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Biomedical subjects

J Ritter

Publications and source records attributed to J Ritter.

At least 55 records · Page 3Linked to original sources
PubMed2000

Vulnerability to depression: cognitive reactivity and parental bonding in high-risk individuals.

Although various conceptual proposals have suggested that disruptions in childhood bonding processes may be linked to the origins of these cognitive structures, little research has tested these proposals. This study assessed the information processing of vulnerable individuals and its relationship to childhood bonding. Formerly depressed (vulnerable) and never depressed (nonvulnerable) individuals participated in a mood induction task followed by an attentional allocation task. Results indicated that vulnerable individuals uniquely diverted attention toward negative stimuli when they were in a negative mood. Furthermore, level of maternal caring was found to be associated with performance on this task for vulnerable individuals in this mood state. These data support the idea that cognitive variables form a pathway between troublesome parental-child/adolescent interactions and depression.

Adolescent↗
PubMed2000

Asparagine synthetase activity in paediatric acute leukaemias: AML-M5 subtype shows lowest activity.

Lack of sufficient cellular activity of asparagine synthetase (AS) in blast cells compared with normal tissue is thought to be the basis of the antileukaemic effect of L-asparaginase in acute lymphoblastic leukaemia (ALL). Although L-asparaginase is routinely used in ALL, its role and value in the treatment of acute myelogenous leukaemia (AML) is still being discussed. To evaluate the pharmacological basis for L-asparaginase treatment, we established pretreatment monitoring of the intracellular AS activity in blast cells of patients with AML and ALL. There was no general difference in AS activity between ALL and AML samples. Significantly lower AS activity, however, was found in the B-lineage ALL subgroups as well as AML-M5.

Adolescent↗
PubMed2000

Pegylated asparaginase (Oncaspar) in children with ALL: drug monitoring in reinduction according to the ALL/NHL-BFM 95 protocols.

Hypersensitivity reactions are relevant adverse effects of asparaginase therapy. Therefore, children treated with native Escherichia coli asparaginase in induction therapy of acute lymphoblastic leukaemia (ALL) or non-Hodgkin's lymphoma (NHL) were switched to the pegylated enzyme for reinduction under drug monitoring. Seventy children, including four patients with allergic reactions during induction, were given one dose of Oncaspar 1,000 U/m2 intravenously. Activity was determined every third or fourth day until it dropped below the limit of quantification. In current reinduction protocols [ALL/NHL-Berlin-Frankfurt-Münster (BFM) 95 trials], four doses of 10,000 U/m2 E. coli asparaginase deplete asparagine for about 2-3 weeks, therefore activities of >/= 100 U/l up to day 14 and >/= 50 U/l up to day 21 were targeted. In 66 patients without an allergic reaction during induction, the mean activity was 606 +/- 313 U/l, 232 +/- 211 U/l and 44 +/- 50 U/l after 1, 2 and 3 weeks respectively. In 44/66 patients, activity was >/= 100 U/l after 14 d. A rapid decline in activity was seen in the remaining 22 patients, including 8/22 patients who showed no activity after 1 week. Toxicity was low and comparable to the native enzymes but, in contrast to about 30% of hypersensitivity reactions with conventional reinduction therapy, no allergic reaction was seen. Substituting 4 x 10,000 U/m2 asparaginase medac for one dose of 1,000 U/m2 Oncaspar was safe and well tolerated. Comparable pharmacokinetic treatment intensity was achieved in about two-thirds of patients.

Adolescent↗
PubMed2000

Primary myelosarcomas are associated with a high rate of relapse: report on 34 children from the acute myeloid leukaemia-Berlin-Frankfurt-Münster studies.

Primary myelosarcomas are rare manifestations of acute myeloid leukaemia (AML) that precede bone marrow involvement. Out of 744 children observed during the AML-Berlin-Frankfurt-Münster (BFM) studies 87 and 93, 34 children presented with extramedullar myelosarcomas and no blasts (n = 21; 2.8%), or a low blast count (n = 13; 1.7%) in the bone marrow. Owing to the initially mild and variable symptoms, in some children (n = 12) diagnostic procedures were delayed and treatment intensity was reduced. At 0.65 +/- 0.13, the cumulative incidence of relapse was significantly higher than in other AML patients (0.28 +/- 0.02). The 5-year event-free survival was 0.19 +/- 0.08 (compared with 0.48 +/- 0.02 in AML-BFM studies 87/93; P(log rank) < 0.03). Overall, 18 out of 34 patients died from disease (estimated 5 year survival 0.44 +/- 0.09 compared with 0.55 +/- 0.02 in the AML-BFM-studies 87/93; P(log rank) = 0.35, n.s.). An early diagnostic workup is needed in children with unusual skin lesions or tumours, considering myelosarcoma as a primary manifestation of AML. Intensive AML-specific chemotherapy is recommended soon after diagnosis.

