage-selective pressure. This observation was repeatedly seen in one murine model (E2a:PBX1) but not in another (Eu-RET), suggesting that the potential for this to occur may depend on the genetic subtype and at what stage the initiating mutation occurred. These results have important clinical implications for the development of antigen-targeting therapies for ALL and, potentially, other cancers. DisclosuresNo relevant conflicts of interest to declare.

Interactive voice response for relapse prevention following cognitive-behavioral therapy for alcohol use disorders: A pilot study.

Relapse after alcoholism treatment is high. Alcohol Therapeutic Interactive Voice Response (ATIVR) is an automated telephone program for posttreatment self-monitoring, skills practice, and feedback. This pilot study examined feasibility of ATIVR. Participants (n = 21; 57% male) had access to ATIVR for 90 days following outpatient group cognitive-behavioral therapy (CBT) to make daily reports of mood, confidence in sobriety, urges to use substances, and actual use. Reports of relapse or risk were followed with additional questions. Participants received personalized therapist feedback based on responses, and could access recorded CBT skill reviews. Pre-post assessments included: alcohol consumption (Timeline Follow-Back), self-efficacy (Situational Confidence Questionnaire), and perceived coping ability (Effectiveness of Coping Behaviors Inventory). Participants called on 59% of scheduled days and continued making calls for an average of 84 days. Following ATIVR, participants gave feedback that ATIVR was easy to use and increased self-awareness. Participants particularly liked the therapist feedback component. Abstinence rate increased significantly during ATIVR (p = .03), and both self-efficacy and coping significantly improved from pre-CBT to post-ATIVR (p < .01). Results indicate ATIVR is feasible and acceptable. Its efficacy should be evaluated in a randomized controlled trial.

A Phase II Study of Lenalidomide for Previously Untreated Deletion (del) 5q Acute Myeloid Leukemia (AML) Patients Age 60 or Older Who Are Not Candidates for Remission Induction Chemotherapy (Southwest Oncology Group Study S0605)

AbstractAbstract 332 Background:Older patients (pts, ≥60 years [yrs]) with AML have a dismal prognosis; the majority are not treated with any type of chemotherapy. Many have antecedent myelodysplastic syndromes (MDS), and 20–30% harbor chromosome 5 abnormalities. Lenalidomide (LEN) yields hematologic responses in 67% of lower-risk MDS pts with the del(5q) cytogenetic lesion, and complete responses (CRs) in 20% of higher-risk del(5q) MDS pts, all with isolated lesions. This Phase II study explores the safety and efficacy of single agent LEN in previously untreated older pts with AML and the del(5q) abnormality. Method:Untreated older pts with AML defined by 2001 World Health Organization criteria (without t(15;17)) who harbored a del(5q) cytogenetic abnormality (alone or in combination with other abnormalities) and who declined or were felt to be poor candidates for intensive induction chemotherapy were eligible. Pts were treated with LEN 50mg daily for up to 28 days as induction therapy. Concomitant cytotoxic or growth factor therapies were not allowed. Pts achieving stable disease or better per day 28 bone marrow assessment received post-remission LEN 10mg daily for 21 days of a 28-day cycle until disease progression or unacceptable toxicities. Enrollment from October 2006 through June 2010 was in 2 stages: 20 pts were registered; if at least 1 CR/CRi was observed using International Working Group response criteria, another 20 pts were to be enrolled. The study was designed with a critical level of 4.7% (erroneously concluding the regimen warrants further study if the true response rate is 5% or less) and power of 92% (probability of concluding that a response rate of 20% warrants further study). Result:Of 41 patients enrolled, 4 were excluded (2 without AML, 1 without del(5q), and 1 died prior to receiving therapy), leaving 37 for toxicity and efficacy analyses. Median age was 74 yrs (range, 60–94), 21 (57%) were female, 33 (89%) white, and 19 (51%) had prior MDS. Median presenting white blood cell count was 2,600 mcl (range, 600–658,000), and 30 (81%) had a performance status of 1. Of the 37 evaluable pts, 29 had pretreatment cytogenetic studies evaluated centrally. Two pts displayed no demonstrable abnormalities (but had del(5q) by fluorescence in situ hybridization); 5 had isolated del (5q); and 22 (76%) had complex karyotypes (≥3 abnormalities). Seven patients were removed from protocol therapy due to toxicities (infection, renal, respiratory, gastrointestinal, and rash), and 4 deaths occurred that were at least possibly related to therapy: 2 respiratory, 1 cardiac, and 1 febrile neutropenia. Five additional patients had grade 4 non-hematologic toxicities: hypocalcemia (2), fatigue (2), infection (1). Fourteen pts (38%) completed protocol induction therapy. Four pts (11%) of the 37 evaluable pts achieved CR/CRi following induction therapy, all of whom had complex karyotypes; 3 of the 4 relapsed after 1, 2, and 4 months, and the 4th died 13 months after CR without a report of relapse. Thirteen (35%) pts had stable disease following induction therapy; 8 went on to protocol post-remission therapy. Thirty-three of the 37 pts have died and the median overall survival was 2 months (95% CI, 1 to 4 months). The follow-up time of the 4 survivors was between 6 and 23 months. Conclusion:LEN as a single agent has modest activity and expected toxicity in older del(5q) AML pts, particularly when compared to other single-agent molecularly-targeted approaches, such as FLT3 inhibitors. Future trials will combine LEN with cytoxic or hypomethylator therapies in older del(5q) AML pts. Disclosures:Sekeres:Celgene: Honoraria. Off Label Use: Lenalidomide in (del)5q AML. Lancet:Celgene: Research Funding. List:Celgene: Research Funding.

