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Biomedical subjects

J Ritter

Publications and source records attributed to J Ritter.

At least 109 records · Page 6Linked to original sources
PubMed1996

Presence of multiple centrioles and primary cilia during growth and early differentiation in the myoblast CO25 cell line.

CO25 cells, a mouse myoblast line, contain multiple centrioles and primary cilia. A most unusual feature has been the finding of large numbers of separate structures in single cells-up to a maximum of nine centrioles, six primary cilia, and 12 of both organelles together. Aberrant multipolar spindles were occasionally seen containing variable numbers of centrioles. This strongly suggests that cells containing supernumerary centrioles and cilia are lost during mitosis, and that additional centriolar structures are generated during each interphase. No change in centriole or primary cilium frequency was detected after inducing the differentiation of myoblasts into myotubes. However, a significant migration of these structures occurred from a perinuclear to a supranuclear position prior to and during the phase of myoblast elongation. This shift was not maintained during cell fusion, when a net migration back to the periphery was observed, suggesting that it may have some function in relation to cell elongation and the change in the pattern of microtubule distribution which occurs as part of the process.

Animals↗
PubMed1996

Therapy of childhood acute myelogenous leukemias.

Acute myelogenous leukemia (AML) accounts for approximately 20% of acute leukemias in children. Although AML is more resistant to chemotherapy than acute lymphoblastic leukemia (ALL), significant progress in improving outcome for AML patients has been achieved over the past 15 years. This can be attributed to intensification of chemotherapy, increased use of bone marrow transplantation, and improved supportive care. Thus 30-50% of children with AML achieve long-term event-free survival with current treatment strategies [61, 66, 85, 96]. This review gives an overview about the evolution of and rationale for current pediatric treatment protocols, with special emphasis on the German Berlin-Frankfurt-Münster (BFM) studies, and discusses new directions for the future.

Antineoplastic Agents↗
PubMed1996

Diagnostic value of endocervical curettage during colposcopy.

A retrospective study including patients with cytology, colposcopy and endocervical curettage (ECC) was carried out to compare ECC outcomes to final diagnosis. ECC was performed in 68 cases for a discordance between cytology and colposcopy and in 85 cases because the lesion was incompletely visible. Complete concordance between ECC and final diagnosis was obtained in 123 cases. ECC overestimated diagnosis in eight cases (5 true false positives) and underestimated it in 20 cases (6 true false negatives). Among the latter, ECC failed to recognize invasion in seven cases. Sensitivity, specificity, positive and negative predictive values of ECC to diagnose high grade cervical intraepithelial neoplasia (CIN) and invasive lesions together were 84%, 97%, 95% and 90%, respectively. Outcomes to diagnose invasive lesions were 22%, 100%, 100% and 95%, respectively. ECC sensitivity to diagnose endocervical lesions is satisfactory but its sensitivity to establish the diagnosis of invasion is very low. Consequently, a conization is advisable when ECC has diagnosed an endocervical lesion, especially a high grade CIN.

Adult↗
PubMed1996

A new germline TP53 gene mutation in a family with Li-Fraumeni syndrome.

This report describes an unusual clinical presentation of Li-Fraumeni syndrome. Family history revealed a mild aggregation of adult cancers in one generation, and an unusual clustering of brain tumours of early childhood in the following generation. In order to evaluate the genetic basis for cancer predisposition in this family, molecular genetic analysis for the occurrence of germline TP53 tumour suppressor gene mutations was performed on 12 siblings of two generations. Indirect mutation analysis was performed by the single-strand conformation polymorphism (SSCP) technique. Alterations were characterised by automated direct fluorescence sequencing analysis. Tumour material was also examined for p53 protein accumulation by immunohistochemistry. Initially, a TP53 gene germline missense mutation was detected in an 11-year-old kindred with acute myeloid leukaemia (AML) following intensive treatment of a brain tumour. In peripheral blood and bone marrow samples of this proband, a reduction to hemizygosity occurred. During AML treatment, detection of LOH of 17p was used as a marker for clonality and treatment control. The mutation was found to be inherited from the proband's mother, who was diagnosed with breast cancer at the age of 48 years. Further, three siblings were carriers, and two are apparently healthy at the age of 21 and 23 years. Knowledge of germline mutations may allow accurate DNA-based carrier diagnosis which is of important clinical significance for treatment strategy and control. Furthermore, the occurrence of unaffected carriers in this family raises questions about appropriate methods of cancer surveillance and counselling for these people.

