High HSP70-membrane expression on leukemic cells from patients with acute myeloid leukemia is associated with a worse prognosis.
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Comparison of the clinical and laboratory characteristics of infants and children with urinary tract infection caused by E. coli (n = 107) or other pathogens (n = 32) yielded a significantly higher association of non-E. coli disease with urinary tract anomalies, younger age, and previous antibiotic treatment. Underlying urinary tract anomalies were noted in 18 patients, of whom 14 (77%) were infected by non-E. coli pathogens. The most frequent anomaly was grade 3-4 vesicoureteral reflux (50%), followed by hydronephrosis (22.7%), ureteropelvic junction obstruction (9%), hypospadias (4.5%), pinpoint meatus (4.5%), and dysplastic kidney (4.5%).
Unmet needs for services, such as housing and psychiatric treatment, are relatively common among HIV-infected individuals; however, the effects of different types of unmet needs on health-care outcomes are not well understood. This study describes unmet psychosocial needs and their relationship with health-care outcomes among individuals receiving HIV care in the southeastern US (n=526). We used multivariate logistic regression to examine the association of seven categories of unmet needs with HIV medication use and adherence. Most participants (84.5%) reported at least one service need in the past year. Nearly half (47%) of participants with service needs reported that at least one need was not met. Participants with one or more unmet needs were less likely to be taking any HIV medications (p = 0.007) and reported poorer medication adherence (p=0.013). The specific unmet needs for benefits (including Social Security, health insurance and prescription coverage) (p = 0.006) and a support group (p=0.040) were associated with being less likely to be taking any HIV medications. Unmet need for mental health-related counseling was associated with poorer medication adherence (p=0.003). Study findings regarding the high level of unmet need and the association of unmet need with poorer outcomes illustrate the importance of interventions to address these needs.
Providing behavioral treatment for mental health and substance use disorders among HIV-infected individuals is critical because these disorders have been associated with negative outcomes such as poorer medication adherence. This study examines the effectiveness of an integrated treatment model for HIV-infected individuals who have both substance use and mental disorders. Study participants (n = 141) were recruited through routine mental health and substance abuse screening at tertiary Infectious Disease clinics in North Carolina. The study participants received integrated mental health and substance abuse treatment for one year and were interviewed at three-month intervals. Using linear regression analyses, we detected statistically significant decreases in participants' psychiatric symptomatology, illicit substance use, alcohol use, and inpatient hospital days. Participants also reported fewer emergency room visits and were more likely to be receiving antiretroviral medications and adequate psychotropic medication regimens at follow-up. No changes in sexual risk, physical health, or medical adherence were detected after treatment participation. This integrated treatment model offers an option for treating HIV-infected individuals with mental health and substance use disorders that can be adapted for use in a variety of psychiatric and medical treatment settings.
Long travel times have been identified as a significant barrier to accessing mental health and other critical services. This study examines whether distance to treatment was a barrier to receiving outpatient mental health and substance abuse care for HIV-positive persons when transportation was provided. Data from a cohort of HIV-positive persons who participated in a year-long substance abuse and mental health treatment programme were examined longitudinally. Transportation, which included buses, taxis, and mileage reimbursement for private transportation, was provided free of charge for participants who needed this assistance. Nearly three-quarters (74%) of participants utilized the transportation services. No statistically significant differences in retention in, or utilization of, the mental health and substance abuse treatment programme were identified by distance to the treatment site. This analysis demonstrated that increased distance to care did not decrease utilization of the treatment programme when transportation was provided to the client when necessary. These results provide preliminary evidence that distance to substance abuse and mental health services need not be a barrier to care for HIV-positive individuals when transportation is provided. Such options may need to be considered when trying to treat geographically dispersed individuals so that efficiencies in treatment can be attained.
Many HIV-positive individuals face multiple barriers to care and therefore frequently experience unmet medical and support services needs. Rural areas often lack the infrastructure to support the delivery of comprehensive HIV services; however, few studies have examined service barriers faced by rural residents with HIV/AIDS, particularly in the South where two-thirds of people living with HIV/AIDS in rural areas reside. We surveyed North Carolina HIV/AIDS case managers (N = 111) employed at state-certified agencies regarding barriers to medical and support services that influence medication adherence for their rural and urban-living clients. For each of the seven barriers assessed (long travel for care, HIV-related stigma, and a lack of transportation; HIV-trained medical practitioners; housing; mental health services and substance abuse treatment), a substantial proportion of case managers (29-67%) reported it was a 'major problem'. For five of the seven barriers, rural case managers were significantly more likely to identify the barrier as a 'major problem'. Multivariate analysis revealed that rural case managers and case managers with more female clients reported a greater number of barriers. Because unmet medical and support service needs may result in poorer outcomes for HIV-positive individuals, barriers to these services must be identified and addressed, particularly in rural areas which may be highly underserved.