Schizophrenia in a worldwide perspective: explaining similarities and differences

Schizophrenia in a worldwide perspective: explaining similarities and differences

Preliminary Results of Southwest Oncology Group Study S0106: An International Intergroup Phase 3 Randomized Trial Comparing the Addition of Gemtuzumab Ozogamicin to Standard Induction Therapy Versus Standard Induction Therapy Followed by a Second Randomization to Post-Consolidation Gemtuzumab Ozogamicin Versus No Additional Therapy for Previously Untreated Acute Myeloid Leukemia.

Abstract 790Study S0106 is an open-label randomized phase III trial to evaluate the benefit and toxicity of adding Gemtuzumab ozogamicin [GO] to standard induction therapy, followed by a post-consolidation randomization to receive either 3 additional doses of GO or no additional therapy [OBS]. Eligible patients were adults (age 18-60) with previously untreated de novo nonM3 AML. Patients were randomized (stratified by age <35 vs 35+) to receive induction therapy with daunorubicin (45 mg/m2 D1,2,3) and cytarabine (100mg/m2/d CI D1-7) and GO (6 mg/m2 D4) [AD+GO] (DeAngelo,2003) versus standard induction therapy with daunorubicin (60 mg/m2 IV D1,2,3) and cytarabine (100mg/m2/d CI D1-7) [AD]. Patients in either arm who failed to achieve aplasia at D14 were retreated with AD. Patients achieving CR received consolidation therapy with 3 courses of high dose cytarabine (3 gm/m2/q12h D1,3,5 every 28 days). Patients remaining in CR after consolidation were eligible for a second randomization (stratified by cytogenetic risk category at diagnosis and use of GO during induction) between 3 doses of GO (5 mg/m2 every 28 days) or OBS.627 patients were registered on study S0106 from May 15, 2004 though July 23, 2009, the cutoff for the second interim analysis of induction outcomes (which by protocol plan was based on the first 456 eligible patients) and first planned interim analysis of disease-free survival measured from the post-consolidation randomization [DFS] (based on the first 64 relapses or deaths). Complete response [CR] rates were 150/277=66% (AD+GO) and 159/229=69% (AD), ruling out the originally hypothesized 12% increase with AD+GO at the prespecified significance level (P<0.0025). Including CRs with incomplete hematologic recovery, the response rates were 74% in both arms. Importantly, relapse-free survival measured from the date of CR [RFS] was not significantly better in the AD+GO arm (hazard ratio [HR]=1.00, 95% confidence interval [CI] 0.69-1.44, P=0.50), unlike preliminary results of the MRC AML15 trial (Burnett, Blood 2006 108: Abstract 13). Among all patients evaluable for induction toxicity, the rate of fatal adverse events [AEs] at least possibly attributable to treatment (most commonly hemorrhage, infection and/or ARDS) was significantly higher in the AD+GO arm (15/260=5.8% vs 2/255=0.8%, P=0.002). One death in the AD+GO arm was attributable to sinusoidal obstruction syndrome (SOS). Notably, the AE rate in the AD+GO arm is similar to previous SWOG AML trials, while the rate in the AD arm is remarkably low (CI 0.1-2.8%). The first planned interim analysis of post-consolidation therapy evaluated 150 patients randomized between GO and OBS, only 7 of whom had unfavorable cytogenetics. 36 GO and 25 OBS patients have relapsed, and one GO and 2 OBS patients have died without report of relapse. DFS was not significantly better in the GO arm (HR=0.66 for OBS compared to GO, CI 0.40-1.08, one-sided P=0.95); moreover the hypothesized benefit of GO (HR=1.5) was rejected at the prespecified significance level (P<0.001). Based on these results – the lack of improvement in CR rate or RFS and the higher fatal induction AE rate on the AD+GO induction arm, and the lack of improvement in DFS on the post-consolidation GO arm – the SWOG DSMC on August 11, 2009 recommended closure of both the induction and post-consolidation randomizations. Among all eligible patients with any follow-up, the estimated median overall survival from study entry was 31 months with AD+GO induction (CI 22-39 months) and 35 months with AD (CI 24-41 months).In this study, the addition of GO to induction therapy or as post-consolidation therapy did not improve the CR rate, RFS, post-consolidation DFS, or overall survival, but was associated with a significantly higher risk of fatal induction adverse events. Disclosures:No relevant conflicts of interest to declare.

