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Biomedical subjects

R Klaassen

Publications and source records attributed to R Klaassen.

15 recordsLinked to original sources
PubMed2006

Disease progression in recently diagnosed patients with inherited marrow failure syndromes: a Canadian Inherited Marrow Failure Registry (CIMFR) report.

BACKGROUND: Inherited bone marrow failure syndromes (IMFSs) are genetic disorders characterized by defective single-lineage or multi-lineage hematopoiesis. IMFS patients are at risk for severe cytopenias, development of marrow cytogenetic abnormalities (MCA), myelodysplasia (MDS), and malignancy. The rate of disease progression and proportion of patients at risk for these complications is currently unclear. We examined recently diagnosed IMFS patients to determine distribution of diagnoses, disease progression and development of significant outcomes. METHODS: The CIMFR is a prospective multi-center study established in 2001 to register all IMFS patients in Canada. Analysis was restricted to patients diagnosed after November 30, 1997. Summary statistics were used to depict the study population while survival was described using the Kaplan-Meier method. RESULTS: 74 CIMFR patients were considered recently diagnosed. Median age at diagnosis was 2.7 years (range, birth to 40.6). Annual follow-up data were available for 53 (72%) patients. The five most prevalent diagnoses were Fanconi anemia (FA), Shwachman-Diamond syndrome (SDS), Diamond-Blackfan anemia (DBA), dyskeratosis congenita (DKC), and Kostmann's neutropenia (KS). Eighteen (24%) patients were unclassifiable. Twenty-eight (53%) follow-up patients had disease progression as indicated by new or worsening cytopenias, new marrow changes, or initiation of transfusion support and/or medical therapy. Fourteen (19%) fulfilled minimal diagnostic criteria for myelodysplasia. Eleven patients had hematopoietic stem cell transplantation (HSCT) by first follow-up. Five patients have died. Survival at 36 months is 89.8 +/- 5.7%. CONCLUSIONS: IMFS patients are often diagnosed at a young age. The relative distribution of diagnoses is similar to previous reviews of published cases; however, 25% of patients are currently unclassifiable. Disease progression has occurred in approximately 50% of follow-up patients. Early mortality is noted. Continued prospective observation of these patients is warranted.

Adolescent↗
PubMed2003

The intercollegiate Basic Surgical Skills Course.

OBJECTIVE: This study was undertaken to establish residents' progress in minimal access surgery (MAS) after attending the Intercollegiate Basic Surgical Skills Course (BSSC) by means of the Xitact LS500 laparoscopy simulator assessment program. METHODS: Twenty-five surgical residents attended the BSSC in Leiden and Eindhoven, The Netherlands. Before and after the course, participants performed three "runs" on the Xitact LS500, featuring a standardized laparoscopic cholecystectomy clip-and-cut task. A control group of 25 interns not attending the course also performed two sessions of three runs. Parameters of interest were "score" and "time for completion of task". RESULTS: No significant differences were found within the resident group for the parameters "time" and "score" when comparing outcomes pre- and post-BSSC. No significant differences were found comparing time and score between residents and interns on each of the six runs, except for time in run 2. Over six runs, both residents and interns became significantly faster. CONCLUSIONS: The Xitact LS500 cholecystectomy simulator did not detect significant improvement in MAS performance among a group of surgical residents attending the BSSC.

Adult↗
PubMed2000

Comparison of in vitro and in vivo developmental toxicity and pharmacokinetics of phenytoin in the rat.

The rat whole embryo culture was compared to an in vivo experiment with regard to embryotoxicity as well as exposure characteristics, using phenytoin as a model compound. Intra-embryonic concentrations and their embryotoxic effects were determined on gestation day 11 after in vitro administration of 50-150 microg/ml or in vivo gavage of 500-1500 mg/kg body-weight on gestation day 10. In addition, exposure kinetics were studied in vivo after a single oral dose on gestation day 10, and developmental defects on gestation day 21 were scored. The embryotoxic effects observed on gestation day 11 were more pronounced after in vitro exposure in comparison to in vivo exposure at similar intra-embryonic concentrations. Exposure of phenytoin on gestation day 10 in vitro via the culture medium resulted in general embryotoxicity on gestation day 11, whereas in vivo effects as determined on gestation day 11 were minimal. Plasma concentrations of phenytoin increased and plateaued around 35 microg/ml during the 48 hr monitoring period. Plasma concentration curves and pharmacokinetic parameters did not show remarkable differences between the dose groups, indicating that absorption is the limiting factor at the dose range used. Although the developmental effects were minimal as observed in vivo on gestation day 11, specific malformations (defects encompassing the urogenital. craniofacial and skeletal systems) were observed on gestation day 21. These findings show that with similar intra-embryonic concentrations of phenytoin the embryotoxicity in rat whole embryo culture was not comparable with the in vivo embryotoxicity as determined on gestation day 11. This discrepancy may at least partly be explained by differences in exposure characteristics.