Poliovirus receptor-related (PRR) proteins belong to the Nectin-adhesion molecules' group, are expressed on endothelial cells and on CD34(+) stem cells and mediate the organization of endothelial and epithelial junctions. There is evidence to suggest, that those receptors could have a role in leukemia. We have studied the expression of PRR molecules PRR1 and PRR2 on mononuclear bone marrow (BM) cells of 55 patients with acute myeloid leukemia (AML) at first diagnosis by FACS-analysis using directly Phycoerythrin-labeled markers (PRR1 clone R1.302.12; PRR2 clone R2.477.1) in combination with other Fluorescein conjugated antibodies to evaluate the blast phenotype in AML. The leukemic gate included blasts and residual monocytes and lymphocytes. A case was defined as positive, if more than 20% of the gated cells expressed the regarding receptor. We could demonstrate, that on average 35% PRR1(+) or 45% PRR2(+) cells in AML were found. Within FAB-types we observed a high PRR1 expression in cases with M3 and M4 and lowest expressions in M0 and M5; a high PRR2 expression was found in cases with M3, M4, M5 and M1 and lowest expressions in M0 and M2. Separating our patients' cohorts in cytogenetic risk groups we could detect a significant higher proportion of PRR1(+) cases (73% vs. 25% of cases, P = 0.009) or PRR1(+) cells (57% vs. 18% of cases, P = 0.001) in the cytogenetic favorable risk vs. poor risk group (75% vs. 32% PRR2(+) cases). Moreover cut-off-values with a maximum probability for a significant differentiation between cases with higher or lower levels of these markers could be found: cases with >78% PRR1(+) and cases with >77% PRR2(+) cells were characterized by a tendency for longer relapse free survival times. Qui-square analyses showed, that 3 of 4 cases with FAB-type M3 (P = 0.03) or a favorable karyotype (P = 0.04) were found in the group with >7% PRR1(+) cells, due to only few cases available a similar correlation, however, could not be found in cases with >78% PRR2(+) cells. We can conclude, that blasts in AML regularly express PRR1 and PRR2. Cases with a high expression of PRR1 or PRR2 are characterized by a more favorable prognosis. With respect to the individual PRR-status the benefit of biological response modifiers as priming agents, differentiation mediators or factors influencing cellular metabolisms inducing factors can be discussed under a new point of view.
Costimulatory molecules such as lymphocyte function-associated antigen (LFA)-1 (CD11a), LFA-3 (CD58), intercellular adhesion molecule (ICAM)-1 (CD54), neuronal cell adhesion molecule (NCAM) (CD56), B7-1 (CD80), or B7-2 (CD86) are important regulatory elements in healthy immunological cascades, but their role in acute myeloid leukemia (AML) has only been rarely investigated. We studied their expression on mononuclear bone marrow (BM) cells from 105 patients with AML at initial diagnosis and evaluated their prognostic significance. Fluorescence-activated cell sorter (FACS) analyses were performed using antibodies directly conjugated with fluorescein. A BM sample was considered positive if more than 20% of the cells in the blast containing gate expressed the respective marker. The surface expression of CD11a (27 of 29 cases positive with an average of 71% positive blasts; 27(+)/29, 71%), CD54 (23(+)/33, 37%), CD56 (24(+)/93, 20%), CD58 (29(+)/29, 95%), CD80 (13(+)/28, 30%), and CD86 (19(+)/29, 39%) was measured. The expression of these markers in different French-American-British (FAB) classification types (M0-M5) was heterogeneous, except for CD56, which showed a higher proportion of positive cells in monocytic subtypes of AML. In addition, cases with a "poor risk" karyotype as well as patients succumbing to "early death" after double induction therapy according to the AML Cooperative Group (CG) protocol were characterized by a high expression of CD56. Relapse-free survival analyses demonstrated that patients with more than 8% CD56(+) cells in the BM relapsed significantly sooner. CD54 was preferentially expressed in AML M4(eo) and in addition in "favorable" cytogenetic risk groups and in cases that had responded to AML-CG therapy. Only very high proportions (>60%) of CD54(+) cells were associated with a lower probability for relapse-free survival. CD80 and CD86 expressions were similar in all FAB types. Patients who had responded to AML-CG therapy showed higher CD80 proportions and lower CD86 proportions compared to the "nonresponder" group. Whereas cases with more than 15% CD80(+) cells had a significantly lower probability for relapse-free survival, only cases with more than 65% CD86(+) were characterized by a significantly lower probability for relapse-free survival. Expression profiles of CD11a and CD58 were not associated with specific FAB types or prognostically relevant groups. We can conclude: (1) Expression of costimulatory molecules in AML is very variable. This reflects the great diversity of immunophenotypes in AML. (2) CD56 is mainly expressed in monocytic subtypes of AML. CD56(+) subtypes of AML seem to be a separate entity with a worse prognosis independent of the karyotype. (3) High expression of some costimulatory molecules correlates with a worse prognosis concerning relapse-free survival times.