Acute Disease↗
PubMed2000

Volatile anesthetics differentially affect immunostimulated expression of inducible nitric oxide synthase: role of intracellular calcium.

BACKGROUND: Nitric oxide released by inducible nitric oxide synthase (iNOS) plays an important role in immune responses and systemic vasodilation in septic shock. Volatile anesthetics have been reported to interfere with signal transduction and gene expression. We studied the effect of volatile anesthetics on activity and expression of iNOS and potential mechanisms of action. METHODS: Nitrite release and iNOS expression were determined using the Griess reaction and Western and Northern blot techniques, respectively, in J774 murine macrophages stimulated with lipopolysaccharide and gamma-interferon in the absence and presence of various concentrations (0.25-2.0 minimum alveolar concentration [MAC]) of volatile anesthetics (i.e., halothane, enflurane, isoflurane, desflurane). Furthermore, potential interference of volatile anesthetics with specific signal transduction pathways was investigated. RESULTS: All volatile anesthetics, studied in a time- and dose-dependent manner, suppressed nitrite production and iNOS expression in J774 macrophages stimulated by lipopolysaccharide or gamma-interferon at clinically relevant concentrations. The inhibition was completely antagonized by ionomycin but unaffected by diacylglycerol, phorbol myristate acetate, and C2-ceramide. In contrast, in cells costimulated by lipopolysaccharide plus gamma-interferon, volatile anesthetics significantly increased nitrite production and iNOS expression independent of ionomycin and other mediators studied. CONCLUSIONS: Volatile anesthetics strongly reduced the mRNA and protein levels of iNOS and NOS activity after a single stimulation with lipopolysaccharide or gamma-interferon, most likely by attenuating intracellular calcium increase. Costimnulation with lipopolysaccharide plus gamma-interferon, however, results in maximum iNOS expression and activity, which are no longer inhibited but are potentiated by volatile anesthetics by unidentified mechanisms.

Adjuvants, Immunologic↗
PubMed2000

Endothelin in septic patients: effects on cardiovascular and renal function and its relationship to proinflammatory cytokines.

OBJECTIVE: To determine the time course of big-endothelin (big-ET) and its relationship to proinflammatory cytokines and organ function in sepsis. DESIGN: Prospective analysis in patients meeting criteria of severe sepsis as part of a multicenter study (RAMSES) with an anti-tumor necrosis factor monoclonal antibody F(ab')2 fragment (afelimomab). SETTING: University hospital intensive care unit. PATIENTS: A total of 23 nontrauma patients with severe sepsis or septic shock and ten multiple trauma patients. Septic patients were randomized for additional experimental treatment when initial interleukin (IL)-6 serum level was above 1000 pg/mL. INTERVENTIONS: Randomized patients received 1.0 mg/kg afelimomab or placebo three times daily over 3 days in addition to standard treatment. In each patient, serial blood samples for plasma big-ET and cytokine determination as well as clinical data were collected over 28 days. MEASUREMENTS AND MAIN RESULTS: Significantly increased concentrations of circulating big-ET were found in patients with severe sepsis as compared with healthy subjects. In septic patients, big-ET plasma levels were higher than in multiple trauma patients, and were more elevated in randomized than in nonrandomized patients. At study entry (day 0), big-ET reached a peak concentration and significantly correlated with IL-6 (r2 = .43) and IL-8 (r2 = .44) in patients with severe sepsis. Moreover, big-ET levels in septic patients, pooled over all observation days, correlated positively with pressure-adjusted heart rate, central venous pressure, pulmonary artery pressure, and pulmonary vascular resistance and correlated inversely with creatinine clearance (r2 = .54, .54, .59, .40, and .51, respectively, p = .0001). In all randomized septic patients, pressure-adjusted heart rate decreased from day 0 to day 2 in parallel with big-ET; however, a significant decrease in big-ET (day 0 to day 2) was only found in patients additionally treated with afelimomab. CONCLUSIONS: In patients with severe sepsis, big-ET plasma levels are markedly increased, even above those of multiple trauma patients, in close relationship to IL-6 and IL-8, and with significant correlation to renal function and pulmonary vascular tone.