Adult↗
PubMed1996

Monitoring of asparaginase activity and asparagine levels in children on different asparaginase preparations.

The antileukaemic enzyme L-asparaginase is used to achieve the greatest possible reduction in blood levels of the amino acid asparagine, an essential factor for the growth of leukaemic blasts. There are two main sources of the enzyme, E. coli and Erwinia. Faced with increasing reports of treatment complications, we established a programme to monitor enzyme activity and asparagine levels in serum, in children receiving treatment for acute lymphoblastic leukaemia (ALL) and non-Hodgkin's lymphoma (NHL). Trough asparagine and asparaginase levels were measured in 49 children on induction treatment with different E. coli preparations (Asparaginase medac, Crasnitin) and in 52 children on re-induction (Asparaginase medac, Crasnitin, and, in the event of allergic reactions, Erwinase) just prior to each sequential application of 10000 U/m2 of asparaginase. Measurements were made by an enzyme assay and an HPLC method. During induction, both Escherichia coli preparations induced the desired reduction in asparagine, but the asparaginase activity with Asparaginase medac was significantly higher than with Crasnitin (median of trough levels 475 versus 74 U/l). Under re-induction treatment (median, Asparaginase medac 528 U/l, Crasnitin 49 U/l, and Erwinase < 20 U/l) complete asparagine depletion was recorded on day 3 in more than 90% of Asparaginase medac samples, more than 60% of Crasnitin samples and in 26% of Erwinase samples. The latter two groups included some children with unchanged asparagine levels and no measurable enzyme activity. Different asparaginase preparations are not readily interchangeable. When Asparaginase medac is used instead of Crasnitin, and identical dose will be associated with significantly higher enzyme activity, well above the level required for complete asparagine depletion. Clinical studies will need to specify both the preparation and the dose to be used. When substitution of an alternative drug is mandatory owing to allergic reactions, monitoring is advisable.

Adolescent↗
PubMed1996

Risk of cervical stenosis after large loop excision or laser conization.

OBJECTIVE: To assess the frequency of cervical stenosis in patients treated by laser conization or the loop electrosurgical excision procedure and to determine the preoperative and therapeutic factors associated with its occurrence. METHODS: Two hundred fifty-five women treated by laser conization and 277 treated by loop electrosurgical excision procedure were followed regularly by postoperative colposcopy for mean periods of 38 and 16 months, respectively. Stenosis was defined as cervical narrowing that prevented insertion of a 2.5-mm Hegar dilator. RESULTS: Thirty-eight cases of cervical stenosis, of which seven were complete, were diagnosed up to 28 months after treatment. The risk of postoperative cervical stenosis was higher for patients over 50 years of age (relative risk [RR] 3.07, 95% confidence interval [95% CI] 1.30, 7.26; P = .031), for those with a totally endocervical lesion (RR 3.79, 95% CI 1.88, 7.62; P = .001), for those with an excision 20 mm high or greater (RR 2.96, 95% CI 1.63, 5.38; P = .005), and for those with laser conization (RR 2.35, 95% CI 1.24, 4.46; P = .009). Parity, menopause, previous treatment for cervical intraepithelial neoplasia, satisfactory colposcopy, size of the lesion, its histologic diagnosis, and the extent of excision did not increase the risk for cervical stenosis. Excision was not as high with loop electrosurgical excision as with laser conization (14.3 +/- 5.0 mm versus 20.2 +/- 6.0 mm). The height of excision (RR 1.95, 95% CI 1.02, 3.76; P = .04) and a totally endocervical lesion (RR 5.07, 95% CI 1.96, 14.44; P = .001) were the only independent factors associated with postoperative stenosis identified by a multivariate analysis using logistic regression. CONCLUSION: The height of excision and a totally endocervical lesion were the main factors associated with cervical stenosis. The decreased risk associated with the loop electrosurgical excision procedure seems to be due to a shorter endocervical excision.