Abnormalities, Drug-Induced↗
PubMed1996

[The effect of the wording of information about side effects on patients' interpretation of reported side effects].

OBJECTIVE: To determine whether changes in the side effects frequency information in a patient information leaflet affects the interpretation of the frequency, the recall of this information and the number of side effects reported. DESIGN: Randomized controlled trial. SETTING: A field experiment was carried out in which three versions of a package insert concerning diclofenac were randomized and tested in 33, 30 and 34 patients respectively. Version 1 contained the original side effects information. In version 2 the frequency descriptors were manipulated (lowered, e.g. 'sometimes' was replaced by 'seldom'). This was because a preliminary investigation had shown that patients make higher assessments of side effect frequencies than the leaflet writers want to convey. In version 3 an introduction was added with general information on side effects. RESULTS: The frequency assessments differed enormously between subjects. Especially the lower frequencies were virtually impossible to convey by means of words. The lower-ranking frequency descriptors did not only result in lower frequency assessments, but also led to lower recall score for side effects mentioned in the text and to a smaller number of side effects actually reported by patients. The only effect of the introduction was to lower the frequency assessments for the side effects following the introductory paragraph. CONCLUSIONS: Side effects with high assessed frequencies were read with more attention. The advantages and disadvantages of numerical frequency statements need to be discussed.

Drug Labeling↗
PubMed1995

[Tyrosine-protein kinase activity in breast neoplasm. Comparison with activity obtained in benign diseases and in normal tissues].

Tyrosine protein kinase (TPK) activity is associated to malignant cellular transformation. This work compares TPK activity in 27 surgical biopsy samples of mammary carcinoma, 10 samples of fibroadenomas, 13 samples of fibrocystic breast disease and 27 samples of normal mammary tissue. TPK activity was determined in tissue homogenates using (Val5) angiotensin II as exogenous substrate. In samples of mammary carcinoma, TPK activity was 33.86 +/- 31.98 pmol P32/mg protein/30 min. This value was significantly higher that those observed in fibrocystic disease (3.92 +/- 2.35), fibroadenomas (13.86 +/- 10.9) and normal tissue (3.56 +/- 3.02).

Adult↗
PubMed1994

[Results of combined treatment of early cervicouterine cancer].

Forty nine patients with carcinoma of the cervix treated with a combined method of preoperative radiation therapy (telecobalto and intracavitary) followed by extrafascial hysterectomy are presented. The average age was 39.6 years old. All tumors measured more than 4 cm, in diameter. The staging was lb = 40; lla = 6; llb = 3. The hysterectomy was done average 7.3 weeks after radiation therapy. Postreatment complications were seen in 32.4% and long term complications were found in 8.1% of the cases. After three years of follow up 91% of the patients were free of neoplastic disease. The 40% of the cases has more than three years follow up. There was 14% of total mortality which includes 10.2% of mortality by cancer. The size of the tumor (initially more than 7 cm, in diameter) and the finding of the tumor tissue in the surgical specimens were found of poor prognosis. There was significant statistical difference in survival between the groups with and without cancer cells in the uterus after hysterectomy (p < 0.01).

Adult↗
PubMed1994

[Uterine leiomyoma: pathology and epidemiology].

Two hundred biopsy reports with uterine myoma histopathological diagnosis were studied 67% of the cases were between 41-50 years of age. Premenopausic patients showed an average number of myomas almost three times higher than the postmenopausic women. The most frequent myoma were those within the walls with a size less than 2 cm. Chronic inespecific cervixitis was the most frequent finding in the cervix pathology, with in 1.5% of the cases. In 2 cases (1%) endometrial adenocarcinoma was found. In 60.5% of the cases one or both tubes and ovaries were removed neither case had malignant alterations. In 51 cases (25.2%) the myoma presented some type of degeneration, the most frequent being the cellular type, 16 out of 200, which represented 8% of the cases; it was considered as presarcomatose type. Presurgical clinical behavior is discussed considering the analysis of these figures and the perspectives of the conservative treatment with the use of new no ablative technique.

Adult↗
PubMed1992

[Ewing's sarcoma of bone in adults: an anatomic-clinical study of 30 cases].