Adult↗
PubMed2000

Prevalence of primary resistance to zidovudine and lamivudine in drug-naive human immunodeficiency virus type-1 infected patients: high proportion of reverse transcriptase codon 215 mutant in circulating lymphocytes and free virus.

The presence of primary zidovudine (AZT)-resistance (mutation T215Y/F) or lamivudine (3TC)-resistance (mutation M184V) was evaluated in 90 drug-naive patients infected with human immunodeficiency virus type-1 (HIV-1) between 1987 and 1997. The proportion of mutant strains in proviral samples or plasma viral samples was determined using a differential hybridization assay. Mutation T215Y/F was found in five (5.6%) patients infected between 1994 and 1997, whereas none of these patients harbored the mutation M184V. The T215Y/F mutation was present in the virus and/or provirus and persisted for at least two years. In one patient, the mutant provirus was associated with only wild-type free virus. Four of these patients were followed, and two were treated subsequently to a regimen containing AZT but with low response. The persistence of primary resistance mutations might depend on the proportion of these mutations at the time of infection, although mutant provirus might not give rise to replicating variants.

Anti-HIV Agents↗
PubMed1999

New strategies in diagnosis and treatment of thrombotic thrombocytopenic purpura: case report and review.

UNLABELLED: The pentad of thrombocytopenia, haemolytic anaemia, mild renal dysfunction, neurological signs and fever, classically characterizes the syndrome of thrombotic thrombocytopenic purpura (TTP). TTP usually occurs in adults but also children have been described with this condition. The disorder may take a relapsing course, termed chronic relapsing TTP (CRTTP), which although very rare, may also begin in childhood. Deficiency of a recently identified enzyme, the von Willebrand factor (vWF)-cleaving protease, seems to play a major role in the development of TTP. We report on a 3-year-old boy with a dramatic but typical clinical course of CRTTP. At the time of diagnosis, neurological deficits and multiple cerebral infarctions had already occurred. In plasma, vWF-cleaving protease was completely absent, both during acute TTP and in remission. There was no protease inhibitor detected. Regular infusions of fresh frozen plasma were successfully given for replacement on a prophylactic basis. CONCLUSION: Assay of von Willebrand factor-cleaving protease helps to diagnose a form of thrombotic thrombocytopenic purpura which may be managed by prophylactic treatment with fresh frozen plasma.

Blood Coagulation Tests↗
PubMed1999

Myelodysplastic syndrome, juvenile myelomonocytic leukemia, and acute myeloid leukemia associated with complete or partial monosomy 7. European Working Group on MDS in Childhood (EWOG-MDS).

We reviewed the clinical features, treatment, and outcome of 100 children with myelodysplastic syndrome (MDS), juvenile myelomonocytic leukemia (JMML), and acute myeloid leukemia (AML) associated with complete monosomy 7 (-7) or deletion of the long arm of chromosome 7 (7q-). Patients with therapy-induced disease were excluded. The morphologic diagnoses according to modified FAB criteria were: MDS in 72 (refractory anemia (RA) in 11, RA with excess of blasts (RAEB) in eight, RAEB in transformation (RAEB-T) in 10, JMML in 43), and AML in 28. The median age at presentation was 2.8 years (range 2 months to 15 years), being lowest in JMML (1.1 year). Loss of chromosome 7 as the sole cytogenetic abnormality was observed in 75% of those with MDS compared with 32% of those with AML. Predisposing conditions (including familial MDS/AML) were found in 20%. Three-year survival was 82% in RA, 63% in RAEB, 45% in JMML, 34% in AML, and 8% in RAEB-T. Children with -7 alone had a superior survival than those with other cytogenetic abnormalities: this was solely due to a better survival in MDS (3-year survival 56 vs 24%). The reverse was found in AML (3-year survival 13% in -7 alone vs 44% in other cytogenetic groups). Stable disease for several years was documented in more than half the patients with RA or RAEB. Patients with RA, RAEB or JMML treated with bone marrow transplantation (BMT) without prior chemotherapy had a 3-year survival of 73%. The morphologic diagnosis was the strongest prognostic factor. Only patients with a diagnosis of JMML fitted what has previously been referred to as the monosomy 7 syndrome. Our data give no support to the concept of monosomy 7 as a distinct syndrome.