Adolescent↗
PubMed1996

Giant multilocular cystadenoma of the prostate.

Giant multilocular prostatic cystadenoma is a rare clinicopathologic entity characterized by benign histology and the ability to enlarge massively. The lesion may arise from the prostate gland either in continuity with the prostatic urethra or separate from it, or it may arise as a lesion distinct from the prostate gland. Obstructive voiding symptoms occur in all reported cases. The use of preoperative radiographic evaluation, such as magnetic resonance imaging, effectively defines the lesion's benign nature and aids in planning surgical extirpation.

Aged↗
PubMed1996

Prenatal diagnosis of unilateral tibial hemimelia.

We describe a case of unilateral tibial agenesis which was initially observed at 21 weeks' gestation. Unlike bilateral tibial hemimelia syndrome, a rare autosomal dominant condition, unilateral tibial agenesis, which accounts for about three-quarters of all newborns with this condition, has not previously been described. This case could have been a sporadic abnormality but, in view of the association with other observations (distal bifurcation of the femur, club foot), could be considered as an autosomal recessive inherited condition with variable penetrance. Ultrasonographic features and the genetic prognosis are discussed.

Adult↗
PubMed1996

Plasma cyclic GMP concentrations and their relationship with changes of blood pressure levels in pre-eclampsia.

BACKGROUND: One of the possible mechanisms responsible for pre-eclampsia is a loss of efficiency of the L-arginine-nitric oxide pathway with subsequent inactivation of the guanylyl cyclases of the vascular smooth muscle cells. As a result there should be a decrease in plasma cyclic 3'-5' guanosine monophosphate (cGMP) concentrations in pre-eclampsia. We assessed the behavior of this nucleotid in the plasma of pre-eclamptic women. SUBJECTS AND METHODS: Sixteen pre-eclamptic women, 16 normotensive pregnant women matched for gestational age and six nonpregnant controls were investigated. Arterial blood pressure was recorded at inclusion time and then once-a-day until the fourth day after delivery concomitantly with the collection of blood samples for determining plasma cGMP, atrial natriuretic peptides (ANP), creatinine, uric acid and platelet counts. Also 24 h urines were simultaneously collected to calculate renal clearance of cGMP. RESULTS: Before the initiation of antihypertensive treatment, plasma cGMP levels were significantly higher (p < 0.01) in pre-eclampsia women as compared both to pregnant normotensive controls and nonpregnant women (7.02 +/- 0.9 versus 4.8 +/- 0.76 versus 1.93 +/- 0.15 pmol.ml-1, p < 0.01). Under antihypertensive treatment, cGMP levels decreased significantly (p < 0.05) to 5.48 +/- 0.9 pmol.ml-1. The increase of plasma cGMP was associated with high ANP levels; the likelihood that a renal impairment could account for an increase in plasma cGMP was ruled out because the clearance of creatinine was not impaired. Similarly the possibility of a significant linear correlation between cGMP levels and blood pressure values or biological data was excluded in these women. CONCLUSION: Plasma cGMP concentrations are increased in pre-eclampsia. They decrease to control values when blood pressure returns to normal values; they indicate enhanced guanylyl cyclase activation by ANP and additional factors, but cannot be considered as a direct index of the severity of pre-eclampsia.

Adult↗
PubMed1996

[Fetal and neonatal immune thrombocytopenias].

Fetal and neonatal immune thrombocytopenias with platelet count less than 150.10(9)/l, result from transplacental passage of maternal platelet-specific antibodies. The main risk of these diseases is severe brain damage or death due to intracranial hemorrhage. Prevention and screening are difficult because of the lack of predicting factors. Only some women are at high risk of fetal thrombocytopenia (HLA DRW 52a HPA-la negative women or women with a previous history of immune thrombocytopenic purpura and having platelet-specific autoantibodies). Antenatal diagnosis and therapy have altered the natural course of fetal alloimmune thrombocytopenia. No prenatal treatment has proved to be effective in autoimmune thrombocytopenia and prenatal diagnosis by fetal blood sampling is controversial. A better knowledge of the pathogenesis of gestational incidental thrombocytopenia in otherwise healthy pregnancies, could define a group at high risk of fetal thrombocytopenia.