Efalizumab-induced thrombocytopenia: report of relapse after re-administration

Although a reversible, sometimes severe, drug-induced thrombocytopenia is a recognized adverse drug reaction (ADR) in patients with psoriasis treated with efalizumab, definite proof for the association of thrombocytopenia with efalizumab is still lacking (currently level II evidence for ADR). We report a patient with psoriasis who had two episodes of reversible thrombocytopenia during efalizumab; the first occurred 5 months after introduction of the medication and the second 4 months after re-introduction of efalizumab for relapsing psoriasis. The development of a second episode of thrombocytopenia on re-exposure to efalizumab provides, for the first time in the literature to our knowledge, definite (level I) ADR evidence for efalizumab-induced thrombocytopenia.

Predicting relapse after cessation of Lamivudine monotherapy for chronic hepatitis B virus infection.

There have been reports of relapse after cessation of lamivudine monotherapy for hepatitis B virus (HBV) infection. The aim of this study was to examine factors that predict posttreatment relapse. Comparison 22 patients who experienced relapse with 11 who did not after cessation of therapy showed that predictive factors for nonrelapse were hepatitis B e antigen seroconversion and duration of undetectable HBV DNA load (<0.7 log IU/mL), as determined by HBV real-time detection direct testing. However, 7 of 12 patients with seroconversion experienced relapse after cessation of therapy. Multivariate analysis revealed that the duration of an undetectable HBV DNA load was the only independent predictive factor for nonrelapse (odds ratio, 0.50; 95% confidence interval, 0.27-0.9). More-prolonged lamivudine therapy is required after seroconversion, and persistent duration of an HBV DNA level of <0.7 log IU/mL for >6 months can more accurately aid in the decision of when to stop lamivudine therapy.

Therapeutic approaches to subcutaneous mycoses.

Subcutaneous mycoses, which are much less common than superficial fungal infections, are characterized by a heterogeneous group of infections that often result from direct penetration of the fungus into the dermis and subcutaneous tissue through traumatic injury. The fungus spreads by local deep tissue invasion from the inoculation site. The disease usually remains localized and then slowly spreads to adjacent tissue and eventually to the lymphatics. More rarely, hematogenous dissemination is observed. There are usually various clinical features and thus a broad range of differential diagnoses. The common subcutaneous mycoses are sporotrichosis, chromoblastomycosis, phaeohyphomycosis, eumycotic mycetoma, and hyalohyphomycosis. Many subcutaneous mycoses are confined to the tropical and subtropical regions, but some, such as sporotrichosis, are also prevalent in temperate regions. Subcutaneous mycoses can occur in healthy individuals. In immunocompromised individuals, these infections can disseminate widely. Treatment usually involves use of antifungal agents and/or surgical excision. Treatment of some serious subcutaneous mycoses remains unresolved, and there have been reports of relapses or progression during therapy and problems with lack of tolerability of antifungal drugs. Identification of the etiologic agent by culture is essential for prognostic and management considerations, since some fungi are more frequently associated with dissemination. Results of antifungal susceptibility tests may provide valuable information for deciding the appropriate method of treatment. Development of new antifungal agents and combination therapies may result in improvement in the management of subcutaneous mycoses in the future.