The records of 30 adult patients with Ewing's sarcoma (ES) of bone treated between 1980 and 1990 at the Institut Curie were studied retrospectively; the diagnosis was reevaluated by histological and immunohistochemical analysis, using HNK and anti-neuron specific enolase (NSE) antibodies. The immunohistological analysis disclosed a significant staining of neoplastic cells in only few of our cases and is therefore of limited interest in the diagnosis of ES. Three groups of patients have been considered according to their clinical presentation: axial, peripheric and initial metastatic disease. The global prognosis is poor: the survival rate is 70% after a follow-up period of one year, and 23% after three years. The evolution was severe for patients with pelvic localization and/or initial metastatic disease. In contrast, five of six patients who are currently free of disease after a mean follow-up period of 42 months presented initial peripheric lesion. Four of these six patients were treated by a combination of surgical, chemical and radiation therapies.

Adolescent↗
PubMed1988

The PI-linked receptor FcRIII is released on stimulation of neutrophils.

Human phagocytic cells express receptors for the constant (Fc) region of immunoglobulin G. Neutrophils carry Fc receptor II (FcRII; CDw32) and FcRIII (CD16) which both bind IgG-containing immune complexes, leading to phagocytosis of the complex and activation of the neutrophil. We find that patients with paroxysmal nocturnal haemoglobinuria (PNH) have only about 10% of the normal levels of FcRIII on their neutrophils, whereas the expression of FcRII is unaffected. We show that FcRIII is a phosphatidyl inositol (PI)-anchored protein in neutrophils. Analysis of FcRIII expression in cells of PNH patients, known to be deficient in PI-linked proteins, suggests FcRIII is not PI-linked in monocytes. We find that the synthesis of FcRIII in neutrophils from PNH patients appears normal, indicating that the defect lies in the PI linkage. This lipid linkage of the receptor on neutrophils suggests that its release may be important for its function, and indeed FcRIII release was observed on stimulation of neutrophils by an inflammatory bacterial peptide (f-Met-Leu-Phe), suggesting a role for FcRIII shedding in inflammatory reactions. Activation of the PNH neutrophils with IgG-coated latex beads appeared normal (although binding of dimer IgG complexes was reduced), indicating that FcRII, rather than FcRIII, is involved in neutrophil stimulation.

Hemoglobinuria, Paroxysmal↗
PubMed1983

Identification and quantification of diethylstilbestrol in the urine of cattle by both low and high resolution gas chromatography mass spectrometry.

A confirmation method which can be used in regulatory screening programs for diethylstilbestrol in the urine of cattle is presented. trans-Diethylstilbestrol is purified from urine by Sep-Pak extraction and high-performance liquid chromatography and converted into its trimethylsilyl derivative. Identification is based on both accurate mass measurement of the molecular ion of trans-diethylstilbestrol trimethylsilyl by gas chromatography high resolution mass spectrometry and determination of the [M + 1] +/[M]+ peak height ratio by selected ion monitoring in low resolution. Specificity is such that on the basis of mass spectrometric data alone, all molecular formulae except those of diethylstilbestrol trimethylsilyl and only one other compound can be excluded. Additional specificity is provided by chromatographic data. The quantification is based on the standard addition method. The average recovery of trans-diethylstilbestrol is 76% with a standard deviation of 18% (n = 23).

Animals↗
PubMed1981

Isotope dilution mass spectrometry of cholesterol in serum.

Isotope dilution mass spectrometry is one of the best candidates for reference and definitive methods for the quantitative measurement of organic compounds. In this study sources of error were investigated. Where possible they were removed, and commercially available equipment had to be modified. The method was applied to the measurement of serum cholesterol. The precision is optimized and in the order of 0.5%. The mean of the recoveries of three measurements is 99.8%. The accuracy of the mean of three measurements is 0.2% if no interferences are present in the gas chromatographic mass spectrometric measurements.

Cholesterol↗
PubMedDate not supplied

Embryotoxicity of carbamazepine in rat postimplantation embryo culture after in vitro exposure via three different routes.

Postimplantation rat embryo culture is used widely for studies of embryotoxic effects on the isolated embryo after in vitro exposure to xenobiotic compounds. In this study, the relevance of three routes of exposure of the embryo in vitro was evaluated using the embryotoxic anticonvulsant carbamazepine. Embryotoxic effects were assessed, and analyses in conceptus tissues were done to reveal uptake and metabolism of the compound. Exposure via the culture medium resulted in neural tube defects and general retardation of growth and development. After injections into the amniotic or exocoelomic space, local membrane adhesions were found. Intra-amniotic exposure caused adhesions of the amniotic membrane with the embryonic neural plate, resulting in trapping of the membrane in the closing neural tube, as well as in open neural tube defects occurring in various areas of the neural tube. Only after exposure via the culture medium were amounts of carbamazepine detectable in the embryonic tissue, correlating with the systemic effects found. It is concluded that uptake from the culture medium via the yolk sac circulation is the relevant exposure route to be used for embryotoxicity effect assessment.

Amnion↗