During the period 1989-1996, we retrospectively investigated 104 children and adolescents with Helicobacter pylori infection diagnosed by gastroscopy. The median age was 12.11 +/- 3.31 years, 55% were female and 45% male. The chief complaint of 92% of the children was abdominal pain, mainly epigastric. The typical macroscopic finding was nodular gastritis. The most common microscopic picture was chronic superficial gastritis with lymphatic follicles and the presence of Helicobacter pylori. We demonstrated correlation between these gastroscopic and histological findings. Children who suffered from peptic ulcer were older than those with nodular gastritis. Most of the Helicobacter pylori positive patients were treated with triple drug therapy. The combination of drugs changed throughout the years according to the newly accepted strategies in the treatment of Helicobacter pylori. The majority of children reported a decrease in symptoms on completion of therapy. Urea breath test was an efficient and convenient method for the follow-up of patients with Helicobacter pylori infection.
OBJECTIVES: Interactions between hemopoietic cells and the stromal microenvironment or immunoreactive cells are mediated by specific cell surface receptors. The expression of those molecules may alter the adhesive qualities (mobility and homing) as well as immune response behavior of leukemic blasts. L-Selectin (CD62L) is suggested to play a role in the redistribution and homing of hemopoietic progenitor cells to the bone marrow (BM). Down-regulation of L-selectin is responsible for mobilization of blasts from the BM into the circulation and ligation of L-selectin stimulates proliferation of progenitor cells. This could have an influence on the process of leukemia. METHOD: We have studied the expression of L-selectin on mononuclear BM cells of 36 acute myeloid leukemia (AML) patients at first diagnosis by FACS analysis using a directly fluorescein isothiocyanate conjugated antibody (clone DRE G56). RESULTS: On average the patients presented with 88% blasts in the BM. The expression tended to be higher in primary (p) AML compared with secondary (s) AML. L-Selectin was very heterogenously expressed in all FAB groups. Highest expression was found in cases with AML-M4 with four of nine cases presenting with an inv(16) karyotype. Separating our patient cohort in cytogenetic risk groups we could detect a significantly higher expression of L-selectin in cases with a 'good risk' karyotype and a very low expression in cases with a 'bad risk' karyotype (P = 0.037). Comparing patients who achieved remission after double induction therapy (responders) with patients who showed persisting disease (non-responders) we found a higher percentage of L-selectin+ cases or cells in the responder group than in the non-responder group, although the differences were not significant because of only five cases in the 'non-responder' group. Evaluating cut-off points greatest differences in relapse-free survival probabilities were found in patients who presented with > or = 30% L-selectin+ BM cells compared with cases with < 30%: 86% of cases with > or = 30% L-selectin+ cells were still in remission after a mean follow up time of only 8 months compared with only 46% in the group with < 30% L-selectin+ cells. CONCLUSIONS: We can conclude that (i) expression of L-selectin on AML blasts is variable. This reveals the great diversitiy of immunophenotypes in AML and might contribute to identify individual blast phenotypes in order to detect minimal residual disease in remission. (ii) Low L-selectin expression correlates with a bad cytogenetic risk, with a lower probability to achieve remission and with a shorter relapse-free survival time. This might reflect a decreased homing of the blasts to the BM as well as an impaired cytotoxic T-cell reaction against leukemic cells. The expression of L-selectin on leukemic blasts might be influenced by different cytokine therapies (e.g. with interferon alpha) and this might result in an altered hematologic reconstitution after cytotoxic therapies as well as in an altered immunologic recognition of blasts.