Algorithms↗
PubMed1996

Revision of the 1990 working formulation for the classification of pulmonary allograft rejection: Lung Rejection Study Group.

In 1990, an international grading scheme for the grading of pulmonary allograft rejection was instituted. The use of this classification has resulted in a uniformity of grading which has allowed inter-institutional collaborations and communication unique in allograft monitoring. In 1995 an expanded group of international pathologists convened and revised the original proposal. This article summarizes the updated classification for pulmonary allograft rejection. In brief, acute rejection is based on perivascular and interstitial mononuclear infiltrates. Each grade of acute rejection should mention the presence of coexistent airway inflammation, the intensity of which may also be graded. Chronic rejection is divided into bronchiolitis obliterans--active or inactive--and vascular atherosclerosis--accelerated arterial or venous sclerosis.

Acute Disease↗
PubMed1996

[Carboplatin and cyclophosphamide in stage Ic-IV ovarian carcinoma: retrospective study of 101 cases].

We report our experience of CBDCA-CPM combination chemotherapy as first line therapy in 101 ovarian cancers. The therapeutic scheme was: initial cytoreductive surgery followed by six chemotherapy cycles (CBDCA 400 mg/m2/d IV dl, CPM 600 mg/m2/d IV dl, dl = d21) and second-look laparotomy. The initial stages were four Ic, three IIa, four IIb, four IIc, 15 IIIa, 28 IIIb, 23 IIIc and 20 IV. After initial surgery, there were 39 macroscopic residual diseases superior to 2 cm, 26 macroscopic residual diseases inferior or equal to 2 cm, four microscopic diseases and no residual disease in 30 cases (unknown in two cases). The overall response rate to chemotherapy was 83% with 56% histologic complete response rate. The main toxicity was haematological with 60% of leucopenia grade III-IV, 52% of thrombopenia grade III-IV. Age at diagnosis, residual disease after first look surgery and length of CA 125 normalization were significant prognostic factors for survival in this series.

Adolescent↗
PubMed1996

Myelodysplasia and acute myelogenous leukemia in Down's syndrome. A report of 40 children of the AML-BFM Study Group.

Forty children with Down's syndrome have been identified among 633 patients in the cooperative pediatric BFM studies for acute myelogenous leukemia (AML) since 1987. The following features were characteristic for these patients: (1) a 500-fold higher than expected incidence of megakaryoblastic leukemia (M7) with a peak incidence under 4 years of age; (2) a myelodysplastic prephase with thrombocytopenia lasting for several months up to a few years; (3) frequent involvement of the red cell lineage as suggested by dyserythropoiesis in the bone marrow; (4) coexpression of the lymphoid cell surface antigen CD7 on the leukemic blasts; (5) absence of the translocation t(1;22), instead presence of complete or partial trisomies involving chromosomes 8 and 1; and (6) a good response to chemotherapy. Nearly half of the patients did not receive any or only palliative chemotherapy and subsequently died. In 21 patients treatment according to the AML-BFM protocols was intended, however, with major dose or protocol reductions in six patients. Four died early, 15 (71%) achieved remission. Nine of 11 patients remaining alive for 0.6-6.5 years had received intensive treatment including high-dose cytosine arabinoside (HD-Ara-C). The 5-year survival estimate of 48% +/- 12% was similar to patients without Down's syndrome. In conclusion, these clinical and biological features suggest that M7 leukemia in children with Down's syndrome (M7-Down) is distinct from megakaryoblastic leukemia in other children. Children with Down's syndrome show a favorable outcome if treated adequately. However, overtreatment should be avoided and life-threatening infections pose a particular problem. Therefore, standard-risk AML therapy (including HD-Ara-C) should be considered in children with Down's syndrome and AML.

Adolescent↗
PubMed1996

[Management of pregnant women with abnormal cervical smears. A series of 146 patients].