Acute Disease↗
PubMed1999

Definition of a standard-risk group in children with AML.

To define paediatric AML patients with a favourable outcome in order to design a risk-adapted therapy, we analysed 489 children under 17 years of age treated similarly in studies AML-BFM 83 and 87. 369 patients (75.4%) achieved remission. Estimated probabilities of survival, event-free survival (EFS) and disease-free survival (DFS) at 5 years were 50% (SE 2%), 43% (SE 2%) and 58% (SE 3%), respectively. Multivariate analysis revealed bone marrow blasts on day 15, morphologically defined risk groups and hyperleucocytosis to be of prognostic value. EFS at 5 years estimated for patients with < or = 5% and >5% blasts on day 15 were 56% (SE 3%) v 27% (SE 4%); for the favourable morphological subgroups (M1/M2 with Auer rods, M3 and M4eo) it was 60% (SE 4%) compared with other patients (33%, SE 3%), P (Kaplan-Meier) = 0.0001 each. Hyperleucocytosis proved to be an independent prognostic factor, indicating a high risk, especially for early failure. The specific karyotypes t(8;21), t(15;17) and inv16 were closely related to the favourable morphology and outcome was in the same range. We conclude that for the definition of a standard-risk group a combination of morphological and response criteria may be sufficient. The standard-risk group defined by favourable morphology and a blast cell reduction on day 15 (not required for M3) comprises 31% of all patients, P survival, pEFS and pDFS at 5 years were 73% (SE 4%), 68% (SE 5%) and 76% (SE 4%), respectively.

Acute Disease↗
PubMed1999

Expression of AC133 and CD117 on candidate normal stem cell populations in childhood B-cell precursor acute lymphoblastic leukaemia.

To identify residual candidate normal progenitor/stem cell populations in childhood B-cell precursor acute lymphoblastic leukaemia (ALL), expression of AC133 and CD117 was analysed on the leukaemic cell clone and on immature B-lineage-negative CD34+CD19- bone marrow cells. 10/25 patients (40%) had no detectable expression of AC133 within the leukaemic cell clone. 24/26 patients (92%) lacked expression of CD117 on the leukaemic blast cell population. In contrast, a distinct AC133-positive cell population was found in 8/8 children with AC133-negative ALL and a CD117-positive cell population could be identified in 12/12 children with CD117-negative ALL, within the CD34+CD19- progenitor/stem cell compartment. These observations provide further evidence that in B-cell precursor ALL, unlike in acute myelogenous leukaemia, it may be possible to distinguish residual normal progenitor/stem cells from the leukaemic cell clone.

AC133 Antigen↗
PubMed1999

What learners and teachers value most in ambulatory educational encounters: a prospective, qualitative study.

PURPOSE: To determine what learners and teachers value most in ambulatory learning encounters and whether the choices of the two groups are in concordance. METHOD: In 1996, the authors surveyed learners and teachers at a walk-in clinic immediately after each of 103 consecutive learning encounters. The participants answered two open-ended questions: (1) What was the one most valuable aspect of this learning encounter? and (2) List one thing that would make it better. Using qualitative analysis methods, two raters categorized the responses; their agreement was substantial (kappa = .75). RESULTS: Half the responses fit five categories: diagnosis (15%), general management (14%), physical examination skills (9%), patient selection (6%), and time issues (6%). The participants most valued general exposure to diagnosis (29%) and general management issues (29%). Regarding their suggestions for improving the encounters, 33% cited structural issues (often "more time"), while 43% had no suggestions ("nothing" or "fine as is"). Substantial concordance existed between the rankings by category of the teachers' and learners' comments, but (1) learners were more likely to rate the educational value of the encounter excellent or very good (64% vs 47%, p < .01); (2) teachers were more likely than medical students (but not interns) to place the most educational value on the physical examination (30% vs 4%, p = .001); and (3) agreement on what was most valuable in any individual encounter was poor (kappa = .03). CONCLUSIONS: In evaluating ambulatory educational encounters, learners and teachers placed highest value on general exposure to diagnosis and disease management; while the most commonly recommended changes related to structural issues, particularly inadequate time. While learners and teachers agreed in general on the relative ranking of teaching activities, they often found different things to be educationally salient in a particular encounter.