Case reports of the reemergence of psychotic symptoms after conversion from brand-name clozapine to a generic formulation

Background: The use of generic drugs has resulted in considerable cost savings; however, whether all generics are truly bioequivalent to their brand-name counterparts is questionable. Although the efficacy of clozapine in the management of treatment-resistant schizophrenia has been well established, reports of relapse after conversion to a generic formulation are becoming more common. Objective: This article presents 7 case studies of patients in a long-term residential care facility who experienced a relapse of psychotic symptoms when the pharmacy inadvertently switched their therapy from brand-name clozapine to a generic formulation. Neither patients, physicians, nor staff of the facility were aware of this switch. Possible reasons for the apparent increased risk of relapse in some patients switched to the generic formulation of clozapine are explored, with reference to US Food and Drug Administration bioequivalence standards and reports. Results: All 7 patients, whose condition had been well stabilized with brand-name clozapine, experienced a rapid and profound deterioration after the switch to the generic formulation. Five patients required hospitalization. All patients responded well when brand-name clozapine was reinstated. Conclusion: The findings suggest that brand-name clozapine and the generic formulation may display important clinical differences, and a comparable therapeutic response may not be achievable despite adequate monitoring. Large, controlled, prospective trials are needed to clarify the potential for treatment failure with the use of generic clozapine.

An unusual cause of large bowel obstruction.

all ages and affects both sexes equally. The effect on vision can be devastating due to retinal arteritis, retinal necrosis and rhegmatogenous retinal detachment. It is most commonly caused by...

Relapsing Pseudomembranous Colitis

Summary:Pseudomembranous colitis secondary to C. difficile and its toxin(s) is a well‐recognized disease in children and usually responds to treatment with oral vancomycin. There are well‐documented reports of relapse in adults after initial successful treatment with vancomycin. This report documents relapse in a child who developed diarrhea following treatment of pseudomembranous colitis. Stool cultures were negative for C. difficile at the end of the initial course of treatment, but the organism was isolated from the stool when the diarrhea recurred. The symptoms improved following a second course of treatment with vancomycin and have not recurred during 8 months of followup monitoring.

Muco-epidermoid tumour of the bronchus in a child

Tinkasimire, a 6 year old Mutoro boy, was admitted in February 1968 complaining of pallor, headache, lassitude and cough. The cough had been present for 24 years and was unproductive. There had been no haemoptysis. He had no other symptoms referable to the respiratory system or to explain his anaemia. On examination. He was a thin boy, markedly anaemic, apathetic, with gross clubbing of fingers and toes. A chest X-ray showed a round, discrete mass in the left lower lobe. Hb was 7.0 g%, normocytic and normo-chromic. His symptoms were attributed to anaemia. He was transfused and in March a left thoracotomy was performed. A mass was found embedded in the left lower lobe, and due to vascularization and adhesions left lower lobectomy was required to remove it. Mediastinal glands appeared normal. Post-operative course. He improved rapidly, his clubbing had disappeared within 6 weeks and no further symptoms have been reported since then. Because of the divided opinions on the histological diagnosis of the tumour removed further attempts were made to define an abdominal primary neoplasm. Abdominal aortography was performed, and in May an exploratory laparotomy was done for the same reason. No evidence of a neoplasm or glandular enlargement was found, and a year later there has been no report of relapse.

Tuberculous meningitis in infants and children.

I. INTRODUCTION THE PAST decade has seen a new and satisfying impetus to the study and treatment of all forms of tuberculosis, but particularly of tuberculous meningitis, a disease heretofore of interest as a diagnostic problem only. 1 However, because of its uniformly fatal outcome, after the establishment of the diagnosis interest in therapeusis was at a low ebb. Since the advent of new antimicrobial agents against tuberculosis, especially streptomycin, p -aminosalicylic acid (PAS), thiazolsulfone (Promizole), and, more recently, isoniazid (isonicotinic acid hydrazide) our attitude toward tuberculous meningitis has become a much more optimistic and positive one. There is no question that the life of a patient with this disease can be prolonged, in many cases for a long period of time. Whether or not these patients are permanently cured, we still do not know. Reports of relapses three to four years after the onset of therapy continue to filter