OBJECTIVES: Evaluation of the value of colposcopy and directed biopsy in the follow-up of pregnant women presenting with abnormal cervical smear. MATERIAL AND METHODS: Retrospective study of 146 patients examined by colposcopy during pregnancy between January 1985 and December 1994. RESULTS: Colposcopy was satisfactory in 86% of patients. Colposcopic impression was concordant with the final diagnosis, overestimated and underestimated in 69%, 18% and 13% of the cases, respectively. Directed biopsies were performed in 115 patients. In one case, bleeding necessitated vaginal packing for 24 hours. Directed biopsy correlated well with the final diagnosis in 87% of low grade CIN and in 90% of high grade CIN. In 4 patients, conisation was performed between 10 and 16 weeks of gestation without subsequent obstetrical complications. CONCLUSION: Colposcopy with directed biopsy is a reliable tool to evaluate abnormal smear during pregnancy.

Adolescent↗
PubMed1996

[Management of hematologic malignancies during pregnancy].

Hodgkin's disease, non-Hodgkin lymphoma or leukemia occurring in a pregnant patient is a rare event. Diagnosis of hematologic malignancies in a pregnant woman usually poses a quandrum of psychological, ethical and medical considerations. All of these situations require a multidisciplinary team. Adequate staging and treatment of hematologic malignancies are complicated by the pregnancy. In the first trimester, termination of the pregnancy should be considered in order to provide the best outcome for the woman and fetus. In this review we have focused on the use of chemotherapy for the pregnant patient. This review reveals that the use of chemotherapy resulted in both objective disease remissions and the subsequent delivery of normal infant.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

[Assessment of the resectability of Wilms' tumors in childhood].

Over the last ten years 62 children were operated for renal tumours. The therapeutic aim in Wilms' tumours is complete macroscopic resection of the primary tumour, assessing resectability as accurately as possible. Overestimating surgical possibilities may lead to intraoperative rupture of the tumour (three cases), while overestimating local tumour extent may result in too much preoperative chemotherapy, which resulted in the life-threatening complication of venous occlusive disease of the hepatic veins (VOD) in three infants. The assessment of resectability may become particularly problematic in bilateral (six cases) or multifocal Wilms' tumours (two cases), and in nephroblastomatosis (two cases), i.e. the persistence of embronal renal tissue, a facultatively precancerous lesion, which requires quarterly sonographic controls and which induced a second metachronous contralateral Wilms' tumour in one child.

Adolescent↗
PubMed1995

Clinical significance of surface antigen expression in children with acute myeloid leukemia: results of study AML-BFM-87.

Immunophenotyping using a panel of 15 antibodies was performed in 267 (87%) and cytogenetic analysis in 196 (64%) of 307 children under 17 years of age enrolled in the AML-BFM-87 study. Treatment consisted of cytosine arabinoside, daunorubicin, etoposide induction and a 6-week seven-drug consolidation chemotherapy, followed by two blocks of high-dose cytosine arabinoside with or without cranial irradiation and maintenance therapy for 1 year. Five-year event-free survival for patients with immunophenotypic data was .43 +/- .03 SE. The diagnostic value of the pan-myeloid reagents CD13, CD33, and CDw65 for the recognition of childhood acute myeloid leukemia (AML) was high with a sensitivity of 98% (positivity of at least one of these antigens), whereas, with the exception of CD41 for French American British (FAB) subtype M7, the expression of single cell-surface antigens showed no correlation with morphologic or cytogenetic subgroups. On the other hand, characteristic subgroups of AML defined by morphologic features and karyotypes could be described by low or high rates of surface antigen expression compared with those of other patients. These immunophenotypic features most probably associated with specific entities include expression of CD34 or CD13 and absence of CD14 or CD4 in M2 with Auer rods/t(8;21); absence of HLA-DR, CD34, and CD14, but expression of CD33 in M3/t(15;17); positivity of either CD34 or CD13 and either CD14 or CD2 for M4Eo/inv(16); and absence of either CD34 or CD13 and expression of either CD33 or CDw65 and either CD15 or CD4 for M5/t(9;11). In FAB M0, negativity of one or two of the three panmyeloid-associated markers (CD13/33/w65) was common; and cytogenetic results frequently showed random abnormalities. Expression of lymphoid-, progenitor- and most myeloid-associated antigens had no influence on the prognosis, whereas the outcome was significantly better for children with M2 with Auer rods, M3, or M4Eo or for those with the associated karyotypes t(8;21);t(15;17) and inv(16) than for other patients.

Acute Disease↗