Ambulatory Care↗
PubMed1999

[Therapeutic results of conization with diathermy].

OBJECTIVE: To assess the frequency, histological grade and time interval of residual and recurrent lesions after loop electrosurgical excision procedure and to analyse their associated risk factors. METHODS: 288 patients treated by loop electrosurgical excision procedure between February 1991 and July 1995 were prospectively included in this study. They agreed to a postoperative cytological and colposcopic follow-up with a first visit between 3 and 6 months after excision, a second one between 9 and 15 months and a third one between 24 and 36 months. We used univariate and multivariate analyses to evaluate the association between clinical variables and residual or recurrent lesions. RESULTS: The pathologic diagnosis of the specimens included 21 normal cervices (7.3%), 35 CIN 1 (12.2%), 43 CIN 2 (14.9%), 180 CIN 3 (62.5%), 1 adenocarcinoma in situ (0.3%) and 8 microinvasive cancers (2.8%). The pathologist considered the excision complete in 244 cases (85%). Among the other 44 patients, 27 had involved endocervical margins, 17 involved exocervical margins but none had both margins involved. The mean postoperative follow-up +/- standard deviation was 39 +/- 13 months (range 24-68 months). Treatment failure, defined as the persistence or recurrence of a cervical lesion, was observed in 20 patients (6.9%) having a squamous cancer stage IB (n = 1), a CIN 3 (n = 15), an adenocarcinoma in situ (n = 1) or a CIN 1 (n = 1). In 6 cases the second treatment was performed before the first cytological and colposcopic visit because of an excision considered incomplete by the pathologist. Overall 19 out of the 20 treatment failures were diagnosed within the first two years of the follow-up. The endocervical localisation of the initial lesion (adjusted RR 13.7; 95% CI 1.3, 150.1; P < 0.05) and incomplete excision (adjusted RR 9.1; 95% CI 3.0, 27.3; P < 0.001) were the only independent risk factors for treatment failure. CONCLUSION: Residual or recurrent lesions occurs rarely after loop electrosurgical excision procedure. They are favoured by totally endocervical lesion and an incomplete excision. With the association of cytology and colposcopy, 95% of treatment failures can be detected in the first 2 postoperative years.

Adult↗
PubMed1999

Leukaemia-associated immunophenotypes (LAIP) are observed in 90% of adult and childhood acute lymphoblastic leukaemia: detection in remission marrow predicts outcome.

Analysis of differentiation antigens on leukaemic blasts is routinely done for diagnostic purposes, i.e. determination of stage of differentiation and lineage assignment. Acute lymphoblastic leukaemias are also frequently characterized by a leukaemia-associated immunophenotype (LAIP), either the coexpression of differentiation antigens physiologically restricted to other stages of differentiation (asynchronous LAIP) or cell lineages (aberrant LAIP). We defined LAIP in 241 consecutive unselected B-lineage (n = 193) and T-lineage (n = 48) ALL by three-colour flow cytometry using directly conjugated monoclonal antibodies. The incidence of LAIP was found to be 91.7%. In 63% of patients two to six leukaemia-associated expression patterns were detected. In order to study the specificity of LAIP in a therapy-relevant setting, remission bone marrow samples from patients with B-lineage ALL were analysed for the expression of T-lineage-associated phenotypes on the normal bone marrow cells and vice versa. The frequency of all T-lineage LAIP+ cells and all aberrant B-lineage LAIP+ cells was <1% in regenerating bone marrow samples at different timepoints. The incidence and clinical significance of LAIP+ cells was studied in 196 remission marrows of 70 ALL patients (55 remaining in CCR, 14 with bone marrow relapse, one with isolated CNS relapse). The presence of >1% LAIP+ at two consecutive timepoints predicted 5/8 bone marrow relapses in B-lineage ALL. The occurrence of LAIP+ cells >1% in T-lineage ALL after induction therapy predicted relapse in 7/7 cases. In conclusion, flow cytometric detection of LAIP+ cells appears to be a powerful tool for the prediction of outcome in ALL.

Adolescent↗