BACKGROUND AND AIM: Although immunization of infants against hepatitis B virus (HBV) is the most effective way to prevent infection, duration of the afforded protection is unknown. Titers of anti-HBV antibodies decline with time, especially during the first few years after vaccination. Anti-HBV antibody levels were measured in the serum of vaccinated children in order to determine the duration of the response afforded by the primary course of HBV vaccine. METHODS: The immunity derived from the HBV vaccine was assessed by measuring antibody levels in 122 healthy children who were vaccinated in a routine vaccination program in Israel. RESULTS: Ninety-four children (77.1%) had detectable antibodies levels (HBsAb titer > or = 10 mIU/ml): 59 (48.4%) of the children had high antibodies levels (HBsAb titer > 100 mIU/ml). Twenty-eight children (22.9%) had undetectable antibodies levels (HBsAb titer < 10 mIU/ml). When the children were divided into three groups according to the time elapsed since vaccination, it was found that the antibody levels declined with time (p < 0.009). Most of the children with undetectable antibody levels belonged to the 5 to 8-y post-vaccination group (36.1% vs 20% and 14.6% for the 2.5 to 5-y and 1 to 2.5-y groups, respectively, p < 0.01). The mean HBsAb declined in relation to the length of time post-vaccination (226.9 +/- 248.2 mIU/ml for 1-2.5 y post-vaccination, 199.0 +/- 235.7 mIU/ml for 2.5-5 y and 90.4 +/- 138.5 for 5-8 y, p < 0.05). No correlation was found between HBsAb titers and gestational age, birthweight and parental origin, although females generated higher mean antibody levels than males (207.3 +/- 217 mIU/ml vs 141.9 +/- 218.9 mIU/ml, p < 0.05). CONCLUSION: Our data demonstrate a steady decline in anti-HBV titers over time after routine vaccination against HBV in Israel. The most significant decline occurred 5-8 y post-vaccination.
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As the systemic administration of etoposide is effective in the treatment of relapsed and metastatic brain tumours, a pilot trial was designed to study the feasibility of intraventricular administration of etoposide in such patients. 14 patients aged 2.1 to 33.2 years were treated with intraventricular etoposide simultaneously with either oral or intravenous chemotherapy with trofosfamide or carboplatin and etoposide. In 59 courses (1-12/patient) 0.5 mg etoposide was administered daily via an indwelling subcutaneous reservoir for 5 consecutive days every 2-5 weeks over a period of 0-11 months. During 15 courses in 5 patients serial CSF samples were obtained and etoposide levels were determined by reversed-phase HPLC. Side effects included transient headache and bacterial meningitis, each during 2 courses. Pharmacokinetic data analysis in the CSF (11 courses, 4 patients) revealed a terminal half-life of 7.4+/-1.2 hours and an AUC of 25.0 +/- 9.5 microg h ml(-1)(mean +/- standard deviation). The volume of distribution at steady state and total clearance exhibited a large interindividual variability with mean values of 0.16 l and 0.46 ml min(-1)respectively. Intraventricularly administered etoposide is well tolerated. CSF peak levels exceed more than 100-fold those achieved with intravenous infusions. Further studies should be focused on optimizing the dose and schedule and on determining the effectiveness of intraventricularly administered etoposide.
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Examination of organizational and financial characteristics of the specialty substance abuse treatment system allows an understanding of how to meet the needs of clients in the system. Further, this assessment may afford insights into how the specialty sector may adapt in the changing environment of managed care. Data from Phase I of the Alcohol and Drug Services Study (ADSS) describe the specialty substance abuse treatment system in terms of type of care, setting, level of affiliation, licensure/accreditation, ownership, revenue sources, client referral sources, client's primary substance of abuse, and managed care. Although the system is largely outpatient and remains substantially two tiered in terms of public/private funding mix, it varies along a number of organizational and financial dimensions which have implications for system structure and facility viability in the changing environment of substance abuse treatment service delivery.
In view of the importance of type and intensity of services during substance abuse treatment, this chapter looks at treatment and support services that substance abuse clients have access to during treatment. Trends in services over recent years are described. Services available to clients in the current treatment system are reviewed. Several facility characteristics affecting access to services are examined. Different ways of defining access to services are discussed. Findings from the Alcohol and Drug Services Study are used to illustrate service patterns in the national substance abuse treatment system. Variations in service patterns by facility characteristics such as type of care, treatment setting, ownership, percent of facility dependence on public revenue, and level of affiliation are analyzed. The implication is that clients who enter into treatment at different types of facilities are likely to have access to certain types of services.